Epidermoid carcinoma of the anal canal

International Journal of Radiation Oncology*Biology*Physics, 1989

From 1972 to 1985, 260 cases of anal canal epidermoid carcinoma were irradiated. Eighteen cases treated for palliation were excluded from the study; 242 (93%) were treated with curative intent. The sex ratio was l/5.5; mean age was 66 years. Histology: 60.3% were well differentiated epidermoid carcinoma; 31.0% moderately differentiated and 8.7%, cloacogenic cases. Staging: Tl: 11.5% T2: 16.1%; T3a: 17%; T3b: 33.5%; and T4: 21.9%. Abnormal inguinal nodes were present in 15.3% of cases. Crude overall survival (Kaplan-Meier) for the 242 cases is 86.4% at 1 year, 63.9% at 3 years, 51.2% at 5 years, and 30.8% at 10 years. Radiation therapy was the sole treatment for 193 cases. No chemotherapy was given. Patients were irradiated by external beam. They received a first course of X rays (mostly 18 MV, some 6 MV) 40 to 45 Gy (box technique) over 4 to 5 weeks in the pelvis. Age and size of tumor were considered when deciding on the target volume. After a rest period of 4 to 6 weeks, a second course of 15 to 20 Gy in 2 weeks was given through a perineal field by electron-beam of suitable energy. The mean total dose was 60.56 Gy and median was 62.5 Gy; the mean overall treatment duration was 85.3 days (median 82 days) and the mean Time Dose Factor including decay factor was 98.96. In this group, 5-year determinate survival was: Tl-T2, 84.5%; T34 74.8%; T3b, 64.9%; T4, 58.9%. In 147/193 patients (76.2%) local control was achieved. The overall anal conservation rate was 62.6%. In 106 cases (55%), the anus had maintained normal function. The 5-year survival rate by N was 73.3% in the absence of inguinal nodes (169 cases) and 36.1% if such nodes were present. There was no significant difference in survival rate according to histological type. In the second group, receiving radiation therapy plus surgery, 33/49 cases (T3b-T4) were irradiated before surgery (median dose 40.5 Gy). Post operative radiation therapy was administered in 16 cases (T3b-T4) (median dose 49.6 Gy). The 5year determinate survival is 53.2% for T3b and 79% for T4. According to the log-rank test, there was no significant difference between survival with radiation therapy alone and radiation therapy plus surgery. Multivariate analysis of the whole group indicated that T stage is the only predictive variable. Non-predictive variables are: nodal status, histology, age, total dose, overall treatment time, and irradiation technique. There is no significant relationship between the complication rate (severe complications: 9.3%) and the aforementioned variables. Because of the homogeneity of the irradiation doses, no significant relationship was found between dose and local control rate or complication rate.

International Journal of Radiation Oncology*Biology*Physics, 1997

We analyzed in a retrospective series of patients treated by conservative irradiation for an epidermoid cancer of the anal canal (ECAC) the prognostic factors of locoregional control (LRC), survival, late severe complications (LSC), and sphincter conservation (SC). Methods and Materials: From 1976 until 1994,118 patients presenting with an ECAC were conservatively treated (mean age, 65 years). According to the 1987 International Union Against Cancer (TNM) classification, they were: 19 Tl, 70 T2,22 T3,7 T4,94 NO,. The treatment started with external beam irradiation (EBI) (36 Gy in 3 weeks or 45 Gy in 5 weeks). Concomitant chemotherapy (5fluorouracil and mltomycin C) was delivered to 31 patients. Two months later, a boost of 20 Gy was delivered by interstitial 19*Ir brachytherapy to 101 patients and EBI in 5. Twelve other patients had an abdomlnoperineal resection (APR). The mean follow-up was 6 years. Results: At 5 years the overall survival was 60%, and specific survival (SS) was 75%; it was 94% for Tl, 79% for T2, 53% for T3, and 19% for T4. In multivariate analysis, tumor size (~4 cm), node involvement, and no response to the EBI were factors of poor prognosis for SS. Thirty-two locoregional recurrences occurred of which 21 were local recurrences in the 106 patients treated by a conservative schedule. Only tumor size and response to the EBI were prognostic factors on multivariate analysis for local and LRC. A total of 17 patients presented with LSC (Grade 3,16 patients, and Grade 4,1 patient), which was treated by APR in 4 patients and colostomy in 11 (of which 7 were definitive). The only significant prognostic factor for LSC in the multivariate analysis was the total extrapolated response dose of irradiation. The definitive rate of SC after conservative treatment in cured patients was 100% for Tl, 82% for T2,58% for T3, and 100% for T4. Since 1989, improvements of the technique have allowed reduction of the LSC in maintaining the same local control. Conclusion: The results of this series are similar to those of the literature. The confirmation of pretherapeutic prognostic factors related to response to the treatment should allow us to adapt the therapeutic intensity for each case to obtain better tumor control, with as few sequelae as possible, to yield a better rate of SC. 0 1997 Elsevier Science Inc.

