C. Berger

Preoperative radiotherapy (RT) for rectal cancer: Predictive factors of tumor downstaging and residual tumor cell density (RTCD): Prognostic implications

PURPOSE To determine predictive factors and prognostic value of tumor downstaging and tumor sterilization after preoperative RT for rectal cancer. METHODS AND MATERIALS Between 1977 and 1994, 167 patients with a histologically proven adenocarcinoma (70 T2, 65 T3, 29 T4, and 3 local recurrences) underwent preoperative RT. Median dose was 44 Gy (5-73 Gy). Surgery was performed in a mean time of 5 weeks after RT. Pathologic specimens have been reviewed by the same pathologist in order to specify the modified Astler Coller classification (MAC), and to quantify the residual tumor cell density (RTCD). RESULTS According to the MAC, there was 9 stage 0 (5%), 10 stage A (6%), 103 stage B1-B3 (62%), and 45 stage C1-C3 (27%) tumors. Seventeen percent and 56% of the patients who received a dose > or = 44 Gy had respectively a 0-A and a B tumor, compared to 4 and 69% in those who received a dose < 44 Gy (p = 0.04). Tumor differentiation and a longer interval before surgery were significantly associated with a more frequent downstaging, and preoperative staging correlated well to the postoperative pathological findings. According to the RTCD, 62 tumors (37%) showed no or only rare foci of residual tumor cells (Group 1); 62 (37%) showed an intermediate RTCD (Group 2); and 43 (26%) a high RTCD (Group 3). No predictive factor of RTCD was statistically significant. In univariate analysis, postoperative staging was a significant prognostic factor, with corresponding 5-year overall survival rates in 0-A, B, and C stages of 92, 67, and 26% (p < 0.01). RTCD was not a prognostic factor. However, overall and disease-free survival rates for patients with complete pathologic response of 83% at 2 and 5 years suggested a better outcome in this subgroup of patients. CONCLUSION The favorable influence of higher doses of preoperative RT on pathologic stage has been observed. Tumor differentiation, preoperative classification and time before surgery were the other predictive factors of tumor downstaging. However, there was no predictive factor of complete pathologic response. Even after preoperative RT, postoperative staging remained a prognostic factor.

Conservative treatment feasibility with induction chemotherapy, surgery, and radiotherapy for patients with breast carcinoma larger than 3 cm

Background. The traditional surgical treatment for operable breast carcinoma larger than 3 cm is mastectomy. To avoid mutilating surgery, the authors administered primary chemotherapy to 158 patients with operable nonmetastatic large breast carcinoma with a TNM classification of T2 greater than 3 cm and T3 with a lymph node status of NO‐N1. Conservative treatment was proposed for patients responding to the chemotherapy and whose tumor was reduced to 3 cm or less. The purpose of the study was to evaluate the feasibility and treatment results of this strategy.

Management of primary anal canal adenocarcinoma: A large retrospective study from the Rare Cancer Network

PURPOSE Primary adenocarcinoma of the anus is a rare tumor. The current standard treatment consists of abdominoperineal resection (APR). The aim of this Rare Cancer Network study was to evaluate the prognostic factors and outcome after the three most commonly used treatment approaches. METHODS AND MATERIALS This multicenter study collected data from 82 patients: 15 with T1 (18%), 34 with T2 (42%), 22 with T3 (27%), and 11 with T4 (13%) tumors according to the TNM classification (International Union Against Cancer, 1997). Patients were separated into, and analyzed according to, three treatment categories: radiotherapy/surgery (RT/S group, n = 45), combined radiochemotherapy (RT/CHT group, n = 31), and APR alone (APR group, n = 6). The main patient characteristics were evenly distributed among the three groups. RESULTS The actuarial locoregional relapse rate at 5 years was 37%, 36%, and 20%, respectively, in the RT/S, RT/CHT, and APR groups (RT/S vs. RT/CHT, p = 0.93; RT/CH vs. APR, p = 0.78). The 3-, 5-, and 10-year overall survival rate was 47%, 29%, and 23% in the RT/S group, 75%, 58%, and 39% in the RT/CHT group, and 42%, 21%, and 21% in the APR group (RT/CHT vs. RT/S, p = 0.027), respectively. The 5- and 10-year disease-free survival rate was 25% and 18% in the RT/S group, 54% and 20% in the RT/CHT group, and 22% and 22% in the APR group (RT/CHT vs. RT/S, p = 0.038), respectively. Multivariate analysis revealed four independent prognostic factors for survival: T stage, N stage, histologic grade, and treatment modality. CONCLUSION Primary adenocarcinoma of the anal canal requires rigorous management. Multivariate analysis showed that T and N stage, histologic grade, and treatment modality are independent prognostic factors for survival. We observed better survival rates after combined RT/CHT. We also recommend using APR only for salvage treatment.

