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Ono K, Hiyoshi Y, Ono A, Ouchi M, Kosumi K, Eto K, Ida S, Iwatsuki M, Baba Y, Miyamoto Y, Kajihara I, Tanaka K, Miyasato Y, Baba H. Locally advanced rectal cancer in a young adult affected with dyskeratosis congenita (Zinsser-Cole-Engman syndrome): a case report. Surg Case Rep 2024; 10:206. [PMID: 39237793 PMCID: PMC11377380 DOI: 10.1186/s40792-024-01985-9] [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: 05/08/2024] [Accepted: 08/01/2024] [Indexed: 09/07/2024] Open
Abstract
BACKGROUND Dyskeratosis congenita (DKC), also known as Zinsser-Cole-Engman syndrome, is a progressive genetic disease with a triad of reticulate skin pigmentation, nail dystrophy, and leukoplakia. Approximately 8-10% of patients with DKC develop malignancies, and cases of colorectal cancer with DKC in young people have been reported previously. CASE PRESENTATION A 25-year-old man with DKC since approximately 10 years of age developed fever and lower abdominal discomfort. Diagnostic imaging revealed locally advanced rectal cancer with lymph node metastasis, direct invasion of the prostate, and pelvic abscess due to tumor microperforation (cT4bN2M0 cStage IIIC). Biopsy showed well to moderately differentiated ductal adenocarcinoma. Genetic testing was negative for RAS and BRAF gene mutations, and microsatellite instability (MSI) testing was also negative. After sigmoid colostomy, the patient was treated with total neoadjuvant therapy (TNT) with systemic chemotherapy (six courses of FOLFOX + panitumumab) followed by chemoradiation therapy (50.4 Gy with capecitabine). After TNT, the primary tumor and metastatic lymph nodes shrank. According to the findings of colonoscopy and magnetic resonance image (MRI), we diagnosed near complete response (near-CR) and decided to follow the patient without surgery by every 3 months re-evaluation. However, 5 months after TNT, tumor regrowth was detected on colonoscopy and imaging, and the patient underwent total pelvic exenteration. He developed paralytic ileus as a postoperative complication, and was discharged on the 38th postoperative day. Pathological examination revealed a residual tumor with invasion of the periprostatic tissue. There was no metastasis in the pararectal and lateral pelvic lymph nodes, but one extramural non-contiguous cancerous extension (tumor deposit) was observed (ypT4bN1cM0 ypStage IIIC). The patient has been free of recurrence for one year after surgery. CONCLUSIONS DKC often develops into various tumors in the digestive system at an early age; therefore, appropriate surveillance may be required. In addition, considering that cancers in patients with DKC occur at a young age, fertility preservation and survivorship are also important, and adequate explanations and care should be provided to patients before and after treatment.
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Affiliation(s)
- Kosuke Ono
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yukiharu Hiyoshi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Asuka Ono
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Mayuko Ouchi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Keisuke Kosumi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Kojiro Eto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Satoshi Ida
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Masaaki Iwatsuki
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yoshifumi Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yuji Miyamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Ikko Kajihara
- Department of Dermatology, Kumamoto University Hospital, Kumamoto, Japan
| | - Kazuhito Tanaka
- Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan
| | - Yuko Miyasato
- Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
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Emile SH, Wignakumar A. Non-operative management of rectal cancer: Highlighting the controversies. World J Gastrointest Surg 2024; 16:1501-1506. [PMID: 38983314 PMCID: PMC11230012 DOI: 10.4240/wjgs.v16.i6.1501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 04/18/2024] [Accepted: 04/23/2024] [Indexed: 06/27/2024] Open
Abstract
There remains much ambiguity on what non-operative management (NOM) of rectal cancer truly entails in terms of the methods to be adopted and the best algorithm to follow. This is clearly shown by the discordance between various national and international guidelines on NOM of rectal cancer. The main aim of the NOM strategy is organ preservation and avoiding unnecessary surgical intervention, which carries its own risk of morbidity. A highly specific and sensitive surveillance program must be devised to avoid patients undergoing unnecessary surgical interventions. In many studies, NOM, often interchangeably called the Watch and Wait strategy, has been shown as a promising treatment option when undertaken in the appropriate patient population, where a clinical complete response is achieved. However, there are no clear guidelines on patient selection for NOM along with the optimal method of surveillance.
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Affiliation(s)
- Sameh Hany Emile
- Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Anjelli Wignakumar
- Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, FL 33331, United States
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Gheller A, Basílio DB, da Costa MCR, Tuma SA, Ferreira OMTA, Lyrio FG, Girardi DDM, de Sousa JB. Identification of radiologic and clinicopathologic variables associated with tumor regression pattern and distribution of cancer cells after short-course radiotherapy and consolidation chemotherapy in patients with rectal cancer. Front Oncol 2024; 14:1386697. [PMID: 38974246 PMCID: PMC11224439 DOI: 10.3389/fonc.2024.1386697] [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: 02/15/2024] [Accepted: 06/10/2024] [Indexed: 07/09/2024] Open
Abstract
Background Knowledge of the pattern of regression and distribution of residual tumor cells may assist in the selection of candidates for rectum-sparing strategies. Objective To investigate and identify factors associated with tumor regression pattern and distribution of residual tumor cells. Methods We conducted a prospective study of patients with T3/T4 N0/N+ adenocarcinoma of the middle and lower third of the rectum (≤10 cm) treated with radiotherapy (5×5 Gy) followed by 6 cycles of CAPOX chemotherapy. The pattern of tumor regression was classified as fragmented or solid. Microscopic intramural spread was measured. We used a model of distribution of residual tumor cells not yet applied to rectal cancer, defined as follows: type I (luminal), type II (invasive front), type III (concentric), and type IV (random). Results Forty patients were included with a median age of 66 years; 23 (57.5%) were men. A fragmented pattern was identified in 18 patients (45.0%), and a solid pattern in 22 (55.0%). Microscopic intramural spread was identified in 25 patients (62.5%), extending from 1 to 18 mm (median, 4 mm). There were 14 cases (35.0%) of microscopic intramural spread ≥10 mm. All cases of fragmented regression pattern, except one, showed microscopic intramural spread. Within the fragmented pattern, microscopic intramural spread was 4-8 mm in 4 cases and ≥10 mm in the remaining cases. All cases of microscopic intramural spread ≥ 10 mm were within the fragmented pattern. Regarding the distribution pattern of residual tumor cells, 11 cases (31.5%) were classified as type I, 14 (40.0%) as type II, 10 (28.5%) as type III, and none as type IV. Carcinoembryonic antigen levels >5 ng/mL, downsizing <50%, residual mucosal abnormality >20 mm, and anatomopathologic lymph node involvement were significantly associated with the occurrence of fragmentation (P<0.05). Having received all 6 cycles of CAPOX chemotherapy and absence of microscopic intramural spread were significantly associated with the type I distribution pattern (P<0.05). Conclusion The occurrence of a fragmented regression pattern is common, as is the presence of microscopic intramural spread. We could identify radiologic and clinicopathologic factors associated with the pattern of tumor regression and a type I distribution pattern.
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Affiliation(s)
- Alexandre Gheller
- Colorectal Surgery Department, Hospital de Base do Distrito Federal, Brasília, DF, Brazil
| | - Dunya Bachour Basílio
- Anatomopathology Department, Hospital de Base do Distrito Federal, Brasília, DF, Brazil
| | | | - Sussen Araújo Tuma
- Anatomopathology Department, Hospital de Base do Distrito Federal, Brasília, DF, Brazil
| | | | | | | | - João Batista de Sousa
- Division of Colorectal Surgery, Universidade de Brasília (UnB), Brasília, DF, Brazil
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Kakish H, Ahmed FA, Ocuin LM, Miller-Ocuin JL, Steinhagen E, Hoehn RS, Mahipal A, Towe CW, Chakrabarti S. Outcome of Patients with Locally Advanced Rectal Cancer Pursuing Non-Surgical Strategy in National Cancer Database. Cancers (Basel) 2024; 16:2194. [PMID: 38927900 PMCID: PMC11202149 DOI: 10.3390/cancers16122194] [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: 05/07/2024] [Revised: 05/30/2024] [Accepted: 06/10/2024] [Indexed: 06/28/2024] Open
Abstract
BACKGROUND Survival data on patients with locally advanced rectal cancer (LARC) undergoing non-operative management (NOM) in a real-world setting are lacking. METHODS We analyzed LARC patients from the National Cancer Database with the following features: treated between 2010 and 2020, age 18-65 years, Charlson comorbidity index (CCI) ≤ 1, received neoadjuvant multiagent chemotherapy plus radiation ≥ 45 Gray, and underwent surgery or NOM. Patients were stratified into two groups: (A) clinical T1-3 tumors with positive nodes (cT1-3N+) and (B) clinical T4 tumors, N+/- (cT4N+/-). We performed a comparative analysis of overall survival (OS) with NOM versus surgery by the Kaplan-Meier method and propensity score matching. Additionally, a multivariable analysis explored the association between NOM and OS. RESULTS NOM exhibited significantly lower OS than surgery in both groups. In cT1-3N+ patients, NOM resulted in a 5-year OS of 73.9% (95% confidence interval [CI] = 69.7-77.6%) versus 84.5% (95% CI = 83.6-85.3%) with surgery (p < 0.001). In the cT4N+/- group, NOM yielded a 5-year OS of 44.5% (95% CI = 37.0-51.8%) versus 72.5% (95% CI = 69.9-74.8%) with surgery (p < 0.001). Propensity score matching and multivariable analyses revealed similar conclusions. CONCLUSION Patients with LARC undergoing NOM versus surgery in real-world settings appear to have inferior survival.
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Affiliation(s)
- Hanna Kakish
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
| | - Fasih A. Ahmed
- Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Lee M. Ocuin
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
| | - Jennifer L. Miller-Ocuin
- Department of Surgery, Division of Colorectal Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
| | - Emily Steinhagen
- Department of Surgery, Division of Colorectal Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
| | - Richard S. Hoehn
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
| | - Amit Mahipal
- Department of Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Christopher W. Towe
- Division of Thoracic and Esophageal Surgery, Department of Surgery, Case Western Reserve School of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
| | - Sakti Chakrabarti
- Department of Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA
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Khalafi S, Riddle M, Harper B, Fikfak V. Perianal Mucinous Adenocarcinoma Found Incidentally From Perianal Mass. Cureus 2023; 15:e48314. [PMID: 38058344 PMCID: PMC10696282 DOI: 10.7759/cureus.48314] [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: 09/22/2023] [Accepted: 11/04/2023] [Indexed: 12/08/2023] Open
Abstract
Anal mucinous adenocarcinomas are very rare and usually arise from anal fistulas. We report a case of a 73-year-old man with a past medical history of hypertension admitted to our facility for evaluation of bleeding from a large, tender, left gluteal perianal mass. The patient reported the mass had been growing for over six years. On examination, an ulcerated, fungating large exophytic lesion was found extending from the anal verge laterally engulfing the left gluteus. The patient was anemic with low hemoglobin and hematocrit, as well as an elevated carcinoembryonic antigen level. A colonoscopy was performed during which an internal opening of a left-sided anal fistula was identified. The mass was biopsied and returned positive for a mucinous adenocarcinoma. Staging imaging including a computed tomography scan of the chest abdomen and pelvis did not show any metastatic disease. A magnetic resonance image of the pelvis revealed a locally invasive, heterogeneous tumor extending from the perianal soft tissue to the posterior wall of the anal canal and lower rectum. The patient was discussed at the interdisciplinary tumor board and completed five weeks of concurrent chemotherapy and radiation with 5-fluorouracil and a total of 28 fractions of radiation. He then underwent abdominoperineal resection with a vertical rectus abdominis myocutaneous flap. The patient was placed in the surgical intensive care unit and subsequently discharged in stable condition on postoperative day 14. This case highlights the presentation, diagnosis, and management of anal mucinous adenocarcinoma.
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Affiliation(s)
- Seyed Khalafi
- Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, USA
| | - Malini Riddle
- Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, USA
| | - Brittany Harper
- Surgery, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, USA
| | - Vid Fikfak
- Surgery, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, USA
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Lee SH. Total neoadjuvant therapy for rectal cancer: evidence and challenge. Ann Coloproctol 2023; 39:301-306. [PMID: 37648423 PMCID: PMC10475808 DOI: 10.3393/ac.2023.00269.0038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 06/28/2023] [Accepted: 06/28/2023] [Indexed: 09/01/2023] Open
Abstract
Recent advances in the management of rectal cancer have dramatically changed the clinical practice of colorectal surgeons because the main focus of rectal cancer treatment has changed from sphincter-saving to an organ-preserving strategies. Modifying the delivery of systemic chemotherapy to improve patients' survival is another progress in colorectal cancer management, known as total neoadjuvant therapy (TNT). TNT is a new strategy used by colorectal surgeons to improve the quality of life and survival of patients after treatment. TNT poses limitations or obstacles, such as overtreatment issues in patients with stage I rectal cancer. However, considering the quality-of-life issues in patients with low-lying rectal cancer necessitating a permanent colostomy, the indication for TNT will be expanded. This review summarizes the recently conducted clinical trials and foresees future perspectives on TNT.
