Anal canal cancer treatment: practical limitations of routine prescription of concurrent chemotherapy and radiotherapy.
Chauveinc L, Buthaud X, Falcou MC, Mosseri V, De la Rochefordiere A, Pierga JY, Girodet J, Salmon RJ.
Radiotherapy Department, Institut Curie, 26 rue d'Ulm, 75248 Paris, Cedex 05, France.
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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+ 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 <55 years, 90% of patients between 56 and 64 years, 45% of patients between 65 and 75 years, and 20% of patients over 75 years (P<0.02).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% (P<0.04). 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=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 (p<0.02). 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.
PMID: 14647138 [PubMed - indexed for MEDLINE]
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Anorectal malignant melanoma: treatment with surgery or radiation therapy, or both.
Moozar KL, Wong CS, Couture J.
Department of Surgery, Princess Margaret Hospital, Toronto, Ont.
INTRODUCTION: Anorectal malignant tumours are increasing in frequency for unknown reasons. Surgery is the principal treatment, and the role of adjuvant therapy has not been defined. We therefore decided to review the experience of the Princess Margaret Hospital in Toronto, a large tertiary care cancer hospital, with respect to the surgical management of anorectal melanoma. METHODS: We reviewed the charts of all registered patients with anorectal malignant melanoma (AMM) treated with surgery or radiotherapy, or both, at the hospital between 1980 and 1999, paying particular attention to survival, and local and distant recurrences. RESULTS: There were 14 patients, all of whom were followed up to the time of death or for a minimum of 28 months for surviving patients. The mean ages at diagnosis were 56 years for men and 68 years for women. Clinical staging was as follows: local, 10 patients; locoregional, 3 patients and metastatic disease, 1 patient. Local therapy included local resection alone in 7 cases and abdominoperineal resection in 7. Seven patients received pelvic irradiation at some time during their disease, using different doses and fractionation schemes. Three of them had concomitant chemotherapy and radiotherapy with no tumour regression. In all 3 patients the lesions was reclassified as AMM and the patient underwent surgery. The other 4 patients had a short course of radiotherapy for palliation after the original lesion recurred. The overall median survival was 12 (range from 3-51) months. Two patients remained alive at last follow-up. Patients managed by local excision had a median survival of 12 (range from 3-51) months, and those managed by abdominoperineal resection had a median survival of 7 (range 5-51) months. Of the 10 patients treated initially with local excision, 6 required reoperation. Three underwent salvage abdominoperineal resection. Six patients were alive 1 year after treatment (median survival 32.5 mo [range from 21-51 mo]). Eight patients had a rapid evolution of their disease with a median survival of 5.5 (range from 3-12) months. Eleven of the 12 patients who died had metastatic disease. CONCLUSIONS: Systemic dissemination is almost universal in patients with AMM. The overall survival was poor regardless of local treatment. There was a 60% failure rate of local excision, which necessitated further surgery. Improving local control is important since some patients will survive up to 3 years.
PMID: 14577706 [PubMed - indexed for MEDLINE]
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Contribution of conformal therapy in the treatment of anal canal carcinoma with combined chemotherapy and radiotherapy: results of a phase II study.
Vuong T, Devic S, Belliveau P, Muanza T, Hegyi G.
Department of Radiation Oncology, McGill University Health Centre, Montreal, Quebec, Canada.
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PURPOSE: To evaluate the feasibility of delivering conformal radiotherapy (RT) and concurrent chemotherapy without a mandatory break in patients with anal canal carcinoma. METHODS AND MATERIALS: Thirty patients with T2-T4 tumors were treated with a combination of 54 Gy in 30 fractions and two cycles of 5-fluorouracil and mitomycin C. Dose-volume histograms were obtained for bone marrow, small bowel, and skin to compare the conventional technique using the Radiation Therapy Oncology Group standard with our conformal technique. RESULTS: The mean dose ratio of the conventional compared with the conformal technique for bone marrow, small bowel, and skin was, respectively, 2.1-2.7, 3.0, and 2.0, in favor of the conformal technique. All patients completed their treatment without a treatment break. An incidence of Grade 3 toxicity for bone marrow, bowel, and skin of 13.3%, 3.3%, and 20%, respectively, was observed. With a median follow-up of 33 months, a 4-year local recurrence-free survival rate of 91% was observed. CONCLUSION: The results of this study have shown that conformal RT leads to a well-tolerated treatment. The treatment time is shortened to 6 weeks. A significant decrease in the acute toxicity rate suggests that by decreasing the "volume factor," conformal RT improves the therapeutic index in patients treated with combined chemotherapy and RT.
