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Yuan W, Lv X, Zhao J, Jia Z, Zhou Q, Zhang H, Dai J, Feng J, Chen W, Jiang W, Liu X. Volumetric histogram analysis of amide proton transfer-weighted imaging for predicting complete tumor response to neoadjuvant chemoradiotherapy in locally advanced rectal adenocarcinoma. Eur Radiol 2025; 35:3158-3168. [PMID: 39623065 DOI: 10.1007/s00330-024-11220-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 09/11/2024] [Accepted: 10/20/2024] [Indexed: 05/16/2025]
Abstract
OBJECTIVES To investigate the potential of histogram analysis applied to pre-treatment amide proton transfer-weighted (APTw) imaging in predicting complete pathological regression (pCR) in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (nCRT). MATERIALS AND METHODS This retrospective study enrolled LARC patients who underwent preoperative rectal magnetic resonance imaging (MRI). Based on histologic assessment, the patients were divided into a pathological complete response (pCR) group or a non-pCR group. APTw histogram features, apparent diffusion coefficient (ADC), and clinical parameters were analyzed. Mann-Whitney U-test, Spearman rank correlation, and univariate and multivariate logistic regression were used for statistical analysis. The predictive performances of different models were evaluated by the receiver operating characteristic curve (ROC). RESULTS One-hundred forty-five patients were included (mean age, 61.6 years ± 11.8 [SD]; 87 men). pCR patients exhibited lower pre-treatment ADC value, higher pre-treatment APTw-10%, APTw-90%, minimum, maximum, median, mean, range, and root mean square (RMS) of the primary tumor compared to non-pCR patients (all p < 0.05). APTw-10%, APTw-90%, maximum, mean, median, minimum, range, and RMS showed negative correlations with the tumor regression grade (TRG) category (r ranged between -0.457 and -0.173; all p < 0.005). Skewness, kurtosis, and entropy exhibited positive correlations with the TRG category (r = 0.278, 0.319, and 0.324, respectively; all p < 0.05). The combined model had a higher AUC of 0.930, with 93.9% sensitivity and 83.9% specificity. CONCLUSION Histogram analysis of pre-treatment APTw may hold promise as a novel approach for predicting the response of LARC patients to nCRT. KEY POINTS Question Predicting response to nCRT is crucial for early stratified management of LARC patients; however, current radiological studies remain inconclusive. Finding LARC patients with pCR is correlated with higher pre-treatment APTw intensity-related and lower shape-related histogram features. Clinical relevance The APTw-histogram model and the APTw-clinical combined model demonstrated strong diagnostic efficacy and clinical practicality in predicting LARC patients' responsiveness to nCRT, offering new insights for early clinical decision-making.
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Affiliation(s)
- Wenjing Yuan
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xia Lv
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jiaxin Zhao
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Ziqi Jia
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qianling Zhou
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hanliang Zhang
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jianhao Dai
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jieping Feng
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Weicui Chen
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Wei Jiang
- Department of Radiotherapy, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, China.
| | - Xian Liu
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
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Kubota S, Wakiya T, Morohashi H, Miura T, Kanda T, Matsuzaka M, Sasaki Y, Sakamoto Y, Hakamada K. Prediction of the Therapeutic Response to Neoadjuvant Chemotherapy for Rectal Cancer Using a Deep Learning Model. J Anus Rectum Colon 2025; 9:202-212. [PMID: 40302856 PMCID: PMC12035344 DOI: 10.23922/jarc.2024-085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 12/08/2024] [Indexed: 05/02/2025] Open
Abstract
Objectives Predicting the response to chemotherapy can lead to the optimization of neoadjuvant chemotherapy (NAC). The present study aimed to develop a non-invasive prediction model of therapeutic response to NAC for rectal cancer (RC). Methods A dataset of the prechemotherapy computed tomography (CT) images of 57 patients from multiple institutions who underwent rectal surgery after three courses of S-1 and oxaliplatin (SOX) NAC for RC was collected. The therapeutic response to NAC was pathologically confirmed. It was then predicted whether they were pathologic responders or non-responders. Cases were divided into training, validation and test datasets. A CT patch-based predictive model was developed using a residual convolutional neural network and the predictive performance was evaluated. Binary logistic regression analysis of prechemotherapy clinical factors showed that none of the independent variables were significantly associated with the non-responders. Results Among the 49 patients in the training and validation datasets, there were 21 (42.9%) and 28 (57.1%) responders and non-responders, respectively. A total of 3,857 patches were extracted from the 49 patients. In the validation dataset, the average sensitivity, specificity and accuracy was 97.3, 95.7 and 96.8%, respectively. Furthermore, the area under the receiver operating characteristic curve (AUC) was 0.994 (95% CI, 0.991-0.997; P<0.001). In the test dataset, which included 750 patches from 8 patients, the predictive model demonstrated high specificity (89.9%) and the AUC was 0.846 (95% CI, 0.817-0.875; P<0.001). Conclusions The non-invasive deep learning model using prechemotherapy CT images exhibited high predictive performance in predicting the pathological therapeutic response to SOX NAC.
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Affiliation(s)
- Shunsuke Kubota
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Taiichi Wakiya
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Hajime Morohashi
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Takuya Miura
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Taishu Kanda
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Masashi Matsuzaka
- Department of Medical Informatics, Hirosaki University Hospital, Hirosaki, Japan
| | - Yoshihiro Sasaki
- Department of Medical Informatics, Hirosaki University Hospital, Hirosaki, Japan
| | - Yoshiyuki Sakamoto
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Kenichi Hakamada
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
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Chen SF, Yang SH, Jiang JK, Wang LW. Outcomes of Postchemoradiotherapy Watch-and-Wait Strategy in Patients With Rectal Cancer: A 20-Year, Single-Center Study. J Surg Oncol 2025; 131:899-907. [PMID: 39635915 DOI: 10.1002/jso.28008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 11/03/2024] [Accepted: 11/09/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND AND OBJECTIVES The watch-and-wait (WW) strategy is a nonsurgical alternative for patients with rectal cancer exhibiting an excellent response to chemoradiotherapy. Studies on the WW strategy have primarily investigated 5-year oncological outcomes; few have focused on longer-term outcomes or the optimal patient selection approach for this therapeutic strategy. METHODS This retrospective study enrolled patients with locally advanced rectal adenocarcinoma who had achieved complete response after chemoradiotherapy. Patients who achieved pathological complete response were categorized into a control group (n = 95) and those who achieved clinical complete response and were managed using the WW strategy were categorized into a case group (n = 33). Kaplan-Meier estimates were calculated for the between-group comparison of survival. RESULTS The median follow-up duration was 89 months. Compared with the control group, the case group exhibited improved long-term sphincter preservation, particularly for low-lying tumors (p = 0.032), and inferior nonlocal-regrowth disease-free survival (p = 0.007). Within the case group, patients achieving a complete response by positron emission tomography exhibited 5-year survival rates similar to those achieving a complete endoscopic response. CONCLUSION The WW strategy is associated with improved sphincter preservation but worse nonlocal-regrowth disease-free survival. The potential of PET in patient selection for this strategy deserves further investigation.
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Affiliation(s)
- Shuo-Fu Chen
- Department of Heavy Particles & Radiation Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shung-Haur Yang
- Department of Surgery, National Yang Ming Chiao Tung University Hospital, Yilan, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Jeng-Kai Jiang
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ling-Wei Wang
- Department of Heavy Particles & Radiation Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
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Karahacioglu D, Atalay HO, Esmer R, Kabaoglu ZU, Senyurek S, Ozata IH, Taskin OÇ, Saka B, Selcukbiricik F, Selek U, Rencuzogullari A, Bugra D, Balik E, Gurses B. What is the predictive value of pretreatment MRI characteristics for achieving a complete response after total neoadjuvant treatment in locally advanced rectal cancer? Eur J Radiol 2025; 185:112005. [PMID: 39970545 DOI: 10.1016/j.ejrad.2025.112005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Revised: 02/04/2025] [Accepted: 02/13/2025] [Indexed: 02/21/2025]
Abstract
OBJECTIVES To investigate the value of pretreatment magnetic resonance imaging (MRI) features in predicting a complete response to total neoadjuvant treatment (TNT) in locally advanced rectal cancer (LARC). METHODS The data of patients who received TNT were analyzed retrospectively. MRI features, including T stage, morphology, length, and volume; the presence of MR-detected extramural venous invasion (mrEMVI), the number of mrEMVI, and the diameter of the largest invaded vein; main vein mrEMVI; presence of MR-detected tumor deposits (mrTDs), the number of mrTDs, and the size of the largest mrTD; MR-detected lymph node status (mrLN); tumor distance from the anal verge; mesorectal fascia involvement (mrMRF + ); and mean apparent diffusion coefficient (ADC) values were recorded. Patients were classified as complete (CRs) or noncomplete responders (non-CRs) according to the pathological/clinical outcomes. For patients managed nonoperatively, a sustained clinical complete response for > 2 years was deemed a surrogate endpoint for complete response. The MRI parameters were categorized into three distinct groups: baseline, advanced, and quantitative features, and were analyzed using multivariable stepwise logistic regression. The ability to predict complete response was evaluated by comparing different combinations of MRI parameters, and performance on an "independent" dataset was estimated using bootstrapped leave-one-out cross-validation (LOOCV). RESULTS The data of 84 patients were evaluated (CRs, n = 44; non-CRs, n = 40). The optimal model, which included baseline and quantitative MRI features, achieved an area under the curve of 0.837 for predicting complete response. Selected predictors were T stage and ADC mean value. Advanced MRI features did not improve the performance of the model. CONCLUSION A multivariable model combining T stage and the ADC mean value can help identify LARC patients who are likely to a achieve complete response before the initiation of TNT.
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Affiliation(s)
- Duygu Karahacioglu
- Department of Radiology, Koç University School of Medicine, Istanbul, Turkey.
| | - Hande Ozen Atalay
- Department of Radiology, Koç University School of Medicine, Istanbul, Turkey
| | - Rohat Esmer
- Koç University School of Medicine, Istanbul, Turkey
| | | | - Sukran Senyurek
- Department of Radiation Oncology, Koç University School of Medicine, Istanbul, Turkey
| | - Ibrahim Halil Ozata
- Department of General Surgery, Koç University School of Medicine, Istanbul, Turkey
| | - Orhun Çig Taskin
- Department of Pathology, Koç University School of Medicine, Istanbul, Turkey
| | - Burcu Saka
- Department of Pathology, Koç University School of Medicine, Istanbul, Turkey
| | - Fatih Selcukbiricik
- Department of Medical Oncology, Koç University School of Medicine, Istanbul, Turkey
| | - Ugur Selek
- Department of Radiation Oncology, Koç University School of Medicine, Istanbul, Turkey
| | - Ahmet Rencuzogullari
- Department of General Surgery, Koç University School of Medicine, Istanbul, Turkey
| | - Dursun Bugra
- Department of General Surgery, Koç University School of Medicine, Istanbul, Turkey; Department of General Surgery, VKV American Hospital, Istanbul, Turkey
| | - Emre Balik
- Department of General Surgery, Koç University School of Medicine, Istanbul, Turkey
| | - Bengi Gurses
- Department of Radiology, Koç University School of Medicine, Istanbul, Turkey
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Kim K, Mercer J, John V, Mathew S, Kochhar R. Imaging Features of Anal Carcinoma after Chemoradiation. Radiographics 2025; 45:e240119. [PMID: 40080437 DOI: 10.1148/rg.240119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/15/2025]
Abstract
Anal cancer is a rare malignancy that is primarily treated with chemoradiation therapy (CRT). Clinical examination of the anal canal after CRT is often limited owing to the patient's discomfort. Therefore, radiologic surveillance plays a fundamental role in treatment response assessment. Currently recommended imaging modalities for posttreatment follow-up include pelvic MRI for local response evaluation and CT for evaluation of possible distant metastases. Patients who demonstrate a complete treatment response undergo regular clinical and imaging surveillance. Cases demonstrating an equivocal treatment response, an incomplete response, or disease progression should be streamlined for biopsy confirmation of the suspicious site and considered for salvage abdominoperineal resection. Radiologic differentiation of post-CRT inflammatory changes versus residual tumor, particularly in the early post-CRT period, can be challenging. However, careful interrogation of T2-weighted MR images correlated with matching diffusion-weighted and apparent diffusion coefficient images can increase reader confidence. The role of fluorine 18-fluorodeoxyglucose (FDG) PET/CT in assessing the response to anal cancer treatment is a debated topic. However, emerging research suggests that FDG PET/CT is complementary to pelvic MRI for accurate treatment response assessment, providing additional metabolic information. In this article, the authors provide a comprehensive review of the post-CRT imaging appearances of anal cancer, including examples from the spectrum of disease responses and therapy-related complications, and describe the strengths and limitations of pelvic MRI and FDG PET/CT. The authors also share the pearls and pitfalls in differentiating residual tumor from posttreatment inflammatory mimics. ©RSNA, 2025 Supplemental material is available for this article.
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Affiliation(s)
- Kyungmin Kim
- From the Department of Radiology, Division of Diagnostics and Support, Christie Hospital, The Christie NHS Foundation Trust, 202 Palatine Rd, Manchester, United Kingdom, M20 2WG (K.K., J.M., V.J., S.M., R.K.); Department of Radiology, Division of Diagnostics and Support, Mersey and West Lancashire Teaching Hospitals NHS Foundation Trust, Prescot, United Kingdom (K.K., V.J.); and Department of Radiology, Division of Diagnostics and Support, Lancashire Teaching Hospitals NHS Foundation Trust, Lancashire, United Kingdom (S.M.)
| | - Joseph Mercer
- From the Department of Radiology, Division of Diagnostics and Support, Christie Hospital, The Christie NHS Foundation Trust, 202 Palatine Rd, Manchester, United Kingdom, M20 2WG (K.K., J.M., V.J., S.M., R.K.); Department of Radiology, Division of Diagnostics and Support, Mersey and West Lancashire Teaching Hospitals NHS Foundation Trust, Prescot, United Kingdom (K.K., V.J.); and Department of Radiology, Division of Diagnostics and Support, Lancashire Teaching Hospitals NHS Foundation Trust, Lancashire, United Kingdom (S.M.)
| | - Victoria John
- From the Department of Radiology, Division of Diagnostics and Support, Christie Hospital, The Christie NHS Foundation Trust, 202 Palatine Rd, Manchester, United Kingdom, M20 2WG (K.K., J.M., V.J., S.M., R.K.); Department of Radiology, Division of Diagnostics and Support, Mersey and West Lancashire Teaching Hospitals NHS Foundation Trust, Prescot, United Kingdom (K.K., V.J.); and Department of Radiology, Division of Diagnostics and Support, Lancashire Teaching Hospitals NHS Foundation Trust, Lancashire, United Kingdom (S.M.)
| | - Smitha Mathew
- From the Department of Radiology, Division of Diagnostics and Support, Christie Hospital, The Christie NHS Foundation Trust, 202 Palatine Rd, Manchester, United Kingdom, M20 2WG (K.K., J.M., V.J., S.M., R.K.); Department of Radiology, Division of Diagnostics and Support, Mersey and West Lancashire Teaching Hospitals NHS Foundation Trust, Prescot, United Kingdom (K.K., V.J.); and Department of Radiology, Division of Diagnostics and Support, Lancashire Teaching Hospitals NHS Foundation Trust, Lancashire, United Kingdom (S.M.)
| | - Rohit Kochhar
- From the Department of Radiology, Division of Diagnostics and Support, Christie Hospital, The Christie NHS Foundation Trust, 202 Palatine Rd, Manchester, United Kingdom, M20 2WG (K.K., J.M., V.J., S.M., R.K.); Department of Radiology, Division of Diagnostics and Support, Mersey and West Lancashire Teaching Hospitals NHS Foundation Trust, Prescot, United Kingdom (K.K., V.J.); and Department of Radiology, Division of Diagnostics and Support, Lancashire Teaching Hospitals NHS Foundation Trust, Lancashire, United Kingdom (S.M.)