Diseases of The Colon & Rectum, 1994

PURPOSE: This study was designed to assess results of chemoradiation therapy for epidermoid carcinoma of the anal canal. METHODS: A retrospective review of records of the prospective database revealed 35 patients who had been diagnosed with anal canal carcinoma and treated with chemoradiotherapy at Wilford Hall USAF Medical Center (tertiary referral hospital) from 1981 to 1991. RESULTS: Patients ranged in age from 35 to 80 (mean, 59) years, and 63 percent were women. Primary tumors ranged from 1 to 8 cm in diameter (mean, 3 cm). The first six patients had an abdominoperineal resection (APR) after chemoradiotherapy, and no residual tumor was identified in the specimens. In the subsequent 29 patients who did not have APR, 5 had moderate problems with anal continence, and one required a diverting colostomy for incontinence. Follow-up ranged from 4 months to 12.9 years (mean, 5.2 years). There were two pelvic recurrences, and three patients developed distal metastasis. Eight patients died during follow-up, including three with recurrent or persistent disease. Five-year survival using life-table analysis was 89 percent. CONCLUSION: Long-term follow-up confirms that chemoradiation remains the preferred therapy for epidermoid carcinoma of the anal canal.

Cancer, 1995

Background. The role of radiotherapy alone in the sterilization of anal canal epidermoid carcinomas of 5 cm or more remains to be assessed. Thus, the outcomes of patients treated with radiotherapy alone (RT) versus those treated with preoperative radiotherapy and surgery (RS) were compared retrospectively. Methods. Between 1972 and 1990,185 patients were treated with curative intent either with RT alone (n = 147) or with RS (n = 38). The Mean tumor length was 6.18 f 1.14 cm and was significantly longer in the RS group (6.55 f 1.29 cm) than in the RT group (6.08 f 1.08 cm) (P = 0.02). The median follow-up was 77 f 57 months and 93 f 60 months (P = 0.23) for the RT and RS groups, respectively. For the RT group, the first course of radiotherapy was 40 to 45 Gy in the pelvis for 4 to 5 weeks; after a rest of 4 to 6 weeks, radiotherapy was boosted an additional 15 to 20 Gy for 2 weeks. The RS patients received 40 to 45 Gy in the pelvis for 4 to 5 weeks, then received surgery after a median period of 54 days. Results. The overall lo-year cancer specific survival rates were 58% in the RT group and 66% in the

