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Taherioun M, Amoli HA, Afrooghe A, Nazar E, Amoli AA, Yazdi SAM. Evaluating the impact of adjuvant chemotherapy on survival outcomes in stage II rectal cancer: a retrospective cohort study. Updates Surg 2025; 77:107-117. [PMID: 39668305 DOI: 10.1007/s13304-024-02055-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Accepted: 11/27/2024] [Indexed: 12/14/2024]
Abstract
Background Rectal cancer, accounting for a significant proportion of colorectal malignancies, presents unique challenges in treatment. Surgery remains the primary curative approach, but recurrence rates post-surgery poses challenges. While neoadjuvant chemoradiation has improved outcomes, the role of adjuvant chemotherapy is still debated. Herein, we aimed to clarify the efficacy of adjuvant chemotherapy in patients with confirmed pathological stage II rectal cancer. Methods In this retrospective single-center study, we investigated the role of adjuvant chemotherapy in 173 patients with biopsy-proven stage II rectal adenocarcinoma. Participants received neoadjuvant chemoradiation followed by open TME surgery, with or without adjuvant chemotherapy. The study was conducted at Sina Hospital between January 2014 and 2019, and analyzed overall survival (OS) and disease-free survival (DFS) outcomes. Propensity score matching (PSM) was used to adjust for potential confounders. Survival outcomes were assessed using Cox proportional hazards models, and sensitivity analysis was conducted using doubly robust estimation. Results Before matching, 173 patients showed significantly improved overall survival (HR:0.33, 95%C:0.22-0.50, p < 0.001) and disease-free survival (HR:0.41, 95%CI:0.28-0.61, p < 0.001) with adjuvant chemotherapy. Age ≥ 70 years was associated with poorer overall survival (HR:1.76, 95%CI:1.08-2.88, p = 0.02). After matching, in 100 patients (50 with chemotherapy, 50 without), adjuvant chemotherapy remained significantly beneficial for both overall and disease-free survival (p < 0.001), while age ≥ 70 years continued to negatively impact overall survival. Conclusion Our findings suggest that adjuvant chemotherapy provides benefits in terms of OS and DFS in stage II rectal cancer following neoadjuvant chemoradiation and TME surgery. Further prospective studies are warranted to confirm these results and optimize treatment strategies.
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Affiliation(s)
- Maryam Taherioun
- Department of Radiation Oncology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Hadi Ahmadi Amoli
- Sina Trauma and Surgery Research Center, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Arya Afrooghe
- Sina Trauma and Surgery Research Center, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Elham Nazar
- Department of Pathology, Sina Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Arian Ahmadi Amoli
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Amir Miratashi Yazdi
- Department of Surgery, Sina Hospital, School of Medicine, Hasan-Abad Square, Tehran University of Medical Sciences, Tehran, 1136746911, Iran.
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Ryu HS, Lee JL, Kim CW, Yoon YS, Park IJ, Lim SB, Hong YS, Kim TW, Yu CS. Effects of Adjuvant Chemotherapy on Oncologic Outcomes in Patients With Stage ⅡA Rectal Cancer Above the Peritoneal Reflection Who Did Not Undergo Preoperative Chemoradiotherapy. Clin Colorectal Cancer 2024; 23:392-401. [PMID: 39033043 DOI: 10.1016/j.clcc.2024.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Accepted: 05/30/2024] [Indexed: 07/23/2024]
Abstract
PURPOSE This study aimed to evaluate the effects of adjuvant chemotherapy (AC) on oncologic outcomes for patients with stage IIA upper rectal cancer and to investigate whether AC is associated with improved survival outcomes. METHODS This retrospective study comprised 432 patients with rectal cancer above the peritoneal reflection who had undergone curative resection without preoperative chemoradiotherapy between 2008 and 2016. This study cohort was divided according to whether AC was received (AC group) or not (no-AC group). Risk factors included obstruction, perforation, poorly-differentiated tumor, lympho-vascular invasion, perineural invasion, resection margin involvement, and < 12 lymph nodes harvested. RESULTS Among the 432 patients, 279 (64.6%) had received AC. The AC group had significantly higher 5-year overall survival (OS) rates than those of the no-AC group (93.2% vs. 84.6%, P = .001). Among patients with ≥ 1 risk factors, the AC group (n = 123) had significantly higher rates of 5-year recurrence-free survival (RFS) (81.6% vs. 64.1%, P = .01) and 5-year OS (88.8% vs. 69.0%, P = .001) than those of the no-AC group (n = 59). No significant difference in survival outcomes was observed between the 2 groups in patients aged > 65 years. CONCLUSION AC was significantly associated with better 5-year RFS and 5-year OS rates in patients with stage IIA rectal cancer above peritoneal reflection who did not receive preoperative chemoradiotherapy, especially in those with ≥ 1 risk factors.
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Affiliation(s)
- Hyo Seon Ryu
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; Department of Surgery, University of Korea, Anam Hospital, Seoul, Korea
| | - Jong Lyul Lee
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
| | - Chan Wook Kim
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Yong Sik Yoon
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - In Ja Park
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Seok-Byung Lim
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Yong Sang Hong
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Tae Won Kim
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Chang Sik Yu
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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3
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Farzaneh CA, Pigazzi A, Duong WQ, Carmichael JC, Stamos MJ, Dekhordi-Vakil F, Dayyani F, Zell JA, Jafari MD. Analysis of delay in adjuvant chemotherapy in locally advanced rectal cancer. Tech Coloproctol 2023; 27:35-42. [PMID: 36042105 DOI: 10.1007/s10151-022-02676-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 07/27/2022] [Indexed: 01/12/2023]
Abstract
BACKGROUND Adjuvant chemotherapy (AC) after neoadjuvant chemoradiation and surgical resection has been the standard of care for locally advanced rectal cancer. However, there are no evidence-based guidelines regarding the optimal timing of AC for rectal cancer. The objective of this study was to evaluate the effect of AC timing on overall survival for rectal cancer. METHODS The National Cancer Database (NCDB) from 2004 to 2016 was queried for primary clinical stage II or III rectal cancer patients who had undergone neoadjuvant chemoradiation followed by surgery and AC. Patients were grouped based on AC initiation: early ≤ 4 weeks, intermediate 4-8 weeks, and delayed ≥ 8 weeks. The primary outcome was overall survival. RESULTS We identified 8722 patients, of which 905 (10.4%) received early AC, 4621 (53.0%) intermediate AC, and 3196 (36.6%) delayed AC. Pathological lymph-node metastasis (ypN +) was positive in 73% of early AC, 74% intermediate AC, and 63% delayed AC (p < 0.05). The 5-year survival probability was 71.1% (95% CI 68-74%) for early AC, 73.2% (95% CI 72-75%) intermediate AC, and 65.8% (95% CI 64-68%) delayed AC (p < 0.001). Using Cox proportional hazard modeling, patients undergoing delayed AC had an associated decreased survival compared to patients receiving early AC (HR 1.18; 95% CI 1.028-1.353, p = 0.018) or intermediate AC (HR 1.28; 95% CI 1.179-1.395, p < 0.01). CONCLUSIONS Delay in AC administration may be associated with decreased 5-year survival. Compared to early or intermediate AC, patients in the delayed AC group were observed to have increased risk of death, despite having lower proportions with ypN + disease. Patients with higher socioeconomic and education status were more likely to receive early chemotherapy.
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Affiliation(s)
- C A Farzaneh
- Department of Surgery, Division of Colon and Rectal Surgery, University of California, Irvine, Orange, CA, USA
| | - A Pigazzi
- Department of Surgery, New York Presbyterian Hospital-Weill Cornell College of Medicine, 525 E 68th Street, Box #172, New York, NY, 10065, USA
| | - W Q Duong
- Department of Surgery, Division of Colon and Rectal Surgery, University of California, Irvine, Orange, CA, USA
| | - J C Carmichael
- Department of Surgery, Division of Colon and Rectal Surgery, University of California, Irvine, Orange, CA, USA
| | - M J Stamos
- Department of Surgery, Division of Colon and Rectal Surgery, University of California, Irvine, Orange, CA, USA
| | - F Dekhordi-Vakil
- Department of Statistics, University of California, Irvine, Irvine, CA, USA
| | - F Dayyani
- Department of Medicine, Division of Hematology/Oncology, University of California, Irvine, Orange, CA, USA
| | - J A Zell
- Department of Medicine, Division of Hematology/Oncology, University of California, Irvine, Orange, CA, USA
| | - M D Jafari
- Department of Surgery, New York Presbyterian Hospital-Weill Cornell College of Medicine, 525 E 68th Street, Box #172, New York, NY, 10065, USA.