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Affiliation(s)
- Suk-Hwan Lee
- Department of Surgery, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul, Korea
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He L, Xiao J, Zheng P, Zhong L, Peng Q. Lymph node regression grading of locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. World J Gastrointest Oncol 2022; 14:1429-1445. [PMID: 36160739 PMCID: PMC9412927 DOI: 10.4251/wjgo.v14.i8.1429] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 04/30/2022] [Accepted: 07/06/2022] [Indexed: 02/05/2023] Open
Abstract
Neoadjuvant chemoradiotherapy (nCRT) and total rectal mesenteric excision are the main standards of treatment for locally advanced rectal cancer (LARC). Lymph node regression grade (LRG) is an indicator of prognosis and response to preoperative nCRT based on postsurgical metastatic lymph node pathology. Common histopathological findings in metastatic lymph nodes after nCRT include necrosis, hemorrhage, nodular fibrosis, foamy histiocytes, cystic cell reactions, areas of hyalinosis, residual cancer cells, and pools of mucin. A number of LRG systems designed to classify the amount of lymph node regression after nCRT is mainly concerned with the relationship between residual cancer cells and regressive fibrosis and with estimating the number of lymph nodes existing with residual cancer cells. LRG offers significant prognostic information, and in most cases, LRG after nCRT correlates with patient outcomes. In this review, we describe the systematic classification of LRG after nCRT, patient prognosis, the correlation with tumor regression grade, and the typical histopathological findings of lymph nodes. This work may serve as a reference to help predict the clinical complete response and determine lymph node regression in patients based on preservation strategies, allowing for the formulation of more accurate treatment strategies for LARC patients, which has important clinical significance and scientific value.
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Affiliation(s)
- Lei He
- School of Medicine, University of Electronic Science and Technology of China, Chengdu 611731, Sichuan Province, China
| | - Juan Xiao
- School of Medicine, University of Electronic Science and Technology of China, Chengdu 611731, Sichuan Province, China
| | - Ping Zheng
- Department of Pathology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, Sichuan Province, China
| | - Lei Zhong
- Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu 610072, Sichuan Province, China
| | - Qian Peng
- Radiation Therapy Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, Sichuan Province, China
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Azamat S, Karaman Ş, Azamat IF, Ertaş G, Kulle CB, Keskin M, Sakin RND, Bakır B, Oral EN, Kartal MG. Complete Response Evaluation of Locally Advanced Rectal Cancer to Neoadjuvant Chemoradiotherapy Using Textural Features Obtained from T2 Weighted Imaging and ADC Maps. Curr Med Imaging 2022; 18:1061-1069. [PMID: 35240976 DOI: 10.2174/1573405618666220303111026] [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: 08/20/2021] [Revised: 12/07/2021] [Accepted: 12/22/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND The prediction of pathological responses for locally advanced rectal cancer using magnetic resonance imaging (MRI) after neoadjuvant chemoradiotherapy (CRT) is a challenging task for radiologists, as residual tumor cells can be mistaken for fibrosis. Texture analysis of MR images has been proposed to understand the underlying pathology. OBJECTIVE This study aimed to assess the responses of lesions to CRT in patients with locally advanced rectal cancer using the first-order textural features of MRI T2-weighted imaging (T2-WI) and apparent diffusion coefficient (ADC) maps. METHODS Forty-four patients with locally advanced rectal cancer (median age: 57 years) who underwent MRI before and after CRT were enrolled in this retrospective study. The first-order textural parameters of tumors on T2-WI and ADC maps were extracted. The textural features of lesions in pathologic complete responders were compared to partial responders using Student's t- or Mann-Whitney U tests. A comparison of textural features before and after CRT for each group was performed using the Wilcoxon rank sum test. Receiver operating characteristic curves were calculated to detect the diagnostic performance of the ADC. RESULTS Of the 44 patients evaluated, 22 (50%) were placed in a partial response group and 50% were placed in a complete response group. The ADC changes of the complete responders were statistically more significant than those of the partial responders (P = 0.002). Pathologic total response was predicted with an ADC cut-off of 1310 x 10-6 mm2/s, with a sensitivity of 72%, a specificity of 77%, and an accuracy of 78.1% after neoadjuvant CRT. The skewness of the T2-WI before and after neoadjuvant CRT showed a significant difference in the complete response group compared to the partial response group (P = 0.001 for complete responders vs. P = 0.482 for partial responders). Also, relative T2-WI signal intensity in the complete response group was statistically lower than that of the partial response group after neoadjuvant CRT (P = 0.006). CONCLUSION As a result of the conversion of tumor cells to fibrosis, the skewness of the T2-WI before and after neoadjuvant CRT was statistically different in the complete response group compared to the partial response group, and the complete response group showed statistically lower relative T2-WI signal intensity than the partial response group after neoadjuvant CRT. Additionally, the ADC cut-off value of 1310 × 10-6 mm2/s could be used as a marker for complete response along with absolute ADC value changes within this dataset.
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Affiliation(s)
- Sena Azamat
- Institute of Biomedical Engineering, Bogazici University, Istanbul, Turkey
- Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
| | - Şule Karaman
- Department of Radiation Oncology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ibrahim Fethi Azamat
- Department of General Surgery, Faculty of Medicine, Koc University, Istanbul, Turke
| | - Gokhan Ertaş
- Biomedical Engineering Department, Yeditepe University, Istanbul, Turkey
| | - Cemil Burak Kulle
- Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Metin Keskin
- Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
- Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | | | - Barış Bakır
- Department of Radiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ethem Nezih Oral
- Department of Radiation Oncology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Merve Gulbiz Kartal
- Department of Radiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Vendrely V, Rivin Del Campo E, Modesto A, Jolnerowski M, Meillan N, Chiavassa S, Serre AA, Gérard JP, Créhanges G, Huguet F, Lemanski C, Peiffert D. Rectal cancer radiotherapy. Cancer Radiother 2021; 26:272-278. [PMID: 34953708 DOI: 10.1016/j.canrad.2021.11.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
We present the updated recommendations of the French society of oncological radiotherapy for rectal cancer radiotherapy. The standard treatment for locally advanced rectal cancer consists in chemoradiotherapy followed by radical surgery with total mesorectal resection and adjuvant chemotherapy according to nodal status. Although this strategy efficiently reduced local recurrences rates below 5% in expert centres, functional sequelae could not be avoided resulting in 20 to 30% morbidity rates. The early introduction of neoadjuvant chemotherapy has proven beneficial in recent trials, in terms of recurrence free and metastasis free survivals. Complete pathological responses were obtained in 15% of tumours treated by chemoradiation, even reaching up to 30% of tumours when neoadjuvant chemotherapy is associated to chemoradiotherapy. These good results question the relevance of systematic radical surgery in good responders. Personalized therapeutic strategies are now possible by improved imaging modalities with circumferential margin assessed by magnetic resonance imaging, by intensity modulated radiotherapy and by refining surgical techniques, and contribute to morbidity reduction. Keeping the same objectives, ongoing trials are now evaluating therapeutic de-escalation strategies, in particular rectal preservation for good responders after neoadjuvant treatment, or radiotherapy omission in selected cases (Greccar 12, Opera, Norad).
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Affiliation(s)
- V Vendrely
- Service d'oncologie radiothérapie, Hôpital Haut-Lévêque, CHU de Bordeaux, avenue de Magellan, 33600 Pessac, France; Inserm U1035, université de Bordeaux, 33000 Bordeaux, France.
| | - E Rivin Del Campo
- Service d'oncologie radiothérapie, hôpital Tenon, Hôpitaux universitaires Est Parisien, Sorbonne université, 75020 Paris, France
| | - A Modesto
- Service d'oncologie radiothérapie, institut Claudius-Regaud, université de Toulouse, 31000 Toulouse, France
| | - M Jolnerowski
- Service universitaire de radiothérapie, Institut de cancérologie de Lorraine centre Alexis-Vautrin, 54000 Nancy, France
| | - N Meillan
- Service d'oncologie radiothérapie, hôpital Pitié Salpêtrière, APHP, Sorbonne université, 75013 Paris, France
| | - S Chiavassa
- Service de physique médicale, Institut de cancérologie de l'Ouest (ICO) centre René-Gauducheau, 44805 Saint-Herblain, France
| | - A-A Serre
- Service d'oncologie radiothérapie, centre Léon-Bérard, 69000 Lyon, France
| | - J-P Gérard
- Service d'oncologie radiothérapie, centre Antoine-Lacassagne, université Côte d'Azur, 06000 Nice, France
| | - G Créhanges
- Service d'oncologie radiothérapie, institut Curie, 26, rue d'Ulm, 75005 Paris, France
| | - F Huguet
- Service d'oncologie radiothérapie, hôpital Tenon, Hôpitaux universitaires Est Parisien, Sorbonne université, 75020 Paris, France
| | - C Lemanski
- Fédération universitaire d'oncologie radiothérapie d'Occitanie Méditerranée, Institut du cancer de Montpellier, université de Montpellier, 34000 Montpellier, France
| | - D Peiffert
- Service universitaire de radiothérapie, Institut de cancérologie de Lorraine centre Alexis-Vautrin, 54000 Nancy, France
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[Rectal cancer: Towards personalized medicine]. Cancer Radiother 2021; 25:650-654. [PMID: 34266737 DOI: 10.1016/j.canrad.2021.06.026] [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: 06/03/2021] [Revised: 06/09/2021] [Accepted: 06/12/2021] [Indexed: 11/24/2022]
Abstract
The standard of care for patients with locally advanced rectal cancer has recently changed and is now based on the concept of total neoadjuvant therapy with the association of radiotherapy and systemic chemotherapy before radical surgery. The addition of noeadjuvant systemic chemotherapy before or after radiotherapy during preoperative course significantly decreased the risk of distant metastases and prolonged disease-free survival after surgery. The risk of recurrence varies among patients and the standard management associating chemotherapy, radiotherapy and surgery may expose many patients to overtreatment and can negatively affect quality of life. In this setting, several ongoing trials evaluate the possibility of less aggressive individually tailored approach based on omission of one of three treatments. In particular, NORAD and PROSPECT trials evaluate whether irradiation could be safely omitted in patients who are good responders to induction chemotherapy and have locally advanced primarily resectable tumor with large predictive circumferential resection margin. In the other hand, the total neoadjuvant therapy had significantly improved the pathological complete response rate, up to 30%, leading the concept of non-operative management and organ-preserving strategies. The phase III GRECCAR 12 study has therefore evaluated the potential benefit of intensification of neoadjuvant chemotherapy whereas OPERA and MORPHEUS trials assessed radiotherapy dose escalation by contact X-ray or brachytherapy for organ-preserving strategies. To date, total neoadjuvant therapy following by radical surgery remains the standard of care but probably less aggressive approach with omission of radiotherapy or surgery will become a new standard in selected patients in next future.
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Long-term outcomes of transanal endoscopic microsurgery for clinical complete response after neoadjuvant treatment in T2-3 rectal cancer. Surg Endosc 2021; 36:2906-2913. [PMID: 34231071 DOI: 10.1007/s00464-021-08583-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 06/02/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND Organ sparing by the transanal endoscopic microsurgery (TEM) procedure is a treatment for patients with locally advanced rectal cancer after chemoradiotherapy (CRT) and complete clinical response (cCR). AIMS To assess the surgical and long-term oncological outcomes of TEM for the treatment in T2-3 rectal cancer after CRT and cCR. METHODS This study was a retrospective review of a prospective database of patients with rectal cancer who underwent TEM after CRT and cCR from April 2011 to March 2020. RESULTS 52 patients underwent TEM during a period of 9 years. This group of patients included 27 females and 25 males. The median age was 62 (32-86) years, lesion size was 2.5 (1-4) cm, and lesion distance from the anal verge 7.3 (4-10) cm. Median operative time was 79.5 (25-120) min and hospital stay was 1 day (14 h-4 days). Morbidity rate was 13.5% and reoperation rate due to major complications was 3.8%. Final histological findings confirmed 34 (65.4%) patients with ypT0, 7 (13.5%), 6 (11.5%), and 5 (9.6%) patients with carcinoma ypT1, ypT2, and ypT3, respectively. After a median follow-up period of 86 (5-107) months, 1 (2.4%) patient had local recurrences and 3 (7.3%) distant metastases. The 5-year disease-free survival was 91.7% and 5-year overall survival 89.5%. CONCLUSION Our experience has shown significant rates of ypT0 and ypT1 associated with excellent long-term results. Performing TEM to treat T2-3N0 rectal cancer after CRT and cCR appears to be an oncologically safe and effective procedure.
