Radiation therapy of anal epidermoid carcinoma

Between 1978 and 1984, 44 consecutive patients with anal epidermoid carcinoma were either given radiation therapy alone (cloacogenic type) or in combination with Bleomycin (squamous type). The patients with small tumors (T1-T2) were treated to 65 Gy or 60 Gy + Bleomycin directly, whereas patients with moderately advanced tumors (T3) were treated to the same radiation dose, only if no evidence of residual disease existed after 50-55 Gy (40-45 Gy + Bleomycin); if a palpable tumor still remained 3 weeks after the irradiation, surgery was performed. Patients with tumors in Stage T4 were treated to 60-65 Gy (+/- Bleomycin) followed by surgery. The outcome has so far been excellent. All but four patients, treated according to the regimen and with no initial metastases, are alive and well; two died postoperatively, one developed urinary bladder recurrence, and one liver metastases. Nineteen patients have a preserved anal function. Only one of the 9 patients also treated with an abdomino-perineal excision had viable tumor at surgery. It is concluded that patients with an anal carcinoma can be safely treated with preservation of the anus in a significant proportion of the cases, and that a combined treatment approach most likely improves survival.     

肛管癌的疗效和预后因素分析

目的 回顾分析原发性肛管癌患者的疗效和预后因素。方法 2000—2011年本中心经治肛管癌患者3l例,鳞癌23例、腺癌8例。Ⅰ~Ⅲ期患者首程采用放疗为主治疗16例、手术为主治疗11例、化疗3例。结果 随访率为90%,随访时间满3年的样本数21例。全组3年总生存(OS)率和无进展生存(PFS)率分别为76%、56%。单因素分析显示临床分期和T分期为OS预后因素(χ²=12.11,P=0.001和χ²=4.64,P=0.031),并与PFS有相关趋势(χ²=2.91,P=0.088和χ²=2.75,P=0.097)。Ⅰ~Ⅲ期鳞癌患者首程放疗为主与手术为主治疗的3年OS率和PFS率均相似(80%与80%,χ²=0.08,P=0.776和78%与67%,χ²=0.17,P=0.697)。放疗患者3级皮肤或黏膜急性不良反应为37%,晚期肛门感觉或功能异常为9%。结论 临床分期、T分期是影响肛管癌患者预后的最主要因素,同期放化疗应作为肛管鳞癌患者根治性治疗手段的首选疗法,应用调强放疗技术有利于患者按计划完成放疗并避免发生严重不良反应。     

Surgical approach for treatment of epidermoid anal carcinoma.

The incidence of malignancy of the anus is rare when compared to colorectal cancer. At The New York Hospital-Cornell Medical Center 43 patients with anal cancer were seen since 1932. Five-year survival for patients treated by local excision, abdominal-perineal resecion, and abdominal perineal resection with associated inguinofemoral groin node dissection was 43%, 66%, and 33%, respectively. Therapy should be guided by location, size, and depth of the local lesion, as well as clinical node status. In general, local excision should be reserved for the most minute lesion. Groin dissection should be carried out when nodes are clinically diseased.     

Induction chemotherapy and radiotherapy in loco-regionally advanced epidermoid carcinoma of the anal canal

Purpose: To evaluate the efficacy of induction chemotherapy in combination with radiotherapy for treatment of loco-regionally advanced epidermoid anal carcinoma.Methods and Materials: Thirty-one patients diagnosed during the period 1989–1994 with loco-regionally advanced cancer of the anal canal (ΦT_max ≥ 4 cm or T4 or N+) were treated with induction chemotherapy consisting of one to three courses of carboplatin (300–375 mg/m² i.v.) and 5-fluorouracil [5,000 mg/(m² × 120 h) i.v.] followed by external beam irradiation ± surgery.Results: The toxicity of the chemotherapy was low. Twenty-nine patients were tumor free after the primary therapy. Kaplan-Meier analyses were made for overall survival, tumor-specific survival, freedom from recurrence, preservation of sphincter, and event-free survival. For these end points the 5-year data were 67, 85, 80, 69, and 51%, respectively.Conclusion: The results are promising but a well-designed randomized trial is needed to further elucidate the role of induction chemotherapy in the treatment of loco-regionally advanced anal carcinoma.     

Proliferation parameters in epidermoid carcinomas of the anal canal.