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4
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Kong JC, Ryan J, Akhurst T, Ngan SY, Michael M, Tie J, Warrier SK, Heriot AG. The predictive value of PET/CT for distant recurrences in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. J Med Imaging Radiat Oncol 2021; 65:917-924. [PMID: 34435447 DOI: 10.1111/1754-9485.13315] [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: 01/17/2021] [Accepted: 07/26/2021] [Indexed: 11/28/2022]
Abstract
INTRODUCTION It is well recognized that pathological complete response (pCR) for locally advanced rectal cancer after neoadjuvant chemoradiotherapy (CRT) confers a positive survival advantage. Despite this, a small proportion of patients can develop distant recurrence, and these are the patients that will likely benefit from adjuvant therapy. This study aims to investigate the role of PET/CT as a functional imaging to stratify patients according to their risk of distant recurrence. METHODS This is a retrospective analysis of a prospectively maintained database in a single quaternary teaching hospital from 2010 to 2019. All consecutive cases of locally advanced rectal cancer with restaging PET/CT were included. The primary outcome measure was 5-year OS and distant recurrence-free survival. RESULTS A pCR and complete metabolic response (CMR) were identified in 47 (18%) patients and 73 (27.4%) patients respectively. Of these, 26 patients had both pCR and CMR and these patients remained free of local and distant recurrence at their last censored date. Patients with both pCR and CMR achieved the highest 5-year overall survival of 96.2%, followed by those with pCR and incomplete CMR (iCMR) of 85.7%, non-pCR and CMR of 85.1% and non-pCR and iCMR of 83.1%. Independent predictors for 5-year distant recurrence-free survival were pathological and PET metabolic response, nodal staging and lymphovascular invasion (LVI). CONCLUSION In conclusion, a PET/CT has the potential to better stratify patients of their risk of distant metastasis. However, a larger validation cohort is required before these findings can be translated to clinical utility.
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Affiliation(s)
- Joseph C Kong
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
| | - Jennifer Ryan
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
| | - Timothy Akhurst
- Division of Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Samuel Y Ngan
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.,Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Michael Michael
- Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.,Division of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Jeanne Tie
- Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.,Division of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
| | - Satish K Warrier
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
| | - Alexander G Heriot
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
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5
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Abstract
PURPOSE OF REVIEW The value of adjuvant chemotherapy in rectal cancer is controversial with opinions varying from 'not be used' since randomized trials have not shown significant gains to 'be used as in colon cancer' as the need is the same and colon and rectal cancers are quite similar. This review will look upon data critically and with open eyes. RECENT FINDINGS With the exception of one randomized phase II trial (ADORE) revealing a significant gain in disease-free survival using one more effective regimen (mFOLFOX) than bolus 5-fluorouracil leucovorin, no new data have been presented. However, bringing up aspects in previous trials, either considered irrelevant for the present situation or overall negative, of what adjuvant treatment can achieve, a small reduction (hazard ratio about 0.8) in the risk of recurrence is present. This reduction is not fundamentally different from that in colon cancer considering that adjuvant treatment for rectal cancer cannot be initiated as rapidly as it can after a colon cancer diagnosis. SUMMARY Adjuvant chemotherapy after rectal cancer surgery reduces recurrence risks but the benefit is limited and for most patients not clinically relevant. Neoadjuvant therapy can be more effective but results from randomized trials are not yet available.
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Glimelius B, Osterman E. Adjuvant Chemotherapy in Elderly Colorectal Cancer Patients. Cancers (Basel) 2020; 12:cancers12082289. [PMID: 32823998 PMCID: PMC7464071 DOI: 10.3390/cancers12082289] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 08/10/2020] [Accepted: 08/12/2020] [Indexed: 12/13/2022] Open
Abstract
The value of adjuvant chemotherapy in elderly patients has been the subject of many overviews, with opinions varying from “not effective”, since randomized trials have not been performed, to “as effective as in young individuals”, based upon many retrospective analyses of randomized trials that have included patients of all ages. In the absence of randomized trials performed specifically with elderly patients, retrospective analyses demonstrate that the influence on the time to tumour recurrence (TTR) may be the same as in young individuals, but that endpoints that include death for any reason, such as recurrence-free survival (RFS), disease-free survival (DFS), and overall survival (OS), are poorer in the elderly. This is particularly true if oxaliplatin has been part of the treatment. The need for adjuvant chemotherapy after colorectal cancer surgery in elderly patients is basically the same as that in younger patients. The reduction in recurrence risks may be similar, provided the chosen treatment is tolerated but survival gains are less. Adding oxaliplatin to a fluoropyrimidine is probably not beneficial in individuals above a biological age of approximately 70 years. If an oxaliplatin combination is administered to elderly patients, three months of therapy is in all probability the most realistic goal.
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Affiliation(s)
- Bengt Glimelius
- Department of Immunology, Genetics and Pathology, Uppsala University, SE-75185 Uppsala, Sweden;
- Correspondence: ; Tel.: +46-18-611-24-32
| | - Erik Osterman
- Department of Immunology, Genetics and Pathology, Uppsala University, SE-75185 Uppsala, Sweden;
- Department of Surgery, Gävle Hospital, Region Gävleborg, SE-80187 Gävle, Sweden
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7
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Noh GT, Han J, Cho MS, Hur H, Lee KY, Kim NK, Min BS. The impact of early adjuvant chemotherapy in rectal cancer. PLoS One 2020; 15:e0228060. [PMID: 32004327 PMCID: PMC6993968 DOI: 10.1371/journal.pone.0228060] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 01/06/2020] [Indexed: 12/15/2022] Open
Abstract
PURPOSES Although adjuvant chemotherapy (AC) has been established as a standard of treatment for advanced rectal cancer, there is no guideline regarding the timing of AC initiation. In this study, we aimed to evaluate the oncologic outcome of early AC initiation and clarify the ideal time to AC among rectal cancer patients receiving preoperative chemo-radiotherapy (preCRT). METHODS The medical records of 719 patients who underwent curative resection followed by AC for rectal cancer were analyzed retrospectively. Data distributions were compared according to the calculated cut-off for AC initiation, survival results, and chemotherapy-induced toxicity. Additionally, patients were divided into two groups according to preCRT status and compared with respect to differences in the optimal time to AC. RESULTS Overall, a cut-off time point of 20 days after surgery for AC initiation was identified as the optimal interval; this yielded a significant difference in disease-free survival but no significant difference in AC toxicity. In the cut-off analysis of patients treated without preCRT, 19 days was identified as the optimal time to AC. However, for patients treated with preCRT, no significant value affected the survival outcome. CONCLUSIONS Earlier initiation of AC (within approximately 3 weeks) was associated with better oncological outcomes among patients with rectal cancer. Additionally, the optimal timing of AC was unclear among patients who received preCRT; this might be attributable to an undetermined role of AC after preCRT or the effects of complications such as anastomotic leakage.