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12
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Aliyev V, Goksel S, Asoglu O. Acute Ischemic Gangrene of the Rectosigmoid Colon in a Patient With Rectal Cancer in the "Watch-and-Wait" Protocol. Cureus 2021; 13:e14998. [PMID: 33996340 PMCID: PMC8117261 DOI: 10.7759/cureus.14998] [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] [Indexed: 11/24/2022] Open
Abstract
Acute rectal ischemia is a rare entity because the rectum has abundant blood supply from the inferior mesenteric, internal iliac, internal pudendal, and marginal artery with rich collaterals. We present a case of an acute ischemic proctosigmoiditis with a history of rectal cancer who completely recovered after total neoadjuvant treatment and was in the “watch-and-wait” protocol. Urgent laparoscopic low anterior resection and protective ileostomy were performed. Causes of acute rectosigmoid ischemia include old age, diabetes, atherosclerosis, previous aortic surgery due to aneurysm, vasculitis, and radiotherapy. Ischemia may be present as only involving the mucosa, which can be managed conservatively, but full-thickness necrosis requires urgent surgical intervention. Endoscopic examination is the gold standard in initial diagnosis. Ischemic gangrene of the rectosigmoid colon is a rare condition and can be life-threatening unless an urgent surgical intervention is performed.
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Affiliation(s)
- Vusal Aliyev
- General and Colorectal Surgery, Maslak Acibadem Hospital, Istanbul, TUR
| | - Suha Goksel
- Pathology, Maslak Acibadem Hospital, Istanbul, TUR
| | - Oktar Asoglu
- General and Colorectal Surgery, Bogazici Academy for Clinical Sciences, Istanbul, TUR
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13
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Meyer VM, Meuzelaar RR, Schoenaker Y, de Groot JW, de Boer E, Reerink O, de Vos tot Nederveen Cappel W, Beets GL, van Westreenen HL. Delayed Surgery after Neoadjuvant Treatment for Rectal Cancer Does Not Lead to Impaired Quality of Life, Worry for Cancer, or Regret. Cancers (Basel) 2021; 13:742. [PMID: 33670120 PMCID: PMC7916848 DOI: 10.3390/cancers13040742] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 02/05/2021] [Accepted: 02/07/2021] [Indexed: 12/24/2022] Open
Abstract
Non operative management of complete clinical responders after neoadjuvant treatment for rectal cancer enjoys an increasing popularity because of the increased functional outcome results. Even a near complete response can evolve in a cCR, and therefore further delaying response assessment is accepted. However, up to 40% of patients will develop a regrowth and will eventually require delayed surgery. It is presently unknown if and to what extent quality of life of these patients is affected, compared to patients who undergo immediate surgery. Between January 2015-May 2020, 200 patients were treated with neoadjuvant therapy of whom 94 received TME surgery. Fifty-one (59%) of 87 alive patients returned the questionnaires: 33 patients who underwent immediate and 18 patients who underwent delayed surgery. Quality of life was measured through the QLQ-C30, QLQ-CR29, and Cancer Worry Scale questionnaires. Regret to participate in repeated response assessment protocol was assessed through the Decision Regret Scale. Exploratory factor analysis (EFA) and a 'known groups comparison' was performed to assess QLQ questionnaires validity in this sample. Higher mean physical function scores (89.2 vs. 77.6, p = 0.03) were observed in the immediate surgery group, which lost significance after correction for operation type (p = 0.25). Arousal for men was higher in the delayed surgery group (20.0 vs. 57.1, p = 0.02). There were no differences between surgical groups for the other questionnaire items. Worry for cancer was lower in the delayed surgery group (10.8 vs. 14.0, p = 0.21). Regret was very low (12-16%). EFA reproduced most QLQ C-30 and CR29 subscales with good internal consistency. Quality of life is not impaired in patients undergoing delayed TME surgery after neoadjuvant treatment for rectal cancer. Moreover, there is very low regret and no increase in worry for cancer. Therefore, from a quality of life perspective, this study supports a repeated response assessment strategy after CRTx for rectal carcinoma to identify all complete responders.
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Affiliation(s)
- Vincent Maurice Meyer
- Department of Surgery, Isala Hospitals, P.O. Box 10400, 8000 GK Zwolle, The Netherlands; (R.R.M.); (Y.S.); (H.L.v.W.)
| | - Richtje R Meuzelaar
- Department of Surgery, Isala Hospitals, P.O. Box 10400, 8000 GK Zwolle, The Netherlands; (R.R.M.); (Y.S.); (H.L.v.W.)
| | - Yvonne Schoenaker
- Department of Surgery, Isala Hospitals, P.O. Box 10400, 8000 GK Zwolle, The Netherlands; (R.R.M.); (Y.S.); (H.L.v.W.)
| | - Jan-Willem de Groot
- Department of Oncology, Isala Hospitals, P.O. Box 10400, 8000 GK Zwolle, The Netherlands;
| | - Edwin de Boer
- Department of Radiology, Isala Hospitals, 8025 AB Zwolle, The Netherlands;
| | - Onno Reerink
- Department of Radiotherapy, Isala Hospitals, 8025 AB Zwolle, The Netherlands;
| | | | - Geerard L Beets
- Department of Surgery, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands;
| | - Henderik L van Westreenen
- Department of Surgery, Isala Hospitals, P.O. Box 10400, 8000 GK Zwolle, The Netherlands; (R.R.M.); (Y.S.); (H.L.v.W.)
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14
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Hayes IP, Milanzi E, Gibbs P, Reece JC. Neoadjuvant Chemoradiotherapy and Tumor Recurrence in Patients with Early T-Stage Cancer of the Lower Rectum. Ann Surg Oncol 2019; 27:1570-1579. [PMID: 31773520 DOI: 10.1245/s10434-019-08105-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND The role neoadjuvant chemoradiotherapy (nCRT) plays in oncological outcomes in early T-stage rectal cancer is uncertain. The present work aims to clarify prognostic outcomes by estimating the effect of nCRT on tumor recurrence prior to major surgery compared with major surgery alone. PATIENTS AND METHODS Prospectively collected data were retrospectively analyzed for patients diagnosed with localized rectal adenocarcinoma ≤ 8 cm from the anal verge, with final histopathology ≤ T2 (≤ ypT2/≤ pT2), regardless of magnetic resonance imaging staging, between 1990 and 2017. As the effect of nCRT on recurrence varied over time, thereby violating the Cox proportional hazards assumption, the effect of nCRT on recurrence hazards was estimated using a time-varying multivariate Cox model over two separate time intervals (≤ 1 year and > 1 year postsurgery) by nCRT. RESULTS Long-course nCRT was associated with a 5.6-fold increase in the hazard of recurrence ≤ 1 year postsurgery [hazard ratio (HR) 5.6; 95% confidence interval (CI) 1.2-24.9; P = 0.02], but there was no increase in recurrence hazards > 1 year (HR 0.84; 95% CI 0.4-2.0; P = 0.70). In subgroup analysis restricted to ≤ mrT2/≤ ypT2 and ≤ pT2 tumors (omitting > mrT2 tumors), the effect of nCRT on recurrence no longer varied over time, indicating that tumor heterogeneity was responsible for the observed increased recurrence hazards ≤ 1 year postsurgery; That is, > mrT2 tumors that were downstaged to ≤ ypT2 after nCRT were responsible for the time-varying effects of nCRT and increased recurrence hazards ≤ 1 year postsurgery. Subsequently, no difference was found in prognostic outcomes either with or without nCRT before surgery in the homogeneous population of ≤ mrT2/≤ ypT2 and ≤ pT2 tumors. CONCLUSIONS No evidence was found to indicate that nCRT prior to surgery reduces tumor recurrence in early T-stage lower rectal cancer compared with surgery alone.
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Affiliation(s)
- Ian P Hayes
- Colorectal Surgery Unit, Suite 2, Private Medical Centre, Royal Melbourne Hospital, Parkville, VIC, Australia. .,Department of Surgery, The University of Melbourne, Parkville, VIC, Australia.
| | - Elasma Milanzi
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, VIC, Australia.,Victorian Centre for Biostatistics, Melbourne, VIC, Australia
| | - Peter Gibbs
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.,Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia.,Department of Medical Oncology, Western Health, Melbourne, VIC, Australia
| | - Jeanette C Reece
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, VIC, Australia.,The University of Melbourne Centre for Cancer Research, The University of Melbourne, Parkville, VIC, Australia
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15
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Nasir I, Fernandez L, Vieira P, Parés O, Santiago I, Castillo-Martin M, Domingos H, Cunha JF, Carvalho C, Heald RJ, Beets GL, Parvaiz A, Figueiredo N. Salvage surgery for local regrowths in Watch & Wait - Are we harming our patients by deferring the surgery? Eur J Surg Oncol 2019; 45:1559-1566. [PMID: 31006589 DOI: 10.1016/j.ejso.2019.04.006] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Revised: 02/23/2019] [Accepted: 04/04/2019] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Rectal cancer surgery conveys significant morbidity/mortality, long-term functional impairment and urinary & sexual dysfunction, especially if associated with neoadjuvant chemoradiotherapy (ChRT). Watch & Wait (W&W) is gaining momentum as an option for patients with clinical complete response (cCR) after ChRT. Approximately 30% will develop a local regrowth (RG) and need deferred surgery. Our study aimed to assess the short-term clinical outcomes after surgery for regrowths. PATIENTS AND METHODS Consecutive rectal cancer patients from a tertiary institution who underwent neoadjuvant ChRT, between January 2013 and October 2018, were identified from a prospectively maintained database. Patients with RG under W&W surveillance were operated - regrowth deferred surgery (RDS) group - and compared to those with persistent disease after ChRT who did undergo surgery - non-deferred surgery (NDS) group. RESULTS Total of 124 patients received neoadjuvant treatment: 46 (37%) underwent surgery for persistent disease; 78 (63%) with cCR entered W&W. Twenty three developed RG and underwent surgery, while 55 remain under surveillance. RDS group had lower tumors than NDS group (2.3 cm ± 2 vs 4.5 cm ± 3, p = 0.002). All RG underwent minimally invasive surgery (MIS). Anastomotic leaks, 30-day morbidity, reintervention and readmission rates were similar. Pathology features and 3-year oncological outcomes were identical between groups. CONCLUSION Patients with initial cCR and local regrowth may be safely managed by deferred surgery. Short-term outcomes suggest equivalent results to patients with incomplete clinical response and immediate radical surgery. Delayed MIS appears to have no negative impact on oncological outcomes.
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Affiliation(s)
- Irfan Nasir
- Colorectal Surgery - Champalimaud Foundation, Lisbon, Portugal
| | - Laura Fernandez
- Colorectal Surgery - Champalimaud Foundation, Lisbon, Portugal
| | - Pedro Vieira
- Colorectal Surgery - Champalimaud Foundation, Lisbon, Portugal
| | - Oriol Parés
- Radiation Oncology - Champalimaud Foundation, Lisbon, Portugal
| | - Inês Santiago
- Radiology - Champalimaud Foundation, Lisbon, Portugal
| | | | - Hugo Domingos
- Colorectal Surgery - Champalimaud Foundation, Lisbon, Portugal
| | - Jose F Cunha
- Colorectal Surgery - Champalimaud Foundation, Lisbon, Portugal
| | - Carlos Carvalho
- Medical Oncology - Champalimaud Foundation, Lisbon, Portugal
| | - Richard J Heald
- Colorectal Surgery - Champalimaud Foundation, Lisbon, Portugal
| | - Geerard L Beets
- Colorectal Surgery - Champalimaud Foundation, Lisbon, Portugal; Surgical Oncology - The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Amjad Parvaiz
- Colorectal Surgery - Champalimaud Foundation, Lisbon, Portugal
| | - Nuno Figueiredo
- Colorectal Surgery - Champalimaud Foundation, Lisbon, Portugal.
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16
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Zhang M, Li J, Ma X, Wang B, Wu J, Gao Y, Tian J, Wang J. The value of magnetic resonance imaging to diagnose pathological complete response of rectal cancer after therapy: A protocol for meta-analysis. Medicine (Baltimore) 2018; 97:e12901. [PMID: 30412091 PMCID: PMC6221727 DOI: 10.1097/md.0000000000012901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Accepted: 09/27/2018] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Although the trends of colorectal incidence rate and mortality have decreased during the past 20 years, however, they are still high. Neoadjuvant chemoradiotherapy is recommended as the standard treatment strategy of local advanced rectal cancer followed by surgery and adjuvant therapy. Predicting pathological complete response (pCR) accurately is relative to the next treatment strategy to avoid extensive therapy. And there are more and more physicians who would like to choose pelvic MRI imaging to evaluate the state of rectal cancer. Therefore, our analysis will aim to assess the value of MRI to predict pCR of rectal cancer after therapy and distinguish which sequence and magnetic strength is the best one to diagnose pCR. METHODS Comprehensive computer-based search will be performed using the PubMed, EMBASE, Cochrane Library, and CBM database (last updated in April 2018), 2 reviewers will extract the related information respectively. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the area under the hierarchical summary receiver-operating characteristic curves will be calculated to estimate the diagnostic accuracy of different sequences and intensities of magnetic resonance imaging. Methodological quality will be assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. RESULTS The results of this analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION The ability of different MRI sequences and magnetic intensities to identify pCR will be evaluated and the best one to diagnose pCR of rectal cancer after therapy will be recommended. ETHICS AND DISSEMINATION Ethics approval and patient consent are not required, as this study is a meta-analysis based on published studies. PROSPERO REGISTRATION NUMBER CRD42018105672.