The American Journal of Surgery, 1984

Squamous carcinoma of the anal canal is a relatively uncommon tumor. It constitutes 1 to 3 percent of cancers in the last 26 cm of the alimentary tract [Is]. Abdominoperineal resection of the rectum has been for a long time the treatment of choice of these tumors for most workers (I-71. Radiotherapy has only been used for patients with advanced tumor or recurrence or for those unable to sustain the surgical risk. Tumor removal implies major surgery, with a high mortality risk in elderly patients who comprise most of the cases [I ,2,6,8]. One effect of abdominoperineal resection is a permanent colostomy with its functional and pyschologic implications. The good results obtained with radiotherapy in a number of patients show that these squamous cell carcinomas of the anal canal are radios9nsitive and even often radiocurable. This is the reason why radiation therapy has been used at the Institut Curie since 1956, when the first cobalt appliance became available [9,10]. For these reasons and in order to sterilize cancer cells and retain normal anal function, we systematically irradiate all the patients presenting with squamous cell anal canal carcinoma. Surgery is used as a secondary procedure only if necessary. The treatment results in 183 patients irradiated between 1968 and 1979 are reported herein. From 1968 through 1979,203 patients were treated at the Institut Curie for anal cancer excluding the anal margin. Patients with adenocarcinoma, melanoma, distant From the lnstitut Curie, Parts, France. Requests fa reprhts should be adbessect to Rsmy J. Salmon. MD, Institute Cur& 28 rue d'Uhn. 75005 Parim, France.

The Lancet, 1996

Background Non-surgical management of anal cancer by radiotherapy alone or combined with chemotherapy has, in uncontrolled studies, yielded similar local tumour control and survival rates to surgery. However, whether the addition of chemotherapy improves outcome without adding to morbidity is not known. Our trial was designed to compare combined modality therapy (CMT) with radiotherapy alone in patients with epidermoid anal cancer. Methods From 856 patients considered for entry to our multicentre trial, 585 patients were randomised to receive initially either 45 Gy radiotherapy in twenty or twenty-five fractions over 4-5 weeks (290 patients) or the same regimen of radiotherapy combined with 5-fluorouracil (1000 mg/m 2 for 4 days or 750 mg/m 2 for 5 days) by continuous infusion during the first and the final weeks of radiotherapy and mitomycin (12 mg/m 2) on day 1 of the first course (295 patients). We assessed clinical response 6 weeks after initial treatment: good responders were recommended for boost radiotherapy and poor responders for salvage surgery. The main endpoint was local-failure rate (6 weeks after initial treatment); secondary endpoints were overall and cause-specific survival. Analysis was by intention-to-treat. Findings In the radiotherapy and CMT arms, respectively, five and three were ineligible, and six and nine died 6 weeks after initial treatment. After a median follow-up of 42 months (interquartile range 28-62), 164 of 279 (59%) radiotherapy patients had a local failure compared with 101 of 283 (36%) CMT patients. This gave a 46% reduction in the risk of local failure in the patients receiving CMT (relative risk 0•54, 95% CI 0•42-0•69, p<0•0001). The risk of death from anal cancer was also reduced in the CMT arm (0•71, 0•53-0•95, p=0•02). There was no overall survival advantage (0•86, 0•67-1•11, p=0•25). Early morbidity was significantly more frequent in the CMT arm (p=0•03), but late morbidity occurred at similar rates. Interpretation Our trial shows that the standard treatment for most patients with epidermoid anal cancer should be a combination of radiotherapy and infused 5-fluorouracil and mitomycin, with surgery reserved for those who fail on this regimen.

ANZ Journal of Surgery, 2004

Through the 1970s patients presenting with anal canal carcinoma were managed with a surgical approach--abdomino-perineal resection. Since then, the pioneering work of Nigro et al. and a series of large clinical trials have clearly demonstrated that combined chemotherapy and radiotherapy result in greater local control, colostomy-free survival and increase in overall patient survival. The aim of the present study is to determine how widely the combined modality approach has been adopted in routine clinical practice and what outcomes are achieved in this setting. All patients with anal cancer treated at three tertiary referral centres over an 11-year period (1991-2001) were identified. Data were collected by a retrospective record review. Our search identified a total of 50 patients: 22 men and 28 women, with a median age of 62 years. Four patients had metastatic disease diagnosed at presentation. Nine patients (18%) were at least 75 years of age and three were known to be HIV positive. Median potential follow up is 52 months. Of the 46 patients treated for cure, 38 received a combination of chemotherapy and radiation, with 79% achieving a complete response. Efficacy was maintained in treated elderly patients (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =75 years). The 5-year survival of the 38 patients with local or locoregional disease who received combined chemoradiation modality was 63%. Overall this series demonstrates that combined chemotherapy and radiotherapy has been adopted as standard treatment with outcome data similar to those reported in the randomized clinical trials. Where possible elderly patients should receive combined modality therapy.

