Carcinoma of Anal Canal (JCOG0903: SMART-AC)

Japanese Journal of Clinical Oncology, 2011

A Phase I/II trial of chemoradiotherapy concurrent with S-1 plus mitomycin C in patients with clinical Stage II/III squamous cell carcinoma of the anal canal was started in Japan. The aim of this trial is to determine the recommended dose of S-1 combined with a fixed dose of mitomycin C plus radiotherapy in Phase I and to evaluate the efficacy and safety in Phase II. The primary endpoint for the Phase II part of this study is the proportion of 3-year event-free survival, in which the following are defined as events: disease progression, residual tumor at the end of chemoradiotherapy, colostomy or death, whichever comes first. Secondary endpoints are progression-free survival, proportion of complete response and adverse events. In the Phase II part of this study, a total of 65 patients will be enrolled from 42 institutions over 6 years.

Clinics and Research in Hepatology and Gastroenterology, 2012

Cancer Medicine

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JAMA, 2008

NAL CANAL CARCINOMA IS AN uncommon malignancy in the United States. Among 1 437 180 new cancer diagnoses projected for the year 2008, approximately 5070 will be new cases of anal canal carcinoma. 1 Anal canal carcinoma has a unique clinical biology that can be distinguished from all other gastrointestinal cancers. It is mostly a local-regional cancer, with a metastatic potential in only 15% of patients, 2 and it is highly sensitive to concurrent chemoradiation, 3 resulting in a cure in 60% of cases. The size of the primary tumor has a direct bearing on the cure rates, 4-6 and the 5-year survival rates decrease precipitously for tumors larger than 5 cm in diameter. 7 Similarly, the presence of nodal metastases results in a reduction in the cure rate. 4,8-10 In addition, with larger primary cancers, the likelihood of lymph node metastases increases. 11-14 Approximately 25% of newly diagnosed anal canal carcinomas are larger than 5 cm in diameter and clinically node-positive. It has been established that chemoradiationismoreeffectivetherapyforsmaller analcanalcarcinomasthanforlargerones. This suggests that a strategy that could reduce the burden of cancer in the primary See also Patient Page.

Cancer, 2011

The purpose of this study was to compare outcomes in patients with anal canal squamous cell carcinoma (SCCA) who were treated with definitive chemoradiotherapy by either intensity-modulated radiation therapy (IMRT) or conventional radiotherapy (CRT). METHODS: Forty-six patients who received definitive chemoradiotherapy from January 1993 to August 2009 were included. Forty-five patients received 5-fluorouracil with mitomycin C (n ¼ 39) or cisplatin (n ¼ 6). Seventeen (37%) were treated with CRT and 29 (63%) with IMRT. The median dose was 54 Gy in both groups. Median follow-up was 26 months (CRT) and 32 months (IMRT). T3-T4 stage (P ¼ .18) and lymph node-positive disease (P ¼ .6) were similar between groups. RESULTS: The CRT group required longer treatment duration (57 days vs 40 days, P < .0001), more treatment breaks (88% vs 34.5%, P ¼ .001), and longer breaks (12 days vs 1.5 days, P < .0001) than patients treated with IMRT. Eleven (65%) patients in the CRT group experienced grade >2 nonhematologic toxicity compared with 6 (21%) patients in the IMRT group (P ¼ .003). The 3-year overall survival (OS), locoregional control (LRC), and progression-free survival were 87.8%, 91.9%, and 84.2%, respectively, for the IMRT groups and 51.8%, 56.7%, and 56.7%, respectively, for the CRT group (all P < .01). On multivariate analysis, T stage, use of IMRT, and treatment duration were associated with OS, and T stage and use of IMRT were associated with LRC. CONCLUSIONS: The use of IMRT was associated with less toxicity, reduced need for treatment breaks, and excellent LRC and OS compared with CRT in patients with SCCA of the anal canal. Cancer 2011;117:3342-51.