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Yacoub H, Zenzri Y, Cherif D, Ben Mansour H, Attia N, Mokrani C, Ben Zid K, Letaief F, Maamouri N, Mezlini A. Predictors of pathological complete response after total neoadjuvant treatment using short course radiotherapy for locally advanced rectal cancer. BMC Gastroenterol 2025; 25:208. [PMID: 40165151 PMCID: PMC11956259 DOI: 10.1186/s12876-025-03709-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 02/18/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Total neoadjuvant treatment (TNT) has become a standard treatment approach for locally advanced rectal cancer (LARC). Patients achieving pathological complete response (pCR) following TNT have better outcomes (overall survival, relapse free survival). However, not all patients treated for LARC with neoadjuvant treatment achieve pCR. AIM The aim of our study was to assess the rate and predictors of pCR. MATERIALS AND METHODS We performed a retrospective study at medical oncology unit in a tertiary care teaching hospital. All consecutive LARC patients without any evidence of distant metastasis who underwent neoadjuvant chemoradiotherapy and surgery between June 2020 and January 2023 were included in the research. Pathological response to neoadjuvant treatment was assessed using Mandard grading system and response was categorized as pCR or not‑pCR. Two different standardized protocols for the neoadjuvant treatment were used: the first group was treated with induction chemotherapy followed by short course radiotherapy and the second group was treated with the RAPIDO protocol. Correlation between different studied parameters and pCR was determined using univariate and multivariate logistic regression analysis. RESULTS The mean age of the 91 included patients (46 men and 45 women) was 58.53 ± 10.3 years. Twenty (22%) were found to have a pCR (Mandard TRG1) in the operative specimen. In univariate analysis, patients less than 60 years, continuation of chemotherapy and patients treated with the induction chemotherapy followed by short course radiotherapy showed a better pCR as compared to patients treated with Rapido protocol (p = 0.043, p = 0.0001 and p = 0.021 respectively). Patients with mucinous component had low pCR rates (p = 0.021). On logistic regression analysis, chemotherapy continuation (OR = 10.27, 95% CI = 2,14-49.32), and absence of mucinous component (OR = 12.6, 95% CI = 3.1-40.32) were significant predictors of pCR. The median survival was 37.7 months. CONCLUSION Mucinous component and chemotherapy interruption are associated with lower pCR rates. Integrating these factors into personalized treatment algorithms may help optimize therapeutic strategies and improve outcomes for patients with LARC.
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Affiliation(s)
- Haythem Yacoub
- Gastroenterolgy department, La Rabta Hospital, Tunis, Tunisia.
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia.
| | - Yosr Zenzri
- Oncology department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Dhouha Cherif
- Gastroenterolgy department, La Rabta Hospital, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Hajer Ben Mansour
- Oncology department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Najla Attia
- Radiotherapy department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Cyrine Mokrani
- Radiotherapy department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Khadija Ben Zid
- Radiotherapy department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Feryel Letaief
- Oncology department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Nadia Maamouri
- Oncology department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Amel Mezlini
- Oncology department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
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Gong X, Ye Z, Shen Y, Song B. Enhancing the role of MRI in rectal cancer: advances from staging to prognosis prediction. Eur Radiol 2025:10.1007/s00330-025-11463-x. [PMID: 40045072 DOI: 10.1007/s00330-025-11463-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 12/19/2024] [Accepted: 01/28/2025] [Indexed: 03/17/2025]
Abstract
Rectal cancer (RC) is one of the major health challenges worldwide. Accurate staging, restaging, invasiveness assessment, and treatment efficacy evaluation are crucial for its clinical management. Magnetic resonance imaging (MRI) plays a significant role in these processes. However, standard MRI techniques, including T2-weighted and diffusion-weighted imaging, have uncertainties in identifying early-stage tumors, high-risk nodules, extramural vascular invasion, and treatment efficacy, potentially leading to inappropriate treatment. Recent advances suggest that the integration of traditional MRI methods, including diffusion-weighted imaging, opposed-phase or contrast-enhanced T1-weighted imaging, as well as emerging synthetic MRI, could address these challenges. Additionally, improvements in imaging technology have spurred research into advanced functional MRI techniques such as diffusion kurtosis imaging and amide proton transfer weighted MRI, yielding promising results in RC assessment. Total neoadjuvant therapy has emerged as a new treatment paradigm for locally advanced RC, with neoadjuvant immunotherapy and chemotherapy offering viable alternatives to neoadjuvant chemoradiotherapy. However, the lack of standards for the early prediction of patient survival and tumor response to neoadjuvant therapy highlights a critical unmet need in matching therapies to suitable patients. Furthermore, organ preservation strategies after neoadjuvant therapy provide personalized options based on tumor response and patient preferences, yet traditional MRI assessments show significant variability. Radiomics and artificial intelligence hold promise for revealing complex patterns in MRI images associated with patient prognosis and treatment response. This review provides an overview of current MRI advancements in RC assessment and emphasizes how future research can refine tailored treatment strategies to improve patient outcomes. KEY POINTS: Question The accurate diagnosis of early-stage rectal tumors, high-risk nodules, treatment responses, and the early prediction of patient survival and therapeutic outcomes remain an unmet need. Findings Visual MRI has improved staging, restaging, and invasiveness evaluation. Advanced MRI, radiomics and artificial intelligence provide significant potential for tumor characterization and outcome prediction. Clinical relevance Advances in visual MRI are improving routine imaging protocols and radiomics and artificial intelligence show promise in enhancing treatment decisions through precise tumor characterization and outcome prediction.
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Affiliation(s)
- Xiaoling Gong
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
| | - Zheng Ye
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
| | - Yu Shen
- Colorectal Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Bin Song
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, China.
- Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China.
- Department of Radiology, Sanya People's Hospital, Sanya, China.
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8
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Jong BK, Yu ZH, Hsu YJ, Chiang SF, You JF, Chern YJ. Deep learning algorithms for predicting pathological complete response in MRI of rectal cancer patients undergoing neoadjuvant chemoradiotherapy: a systematic review. Int J Colorectal Dis 2025; 40:19. [PMID: 39833443 PMCID: PMC11753312 DOI: 10.1007/s00384-025-04809-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/08/2025] [Indexed: 01/22/2025]
Abstract
PURPOSE This systematic review examines the utility of deep learning algorithms in predicting pathological complete response (pCR) in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (nCRT). The primary goal is to evaluate the performance of MRI-based artificial intelligence (AI) models and explore factors affecting their diagnostic accuracy. METHODS The review followed PRISMA guidelines and is registered with PROSPERO (CRD42024628017). Literature searches were conducted in PubMed, Embase, and Cochrane Library using keywords such as "artificial intelligence," "rectal cancer," "MRI," and "pathological complete response." Articles involving deep learning models applied to MRI for predicting pCR were included, excluding non-MRI data and studies without AI applications. Data on study characteristics, MRI sequences, AI model details, and performance metrics were extracted. Quality assessment was performed using the PROBAST tool. RESULTS Out of 512 initial records, 26 studies met the inclusion criteria. Most studies demonstrated promising diagnostic performance, with AUC values for external validation typically exceeding 0.8. The use of T2W and diffusion-weighted imaging (DWI) MRI phases enhanced model accuracy compared to T2W alone. Larger datasets generally correlated with improved model performance. However, heterogeneity in model designs, MRI protocols, and the limited integration of clinical data were noted as challenges. CONCLUSION AI-enhanced MRI demonstrates significant potential in predicting pCR in rectal cancer, particularly with T2W + DWI sequences and larger datasets. While integrating clinical data remains controversial, standardizing methodologies and expanding datasets will further enhance model robustness and clinical utility.
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Affiliation(s)
- Bor-Kang Jong
- Colorectal Section, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Zhen-Hao Yu
- Colorectal Section, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yu-Jen Hsu
- Colorectal Section, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Sum-Fu Chiang
- Colorectal Section, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jeng-Fu You
- Colorectal Section, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yih-Jong Chern
- Colorectal Section, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
- School of Medicine, Chang Gung University, Taoyuan, Taiwan.
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Eijkelenkamp H, Grimbergen G, McDonald B, Rutgers R, Schakel T, Beijst C, Philippens M, Meijer G, Intven M. Repeatability of rectal cancer apparent diffusion coefficient measurements on a 1.5 T MR-linac. Phys Imaging Radiat Oncol 2025; 33:100720. [PMID: 40104214 PMCID: PMC11914820 DOI: 10.1016/j.phro.2025.100720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 01/26/2025] [Accepted: 01/28/2025] [Indexed: 03/20/2025] Open
Abstract
The repeatability of the apparent diffusion coefficient (ADC) during radiotherapy for rectal cancer on a 1.5 T MR-linac was investigated by acquiring two sequential diffusion-weighted imaging (DWI) sequences at each fraction. In 109 treatment sessions involving 22 patients, tumors were separately delineated on the b500 images. ADC maps were generated with all b-values (0, 30, 150, and 500 s/mm2) on the MR-linac, and the median ADC values were used in Bland-Altman analyses. A relative repeatability coefficient of 17.0 % was determined, providing a threshold to differentiate between measurement variability and true treatment response. This threshold can be used for potential response monitoring and personalized treatment adjustments.
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Affiliation(s)
- Hidde Eijkelenkamp
- University Medical Center Utrecht, Department of Radiotherapy, Utrecht, the Netherlands
| | - Guus Grimbergen
- University Medical Center Utrecht, Department of Radiotherapy, Utrecht, the Netherlands
| | - Brigid McDonald
- University of Texas MD Anderson Cancer Center, Department of Radiation Oncology, Houston, USA
| | - Reijer Rutgers
- University Medical Center Utrecht, Department of Radiotherapy, Utrecht, the Netherlands
| | - Tim Schakel
- University Medical Center Utrecht, Department of Radiotherapy, Utrecht, the Netherlands
| | - Casper Beijst
- University Medical Center Utrecht, Department of Radiotherapy, Utrecht, the Netherlands
| | - Marielle Philippens
- University Medical Center Utrecht, Department of Radiotherapy, Utrecht, the Netherlands
| | - Gert Meijer
- University Medical Center Utrecht, Department of Radiotherapy, Utrecht, the Netherlands
| | - Martijn Intven
- University Medical Center Utrecht, Department of Radiotherapy, Utrecht, the Netherlands
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10
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Demidova EV, Czyzewicz P, Hasan A, Avkshtol V, Lesh RW, Handorf E, Devarajan K, Schultz BM, James JD, Connolly DC, Einarson MB, Baldwin D, Golemis EA, Meyer JE, Arora S. Optimizing and Validating Systemic DNA Damage Response Profiling to Predict Neoadjuvant Chemoradiation Response in Rectal Cancer. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.11.22.24317789. [PMID: 39606370 PMCID: PMC11601745 DOI: 10.1101/2024.11.22.24317789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2024]
Abstract
Purpose This study aimed to stratify patients with locally advanced rectal cancer (LARC) based on their response to neoadjuvant chemoradiation therapy (nCRT) using DNA damage response (DDR)-related proteins measured in peripheral blood monocytes (PBMCs). We optimized and validated an innovative assay to quantify these proteins, providing a predictive framework for nCRT response. Experimental Design We used PBMCs collected from LARC patients either before or after standard course of ∼5.5 weeks of nCRT, with patients categorized by neoadjuvant rectal (NAR) score. DDR was assessed by immunofluorescence (γH2AX S139 foci), and by Luminex multi-analyte platform (xMAP) assay providing semi-quantitative assessment of phosphorylated Chk1 S345 , Chk2 T68 , γH2AX S139 , p53 S15 and total ATR, MDM2, p21. Assay performance was evaluated using reference controls and banked PBMCs from healthy controls (n=50). Results PBMCs from poor responders (PoR; NAR >14; n=21) had significantly lower γH2AX S139 foci than complete responders (CR; NAR <1; n=21) (p<0.0001), with no significant differences between pre- and post-nCRT samples (p=0.4961). The xMAP assay performance assessment showed linear sample curves, precision with acceptable inter- and intra-assay coefficients of variability, and high reproducibility with ∼1% outliers in replicates. Clinical associations using the xMAP assay found levels of six proteins (ATR, MDM2, Chk1 S345 , Chk2 T68 , γH2AX S139 , p53 S15 ) significantly differentiating CRs from PoRs (p ≤ 1e-5). Univariate CART analysis determined thresholds that segregated PoRs from CRs with high precision (p<0.001). Conclusion We optimized an assay to assess DDR proteins in PBMCs and identified specific proteins, along with their threshold levels, that can accurately predict response to nCRT in patients with LARC. Translational Relevance Although neoadjuvant chemoradiation therapy followed by surgery is the standard of care for patients with locally advanced rectal cancer (LARC), many patients do not benefit from this treatment and suffer from its side effects. The motivation for this study was to reliably identify patients with LARC who will or will not respond to treatment, thereby permitting more effective direction of therapy only to likely responders. In this report, we describe identification and optimization of a novel multianalyte assay for patients diagnosed with LARC. This assay uses a Luminex xMAP platform to detect DNA damage response (DDR) signaling proteins in peripheral blood monocytes of pre-treatment patients. This assay, detecting the DDR proteins, effectively segregates responders from non-responders (p ≤ 1e-5), supporting optimization of treatment efficacy and reduction of unnecessary toxicity, thus advancing personalized medicine in oncology.
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11
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Zhang X, Lin Z, Feng Y, Lin Z, Tao K, Zhang T, Lan X. Predicting Pathologic Complete Response in Locally Advanced Rectal Cancer with [ 68Ga]Ga-FAPI-04 PET, [ 18F]FDG PET, and Contrast-Enhanced MRI: Lesion-to-Lesion Comparison with Pathology. J Nucl Med 2024; 65:1548-1556. [PMID: 39353648 DOI: 10.2967/jnumed.124.267581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 08/13/2024] [Indexed: 10/04/2024] Open
Abstract
Neoadjuvant therapy in patients with locally advanced rectal cancer (LARC) has achieved good pathologic complete response (pCR) rates, potentially eliminating the need for surgical intervention. This study investigated preoperative methods for predicting pCR after neoadjuvant short-course radiotherapy (SCRT) combined with immunochemotherapy. Methods: Treatment-naïve patients with histologically confirmed LARC were enrolled from February 2023 to July 2023. Before surgery, the patients received neoadjuvant SCRT followed by 2 cycles of capecitabine and oxaliplatin plus camrelizumab. 68Ga-labeled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI-04) PET/MRI, [18F]FDG PET/CT, and contrast-enhanced MRI were performed before treatment initiation and before surgery in each patient. PET and MRI features and the size and number of lesions were also collected from each scan. Each parameter's sensitivity, specificity, and diagnostic cutoff were derived via receiver-operating-characteristic curve analysis. Results: Twenty eligible patients (13 men, 7 women; mean age, 60.2 y) were enrolled and completed the entire trial, and all patients had proficient mismatch repair or microsatellite-stable LARC. A postoperative pCR was achieved in 9 patients (45.0%). In the visual evaluation, both [68Ga]Ga-FAPI-04 PET/MRI and [18F]FDG PET/CT were limited to forecasting pCR. Contrast-enhanced MRI had a low sensitivity of 55.56% to predict pCR. In the quantitative evaluation, [68Ga]Ga-FAPI-04 change in SULpeak percentage, where SULpeak is SUVpeak standardized by lean body mass, had the largest area under the curve (0.929) with high specificity (sensitivity, 77.78%; specificity, 100.0%; cutoff, 63.92%). Conclusion: [68Ga]Ga-FAPI-04 PET/MRI is a promising imaging modality for predicting pCR after SCRT combined with immunochemotherapy. The SULpeak decrease exceeding 63.92% may provide valuable guidance in selecting patients who can forgo surgery after neoadjuvant therapy.