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Affiliation(s)
- Mei Zhang
- Radiology Department, Gansu Provincial Cancer Hospital
| | - Jipin Li
- The Second Clinical Medical College of Lanzhou University
| | - Xueni Ma
- The Second Clinical Medical College of Lanzhou University
| | - Bo Wang
- Department of Nursing, Rehabilitation Center Hospital of Gansu Province, Lanzhou
| | - Jiarui Wu
- Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing
| | - Ya Gao
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University
| | - Jinhui Tian
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University
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17
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Holliday EB, Allen PK, Elhalawani H, Abdel-Rahman O. Outcomes of patients in the national cancer database treated non-surgically for localized rectal cancer. J Gastrointest Oncol 2018; 9:589-600. [PMID: 30151255 DOI: 10.21037/jgo.2018.03.06] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Background Some patients undergo a non-operative approach to localized rectal adenocarcinoma either because they decline surgery or because their medical comorbidities preclude surgical intervention. Published studies reporting excellent outcomes with a "wait-and-see" approach have been small and highly-selected. We aimed to analyze survival outcomes and prognostic factors for patients with localized rectal adenocarcinoma in the National Cancer Database (NCDB) undergoing definitive radiation without surgical intervention. Methods The NCDB was queried for patients with non-metastatic rectal adenocarcinoma treated with definitive radiotherapy who did not undergo a surgical resection either because the patient refused surgery, surgery was medically contraindicated, or surgery was otherwise unplanned. Patient, tumor and treatment-related characteristics were compared between those treated with 45-50.3 Gray (Gy), 50.4-54 Gy and >54 Gy. Survivals were compared using the Log-Rank test. Univariate and multivariate Cox regression analyses were performed. Survivals were then compared utilizing a robust inverse-probability-weighted regression adjustment method with nearest-neighbor matching. Results Eight thousand four hundred and eight patients were included for analysis. After case-matching and adjusting for significant prognostic factors, patients receiving 50.4-54 Gy had a significantly longer median, 1- and 5-year overall survival (OS) (49.4 months, 85.8%, 44.7%) compared with patients receiving 45-50.3 or >54 Gy (37.2 months, 79.2%, 38.4% and 34.2 months, 84.5%, 35.3%, respectively; Log rank P value <0.0001). Conclusions In an unselected group of patients treated at NCDB-participating institutions, survival rates with a non-surgical approach to non-metastatic rectal adenocarcinoma are much lower than those reported in well-selected single-institutional studies. Moderate dose escalation from 50.4-54 Gy was associated with better OS compared with doses <50.4 Gy or >54 Gy after adjusting for significant covariant.
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Affiliation(s)
- Emma B Holliday
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Pamela K Allen
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Hesham Elhalawani
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Omar Abdel-Rahman
- Clinical Oncology Department, Faculty of Medicine, Ain shams University, Cairo, Egypt
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18
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Loftås P, Sturludóttir M, Hallböök O, Almlöv K, Arbman G, Blomqvist L. Assessment of remaining tumour involved lymph nodes with MRI in patients with complete luminal response after neoadjuvant treatment of rectal cancer. Br J Radiol 2018; 91:20170938. [PMID: 29668301 DOI: 10.1259/bjr.20170938] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
OBJECTIVE To assess the accuracy of MRI to predict remaining lymph node metastases in patients with complete pathological luminal response (ypT0) after neoadjuvant therapy. METHODS Data from a national registry were used. 19 patients with histopathologically remaining lymph node metastases (ypT0N+) were identified. Another 19 patients without lymph node metastases (ypT0N0) were used as matched controls. Two radiologists blinded to all patient information evaluated staging and restaging MRI that was compared to histopathological findings of the resected specimen. RESULTS The average size of the largest lymph node on restaging MRI was significantly larger (4.5 mm) in the ypT0N+ group than in the ypT0N0 group (2.6 mm) (p = 0.04). Presence of ypN+ was correctly predicted by MRI in 7 of 19 patients. In patients without lymph node metastases (ypT0N0), these were correctly classified by MRI in 16 of 19 patients. All patients who had MR-identified lymph nodes larger than 8 mm at restaging were ypTN+. The sensitivity, specificity, positive predictive value and negative for prediction of remaining lymph node metastasis with MRI were 37, 84, 70 and 57%. CONCLUSION In patients with ypT0 in rectal cancer after neoadjuvant treatment, remaining regional lymph node metastases cannot safely be predicted by restaging MRI alone using presently known criteria. Presence of a lymph node over 8 mm on restaging MRI strongly indicates yPN+. Advances in knowledge: This is one of the first studies on MRI lymph node assessment after chemo-radiotherapy (CRT) in luminal complete response.
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Affiliation(s)
- Per Loftås
- 1 Department of Surgery, Institution for clinical and experimental medicine, Linköping University , Linköping , Sweden
| | - Margrét Sturludóttir
- 2 Department of Diagnostic Radiology, Karolinska University hospital , Stockholm , Sweden.,3 Department of Molecular Medicine and Surgery, Karolinska Institutet , Stockholm , Sweden
| | - Olof Hallböök
- 1 Department of Surgery, Institution for clinical and experimental medicine, Linköping University , Linköping , Sweden
| | - Karin Almlöv
- 4 Department of Surgery, Institution for clinical and experimental medicine, Linköping University , Norrköping , Sweden
| | - Gunnar Arbman
- 4 Department of Surgery, Institution for clinical and experimental medicine, Linköping University , Norrköping , Sweden
| | - Lennart Blomqvist
- 2 Department of Diagnostic Radiology, Karolinska University hospital , Stockholm , Sweden.,3 Department of Molecular Medicine and Surgery, Karolinska Institutet , Stockholm , Sweden
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19
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Abstract
BACKGROUND Neoadjuvant chemoradiotherapy followed by an optimal surgery is the standard treatment for patients with locally advanced rectal cancer. FDG-PET/CT is commonly used as the modality for assessing the effect of chemoradiotherapy. OBJECTIVE The purpose of this study was to investigate whether PET/CT-based volumetry could contribute to the prediction of pathological complete response or prognosis after neoadjuvant chemoradiotherapy. DESIGN This was a retrospective cohort study. SETTINGS This study was conducted at a single research center. PATIENTS Ninety-one consecutive patients with locally advanced rectal cancer were enrolled between January 2005 and December 2015. INTERVENTION Patients underwent PET/CT before and after neoadjuvant chemoradiotherapy. MAIN OUTCOME MEASURES Maximum standardized uptake value and total lesion glycolysis on PET/CT before and after neoadjuvant chemoradiotherapy were calculated using isocontour methods. Correlations between these variables and clinicopathological factors and prognosis were assessed. RESULTS PET/CT-associated variables before chemoradiotherapy were not correlated with either clinicopathological factors or prognosis. Maximum standardized uptake value was associated with pathological complete response, but total lesion glycolysis was not. Maximum standardized uptake value correlated with ypT, whereas total lesion glycolysis correlated with both ypT and ypN. High total lesion glycolysis was associated with a considerably poorer prognosis; the 5-year recurrence rate was 65% and the 5-year mortality rate 42%, whereas in lesions with low total lesion glycolysis, these were 6% and 2%. On multivariate analysis, high total lesion glycolysis was an independent risk factor for recurrence (HR = 4.718; p = 0.04). LIMITATIONS The gain in fluoro-2-deoxy-D-glucose uptake may differ between scanners, thus the general applicability of this threshold should be validated. CONCLUSIONS In patients with locally advanced rectal cancer, high total lesion glycolysis after neoadjuvant chemoradiotherapy is strongly associated with a worse prognosis. Total lesion glycolysis after chemoradiotherapy may be a promising preoperative predictor of recurrence and death. See Video Abstract at http://links.lww.com/DCR/A464.
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20
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Abstract
Dramatic progress has deeply moved rectal cancer management. Tailoring of treatment allow to select participants according to initial prognostic factors (radiotherapist) or tumoral response (surgeon). Today, this management must keep in mind tumoral initial staging, prognostic at the time of diagnosis, tumoral response and characteristic, and patient's motivation. The result of this patient care is more than oncologic, it is also functional.
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Affiliation(s)
- P Rouanet
- ICM Val-d'Aurelle, 208, rue des Apothicaires, 34298 Montpellier, France.
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21
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Battersby NJ, Dattani M, Rao S, Cunningham D, Tait D, Adams R, Moran BJ, Khakoo S, Tekkis P, Rasheed S, Mirnezami A, Quirke P, West NP, Nagtegaal I, Chong I, Sadanandam A, Valeri N, Thomas K, Frost M, Brown G. A rectal cancer feasibility study with an embedded phase III trial design assessing magnetic resonance tumour regression grade (mrTRG) as a novel biomarker to stratify management by good and poor response to chemoradiotherapy (TRIGGER): study protocol for a randomised controlled trial. Trials 2017; 18:394. [PMID: 28851403 PMCID: PMC5576102 DOI: 10.1186/s13063-017-2085-2] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Accepted: 07/03/2017] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Pre-operative chemoradiotherapy (CRT) for MRI-defined, locally advanced rectal cancer is primarily intended to reduce local recurrence rates by downstaging tumours, enabling an improved likelihood of curative resection. However, in a subset of patients complete tumour regression occurs implying that no viable tumour is present within the surgical specimen. This raises the possibility that surgery may have been avoided. It is also recognised that response to CRT is a key determinant of prognosis. Recent radiological advances enable this response to be assessed pre-operatively using the MRI tumour regression grade (mrTRG). Potentially, this allows modification of the baseline MRI-derived treatment strategy. Hence, in a 'good' mrTRG responder, with little or no evidence of tumour, surgery may be deferred. Conversely, a 'poor response' identifies an adverse prognostic group which may benefit from additional pre-operative therapy. METHODS/DESIGN TRIGGER is a multicentre, open, interventional, randomised control feasibility study with an embedded phase III design. Patients with MRI-defined, locally advanced rectal adenocarcinoma deemed to require CRT will be eligible for recruitment. During CRT, patients will be randomised (1:2) between conventional management, according to baseline MRI, versus mrTRG-directed management. The primary endpoint of the feasibility phase is to assess the rate of patient recruitment and randomisation. Secondary endpoints include the rate of unit recruitment, acute drug toxicity, reproducibility of mrTRG reporting, surgical morbidity, pathological circumferential resection margin involvement, pathology regression grade, residual tumour cell density and surgical/specimen quality rates. The phase III trial will focus on long-term safety, regrowth rates, oncological survival analysis, quality of life and health economics analysis. DISCUSSION The TRIGGER trial aims to determine whether patients with locally advanced rectal cancer can be recruited and subsequently randomised into a control trial that offers MRI-directed patient management according to radiological response to CRT (mrTRG). The feasibility study will inform a phase III trial design investigating stratified treatment of good and poor responders according to 3-year disease-free survival, colostomy-free survival as well as an increase in cases managed without a major resection. TRIAL REGISTRATION ClinicalTrials.gov, ID: NCT02704520 . Registered on 5 February 2016.