PURPOSE: In a prospective study, we assessed the proliferation parameters in primary epidermoid carcinomas of the anal canal, and results were compared with those in cervical carcinomas. METHODS: Between January 1992 and December 1996, 32 patients with primary epidermoid carcinoma of the anal canal were studied prospectively. Patients were given i.v. bromodeoxyuridine and proliferation parameters were obtained using flow cytometry. The treatment protocol consisted of radiation therapy (XRT) (24 Gy/12-3.5 week split-28 Gy/14) and concurrent 5-fluorouracil and mitomycin C. Proliferation parameters were not obtained in six patients, leaving 26 patients in the analysis. There were 16 females and ten males, with two T1, 16 T2, five T3 and three T4 lesions. Median follow-up was 3.6 years. There were 22 squamous cell and four basaloid carcinomas. Six tumors were aneuploid. RESULTS: Median values for T(s) and S-phase fraction were 7.7 h and 8.2%, respectively. The median LI was 6.8% (0.9-35.7%), and the median T(pot) was 4.1 days (0.9-30 days). There was no correlation of LI or T(pot) with gender, age, tumor stage, size or histology. Local failure was observed in five patients (T(pot)>4.1 days, n=3; LI>6.8%, n=4). Isolated regional failure or distant disease in the absence of local failure was not observed. The small number of outcome events precluded a definitive analysis of the prognostic role of LI and T(pot). Values for the proliferation parameters were similar to those in our updated study of patients with carcinoma of the uterine cervix (n=107), median LI of 6.7% and median T(pot) of 5.5 days. CONCLUSIONS: We conclude that proliferation parameters in anal carcinomas are similar to those in cervical carcinomas. Rapid tumor proliferation does not have an apparent adverse impact on outcome in anal carcinomas managed by split-course XRT with concurrent 5-florouracil and mitomycin C.     

A new approach to the management of epidermoid carcinoma of the anal canal

Until recently most squamous cell carcinomas of the anal canal were treated by radical surgery. Radiation therapy was only considered for palliation in case of inoperable tumors. Important progress has been made in the knowledge of the natural history of the disease and in the field of radiotherapy. Anal canal squamous cell carcinoma should not be treated any longer by the same procedure as adenocarcinoma of the lower rectum, because both these diseases differ markedly. Multimodality therapy with radiotherapy as first approach has been considered. This series of 121 cases treated since 1971 and followed more than three years suggests that three protocols based on irradiation followed or not by surgery should be used according to the extent of the disease. Of the 72 patients with resectable tumor, the five-year survival rate was 65%. Three-quarters of the patients cured had normal anal function. The rate of death from cancer was 18%. The method requires an accurate assessment of the extent of the tumor and of its pelvic lymphatic spread. Great care must be taken in planning treatment in a close cooperation between radiotherapist and surgeon.     

Prognostic role of p53 protein expression in epidermoid carcinoma of the anal canal.

PURPOSE: To assess the prognostic significance of p53 protein expression in patients with primary epidermoid carcinoma of the anal canal managed by radiation therapy (XRT), 5-fluorouracil (5-FU), and mitomycin C (MMC). METHODS AND MATERIALS: From January 1991 to December 1993, 58 consecutive patients with primary epidermoid carcinoma of the anal canal were treated in a prospectively designed protocol of XRT (24 Gy/12--3(1/2) wk split--28 Gy/14) and concurrent 5-FU (1000 mg/m2/day 1-4) and MMC (10 mg/m2 day 1) of each cycle of XRT. Paraffin-embedded tumor samples were unavailable in 9 patients, leaving 49 patients in the study. Expression of p53 protein was studied using immunohistochemistry and quantified as percent tumor nuclei showing positive staining. Actuarial survival and disease-free survival (DFS) rates were estimated by the Kaplan-Meier method, and compared using the log-rank test. A Cox proportional hazard model was used for the multivariable analysis. RESULTS: There were 6 T1, 26 T2, 7 T3, and 10 T4 lesions. Primary tumor sizes ranged from 1-15 cm with a median of 4 cm. There were 6 patients with nodal metastases. Median follow-up was 4.5 years. Positive nuclear immunostaining for p53 was observed in 40 of 49 patients. The median percent positive staining was 5%, with 13, 9, and 18 patients showing staining in <5%, 5 to <10%, and 10-50% of tumor nuclei respectively. There was no correlation of percent p53 staining with gender, age, tumor stage, size, or histology. Local, regional, and distant failures were observed in 12, 2, and 2 patients respectively. The 5-yr survival and DFS were 84% and 64% respectively. In univariate analysis, the only prognostic variable for survival was gender. For DFS, advanced T category and large tumor size were predictive of poor DFS. In multivariate analysis, poor DFS was associated with high T category (p = 0.0008), basaloid histology (p = 0.001), male gender (p = 0.002), and increasing percent of p53 protein expression (p = 0.01). CONCLUSIONS: It is concluded that expression for p53 protein is present in a high percentage of patients with epidermoid carcinoma of the anal canal. For patients managed with combined XRT, 5-FU, and MMC, percent p53 protein expression is of prognostic value for DFS independent of other clinical factors such as T category, gender, and histology.     