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Affiliation(s)
- Gyoung Tae Noh
- Department of Surgery, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Jeonghee Han
- Department of Surgery, Hallym University College of Medicine, Seoul, South Korea
| | - Min Soo Cho
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Hyuk Hur
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Kang Young Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Nam Kyu Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Byung Soh Min
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
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8
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Park YY, Lee KY, Kim NK, Lee SB, Kim GR, Min BS, Oh ST. Impact of Adjuvant Chemotherapy Completion on Oncologic Outcomes in ypTNMstage 2 Rectal Cancer Patients. Ann Coloproctol 2020; 35:335-341. [PMID: 31937073 PMCID: PMC6968722 DOI: 10.3393/ac.2019.03.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2019] [Accepted: 03/10/2019] [Indexed: 10/28/2022] Open
Abstract
PURPOSE Adjuvant chemotherapy (aCT) in rectal cancer patients who have undergone curative resection after neoadjuvant chemoradiation (nCRT) is controversial. We aimed to investigate the benefits of using aCT and the clinical impact of completing aCT in ypstage 2 rectal cancer patients. METHODS We retrospectively reviewed clinicopathological data from patients who had undergone radical resection after nCRT between January 2006 and December 2012. In total, 152 patients with ypT3/4N0M0 rectal cancer were included. Of these patients, 139 initiated aCT, while 13 did not receive aCT (no-aCT). Among those who received aCT, 132 patients completed their planned cycles (aCT-completion) whereas 7 did not (aCT-incompletion). All patients received longcourse chemoradiation; a 5-fluorouracil-based regimen was used for nCRT in most patients. The prognostic factors affecting disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS The median follow-up duration was 41 months. Demographic data did not differ significantly among the 3 groups. In multivariate analysis, open surgery, a tumor size >2 cm, retrieval of <12 lymph nodes, circumferential resection margin (CRM) positivity and aCT incompletion were independent prognostic factors for poor DFS. Old age (≥60 years), open surgery, CRM positivity, aCT incompletion, and lack of aCT initiation compared to aCT completion were independent prognostic factors for poor OS. CONCLUSION In ypstage 2 rectal cancer patients, aCT after nCRT and total mesorectal excision affected both DFS and OS; however, only patients who completed planned aCT exhibited survival benefits. Therefore, improving patients' compliance with the completion of aCT is desirable.
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Affiliation(s)
- Youn Young Park
- Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kang Young Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.,OpenNBI Convergence Technology Laboratory, Avison Biomedical Research Centre, Yonsei University College of Medicine, Seoul, Korea
| | - Nam Kyu Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Sat Byol Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.,OpenNBI Convergence Technology Laboratory, Avison Biomedical Research Centre, Yonsei University College of Medicine, Seoul, Korea
| | - Ga Ram Kim
- Department of Radiology, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Byung Soh Min
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.,OpenNBI Convergence Technology Laboratory, Avison Biomedical Research Centre, Yonsei University College of Medicine, Seoul, Korea
| | - Seong-Taek Oh
- Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Buccafusca G, Proserpio I, Tralongo AC, Rametta Giuliano S, Tralongo P. Early colorectal cancer: diagnosis, treatment and survivorship care. Crit Rev Oncol Hematol 2019; 136:20-30. [PMID: 30878125 DOI: 10.1016/j.critrevonc.2019.01.023] [Citation(s) in RCA: 122] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Revised: 12/29/2018] [Accepted: 01/29/2019] [Indexed: 12/11/2022] Open
Abstract
CRC is the third most commonly diagnosed malignancy and the fourth leading cause of cancer-related death in the world. With advances in treatment, colorectal cancer is being transformed from a deadly disease to an illness that is increasingly curable. With this transformation has come increased interest in the unique problems, risks, needs, and concerns of survivors who have completed treatment and are cancer-free. They often suffer late/long-term side effects of therapies that may compromise their QoL such as fatigue, sleep difficulty, fear of recurrence, anxiety, depression, negative body image, sensory neuropathy, gastrointestinal problems, urinary incontinence, and sexual dysfunction. In this review, we discuss what is known about early colorectal diagnosis, staging, treatments and their long-term effects on quality of life and survivorship care.
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Affiliation(s)
- Gabriella Buccafusca
- UOC Oncologia Medica, Ospedale Umberto I, Via Giuseppe Testaferrata 1, 96100, Siracusa, Italy
| | - Ilaria Proserpio
- UOC Oncologia Medica, ASST Settelaghi, Ospedale di Circolo e Fondazione Macchi, Via Francesco Guicciardini 9, 21100, Varese, Italy
| | - Antonino Carmelo Tralongo
- UOC Oncologia Medica, ASST Settelaghi, Ospedale di Circolo e Fondazione Macchi, Via Francesco Guicciardini 9, 21100, Varese, Italy
| | | | - Paolo Tralongo
- UOC Oncologia Medica, Ospedale Umberto I, Via Giuseppe Testaferrata 1, 96100, Siracusa, Italy.
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10
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Poulsen LØ, Yilmaz MK, Ljungmann K, Jespersen N, Wille-Jørgensen P, Petersen LN, Falkmer U. Local recurrence rate in a national Danish patient cohort after curative treatment for rectal cancer. Acta Oncol 2018; 57:1639-1645. [PMID: 30169998 DOI: 10.1080/0284186x.2018.1497299] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
AIM Several trials have shown that preoperative (chemo)radiotherapy (CRT) reduces local recurrence rates (LRRs) in rectal cancer (RC). The use of CRT varies greatly between countries. It is unknown whether the restrictive use of CRT in Denmark results in a higher LRR relative to other countries. The aim was to evaluate the LRR in a national Danish consecutive cohort of patients with RC. METHODS All data from patients with RC in Denmark in 2009-2010 who were operated on with curative intent were retrieved from the Danish Colorectal Cancer Group database. Patients with metastases at the time of diagnosis, patients with synchronous colon cancer, and patients, in whom only local surgical procedures were performed, were excluded. In total, 1633 patients met the inclusion criteria. Clinical follow-up was at least five years with a cut-off date of 31 December 2015. RESULTS Clinical follow-up was 5.4 years (median) with an interquartile range of 4.5-6.1 years. Of all included patients, 479 (29%) were treated with preoperative long-course CRT. Local recurrence was found in 68 patients, resulting in an LRR of 4.2%, and 182 (11%) patients developed distant metastases. Five-year overall survival was 74% (95% CI: 71.64-75.91). CONCLUSIONS Five-year follow-up of curatively treated patients with RC in Denmark revealed a low LRR. This figure is identical to those reported in other Nordic countries, despite Denmark's considerably stricter guidelines for CRT. The obtained results justify the currently adopted restrictive use of preoperative CRT in Denmark.
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Affiliation(s)
- L. Ø. Poulsen
- Department of Oncology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - M. K. Yilmaz
- Department of Oncology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg
| | - K. Ljungmann
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
| | - N. Jespersen
- Gastrounit, Surgical Division, Hvidovre University Hospital, Copenhagen, Denmark
| | - P. Wille-Jørgensen
- Abdominal Disease Center K, Bispebjerg University Hospital, Copenhagen, Denmark
| | - L. N. Petersen
- Department of Oncology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
| | - U.G. Falkmer
- Department of Oncology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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11
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Affiliation(s)
- Bengt Glimelius
- Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden
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12
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Wang X, Yu Y, Meng W, Jiang D, Deng X, Wu B, Zhuang H, Wang C, Shen Y, Yang L, Zhu H, Cheng K, Zhao Y, Li Z, Qiu M, Gou H, Bi F, Xu F, Zhong R, Bai S, Wang Z, Zhou Z. Total neoadjuvant treatment (CAPOX plus radiotherapy) for patients with locally advanced rectal cancer with high risk factors: A phase 2 trial. Radiother Oncol 2018; 129:300-305. [PMID: 30381141 DOI: 10.1016/j.radonc.2018.08.027] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Revised: 08/15/2018] [Accepted: 08/28/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND PURPOSE To evaluate the safety and efficacy of Total neoadjuvant treatment (TNT) in patients with rectal cancer with high risk factors. METHODS AND MATERIALS We did this phase 2 trial in patients who were diagnosed with stage II-III rectal cancer with at least one of the high risk factors. Three cycles of induction CAPOX were followed by pelvic radiotherapy of 50.4 Gy/28 fractions and two cycles of concurrent CAPOX. Three cycles of consolidation CAPOX were delivered after radiotherapy. Primary endpoints were pathological complete response (pCR) and R0 resection. RESULTS Fifty patients were enrolled and 47 patients were evaluable. A total of 34 patients (72.3%) completed 6 to 8 cycles of chemotherapy and 46 patients (98%) completed the planned radiotherapy. 17 patients (36%) achieved a pCR or clinical complete response (cCR). Three cCR patients (6.4%) refused the operation and selected a watch-and-wait approach. The most common grade 3 or worse adverse events were leucopenia (10.6%) and radiation dermatitis (6.4%). The major surgical complications included pelvic abscesses/infection in 2 patients (4.3%), anastomotic leakage and hemorrhage in1 patient (2.2%), respectively, which were all addressed with conservative management. CONCLUSIONS TNT is effective and safe in patients with locally advanced rectal cancer with high risk factors. Long-term efficacies of TNT need to be further evaluated. This trial is registered with Chinese Clinical Trial Registry, number ChiCTR-OIN-17012284.