British Journal of Cancer, 2003

This study is an analysis of the criteria considered when prescribing concomitant chemotherapy and radiotherapy, as a routine treatment for patients with anal canal cancer, and related complications. Between 1990 and 1996, 67 patients were treated at Institut Curie for invasive, nonmetastatic cancer of the anal canal. Median age was 65 years (range, 35 -90 years). TNM stage distribution was as follows: seven T1, 17 T2, 27 T3, 16 T4, and 22 N þ patients. A total of 29 patients (i.e., five T1/T2, and 24 T3/T4) received concurrent chemotherapy and radiotherapy. Radiotherapy volumes and dose and prescribed dose for chemotherapy were not statistically different from one group of patients to another. Only 55% of T3/T4 patients underwent standard chemoradiation treatment for anal canal cancer. Age was the one of main factor in determining if the patient would undergo concomitant chemotherapy or not. For the T3/T4 patients, concomitant chemotherapy was prescribed to 69% of patients o55 years, 90% of patients between 56 and 64 years, 45% of patients between 65 and 75 years, and 20% of patients over 75 years (Po0.02).Overall survival at 4 years was 66%. The 4 years overall survival rate of T3/T4 patients, who underwent concomitant chemotherapy, was 72%, and that of T3/T4 patient who did not, was 34% (Po0.04). The patients who did not undergo chemotherapy were significantly older. The difference in cause-specific survival rates (72 vs 48%) was not significant. Relapse-free interval without local recurrence at 4 years was 70%. Relapse-free interval of T3/T4 patients was 78% with chemotherapy and 60% without chemotherapy (p ¼ NS). Rates of treatment discontinuation and early toxicity were not statistically different. Late complications occurred in 33 patients, eight of whom had grade 2/3 tumours. At 2 years, complications occurred in 39% of patients who had undergone concomitant chemotherapy, and in 20% of patients who had not (po0.02). Differences in grade 2/3 complications were not significant. In conclusion, although radiotherapy with concomitant chemotherapy is considered the current 'gold-standard' treatment for anal canal cancer, in our daily experience, only 55% of our T3/T4 patients have undergone this treatment. The remainder did not undergo chemotherapy mainly because they were deemed too old. In this series, no increase in local control and cause-specific survival was observed in patients who received concomitant chemotherapy; this may be due to the small number of patients included in the series. The increased rate of late complications observed in patients who received the combined treatment, however, provides evidence that this treatment should be restricted to younger patients without comorbidity and therefore justifies our position. Perhaps reduction of doses of chemotherapy must be discussed for older patients.

Cancer Medicine, 2019

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International Journal of Radiation Oncology*Biology*Physics, 2013

Purpose-A multi-institutional phase II trial assessed the utility of dose-painted IMRT (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% as compared to the conventional radiation/5FU/MMC arm from RTOG 9811. Methods and Materials-T2-4N0-3M0 anal cancer patients received 5FU and MMC days 1 and 29 of DP-IMRT, prescribed per stage-T2N0: 42Gy elective nodal and 50.4Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3: 45Gy elective nodal, 50.4Gy ≤ 3cm or 54Gy > 3cm metastatic nodal and 54Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator's ability to perform DP-IMRT.

RTOG 0529 assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing the acute morbidity of 5-fluorouracil/mitomycin-C chemoradiation for T2-4N0-3M0 anal cancer. With 52 evaluable patients, the primary endpoint of reducing grade 2 combined gastrointestinal and genitourinary Purpose: A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing grade 2þ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% compared with the conventional radiation/5FU/MMC arm from RTOG 9811. Methods and Materials: T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy 3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator's ability to perform DP-IMRT. Results: Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II, 25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2þ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2þ hematologic, 73% (9811 85%, PZ.032), grade 3þ gastrointestinal, 21% (9811 36%, PZ.0082), acute adverse events by 15% compared with the RTOG 9811 5-fluorouracil/mitomycin-C arm using standard radiation techniques was not met. However, DP-IMRT yielded significant sparing of acute grade 2þ hematologic, grade 3þ dermatologic, and gastrointestinal toxicity. and grade 3þ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations. Conclusions: Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2þ hematologic and grade 3þ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved feasible, the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials.

Acta Oncologica, 2006

The number of elderly patients with cancer is steadily increasing in developed countries and their treatment is a growing challenge for oncological departments. Anal cancer is the first tumour in which chemoradiotherapy with the intent of organ preservation has largely replaced surgery and is an interesting model of modern multimodal oncological treatment. At the Department of Oncology of the Helsinki University Central Hospital we have treated all patients irrespective of age following the same guidelines if there have been no specific contraindications on the basis of intercurrent diseases. The results suggest that the chemoradiotherapy protocol used in the treatment of anal cancer is reasonably well tolerated in elderly patients and the tumour control is comparable to those achieved in younger patients. After successful cancer therapy the life expectancy in these patients can be very long.