American Journal of Clinical Oncology, 2010

To review the outcomes of definitive radiotherapy (RT) alone or combined with chemotherapy (CT) in the treatment of squamous cell carcinoma of the anal canal. Methods: Between November 1968 and June 2005, 69 patients were treated with curative intent at the University of Florida. Distribution according to T stage was: T 1 , 11 (16%); T 2 , 29 (42%); T 3 , 21 (30%); and T 4 , 8 (12%). Distribution according to N stage was: N 0 , 53 (77%); N 1 , 3 (4%); N 2 , 7 (10%); and N 3 , 6 (9%). RT consisted of external beam RT (EBRT) in 30 patients (43%) and EBRT plus brachytherapy in 39 patients (57%). Thirtyeight patients (55%) received adjuvant CT: mitomycin C and fluorouracil, 21 patients (30%); cisplatin plus fluorouracil, 16 patients (23%); and other, 1 patient (1%). Median follow-up for all patients was 7.9 years (range: 0.1-17.3 years). One patient who was disease-free was lost to follow-up at 129 months. Results: The 5-year local control rates were: T 1 , 100%; T 2 , 93%; T 3 , 70%; T 4 , 88%; and overall, 86%. The 5-year regional control rates were: N 0 , 96%; N 1 and N 2 , 89%; N 3 , 100%; and overall, 96%. The 5-year colostomy-free survival rates were: T 1 , 82%; T 2 , 89%; T 3 , 65%; T 4 , 38%; and overall, 74%. The 5-year cause-specific and overall survival rates were: stage I, 100% and 64%; stage II, 86% and 70%; stage III, 80% and 76%; and overall, 87% and 71%, respectively. Seven patients (10%) developed Radiation Therapy Oncology Group grade 3 late complications and 4 additional patients (6%) experienced grade 4 late complications. A fatal acute complication occurred in 1 patient (1%). Conclusion: The likelihood of cure and colostomy-free survival after EBRT alone or combined with brachytherapy is relatively high and likely improved by adjuvant CT. The acute toxicity of treatment is significant; the major risk is neutropenia and sepsis. Patients with advanced T 4 cancers that result in sphincter dysfunction requiring a pretreatment colostomy will usually have a permanent colostomy. FIGURE 2. Colostomy-free survival.

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.

Radiotherapy and Oncology, 2010

Purpose: To perform a systematic analysis of clinical data of presentation, treatment, outcome, toxicity, survival and other associated prognostic factors of the patients of anal canal who received treatment at our hospital. Methods and materials: The medical records of 257 patients treated with radiotherapy with or without chemotherapy from the year 1985 to 2005 were studied. Results: Median follow-up was 36 months. Complete clinical response after radiotherapy was 74.4% in the whole group. The 5 years overall (OAS) and disease-free (DFS) survival for the whole group was 71.5% and 61%, respectively. Patients with T1-2 tumors which received the radiation dose between 55 and 60 Gy had superior locoregional control, DFS and OAS. Similarly T3-4 tumors receiving radiation dose more than 60 Gy independently improved the locoregional control, DFS and OAS irrespective of the nodal status and addition of chemotherapy. Conclusions: Radiation dose of 56-60 Gy for T1 and T2 and 65 Gy for T3 and T4 tumors along with concurrent chemotherapy is required to achieve better local control, disease-free survival and overall survival, with acceptable toxicity. Ó