Anal cancer – What is the optimum chemoradiotherapy?

Vinayan, A.; Glynne‐Jones, Rob

doi:10.1016/j.bpg.2016.06.005

Cited by 11 publications

(12 citation statements)

References 71 publications

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“…4 Treatment with concurrent chemoradiotherapy is associated with a 3-year local control rate of 75% to 90% and a colostomy-free survival rate of 40% to 50%. 23 Although over time there have been numerous improvements in care provided during the administration of radiotherapy, such as the advent of intensitymodulated radiotherapy and better supportive care to address gastrointestinal tract and hematologic toxic effects from concurrent chemoradiotherapy, more than 30% of patients still experience severe toxic effects during treatment. 17 Although there is a large body of data that support the benefits of chemoradiotherapy in the management of SCCAC, patients with T1N0 tumors have not been included in these studies.…”

Section: Resultsmentioning

confidence: 99%

Management of Stage I Squamous Cell Carcinoma of the Anal Canal

et al. 2018

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IMPORTANCE The incidence of squamous cell carcinoma of the anal canal (SCCAC) is increasing. Although standard management of SCCAC includes the use of concurrent chemotherapy and radiotherapy (chemoradiotherapy), data are lacking on potentially less morbid, alternative management strategies, such as local excision, among patients with node-negative T1 disease. OBJECTIVES To examine the use of local excision among patients with T1 SCCAC and to compare overall survival relative to those who received standard treatment with chemoradiotherapy. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study assessed 2243 patients in the National Cancer Database (2004-2012) between 18 and 80 years of age with T1N0M0 SCCAC. The association between the type of treatment received and overall risk of death was evaluated using multivariable Cox proportional hazards regression models. Data analysis was performed from June 29, 2016, to April 17, 2017. MAIN OUTCOMES AND MEASURES Overall survival. RESULTS Among 2243 patients with T1N0 SCCAC, 503 (22.4%) were treated with local excision alone (mean [SD] age, 54.5 [12.1] years; 240 [47.7%] male; 419 [83.3%] white) and 1740 with chemoradiotherapy (mean [SD] age, 57.0 [10.6] years; 562 [32.3%] male; 1547 [88.9%] white). Among those treated with chemoradiotherapy, 12 patients underwent a subsequent abdominoperineal resection. There was a statistically significant increase in the use of local excision during the study period (34 [17.3%] in 2004 to 68 [30.8%] in 2012; trend test, P < .001). This increase in use was observed among patients with primary tumors that measured 1 cm or smaller and greater than 1 cm to 2 cm or smaller (trend test, P < .001 for both). Overall survival at 5 years was not significantly different for the 2 management strategies (85.3% in the local excision cohort and 86.8% in the chemoradiotherapy cohort; log-rank test, P = .93). Overall risk of death was not significantly different for local excision alone relative to that for treatment with chemoradiotherapy (hazard ratio, 1.06; 95% CI, 0.78-1.44). These findings were robust when stratified by tumor size and when patients who underwent abdominoperineal resection after chemoradiotherapy were excluded. CONCLUSIONS AND RELEVANCE The use of local excision alone for the management of T1N0 SCCAC has significantly increased over time, with no clear decrement in overall survival. Because local excision may represent a lower-cost, less morbid treatment option for select patients with SCCAC, future studies are needed to better delineate its role and efficacy relative to the current standard of chemoradiotherapy.

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Section: Resultsmentioning

confidence: 99%

Management of Stage I Squamous Cell Carcinoma of the Anal Canal

et al. 2018

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“…Most cases (approximately 85%) are squamous cell carcinoma of the anus and anal canal (SCCA) with the remaining cases attributed to adenocarcinoma (10%) or other types (5%) ( Nelson et al , 2013 ). Small (T1) tumours may be treated with surgical excision alone, but for most tumours, the standard of care is combination chemo-radiotherapy ( Glynne-Jones et al , 2009 ), which achieves good responses with complete tumour regression in 80–90% of cases ( Vinayan and Glynne-Jones, 2016 ). However, acute toxicities resulting from current treatment regimens are common and patients can suffer long-term effects, including bowel, bladder and sexual dysfunction, and more rarely lower limb venous thrombosis ( Ghosn et al , 2015 ).…”