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Affiliation(s)
- Nick J. Battersby
- Pelican Cancer Foundation, The Ark, Basingstoke, RG24 9NN UK
- North Hampshire Hospital Foundation Trust, Basingstoke, RG24 9NA UK
| | - Mit Dattani
- Pelican Cancer Foundation, The Ark, Basingstoke, RG24 9NN UK
| | - Sheela Rao
- Department of Medicine Royal Marsden Hospital Sutton, Sutton, SM2 5PT UK
| | - David Cunningham
- Department of Medicine Royal Marsden Hospital Sutton, Sutton, SM2 5PT UK
| | - Diana Tait
- Department of Medicine Royal Marsden Hospital Sutton, Sutton, SM2 5PT UK
| | - Richard Adams
- Velindre Cancer Centre Velindre Hospital Cardiff, Cardiff, CF4 7XL UK
| | - Brendan J. Moran
- Pelican Cancer Foundation, The Ark, Basingstoke, RG24 9NN UK
- North Hampshire Hospital Foundation Trust, Basingstoke, RG24 9NA UK
| | - Shelize Khakoo
- Gastrointestinal Unit Royal Marsden Hospital Sutton, Sutton, SM2 5PT UK
| | - Paris Tekkis
- Department of Colorectal Surgery, Royal Marsden Hospital London, London, SW3 6JJ UK
| | - Shahnawaz Rasheed
- Department of Colorectal Surgery, Royal Marsden Hospital London, London, SW3 6JJ UK
| | - Alex Mirnezami
- Department of Surgery and Department for Tissue Microarray analysis, University of Southampton, Southampton, SO16 6YD UK
| | - Philip Quirke
- Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, Wellcome Trust Brenner Building, St. James’s University Hospital, Leeds, LS9 7TF UK
| | - Nicholas P. West
- Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, Wellcome Trust Brenner Building, St. James’s University Hospital, Leeds, LS9 7TF UK
| | - Iris Nagtegaal
- Department of Pathology Radboud University, Nijmegen, 6500HB Netherlands
| | - Irene Chong
- Division of Molecular Pathology Institute of Cancer Research, London, SW3 6JB UK
| | - Anguraj Sadanandam
- Division of Molecular Pathology Institute of Cancer Research, London, SW3 6JB UK
| | - Nicola Valeri
- Division of Molecular Pathology Institute of Cancer Research, London, SW3 6JB UK
| | - Karen Thomas
- Statistics Unit, R&D Royal Marsden Hospital Sutton, Sutton, SM2 5PT UK
| | - Michelle Frost
- Department of Radiology, Royal Marsden Hospital Sutton, Sutton, SM2 5PT UK
| | - Gina Brown
- Department of Radiology, Royal Marsden Hospital Sutton, Sutton, SM2 5PT UK
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Baseline T Classification Predicts Early Tumor Regrowth After Nonoperative Management in Distal Rectal Cancer After Extended Neoadjuvant Chemoradiation and Initial Complete Clinical Response. Dis Colon Rectum 2017; 60:586-594. [PMID: 28481852 DOI: 10.1097/dcr.0000000000000830] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Selected patients with rectal cancer and complete clinical response after neoadjuvant chemoradiation have been managed nonoperatively with acceptable outcomes. However, ≈20% of these patients will develop early tumor regrowth. Identification of these patients could select candidates for more intensive follow-up. OBJECTIVE The purpose of this study was to investigate the influence of baseline radiological T classification on recurrences after a complete clinical response managed nonoperatively after chemoradiation. DESIGN This was a retrospective review of a prospective collected database. SETTINGS The study was conducted at a single center. PATIENTS Patients with distal rectal cancer (cT2-4N0-2M0) undergoing extended chemoradiation (54 Gy + 5-fluorouracil-based chemotherapy) were eligible. Patients were reassessed for tumor response at 10 weeks after radiation completion. Patients with complete clinical response (clinical, radiological, and endoscopic) were managed nonoperatively and strictly followed. MAIN OUTCOMES MEASURES Complete clinical response rates, early tumor regrowth rates (<12 mo), local recurrence-free survival, and distant metastases-free survival were measured. RESULTS A total of 91 consecutive patients with rectal cancer underwent extended chemoradiation. Sixty-one patients developed initial complete clinical response (67%). cT2 patients developed similar initial complete clinical response rates compared with cT3/T4 (72% vs 63%; p = 0.403). Early tumor regrowths were more frequent among baseline cT3/4 when compared with cT2 patients (30% vs 3%; p = 0.007). There were no differences in late local recurrences (p = 0.593) or systemic recurrences (p = 0.387). Local recurrence-free survival was significantly better for cT2 patients at 1 year (96% vs 69%; p = 0.009). After Cox regression analysis, baseline T stage was an independent predictor of improved local recurrence-free survival at 1 year (p = 0.03; OR = 0.09 (95% CI, 0.01-0.81)). LIMITATIONS This study was limited by its small sample size, retrospective nature, and short follow-up. CONCLUSIONS cT2 patients who develop complete clinical response after extended chemoradiation managed nonoperatively are less likely to develop early tumor regrowths when compared with cT3/4 patients. cT3/4 patients should undergo more intensive follow-up after a complete clinical response to allow for early detection of early regrowths.
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Kusters M, Slater A, Betts M, Hompes R, Guy RJ, Jones OM, George BD, Lindsey I, Mortensen NJ, James DR, Cunningham C. The treatment of all MRI-defined low rectal cancers in a single expert centre over a 5-year period: is there room for improvement? Colorectal Dis 2016; 18:O397-O404. [PMID: 27313145 DOI: 10.1111/codi.13409] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2016] [Accepted: 05/08/2016] [Indexed: 12/13/2022]
Abstract
AIM Outcomes following treatment for low rectal cancer still remain inferior to those for upper rectal cancer. A clear definition of 'low' rectal cancer is lacking and consensus is more likely using a definition based on MRI criteria. This study aimed to determine disease presentation and treatment outcome of low rectal cancer based on a strict anatomical definition. METHOD A low rectal cancer was defined as one with a lower border below the pelvic attachment of the levator muscles on sagittal MRI. One hundred and eighty consecutive patients with tumours defined by this criterion between 2006 and 2011 were identified from a prospectively managed departmental database. RESULTS One hundred and eighteen patients (66%) underwent curative resection and 12 (7%) palliative resection. Eleven patients (6%) were entered into a 'watch and wait' (W&W) protocol; 10 others (5%) were not fit to undergo any operation. Some 26 patients (14%) had nonresectable local or metastatic disease. An R0 resection was the most important factor influencing survival after curative surgery. R+ resections occurred in 12% of non-abdominoperineal excisions, 11% of abdominoperineal excisions and 47% of extended resections. Overall survival was similar in the curative resections compared with the W&W patients. In 23 of the 96 (24%) treated with neoadjuvant chemoradiotherapy there was a persistent clinical or a pathological complete response. CONCLUSION In curative resections, a clear margin is the most important determinant of survival. In 24% of the patients treated with neoadjuvant chemoradiotherapy, surgery could potentially have been avoided. There is scope for improvement in the treatment of locally advanced rectal cancers.
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Affiliation(s)
- M Kusters
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands. .,Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands.
| | - A Slater
- Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - M Betts
- Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - R Hompes
- Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - R J Guy
- Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - O M Jones
- Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - B D George
- Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - I Lindsey
- Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - N J Mortensen
- Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - D R James
- Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - C Cunningham
- Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
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Millard T, Kunk PR, Ramsdale E, Rahma OE. Current debate in the oncologic management of rectal cancer. World J Gastrointest Oncol 2016; 8:715-724. [PMID: 27795811 PMCID: PMC5064049 DOI: 10.4251/wjgo.v8.i10.715] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2016] [Revised: 07/01/2016] [Accepted: 08/29/2016] [Indexed: 02/05/2023] Open
Abstract
Despite the considerable amount of research in the field, the management of locally advanced rectal cancer remains a subject to debate. To date, effective treatment centers on surgical resection with the standard approach of total mesorectal resection. Radiation therapy and chemotherapy have been incorporated in order to decrease local and systemic recurrence. While it is accepted that a multimodality treatment regimen is indicated, there remains significant debate for how best to accomplish this in regards to order, dosing, and choice of agents. Preoperative radiation is the standard of care, yet remains debated with the option for chemoradiation, short course radiation, and even ongoing studies looking at the possibility of leaving radiation out altogether. Chemotherapy was traditionally incorporated in the adjuvant setting, but recent reports suggest the possibility of improved efficacy and tolerance when given upfront. In this review, the major studies in the management of locally advanced rectal cancer will be discussed. In addition, future directions will be considered such as the role of immunotherapy and ongoing trials looking at timing of chemotherapy, inclusion of radiation, and non-operative management.
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Bayram I, Bakir B, Kartal MG, Kunduz E, Bayram O, Turkay R, Asoglu O, Kapran Y. The role of MRI with diffusion-weighted imaging in restaging rectal cancers after neoadjuvant chemoradiotherapy. ACTA ACUST UNITED AC 2016. [DOI: 10.4102/sajr.v20i1.967] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
Background: It is challenging to restage rectal cancer at MRI, in patients who have had neoadjuvant chemoradiotherapy.Objective: To investigate the accuracy of MRI with diffusion-weighted imaging (DWI) in the restaging of rectal cancer.Materials and methods: Pre- and post-neoadjuvant chemoradiotherapy MRI examinations of 35 patients diagnosed with locally advanced rectal cancer were evaluated and subsequently compared with post-operative pathology results.Results: The accuracy of MRI with DWI to determine the T-stage status was calculated as 54.28%. Kappa statistics revealed poor concordance with pathology results, with a κ value of 0.212 ± 0.114 (p = 0.028). The apparent diffusion coefficient (ADC) values measured after the neoadjuvant chemotherapy revealed a significant increase when compared with pre-treatment ADC values (p < 0.000001). MRI accuracy rate for lymph node involvement was calculated as 57.14% with a κ value of 0.001 (p = 0.989). MRI had 80% sensitivity and 100% specificity in determining mesorectal fascia involvement, with a calculated positive predictive value of 100% and a calculated negative predictive value of 96%. The accuracy of MRI in overall staging according to the TNM staging system was 28%.Conclusion: The accuracy of MRI in restaging rectal cancer is not yet sufficient and is not on par with the accuracy of MRI in the primary staging of the disease. This is attributed to post-treatment changes. Adding DWI to the protocol is promising, but more expanded data are required.
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Diffusion-weighted MRI for Early Prediction of Treatment Response on Preoperative Chemoradiotherapy for Patients With Locally Advanced Rectal Cancer: A Feasibility Study. Ann Surg 2016; 263:522-8. [PMID: 26106836 DOI: 10.1097/sla.0000000000001311] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE This study investigates the predictive value of diffusion-weighted magnetic resonance imaging (DW-MRI) for good pathological response at different time points during and after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer. BACKGROUND Preoperative CRT followed by total mesorectal excision (TME) is the standard of care for locally advanced rectal cancer. The use of standard radical surgery in good treatment responders after CRT is being questioned. METHODS Patients with locally advanced rectal adenocarcinoma were treated with preoperative CRT followed by surgery. DW-MRI scans were performed before CRT, during the third week of CRT, 4 weeks post-CRT and presurgery. Tumor apparent diffusion coefficient (ADC) values were acquired from the DW-MRI scans. After surgery the pathological tumor regression grade was assessed according to the classification by Mandard et al [Cancer. 1994;73:2680-2686]. Patients with pathological complete or near-complete response (tumor regression grade 1-2) were classified as good responders (GRs). RESULTS Twenty-two patients participated of which 9 were GRs (41%). Pre-CRT ADC values were lower in good versus moderate/poor responders (P = 0.04). ADC values during CRT and four weeks post-CRT were higher in GR. ADC values presurgery did not differ between response groups. For all time points the relative ADC increase (ΔADC) compared to the ADC pre-CRT was higher in GR (P < 0.001). The ΔADC during CRT and four weeks post-CRT were the best predictive parameters for pathological good response. CONCLUSIONS This study shows that DW-MRI is feasible to select good treatment responders during preoperative CRT for locally advanced rectal cancer.
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Impact of Organ-Preserving Strategies on Anorectal Function in Patients with Distal Rectal Cancer Following Neoadjuvant Chemoradiation. Dis Colon Rectum 2016; 59:264-9. [PMID: 26953984 DOI: 10.1097/dcr.0000000000000543] [Citation(s) in RCA: 98] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Organ-preserving strategies have been considered for patients with distal rectal cancer and complete or near-complete response to neoadjuvant chemoradiation to avoid the functional consequences of radical surgery. Transanal endoscopic microsurgery and no immediate surgery (watch and wait) have been considered in selected patients. OBJECTIVE The aim of this study is to compare anorectal function following these 2 organ-preserving strategies (transanal endoscopic microsurgery and watch and wait) for rectal cancer with complete or near-complete response to neoadjuvant chemoradiation. DESIGN This study is based on the comparison of prospectively collected data. SETTINGS This study was conducted at a single center. PATIENTS Consecutive patients with distal rectal cancer undergoing neoadjuvant chemoradiation (50.4-54 Gy and 5-fluorouracil-based chemotherapy) were prospectively studied. Patients with complete clinical response were managed by watch and wait. Patients with near-complete response (≤3 cm, ycT1-2N0) were managed by transanal endoscopic microsurgery. MAIN OUTCOME MEASURES Functional outcomes were determined by anorectal manometry and Fecal Incontinence Index and Quality of Life assessment. RESULTS Two groups of patients were included in the study. Twenty-nine patients with near-complete response undergoing transanal endoscopic microsurgery and 53 with complete response after watch and wait were assessed. Baseline features were similar between groups. Patients undergoing transanal endoscopic microsurgery had worse resting/squeeze pressures (p = 0.004) and rectal capacity (p = 0.002). In addition, their incontinence scores (2.3 vs. 6.5; p < 0.001) and quality-of-life questionnaire responses (in all domains; p ≤ 0.01) were significantly worse in comparison with patients undergoing watch and wait. LIMITATIONS This study was limited by the small sample size and the absence of baseline anorectal function information. CONCLUSIONS Nonoperative management of patients with complete clinical response following chemoradiation results in better anorectal function in comparison with patients with near-complete response managed by transanal endoscopic microsurgery. In the absence of clinically detectable residual cancer, this latter approach may result in significant worsening of anorectal function.