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Affiliation(s)
- Xin Wang
- Department of Abdominal Cancer, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Yongyang Yu
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Wenjian Meng
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Dan Jiang
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiangbing Deng
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Bing Wu
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Hua Zhuang
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, China
| | - Cun Wang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yali Shen
- Department of Abdominal Cancer, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Lie Yang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Hong Zhu
- Department of Abdominal Cancer, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Ke Cheng
- Department of Abdominal Cancer, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yaqin Zhao
- Department of Abdominal Cancer, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Zhiping Li
- Department of Abdominal Cancer, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Memg Qiu
- Department of Abdominal Cancer, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Hongfeng Gou
- Department of Abdominal Cancer, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Feng Bi
- Department of Abdominal Cancer, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Feng Xu
- Department of Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Rrenmin Zhong
- Radiation Physics Center, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Sen Bai
- Radiation Physics Center, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Ziqiang Wang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.
| | - Zongguang Zhou
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.
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13
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Wang SJ, Hathout L, Malhotra U, Maloney-Patel N, Kilic S, Poplin E, Jabbour SK. Decision-Making Strategy for Rectal Cancer Management Using Radiation Therapy for Elderly or Comorbid Patients. Int J Radiat Oncol Biol Phys 2018; 100:926-944. [PMID: 29485072 PMCID: PMC11131033 DOI: 10.1016/j.ijrobp.2017.12.261] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2017] [Revised: 11/14/2017] [Accepted: 12/11/2017] [Indexed: 02/07/2023]
Abstract
Rectal cancer predominantly affects patients older than 70 years, with peak incidence at age 80 to 85 years. However, the standard treatment paradigm for rectal cancer oftentimes cannot be feasibly applied to these patients owing to frailty or comorbid conditions. There are currently little information and no treatment guidelines to help direct therapy for patients who are elderly and/or have significant comorbidities, because most are not included or specifically studied in clinical trials. More recently various alternative treatment options have been brought to light that may potentially be utilized in this group of patients. This critical review examines the available literature on alternative therapies for rectal cancer and proposes a treatment algorithm to help guide clinicians in treatment decision making for elderly and comorbid patients.
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Affiliation(s)
- Shang-Jui Wang
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
| | - Lara Hathout
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
| | - Usha Malhotra
- Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
| | - Nell Maloney-Patel
- Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
| | - Sarah Kilic
- Rutgers New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, New Jersey
| | - Elizabeth Poplin
- Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
| | - Salma K Jabbour
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
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14
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Babaei M, Jansen L, Balavarca Y, Sjövall A, Bos A, van de Velde T, Moreau M, Liberale G, Gonçalves AF, Bento MJ, Ulrich CM, Schrotz-King P, Lemmens V, Glimelius B, Brenner H. Neoadjuvant Therapy in Rectal Cancer Patients With Clinical Stage II to III Across European Countries: Variations and Outcomes. Clin Colorectal Cancer 2018; 17:e129-e142. [PMID: 29074354 PMCID: PMC6002839 DOI: 10.1016/j.clcc.2017.09.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Accepted: 09/20/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND Neoadjuvant therapy improves survival of patients with clinical stage II and III rectal cancer in clinical trials. In this study, we investigated the administration of neoadjuvant radiotherapy (neo-RT) and neoadjuvant chemoradiotherapy (neo-CRT) and its association with survival in resected patients in 2 European countries (The Netherlands and Sweden) and at 3 specialist centers. MATERIALS AND METHODS Administration of neoadjuvant treatment (all registries) and overall survival after surgery in The Netherlands and Sweden were assessed. Hazard ratios (HRs) were obtained using Cox regression adjusted for potential confounders. RESULTS A total of 16,095 rectal cancer patients with clinical stage II and III were eligible for analyses. Large variations in administration of neo-RT and neo-CRT were observed. Elderly patients less often received neo-RT and neo-CRT. Patients with stage III disease received neo-CRT more frequently than neo-RT. Administration of neo-RT versus surgery without neoadjuvant treatment was significantly associated with improved survival in The Netherlands (HR, 0.62; 95% confidence interval [CI], 0.53-0.73) as well as in Sweden (HR, 0.79; 95% CI, 0.69-0.90). Administration of neo-CRT was associated with enhanced survival in The Netherlands (HR, 0.62; 95% CI, 0.50-0.78) but not in Sweden (HR, 0.97; 95% CI, 0.80-1.18). The mortality of patients treated with neo-CRT compared with neo-RT showed inconsistent results in population-based centers. CONCLUSIONS Our results support an association of neo-RT with enhanced survival among stage II and III rectal cancer patients. Comparing neo-CRT with neo-RT, larger variations and inconsistent results with respect to survival were observed across centers.
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Affiliation(s)
- Masoud Babaei
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Lina Jansen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Yesilda Balavarca
- Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany
| | - Annika Sjövall
- Center for Digestive Diseases, Karolinska Institutet, Sweden
| | - Amanda Bos
- Comprehensive Cancer Organization The Netherlands, Utrecht, The Netherlands; Department of Public Health, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Tony van de Velde
- Biometrics Department, the Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Michel Moreau
- Datacenter, Institute Jules Bordet, Bruxelles, Belgium
| | | | | | | | - Cornelia M Ulrich
- Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany
| | - Petra Schrotz-King
- Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany
| | - Valery Lemmens
- Comprehensive Cancer Organization The Netherlands, Utrecht, The Netherlands; Department of Public Health, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Bengt Glimelius
- Department of Immunology, Genetics and Pathology, Section of Experimental and Clinical Oncology, Uppsala University, Uppsala, Sweden
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany.
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15
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Glimelius B, Martling A. What conclusions can be drawn from the Stockholm III rectal cancer trial in the era of watch and wait? Acta Oncol 2017; 56:1139-1142. [PMID: 28686505 DOI: 10.1080/0284186x.2017.1344359] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- B. Glimelius
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala
| | - A. Martling
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
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16
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Carvalho C, Glynne-Jones R. Challenges behind proving efficacy of adjuvant chemotherapy after preoperative chemoradiation for rectal cancer. Lancet Oncol 2017; 18:e354-e363. [DOI: 10.1016/s1470-2045(17)30346-7] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Revised: 03/09/2017] [Accepted: 03/13/2017] [Indexed: 12/11/2022]
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Glimelius B. On a prolonged interval between rectal cancer (chemo)radiotherapy and surgery. Ups J Med Sci 2017; 122:1-10. [PMID: 28256956 PMCID: PMC5361426 DOI: 10.1080/03009734.2016.1274806] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2016] [Revised: 12/08/2016] [Accepted: 12/16/2016] [Indexed: 12/25/2022] Open
Abstract
Preoperative radiotherapy (RT) or chemoradiotherapy (CRT) is often required before rectal cancer surgery to obtain low local recurrence rates or, in locally advanced tumours, to radically remove the tumour. RT/CRT in tumours responding completely can allow an organ-preserving strategy. The time from the end of the RT/CRT to surgery or to the decision not to operate has been prolonged during recent years. After a brief review of the literature, the relevance of the time interval to surgery is discussed depending upon the indication for RT/CRT. In intermediate rectal cancers, where the aim is to decrease local recurrence rates without any need for down-sizing/-staging, short-course RT with immediate surgery is appropriate. In elderly patients at risk for surgical complications, surgery could be delayed 5-8 weeks. If CRT is used, surgery should be performed when the acute radiation reaction has subsided or after 5-6 weeks. In locally advanced tumours, where CRT is indicated, the optimal delay is 6-8 weeks. In patients not tolerating CRT, short-course RT with a 6-8-week delay is an alternative. If organ preservation is a goal, a first evaluation should preferably be carried out after about 6 weeks, with planned surgery for week 8 if the response is inadequate. In case the response is good, a new evaluation should be carried out after about 12 weeks, with a decision to start a 'watch-and-wait' programme or operate. Chemotherapy in the waiting period is an interesting option, and has been the subject of recent trials with promising results.