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Affiliation(s)
- Xiao Zhang
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, China
- Key Laboratory of Biological Targeted Therapy, Ministry of Education, Wuhan, China
| | - Zhenyu Lin
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and
| | - Yuan Feng
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, China
- Key Laboratory of Biological Targeted Therapy, Ministry of Education, Wuhan, China
| | - Zhaoguo Lin
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, China
- Key Laboratory of Biological Targeted Therapy, Ministry of Education, Wuhan, China
| | - Kaixiong Tao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and
| | - Xiaoli Lan
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;
- Hubei Key Laboratory of Molecular Imaging, Wuhan, China
- Key Laboratory of Biological Targeted Therapy, Ministry of Education, Wuhan, China
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12
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Bratu LD, Schenker M, Stovicek PO, Schenker RA, Mehedințeanu AM, Berisha TC, Donoiu A, Mogoantă SȘ. Retrospective Evaluation of the Efficacy of Total Neoadjuvant Therapy and Chemoradiotherapy Neoadjuvant Treatment in Relation to Surgery in Patients with Rectal Cancer. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:656. [PMID: 38674302 PMCID: PMC11052151 DOI: 10.3390/medicina60040656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 04/14/2024] [Accepted: 04/16/2024] [Indexed: 04/28/2024]
Abstract
Background and Objective: In the therapeutic strategy of rectal cancer, radiotherapy has consolidated its important position and frequent use in current practice due to its indications as neoadjuvant, adjuvant, definitive, or palliative treatment. In recent years, total neoadjuvant therapy (TNT) has been established as the preferred regimen compared to concurrent neoadjuvant chemoradiotherapy (CRT). In relation to better outcomes, the percentage of patients who achieved pathological complete response (pCR) after neoadjuvant treatment is higher in the case of TNT. This study aimed to analyze the response to TNT compared to neoadjuvant CRT regarding pCR rate and the change in staging after surgical intervention. Materials and Methods: We performed a retrospective study on 323 patients with rectal cancer and finally analyzed the data of 201 patients with neoadjuvant treatment, selected based on the inclusion and exclusion criteria. Patients received CRT neoadjuvant therapy or TNT neoadjuvant therapy with FOLFOX or CAPEOX. Results: Out of 157 patients who underwent TNT treatment, 19.74% had pathological complete response, whereas in the group with CRT (n = 44), those with pCR were 13.64%. After neoadjuvant treatment, the most frequent TNM classifications were ypT2 (40.30%) and ypN0 (79.10%). The statistical analysis of the postoperative disease stage, after neoadjuvant therapy, showed that the most frequent changes were downstaging (71.14%) and complete response (18.41%). Only four patients (1.99%) had an upstaging change. The majority of patients (88.56%) initially presented clinical evidence of nodal involvement whereas only 20.9% of the patients still presented regional disease at the time of surgical intervention. Conclusions: By using TNT, a higher rate of stage reduction is obtained compared to the neoadjuvant CRT treatment. The post-neoadjuvant-treatment imagistic evaluation fails to accurately evaluate the response. A better response to TNT was observed in young patients.
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Affiliation(s)
- Lucian Dragoș Bratu
- Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania (T.C.B.); (A.D.)
- Sf. Nectarie Oncology Center, 200347 Craiova, Romania; (R.A.S.); (A.M.M.)
| | - Michael Schenker
- Sf. Nectarie Oncology Center, 200347 Craiova, Romania; (R.A.S.); (A.M.M.)
- Department of Oncology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Puiu Olivian Stovicek
- Sf. Nectarie Oncology Center, 200347 Craiova, Romania; (R.A.S.); (A.M.M.)
- Department of Pharmacology, Faculty of Nursing, Târgu Jiu Subsidiary, Titu Maiorescu University, 040441 Bucharest, Romania
| | | | | | - Tradian Ciprian Berisha
- Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania (T.C.B.); (A.D.)
- Sf. Nectarie Oncology Center, 200347 Craiova, Romania; (R.A.S.); (A.M.M.)
| | - Andreas Donoiu
- Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania (T.C.B.); (A.D.)
- 3rd General Surgery Clinic, Emergency County Hospital, 200642 Craiova, Romania;
| | - Stelian Ștefăniță Mogoantă
- 3rd General Surgery Clinic, Emergency County Hospital, 200642 Craiova, Romania;
- Department of Surgery, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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13
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Zhong X, Zeng G, Zhang L, You S, Fu Y, He W, Liao G. Prediction of pathologic complete response to neoadjuvant chemoradiation in locally advanced rectal cancer. Front Oncol 2024; 14:1361300. [PMID: 38529385 PMCID: PMC10961458 DOI: 10.3389/fonc.2024.1361300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Accepted: 02/19/2024] [Indexed: 03/27/2024] Open
Abstract
Purpose To investigate the predictive factors of pathologic complete response (pCR) in locally advanced rectal cancer (LARC) patients who had been treated with neoadjuvant chemoradiation (nCRT). Methods and materials For this retrospective study, 53 LARC patients (37 males and 16 females; age range 25 to 79 years) were selected. Clinical characteristics, baseline mrTNM staging, MR gross tumor volumes (GTV), and pCR were evaluated. The diagnostic accuracy of GTV for predicting pCR was calculated. Results Among 53 LARC patients, 15 patients achieved pCR (28.3%), while 38 patients achieved non-pCR. Only three (5.7%) out of 53 patients did not downstage after nCRT. GTV and tumor differentiation were the significant prognostic parameters for predicting pCR. A tumor volume threshold of 21.1 cm3 was determined as a predictor for pCR, with a sensitivity of 84% and specificity of 47%. In addition, GTV was associated with mrN stage, circumferential resection margin (CRM) status, extramural vascular invasion (EMVI) status, and pretreatment serum CEA level. Conclusion Tumor volume and tumor differentiation have significant predictive values in preoperative assessment of pCR among LARC patients. These findings aid clinicians to discriminate those patients who may likely benefit from preoperative regimens and to make optimal treatment plans.
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Affiliation(s)
- Xiaoling Zhong
- Department of Radiology, Shenzhen People's Hospital (The Second Clinical Medical College of Jinan University, the First Affiliated Hospital of Southern University of Science and Technology), Shenzhen, Guangdong, China
| | - Guohua Zeng
- Department of Radiology, Shenzhen People's Hospital (The Second Clinical Medical College of Jinan University, the First Affiliated Hospital of Southern University of Science and Technology), Shenzhen, Guangdong, China
| | - Lixiang Zhang
- Department of Radiology, Shenzhen People's Hospital (The Second Clinical Medical College of Jinan University, the First Affiliated Hospital of Southern University of Science and Technology), Shenzhen, Guangdong, China
| | - Shuyuan You
- Department of Pathology, Shenzhen People's Hospital (The Second Clinical Medical College of Jinan University, the First Affiliated Hospital of Southern University of Science and Technology), Shenzhen, China
| | - Yuxiang Fu
- Department of Gastrointestinal surgery, Shenzhen People's Hospital (The Second Clinical Medical College of Jinan University, the First Affiliated Hospital of Southern University of Science and Technology), Shenzhen, China
| | - Wan He
- Department of Oncology, Shenzhen People's Hospital (The Second Clinical Medical College of Jinan University, the First Affiliated Hospital of Southern University of Science and Technology), Shenzhen, China
| | - Guixiang Liao
- Department of Radiation Oncology, Shenzhen People's Hospital (The Second Clinical Medical College of Jinan University, the First Affiliated Hospital of Southern University of Science and Technology), Shenzhen, China
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14
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Hanekamp BA, Viktil E, Slørdahl KS, Dormagen JB, Kløw NE, Malinen E, Brunborg C, Guren MG, Schulz A. Magnetic resonance imaging of anal cancer: tumor characteristics and early prediction of treatment outcome. Strahlenther Onkol 2024; 200:19-27. [PMID: 37429949 PMCID: PMC10784345 DOI: 10.1007/s00066-023-02114-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Accepted: 06/18/2023] [Indexed: 07/12/2023]
Abstract
PURPOSE To analyze tumor characteristics derived from pelvic magnetic resonance imaging (MRI) of patients with squamous cell carcinoma of the anus (SCCA) before and during chemoradiotherapy (CRT), and to compare the changes in these characteristics between scans of responders vs. nonresponders to CRT. METHODS We included 52 patients with a pelvic 3T MRI scan prior to CRT (baseline scan); 39 of these patients received an additional scan during week 2 of CRT (second scan). Volume, diameter, extramural tumor depth (EMTD), and external anal sphincter infiltration (EASI) of the tumor were assessed. Mean, kurtosis, skewness, standard deviation (SD), and entropy values were extracted from apparent diffusion coefficient (ADC) histograms. The main outcome was locoregional treatment failure. Correlations were evaluated with Wilcoxon's signed rank-sum test and Pearson's correlation coefficient, quantile regression, univariate logistic regression, and area under the ROC curve (AUC) analyses. RESULTS In isolated analyses of the baseline and second MRI scans, none of the characteristics were associated with outcome. Comparison between the scans showed significant changes in several characteristics: volume, diameter, EMTD, and ADC skewness decreased in the second scan, although the mean ADC increased. Small decreases in volume and diameter were associated with treatment failure, and these variables had the highest AUC values (0.73 and 0.76, respectively) among the analyzed characteristics. CONCLUSION Changes in tumor volume and diameter in an early scan during CRT could represent easily assessable imaging-based biomarkers to eliminate the need for analysis of more complex MRI characteristics.
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Affiliation(s)
- Bettina A Hanekamp
- Department of Radiology, Oslo University Hospital Ullevål, Oslo, Norway.
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
| | - Ellen Viktil
- Department of Radiology, Oslo University Hospital Ullevål, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Kathinka S Slørdahl
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Oncology, Oslo University Hospital Ullevål, Oslo, Norway
| | | | - Nils E Kløw
- Department of Radiology, Oslo University Hospital Ullevål, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Eirik Malinen
- Department of Physics, University of Oslo, Oslo, Norway
- Department of Medical Physics, Oslo University Hospital, Oslo, Norway
| | - Cathrine Brunborg
- Oslo Centre for Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, Oslo, Norway
| | - Marianne G Guren
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Oncology, Oslo University Hospital Ullevål, Oslo, Norway
| | - Anselm Schulz
- Department of Radiology, Oslo University Hospital Ullevål, Oslo, Norway
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15
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Schurink NW, van Kranen SR, van Griethuysen JJM, Roberti S, Snaebjornsson P, Bakers FCH, de Bie SH, Bosma GPT, Cappendijk VC, Geenen RWF, Neijenhuis PA, Peterson GM, Veeken CJ, Vliegen RFA, Peters FP, Bogveradze N, El Khababi N, Lahaye MJ, Maas M, Beets GL, Beets-Tan RGH, Lambregts DMJ. Development and multicenter validation of a multiparametric imaging model to predict treatment response in rectal cancer. Eur Radiol 2023; 33:8889-8898. [PMID: 37452176 PMCID: PMC10667134 DOI: 10.1007/s00330-023-09920-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/18/2023]
Abstract
OBJECTIVES To develop and validate a multiparametric model to predict neoadjuvant treatment response in rectal cancer at baseline using a heterogeneous multicenter MRI dataset. METHODS Baseline staging MRIs (T2W (T2-weighted)-MRI, diffusion-weighted imaging (DWI) / apparent diffusion coefficient (ADC)) of 509 patients (9 centres) treated with neoadjuvant chemoradiotherapy (CRT) were collected. Response was defined as (1) complete versus incomplete response, or (2) good (Mandard tumor regression grade (TRG) 1-2) versus poor response (TRG3-5). Prediction models were developed using combinations of the following variable groups: (1) Non-imaging: age/sex/tumor-location/tumor-morphology/CRT-surgery interval (2) Basic staging: cT-stage/cN-stage/mesorectal fascia involvement, derived from (2a) original staging reports, or (2b) expert re-evaluation (3) Advanced staging: variables from 2b combined with cTN-substaging/invasion depth/extramural vascular invasion/tumor length (4) Quantitative imaging: tumour volume + first-order histogram features (from T2W-MRI and DWI/ADC) Models were developed with data from 6 centers (n = 412) using logistic regression with the Least Absolute Shrinkage and Selector Operator (LASSO) feature selection, internally validated using repeated (n = 100) random hold-out validation, and externally validated using data from 3 centers (n = 97). RESULTS After external validation, the best model (including non-imaging and advanced staging variables) achieved an area under the curve of 0.60 (95%CI=0.48-0.72) to predict complete response and 0.65 (95%CI=0.53-0.76) to predict a good response. Quantitative variables did not improve model performance. Basic staging variables consistently achieved lower performance compared to advanced staging variables. CONCLUSIONS Overall model performance was moderate. Best results were obtained using advanced staging variables, highlighting the importance of good-quality staging according to current guidelines. Quantitative imaging features had no added value (in this heterogeneous dataset). CLINICAL RELEVANCE STATEMENT Predicting tumour response at baseline could aid in tailoring neoadjuvant therapies for rectal cancer. This study shows that image-based prediction models are promising, though are negatively affected by variations in staging quality and MRI acquisition, urging the need for harmonization. KEY POINTS This multicenter study combining clinical information and features derived from MRI rendered disappointing performance to predict response to neoadjuvant treatment in rectal cancer. Best results were obtained with the combination of clinical baseline information and state-of-the-art image-based staging variables, highlighting the importance of good quality staging according to current guidelines and staging templates. No added value was found for quantitative imaging features in this multicenter retrospective study. This is likely related to acquisition variations, which is a major problem for feature reproducibility and thus model generalizability.
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Affiliation(s)
- Niels W Schurink
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | - Simon R van Kranen
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Joost J M van Griethuysen
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | - Sander Roberti
- Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Petur Snaebjornsson
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Frans C H Bakers
- Department of Radiology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Shira H de Bie
- Department of Radiology, Deventer Ziekenhuis, Schalkhaar, The Netherlands
| | - Gerlof P T Bosma
- Department of Interventional Radiology, Elisabeth Tweesteden Hospital, Tilburg, The Netherlands
| | - Vincent C Cappendijk
- Department of Radiology, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands
| | - Remy W F Geenen
- Department of Radiology, Northwest Clinics, Alkmaar, The Netherlands
| | | | | | - Cornelis J Veeken
- Department of Radiology, IJsselland Hospital, Capelle aan den IJssel, The Netherlands
| | - Roy F A Vliegen
- Department of Radiology, Zuyderland Medical Center, Heerlen, The Netherlands
| | - Femke P Peters
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Nino Bogveradze
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
- Department of Radiology, Acad. F. Todua Medical Center, Research Institute of Clinical Medicine, Tbilisi, Georgia
| | - Najim El Khababi
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | - Max J Lahaye
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | - Monique Maas
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | - Geerard L Beets
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
- Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Regina G H Beets-Tan
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
- Institute of Regional Health Research, University of Southern Denmark, Vejle, Denmark
| | - Doenja M J Lambregts
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands.
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16
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Amintas S, Giraud N, Fernandez B, Dupin C, Denost Q, Garant A, Frulio N, Smith D, Rullier A, Rullier E, Vuong T, Dabernat S, Vendrely V. The Crying Need for a Better Response Assessment in Rectal Cancer. Curr Treat Options Oncol 2023; 24:1507-1523. [PMID: 37702885 PMCID: PMC10643426 DOI: 10.1007/s11864-023-01125-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/09/2023] [Indexed: 09/14/2023]
Abstract
OPINION STATEMENT Since total neoadjuvant treatment achieves almost 30% pathologic complete response, organ preservation has been increasingly debated for good responders after neoadjuvant treatment for patients diagnosed with rectal cancer. Two organ preservation strategies are available: a watch and wait strategy and a local excision strategy including patients with a near clinical complete response. A major issue is the selection of patients according to the initial tumor staging or the response assessment. Despite modern imaging improvement, identifying complete response remains challenging. A better selection could be possible by radiomics analyses, exploiting numerous image features to feed data characterization algorithms. The subsequent step is to include baseline and/or pre-therapeutic MRI, PET-CT, and CT radiomics added to the patients' clinicopathological data, inside machine learning (ML) prediction models, with predictive or prognostic purposes. These models could be further improved by the addition of new biomarkers such as circulating tumor biomarkers, molecular profiling, or pathological immune biomarkers.
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Affiliation(s)
- Samuel Amintas
- Tumor Biology and Tumor Bank Laboratory, CHU Bordeaux, F-33600, Pessac, France.
- BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux, F-33000, Bordeaux, France.
| | - Nicolas Giraud
- Department of Radiation Oncology, CHU Bordeaux, F-33000, Bordeaux, France
| | | | - Charles Dupin
- BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux, F-33000, Bordeaux, France
- Department of Radiation Oncology, CHU Bordeaux, F-33000, Bordeaux, France
| | - Quentin Denost
- Bordeaux Colorectal Institute, F-33000, Bordeaux, France
| | - Aurelie Garant
- UT Southwestern Department of Radiation Oncology, Dallas, USA
| | - Nora Frulio
- Radiology Department, CHU Bordeaux, F-33600, Pessac, France
| | - Denis Smith
- Department of Digestive Oncology, CHU Bordeaux, F-33600, Pessac, France
| | - Anne Rullier
- Histology Department, CHU Bordeaux, F-33000, Bordeaux, France
| | - Eric Rullier
- BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux, F-33000, Bordeaux, France
- Surgery Department, CHU Bordeaux, F-33600, Pessac, France
| | - Te Vuong
- Department of Radiation Oncology, McGill University, Jewish General Hospital, Montreal, Canada
| | - Sandrine Dabernat
- BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux, F-33000, Bordeaux, France
- Biochemistry Department, CHU Bordeaux, F-33000, Bordeaux, France
| | - Véronique Vendrely
- BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux, F-33000, Bordeaux, France
- Department of Radiation Oncology, CHU Bordeaux, F-33000, Bordeaux, France
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17
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Ou X, van der Reijd DJ, Lambregts DMJ, Grotenhuis BA, van Triest B, Beets GL, Beets-Tan RGH, Maas M. Sense and non-sense of imaging in the era of organ preservation for rectal cancer. Br J Radiol 2023; 96:20230318. [PMID: 37750870 PMCID: PMC10607404 DOI: 10.1259/bjr.20230318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 07/17/2023] [Accepted: 08/01/2023] [Indexed: 09/27/2023] Open
Abstract
This review summarizes the current applications and benefits of imaging modalities for organ preservation in the treatment of rectal cancer. The concept of organ preservation in the treatment of rectal cancer has revolutionized the way rectal cancer is managed. Initially, organ preservation was limited to patients with locally advanced rectal cancer who needed neoadjuvant therapy to reduce tumor size before surgery and achieved complete response. However, neoadjuvant therapy is now increasingly utilized for smaller and less aggressive tumors to achieve primary organ preservation. Additionally, more intensive neoadjuvant strategies are employed to improve complete response rates and increase the chances of successful organ preservation. The selection of patients for organ preservation is a critical component of treatment, and imaging techniques such as digital rectal exam, endoscopy, and MRI are commonly used for this purpose. In this review, we provide an overview of what imaging modalities should be chosen and how they can aid in the selection and follow-up of patients undergoing organ-preserving strategies.
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Affiliation(s)
| | | | | | | | - Baukelien van Triest
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
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18
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Li C, Chen H, Zhang B, Fang Y, Sun W, Wu D, Su Z, Shen L, Wei Q. Radiomics Signature Based on Support Vector Machines for the Prediction of Pathological Complete Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer. Cancers (Basel) 2023; 15:5134. [PMID: 37958309 PMCID: PMC10648149 DOI: 10.3390/cancers15215134] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 10/15/2023] [Accepted: 10/19/2023] [Indexed: 11/15/2023] Open
Abstract
The objective of this study was to evaluate the discriminative capabilities of radiomics signatures derived from three distinct machine learning algorithms and to identify a robust radiomics signature capable of predicting pathological complete response (pCR) after neoadjuvant chemoradiotherapy in patients diagnosed with locally advanced rectal cancer (LARC). In a retrospective study, 211 LARC patients were consecutively enrolled and divided into a training cohort (n = 148) and a validation cohort (n = 63). From pretreatment contrast-enhanced planning CT images, a total of 851 radiomics features were extracted. Feature selection and radiomics score (Radscore) construction were performed using three different machine learning methods: least absolute shrinkage and selection operator (LASSO), random forest (RF) and support vector machine (SVM). The SVM-derived Radscore demonstrated a strong correlation with the pCR status, yielding area under the receiver operating characteristic curves (AUCs) of 0.880 and 0.830 in the training and validation cohorts, respectively, outperforming the RF and LASSO methods. Based on this, a nomogram was developed by combining the SVM-based Radscore with clinical indicators to predict pCR after neoadjuvant chemoradiotherapy. The nomogram exhibited superior predictive power, achieving AUCs of 0.910 and 0.866 in the training and validation cohorts, respectively. Calibration curves and decision curve analyses confirmed its appropriateness. The SVM-based Radscore demonstrated promising performance in predicting pCR for LARC patients. The machine learning-driven nomogram, which integrates the Radscore and clinical indicators, represents a valuable tool for predicting pCR in LARC patients.
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Affiliation(s)
- Chao Li
- Department of Radiation Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; (C.L.); (H.C.); (B.Z.); (W.S.); (D.W.); (Z.S.)
| | - Haiyan Chen
- Department of Radiation Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; (C.L.); (H.C.); (B.Z.); (W.S.); (D.W.); (Z.S.)
| | - Bicheng Zhang
- Department of Radiation Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; (C.L.); (H.C.); (B.Z.); (W.S.); (D.W.); (Z.S.)
| | - Yimin Fang
- Department of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China;
| | - Wenzheng Sun
- Department of Radiation Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; (C.L.); (H.C.); (B.Z.); (W.S.); (D.W.); (Z.S.)
| | - Dang Wu
- Department of Radiation Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; (C.L.); (H.C.); (B.Z.); (W.S.); (D.W.); (Z.S.)
| | - Zhuo Su
- Department of Radiation Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; (C.L.); (H.C.); (B.Z.); (W.S.); (D.W.); (Z.S.)
| | - Li Shen
- Department of Radiation Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; (C.L.); (H.C.); (B.Z.); (W.S.); (D.W.); (Z.S.)
| | - Qichun Wei
- Department of Radiation Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; (C.L.); (H.C.); (B.Z.); (W.S.); (D.W.); (Z.S.)
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19
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El Khababi N, Beets-Tan RGH, Tissier R, Lahaye MJ, Maas M, Curvo-Semedo L, Dresen RC, Nougaret S, Beets GL, Lambregts DMJ. Predicting response to chemoradiotherapy in rectal cancer via visual morphologic assessment and staging on baseline MRI: a multicenter and multireader study. Abdom Radiol (NY) 2023; 48:3039-3049. [PMID: 37358604 PMCID: PMC10480283 DOI: 10.1007/s00261-023-03961-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 05/11/2023] [Accepted: 05/13/2023] [Indexed: 06/27/2023]
Abstract
PURPOSE Pre-treatment knowledge of the anticipated response of rectal tumors to neoadjuvant chemoradiotherapy (CRT) could help to further optimize the treatment. Van Griethuysen et al. proposed a visual 5-point confidence score to predict the likelihood of response on baseline MRI. Aim was to evaluate this score in a multicenter and multireader study setting and compare it to two simplified (4-point and 2-point) adaptations in terms of diagnostic performance, interobserver agreement (IOA), and reader preference. METHODS Twenty-two radiologists from 14 countries (5 MRI-experts,17 general/abdominal radiologists) retrospectively reviewed 90 baseline MRIs to estimate if patients would likely achieve a (near-)complete response (nCR); first using the 5-point score by van Griethuysen (1=highly unlikely to 5=highly likely to achieve nCR), second using a 4-point adaptation (with 1-point each for high-risk T-stage, obvious mesorectal fascia invasion, nodal involvement, and extramural vascular invasion), and third using a 2-point score (unlikely/likely to achieve nCR). Diagnostic performance was calculated using ROC curves and IOA using Krippendorf's alpha (α). RESULTS Areas under the ROC curve to predict the likelihood of a nCR were similar for the three methods (0.71-0.74). IOA was higher for the 5- and 4-point scores (α=0.55 and 0.57 versus 0.46 for the 2-point score) with best results for the MRI-experts (α=0.64-0.65). Most readers (55%) favored the 4-point score. CONCLUSIONS Visual morphologic assessment and staging methods can predict neoadjuvant treatment response with moderate-good performance. Compared to a previously published confidence-based scoring system, study readers preferred a simplified 4-point risk score based on high-risk T-stage, MRF involvement, nodal involvement, and EMVI.
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Affiliation(s)
- Najim El Khababi
- Department of Radiology, The Netherlands Cancer Institute, P.O. Box 90203, 1106 BE, Amsterdam, The Netherlands
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | - Regina G H Beets-Tan
- Department of Radiology, The Netherlands Cancer Institute, P.O. Box 90203, 1106 BE, Amsterdam, The Netherlands
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | - Renaud Tissier
- Biostatistics Unit, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Max J Lahaye
- Department of Radiology, The Netherlands Cancer Institute, P.O. Box 90203, 1106 BE, Amsterdam, The Netherlands
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | - Monique Maas
- Department of Radiology, The Netherlands Cancer Institute, P.O. Box 90203, 1106 BE, Amsterdam, The Netherlands
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | - Luís Curvo-Semedo
- Department of Radiology, Faculty of Medicine, Centro Hospitalar e Universitario de Coimbra EPE, University of Coimbra, Coimbra, Portugal
| | - Raphaëla C Dresen
- Department of Radiology, University Hospitals Leuven, Leuven, Belgium
| | - Stephanie Nougaret
- Medical Imaging Department, Montpellier Cancer Institute, Montpellier Cancer Research Institute (U1194), University of Montpellier, Montpellier, France
| | - Geerard L Beets
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
- Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Doenja M J Lambregts
- Department of Radiology, The Netherlands Cancer Institute, P.O. Box 90203, 1106 BE, Amsterdam, The Netherlands.
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands.
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20
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Kaanders JHAM, Bussink J, Aarntzen EHJG, Braam P, Rütten H, van der Maazen RWM, Verheij M, van den Bosch S. [18F]FDG-PET-Based Personalized Radiotherapy Dose Prescription. Semin Radiat Oncol 2023; 33:287-297. [PMID: 37331783 DOI: 10.1016/j.semradonc.2023.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/20/2023]
Abstract
PET imaging with 2'-deoxy-2'-[18F]fluoro-D-glucose ([18F]FDG) has become one of the pillars in the management of malignant diseases. It has proven value in diagnostic workup, treatment policy, follow-up, and as prognosticator for outcome. [18F]FDG is widely available and standards have been developed for PET acquisition protocols and quantitative analyses. More recently, [18F]FDG-PET is also starting to be appreciated as a decision aid for treatment personalization. This review focuses on the potential of [18F]FDG-PET for individualized radiotherapy dose prescription. This includes dose painting, gradient dose prescription, and [18F]FDG-PET guided response-adapted dose prescription. The current status, progress, and future expectations of these developments for various tumor types are discussed.
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Affiliation(s)
- Johannes H A M Kaanders
- Department of Radiation Oncology, Radboud university medical center, Nijmegen, The Netherlands..
| | - Johan Bussink
- Department of Radiation Oncology, Radboud university medical center, Nijmegen, The Netherlands
| | - Erik H J G Aarntzen
- Department of Medical Imaging, Radboud university medical center, Nijmegen, The Netherlands
| | - Pètra Braam
- Department of Radiation Oncology, Radboud university medical center, Nijmegen, The Netherlands
| | - Heidi Rütten
- Department of Radiation Oncology, Radboud university medical center, Nijmegen, The Netherlands
| | | | - Marcel Verheij
- Department of Radiation Oncology, Radboud university medical center, Nijmegen, The Netherlands
| | - Sven van den Bosch
- Department of Radiation Oncology, Radboud university medical center, Nijmegen, The Netherlands
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21
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Vuijk FA, Feshtali Shahbazi S, Noortman WA, van Velden FH, Dibbets-Schneider P, Marinelli AW, Neijenhuis PA, Schmitz R, Ghariq E, Velema LA, Peters FP, Smit F, Peeters KC, Temmink SJ, Crobach SA, Putter H, Vahrmeijer AL, Hilling DE, de Geus-Oei LF. Baseline and early digital [ 18 F]FDG PET/CT and multiparametric MRI contain promising features to predict response to neoadjuvant therapy in locally advanced rectal cancer patients: a pilot study. Nucl Med Commun 2023; 44:613-621. [PMID: 37132268 PMCID: PMC10246883 DOI: 10.1097/mnm.0000000000001703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 03/28/2023] [Indexed: 05/04/2023]
Abstract
OBJECTIVE In this pilot study, we investigated the feasibility of response prediction using digital [ 18 F]FDG PET/computed tomography (CT) and multiparametric MRI before, during, and after neoadjuvant chemoradiation therapy in locally advanced rectal cancer (LARC) patients and aimed to select the most promising imaging modalities and timepoints for further investigation in a larger trial. METHODS Rectal cancer patients scheduled to undergo neoadjuvant chemoradiation therapy were prospectively included in this trial, and underwent multiparametric MRI and [ 18 F]FDG PET/CT before, 2 weeks into, and 6-8 weeks after chemoradiation therapy. Two groups were created based on pathological tumor regression grade, that is, good responders (TRG1-2) and poor responders (TRG3-5). Using binary logistic regression analysis with a cutoff value of P ≤ 0.2, promising predictive features for response were selected. RESULTS Nineteen patients were included. Of these, 5 were good responders, and 14 were poor responders. Patient characteristics of these groups were similar at baseline. Fifty-seven features were extracted, of which 13 were found to be promising predictors of response. Baseline [T2: volume, diffusion-weighted imaging (DWI): apparent diffusion coefficient (ADC) mean, DWI: difference entropy], early response (T2: volume change, DWI: ADC mean change) and end-of-treatment presurgical evaluation MRI (T2: gray level nonuniformity, DWI: inverse difference normalized, DWI: gray level nonuniformity normalized), as well as baseline (metabolic tumor volume, total lesion glycolysis) and early response PET/CT (Δ maximum standardized uptake value, Δ peak standardized uptake value corrected for lean body mass), were promising features. CONCLUSION Both multiparametric MRI and [ 18 F]FDG PET/CT contain promising imaging features to predict response to neoadjuvant chemoradiotherapy in LARC patients. A future larger trial should investigate baseline, early response, and end-of-treatment presurgical evaluation MRI and baseline and early response PET/CT.
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Affiliation(s)
| | | | - Wyanne A. Noortman
- Department of Radiology, Section of Nuclear Medicine, Leiden University Medical Center
- Biomedical Photonic Imaging Group, University of Twente, Enschede
| | | | | | | | | | | | - Eidrees Ghariq
- Department of Radiology, Leiden University Medical Center, Leiden
| | - Laura A. Velema
- Department of Radiation Oncology, Leiden University Medical Center
| | - Femke P. Peters
- Department of Radiation Oncology, Leiden University Medical Center
- Department of Radiation Oncology, Antoni van Leeuwenhoek Hospital, Amsterdam
| | - Frits Smit
- Department of Radiology, Section of Nuclear Medicine, Leiden University Medical Center
| | | | | | | | - Hein Putter
- Department of Medical Statistics, Leiden University Medical Center, Leiden
| | | | - Denise E. Hilling
- Department of Surgery, Leiden University Medical Center
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam
- Department of Surgery, Ijsselland Ziekenhuis, Capelle a/d IJssel
| | - Lioe-Fee de Geus-Oei
- Department of Radiology, Section of Nuclear Medicine, Leiden University Medical Center
- Biomedical Photonic Imaging Group, University of Twente, Enschede
- Department of Radiation Science & Technology, Technical University Delft, The Netherlands
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22
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Tey J, Tan JK, Tan KK, Soon YY, Loi HY, Mohamed JSA, Bakulbhai PA, Ang B, Liang TY. Restaging of rectal cancer with hybrid positron emission tomography magnetic resonance imaging after preoperative chemoradiotherapy. ANNALS OF THE ACADEMY OF MEDICINE, SINGAPORE 2023; 52:289-295. [PMID: 38904510 DOI: 10.47102/annals-acadmedsg.2022378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/22/2024]
Abstract
INTRODUCTION This study determines the sensitivity and specificity of positron emission tomography/magnetic resonance imaging (PET/MRI) parameters in predicting treatment response in patients with localised rectal cancer who have undergone preoperative chemoradiotherapy (CRT). METHOD Patients with stage I-III adenocarcinoma of the rectum planned for preoperative CRT followed by surgery were recruited. Patients had PET/MRI scans at baseline and 6-8 weeks post-CRT. Functional MRI and PET parameters were assessed for their diagnostic accuracy for tumour regression grade (TRG). Nonparametric receiver operating characteristic analysis was employed to determine the area under the ROC curve (AUC), and the sensitivity and specificity of each quantile cut-off. RESULTS A total of 31 patients were recruited, of whom 20 completed study protocol. All patients included had mid or lower rectal tumours. There were 16 patients (80%) with node-positive disease at presentation. The median time to surgery was 75.5 days (range 52-106 days). Histopathological assessment revealed 20% good responders (TRG 1/2), and the remaining 80% of patients had a poor response (TRG 3/4). When predicting good responders, the AUC values for percent maximum thickness reduction and percent apparent diffusion coefficient (ADC) change were 0.82 and 0.73, respectively. A maximum thickness reduction cut-off of >47% and a percent ADC change of >20% yielded a sensitivity and specificity of 75%/95% and 75%/73%, respectively. CONCLUSION Parameters such as percent maximum thickness reduction and percent ADC change may be useful for predicting good responders in patients undergoing preoperative CRT for rectal cancer. Larger studies are warranted to establish the utility of PET/MRI in rectal cancer staging.