Publication Types:
- Clinical Trial
- Clinical Trial, Phase II
PMID: 12788191 [PubMed - indexed for MEDLINE]
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Concurrent chemoradiotherapy for squamous cell carcinoma of the anus using a shrinking field radiotherapy technique without a boost.
Melcher AA, Sebag-Montefiore D.
Leeds Cancer Centre, Cookridge Hospital, Hospital Lane, Leeds, West Yorkshire LS16 6QB, UK.
Chemoradiotherapy (CRT) is now widely accepted as the primary treatment modality for squamous cell cancer of the anus. While randomised trials have clearly shown CRT to be more effective than radiotherapy alone, there remains uncertainty over the optimal integration of chemotherapy and radiation. We describe a series of 50 patients treated by a site specialist gastrointestinal nonsurgical oncologist with CRT at a single UK centre. Chemotherapy comprised mitomycin C (MMC) (day 1) and 5-fluorouracil (5-FU) (days 1-4, and 29-32), concurrent with 50 Gy in 25 fractions radiation, using a two-phase shrinking field technique. A radiation boost was not planned. At a median follow-up of 48 months, 11 (22%) of the patients have failed locally, of which three have been surgically salvaged. Nine (18%) have died of anal cancer. These results are comparable with those from large randomised studies, and suggest that a two-phase shrinking field radiotherapy technique with no boost, concurrent with MMC/5-FU chemotherapy, is an effective regimen for this disease. The CRT regimen described here provides the basis for the 'control arm' of the current UK-randomised CRT trial in anal cancer (ACT2).
PMID: 12778060 [PubMed - indexed for MEDLINE]
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Shortened irradiation scheme, continuous infusion of 5-fluorouracil and fractionation of mitomycin C in locally advanced anal carcinomas. Results of a phase II study of the European Organization for Research and Treatment of Cancer. Radiotherapy and Gastrointestinal Cooperative Groups.
Bosset JF, Roelofsen F, Morgan DA, Budach V, Coucke P, Jager JJ, Van der Steen-Banasik E, Triviere N, Stuben G, Puyraveau M, Mercier M; European Organization for Research and Treatment of Cancer. Radiotherapy and Gastrointestinal Cooperative Groups.
Radiotherapy Department, Besancon University Hospital, Besancon, France.
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The European Organization for Research and Treatment of Cancer (EORTC) 22861 randomised trial established that combined radiochemotherapy is the standard treatment for locally advanced anal cancer. This EORTC phase II study (#22953) tests the feasibility of reducing the gap between sequences to 2 weeks, to deliver Mitomycin C (MMC) in each radiotherapy sequence and 5-FU continuously during the treatment. The first sequence consisted of 36 Gy over 4 weeks. 5-FU 200 mg/m(2)/days 1-26, MMC 10 mg/m(2)/day 1 gap 16 days. Then a second sequence of 23.4 Gy over 17 days, 5-FU 200 mg/m(2)/days 1-17 and, MMC 10 mg/m(2)/day 1 was given. 43 patients with a World Health Organization (WHO) status of 0 (n=27) or 1 (n=16) and with T2-T4, N0-3 tumours were included. Compliance with the planned treatment, doses and duration was 93%. The complete response rate was 90.7%. Grade 3 toxicities of 28, 12 and 2% were observed for skin, diarrhoea and haematological toxicities, respectively. The 3-year estimated rates for trials 22861 and 22953 are: 68 and 88% for local control; 72 and 81% for colostomy-free interval, 62 and 84% for severe late toxicity-free interval, and 70 and 81% for survival, respectively. The 22953 scheme is feasible and the results are promising. This is now considered as the new standard scheme by the EORTC.