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Affiliation(s)
- Bengt Glimelius
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
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18
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Ozyurt H, Ozden AS, Ozgen Z, Gemici C, Yaprak G. Pre- and post-surgery treatments in rectal cancer: a long-term single-centre experience. ACTA ACUST UNITED AC 2017; 24:e24-e34. [PMID: 28270729 DOI: 10.3747/co.24.3229] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Our study evaluated long-term survival outcomes in rectal cancer patients treated with preoperative radiotherapy, and the impact on survival of concomitant and postoperative adjuvant chemotherapy (ctx), among other prognostic factors. METHODS The study included 196 patients [median age: 58 years (range: 20-86 years); 63.0% men] with locally advanced rectal carcinoma and, in some cases, resectable liver metastasis. Rates of distant metastasis and local recurrence and of 5-year distant metastasis-free survival (dmfs) and overall survival (os) were determined. RESULTS The 5-year os rate was 57.0%, with a median duration of 81.5 months (95% confidence interval: 73.7 months to 89.4 months), and the 5-year dmfs rate was 54.1%, with a median duration of 68.4 months (95% confidence interval: 40.4 months to 96.4 months). Prognostic factors for higher os and dmfs rates were downstaging (p = 0.013 and p = 0.005 respectively), radiotherapy dose (50 Gy vs. 56 Gy or 45-46 Gy, both p = 0.002), and concomitant ctx use (p = 0.004 and p = 0.001) and type (5-fluorouracil-leucovorin-folinic acid vs. tegafur-folinic acid, p = 0.034 and p = 0.043). Adjuvant ctx after neoadjuvant long-term concomitant chemoradiotherapy (ccrt) and surgery was associated with better 5-year os rates for postoperative T0-T3 disease (p = 0.003) and disease at all lymph node stages (p = 0.001). CONCLUSIONS Our findings revealed a favourable survival outcome with long-term fractionated irradiation and concomitant 5-fluorouracil-based ctx, achieving 5-year os and dmfs rates of 57.0% and 54.1% respectively. Preoperative administration of radiotherapy (50 Gy) and postoperative adjuvant ctx were associated with a significant survival benefit. Radiation doses above 50 Gy and the interval between ccrt and surgery had no significant effect on survival.
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Affiliation(s)
- H Ozyurt
- Department of Radiation Oncology, Dr. Lutfi Kirdar Kartal Training and Research Hospital, and
| | - A S Ozden
- Department of Radiation Oncology, Dr. Lutfi Kirdar Kartal Training and Research Hospital, and
| | - Z Ozgen
- Department of Radiation Oncology, Marmara University Faculty of Medicine, Istanbul, Turkey
| | - C Gemici
- Department of Radiation Oncology, Dr. Lutfi Kirdar Kartal Training and Research Hospital, and
| | - G Yaprak
- Department of Radiation Oncology, Dr. Lutfi Kirdar Kartal Training and Research Hospital, and
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19
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Glimelius B. What is most relevant in preoperative rectal cancer chemoradiotherapy - the chemotherapy, the radiation dose or the timing to surgery? Acta Oncol 2016; 55:1381-1385. [PMID: 27879164 DOI: 10.1080/0284186x.2016.1254817] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Affiliation(s)
- Bengt Glimelius
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
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20
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Stanisavljević L, Myklebust MP, Leh S, Dahl O. LGR5 and CD133 as prognostic and predictive markers for fluoropyrimidine-based adjuvant chemotherapy in colorectal cancer. Acta Oncol 2016; 55:1425-1433. [PMID: 27435662 DOI: 10.1080/0284186x.2016.1201215] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Expression of leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) gene is associated with a metastatic phenotype and poor prognosis in colorectal cancer (CRC). CD133 expression is a putative cancer stem cell marker and a proposed prognostic marker in CRC, whereas the predictive value of CD133 expression for effect of adjuvant chemotherapy in CRC is unclear. MATERIAL AND METHODS For the study of LGR5 mRNA and CD133 expression, tissue microarrays from 409 primary CRC stage II and III tumors, where patients had been randomized to adjuvant chemotherapy or surgery only, were available. LGR5 mRNA and CD133 expression were assessed by in situ hybridization (ISH) and immunohistochemistry (IHC), respectively. LGR5 mRNA and CD133 expression as prognostic and predictive markers were evaluated by univariate and multivariate analyses. RESULTS For all CRC patients, positive LGR5 mRNA and CD133 expression were associated with classic adenocarcinoma histology type (p = 0.001 and p = 0.014, respectively). Positive LGR5 mRNA expression was also associated with smaller tumor diameter for CRC stage II (p = 0.005), but not for CRC stage III (p = 0.054). For CRC stage II, lack of LGR5 mRNA expression was associated with longer time to recurrence (TTR) in Kaplan-Meier (p = 0.045) and in multivariate Cox analysis (HR 0.27, 95% CI 0.08-0.95, p = 0.041). For colon cancer stage III patients, lack of CD133 expression was associated with better effect of adjuvant chemotherapy (p = 0.016) in Kaplan-Meier univariate analysis, but the interaction between CD133 and adjuvant chemotherapy was not statistically significant in multivariate analysis (HR 0.59, 95% CI 0.18-1.89, p = 0.374). CONCLUSION LGR5 mRNA expression is a prognostic factor for CRC stage II patients, whereas the value of CD133 expression as prognostic and predictive biomarker is inconclusive.
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Affiliation(s)
| | - Mette P. Myklebust
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
| | - Sabine Leh
- Department of Pathology, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Olav Dahl
- Department of Clinical Science, University of Bergen, Bergen, Norway
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
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Nikberg M, Chabok A, Letocha H, Kindler C, Glimelius B, Smedh K. Lymphovascular and perineural invasion in stage II rectal cancer: a report from the Swedish colorectal cancer registry. Acta Oncol 2016; 55:1418-1424. [PMID: 27732105 DOI: 10.1080/0284186x.2016.1230274] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Adjuvant chemotherapy for stage II and III rectal cancer patients is a matter of discussion. The aim of the present study was to evaluate the prognostic value of lymphovascular (LVI) and perineural (PNI) invasion in stage II rectal cancer on a national level. MATERIALS AND METHODS Clinico-pathological factors associated with disease-free survival (DFS) and time to recurrence in stage II rectal cancer patients were analyzed from patient data registered in the Swedish Colorectal Cancer Registry between 2006 and 2012. RESULTS Of 2649 patients with TNM stage II disease, 1395 (53%) received preoperative radiotherapy and 456 (17%) preoperative chemoradiotherapy. LVI and PNI were detected in 387 (15%) and 269 (10%) patients, respectively. Adjuvant chemotherapy was planned in 14%, but more often if LVI or PNI was detected (25% and 31%, respectively, p < .001 for both). The three-year DFS and time to recurrence were 78% and 17%, respectively. Both LVI and PNI indicated worse outcome. In patients not receiving postoperative chemotherapy, the risks of recurrence after three years were 20% if LVI was seen and 22% if PNI was detected (p < .001 for both). In the absence of LVI and PNI, it was 13% and 12%, respectively. In a multivariate Cox regression analysis, patients with LVI (hazard ratio 1.44, 95% CI 1.09-1.90; p = .011) and PNI (hazard ratio 1.80, 95% CI 1.34-2.43, p < .001) had significantly increased risks of recurrence. CONCLUSIONS Stage II rectal cancer patients with LVI and PNI have an increased risk of recurrence which emphasizes the need to properly evaluate the role of adjuvant chemotherapy particularly in these subgroups.