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Affiliation(s)
- Jeremy Tey
- Department of Radiation Oncology, National University Cancer Institute, Singapore
| | - Jarrod Kh Tan
- Division of Colorectal Surgery, Department of Surgery, National University of Singapore
| | - Ker-Kan Tan
- Division of Colorectal Surgery, Department of Surgery, National University of Singapore
| | - Yu Yang Soon
- Department of Radiation Oncology, National University Cancer Institute, Singapore
| | - Hoi Yin Loi
- Department of Nuclear Medicine, National University Hospital, Singapore
| | | | | | - Bertrand Ang
- Department of Radiology, National University Hospital, Singapore
| | - Thian Yee Liang
- Department of Radiology, National University Hospital, Singapore
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Manoochehry S, Rasouli HR, Ahmadpour F, Keramati A. Evaluation of the role of inflammatory blood markers in predicting the pathological response after neoadjuvant chemoradiation in patients with locally advanced rectal cancer. Radiat Oncol J 2023; 41:81-88. [PMID: 37403350 DOI: 10.3857/roj.2023.00115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 05/09/2023] [Indexed: 07/06/2023] Open
Abstract
PURPOSE This study aimed to evaluate the role of inflammatory blood markers in predicting the pathological response rate after neoadjuvant chemoradiation (neo-CRT) in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS In this prospective cohort study, we analyzed the data of patients with LARC who underwent neo-CRT and surgical removal of the rectal mass between 2020 and 2022 in a tertiary medical center. Patients were examined weekly during chemoradiation and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune inflammation index (SII) were calculated from weekly laboratory data. Wilcoxon signed-ranks and logistic regression analysis were utilized to determine whether any laboratory parameters during different time point assessments or their relative changes could predict the tumor response based on a permanent pathology review. RESULTS Thirty-four patients were recruited for the study. Eighteen patients (53%) achieved good pathologic response. Statistical analysis by Wilcoxon signed-ranks method indicated significant rises in NLR, PLR, MLR, and SII on weekly assessments during chemoradiation. Having an NLR over 3.21 during chemoradiation was correlated with the response on a Pearson chi-squared test (p = 0.04). Also, a significant correlation was found between the PLR ratio over 1.8 and the response (p = 0.02). NLR ratio over 1.82 marginally missed a significant correlation with the response (p = 0.13). On multivariate analysis, a PLR ratio over 1.8 showed a trend for response (odds ratio = 10.4; 95% confidence interval, 0.9-123; p = 0.06). CONCLUSION In this study, PLR ratio as an inflammatory marker showed a trend in the prediction of response in permanent pathology to neo-CRT.
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Affiliation(s)
- Shahram Manoochehry
- Trauma Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Hamid Reza Rasouli
- Trauma Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Fathollah Ahmadpour
- Trauma Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Alireza Keramati
- Trauma Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
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Wurschi GW, Güllmar D, Gaßler N, Clement J, Kesselmeier M, Müller-Wurschi JJ, Settmacher U, Mothes H, Helfritzsch H, Liebe Y, Franiel T, Mäurer MA, Ernst T, Nicolay NH, Wittig A. Planning adaptive treatment by longitudinal response assessment implementing MR imaging, liquid biopsy and analysis of microenvironment during neoadjuvant treatment of rectal cancer (PRIMO). Medicine (Baltimore) 2023; 102:e33575. [PMID: 37115093 PMCID: PMC10146036 DOI: 10.1097/md.0000000000033575] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 03/30/2023] [Indexed: 04/29/2023] Open
Abstract
INTRODUCTION Conducting neoadjuvant chemoradiotherapy (CRT) and additional preoperative consolidating chemotherapy (CTx), that is, total neoadjuvant therapy (TNT), improves local control and complete response (CR) rates in locally advanced rectal cancer (LARC), putting the focus on organ preservation concepts. Therefore, assessing response before surgery is crucial. Some LARC patients would either not benefit from intensification by TNT or may reach CR, making resection not mandatory. Treatment of LARC should therefore be based on patient individual risk and response to avoid overtreatment.The "PRIMO" pilot study aims to determine early response assessment to form a basis for development and validation of a noninvasive response prediction model by a subsequent prospective multicenter trial, which is highly needed for individual, response-driven therapy adaptions. METHODS PRIMO is a prospective observational cohort study including adult patients with LARC receiving neoadjuvant CRT. At least 4 multiparametric magnetic resonance imaging (MRI) scans (diffusion-weighted imaging [DWI] and hypoxia-sensitive sequences) as well as repeated blood samples in order to analyze circulating tumor cells (CTC) and cell-free tumor DNA (ctDNA) are scheduled. Pelvic radiotherapy (RT, 50.4 Gy) will be performed in combination with a 5-fluorouracil/oxaliplatin regimen in all patients (planned: N = 50), succeeded by consolidation CTx (FOLFOX4) if feasible. Additional (immuno)histochemical markers, such as tumor-infiltrating lymphocytes (TIL) and programmed death ligand 1 (PD-L1) status will be analyzed before and after CRT. Routine resection is scheduled subsequently, nonoperative management is offered alternatively in case of clinical CR (cCR).The primary endpoint is pathological response; secondary endpoints comprise longitudinal changes in MRI as well as in CTCs and TIL. These are evaluated for early response prediction during neoadjuvant therapy, in order to develop a noninvasive response prediction model for subsequent analyses. DISCUSSION Early response assessment is the key in differentiating "good" and "bad" responders during neoadjuvant CRT, allowing adaption of subsequent therapies (additional consolidating CTx, organ preservation). This study will contribute in this regard, by advancing MR imaging and substantiating new surrogate markers. Adaptive treatment strategies might build on these results in further studies.
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Affiliation(s)
- Georg W. Wurschi
- Department of Radiotherapy and Radiation Oncology, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany
- Clinician Scientist Program, Interdisciplinary Center for Clinical Research (IZKF), Jena University Hospital, Jena, Germany
| | - Daniel Güllmar
- Medical Physics Group, Institute of Diagnostic and Interventional Radiology (IDIR), Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany
| | - Nikolaus Gaßler
- Section of Pathology, Institute of Forensic Medicine, Jena University Hospital, Jena, Germany
| | - Joachim Clement
- Department of Hematology and Medical Oncology, Jena University Hospital, Jena, Germany
| | - Miriam Kesselmeier
- Institute of Medical Statistics, Computer and Data Sciences (IMSID), Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany
| | | | - Utz Settmacher
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany
| | - Henning Mothes
- Department of General, Visceral and Vascular Surgery, Sophien- und Hufeland-Klinikum Weimar, Weimar, Germany
| | - Herry Helfritzsch
- Department of General, Visceral and Thoracic Surgery, Thuringia-Clinic Saalfeld Georgius Agricola, Saalfeld, Germany
| | - Yves Liebe
- Department of General and Visceral Surgery, SRH Klinikum Burgenlandkreis Naumburg, Naumburg, Germany
| | - Tobias Franiel
- Institute of Diagnostic and Interventional Radiology (IDIR), Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany
| | - Matthias A. Mäurer
- Department of Radiotherapy and Radiation Oncology, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany
- Clinician Scientist Program, Interdisciplinary Center for Clinical Research (IZKF), Jena University Hospital, Jena, Germany
| | - Thomas Ernst
- University Tumor Center (UTC), Jena University Hospital, Jena, Germany
| | - Nils H. Nicolay
- Department of Radiation Oncology, University of Leipzig Medical Center, Leipzig, Germany
| | - Andrea Wittig
- Department of Radiotherapy and Radiation Oncology, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany
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25
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Jayaprakasam VS, Alvarez J, Omer DM, Gollub MJ, Smith JJ, Petkovska I. Watch-and-Wait Approach to Rectal Cancer: The Role of Imaging. Radiology 2023; 307:e221529. [PMID: 36880951 PMCID: PMC10068893 DOI: 10.1148/radiol.221529] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 11/09/2022] [Accepted: 11/14/2022] [Indexed: 03/08/2023]
Abstract
The diagnosis and treatment of rectal cancer have evolved dramatically over the past several decades. At the same time, its incidence has increased in younger populations. This review will inform the reader of advances in both diagnosis and treatment. These advances have led to the watch-and-wait approach, otherwise known as nonsurgical management. This review briefly outlines changes in medical and surgical treatment, advances in MRI technology and interpretation, and landmark studies or trials that have led to this exciting juncture. Herein, the authors delve into current state-of-the-art methods to assess response to treatment with MRI and endoscopy. Currently, these methods for avoiding surgery can be used to detect a complete clinical response in as many as 50% of patients with rectal cancer. Finally, the limitations of imaging and endoscopy and future challenges will be discussed.
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Affiliation(s)
- Vetri Sudar Jayaprakasam
- From the Departments of Radiology (V.S.J., M.J.G., I.P.) and Surgery
(J.A., D.M.O., J.J.S.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave,
Box 29, New York, NY 10065
| | - Janet Alvarez
- From the Departments of Radiology (V.S.J., M.J.G., I.P.) and Surgery
(J.A., D.M.O., J.J.S.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave,
Box 29, New York, NY 10065
| | - Dana M. Omer
- From the Departments of Radiology (V.S.J., M.J.G., I.P.) and Surgery
(J.A., D.M.O., J.J.S.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave,
Box 29, New York, NY 10065
| | - Marc J. Gollub
- From the Departments of Radiology (V.S.J., M.J.G., I.P.) and Surgery
(J.A., D.M.O., J.J.S.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave,
Box 29, New York, NY 10065
| | - J. Joshua Smith
- From the Departments of Radiology (V.S.J., M.J.G., I.P.) and Surgery
(J.A., D.M.O., J.J.S.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave,
Box 29, New York, NY 10065
| | - Iva Petkovska
- From the Departments of Radiology (V.S.J., M.J.G., I.P.) and Surgery
(J.A., D.M.O., J.J.S.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave,
Box 29, New York, NY 10065
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Horvat N, El Homsi M, Miranda J, Mazaheri Y, Gollub MJ, Paroder V. Rectal MRI Interpretation After Neoadjuvant Therapy. J Magn Reson Imaging 2023; 57:353-369. [PMID: 36073323 PMCID: PMC9851947 DOI: 10.1002/jmri.28426] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 08/23/2022] [Accepted: 08/25/2022] [Indexed: 02/01/2023] Open
Abstract
In recent years, several key advances in the management of locally advanced rectal cancer have been made, including the implementation of total mesorectal excision as the standard surgical approach; use of neoadjuvant chemoradiotherapy in selected patients with a high risk of local recurrence, and finally, adoption of organ preservation strategies, through either local excision or nonoperative management in selected patients with clinical complete response following neoadjuvant chemoradiotherapy. This review aims to shed light on the role of rectal MRI in the assessment of treatment response after neoadjuvant therapy, which is especially important given the growing feasibility of nonoperative management. First, an overview of current neoadjuvant therapies and response assessment based on digital rectal examination, endoscopy, and MRI will be provided. Second, the use of a high-quality restaging rectal MRI protocol will be presented. Third, a step-by-step approach to assessing treatment response on restaging rectal MRI following neoadjuvant treatment will be outlined, acknowledging challenges faced by radiologists during MRI interpretation. Finally, research related to response assessment will be discussed. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.
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Affiliation(s)
- Natally Horvat
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Maria El Homsi
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Joao Miranda
- Department of Radiology, University of Sao Paulo, Sao Paulo, Brazil
| | - Yousef Mazaheri
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Marc J. Gollub
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Viktoriya Paroder
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Boubaddi M, Fleming C, Vendrely V, Frulio N, Salut C, Rullier E, Denost Q. Feasibility study of a Response Surveillance Program in locally advanced mid and low rectal cancer to increase organ preservation. Eur J Surg Oncol 2023; 49:237-243. [PMID: 36114048 DOI: 10.1016/j.ejso.2022.08.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 08/02/2022] [Accepted: 08/25/2022] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND Assessment of tumor response in rectal cancer after neoadjuvant treatment by MRI (Tumour Regression Grade, TRG 1-5) is well standardized. The overall timing and method of defining complete response (cCR) remain controversial. The aim of this work was to evaluate the feasibility of a defined Response Surveillance Program (RSP) to increase organ preservation for locally advanced rectal cancer after neoadjuvant treatment. METHODS A standardized program of clinical (CR), radiological (RR) and metabolic (MR) assessment of tumor response is defined over a 6 month period from completion of NACRT with formal assessment performed every 2 months (M). Patients with TRG1-3 at M2 and TRG1-2 at M4 continue in the program up to M6 assessment. Patients managed with this protocol from 2016 to 2020 were analyzed. The primary endpoint was rectal preservation rate. Secondary endpoints included disease-free survival and overall survival at 3 years. RESULT 314 potentially suitable patients were enrolled in the RSP and 50 patients completed the six month program and were successfully enrolled into watch and wait. Fourteen (28%) were T2 tumor stage, 27 (54%) T3 and nine (18%) were T4. During watch and wait, patients with locoregional recurrence (n = 11) were treated with local excision (n = 3), endocavitary radiotherapy (n = 1), TME (n = 5) and APR (n = 2). With a median follow-up of 32 months, the rectal preservation rate was 88%, with a 3-year disease-free survival of 67% and an overall survival of 98%. CONCLUSION This study validates the feasibility of the practical implementation of a Response Surveillance Program to increase organ preservation rates without compromising oncological outcomes in rectal cancer.
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Affiliation(s)
| | | | | | - Nora Frulio
- Department of Radiology, CHU, Bordeaux, France
| | | | - Eric Rullier
- Department of Colorectal Surgery, CHU, Bordeaux, France
| | - Quentin Denost
- Department of Colorectal Surgery, CHU, Bordeaux, France.
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Fleming C, Vendrely V, Rullier E, Denost Q. Organ preservation in rectal cancer: review of contemporary management. Br J Surg 2022; 109:695-703. [PMID: 35640118 DOI: 10.1093/bjs/znac140] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 03/21/2022] [Accepted: 04/14/2022] [Indexed: 01/03/2025]
Abstract
BACKGROUND Organ preservation as a successful management for rectal cancer is an evolving field. Refinement of neoadjuvant therapies and extended interval to response assessment has improved tumour downstaging and cCR rates. METHODS This was a narrative review of the current evidence for all aspects of organ preservation in rectal cancer management, together with a review of the future direction of this field. RESULTS Patients can be selected for organ preservation opportunistically, based on an unexpectedly good tumour response, or selectively, based on baseline tumour characteristics that predict organ preservation as a viable treatment strategy. Escalation in oncological therapy and increasing the time interval from completion of neaodjuvant therapy to tumour assessment may further increase tumour downstaging and complete response rates. The addition of local excision to oncological therapy can further improve organ preservation rates. Cancer outcomes in organ preservation are comparable to those of total mesorectal excision, with low regrowth rates reported in patients who achieve a complete response to neoadjuvant therapy. Successful organ preservation aims to achieve non-inferior oncological outcomes together with improved functionality and survivorship. Future research should establish consensus of follow-up protocols, and define criteria for oncological and functional success to facilitate patient-centred decision-making. CONCLUSION Modern neoadjuvant therapy for rectal cancer and increasing the interval to tumour response increases the number of patients who can be managed successfully with organ preservation in rectal cancer, both as an opportunistic event and as a planned treatment strategy.