Publication Types:
- Clinical Trial
- Clinical Trial, Phase II
- Multicenter Study
- Randomized Controlled Trial
PMID: 12504657 [PubMed - indexed for MEDLINE]
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Induction chemotherapy followed by radiotherapy in the treatment of anal cancer.
Lee DH, Kim I, Song HH, Jung JY, Kim DY, Lee KW, Kim TY, Heo DS, Bang YJ, Ha SW, Park JG, Kim NK.
Department of Internal Medicine, Seoul National University College of Medicine, Korea.
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This study was conducted to investigate the efficacy of the induction chemotherapy followed by radiotherapy in anal cancer. Twenty-three patients diagnosed with anal cancer between March 1991 and February 1999 were treated with induction chemotherapy with 5-fluorouracil based regimens followed by external beam radiation. After a median follow-up of 78 months, the overall survival and the disease-free survival at 5 years was 71.3 and 67.5%, respectively. The colostomy-free survival at 5 years was 91%, as the inguinal lymph nodes were the most frequent site of relapse. Serious side effects did not occur and late complications did not develop either. Induction chemotherapy followed by radiotherapy in patients with anal cancer is effective in terms of its response and preserving the anal sphincter without serious acute and late complications.
PMID: 12469152 [PubMed - indexed for MEDLINE]
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Sphincter-sparing local excision and adjuvant radiation for anal-rectal melanoma.
Ballo MT, Gershenwald JE, Zagars GK, Lee JE, Mansfield PF, Strom EA, Bedikian AY, Kim KB, Papadopoulos NE, Prieto VG, Ross MI.
Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
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PURPOSE: To evaluate the outcome and toxicity of a sphincter-sparing treatment strategy in the management of patients with anal-rectal melanoma. PATIENTS AND METHODS: Between 1989 and 2000, 23 patients with invasive anal-rectal melanoma were managed with sphincter-sparing surgical resection and adjuvant radiation. Surgery consisted of primary local excision, as well as dissection for patients with documented regional nodal disease. Adjuvant radiation was delivered using a hypofractionated regimen of 30 Gy in five fractions over 2.5 weeks. Adjuvant systemic therapy was delivered to nine patients: cytotoxic chemotherapy in seven and immunotherapy in two. RESULTS: After a median follow-up of 32 months, 15 patients had relapsed and 15 patients had died. The actuarial 5-year overall, disease-specific, disease-free, and distant metastasis-free survival rates were 31%, 36%, 37%, and 35%, respectively. The actuarial 5-year local and regional nodal control rates were 74% and 84%, respectively. No patient had locoregional failure as the sole site of failure and no patient required salvage abdominoperineal resection (APR). By univariate analysis, patients with nodal disease at presentation had a decreased actuarial 5-year disease-specific (0% v 45%, P =.004), disease-free (0% v 45%, P <.001), and distant metastasis-free survival (0% v 42%, P <.001). The actuarial complication-free survival rate was 71%. Two patients developed mild scrotal edema (grade 1), and four patients developed moderate proctitis requiring prolonged medical management (grade 2). CONCLUSION: Sphincter-sparing local excision and adjuvant radiation is well tolerated and can effectively control local-regional disease while avoiding the functional morbidity of APR.
PMID: 12454112 [PubMed - indexed for MEDLINE]
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Radiation therapy for epidermoid carcinoma of the anal canal, clinical and treatment factors associated with outcome.
Myerson RJ, Kong F, Birnbaum EH, Fleshman JW, Kodner IJ, Picus J, Ratkin GA, Read TE, Walz BJ.