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Nodal involvement in luminal complete response after neoadjuvant treatment for rectal cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2016; 42:801-7. [PMID: 27146960 DOI: 10.1016/j.ejso.2016.03.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2015] [Revised: 03/10/2016] [Accepted: 03/16/2016] [Indexed: 11/23/2022]
Abstract
BACKGROUND Pathological complete response (pCR) after neoadjuvant therapy in rectal cancer is correlated with improved survival. There is limited knowledge on the incidence of pCR at a national level with uniform guidelines. The aim of this prospective register-based study was to investigate the incidence and outcome of pCR in relation to neoadjuvant therapy in a national cohort. METHOD All patients abdominally operated for rectal cancer between 2007 and 2012 (n = 7885) were selected from The Swedish Colo-rectal Cancer Register. Twenty-six per cent (n = 2063) had neoadjuvant therapy with either long or short course radiotherapy with >4 weeks delay with the potential to achieve pCR. The primary endpoints were pCR and survival in relation to neoadjuvant therapy. RESULTS Complete eradication of the luminal tumor, ypT0 was found in 161 patients (8%). In 83% of the ypT0 the regional lymph nodes were tumor negative (ypT0N0), 12% had 1-3 positive lymph nodes (ypT0N1) and 4% had more than three positive lymph nodes (ypT0N2). There was significantly greater survival with ypT0 compared to ypT+ (hazard ratio 0.38 (C.I 0.25-0.58)) and survival was significantly greater in patients with ypT0N0 compared to ypT0N1-2 (hazard ratio 0.36 (C.I 0.15-0.86)). In ypT0, cT3-4 tumors had the greater risk of node-positivity. The added use of chemotherapy resulted in 10% ypT0 compared to 5.1% in the group without chemotherapy (p < 0.00004). CONCLUSION Luminal pathological complete response occurred in 8%, 16% of them had tumor positive nodes. The survival benefit of luminal complete response is dependent upon nodal involvement status.
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Lopez-Lopez V, Abrisqueta J, Lujan J, Hernández Q, Ono A, Parrilla P. Utility of rectoscopy in the assessment of response to neoadjuvant treatment for locally advanced rectal cancer. Saudi J Gastroenterol 2016; 22:148-53. [PMID: 26997222 PMCID: PMC4817299 DOI: 10.4103/1319-3767.178526] [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: 07/14/2015] [Accepted: 09/05/2015] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND/AIMS The management of locally advanced rectal cancer has changed substantially over the last few decades with neoadjuvant chemoradiotherapy. The aim of the present study is to compare the results between neoadjuvant post-treatment rectoscopy and the anatomopathological findings of the surgical specimen. PATIENTS AND METHODS We conducted a prospective study of 67 patients with locally advanced adenocarcinoma of the rectum (stages II and III). Two groups were established: One with complete clinical response (cCR) and one without (non-cCR), based on the findings at rectoscopy. Assessment of tumor regression grade in the surgical specimen was determined using Mandard's tumor regression scale. RESULTS Seventeen patients showed a cCR. Thirty-five biopsies were negative and 32 were positive for malignancy. All the cCR patients had a negative biopsy (P < 0.0001). All 32 positive biopsies revealed the presence of adenocarcinoma, and of the 35 negative biopsies, 18 had no malignancy and 17 were diagnosed with adenocarcinoma (P < 0.0001). Sixteen of the 17 cCR patients showed a complete pathological response and one patient showed the presence of adenocarcinoma. Of the 50 non-cCR patients 48 revealed the presence of adenocarcinoma and two had absence of malignancy. According to the Mandard classification, 16 of the 17 cCR patients were grade I and 1 grade II; 2 non-cCR patients were grade I, 7 grade II, 13 grade III, 19 grade IV, and 9 grade V. CONCLUSIONS Endoscopic and histological findings could be determinants in the assessment of response to neoadjuvant treatment.
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Affiliation(s)
- Victor Lopez-Lopez
- Department of General Surgery, Colorectal Unit, Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
| | - Jesús Abrisqueta
- Department of General Surgery, Colorectal Unit, Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
| | - Juán Lujan
- Department of General Surgery, Colorectal Unit, Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
| | - Quiteria Hernández
- Department of General Surgery, Colorectal Unit, Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
| | - Akiko Ono
- Division of Gastroenterology, Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
| | - Pascual Parrilla
- Department of General Surgery, Colorectal Unit, Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
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30
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Behrenbruch C, Ryan J, Lynch C, Wynn G, Heriot A. Complete clinical response to neoadjuvant chemoradiotherapy for rectal cancer: an Australasian perspective. ANZ J Surg 2015; 85:103-4. [PMID: 25732390 DOI: 10.1111/ans.12441] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Cori Behrenbruch
- Department of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
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31
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Perez RO, Habr-Gama A, São Julião GP, Proscurshim I, Fernandez LM, de Azevedo RU, Vailati BB, Fernandes FA, Gama-Rodrigues J. Transanal Endoscopic Microsurgery (TEM) Following Neoadjuvant Chemoradiation for Rectal Cancer: Outcomes of Salvage Resection for Local Recurrence. Ann Surg Oncol 2015; 23:1143-8. [PMID: 26577119 DOI: 10.1245/s10434-015-4977-2] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Indexed: 12/25/2022]
Abstract
BACKGROUND Transanal endoscopic microsurgery (TEM) has been considered an alternative for selected patients with rectal cancer following neoadjuvant chemoradiation (CRT). Immediate total mesorectal completion for all patients with unfavorable pathological features would result in unnecessary protectomies in a significant proportion of patients. Instead, salvage total mesorectal excision (TME) could be restricted for patients developing local recurrence. The aim of the present study is to determine oncological outcomes of salvage resection for local recurrences following CRT and TEM. METHODS Consecutive patients undergoing TEM following neoadjuvant CRT for rectal cancer were reviewed. Patients with "near" complete response to CRT (≤3 cm; ycT1-2N0) were offered TEM. Salvage surgery was attempted in the event of a local recurrence. RESULTS A total of 53 patients were managed by CRT followed by TEM. Unfavorable pathological features were present in 36 patients (68 %). None of the patients underwent immediate completion TME. There were 12 patients who developed local recurrence resulting in a 2-year local recurrence-free survival of 77 % (95 % CI, 53-100 %). Of these patients, 9 developed exclusively local recurrences, and all had at least 1 unfavorable pathological feature in the specimen after TEM (100 %). Eight patients (8 of 9) underwent salvage resection (abdominoperineal resection [APR] in 87 %) with CRM+ in 7 of 8 patients (87 %). Four patients developed local re-recurrence after a median 36 months of follow-up. The 2-year local re-recurrence free survival was 60 %. CONCLUSIONS Salvage resection for local recurrence following CRT and TEM is associated with high rates of R1 resection (CRM+) and local re-recurrence. Immediate completion of TME should be considered for patients with unfavorable pathological features after TEM.
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Affiliation(s)
- Rodrigo Oliva Perez
- Angelita and Joaquim Gama Institute, São Paulo, Brazil. .,Colorectal Surgery Division, University of São Paulo School of Medicine, São Paulo, Brazil. .,São Paulo Branch, Ludwig Institute for Cancer Research, São Paulo, Brazil.
| | - Angelita Habr-Gama
- Angelita and Joaquim Gama Institute, São Paulo, Brazil.,University of São Paulo School of Medicine, São Paulo, Brazil
| | | | | | | | - Rafael Ulysses de Azevedo
- Angelita and Joaquim Gama Institute, São Paulo, Brazil.,University of São Paulo School of Medicine, São Paulo, Brazil
| | | | - Felipe Alexandre Fernandes
- Angelita and Joaquim Gama Institute, São Paulo, Brazil.,University of São Paulo School of Medicine, São Paulo, Brazil
| | - Joaquim Gama-Rodrigues
- Angelita and Joaquim Gama Institute, São Paulo, Brazil.,University of São Paulo School of Medicine, São Paulo, Brazil
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Habr-Gama A, São Julião GP, Perez RO. Nonoperative management of rectal cancer: identifying the ideal patients. Hematol Oncol Clin North Am 2015; 29:135-51. [PMID: 25475576 DOI: 10.1016/j.hoc.2014.09.004] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Neoadjuvant chemoradiation (CRT) is considered one of the preferred treatment strategies for patients with locally advanced rectal cancer. This strategy may lead to significant tumor regression, ultimately leading to a complete pathologic response in up to 42% of patients. Assessment of tumor response following CRT and before radical surgery may identify patients with a complete clinical response who could possibly be managed nonoperatively with strict follow-up (watch-and-wait strategy). The present article deals with critical issues regarding appropriate selection of patients for this approach.
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Affiliation(s)
- Angelita Habr-Gama
- Angelita and Joaquim Gama Institute, Rua Manoel da Nóbrega 1564, Paraiso, São Paulo 04001-005, Brazil; University of São Paulo School of Medicine, Rua Manoel da Nóbrega 1564, Paraiso, São Paulo 04001-005, Brazil.
| | | | - Rodrigo O Perez
- Angelita and Joaquim Gama Institute, Rua Manoel da Nóbrega 1564, Paraiso, São Paulo 04001-005, Brazil; Colorectal Surgery Division, Department of Gastroenterology, University of São Paulo School of Medicine, Rua Manoel da Nóbrega 1564, Paraiso, São Paulo 04001-005, Brazil
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Illum H, Wang DH, Dowell JE, Hittson WJ, Torrisi JR, Meyer J, Huerta S. Phase I dose escalation trial of nitroglycerin in addition to 5-fluorouracil and radiation therapy for neoadjuvant treatment of operable rectal cancer. Surgery 2015; 158:460-5. [PMID: 25964028 DOI: 10.1016/j.surg.2015.04.007] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2015] [Revised: 01/27/2015] [Accepted: 04/10/2015] [Indexed: 12/17/2022]
Abstract
BACKGROUND Nitric oxide donors decreased cell survival in vitro and tumor load in vivo in models of rectal cancer subjected to ionizing radiation. Nitroglycerin (NTG) transdermal patches, added to chemotherapy, have been shown to improve outcomes in lung cancer patients. METHODS This open-label, nonrandomized, multicohort, dose escalation, phase I trial had a primary endpoint to evaluate the safety, tolerability, feasibility, dose-limiting toxicity and maximum tolerated dose of topical NTG in addition to 5-fluorouracil and radiation therapy for neoadjuvant treatment of locoregionally advanced operable rectal cancer. The secondary endpoint was rate of pathologic complete response (pCR). Patients were assigned to 3 sequential cohorts of escalating dose levels of commercially available NTG patches (0.2, 0.4, and 0.6 mg/h), each cohort was intended to consist of 3 patients. RESULTS Thirteen patients were enrolled in the trial as specified in the dose escalation protocol. They were all male with a median age of 59.4 ± 2.5 (SEM) years. The observed toxicities were mild to moderate and manageable. Four patients developed asymptomatic grade 3 lymphopenia during the chemoradiation that resolved promptly upon completion. One patient had a non-ST segment elevation MI and 1 patient developed diarrhea. None of these toxicities were attributed to NTG except for 1 patient who developed a grade 3 headache. This required an additional group of patients at the same dose and no other patient experienced headaches. pCR was 17%. CONCLUSION NTG patches are well-tolerated and it is feasible to proceed with a phase II trial at the maximum dose examined (0.6 mg/h).
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Affiliation(s)
- Henrik Illum
- VA North Texas Health Care System Department of Hematology Oncology, Radiation Oncology, and Surgery/University of Texas Southwestern, Department of Surgery and Radiation Oncology, Dallas, TX
| | - David H Wang
- VA North Texas Health Care System Department of Hematology Oncology, Radiation Oncology, and Surgery/University of Texas Southwestern, Department of Surgery and Radiation Oncology, Dallas, TX
| | - Jonathan E Dowell
- VA North Texas Health Care System Department of Hematology Oncology, Radiation Oncology, and Surgery/University of Texas Southwestern, Department of Surgery and Radiation Oncology, Dallas, TX
| | - William J Hittson
- VA North Texas Health Care System Department of Hematology Oncology, Radiation Oncology, and Surgery/University of Texas Southwestern, Department of Surgery and Radiation Oncology, Dallas, TX
| | - John R Torrisi
- VA North Texas Health Care System Department of Hematology Oncology, Radiation Oncology, and Surgery/University of Texas Southwestern, Department of Surgery and Radiation Oncology, Dallas, TX
| | - Jeffrey Meyer
- VA North Texas Health Care System Department of Hematology Oncology, Radiation Oncology, and Surgery/University of Texas Southwestern, Department of Surgery and Radiation Oncology, Dallas, TX
| | - Sergio Huerta
- VA North Texas Health Care System Department of Hematology Oncology, Radiation Oncology, and Surgery/University of Texas Southwestern, Department of Surgery and Radiation Oncology, Dallas, TX.