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Affiliation(s)
| | | | - Eric Rullier
- Department of Colorectal Surgery, CHU de Bordeaux, Bordeaux, France
| | - Quentin Denost
- Department of Colorectal Surgery, CHU de Bordeaux, Bordeaux, France
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Wichtmann BD, Albert S, Zhao W, Maurer A, Rödel C, Hofheinz RD, Hesser J, Zöllner FG, Attenberger UI. Are We There Yet? The Value of Deep Learning in a Multicenter Setting for Response Prediction of Locally Advanced Rectal Cancer to Neoadjuvant Chemoradiotherapy. Diagnostics (Basel) 2022; 12:1601. [PMID: 35885506 PMCID: PMC9317842 DOI: 10.3390/diagnostics12071601] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 06/26/2022] [Accepted: 06/28/2022] [Indexed: 11/17/2022] Open
Abstract
This retrospective study aims to evaluate the generalizability of a promising state-of-the-art multitask deep learning (DL) model for predicting the response of locally advanced rectal cancer (LARC) to neoadjuvant chemoradiotherapy (nCRT) using a multicenter dataset. To this end, we retrained and validated a Siamese network with two U-Nets joined at multiple layers using pre- and post-therapeutic T2-weighted (T2w), diffusion-weighted (DW) images and apparent diffusion coefficient (ADC) maps of 83 LARC patients acquired under study conditions at four different medical centers. To assess the predictive performance of the model, the trained network was then applied to an external clinical routine dataset of 46 LARC patients imaged without study conditions. The training and test datasets differed significantly in terms of their composition, e.g., T-/N-staging, the time interval between initial staging/nCRT/re-staging and surgery, as well as with respect to acquisition parameters, such as resolution, echo/repetition time, flip angle and field strength. We found that even after dedicated data pre-processing, the predictive performance dropped significantly in this multicenter setting compared to a previously published single- or two-center setting. Testing the network on the external clinical routine dataset yielded an area under the receiver operating characteristic curve of 0.54 (95% confidence interval [CI]: 0.41, 0.65), when using only pre- and post-therapeutic T2w images as input, and 0.60 (95% CI: 0.48, 0.71), when using the combination of pre- and post-therapeutic T2w, DW images, and ADC maps as input. Our study highlights the importance of data quality and harmonization in clinical trials using machine learning. Only in a joint, cross-center effort, involving a multidisciplinary team can we generate large enough curated and annotated datasets and develop the necessary pre-processing pipelines for data harmonization to successfully apply DL models clinically.
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Affiliation(s)
- Barbara D. Wichtmann
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, 53127 Bonn, Germany;
| | - Steffen Albert
- Computer Assisted Clinical Medicine, Mannheim Institute for Intelligent Systems in Medicine, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; (S.A.); (F.G.Z.)
| | - Wenzhao Zhao
- Data Analysis and Modeling, Mannheim Institute for Intelligent Systems in Medicine (MIISM), Medical School Mannheim, Central Institute for Scientific Computing (IWR), Central Institute for Computer Engineering (ZITI), CZS Heidelberg Center for Model-Based AI, Heidelberg University, 69047 Heidelberg, Germany; (W.Z.); (J.H.)
| | - Angelika Maurer
- Clinical Functional Imaging, Department of Diagnostic and Interventional Radiology, University Hospital Bonn, 53127 Bonn, Germany;
| | - Claus Rödel
- Department of Radiotherapy and Oncology, University Hospital Frankfurt, 60596 Frankfurt am Main, Germany;
| | - Ralf-Dieter Hofheinz
- Department of Medicine III, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany;
| | - Jürgen Hesser
- Data Analysis and Modeling, Mannheim Institute for Intelligent Systems in Medicine (MIISM), Medical School Mannheim, Central Institute for Scientific Computing (IWR), Central Institute for Computer Engineering (ZITI), CZS Heidelberg Center for Model-Based AI, Heidelberg University, 69047 Heidelberg, Germany; (W.Z.); (J.H.)
| | - Frank G. Zöllner
- Computer Assisted Clinical Medicine, Mannheim Institute for Intelligent Systems in Medicine, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; (S.A.); (F.G.Z.)
| | - Ulrike I. Attenberger
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, 53127 Bonn, Germany;
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Chen L, Liu X, Zhang W, Qin S, Wang Y, Lin J, Chen Q, Liu G. The predictive value of tumor volume reduction ratio on three-dimensional endorectal ultrasound for tumor response to chemoradiotherapy for locally advanced rectal cancer. ANNALS OF TRANSLATIONAL MEDICINE 2022; 10:666. [PMID: 35845508 PMCID: PMC9279805 DOI: 10.21037/atm-22-2418] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 06/08/2022] [Indexed: 01/04/2023]
Abstract
Background Preoperative chemoradiotherapy remains part of the standard treatment for patients with locally advanced rectal cancer. Subsequent treatment individualization requires accurate prediction of tumor response to chemoradiotherapy. Three-dimensional endorectal ultrasound (3D-ERUS) can automatically capture and store the images of the rectal wall and rectal cancer with high resolution. In this study, we aimed to assess the correlation and predictive value between tumor volume changes measured on 3D-ERUS and the histopathological tumor response after chemoradiotherapy for patients with locally advanced rectal cancer. Methods A total of 54 patients with locally advanced rectal cancer who underwent chemoradiotherapy and had complete 3D-ERUS data pre-and post-chemoradiotherapy were enrolled in the study. The tumor volume pre-and post-chemoradiotherapy was measured manually on 3D-ERUS, and the tumor volume reduction ratio was calculated. The histopathological tumor regression grade (TRG) was used to assess tumor response. The differences in volumetry parameters were compared between groups with varying tumor response. The diagnostic efficacy of the tumor volume reduction ratio was evaluated by the receiver operating characteristic (ROC) curve. Results The mean age of all patients was 55.19±12.46 years. The relative proportions of TRG 0–3 were 29.6% (16/54), 16.6% (9/54), 50% (27/54), and 3.8% (2/54), respectively. The median tumor volumes post-chemoradiotherapy in good responders (TRG 0–1, median tumor volume =3.26 cm3) and the complete response group (TRG 0, median tumor volume =2.61 cm3) were smaller than those in poor responders (TRG 2–3, median tumor volume =5.43 cm3) and the partial response group (TRG 1–3, median tumor volume =4.00 cm3), while tumor volume reduction ratios were higher than those of poor responders (79.32% vs. 59.67%) and the partial response group (82.22% vs. 61.64%), with significant differences (all P values <0.05). The ROC curves showed that the cut-off values of the tumor volume reduction ratio to predict good responders and complete response were 67.77% and 72.02%, respectively. The corresponding areas under the curve in the prediction of good responders and complete response were 0.830 and 0.829, respectively. Conclusions The tumor volume reduction ratio measured on 3D-ERUS might be a helpful indicator for tumor response in patients with locally advanced rectal cancer.
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Affiliation(s)
- Limei Chen
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaoyin Liu
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wenjing Zhang
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Si Qin
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yimin Wang
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jing Lin
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qiu Chen
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Guangjian Liu
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Simulation CT-based radiomics for prediction of response after neoadjuvant chemo-radiotherapy in patients with locally advanced rectal cancer. Radiat Oncol 2022; 17:84. [PMID: 35484597 PMCID: PMC9052564 DOI: 10.1186/s13014-022-02053-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Accepted: 04/11/2022] [Indexed: 02/08/2023] Open
Abstract
Background To report on the discriminative ability of a simulation Computed Tomography (CT)-based radiomics signature for predicting response to treatment in patients undergoing neoadjuvant chemo-radiation for locally advanced adenocarcinoma of the rectum. Methods Consecutive patients treated at the Universities of Tübingen (from 1/1/07 to 31/12/10, explorative cohort) and Florence (from 1/1/11 to 31/12/17, external validation cohort) were considered in our dual-institution, retrospective analysis. Long-course neoadjuvant chemo-radiation was performed according to local policy. On simulation CT, the rectal Gross Tumor Volume was manually segmented. A feature selection process was performed yielding mineable data through an in-house developed software (written in Python 3.6). Model selection and hyper-parametrization of the model was performed using a fivefold cross validation approach. The main outcome measure of the study was the rate of pathologic good response, defined as the sum of Tumor regression grade (TRG) 3 and 4 according to Dworak’s classification.
Results Two-hundred and one patients were included in our analysis, of whom 126 (62.7%) and 75 (37.3%) cases represented the explorative and external validation cohorts, respectively. Patient characteristics were well balanced between the two groups. A similar rate of good response to neoadjuvant treatment was obtained in in both cohorts (46% and 54.7%, respectively; p = 0.247). A total of 1150 features were extracted from the planning scans. A 5-metafeature complex consisting of Principal component analysis (PCA)-clusters (whose main components are LHL Grey-Level-Size-Zone: Large Zone Emphasis, Elongation, HHH Intensity Histogram Mean, HLL Run-Length: Run Level Variance and HHH Co-occurence: Cluster Tendency) in combination with 5-nearest neighbour model was the most robust signature. When applied to the explorative cohort, the prediction of good response corresponded to an average Area under the curve (AUC) value of 0.65 ± 0.02. When the model was tested on the external validation cohort, it ensured a similar accuracy, with a slightly lower predictive ability (AUC of 0.63).
Conclusions Radiomics-based, data-mining from simulation CT scans was shown to be feasible and reproducible in two independent cohorts, yielding fair accuracy in the prediction of response to neoadjuvant chemo-radiation.
Supplementary Information The online version contains supplementary material available at 10.1186/s13014-022-02053-y.
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Boktor RR, Lee ST, Scott AM. PET/CT imaging in colorectal carcinoma. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00033-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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Polverari G, Penna D, Cassalia L, Deandreis D, Pelosi E. Diagnostic Applications of Nuclear Medicine: Colorectal Cancer. NUCLEAR ONCOLOGY 2022:919-932. [DOI: 10.1007/978-3-031-05494-5_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Aryan M, Read T, Goldstein L, Burriss N, Grajo JR, Moser P, George TJ, Tan S, Iqbal A. Utility of Restaging MRI Following Neoadjuvant Chemoradiotherapy for Stage II-III Rectal Adenocarcinoma. Cureus 2021; 13:e19037. [PMID: 34858737 PMCID: PMC8612598 DOI: 10.7759/cureus.19037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/25/2021] [Indexed: 11/12/2022] Open
Abstract
Background Magnetic resonance imaging (MRI) is currently utilized for the pretreatment staging of locally advanced rectal cancer; however, there is no consensus regarding the utility of repeat MRI for restaging following neoadjuvant chemoradiotherapy (CRT). In this study, we aimed to investigate the clinical utility of restaging MRI after CRT in patients with clinical stage II-III rectal cancer. Methodology We performed a retrospective observational study at a tertiary care hospital. Our study population included patients with clinical stage II-III rectal cancer treated with neoadjuvant CRT who underwent both pre- and post-CRT MRI followed by surgical resection from 2012 to 2017. MRIs were reviewed by radiologists with an interest in rectal cancer MRI imaging using a standardized template. The utility of post-CRT MRI was evaluated by assessing its impact on change in surgical planning, concordance with pathologic staging, and prediction of surgical margins. Results A total of 30 patients were included in the study; 67% had clinical stage III and 33% had stage II disease based on pre-CRT MRI. Post-CRT MRI findings did not lead to a change in the originally outlined surgical plan in any patient. Compared to pre-CRT MRI, post-CRT MRI was not significantly more accurate in predicting T stage (k = 0.483), N stage (k = 0.268), or positive surgical margins (k = 0.839). Conclusions Due to poor concordance with pathologic staging, inability to more accurately predict surgical margin status and the absence of a demonstrable change in surgical treatment, post-CRT restaging with MRI, in its current form, appears to be of limited clinical utility.
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Affiliation(s)
- Mahmoud Aryan
- Department of Surgery, University of Florida College of Medicine, Gainesville, USA
| | - Thomas Read
- Department of Surgery, University of Florida College of Medicine, Gainesville, USA
| | - Lindsey Goldstein
- Department of Surgery, University of Florida College of Medicine, Gainesville, USA
| | - Nathan Burriss
- Department of Surgery, University of Florida College of Medicine, Gainesville, USA
| | - Joseph R Grajo
- Department of Radiology, University of Florida College of Medicine, Gainesville, USA
| | - Patricia Moser
- Department of Radiology, University of Florida College of Medicine, Gainesville, USA
| | - Thomas J George
- Department of Hematology and Oncology, University of Florida College of Medicine, Gainesville, USA
| | - Sanda Tan
- Department of Surgery, University of Florida College of Medicine, Gainesville, USA
| | - Atif Iqbal
- Department of Surgery, University of Florida College of Medicine, Gainesville, USA
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Pyo DH, Choi JY, Lee WY, Yun SH, Kim HC, Huh JW, Park YA, Shin JK, Cho YB. A Nomogram for Predicting Pathological Complete Response to Neoadjuvant Chemoradiotherapy Using Semiquantitative Parameters Derived From Sequential PET/CT in Locally Advanced Rectal Cancer. Front Oncol 2021; 11:742728. [PMID: 34676170 PMCID: PMC8523984 DOI: 10.3389/fonc.2021.742728] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 09/14/2021] [Indexed: 12/25/2022] Open
Abstract
We evaluated the predictive value of semiquantitative volumetric parameters derived from sequential PET/CT and developed a nomogram to predict pathological complete response (pCR) in patients with rectal cancer treated by neoadjuvant chemoradiotherapy (nCRT). From April 2008 to December 2013, among the patients who underwent nCRT, those who were taken sequential PET/CT before and after nCRT were included. MRI-based staging and semiquantitative parameters of PET/CT including standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were evaluated before and after nCRT. Multivariable analysis was performed to select significant predictors to construct a nomogram. Sensitivity, specificity, accuracy, and area under the receiver operating characteristics curve (AUC) of the model were evaluated to determine its performance. Among 137 eligible patients, 17 (12.4%) had pCR. All post-PET/CT parameters showed significant differences between pCR and non-pCR groups. Patients were randomly assigned to a training group (91 patients) and a validation group (46 patients). In multivariable analysis with the training group, post-CEA, post-MRI T staging, post-SUVmax, and post-MTV were significantly associated with pCR. There was no significant pre-nCRT variable for predicting pCR. Using significant predictors, a nomogram was developed. Sensitivity, specificity, accuracy, and AUC of the nomogram were 0.882, 0.808, 0.848, and 0.884 with the training group and 0.857, 0.781, 0.783, and 0.828 with the validation group, respectively. This model showed the better performance than other predictive models that did not contain PET/CT parameters. A nomogram containing semiquantitative post-PET/CT could effectively select candidates for organ-sparing strategies.
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Affiliation(s)
- Dae Hee Pyo
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Joon Young Choi
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Woo Yong Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.,Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, South Korea
| | - Seong Hyeon Yun
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Hee Cheol Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jung Wook Huh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yoon Ah Park
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jung Kyong Shin
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yong Beom Cho
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.,Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, South Korea.,Department of Biopharmaceutical Convergence, Sungkyunkwan University, Seoul, South Korea
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Oh SY, Park IJ, Kim YIL, Lee JL, Kim CW, Yoon YS, Lim SB, Yu CS, Kim JC. Comparison between Local Excision and Radical Resection for the Treatment of Rectal Cancer in ypT0-1 Patients: An Analysis of the Clinicopathological Factors and Survival Rates. Cancers (Basel) 2021; 13:4823. [PMID: 34638307 PMCID: PMC8507625 DOI: 10.3390/cancers13194823] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 09/23/2021] [Accepted: 09/23/2021] [Indexed: 02/06/2023] Open
Abstract
Tumors with good response to preoperative chemoradiotherapy have a favorable prognosis, and these findings raise interest in rectum-sparing strategies. This study aimed to compare the oncologic outcome between local excision and radical resection in ypT0-1 patients and to analyze prognostic factors. Patients with primary rectal cancer diagnosed with ypT0-1 after PCRT followed by either radical resection (RR) or local excision (LE) between 2005 and 2014 were included in this study (LE = 78, RR = 442). Clinicopathologic features, recurrence-free survival (RFS), and OS were analyzed. There was no statistically significant difference in the RFS and OS between the LE and RR groups. Clinical T stage (cT3-4) before PCRT was related to RFS and in the LE group (p = 0.022). Lymph node metastasis (HR: 4.884, 95% confidence interval: 2.451-9.732, p < 0.001) in the final pathology was the only factor associated with RFS, showing a statistically significant difference in the RR group. Lymph node metastasis and age were associated with OS in the RR group. This study confirms the oncologic feasibility of LE in ypT0-1 rectal cancer after PCRT. Additionally, careful patient selection with higher accuracy modalities should be updated to improve treatment outcomes of LE.
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Affiliation(s)
| | - In Ja Park
- Asan Medical Center, Department of Colon and Rectal Surgery, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.Y.O.); (Y.I.K.); (J.-L.L.); (C.W.K.); (Y.S.Y.); (S.-B.L.); (C.S.Y.); (J.C.K.)