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Affiliation(s)
- Maziar Nikberg
- Department of Surgery, Centre for Clinical Research of Uppsala University, Västmanland’s Hospital Västerås, Västerås, Sweden
| | - Abbas Chabok
- Department of Surgery, Centre for Clinical Research of Uppsala University, Västmanland’s Hospital Västerås, Västerås, Sweden
| | - Henry Letocha
- Department of Oncology, Centre for Clinical Research of Uppsala University, Västmanland’s Hospital Västerås, Västerås, Sweden
| | - Csaba Kindler
- Department of Pathology, Centre for Clinical Research of Uppsala University, Västmanland’s Hospital Västerås, Västerås, Sweden
| | - Bengt Glimelius
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
| | - Kenneth Smedh
- Department of Surgery, Centre for Clinical Research of Uppsala University, Västmanland’s Hospital Västerås, Västerås, Sweden
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22
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Lutz MP, Zalcberg JR, Glynne-Jones R, Ruers T, Ducreux M, Arnold D, Aust D, Brown G, Bujko K, Cunningham C, Evrard S, Folprecht G, Gerard JP, Habr-Gama A, Haustermans K, Holm T, Kuhlmann KF, Lordick F, Mentha G, Moehler M, Nagtegaal ID, Pigazzi A, Pucciarelli S, Roth A, Rutten H, Schmoll HJ, Sorbye H, Van Cutsem E, Weitz J, Otto F. Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controversial issues in the primary treatment of rectal cancer. Eur J Cancer 2016; 63:11-24. [PMID: 27254838 DOI: 10.1016/j.ejca.2016.04.010] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Revised: 04/10/2016] [Accepted: 04/17/2016] [Indexed: 01/12/2023]
Abstract
Primary treatment of rectal cancer was the focus of the second St. Gallen European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Cancer Conference. In the context of the conference, a multidisciplinary international expert panel discussed and voted on controversial issues which could not be easily answered using published evidence. Main topics included optimal pretherapeutic imaging, indication and type of neoadjuvant treatment, and the treatment strategies in advanced tumours. Here we report the key recommendations and summarise the related evidence. The treatment strategy for localised rectal cancer varies from local excision in early tumours to neoadjuvant radiochemotherapy (RCT) in combination with extended surgery in locally advanced disease. Optimal pretherapeutic staging is a key to any treatment decision. The panel recommended magnetic resonance imaging (MRI) or MRI + endoscopic ultrasonography (EUS) as mandatory staging modalities, except for early T1 cancers with an option for local excision, where EUS in addition to MRI was considered to be most important because of its superior near-field resolution. Primary surgery with total mesorectal excision was recommended by most panellists for some early tumours with limited risk of recurrence (i.e. cT1-2 or cT3a N0 with clear mesorectal fascia on MRI and clearly above the levator muscles), whereas all other stages were considered for multimodal treatment. The consensus panel recommended long-course RCT over short-course radiotherapy for most clinical situations where neoadjuvant treatment is indicated, with the exception of T3a/b N0 tumours where short-course radiotherapy or even no neoadjuvant therapy were regarded to be an option. In patients with potentially resectable tumours and synchronous liver metastases, most panel members did not see an indication to start with classical fluoropyrimidine-based RCT but rather favoured preoperative short-course radiotherapy with systemic combination chemotherapy or alternatively a liver-first resection approach in resectable metastases, which both allow optimal systemic therapy for the metastatic disease. In general, proper patient selection and discussion in an experienced multidisciplinary team was considered as crucial component of care.
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Affiliation(s)
| | - John R Zalcberg
- Department of Epidemiology and Preventive Medicine, School of Public Health, Monash University, The Alfred Centre, Melbourne, Australia
| | - Rob Glynne-Jones
- Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, UK
| | - Theo Ruers
- The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Michel Ducreux
- Gustave Roussy, Université Paris-Saclay, Département de Médecine, Villejuif, France
| | - Dirk Arnold
- CUF Hospitals, Oncology Center, Lisbon, Portugal
| | - Daniela Aust
- Universitätsklinikum Carl Gustav Carus, Dresden, Germany
| | - Gina Brown
- Department of Diagnostic Imaging, The Royal Marsden NHS Foundation Trust, London, UK
| | - Krzysztof Bujko
- The Maria Sklodowska-Curie Memorial Cancer Centre, Warsaw, Poland
| | | | - Serge Evrard
- Institut Bergonié, Université de Bordeaux, Bordeaux, France
| | | | | | | | - Karin Haustermans
- Department of Radiation Oncology, University Hospitals Leuven, Belgium
| | - Torbjörn Holm
- Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
| | | | - Florian Lordick
- University Cancer Center Leipzig (UCCL), University Medicine Leipzig, Germany
| | | | - Markus Moehler
- I. Med. Klinik und Poliklinik, Johannes Gutenberg Universität Mainz, Mainz, Germany
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Alessio Pigazzi
- Department of Surgery, University of California, Irvine, CA, USA
| | | | | | - Harm Rutten
- Catharina Hospital Eindhoven, Eindhoven and GROW: School of Oncology and Developmental Biology, University Maastricht, Maastricht, The Netherlands
| | - Hans-Joachim Schmoll
- Department of Oncology/Haematology, Martin-Luther-University Halle, Halle (Saale), Germany
| | - Halfdan Sorbye
- Department of Oncology, Haukeland University Hospital, University of Bergen, Norway; Department of Clinical Science, Haukeland University Hospital, University of Bergen, Norway
| | - Eric Van Cutsem
- Digestive Oncology, University Hospitals Gasthuisberg/Leuven, Leuven, Belgium
| | - Jürgen Weitz
- Universitätsklinikum Carl Gustav Carus, Dresden, Germany
| | - Florian Otto
- Tumor- und Brustzentrum ZeTuP, St. Gallen, Switzerland
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Wang Z, Wang X, Li J, Yang C, Xing Z, Chen R, Xu F. HMGB1 knockdown effectively inhibits the progression of rectal cancer by suppressing HMGB1 expression and promoting apoptosis of rectal cancer cells. Mol Med Rep 2016; 14:1026-32. [PMID: 27220399 DOI: 10.3892/mmr.2016.5340] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Accepted: 05/03/2016] [Indexed: 11/05/2022] Open
Abstract
Rectal cancer is a malignant gastrointestinal tumor, which is associated with high morbidity and mortality. High‑mobility group protein 1 (HMGB1) is widely present in the nucleus of eukaryotic cells, and is highly conserved between humans and rodents. Recently, HMGB1 has been reported to be involved in the progression and metastasis of human cancer; however, its role in the development and metastasis of human rectal cancer remains unclear. The present study detected the expression levels of HMGB1 in pathological specimens from patients with clinically identified rectal cancer using immunohistochemistry and western blotting. The results demonstrated that HMGB1 was highly expressed in samples from patients with rectal cancer. The positive rate of HMGB1 in rectal cancer tissues was 96.08% (49/51), which was significantly higher compared with 3.92% (2/51) in normal tissues. In addition, western blotting indicated that HMGB1 was distributed and located not only in the nucleus, but also in the cytoplasm of colorectal cancer cells. HMGB1‑specific short hairpin (sh)RNA was used to silence the endogenous expression of HMGB1 in colorectal cancer cells. A functional assay demonstrated that knockdown of endogenous HMGB1 expression significantly inhibited the proliferation of SW620 and Colo320 cells. Furthermore, western blotting revealed that knockdown of endogenous HMGB1 expression contributed to activation of caspase‑3 and the substrate poly (ADP‑ribose) polymerase. The expression levels of B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax) were also detected by western blotting. As expected, decreased levels of Bcl‑2 and increased levels of Bax were detected in the HMGB1 shRNA‑transfected colorectal cancer cells, and the Bax/Bcl‑2 ratio was increased in HMGB1 shRNA‑transfected cells. These data indicated that HMGB1 may act as an oncogene in rectal cancer, and knockdown of endogenous HMGB1 expression may significantly inhibit the proliferation of colorectal cancer cells and promote apoptosis of tumor cells. Further research regarding the mechanisms underlying the effects of HMGB1 on the progression of rectal cancer may provide novel targets for the treatment of rectal cancer, and provide a theoretical reference for clinical treatment.