Enhanced acute toxicity in oropharynx carcinoma treated with radiotherapy and concomitant cisplatin, 5-fluorouracil and mitomycin C.

The aim of this study was to establish the feasibility of giving concomitant radiotherapy and 3 cycles of chemotherapy with cisplatin (CDDP), 5-fluorouracil (5-FU) and mitomycin C (MMC) in locally advanced inoperable oropharyngeal cancer. From March 1990 to September 1993, 27 male patients (mean age 55 years) were included in this study. 3 patients (11%) were T2N0, 19 (70%) T3 (T3N0: n = 9, T3N1: n = 1, T3N2: n = 5, T3N3: n = 4), and 5 (19%) T4 (T4N0: n = 1, T4N1: n = 1, T4N2: n = 2, T4N3: n = 1). All patients received conventional radiotherapy delivering 70 Gy in 35 fractions and 52 days, and three cycles of chemotherapy starting on day 1, 21 and 42 with CDDP 20 mg/m2 and 5-FU 400 mg/m2 day 1 to day 4, and MMC 10 mg/m2 day 1. With a mean follow-up of 34 months (17-59), 10 patients (37%) were alive and free of disease. Among the 17 other patients, 8 died of cancer. Crude locoregional control rate was 78%, and probability of local control at 1 and 2 years was 85 and 80%, respectively. One- and 2-year survival rates were 48 and 31%, respectively, for both overall and disease-free survival. Grade 3 or 4 mucositis occurred in 22 patients (81%); enteral feeding was necessary for 63%; mean weight loss was 5.7 kg. Grade > 2 thrombocytopenia occurred in 11 patients (41%), grade > 2 neutropenia in 8 patients (29%), grade > 2 anaemia in 4 patients (15%). Febrile neutropenia or aplasia occurred in 5 patients (19%). 2 patients (7%) died during treatment of haematological or infectious complications related to the treatment. Another patient died 1 month after treatment with grade 4 thrombocytopenia and septicaemia. In conclusion, a high complete response rate has been achieved with this concomitant chemo- and radiotherapy, but with severe digestive and haematological toxicity. Addition of MMC to 5-FU and CDDP might have been responsible for this increased toxicity. This therapeutic combination is therefore not routinely feasible.

Concomitant Chemoradiotherapy Using Carboplatin, Tegafur-Uracil and Leucovorin for Stage III and IV Head-and-Neck Cancer: Results of GORTEC Phase II Study

PURPOSE Concomitant chemoradiotherapy is the standard treatment of locally advanced, nonresectable, head-and-neck squamous cell carcinoma. However, the optimal chemotherapy regimen is still controversial. The objective of this Phase II study was to evaluate the feasibility and efficacy of a concomitant treatment using tegafur-uracil, leucovorin, carboplatin, and radiotherapy. METHODS AND MATERIALS A total of 77 patients with head-and-neck squamous cell carcinoma Stage III and IVA were enrolled between October 2003 and July 2005. Of the 77 patients, 72 were eligible. They were treated with tegafur-uracil (300 mg/m(2)/d) and leucovorin (75 mg/d) from Days 1 to 19 and from Days 29 to 47 and carboplatin (70 mg/m(2) intravenously for 4 consecutive days), in three cycles every 21 days. Conventional radiotherapy was delivered to a total dose of 70 Gy in 35 fractions. RESULTS With a mean follow-up of 22.8 months, the 3-year locoregional control, overall survival and disease-free survival actuarial rate was 33.1%, 41.9%, and 27.2%, respectively. The compliance of the treatment was correct. The main acute toxicity was mucositis, with 62% Grade 3-4. Three patients (4.2%) died of acute toxicity. The incidence and severity of late toxicity was acceptable, with 32% Grade 3 and no Grade 4 toxicity. CONCLUSION The protocol of concomitant chemoradiotherapy using tegafur-uracil, leucovorin, and carboplatin for locally advanced unresectable head-and-neck squamous cell carcinoma is feasible. The compliance was correct. The incidence and severity of the acute and late toxicities were acceptable, but not improved. The efficacy of this regimen seems equivalent to the main protocols of concurrent chemoradiotherapy. It represents a possible alternative for patients without an intravenous catheter.