Preoperative chemotherapy and radiotherapy in the management of epidermoid carcinoma of the anal canal

Sixteen patients affected by epidermoid carcinoma of the anal canal were treated preoperatively by means of an i.v. infusion of mitomycin C (15 mg/m2) on day 1 and 5-fluorouracil (750 mg/m2) days 1 to 5, followed by radiotherapy (3000 R in 3 weeks). Four to 6 weeks after the end of radiotherapy the response to the preoperative treatment was evaluated by means of biopsy. A reduction of the neoplastic mass was observed in 13 of the 16 patients. An evident correlation exists between the stage of the tumor and 1) the response to preoperative treatment, 2) local recurrence, and 3) long-term survival. In fact: 3/4 T1 patients reached a complete response (CR), and 1/4 T1, 5/5 T2 and 4/7 T3 patients achieved a partial response (PR); only 3/7 T3 patients never responded to preoperative treatment. After the initial surgery, only T2 (3/5) and T3 (4/7) patients underwent a second operation for a recurrence. Overall survival at 42 months was 62.5% (T1, 100%; T2, 80%; T3, 28.5%).     

Lymphatic mapping and sentinel lymph node biopsy in epidermoid carcinoma of the anal canal

Aim

Although 15–25% of patients with anal cancer present with superficial inguinal lymph node metastases but the routine application of groin irradiation is controversial because of serious side effects. Inguinal sentinel lymph node biopsy (SLNB) can be used to select patients appropriately for inguinal radiation. The study evaluates the efficiency and clinical impact of SLNB.

Methods

Forty patients with anal cancer underwent 1 ml Tc^99m-Nanocolloid injection in four sites around the tumour. Patients with inguinal radio colloid enrichment were selected for sentinel lymph node biopsy (SLNB). Lymph node status was examined by haematoxylin and eosin (H&E) as well as immunohistochemistry-staining. All SLN-positive patients were scheduled for inguinal radiation; SLN-negative patients with T1 and early T2 tumours were not scheduled for inguinal radiation.

Results

SLN were detected in 36/40 patients. Three common patterns of lymphatic drainage were observed: mesenterial, iliacal and inguinal. Twenty patients with inguinal SLN underwent SLN-biopsy. 6/20 patients were SLN-positive. In 10/20 patients SLNB altered the therapy plan – four patients with T1-tumours and positive SLN had additional groin irradiation, whereas 6 patients with small T2-tumors and tumour-free inguinal SLN did not undergo inguinal irradiation.

Conclusions

Inguinal sentinel node biopsy in anal cancer is efficient and could assist in the decision for inguinal radiation. The validity and safety of the proposed therapeutic algorithm has to be proven by a larger, prospective study.     

Prognosis of epidermoid anal carcinoma regression after conservative treatment

The prospective study was concerned with definition of the clinical and therapeutic factors behind poor response of anal cancer to radio- (RT) or chemoradiotherapy (CRT). Out of 64 female and 8 male patients at the mean age of 57 (33-81), thirty six had split-course of 60-65 Gy (RT), twenty--60-65 Gy, 5-FU and mitomycin C (CRT) and eighteen--up to 55-65 Gy (1.5 Gy--session 1, 1.0 Gy--session 2) (hyper-fractionated RT) plus 5-FU, for squamous cell anal carcinoma. There was no endorectal ultrasound evidence of perirectal lymph node involvement (uN0): T1-2uN-M0 (n=46), T3-4uN0M0 (n=11), uN1 or N2-3 (groin or endorectal ultrasound: T1-2uN-M0 (n=46), T3-4uN0M0 (n=11), uN1 or N2-3 (groin metastases) were detected in 7 patients: T1-2uN1-2M0 (n=7), T3-4N1-3M0 (n=10). Endorectal ultrasound staging (ERUS) used a linear 7.5 MHz transducer. The uTNM system was devised on the basis of tumor invasion parameters. There were no tumors confined to the subendothelial layer of the anal canal (uT1); 24 (32.4%) tumors were confined to the internal anal sphincter (uT2); 19 (25.7%) invaded the external anal sphincter (uT3) and 31 (41.9%)--levator ani (uT4). All carcinomas T4 (n=9) corresponded to the uT4 category. Only T-stage and tumor invasion (uT) proved significant prognostic variables. Complete response of T1-2 was 79.2%, T3-4--33.3% (p=0.0003); uT2--95.8%, uT3--68.4%, and uT4--41.9% (except T4) (p=0.0001). In multivariate logistic analysis, uT alone appeared an independent variable (p=0.015). ERUS uTNM staging is more effective in prognosis for RT and CRT and, therefore, should be recommended for preliminary management of epidermoid anal carcinoma.     