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Prolonged time to surgery after neoadjuvant chemoradiotherapy increases histopathological response without affecting survival in patients with esophageal or junctional cancer. Ann Surg 2015; 260:807-13; discussion 813-4. [PMID: 25379852 DOI: 10.1097/sla.0000000000000966] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
OBJECTIVE To determine the relation between time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) and pathologically complete response (pCR), surgical outcome, and survival in patients with esophageal cancer. BACKGROUND Standard treatment for potentially curable esophageal cancer is nCRT plus surgery after 4 to 6 weeks. In rectal cancer patients, evidence suggests that prolonged TTS is associated with a higher pCR rate and possibly with better survival. METHODS We identified patients treated with nCRT plus surgery for esophageal cancer between 2001 and 2011. TTS (last day of radiotherapy to day of surgery) varied mainly for logistical reasons. Minimal follow-up was 24 months. The effect of TTS on pCR rate, postoperative complications, and survival was determined with (ordinal) logistic, linear, and Cox regression, respectively. RESULTS In total, 325 patients were included. Median TTS was 48 days (p25-p75=40-60). After 45 days, TTS was associated with an increased probability of pCR [odds ratio (OR)=1.35 per additional week of TSS, P=0.0004] and a small increased risk of postoperative complications (OR=1.20, P<0.001). Prolonged TTS had no effect on disease-free and overall survivals (HR=1.00 and HR=1.06 per additional week of TSS, P=0.976 and P=0.139, respectively). CONCLUSIONS Prolonged TTS after nCRT increases the probability of pCR and is associated with a slightly increased probability of postoperative complications, without affecting disease-free and overall survivals. We conclude that TTS can be safely prolonged from the usual 4 to 6 weeks up to at least 12 weeks, which facilitates a more conservative wait-and-see strategy after neoadjuvant chemoradiotherapy to be tested.
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Cai G, Zhu J, Palmer JD, Xu Y, Hu W, Gu W, Cai S, Zhang Z. CAPIRI-IMRT: a phase II study of concurrent capecitabine and irinotecan with intensity-modulated radiation therapy for the treatment of recurrent rectal cancer. Radiat Oncol 2015; 10:57. [PMID: 25889149 PMCID: PMC4353448 DOI: 10.1186/s13014-015-0360-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Accepted: 02/16/2015] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND This study investigated the local effect and acute toxicity of irinotecan and capecitabine with concurrent intensity-modulated radiation therapy (IMRT) for the treatment of recurrent rectal cancer without prior pelvic irradiation. METHODS Seventy-one patients diagnosed with recurrent rectal cancer who did not previously receive pelvic irradiation were treated in our hospital from October 2009 to July 2012. Radiotherapy was delivered to the pelvis, and IMRT of 45 Gy (1.8 Gy per fraction), followed by a boost of 10 Gy to 16 Gy (2 Gy per fraction), was delivered to the recurrent sites. The concurrent chemotherapy regimen was 50 mg/m(2) irinotecan weekly and 625 mg/m(2) capecitabine twice daily (Mon-Fri). Radical surgery was recommended for medically fit patients without extra-pelvic metastases. The patients were followed up every 3 months. Tumor response was evaluated using CT/MRIs according to the RECIST criteria or postoperative pathological findings. NCI-CTC 3.0 was used to score the toxicities. RESULTS Forty-eight patients (67.6%) had confirmed recurrent rectal cancer without extra pelvic metastases, and 23 patients (32.4%) had extra pelvic metastases. Fourteen patients (19.7%) underwent radical resections (R0) post-chemoradiation. A pathologic complete response was observed in 7 of 14 patients. A clinical complete response was observed in 4 patients (5.6%), and a partial response was observed in 22 patients (31.0%). Only 5 patients (7.0%) showed progressive disease during or shortly after treatment. Of 53 symptomatic patients, clinical complete and partial symptom relief with chemoradiation was achieved in 56.6% and 32.1% of patients, respectively. Only 2 patients (2.8%) experienced grade 4 leukopenia. The most common grade 3 toxicity was diarrhea (16 [22.5%] patients). The median follow-up was 31 months. The cumulative local progression-free survival rate was 74.2% and 33.9% at 1 and 3 years after chemoradiation, respectively. The cumulative total survival rate was 80.1% and 36.5% at 1 and 3 years after chemoradiation, respectively. CONCLUSIONS This study revealed that concurrent irinotecan and capecitabine with IMRT significantly relieves local symptoms and exhibits promising efficacy with manageable toxicities in recurrent rectal cancer without prior pelvic irradiation. Improving the rate of R0 resections will be investigated in a future study.
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Affiliation(s)
- Gang Cai
- Department of Radiation Oncology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, China.
| | - Ji Zhu
- Department of Radiation Oncology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, China.
| | - Joshua D Palmer
- Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
| | - Ye Xu
- Department of Radiation Oncology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, China.
| | - Weigang Hu
- Department of Radiation Oncology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, China.
| | - Weilie Gu
- Department of Radiation Oncology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, China.
| | - Sanjun Cai
- Department of Radiation Oncology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, China.
| | - Zhen Zhang
- Department of Radiation Oncology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, China.
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Waage JER, Bach SP, Pfeffer F, Leh S, Havre RF, Ødegaard S, Baatrup G. Combined endorectal ultrasonography and strain elastography for the staging of early rectal cancer. Colorectal Dis 2015; 17:50-6. [PMID: 25176033 DOI: 10.1111/codi.12764] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Accepted: 06/27/2014] [Indexed: 12/22/2022]
Abstract
AIM Strain elastography is a novel approach to rectal tumour evaluation. The primary aim of this study was to correlate elastography to pT stages of rectal tumours and to assess the ability of the method to differentiate rectal adenomas (pT0) from early rectal cancer (pT1-2). Secondary aims were to compare elastography with endorectal ultrasonography (ERUS) and to propose a combined strain elastography and ERUS staging algorithm. METHOD In all, 120 consecutive patients with a suspected rectal tumour were examined in this staging study. Patients receiving surgery without neoadjuvant radiotherapy were included (n = 59). All patients were examined with ERUS and elastography. Treatment decisions were made by multidisciplinary team (MDT) assessment, without considering the strain elastography examination. RESULTS Histopathology identified 21 adenomas, 13 pT1, 9 pT2, 15 pT3 and one pT4. Mean elastography strain ratios were predictive of T stage (P = 0.01). Differentiation of adenomas from early rectal cancer (pT1-2) had sensitivity, specificity and accuracy of 0.82, 0.86 and 0.84 for elastography and 0.82, 0.62 and 0.72 for ERUS. A combined staging algorithm was developed to identify tumours eligible for local resection. Based on MDT evaluation 32% of tumours later identified as pT0 or pT1 were treated with total mesorectal excision, even though a local excision might have sufficed. Combined ERUS and elastography evaluation would have significantly reduced this number to 9% (P = 0.008). CONCLUSION Elastography may improve the staging of adenomas and early rectal cancer compared with ERUS alone. Combined ERUS and elastography assessment is likely to further improve the selection of patients for local resection.
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Affiliation(s)
- J E R Waage
- Department of Surgery, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway
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Meng X, Huang Z, Wang R, Yu J. Prediction of response to preoperative chemoradiotherapy in patients with locally advanced rectal cancer. Biosci Trends 2014; 8:11-23. [PMID: 24647108 DOI: 10.5582/bst.8.11] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Preoperative chemoradiotherapy (CRT) combined with surgery has become a standard treatment strategy for patients with locally advanced rectal cancer (LARC). The pathological response is an important prognostic factor for LARC. The variety of tumor responses has increased the need to find a useful predictive model for the response to CRT to identify patients who will really benefit from this multimodal treatment. Magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), serum carcinoembryogenic antigen (CEA), molecular biomarkers analyzed by immunohistochemistry and gene expression profiling are the most used predictive models in LARC. The majority of predictors have yielded encouraging results, but there is still controversy. Diffusion-weighted MRI may be the best model to detect the dynamic changes of rectal cancer and predict the response at an early stage. Gene expression profiling and single nucleotide polymorphisms hold considerable promise to unveil the underlying complex genetics of response to CRT. Because each parameter has its own inherent shortcomings, combined models may be the future trend to predict the response.
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Affiliation(s)
- Xiangjiao Meng
- Department of Radiation Oncology and Key Laboratory of Radiation Oncology of Shandong Province, Department of Radiation Oncology of Shandong Cancer Hospital and Institute
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Mirbagheri N, Kumar B, Deb S, Poh BR, Dark JG, Leow CC, Teoh WMK. Lymph node status as a prognostic indicator after preoperative neoadjuvant chemoradiotherapy of rectal cancer. Colorectal Dis 2014; 16:O339-46. [PMID: 24916286 DOI: 10.1111/codi.12682] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Accepted: 03/29/2014] [Indexed: 02/08/2023]
Abstract
AIM The primary aim of this study was to examine lymph node status after neoadjuvant chemoradiotherapy (CRT) using a novel scoring system describing the pathological lymph node regression grade. The proposed scoring system was based on the percentage of fibrosis and the presence of residual tumour amount. The secondary aim of the study was to assess the oncological impact of this scoring system. METHOD The project was a retrospective cohort study over a 10-year period. Two hundred and two patients with rectal cancer who had received CRT followed by curative surgery were included. A histopathologist prospectively scored each specimen and the impact of the scoring system on survival and recurrence was analysed. RESULTS One hundred and ninety patients completed long-course preoperative CRT and formed the basis of the study. Overall, 40 recurrences (local and distant) were observed over a median follow-up of 36 months. The lymph node regression score was a significant predictor of tumour recurrence (hazard ratio 1.273, 95% CI 1.048-1.548; P = 0.015). The overall mortality rate was 21%, and a lower lymph node regression score was correlated with an improved survival curve (P = 0.01). CONCLUSION The results demonstrate that lymph node response to neoadjuvant CRT based on a nodal regression scoring system is related to recurrence.
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Affiliation(s)
- N Mirbagheri
- Department of Academic Surgery, Dandenong Hospital, Melbourne, Victoria, Australia
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Ramzan Z, Nassri AB, Huerta S. Genotypic characteristics of resistant tumors to pre-operative ionizing radiation in rectal cancer. World J Gastrointest Oncol 2014; 6:194-210. [PMID: 25024812 PMCID: PMC4092337 DOI: 10.4251/wjgo.v6.i7.194] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Revised: 03/19/2014] [Accepted: 05/08/2014] [Indexed: 02/05/2023] Open
Abstract
Due to a wide range of clinical response in patients undergoing neo-adjuvant chemoradiation for rectal cancer it is essential to understand molecular factors that lead to the broad response observed in patients receiving the same form of treatment. Despite extensive research in this field, the exact mechanisms still remain elusive. Data raging from DNA-repair to specific molecules leading to cell survival as well as resistance to apoptosis have been investigated. Individually, or in combination, there is no single pathway that has become clinically applicable to date. In the following review, we describe the current status of various pathways that might lead to resistance to the therapeutic applications of ionizing radiation in rectal cancer.
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Abstract
The role and sequencing of radiotherapy in the management of T3-4 or node-positive rectal cancer has evolved over the last few decades. Given the significant local failure rate following surgery alone, both preoperative and postoperative chemotherapy and radiotherapy have been studied to decrease local and systemic failure and improve survival in these patients. This review discusses current indications and controversies for treatment of stage II-III rectal cancer patients.
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Affiliation(s)
- Miranda B Kim
- Massachusetts General Hospital, Radiation Oncology, 100 Blossom Street, Boston, MA, 02114, USA
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Hong JSY, Young CJ, Solomon MJ. Observational study of decision making concerning radiotherapy in rectal cancer. Int J Surg 2014; 12:390-393. [PMID: 24686031 DOI: 10.1016/j.ijsu.2014.03.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2013] [Revised: 03/09/2014] [Accepted: 03/24/2014] [Indexed: 11/21/2022]
Abstract
AIM To understand how surgeons arrive at a decision in the complex and controversial field of radiotherapy in rectal cancer by identifying which variables are important in this decision and to assess the influence of age, training, area of practice and access to radiotherapy on decisions in this field. METHODS A self-administered survey was distributed to 150 members of the CSSANZ. They were asked to rank the importance of 33 variables considered when making decisions to use radiotherapy in the treatment of rectal cancer. The responses were assessed for association of surgeon age, area of practise or access to radiotherapy with decisions in this field. RESULTS A hierarchy of variables was produced which showed tumour characteristics had the highest average importance, higher than that attained by patient characteristics and side effects. There were subtle but statistically significant differences in the ranking of importance when surgeons were grouped by age, site of subspeciality training, site of practise and availability of radiotherapy service. CONCLUSION This study identifies a hierarchy of variables used in decision making concerning radiotherapy in rectal cancer treatment, which may be used in heuristic decision making. Decisions on using radiotherapy are influenced by age, site of practise, site of training, and the presence of radiotherapy on site.