Abdomino pelvic irradiation after second-look laparotomy for stage III ovarian carcinoma

OBJECTIVE The purpose of this retrospective analysis of 34 patients with stage III ovarian carcinoma was to review results and morbidity of whole abdominal irradiation after surgery and chemotherapy. METHODS AND MATERIALS All of the 34 patients had reached a complete clinical remission after first cytoreductive surgery and chemotherapy. After second-look laparotomy each patient underwent whole abdominal irradiation. Except for two patients with chronic myelosuppression, the dose administered was of 22.5 Gy to the abdominal cavity with a boost of 22.5 Gy added to the pelvis. RESULTS Three and 5-year overall survival rates were 62% and 43%, respectively. Three and 5-year disease-free survival rates were 53% and 38%. Twenty-three patients (68%) developed local relapse or local disease progression. Metastasis occurred in five cases and were always associated with an abdominal cavity recurrence. Residual disease after first cytoreductive surgery appeared as a prognostic factor in univariate analysis. Patients with unresected residuum had a 5-year survival probability of 35% versus 83% for patients without residual disease. We observed 12% grade-3 intestinal toxicities and one fatal case of radiation enteritis. CONCLUSION Despite its curative potential, the long term benefit of whole abdominal irradiation in the multimodality treatment of advanced ovarian carcinoma must be evaluated in well designed controlled trials.

707 Prognostic value and predictive factors of tumor sterilization after preoperative radiotherapy for rectal cancer

Between 07/1977 and 10/1993, 147 patients (pts) received preoperative radiotherapy (RT) for rectal adenocarcinoma. There was 64 T2, 56 T3, 25 T4 tumors and 2 relapses after prior surgery. Median total dose of RT was 44 Gy (5–73 Gy), median fractionation 5 fractions (1–5) of 2 Gy (1.5–5 Gy) per week, and median duration of RT 5 weeks (1 day–9 weeks). Seventy-nine pts were treated with a 2-field technique, 66 pts with a 4-field technique and 2 pts with a direct perineal field. Median treated volume was 4.4 liters (1.2–9.4). One hundred and twenty pts were treated with X25 MV, the other 27 pts with 1.25 Mev 60 Co. All irradiated rectal tumors have been reanalyzed by the same pathologist in order to quantify tumor sterilization. Three groups were individualized according to the residual tumor cell density (RTCD): absence or low, intermediate and high. All pts underwent surgery in a median delay of 4 weeks. Fifty-five tumors (37%) showed no (9/147) or low (46/147) RTCD; 51 (35%) showed an intermediate RTCD and 39 (27%) a high RTCD. The distribution of the pts according to age, tumor stage, tumor location, delay before surgery and RT parameters (total dose, fractionation, duration of treatment, 2 or 4-field technique, treated volume, X25 MV or 1.25 Mev 60 Co photons) was not statistically different in the 3 groups. Five-year actuarial survival rates were 100% in the group of pts with no RTCD, 54% in the group with low RTCD, 44% in the group with intermediate RTCD and 53% in the group with high RTCO. The difference did not reach significance, probably because of the small number of sterilized tumors. These results suggest however that tumor sterilization is a favorable prognostic factor after preoperative RT in rectal cancer.