Intensity-modulated radiation therapy versus conventional radiation therapy for squamous cell carcinoma of the anal canal

BACKGROUND:

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 = 39) or cisplatin (n = 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 = .18) and lymph node‐positive disease (P = .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 = .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 = .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. © 2011 American Cancer Society.     

Multi-modality therapy for epidermoid carcinoma of the anus.

Three patients presenting with surgically incurable epidermoid carcinoma of the anus were treated by radiation therapy and chemotherapy consisting of 5 fluorouracil and Mitomycin C. The first patient succumbed during the course of her therapy. The second patient is alive and well without definite evidence of disease nearly 1 1/2 years after initiation of therapy. The third patient underwent abdominoperineal resection after radiation and chemotherapy; pathologic examination revealed no residual carcinoma and the patient is well nearly 1 year after surgery. A fourth patient with previously treated epidermoid carcinoma of the anus presented with biopsy-proven pulmonary metastasis and was placed on the chemotherapeutic regimen alone. Six weeks later his chest X-ray showed essentially complete disappearance of the metastatic nodules. This experience suggests that multimodality therapy may increase salvage in even locally far-advanced and metastatic epidermoid anal carcinoma.     

Squamous cell carcinoma of the anal canal and anal margin

Squamous cell carcinomas of the anal canal and margin are relatively uncommon neoplasms of the distal gastrointestinal tract and surrounding skin. The major risk factors for tumor development have been defined through various epidemiologic studies. Randomized, phase III trials have defined the standard of care for anal cancer tumors to be a combined modality approach of radiation therapy and chemotherapy. This nonsurgical, organ-sparing regimen results in good anal sphincter function in the majority of patients, and treatment efficacy is favorable when compared with historic surgical series. Anal margin tumors are staged and treated as skin cancers, with a more favorable prognosis.     

Epidermoid carcinoma of the anal canal

The charts of 67 patients treated for epidermoid carcinoma of the surgical anal canal were reviewed. The clinical presentation, type of surgical procedure performed, lymph node status of the pararectal and inguinal nodes, time of recurrence, site of recurrence, and median survival from the date of primary surgery and from the date of recurrence were determined. There were 55 patients (82%) who had a minimum of 5 years' follow-up since initial treatment. Optimal surgical treatment requires an abdominoperineal resection with wide dissection of the ischiorectal fossa and perineum in all patients, as well as an en bloc excision of the posterior vaginal wall in women. Although excision of the posterior vaginal wall improves the disease-free interval, median survival is not altered, compared with the group without vaginectomy. The predominant sites of local recurrence in men are the pelvis and perineum, and in women, the pelvis and posterior vaginal wall. The status of the pararectal lymph nodes from the operative specimen can give accurate information about the relative risk of recurrence. The presence of inguinal lymph node metastases represents a poor prognosis because of a close association with systemic metastases.     

Efficacy of radiation therapy alone for limited squamous cell carcinoma of the anal canal

From 1973-1986, thirty-five patients with limited squamous cell carcinoma of the anal canal underwent definitive radiation therapy only. There were twenty females and fifteen males with average ages of 65 and 53 years, respectively. Twelve of the fifteen males were admittedly homosexual. The primary lesions were less than 5 cm in maximum dimension and were confined to the anal canal. Two patients presented with regional adenopathy. Chemotherapy was not used in any case. Treatment plans were individualized but usually included whole pelvis and boost external beam irradiation. The average tumor dose was 6395 cGy (range 4525-7550 cGy). One interstitial Ir-192 implant was performed. Local control was 77% (27/35) following radiation therapy alone. Seven of the eight failures were salvaged surgically, five by abdominoperineal resection and two by local excision, for an overall rate of 97% (34/35). The 5-year actuarial disease-free survival is 92%. Only two patients have disseminated and/or died of neoplasm. Anal continence was retained in 80% (28/35). Early and late complication rates were acceptable.     

Hydronephrosis associated with colorectal carcinoma: treatment and outcome.

