/pdf/pathology-and-genetics-of-tumours-of-the-digestive-system-3xy9cwrc3c.pdf

Pathology and genetics of tumours of the digestive system

Pathology and genetics: Tumours of the digestive system

Summary Anal cancer is an uncommon tumour that represents 4% of all cancers of the lower gastrointestinal tract. Its pathogenesis and treatment have undergone substantial reassessment over the past two decades, and this is likely to continue. Anal cancer can be cured by synchronous chemoradiotherapy, a treatment that both enables anal continence to be retained and reserves abdominoperineal resection of the rectum and anal canal (with formation of a permanent colostomy) for recurrent or residual disease after primary chemoradiotherapy. Overall, survival from anal cancer is now around 70–80% at 5 years. Future challenges will be influenced by an increasing incidence due to human papillomavirus and HIV infection, more accurate characterisation and treatment of early (in situ) disease, and optimisation of chemoradiation regimens.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(04)01410-X.pdf

Cancer of the anal canal

Purpose: To evaluate patterns of locoregional failure, and predictors of recurrence and survival in patients treated with chemoradiation for anal cancer. Methods and Materials: Between September 1992 and August 2004, 167 patients with nonmetastatic squamous cell anal carcinoma were treated with definitive chemoradiation. The median dose of radiotherapy was 5500 cGy. Concurrent chemotherapy was given with 5-fluorouracil and cisplatin in 117 patients, 5-fluorouracil and mitomycin C in 24 patients, and other regimens in 26 patients. Results: The estimated 3-year rates of locoregional control, distant control, disease-free survival, and overall survival were 81%, 88%, 67%, and 84%, respectively. Multivariate analysis showed that higher T stage and N stage independently predicted for a higher rate of locoregional failure; higher N stage and basaloid subtype independently predicted for a higher rate of distant metastasis; and higher N stage and positive human immunodeficiency virus status independently predicted for a lower rate of overall survival. Among the patients who had locoregional failure, 18 (75%) had failure involving the anus or rectum, 5 (21%) had other pelvic recurrences, and 1 (4%) had inguinal recurrence. The 5 pelvic recurrences all occurred in patients with the superior border of the radiotherapy field at the bottom of the sacroiliac joint. Conclusions: Trials of more aggressive and innovative locoregional and systemic therapies are warranted in high-risk patients, based on their T and N stages. The majority of locoregional failures involve the anus and rectum, whereas inguinal recurrences occur rarely. Placing the superior border of the radiotherapy field at L5/S1 could potentially reduce pelvic recurrences.

Predictors and Patterns of Recurrence After Definitive Chemoradiation for Anal Cancer

BACKGROUND

The authors performed a specific analysis of the clinical significance of inguinal lymph nodes metastases in patients with anal canal carcinoma (ACC)



METHODS

A retrospective analysis was conducted of 270 patients who were treated in Lyon between 1980 and 1996 with radiotherapy with curative intent for ACC: No elective irradiation of clinically normal inguinal areas was performed Patients with metastatic inguinal lymph nodes were treated with inguinal dissection and postoperative irradiation with a dose of 50 grays over 5 weeks Concomitant chemoradiation, usually with a regimen of fluorouracil and cisplatinum, was given to 159 patients



RESULTS

The median follow-up for the whole series was 72 months Synchronous inguinal metastases were observed in 10% of patients (n = 27; the rate was 16% for patients with T3–T4 lesions), and the 5-year overall survival rate was 544% Metachronous inguinal metastases were seen in 19 patients (78%), and the 5-year overall survival rate of these patients was 414% An original finding was that, when the primary tumor clearly was located on a single lateral side of the anal canal, the inguinal lymphatic metastases was always homolateral to it (36 of 36 synchronous plus metachronous tumors)



CONCLUSIONS

The data from this series of patients and a review of the literature are in favor of a selective approach in the management of inguinal lymph node involvement for patients with ACC, depending on the disease stage and the location of the primary tumors Cancer 2001;92:77–84 © 2001 American Cancer Society

Management of inguinal lymph node metastases in patients with carcinoma of the anal canal: experience in a series of 270 patients treated in Lyon and review of the literature.

We analyzed in a retrospective series of patients treated by conservative irradiation for an epidermiol 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 T1, 70 T2, 22 T3, 7 T4, 94 N0, and 24 N1–3. The treatment started with external beam irradiation (EBI) (36 Gy in 3 weeks or 45 Gy in 5 weeks). Concomitant chemotherapy (5-fluorouracil and mitomycin C) was delivered to 31 patients. Two months later, a boost of 20 Gy was delivered by interstitial 192 Ir brachytherapy to 101 patients and EBI in 5. Twelve other patients had an abdominoperineal 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 T1, 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 T1, 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 of obtain better tumor control, with as few sequele as possible, to yield a better rate of SC.

Conservative treatment by irradiation of epidermoid cancers of the anal canal: Prognostic factors of tumoral control and complications

l Clinical Investigation CONSERVATIVE TREATMENT BY IRRADIATION OF EPIDERMOID CANCERS OF THE ANAL CANAL: PROGNOSTIC FACTORS OF TUMORAL CONTROL AND COMPLICATIONS

Purpose: The salvage brachytherapy performed in patients presenting velotonsillar carcinoma in a previously irradiated field is evaluated in terms of local control, complications and survival. Methods and Materials: Between 1976 and 1990, 73 patients presenting with velotonsillar squamous cell carcinoma in a previously irradiated area were treated at Center Alexis Vautrin with brachytherapy alone using an 192 Ir implant (afterloading technique) with curative intent. According to the UICC 1987 TNM classification, there were 45 T 1 N 0 , 20 T 2 N 0 , one T 3 N o , one T 3 N 2 and six T x N x . Results: The 5-year actuarial local control for T 1 N 0 and T 2 N 0 are 80% and 67% respectively. The regional relapse rate was 10% in both groups. Grade 2 complications occured in 13% of patients and these were neither related to the volume treated nor the dose rate. There were no Grade 3 or 4 complications. The 5-year specific survival is 64%, with a plateau after the 5th year, but the 5-year overall survival is only 30%. Fourty-two percent of the patients in this series died from another carcinoma. All but two of these were related to continued alcohol and tobacco intoxication. Conclusion: We conclude that brachytherapy alone (60 Gy) is optimal treatment for patients presenting with velontonsillar carcinoma in a previously irradiated field. The greatest challenge is the screening of these patients and the prevention of subsequent head and neck cancers. Recognizing the fact that these patients are at high risk for subsequent malignancies of upper aerodigestive tract, lung and esophagus, close surveillance is necessary for: (a) early diagnosis and prompt treatment; and (b) development of prevention strategies of field cancerization.

Daniel Dartois

Papers

Conservative treatment by irradiation of epidermoid cancers of the anal canal: Prognostic factors of tumoral control and complications

l Clinical Investigation CONSERVATIVE TREATMENT BY IRRADIATION OF EPIDERMOID CANCERS OF THE ANAL CANAL: PROGNOSTIC FACTORS OF TUMORAL CONTROL AND COMPLICATIONS

Salvage irradiation by brachytherapy of velotonsillar squamous cell carcinoma in a previously irradiated field: results in 73 cases.