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Lutsyk M, Awawda M, Gourevich K, Ben Yosef R. Tumor Volume as Predictor of Pathologic Complete Response Following Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer. Am J Clin Oncol 2021; 44:482-486. [PMID: 34269693 DOI: 10.1097/coc.0000000000000846] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
PURPOSE Neoadjuvant chemoradiation followed by surgery is the current standard of care in the treatment of locally advanced rectal cancer. Those who achieved pathologic complete response, following this standard of care, complete pathologic response (pCR) had better outcome. Until now there are no reliable clinical parameters to predict this response. The purpose of the study was to evaluate whether tumor volume may serve as a predictive factor in patients treated with neoadjuvant chemoradiotherapy. MATERIALS AND METHODS Between September 2015 and September 2019, patients diagnosed with stage IIA to IIIC rectal adenocarcinoma, who were treated with neoadjuvant chemoradiation, were enrolled to this study. All patients underwent rectal ultrasound, pelvic magnetic resonance imaging, fluorodeoxyglucose-positron emission tomography-computed tomography and the diagnosis was confirmed by pathology report. Radiation therapy was consisted of 50 Gy delivered to the tumor site, 2 Gy a day, 5 times a week and to the pelvic lymph nodes for a total of 45 Gy in 1.8 Gy a day, 5 times a week. The gross tumor volume (GTV) was contoured by radiation oncology expert, reviewed by radiology and nuclear medicine expert and approved by radiation therapy tumor board. Chemotherapy was consisted of either capecitabine 875 mg/m2 twice a day or continuous. IV infusion of 5 fluorouracil 375 mg/m2 for 4 consecutive days in a 3 weeks apart. Operation, either low anterior or abdominoperineal resection was carried out 6 to 8 weeks following completion of treatment. Patients were assigned to either complete pathologic response (pCR) or non-pCR groups. GTV, among other clinical and treatment parameters, were evaluated for prediction of pCR. Statistical methods included independent t test, logistic regression, area under the curve-receiver operating characteristic, Bayesian independent statistics and multilayer perceptron model. RESULTS One hundred ninety-three patients were enrolled to this study, 6 were excluded due to metastatic disease detected at the time of operation. Seventy had stage II and 117 had stage III. Forty-four of 187 (23.5%) patients achieved pCR and 143 patients had either partial or no response/progressive disease. Among the 44 pCR group, 21 had stage II and 23 had stage III disease. Treatment interruption, defined as either a delay of up to 1 week in radiation, and a dose reduction to 75%, was occurred in 42 patients. Sex, ethnicity, distance from anal verge to tumor, height, weight, age, delivered radiation dose, radiotherapy techniques, clinical T and N stage and GTV were evaluated for prediction of pCR. GTV at the volume of <39.5 cm3 was the only significant predictive factor to detect pCR by logistic regression model (P<0.01) and by Bayesian independent test (P=0.026). Area under the receiver operating characteristic curve of GTV <39.5 cm3 showed area under the curve of 0.715 (P=0.009) for stage II and area under the curve of 0.62 (P>0.05) for stage III. CONCLUSION GTV may serve as a predictive factor for achieving pCR in locally advanced rectal cancer after neoadjuvant chemoradiotherapy.
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Affiliation(s)
| | | | | | - Rahamim Ben Yosef
- Radiation Therapy Unit, Oncology Institute
- Technion School of Medicine, Haifa, Israel
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38
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Lapa C, Nestle U, Albert NL, Baues C, Beer A, Buck A, Budach V, Bütof R, Combs SE, Derlin T, Eiber M, Fendler WP, Furth C, Gani C, Gkika E, Grosu AL, Henkenberens C, Ilhan H, Löck S, Marnitz-Schulze S, Miederer M, Mix M, Nicolay NH, Niyazi M, Pöttgen C, Rödel CM, Schatka I, Schwarzenboeck SM, Todica AS, Weber W, Wegen S, Wiegel T, Zamboglou C, Zips D, Zöphel K, Zschaeck S, Thorwarth D, Troost EGC. Value of PET imaging for radiation therapy. Strahlenther Onkol 2021; 197:1-23. [PMID: 34259912 DOI: 10.1007/s00066-021-01812-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 06/09/2021] [Indexed: 12/13/2022]
Abstract
This comprehensive review written by experts in their field gives an overview on the current status of incorporating positron emission tomography (PET) into radiation treatment planning. Moreover, it highlights ongoing studies for treatment individualisation and per-treatment tumour response monitoring for various primary tumours. Novel tracers and image analysis methods are discussed. The authors believe this contribution to be of crucial value for experts in the field as well as for policy makers deciding on the reimbursement of this powerful imaging modality.
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Affiliation(s)
- Constantin Lapa
- Nuclear Medicine, Medical Faculty, University of Augsburg, Augsburg, Germany
| | - Ursula Nestle
- Department of Radiation Oncology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany
- Department of Radiation Oncology, Kliniken Maria Hilf, Mönchengladbach, Germany
| | - Nathalie L Albert
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Christian Baues
- Department of Radiation Oncology, Cyberknife and Radiotherapy, Medical Faculty, University Hospital Cologne, Cologne, Germany
| | - Ambros Beer
- Department of Nuclear Medicine, Ulm University Hospital, Ulm, Germany
| | - Andreas Buck
- Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Volker Budach
- Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - Rebecca Bütof
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
| | - Stephanie E Combs
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
- Department of Radiation Oncology, Technical University of Munich (TUM), Klinikum rechts der Isar, Munich, Germany
- Department of Radiation Sciences (DRS), Institute of Radiation Medicine (IRM), Neuherberg, Germany
| | - Thorsten Derlin
- Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany
| | - Matthias Eiber
- Department of Nuclear Medicine, Technical University of Munich (TUM), Klinikum rechts der Isar, Munich, Germany
| | - Wolfgang P Fendler
- Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany
| | - Christian Furth
- Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Cihan Gani
- German Cancer Consortium (DKTK), Partner Site Tübingen, and German Cancer Research Center (DKFZ), Heidelberg, Germany
- Department of Radiation Oncology, University of Tübingen, Tübingen, Germany
| | - Eleni Gkika
- Department of Radiation Oncology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany
| | - Anca-L Grosu
- Department of Radiation Oncology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany
| | - Christoph Henkenberens
- Department of Radiotherapy and Special Oncology, Medical School Hannover, Hannover, Germany
| | - Harun Ilhan
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Steffen Löck
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
| | - Simone Marnitz-Schulze
- Department of Radiation Oncology, Cyberknife and Radiotherapy, Medical Faculty, University Hospital Cologne, Cologne, Germany
| | - Matthias Miederer
- Department of Nuclear Medicine, University Hospital Mainz, Mainz, Germany
| | - Michael Mix
- Department of Nuclear Medicine, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany
| | - Nils H Nicolay
- Department of Radiation Oncology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany
| | - Maximilian Niyazi
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
| | - Christoph Pöttgen
- Department of Radiation Oncology, West German Cancer Centre, University of Duisburg-Essen, Essen, Germany
| | - Claus M Rödel
- German Cancer Consortium (DKTK), Partner Site Frankfurt, and German Cancer Research Center (DKFZ), Heidelberg, Germany
- Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Frankfurt, Germany
| | - Imke Schatka
- Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | | | - Andrei S Todica
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Wolfgang Weber
- Department of Nuclear Medicine, Technical University of Munich (TUM), Klinikum rechts der Isar, Munich, Germany
| | - Simone Wegen
- Department of Radiation Oncology, Cyberknife and Radiotherapy, Medical Faculty, University Hospital Cologne, Cologne, Germany
| | - Thomas Wiegel
- Department of Radiation Oncology, Ulm University Hospital, Ulm, Germany
| | - Constantinos Zamboglou
- Department of Radiation Oncology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany
| | - Daniel Zips
- German Cancer Consortium (DKTK), Partner Site Tübingen, and German Cancer Research Center (DKFZ), Heidelberg, Germany
- Department of Radiation Oncology, University of Tübingen, Tübingen, Germany
| | - Klaus Zöphel
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
- National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany
- Department of Nuclear Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
- Department of Nuclear Medicine, Klinikum Chemnitz gGmbH, Chemnitz, Germany
| | - Sebastian Zschaeck
- Department of Radiation Oncology, Charité-Universitätsmedizin Berlin, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Daniela Thorwarth
- German Cancer Consortium (DKTK), Partner Site Tübingen, and German Cancer Research Center (DKFZ), Heidelberg, Germany
- Section for Biomedical Physics, Department of Radiation Oncology, University of Tübingen, Tübingen, Germany
| | - Esther G C Troost
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.
- National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.
- German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
- Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology-OncoRay, Dresden, Germany.
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Lapa C, Nestle U, Albert NL, Baues C, Beer A, Buck A, Budach V, Bütof R, Combs SE, Derlin T, Eiber M, Fendler WP, Furth C, Gani C, Gkika E, Grosu AL, Henkenberens C, Ilhan H, Löck S, Marnitz-Schulze S, Miederer M, Mix M, Nicolay NH, Niyazi M, Pöttgen C, Rödel CM, Schatka I, Schwarzenboeck SM, Todica AS, Weber W, Wegen S, Wiegel T, Zamboglou C, Zips D, Zöphel K, Zschaeck S, Thorwarth D, Troost EGC. Value of PET imaging for radiation therapy. Nuklearmedizin 2021; 60:326-343. [PMID: 34261141 DOI: 10.1055/a-1525-7029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
This comprehensive review written by experts in their field gives an overview on the current status of incorporating positron emission tomography (PET) into radiation treatment planning. Moreover, it highlights ongoing studies for treatment individualisation and per-treatment tumour response monitoring for various primary tumours. Novel tracers and image analysis methods are discussed. The authors believe this contribution to be of crucial value for experts in the field as well as for policy makers deciding on the reimbursement of this powerful imaging modality.
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Affiliation(s)
- Constantin Lapa
- Nuclear Medicine, Medical Faculty, University of Augsburg, Augsburg, Germany
| | - Ursula Nestle
- Department of Radiation Oncology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.,German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany.,Department of Radiation Oncology, Kliniken Maria Hilf, Mönchengladbach, Germany
| | - Nathalie L Albert
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Christian Baues
- Department of Radiation Oncology, Cyberknife and Radiotherapy, Medical Faculty, University Hospital Cologne, Cologne, Germany
| | - Ambros Beer
- Department of Nuclear Medicine, Ulm University Hospital, Ulm, Germany
| | - Andreas Buck
- Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Volker Budach
- Department of Radiation Oncology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - Rebecca Bütof
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.,OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
| | - Stephanie E Combs
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.,Department of Radiation Oncology, Technical University of Munich (TUM), Klinikum rechts der Isar, Munich, Germany.,Department of Radiation Sciences (DRS), Institute of Radiation Medicine (IRM), Neuherberg, Germany
| | - Thorsten Derlin
- Department of Nuclear Medicine, Hannover Medical School, Germany
| | - Matthias Eiber
- Department of Nuclear Medicine, Technical University of Munich (TUM), Klinikum rechts der Isar, Munich, Germany
| | - Wolfgang P Fendler
- Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany
| | - Christian Furth
- Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Cihan Gani
- German Cancer Consortium (DKTK), Partner Site Tübingen, and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Radiation Oncology, University of Tübingen, Tübingen, Germany
| | - Eleni Gkika
- Department of Radiation Oncology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany
| | - Anca L Grosu
- Department of Radiation Oncology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.,German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany
| | | | - Harun Ilhan
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Steffen Löck
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.,OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
| | - Simone Marnitz-Schulze
- Department of Radiation Oncology, Cyberknife and Radiotherapy, Medical Faculty, University Hospital Cologne, Cologne, Germany
| | - Matthias Miederer
- Department of Nuclear Medicine, University Hospital Mainz, Mainz, Germany
| | - Michael Mix
- Department of Nuclear Medicine, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany
| | - Nils H Nicolay
- Department of Radiation Oncology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.,German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany
| | - Maximilian Niyazi
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany.,German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
| | - Christoph Pöttgen
- Department of Radiation Oncology, West German Cancer Centre, University of Duisburg-Essen, Essen, Germany
| | - Claus M Rödel
- German Cancer Consortium (DKTK), Partner Site Frankfurt, and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Radiotherapy and Oncology, Goethe University Frankfurt, Frankfurt, Germany
| | - Imke Schatka
- Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | | | - Andrei S Todica
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Wolfgang Weber
- Department of Nuclear Medicine, Technical University of Munich (TUM), Klinikum rechts der Isar, Munich, Germany
| | - Simone Wegen
- Department of Radiation Oncology, Cyberknife and Radiotherapy, Medical Faculty, University Hospital Cologne, Cologne, Germany
| | - Thomas Wiegel
- Department of Radiation Oncology, Ulm University Hospital, Ulm, Germany
| | - Constantinos Zamboglou
- Department of Radiation Oncology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.,German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany
| | - Daniel Zips
- German Cancer Consortium (DKTK), Partner Site Tübingen, and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Radiation Oncology, University of Tübingen, Tübingen, Germany
| | - Klaus Zöphel
- OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.,National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.,German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Nuclear Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.,Department of Nuclear Medicine, Klinikum Chemnitz gGmbH, Chemnitz, Germany
| | - Sebastian Zschaeck
- Department of Radiation Oncology, Charité-Universitätsmedizin Berlin, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Daniela Thorwarth
- German Cancer Consortium (DKTK), Partner Site Tübingen, and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Section for Biomedical Physics, Department of Radiation Oncology, University of Tübingen, Tübingen, Germany
| | - Esther G C Troost
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.,OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.,National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.,German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany
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40
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Perspectives for circulating tumor DNA in clinical management of colorectal cancer. Int J Clin Oncol 2021; 26:1420-1430. [PMID: 34185174 DOI: 10.1007/s10147-021-01937-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 05/11/2021] [Indexed: 10/21/2022]
Abstract
Growing evidence has demonstrated that circulating tumor DNA (ctDNA) detection in colorectal cancer might be a promising approach to address current important clinical questions. During chemotherapy for metastatic colorectal cancer, tumor cells acquire potential resistance by generating additional somatic mutations related to therapeutic resistance. ctDNA can capture the tumor landscape, including heterogeneity, which might provide the opportunity for additional treatment options. Moreover, ctDNA detection is advantageous, because it can monitor tumor heterogeneity serially, in a non-invasive manner. ctDNA is considered valid for detecting minimal residual disease after a curable resection. By utilizing ctDNA detection, adjuvant chemotherapy for patients with stage II-III colorectal cancer might be omitted for patients at low risk of recurrence; or conversely, adjuvant chemotherapy might be highly recommended for patients at high risk, based on ctDNA findings. During multidisciplinary treatments for locally advanced rectal cancer, it is essential to monitor the responses to sequential treatments to make appropriate decisions. Currently, these decisions are mainly based on radiological or pathological findings. ctDNA can add value by providing the real-time status of locally advanced rectal cancer. In this review, we summarized the current evidence and discussed future strategies for using ctDNA in the treatment of colorectal cancer.
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Image-based deep learning model for predicting pathological response in rectal cancer using post-chemoradiotherapy magnetic resonance imaging. Radiother Oncol 2021; 161:183-190. [PMID: 34139211 DOI: 10.1016/j.radonc.2021.06.019] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 06/08/2021] [Accepted: 06/08/2021] [Indexed: 12/29/2022]
Abstract
INTRODUCTION To develop an image-based deep learning model for predicting pathological response in rectal cancer using post-chemoradiotherapy magnetic resonance (MR) imaging. MATERIALS AND METHODS A total of 466 patients with locally advanced rectal cancer who received preoperative chemoradiotherapy followed by surgical resection were collected from single center, among whom 113 (24.3%) were allocated to the holdout testing set. Complete response (pCR) was defined as Dworak tumor regression grade (TRG) 4, while good response (GR) was defined as TRG 3 or 4. Based on post-chemoradiotherapy T2-weighted axial MR images, two deep learning models were developed to predict pCR and GR, respectively. The prediction performance of the deep learning models was evaluated in the testing set and was compared to that of a senior radiologist and a radiation oncologist. RESULTS The deep learning model showed an area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 0.76, 0.30, 0.96, 0.67, 0.87, and 85.0% for predicting pCR and 0.72, 0.54, 0.81, 0.60, 0.77, and 71.7% for predicting GR, respectively. The deep learning model had a superior predictive performance than the observers. Fair agreement between the ground truth and the model was shown for pCR prediction (kappa = 0.34) and GR prediction (kappa = 0.36). CONCLUSIONS The post-chemoradiotherapy T2-weighted axial MR image-based deep learning model showed acceptable performance in predicting pCR or GR in patients with rectal cancer, compared with human observers.