AIM: Obstruction of the upper urinary tract, hydronephrosis, is not uncommon in the context of primary or recurrent colorectal cancer (CRC). Its presence poses a therapeutic dilemma. This study focuses on the significance of hydronephrosis as a prognostic marker for CRC by analysing the resectability and survival rates of patients affected. PATIENTS AND METHODS: Retrospective data of 52 patients with hydronephrosis were analysed. Ten had primary CRC at different sites and 42 developed hydronephrosis 1-84 months following resection of a primary CRC. Twenty eight had unilateral and 24 bilateral hydronephrosis. RESULTS: In 10 patients with primary CRC and in 38 of those with a history of CRC, hydronephrosis was secondary to malignant obstruction. In four it was related to iatrogenic injury to the urinary tract. Complete surgical resection was possible in five patients (10%) with malignant obstruction. The remaining 90% underwent palliative or no surgical treatment due to diffuse metastasis or extensive local disease. No difference in survival was found between these two groups (6 vs 8 months) nor when comparing CEA levels, Duke's staging, or unilateral vs bilateral hydronephrosis. Patients with benign obstruction were treated by a ureteric stent, leading to resolution of hydronephrosis. All four are alive. CONCLUSIONS: Malignant hydronephrosis, secondary to primary or recurrent CRC, represents local manifestation of a disseminated disease with almost no probability of long-term survival and cure. It would seem that patients with such disease do not benefit from aggressive operations. Copyright Harcourt Publishers Limited.     

Radiation therapy for adjunctive treatment of adrenal cortical carcinoma.

Adrenocortical carcinoma is a rare disease which is primarily approached surgically. There have been few reports of the efficacy of radiation therapy and, for the most part, these have been anecdotal. This paper reports on the potential adjuvant role of radiation therapy after surgical excision of primary adrenal cortical carcinoma and also comments about the efficacy of palliative radiation therapy for metastases. We have identified eight patients treated for adrenal cortical carcinomas at Hahnemann University Hospital (HUH) from 1962 until the present and have also identified five patients with the same diagnosis at Philadelphia General Hospital (PGH) from 1962 until its close in 1975. These two groups are examined separately. In the PGH group, in which two patients were diagnosed at autopsy and only one patient was treated by radiation therapy, the median survival was between 0 and 1 month for Stage IV disease with the only patient surviving to 6 months being that patient receiving radiation therapy. In the HUH group, five of eight patients were treated adjunctively after diagnosis, one was not and two received palliative therapy. The median survival for treated Stage III patients was between 34 months and 7 years. The suggestion, based on a limited patient series, is that patients treated postoperatively to the tumor bed and nodal areas in Stage III disease may have improved survival over historic series and improved local control.     

Squamous cell carcinoma of the anal canal

PURPOSE: To report the results of primary radiotherapy for treatment of anal canal carcinoma from the University of Florida series and review issues related to treatment of this disease. METHODS AND MATERIALS: Forty-nine patients were treated with primary radiation therapy (RT) for cure. Patients had a minimum 2-year follow-up (median, 9.8 years). After 1990, patients with lesions of at least 3 cm also received chemotherapy with fluorouracil (1000 mg/m(2)) plus cisplatin (100 mg/m(2)) or mitomycin (10-15 mg/m(2)) if medically fit (n = 26). RT was delivered with a 4-field box technique to deliver 45 Gy in 25 fractions. The inguinal nodes were treated daily using electrons to supplement the dose in that region to a total dose of 45 Gy if clinically negative or about 60 Gy if involved. There were no planned breaks. A 10- to 15-Gy boost was delivered using interstitial iridium 192 implant (n = 32), en face (60)Co field (n = 5), or external-beam photon fields (n = 11). RESULTS: Local control rates at 5 years were 100% for T1N0, 92% for T2N0 or N1, 75% for T3N0, 67% for T4N0, 88% for T4N(pos) or T(any)N2-3, and 85% overall. With surgical salvage, ultimate local control rates were 100%, 100%, 81%, 100%, and 88%, respectively, with 92% overall. Cause-specific survival rates at 5 years were 100% for Stage I, 88% for Stage II, 100% for Stage IIIA, and 70% for Stage IIIB. Absolute survival rates at 5 years were 62%, 68%, 100%, and 70%. Sphincter preservation rates were 83%, 79%, 75%, and 100% by stage and 81% overall. There was an improvement in local control with the addition of chemotherapy in more advanced disease, but it was not significant. There was an increase in acute toxicity with the addition of chemotherapy (12% > or = Grade 4) but not long-term toxicity. Late toxicity requiring colostomy occurred in 6% of patients and consisted of soft tissue necrosis. CONCLUSIONS: The majority of patients with anal canal carcinoma can be treated with curative intent using a sphincter-sparing approach of radiation with or without chemotherapy even with advanced disease. With the addition of chemotherapy to radiation, there is an increased risk of acute toxicity and about 1-2% incidence of toxic death. Smaller tumors (T1 and early T2) probably do not require the addition of chemotherapy.