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Affiliation(s)
- Zhiwei Wang
- Qingdao Medical College, Qingdao University, Qingdao, Shandong 266042, P.R. China
| | - Xiaoyan Wang
- Healthcare Ward, Qingdao Central Medical Group, Qingdao, Shandong 266042, P.R. China
| | - Jiantian Li
- Department of Gastrointestinal and Anorectal Surgery, Qingdao Central Medical Group, Qingdao, Shandong 266042, P.R. China
| | - Cheng Yang
- Department of Gastrointestinal and Anorectal Surgery, Qingdao Central Medical Group, Qingdao, Shandong 266042, P.R. China
| | - Zhiyuan Xing
- Qingdao Medical College, Qingdao University, Qingdao, Shandong 266042, P.R. China
| | - Ruiyun Chen
- Department of Gastrointestinal and Anorectal Surgery, Qingdao Central Medical Group, Qingdao, Shandong 266042, P.R. China
| | - Fei Xu
- Department of Gastrointestinal and Anorectal Surgery, Qingdao Central Medical Group, Qingdao, Shandong 266042, P.R. China
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Russo S, Steele S, Fredman E, Biswas T. Current topics in the multimodality treatment of locally advanced rectal cancer. Future Oncol 2016; 12:963-79. [PMID: 26880222 DOI: 10.2217/fon.16.12] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The multimodality approach to the treatment of locally advanced rectal cancer has evolved to include neoadjuvant radiotherapy with or without concurrent chemotherapy, total mesorectal excision and adjuvant fluoropyrimidine-based chemotherapy. Though this broad strategy has yielded improvements in local control compared with historical data, overall survival remains largely unchanged. Current investigations focus on improving patient selection through new imaging modalities, improving surgical techniques, incorporating more aggressive systemic treatment regimens and the selective use of radiation. Here, we review emerging data regarding newer staging techniques, neoadjuvant chemotherapy, optimal timing of surgery, selective use of radiation and nonoperative approaches to the management of locally advanced rectal cancers.
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Affiliation(s)
- Suzanne Russo
- Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, USA
| | - Scott Steele
- Department of Surgery, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, USA
| | - Elisha Fredman
- Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, USA
| | - Tithi Biswas
- Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, USA
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25
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Adjuvant Chemotherapy in Rectal Cancer after Chemoradiotherapy. Clin Oncol (R Coll Radiol) 2016; 28:140-145. [DOI: 10.1016/j.clon.2015.11.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Revised: 11/08/2015] [Accepted: 11/09/2015] [Indexed: 01/27/2023]
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Matsunaga M, Miwa K, Oka Y, Nagasu S, Sakaue T, Fukahori M, Ushijima T, Akagi Y. mFOLFOX6 Chemotherapy after Resection of Anal Canal Mucinous Adenocarcinoma. Case Rep Oncol 2016; 9:280-4. [PMID: 27239184 PMCID: PMC4881242 DOI: 10.1159/000446066] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Because of their rarity, there are no clear guidelines for the treatment of anal carcinomas; such tumors are normally subjected to the same modalities as recommended for rectal cancer. We report a patient with anal canal mucinous adenocarcinoma, with metastases in the pararectal and right inguinal lymph nodes, who was treated with abdominoperineal resection followed by mFOLFOX6 chemotherapy for 6 months (12 cycles). The patient has remained recurrence-free thus far, approximately 2 years since the surgery. As the optimal treatments for anal carcinomas have not been fully elucidated, we present this case to highlight a possible course of action for such patients that appears to be effective and promising.
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Affiliation(s)
- Mototsugu Matsunaga
- Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Fukuoka, Japan
| | - Keisuke Miwa
- Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Fukuoka, Japan
| | - Yosuke Oka
- Department of Surgery, Kurume University School of Medicine, Fukuoka, Japan
| | - Sachiko Nagasu
- Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Fukuoka, Japan
- Department of Surgery, Kurume University School of Medicine, Fukuoka, Japan
| | - Takahiko Sakaue
- Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Fukuoka, Japan
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan
| | - Masaru Fukahori
- Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Fukuoka, Japan
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan
| | - Tomoyuki Ushijima
- Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Fukuoka, Japan
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan
| | - Yoshito Akagi
- Department of Surgery, Kurume University School of Medicine, Fukuoka, Japan
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Milinis K, Thornton M, Montazeri A, Rooney PS. Adjuvant chemotherapy for rectal cancer: Is it needed? World J Clin Oncol 2015; 6:225-236. [PMID: 26677436 PMCID: PMC4675908 DOI: 10.5306/wjco.v6.i6.225] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 08/01/2015] [Accepted: 09/08/2015] [Indexed: 02/06/2023] Open
Abstract
Adjuvant chemotherapy has become a standard treatment of advanced rectal cancer in the West. The benefits of adjuvant chemotherapy after surgery alone have been well established. However, controversy surrounds the use adjuvant chemotherapy in patients who received preoperative chemoradiotherapy, despite it being recommended by a number of international guidelines. Results of recent multicentre randomised control trials showed no benefit of adjuvant chemotherapy in terms of survival and rates of distant metastases. However, concerns exist regarding the quality of the studies including inadequate staging modalities, out-dated chemotherapeutic regimens and surgical approaches and small sample sizes. It has become evident that not all the patients respond to adjuvant chemotherapy and more personalised approach should be employed when considering the benefits of adjuvant chemotherapy. The present review discusses the strengths and weaknesses of the current evidence-base and suggests improvements for future studies.
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Affiliation(s)
- Bengt Glimelius
- a Department of Immunology, Genetics and Pathology , Uppsala University , Uppsala , Sweden
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29
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Affiliation(s)
- Bengt Glimelius
- a Department of Immunology , Genetics and Pathology, Uppsala University , Uppsala , Sweden
| | - Nina Cavalli-Björkman
- a Department of Immunology , Genetics and Pathology, Uppsala University , Uppsala , Sweden
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30
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Grau C, Overgaard J, Høyer M, Tanderup K, Lindegaard JC, Muren LP. Biology-guided adaptive radiotherapy (BiGART) is progressing towards clinical reality. Acta Oncol 2015; 54:1245-50. [PMID: 26390238 DOI: 10.3109/0284186x.2015.1076992] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Cai Grau
- a Department of Oncology , Aarhus University Hospital , Aarhus , Denmark
| | - Jens Overgaard
- b Department of Experimental Clinical Oncology , Aarhus University Hospital , Aarhus , Denmark
| | - Morten Høyer
- a Department of Oncology , Aarhus University Hospital , Aarhus , Denmark
| | - Kari Tanderup
- a Department of Oncology , Aarhus University Hospital , Aarhus , Denmark
- c Department of Medical Physics , Aarhus University Hospital , Aarhus , Denmark
| | | | - Ludvig Paul Muren
- a Department of Oncology , Aarhus University Hospital , Aarhus , Denmark
- c Department of Medical Physics , Aarhus University Hospital , Aarhus , Denmark
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Sastre J, Serrano JJ, Fernández C, Ramirez C, Ortega L, García-Paredes B, Corona J, Alfonso R, Córdoba S, Díaz-Rubio E. Risk-Adapted Adjuvant Chemotherapy After Concomitant Fluoropyrimidine-Radiotherapy Neoadjuvant Treatment for Patients With Resectable CT3-4 or N+ Rectal Cancer: Five-Year Disease-Free Survival Results of a Single-Center Series. Clin Colorectal Cancer 2015; 15:128-34. [PMID: 26385572 DOI: 10.1016/j.clcc.2015.08.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2015] [Revised: 07/31/2015] [Accepted: 08/10/2015] [Indexed: 11/26/2022]
Abstract
BACKGROUND Providing adjuvant chemotherapy in locally advanced rectal cancer after neoadjuvant chemoradiation is currently a matter of debate. Recommendations from clinical guidelines range from offering no treatment to oxaliplatin-based combinations. We present a risk-adapted approach based on the response to initial chemoradiation as the strongest prognostic factor for disease-free survival (DFS). PATIENTS AND METHODS One hundred one patients were treated at a single institution with preoperative long-course radiotherapy plus concurrent fluoropyrimidines. Patients with disease downstaged to pT0-2N0 received adjuvant fluoropyrimidines alone, while the remaining received an oxaliplatin-based combination. The primary study end point was 5-year DFS. RESULTS Overall, the disease of 54 patients was downstaged to pT0-2N0 (53.5%), while that of 47 patients was staged as pT3-4 or N+ (46.5%) after surgery. In the intention-to-treat analysis, 5-year DFS for patients in the good-prognosis group (downstaging to pT0-2 N0) and for those with poor prognosis (pT3-4 or N+) were 79.4% and 66.3%, respectively (hazard ratio, 0.489; P = .043). Downstaging and pN+ were independent prognostic factors for DFS. CONCLUSION A risk-adapted adjuvant therapy strategy based on pathologic stage after neoadjuvant chemoradiation is feasible and achieves high rates of 5-year DFS. Patients with good prognostic factors can be treated with adjuvant fluoropyrimidines alone, thus permitting the avoidance of oxaliplatin-derived toxicities.