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confidence: 99%

No additional prognostic value for MRE11 in squamous cell carcinomas of the anus treated with chemo-radiotherapy

et al. 2017

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Background:The majority of anal cancers (84–95%) are driven by infection with human papillomavirus (HPV). HPV-positive tumours show significantly better responses to chemo-radiotherapy when compared with HPV-negative tumours. HPV infection is linked to alterations in DNA damage response proteins, including MRE11. MRE11 is a potential predictive biomarker for response to radiotherapy in muscle-invasive bladder cancer and may hold predictive power in other cancers.Methods:Using a previously reported cohort, we evaluated the levels of MRE11 in anal cancer and assessed its predictive value in this disease.Results:We found no association between the level of MRE11 and relapse-free survival following chemo-radiotherapy.Conclusions:MRE11 has no predictive value in the analysis of relapse-free survival after chemo-radiotherapy in anal cancer and does not add to the prognostic value of p16 and tumour-infiltrating lymphocyte scores. Further investigation into the role of DNA repair proteins in anal cancer is required.

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“… 1 , 46 MMC has been suggested to convert unresectable patients to surgical candidates, 42 enhance the therapeutic effects of adjuvant CRT, 47 and improve local control 48 in periampullary adenocarcinoma. Although it has not been extensively studied in PDAC, MMC has been used in other cancers such as anal cancer, 49 , 50 , 51 and recent studies suggest its promising role in PDAC patients with a family history of PDAC and/or carcinomas with an inactivating mutation in a Fanconi anemia pathway gene (such as BRCA1, BRCA2 , or PALB2 ). 18 , 19 , 20 , 21 , 22 , 23 Study results from trial A demonstrated that having a family history of PDAC specifically resulted in a borderline significant improvement in OS (164.4 vs 28.7 months, P = .058).…”

Section: Discussionmentioning

confidence: 99%

Long-term analysis of 2 prospective studies that incorporate mitomycin C into an adjuvant chemoradiation regimen for pancreatic and periampullary cancers

Schunke

Rosati

Zahurak

et al. 2018

Advances in Radiation Oncology

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PurposeThe purpose of this study was to report toxicity and long-term survival outcomes of 2 prospective trials evaluating mitomycin C (MMC) with 5-fluorouracil–based adjuvant chemoradiation in resected periampullary adenocarcinoma.Methods and materialsFrom 1996 to 2002, 119 patients received an adjuvant 4-drug chemotherapy regimen of 5-fluorouracil, leucovorin, MMC, and dipyridamole with chemoradiation on 2 consecutive trials (trials A and B). Trial A patients received upfront chemoradiation (50 Gy split-course, 2.5 Gy/fraction) followed by 4 cycles of the 4-drug chemotherapy with bolus 5-fluorouracil. Trial B patients received 1 cycle of the 4-drug chemotherapy with continuous infusion 5-fluorouracil followed by continuous chemoradiation (45-54 Gy, 1.8 Gy/fraction) and 2 additional cycles of chemotherapy. Cox proportional hazards models were performed to identify prognostic factors for overall survival (OS).ResultsOf the 62 trial A patients, 61% had pancreatic and 39% nonpancreatic periampullary carcinomas. Trial B (n = 57) consisted of 68% pancreatic and 32% nonpancreatic periampullary carcinomas. Resection margin and lymph node status were similar for both trials. Median follow-up was longer for trial A than trial B (197.5 vs 107.0 months), with median OS of 32.2 and 24.2 months, respectively. Rates of 3-, 5-, and 10-year OS were 48%, 31%, and 26% in trial A and 32%, 23%, and 9% in trial B. On multivariate analysis, lymph node–positive resection was the strongest prognostic factor for OS. A pancreatic primary and positive margin status were also associated with inferior survival (P < .05). Rates of grade ≥3 treatment-related toxicity in trials A and B were 2% and 7%, respectively.ConclusionsThis is the first study to report long-term outcomes of MMC with 5-fluorouracil–based adjuvant chemoradiation in periampullary cancers. Because MMC may be considered in DNA repair-deficient carcinomas, randomized trials are needed to determine the true benefit of adjuvant MMC.

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Anal cancer – What is the optimum chemoradiotherapy?

Cited by 11 publications

References 71 publications

Management of Stage I Squamous Cell Carcinoma of the Anal Canal

Management of Stage I Squamous Cell Carcinoma of the Anal Canal

No additional prognostic value for MRE11 in squamous cell carcinomas of the anus treated with chemo-radiotherapy

Long-term analysis of 2 prospective studies that incorporate mitomycin C into an adjuvant chemoradiation regimen for pancreatic and periampullary cancers

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