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Affiliation(s)
- Jonathan S Y Hong
- Department of Colorectal Surgery, Royal Prince Alfred Hospital, NSW, Australia; Surgical Outcomes Research Centre (SOuRCe), School of Public Health, University of Sydney & Sydney Local Health Network, Australia
| | - Christopher J Young
- Department of Colorectal Surgery, Royal Prince Alfred Hospital, NSW, Australia.
| | - Michael J Solomon
- Department of Colorectal Surgery, Royal Prince Alfred Hospital, NSW, Australia; Surgical Outcomes Research Centre (SOuRCe), School of Public Health, University of Sydney & Sydney Local Health Network, Australia
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Ilbawi AM, Simianu VV, Millie M, Soriano P. Wide local excision of perianal mucinous adenocarcinoma. J Clin Oncol 2014; 33:e16-8. [PMID: 24590647 DOI: 10.1200/jco.2012.48.5722] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Affiliation(s)
- André M Ilbawi
- University of Washington School of Medicine, Seattle, WA
| | - Vlad V Simianu
- University of Washington School of Medicine, Seattle, WA
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Ilbawi AM, Simianu VV, Millie M, Soriano P. Wide local excision of perianal mucinous adenocarcinoma. J Clin Oncol 2014; 3:483-5. [PMID: 24590647 DOI: 10.1016/j.ijscr.2012.05.017] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Accepted: 05/23/2012] [Indexed: 11/17/2022] Open
Affiliation(s)
- André M Ilbawi
- University of Washington School of Medicine, Seattle, WA
| | - Vlad V Simianu
- University of Washington School of Medicine, Seattle, WA
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Perfect treatment in an imperfect world: surgery alone or radiation for node positive rectal cancer? Dis Colon Rectum 2014; 57:130-2. [PMID: 24316957 DOI: 10.1097/dcr.0000000000000000] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Residual Esophageal Cancer after Neoadjuvant Chemoradiotherapy Frequently Involves the Mucosa and Submucosa. Ann Surg 2013; 258:678-88; discussion 688-9. [DOI: 10.1097/sla.0b013e3182a6191d] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Maggiori L, Bretagnol F, Aslam MI, Guedj N, Zappa M, Ferron M, Panis Y. Does pathologic response of rectal cancer influence postoperative morbidity after neoadjuvant radiochemotherapy and total mesorectal excision? Surgery 2013; 155:468-75. [PMID: 24439750 DOI: 10.1016/j.surg.2013.10.020] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2013] [Accepted: 10/17/2013] [Indexed: 12/19/2022]
Abstract
BACKGROUND A pathologic complete response (pCR) can be observed in up to 25% of patients after preoperative chemoradiotherapy for rectal cancer and is associated with an improved long-term prognosis. However, few data are available regarding the effect of pCR on postoperative morbidity. This study aimed to assess the impact of the pCR on postoperative outcomes after laparoscopic total mesorectal excision (TME). METHODS A prospectively maintained database (2006-2011) was reviewed for all consecutive patients (n = 143) undergoing laparoscopic TME for mid or low rectal cancer after neoadjuvant chemoradiotherapy. Postoperative data were compared for pCR-group and non-pCR-group. A pCR was defined as the absence of gross and microscopic tumor in the specimen, irrespective of the nodal status (ypT0). RESULTS Thirty-three patients (23%) had a pCR. Median operating time was greatly shorter in the pCR-group (230 minutes, 180-360), compared with the non-pCR-group (240 minutes, 130-420, P = .02). Lymph node involvement was noted for 12% of the patients in the pCR-group and 33% of the patients in the non-pCR-group (P = .91). Clavien Dindo grade 3 and 4 complications (6% vs 22%, P = .04), infection related morbidity (47% vs 76%, P = .04), and clinical anastomotic leakage rates (9% vs 29%, P = .02) were lesser in the pCR group compared with the non-pCR group. Mean duration of hospital stay was lesser in the pCR-group (9 vs 12 days, P = .01). CONCLUSION This study showed that Clavien Dindo grade 3 and 4 complications, including anastomosis leakage, and infection related complications rates were lesser in patients with pathologic complete response after RCT and laparoscopic TME for rectal cancer.
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Affiliation(s)
- Léon Maggiori
- Department of Colorectal Surgery, Pôle des Maladies de l'Appareil Digestif (PMAD), Beaujon Hospital (AP-HP), 100 boulevard du Général Leclerc, 92118 Clichy, France
| | - Frédéric Bretagnol
- Department of Colorectal Surgery, Pôle des Maladies de l'Appareil Digestif (PMAD), Beaujon Hospital (AP-HP), 100 boulevard du Général Leclerc, 92118 Clichy, France
| | - Muhammad I Aslam
- Department of Colorectal Surgery, Pôle des Maladies de l'Appareil Digestif (PMAD), Beaujon Hospital (AP-HP), 100 boulevard du Général Leclerc, 92118 Clichy, France; Department of Cancer Studies and Molecular Medicine, University of Leicester, University Hospitals of Leicester NHS Trust, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, UK
| | - Nathalie Guedj
- Department of Pathology, Pôle des Maladies de l'Appareil Digestif (PMAD), Beaujon Hospital (AP-HP), 100 boulevard du Général Leclerc, 92118 Clichy, France
| | - Magaly Zappa
- Department of Radiology, Pôle des Maladies de l'Appareil Digestif (PMAD), Beaujon Hospital (AP-HP), 100 boulevard du Général Leclerc, 92118 Clichy, France
| | - Marianne Ferron
- Department of Colorectal Surgery, Pôle des Maladies de l'Appareil Digestif (PMAD), Beaujon Hospital (AP-HP), 100 boulevard du Général Leclerc, 92118 Clichy, France
| | - Yves Panis
- Department of Colorectal Surgery, Pôle des Maladies de l'Appareil Digestif (PMAD), Beaujon Hospital (AP-HP), 100 boulevard du Général Leclerc, 92118 Clichy, France.
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Intven M, Reerink O, Philippens MEP. Repeatability of diffusion-weighted imaging in rectal cancer. J Magn Reson Imaging 2013; 40:146-50. [PMID: 24127172 DOI: 10.1002/jmri.24337] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2013] [Accepted: 07/10/2013] [Indexed: 11/08/2022] Open
Abstract
PURPOSE Serial diffusion-weighted MRI (DW-MRI) measurements of the apparent diffusion coefficient (ADC) of rectal tumors are used for rectal cancer response evaluation after neo-adjuvant treatment. In this study, we determined the repeatability of DW-MRI to distinguish therapy-related response from measurement variations. MATERIALS AND METHODS In 18 patients with rectal cancer on five consecutive days, 1.5 Tesla (T) MR imaging was performed including two identical DW-MRI sequences. The repeatability of the tumor ADC measurements and the intraobserver ADC variation were depicted in a Bland-Altman plot. The repeatability coefficient was calculated as the range of ADC values of two identical DWI measurements for 95% of subjects. It was expressed as percentage of the mean ADC value. RESULTS Three females and 15 males were included. The mean tumor ADC value was 1.15 × 10(-3) mm(2)/s (SD 0.07 × 10(-3) mm(2)). The repeatability coefficient of the ADC value was 9.8% and for the intraobserver repeatability 4.7%. CONCLUSION In serial DW-MRI for rectal cancer treatment response evaluation, a repeatability coefficient of 9.8% has to be considered to account for measurement variations in rectal tumor ADC. These variations represent observer judgement and patient and MR spectrometer induced variations.
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Affiliation(s)
- Martijn Intven
- Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands
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Watch and wait approach following extended neoadjuvant chemoradiation for distal rectal cancer: are we getting closer to anal cancer management? Dis Colon Rectum 2013; 56:1109-17. [PMID: 24022527 DOI: 10.1097/dcr.0b013e3182a25c4e] [Citation(s) in RCA: 319] [Impact Index Per Article: 26.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND No immediate surgery (Watch and Wait) has been considered in select patients with complete clinical response after neoadjuvant chemoradiation to avoid postoperative morbidity and functional disorders after radical surgery. OBJECTIVE The purpose of this study was to demonstrate the long-term results of patients who had a complete clinical response following an alternative chemoradiation regimen and were managed nonoperatively. DESIGN This is a prospective study. SETTINGS This study was conducted at a single center. PATIENTS Seventy consecutive patients with T2-4N0-2M0 distal rectal cancer were studied. Neoadjuvant chemoradiotherapy included 54 Gy and 5-fluorouracil/leucovorin delivered in 6 cycles every 21 days. Patients were assessed for tumor response at 10 weeks from radiation completion. Patients with incomplete clinical response were referred to immediate surgery. Patients with complete clinical response were not immediately operated on and were monitored. MAIN OUTCOME MEASURES The primary outcomes measured were the initial complete clinical response rates after 10 weeks and the sustained complete clinical response rates after 12 months from chemoradiotherapy. RESULTS One patient died during chemoradiotherapy because of cardiac complications. Forty-seven (68%) patients had initial complete clinical response. Of these, 8 developed local regrowth within the first 12 months of follow-up (17%). Thirty-nine sustained complete clinical response at a median follow-up of 56 months (57%). An additional 4 patients (10%) developed late local recurrences (>12 months of follow-up). Overall, 35 patients never underwent surgery (50%). LIMITATIONS This study is limited by the short follow-up and small sample size. CONCLUSION Extended chemoradiation therapy with additional chemotherapy cycles and 54 Gy of radiation may result in over 50% of sustained (>12 months) complete clinical response rates that may ultimately avoid radical rectal resection. Local failures occur more frequently during the initial 12 months of follow-up in up to 17% of cases, whereas late recurrences are less common but still possible, leading to 50% of patients who never required surgery. Strict follow-up may allow salvage therapy in the majority of these patients (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A113.).
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Nardi PD, Carvello M. How reliable is current imaging in restaging rectal cancer after neoadjuvant therapy? World J Gastroenterol 2013; 19:5964-5972. [PMID: 24106396 PMCID: PMC3785617 DOI: 10.3748/wjg.v19.i36.5964] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Revised: 05/21/2013] [Accepted: 07/17/2013] [Indexed: 02/06/2023] Open
Abstract
In patients with advanced rectal cancer, neoadjuvant chemo radiotherapy provides tumor downstaging and downsizing and complete pathological response in up to 30% of cases. After proctectomy complete pathological response is associated with low rates of local recurrence and excellent long term survival. Several authors claim a less invasive surgery or a non operative policy in patients with partial or clinical complete response respectively, however to identify patients with true complete pathological response before surgical resection remains a challenge. Current imaging techniques have been reported to be highly accurate in the primary staging of rectal cancer, however neoadjuvant therapy course produces deep modifications on cancer tissue and on surrounding structures such as overgrowth fibrosis, deep stroma alteration, wall thickness, muscle disarrangement, tumor necrosis, calcification, and inflammatory infiltration. As a result, the same imaging techniques, when used for restaging, are far less accurate. Local tumor extent may be overestimated or underestimated. The diagnostic accuracy of clinical examination, rectal ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography using 18F-fluoro-2'-deoxy-D-glucose ranges between 25% and 75% being less than 60% in most studies, both for rectal wall invasion and for lymph nodes involvement. In particular the ability to predict complete pathological response, in order to tailor the surgical approach, remains low. Due to the radio-induced tissue modifications, combined with imaging technical aspects, low rate accuracy is achieved, making modern imaging techniques still unreliable in restaging rectal cancer after chemo-radiotherapy.
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Yu CS, Yun HR, Shin EJ, Lee KY, Kim NK, Lim SB, Oh ST, Kang SB, Choi WJ, Lee WY. Local excision after neoadjuvant chemoradiation therapy in advanced rectal cancer: a national multicenter analysis. Am J Surg 2013; 206:482-7. [PMID: 23849272 DOI: 10.1016/j.amjsurg.2013.01.042] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2012] [Revised: 01/17/2013] [Accepted: 01/24/2013] [Indexed: 12/15/2022]
Abstract
BACKGROUND The aim of the current study was to evaluate the clinical availability of local excision (LE) for advanced rectal cancer without lymph node metastasis after neoadjuvant chemoradiation therapy (nCRT) in Korea. METHODS From June 2000 to October 2009, 40 patients with cT2-3N0M0 rectal cancer underwent nCRT followed by LE according to a retrospective multicenter analysis. RESULTS Of the 40 patients, 22 were men and 18 were women. Eighteen patients were cT2, and 22 patients were cT3. The median follow-up duration was 38 months. Three patients (7.5%) had morbidity after LE. Four patients (10%) had recurrence (local recurrence [1 patient] and systemic metastasis [3 patients]). The 3-year disease-free survival rate was 85.9%. Only pCR was a recurrence-related prognostic factor (P = .040). CONCLUSIONS Although the current study was not a randomized controlled study, LE after nCRT in T2-3N0 rectal cancer patients appears to be a safe and effective treatment, especially in pCR patients.
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Affiliation(s)
- Chang Sik Yu
- Department of Surgery, University of Ulsan College of Medicine & Asan Medical Center, Seoul, Korea
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