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Affiliation(s)
- Javier Sastre
- Department of Medical Oncology, Hospital Clínico San Carlos, Madrid, Center affiliated to Red Temática de Investigación Cooperativa (RD06/0020/0021) Instituto Carlos III, Spanish Ministry of Science and Innovation, Spain.
| | - Juan Jose Serrano
- Department of Medical Oncology, Hospital Clínico San Carlos, Madrid, Center affiliated to Red Temática de Investigación Cooperativa (RD06/0020/0021) Instituto Carlos III, Spanish Ministry of Science and Innovation, Spain
| | - Cristina Fernández
- Biostatistic and Preventive Medicine Department, Hospital Clínico San Carlos, Madrid, Spain
| | - Carmen Ramirez
- Department of Medical Oncology, Hospital Clínico San Carlos, Madrid, Center affiliated to Red Temática de Investigación Cooperativa (RD06/0020/0021) Instituto Carlos III, Spanish Ministry of Science and Innovation, Spain
| | - Luis Ortega
- Pathology Department, Hospital Clínico San Carlos, Madrid, Spain
| | - Beatriz García-Paredes
- Department of Medical Oncology, Hospital Clínico San Carlos, Madrid, Center affiliated to Red Temática de Investigación Cooperativa (RD06/0020/0021) Instituto Carlos III, Spanish Ministry of Science and Innovation, Spain
| | - Juan Corona
- Radiation Oncology Department, Hospital Clínico San Carlos, Madrid, Spain
| | - Rosario Alfonso
- Department of Medical Oncology, Hospital Clínico San Carlos, Madrid, Center affiliated to Red Temática de Investigación Cooperativa (RD06/0020/0021) Instituto Carlos III, Spanish Ministry of Science and Innovation, Spain
| | - Sofía Córdoba
- Radiation Oncology Department, Hospital Clínico San Carlos, Madrid, Spain
| | - Eduardo Díaz-Rubio
- Department of Medical Oncology, Hospital Clínico San Carlos, Madrid, Center affiliated to Red Temática de Investigación Cooperativa (RD06/0020/0021) Instituto Carlos III, Spanish Ministry of Science and Innovation, Spain
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Oki E, Ando K, Kasagi Y, Zaitsu Y, Sugiyama M, Nakashima Y, Sonoda H, Ohgaki K, Saeki H, Maehara Y. Recent advances in multidisciplinary approach for rectal cancer. Int J Clin Oncol 2015; 20:641-9. [PMID: 26100273 DOI: 10.1007/s10147-015-0858-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Accepted: 06/03/2015] [Indexed: 01/16/2023]
Abstract
Surgery is a major treatment option for rectal cancer, and total mesorectal excision has been demonstrated to be advantageous in terms of oncological outcome and thus has been the standard surgical approach. Radiotherapy before or after radical surgery is the optimal treatment to control local recurrence of advanced rectal cancer. To date, in many countries, the combination of neoadjuvant concurrent chemotherapy and radiotherapy is considered the standard therapy. A more recent interest in neoadjuvant therapy has been the use of oxaliplatin or targeted agents for neoadjuvant chemoradiotherapy. However, despite many trials of oxaliplatin and targeted agents, 5-FU-based concurrent chemoradiotherapy has remained the only standard treatment option. Postoperative adjuvant chemotherapy with neoadjuvant chemoradiotherapy or induction chemotherapy with neoadjuvant chemoradiotherapy may further improve patient survival, as some clinical studies recently indicated. In Japan, neoadjuvant therapy is not the standard treatment method, because surgery with lateral lymph node dissection is usually performed and this type of surgery may reduce recurrence rate as does radiation therapy. The phase III study to evaluate the oncological effect of the Japanese standard operation (mesorectal excision, ME) with lateral lymph node dissection in comparison with ME alone for clinical stage II and III lower rectal cancer is currently ongoing.
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Affiliation(s)
- Eiji Oki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan,
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Bujko K, Glimelius B, Valentini V, Michalski W, Spalek M. Postoperative chemotherapy in patients with rectal cancer receiving preoperative radio(chemo)therapy: A meta-analysis of randomized trials comparing surgery ± a fluoropyrimidine and surgery + a fluoropyrimidine ± oxaliplatin. Eur J Surg Oncol 2015; 41:713-23. [PMID: 25911110 DOI: 10.1016/j.ejso.2015.03.233] [Citation(s) in RCA: 90] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2014] [Revised: 03/23/2015] [Accepted: 03/26/2015] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND There is no consensus on the role of postoperative chemotherapy in patients with rectal cancer who have received preoperative radio(chemo)therapy. MATERIALS AND METHODS A systematic review and meta-analysis were performed of trials that used preoperative radio(chemo)therapy and randomized patients either between postoperative chemotherapy and observation or between a fluoropyrimidine only (FU-only) and a fluoropyrimidine with oxaliplatin (FU-OXA) as postoperative chemotherapy. RESULTS Five randomized studies compared postoperative chemotherapy with observation in a total of 2398 patients. None of these trials demonstrated a statistically significant benefit of chemotherapy for OS and DFS. The pooled differences in OS and DFS did not differ statistically significantly between the chemotherapy group and the observation group. The hazard ratios (HRs) and 95% confidence intervals (CIs) were 0.95 (CI: 0.82-1.10), P = 0.49 and 0.92 (CI: 0.80-1.04), P = 0.19, respectively. In the subgroup of trials in which randomization was performed after surgery (n = 753), a statistically significant positive pooled chemotherapy effect was observed for DFS (HR = 0.79, 95% CI: 0.62-1.00, P = 0.047), but not for OS (P = 0.39). Four randomized trials compared adjuvant FU-OXA with adjuvant FU-only in 2710 patients. In two trials, the difference in DFS between groups was statistically significant in favour of FU-OXA, and in the other two trials, the difference was not significant. The pooled difference in DFS between the FU-OXA group and the FU-only group was not statistically significant: HR = 0.84 (CI: 0.66-1.06), P = 0.15. CONCLUSION The use of postoperative chemotherapy in patients with rectal cancer receiving preoperative radio(chemo)therapy is not based on strong scientific evidence.
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Affiliation(s)
- K Bujko
- Department of Radiotherapy II, M. Sklodowska-Curie Memorial Cancer Centre, Warsaw, Poland.
| | - B Glimelius
- Department of Radiology, Oncology, and Radiation Science, Uppsala University, Uppsala, Sweden
| | - V Valentini
- Department of Radiation Oncology, Università Cattolica S Cuore, Rome, Italy
| | - W Michalski
- Bioinformatics and Biostatistics Unit, M. Sklodowska-Curie Memorial Cancer Centre, Warsaw, Poland
| | - M Spalek
- Department of Radiotherapy II, M. Sklodowska-Curie Memorial Cancer Centre, Warsaw, Poland
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34
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Glimelius B. Adjuvant chemotherapy for patients with rectal cancer - will the controversy be resolved? Acta Oncol 2015; 54:433-6. [PMID: 25783749 DOI: 10.3109/0284186x.2015.1024331] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Affiliation(s)
- Bengt Glimelius
- Uppsala University, Department of Immunology, Genetics and Pathology , Akademiska Sjukhuset, Uppsala , Sweden
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