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Vuijk FA, van de Water C, Lent-van Vliet S, van der Valk MJM, Simmer F, van de Velde CJH, Vahrmeijer AL, Nagtegaal ID, Hilling DE. Intra-Tumoral Genomic Heterogeneity in Rectal Cancer: Mutational Status Is Dependent on Preoperative Biopsy Depth and Location. Cancers (Basel) 2021; 13:cancers13092271. [PMID: 34065112 PMCID: PMC8125993 DOI: 10.3390/cancers13092271] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 04/18/2021] [Accepted: 04/28/2021] [Indexed: 01/09/2023] Open
Abstract
Neoadjuvant therapy before surgical resection is indicated for patients with locally advanced rectal cancer. However, a significant number of patients show minimal or no response to neoadjuvant therapy. Unfortunately, we are currently unable to predict response and identify non-responding patients before neoadjuvant treatment is given. Genomic mutational status might provide valuable prognostic information. However, it is unclear whether predictions based on genomic mutational status in single preoperative biopsies are reliable due to intra-tumoral heterogeneity. In this study we aim to investigate the reliability of genomic mutations found in single pre-operative biopsies by comparing genomic mutations to four other locations within the same tumor using next generation sequencing. Rectal cancer patients undergoing primary resection without neoadjuvant therapy were included. From each patient, one biopsy, two deep and two superficial samples were obtained and sequenced using a targeted next generation sequencing gene panel. Concordance between these five samples was assessed. In this feasibility study we included 11 patients. In 7 out of 11 (64%) patients, all 5 samples showed concordant mutations. In 4 out of 11 patients (36%) discordant mutations were observed. In conclusion, assessment of mutational status on a single pre-operative biopsy shows discordance with tumor tissue from other locations in 36% of cases. These results warrant careful interpretation of biopsy material analysis, as these might be influenced by tumor heterogeneity.
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Affiliation(s)
- Floris A. Vuijk
- Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (F.A.V.); (M.J.M.v.d.V.); (C.J.H.v.d.V.); (A.L.V.)
| | - Carlijn van de Water
- Department of Pathology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands; (C.v.d.W.); (S.L.-v.V.); (F.S.); (I.D.N.)
| | - Shannon Lent-van Vliet
- Department of Pathology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands; (C.v.d.W.); (S.L.-v.V.); (F.S.); (I.D.N.)
| | - Maxime J. M. van der Valk
- Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (F.A.V.); (M.J.M.v.d.V.); (C.J.H.v.d.V.); (A.L.V.)
| | - Femke Simmer
- Department of Pathology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands; (C.v.d.W.); (S.L.-v.V.); (F.S.); (I.D.N.)
| | - Cornelis J. H. van de Velde
- Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (F.A.V.); (M.J.M.v.d.V.); (C.J.H.v.d.V.); (A.L.V.)
| | - Alexander L. Vahrmeijer
- Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (F.A.V.); (M.J.M.v.d.V.); (C.J.H.v.d.V.); (A.L.V.)
| | - Iris D. Nagtegaal
- Department of Pathology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands; (C.v.d.W.); (S.L.-v.V.); (F.S.); (I.D.N.)
| | - Denise E. Hilling
- Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (F.A.V.); (M.J.M.v.d.V.); (C.J.H.v.d.V.); (A.L.V.)
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
- Correspondence:
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Shao Y, Zhang YX, Chen HH, Lu SS, Zhang SC, Zhang JX. Advances in the application of artificial intelligence in solid tumor imaging. Artif Intell Cancer 2021; 2:12-24. [DOI: 10.35713/aic.v2.i2.12] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 04/02/2021] [Accepted: 04/20/2021] [Indexed: 02/06/2023] Open
Affiliation(s)
- Ying Shao
- Department of Laboratory Medicine, People Hospital of Jiangying, Jiangying 214400, Jiangsu Province, China
| | - Yu-Xuan Zhang
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Huan-Huan Chen
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Shan-Shan Lu
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Shi-Chang Zhang
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Jie-Xin Zhang
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
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Boldrini L, Intven M, Bassetti M, Valentini V, Gani C. MR-Guided Radiotherapy for Rectal Cancer: Current Perspective on Organ Preservation. Front Oncol 2021; 11:619852. [PMID: 33859937 PMCID: PMC8042309 DOI: 10.3389/fonc.2021.619852] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 02/08/2021] [Indexed: 12/18/2022] Open
Abstract
Online MRI-guided radiotherapy (MRgRT) is one of the most recent technological advances in radiotherapy. MRgRT permits the visualization of tumorous and healthy tissue while the patient is on the treatment table and online daily plan adaptations following the observed anatomical changes. In the context of rectal cancer, online MRgRT is a very promising modality due to the pronounced geographical variability of tumor tissues and the surrounding healthy tissues. This current paper will discuss the possible applications of online MRgRT, in particular, in terms of radiotherapy dose escalation and response prediction in organ preservation approaches for rectal cancer.
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Affiliation(s)
- Luca Boldrini
- Unità Operativa Complessa Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Roma, Italy
- Istituto di Radiologia, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Martijn Intven
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, Netherlands
| | - Michael Bassetti
- Department of Human Oncology, University of Wisconsin-Madison, Madison, WI, United States
| | - Vincenzo Valentini
- Unità Operativa Complessa Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Roma, Italy
- Istituto di Radiologia, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Cihan Gani
- Department of Radiation Oncology, Eberhard Karls Universität Tübingen, Tübingen, Germany
- German Cancer Consortium (DKTK), Partner Site, Tübingen, Germany
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Byrd DR, Brierley JD, Baker TP, Sullivan DC, Gress DM. Current and future cancer staging after neoadjuvant treatment for solid tumors. CA Cancer J Clin 2021; 71:140-148. [PMID: 33156543 DOI: 10.3322/caac.21640] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 07/17/2020] [Accepted: 08/11/2020] [Indexed: 12/13/2022] Open
Abstract
Until recently, cancer registries have only collected cancer clinical stage at diagnosis, before any therapy, and pathological stage after surgical resection, provided no treatment has been given before the surgery, but they have not collected stage data after neoadjuvant therapy (NAT). Because NAT is increasingly being used to treat a variety of tumors, it has become important to make the distinction between both the clinical and the pathological assessment without NAT and the assessment after NAT to avoid any misunderstanding of the significance of the clinical and pathological findings. It also is important that cancer registries collect data after NAT to assess response and effectiveness of this treatment approach on a population basis. The prefix y is used to denote stage after NAT. Currently, cancer registries of the American College of Surgeons' Commission on Cancer only partially collect y stage data, and data on the clinical response to NAT (yc or posttherapy clinical information) are not collected or recorded in a standardized fashion. In addition to NAT, nonoperative management after radiation and chemotherapy is being used with increasing frequency in rectal cancer and may be expanded to other treatment sites. Using examples from breast, rectal, and esophageal cancers, the pathological and imaging changes seen after NAT are reviewed to demonstrate appropriate staging.
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Affiliation(s)
- David R Byrd
- Department of Surgery, University of Washington, Seattle, Washington
| | - James D Brierley
- Department of Radiation Oncology, Princess Margaret Cancer Center, University of Toronto, Toronto, Ontario, Canada
| | - Thomas P Baker
- The Joint Pathology Center, Defense Health Agency, National Capital Region Medical Directorate, Silver Spring, Maryland
| | - Daniel C Sullivan
- Department of Radiology, Duke University Medical Center, Durham, North Carolina
| | - Donna M Gress
- American Joint Committee on Cancer, American College of Surgeons, Chicago, Illinois
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Studying local tumour heterogeneity on MRI and FDG-PET/CT to predict response to neoadjuvant chemoradiotherapy in rectal cancer. Eur Radiol 2021; 31:7031-7038. [PMID: 33569624 DOI: 10.1007/s00330-021-07724-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 12/24/2020] [Accepted: 01/27/2021] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To investigate whether quantifying local tumour heterogeneity has added benefit compared to global tumour features to predict response to chemoradiotherapy using pre-treatment multiparametric PET and MRI data. METHODS Sixty-one locally advanced rectal cancer patients treated with chemoradiotherapy and staged at baseline with MRI and FDG-PET/CT were retrospectively analyzed. Whole-tumour volumes were segmented on the MRI and PET/CT scans from which global tumour features (T2Wvolume/T2Wentropy/ADCmean/SUVmean/TLG/CTmean-HU) and local texture features (histogram features derived from local entropy/mean/standard deviation maps) were calculated. These respective feature sets were combined with clinical baseline parameters (e.g. age/gender/TN-stage) to build multivariable prediction models to predict a good (Mandard TRG1-2) versus poor (Mandard TRG3-5) response to chemoradiotherapy. Leave-one-out cross-validation (LOOCV) with bootstrapping was performed to estimate performance in an 'independent' dataset. RESULTS When using only imaging features, local texture features showed an AUC = 0.81 versus AUC = 0.74 for global tumour features. After internal cross-validation (LOOCV), AUC to predict a good response was the highest for the combination of clinical baseline variables + global tumour features (AUC = 0.83), compared to AUC = 0.79 for baseline + local texture and AUC = 0.76 for all combined (baseline + global + local texture). CONCLUSION In imaging-based prediction models, local texture analysis has potential added value compared to global tumour features to predict response. However, when combined with clinical baseline parameters such as cTN-stage, the added value of local texture analysis appears to be limited. The overall performance to predict response when combining baseline variables with quantitative imaging parameters is promising and warrants further research. KEY POINTS • Quantification of local tumour texture on pre-therapy FDG-PET/CT and MRI has potential added value compared to global tumour features to predict response to chemoradiotherapy in rectal cancer. • However, when combined with clinical baseline parameters such as cTN-stage, the added value of local texture over global tumour features is limited. • Predictive performance of our optimal model-combining clinical baseline variables with global quantitative tumour features-was encouraging (AUC 0.83), warranting further research in this direction on a larger scale.
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A Comprehensive Evaluation of Associations Between Routinely Collected Staging Information and The Response to (Chemo)Radiotherapy in Rectal Cancer. Cancers (Basel) 2020; 13:cancers13010016. [PMID: 33375133 PMCID: PMC7792936 DOI: 10.3390/cancers13010016] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 12/10/2020] [Accepted: 12/17/2020] [Indexed: 12/22/2022] Open
Abstract
Simple Summary Rectal cancer patients are often treated with radiotherapy, either alone or combined with chemotherapy, prior to surgery to enable radical surgery on a non-resectable tumor or to lower the recurrence risk. For some patients, the tumor disappears completely after preoperative treatment, while others experience little or no benefit. Accurate prediction of therapy response before treatment is of great importance for a personalized treatment approach and intentional organ preservation. We performed a comprehensive evaluation of the predictive capacity of all routinely collected staging information at diagnosis in a population-based, completely staged patient material of 383 patients representing a real-life clinical situation. Size or stage of the rectal tumor were independent predictors of excellent response irrespective of preoperative treatment, with small/early-stage tumors being significantly more likely to reach a complete response. Levels of the tumor marker carcinoembryonic antigen (CEA) above upper normal limit halved the chance of response. Abstract Radiotherapy (RT) or chemoradiotherapy (CRT) are frequently used in rectal cancer, sometimes resulting in complete tumor remission (CR). The predictive capacity of all clinical factors, laboratory values and magnetic resonance imaging parameters performed in routine staging was evaluated to understand what determines an excellent response to RT/CRT. A population-based cohort of 383 patients treated with short-course RT (5 × 5 Gy in one week, scRT), CRT, or scRT with chemotherapy (scRT+CT) and having either had a delay to surgery or been entered into a watch-and-wait program were included. Complete staging according to guidelines was performed and associations between investigated variables and CR rates were analyzed in univariate and multivariate analyses. In total, 17% achieved pathological or clinical CR, more often after scRT+CT and CRT than after scRT (27%, 18% and 8%, respectively, p < 0.001). Factors independently associated with CR included clinical tumor stage, small tumor size (<3 cm), tumor level, and low CEA-value (<3.8 μg/L). Size or stage of the rectal tumor were associated with excellent response in all therapy groups, with small or early stage tumors being significantly more likely to reach CR (p = 0.01 (scRT), p = 0.01 (CRT) and p = 0.02 (scRT+CT). Elevated level of carcinoembryonic antigen (CEA) halved the chance of response. Extramural vascular invasion (EMVI) and mucinous character may indicate less response to RT alone.
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Haak HE, Maas M, Trebeschi S, Beets-Tan RGH. Modern MR Imaging Technology in Rectal Cancer; There Is More Than Meets the Eye. Front Oncol 2020; 10:537532. [PMID: 33117678 PMCID: PMC7578261 DOI: 10.3389/fonc.2020.537532] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 09/02/2020] [Indexed: 12/29/2022] Open
Abstract
MR imaging (MRI) is now part of the standard work up of patients with rectal cancer. Restaging MRI has been traditionally used to plan the surgical approach. Its role has recently increased and been adopted as a valuable tool to assist the clinical selection of clinical (near) complete responders for organ preserving treatment. Recently several studies have addressed new imaging biomarkers that combined with morphological provides a comprehensive picture of the tumor. Diffusion-weighted MRI (DWI) has entered the clinics and proven useful for response assessment after chemoradiotherapy. Other functional (quantitative) MRI technologies are on the horizon including artificial intelligence modeling. This narrative review provides an overview of recent advances in rectal cancer (re)staging by imaging with a specific focus on response prediction and evaluation of neoadjuvant treatment response. Furthermore, directions are given for future research.
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Affiliation(s)
- Hester E Haak
- Department of Radiology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, Netherlands.,Department of Surgery, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, Netherlands.,GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, Netherlands
| | - Monique Maas
- Department of Radiology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, Netherlands
| | - Stefano Trebeschi
- Department of Radiology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, Netherlands.,GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, Netherlands
| | - Regina G H Beets-Tan
- Department of Radiology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, Netherlands.,GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, Netherlands.,Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
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Abstract
At the moment, international guidelines for rectal cancer suggest to consider F-FDG PET/CT scan in a few conditions: (1) at disease presentation in case of suspected or proven metastatic synchronous adenocarcinoma with potentially curable M1 disease; (2) in the recurrence workup for serial carcinoembryonic antigen level elevation; (3) in the recurrence workup with metachronous metastases documented by CT, MRI, or biopsy; (4) in case of strong contraindication to IV contrast agent administration; and (5) to evaluate an equivocal finding on a contrast-enhanced CT or MRI. PET/CT is not indicated in the follow-up or surveillance of rectal cancer. On the other hand, an attentive evaluation of the literature shows that PET/CT may also be used in some circumstances with significant levels of diagnostic accuracy. This review article aims to emphasize differences between current international guidelines and scientific literature in the role of PET/CT in rectal cancer.
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Onal Y, Samanci C. The Role of Diffusion-weighted Imaging in Patients with Gastric Wall Thickening. Curr Med Imaging 2020; 15:965-971. [PMID: 32013813 DOI: 10.2174/1573405614666181115120109] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Revised: 10/18/2018] [Accepted: 10/26/2018] [Indexed: 01/20/2023]
Abstract
BACKGROUND Gastric cancer is the second leading cause of cancer death worldwide. AIMS In the benign and malign gastric pathologies, we measured the Apparent Diffusion Coefficient (ADC) value from the thickened section of the stomach wall. We assessed the diagnostic value of ADC and we wanted to see whether this value could be used to diagnose gastric pathologies. STUDY DESIGN This study has a prospective study design. METHODS A total of 90 patients, 27 with malign gastric pathologies 63 with benign gastric pathologies with Gastric Wall (GW) thickening in multidector CT, were evaluated by T2 weighted axial MR imaging and Diffusion-Weighted Imaging (DWI). Measurements were made both from the thickened wall and from the normal GW. Also, a new method called GW/spine ADC ratio was performed in image analysis. The value found after ADC measurement from the GW was proportioned to the spinal cord ADC value in the same section. RESULTS The ADC values measured from the pathological wall in patients with gastric malignancy (1.115 ± 0.156 x10-3 mm2/s) were significantly lower than the healthy wall measurements (1.621 ± 0.292 × 10-3 mm2/s) and benign gastric diseases (1.790± 0.359 x10-3 mm2/s). GW/spine ADC ratio was also lower in gastric malignancy group. CONCLUSION ADC measurement in DWI can be used to distinguish between benign and malign gastric pathologies.
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Affiliation(s)
- Yilmaz Onal
- Department of Radiology, Sultan Abdulhamid Han Training and Research Hospital, Haydarpasa, Istanbul, Turkey
| | - Cesur Samanci
- Department of Radiology, Sultan Abdulhamid Han Training and Research Hospital, Haydarpasa, Istanbul, Turkey
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