Radiation Oncology Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
BACKGROUND AND PURPOSE: In recent years, treatment with combined chemotherapy and radiation has become the standard of care for epidermoid carcinoma of the anus. However, optimal radiotherapy techniques and doses are not well established. MATERIALS AND METHODS: During the period 1975-1997, 106 patients with epidermoid carcinoma of the anal canal underwent radiation therapy. Treatment policies evolved from radiation therapy alone or with surgery, to combined chemotherapy and radiation followed by surgery, to combined chemotherapy and radiation. RESULTS: Overall 74% of patients were NED (no evidence of disease) at last follow-up. The most important clinical correlate with ultimate freedom from disease (includes the contribution of salvage surgery) was extent of disease. The 5-year ultimate freedom from disease was 87+/-5% for T1/T2N0, 78+/-10% for T3N0 (15% salvaged by surgery), and 43+/-10% for either T4N0 or any N+ lesions (P<0.001, Tarone-Ware). There was no difference between planned vs. expectant surgery (5-year ultimate NED: 67+/-11% planned surgery vs. 73+/-5% expectant surgery). The most important correlate with late toxicity was a history of major pelvic surgery (surgical vs. non-surgical group: P=0.013, Fisher's exact test, two-tailed summation). Thirty-three additional malignancies have been seen in 26 patients. The most common additional malignancies were gynecologic (nine cases), head and neck (six cases), and lung cancer (five cases). CONCLUSIONS: For T1/T2N0 disease, moderate doses of radiation combined with chemotherapy provided adequate treatment. T4N0 and N+ lesions are the most appropriate candidates for investigational protocols evaluating dose intensification. T3N0 tumors may also be appropriate for investigation; however, dose intensification may ultimately prove counterproductive if the cure rate is not improved and salvage surgery is rendered more difficult. The volume of irradiated small bowel should be minimized for patients who have a past history of major pelvic surgery or who (because of locally advanced tumors) may need salvage surgery in the future. Because of the occurrence of additional malignancy, patients with anal cancer should receive general oncologic screening in long-term follow-up.
PMID: 11578724 [PubMed - indexed for MEDLINE]
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The impact of gap duration on local control in anal canal carcinoma treated by split-course radiotherapy and concomitant chemotherapy.
Weber DC, Kurtz JM, Allal AS.
Radiation Oncology Department of the University Hospital, Geneva, Switzerland.
PURPOSE: To investigate the potential benefit of reducing the intersequence gap in patients with anal cancer treated with split-course chemoradiotherapy. METHODS: The study group consisted of 90 patients with anal squamous carcinoma treated between 1981 and 1998, using concomitant chemotherapy (CT) and radiation (RT). Median age was 65 years (range 41-87). RT was delivered in a split course, with a median gap of 37.5 days (range 4-97) between sequences. First (pelvic) sequence delivered a median dose of 40 Gy (range 36-50.4), using AP/PA megavoltage photon beams. Boost treatment (median dose 20 Gy, range 13-26) consisted of either Iridium-192 implantation (49 patients) or external beam RT (41 patients). CT consisted of 1-2 cycles of a 5-day continuous infusion of 5-fluorouracil and bolus mitomycin C, usually administered during the first week of each RT course. Median follow-up was 76.2 months. Univariate and multivariate analyses were performed to determine the factors associated with locoregional control (LRC). RESULTS: Five-year actuarial LRC was 72.5%. Factors associated with poorer LRC (univariate) were: age < or = 65, male gender, and gap > 37.5 days. Number of CT cycles (1 vs. 2 or more), boost technique (brachytherapy vs. external), and T-stage were not significantly associated with LRC. In multivariate analysis, only age (p = 0.01), and gap (p = 0.02) retained their significance. In patients older than 65 years, LRC was 92.3% and 75% for shorter and longer gaps, respectively. In younger patients, the corresponding values for LRC were 73.7% and 50%. CONCLUSION: In anal cancers, split-course RT with > 50 Gy dose delivery is difficult to avoid because of acute toxicity. The present analysis suggests that shortening the gap contributes to optimizing LRC. Gaps longer than 5 weeks correlated with poorer LRC, with especially unsatisfactory results observed in younger patients.
PMID: 11395235 [PubMed - indexed for MEDLINE]
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