Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial.

BACKGROUND: Breast cancer becomes lethal when visceral metastases develop. At this stage, anti-cancer treatments aim at relieving symptoms and delaying death without resulting in additional toxicity. On the basis of their differential anti-oxidant defence level, tumour cells can be made more sensitive to chemotherapy than non-tumour cells when membrane lipids are enriched with docosahexaenoic acid (DHA), a peroxidisable and oxidative-stress-inducing lipid of marine origin. METHODS: This open-label single-arm phase II study evaluated the safety and efficacy (response rate), as primary end points, of the addition of 1.8 g DHA daily to an anthracycline-based chemotherapy (FEC) regimen in breast cancer patients (n = 25) with rapidly progressing visceral metastases. The secondary end points were time to progression (TTP) and overall survival (OS). RESULTS: The objective response rate was 44%. With a mean follow-up time of 31 months (range 2-96 months), the median TTP was 6 months. Median OS was 22 months and reached 34 months in the sub-population of patients (n = 12) with the highest plasma DHA incorporation. The most common grade 3 or 4 toxicity was neutropaenia (80%). CONCLUSION: DHA during chemotherapy was devoid of adverse side effects and can improve the outcome of chemotherapy when highly incorporated. DHA has a potential to specifically chemosensitise tumours.

[Concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conservative surgery enhances late toxicities]. / La chimiothérapie concomitante de la radiothérapie augmente la toxicité tardive après chirurgie conservatrice du cancer du sein.

PURPOSE: In 1996, a multicenter randomized study comparing after breast-conservative surgery, sequential vs concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) was initiated (ARCOSEIN study). Seven hundred sixteen patients were included in this trial. After a median follow-up of 6.7 (4.3-9) years, we decided to prospectively evaluate the late effects of these two strategies. PATIENTS AND METHODS: A total of 297 patients were asked to follow-up from the five larger including institutions. Seventy-two percent (214 patients) were eligible for late toxicity. After breast-conserving surgery with axillary dissection, patients were treated either with sequential treatment with CT first followed by RT (arm A) or CT administered concurrently with RT (arm B). In all patients, CT regimen combined mitoxantrone (12 mg/m(2)), 5-FU (500 mg/m(2)), and cyclophosphamide (500 mg/m(2)), 6 cycles (day 1-day 21). In arm B, patients received concurrently the first 3 cycles of CT with RT. In arm A, RT started 3 to 5 weeks after the 6th cycle of CT. Conventional RT was delivered to the whole breast using a 2 Gy-fraction protocol to a total dose of 50 Gy (+/-boost to the primary tumour bed). The assessment of toxicity was blinded to treatment and was graded by the radiation oncologist according to the LENT-SOMA scale. Skin pigmentation was also evaluated using a personal 5-points scoring system (excellent, good, moderate, poor, very poor). RESULTS: Among the 214 evaluated patients, 107 were treated in each arm. The two populations were homogeneous for patients', tumors' and treatment characteristics. Subcutaneous fibrosis (SF), telengectasia (T), skin pigmentation (SP), and breast atrophy (BA) were significantly increased in arm B. Twenty patients experienced grade superior or equal to 2 (SF) in arm B vs five in arm A (P=0.003). Twenty-five and seven patients showed grade superior or equal to 2 (T) in arm B and A, respectively (P=0.001). Forty-four and twenty patients showed grade superior or equal to 2 (BA) in arm B and A, respectively (P=0.0006). Thirty patients experienced grade superior or equal to 3 (SP) in arm B vs fifteen in arm A (P=0.02). No statistical difference was observed between the two arms concerning grade superior or equal to 2 pain, breast oedema, and lymphoedema. No deaths were caused by late toxicity. CONCLUSION: Following breast conserving surgery, the concurrent use of CT with RT is significantly associated with an increase incidence of grade 2 or greater late side effects.

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.

Low alpha-linolenic acid content of adipose breast tissue is associated with an increased risk of breast cancer.

Data derived from experimental studies suggest that alpha-linolenic acid may have a protective effect in breast cancer. Observations obtained from epidemiological studies have not allowed conclusions to be drawn about a potential protective effect of dietary alpha-linolenic acid on breast cancer, possibly because of methodological issues. This case-control study conducted in an homogeneous population from a central area in France was designed to explore the hypothesis that alpha-linolenic acid inhibits breast cancer, using fatty acid levels in adipose breast tissue as a biomarker of past qualitative dietary intake of fatty acids. Biopsies of adipose breast tissue at the time of diagnosis were obtained from 123 women with invasive non-metastatic breast carcinoma. 59 women with benign breast disease served as controls. Individual fatty acids were analysed by capillary gas chromatography. An unconditional logistic regression model was used to obtain odds ratio estimates whilst adjusting for age, menopausal status and body mass index (BMI). No association was found between fatty acids (saturates, monounsaturates, long-chain polyunsaturates n-6 or n-3) and the disease, except for alpha-linolenic acid which showed an inverse association with the risk of breast cancer. The relative risk of breast cancer for women in the highest quartile of adipose breast tissue alpha-linolenic acid level was 0.36 (95% confidence interval=0.12-1.02) compared with those in the lowest quartile (P trend=0.026), suggesting a protective effect of alpha-linolenic acid in the risk of breast cancer. The effects of dietary alpha-linolenic on the risk of breast cancer warrant further study.

Radical hysterectomy for stage I and II endometrial carcinoma: a retrospective analysis of 179 cases.

Total hysterectomy with bilateral salpingo oophorectomy is the traditional treatment for endometrial carcinoma. In an effort to improve local control rates, we have surgically treated our Stage I and II patients with radical hysterectomy and pelvic lymphadenectomy (RH-PL). Between 1976 and 1987 we have treated 179 patients with endometrial adenocarcinoma (125 Stage I and 54 Stage II) with the following modalities. Uterovaginal brachytherapy (60 Gy) was performed first and then 6 weeks later an RH-PL was performed. Twenty-nine patients received external pelvic irradiation (45 Gy) because of tumor invasion beyond the internal two-thirds of the myometrium and/or lymph node involvement. The local control rate was 87% (92% for Stage I, 76% for Stage II). Distant metastases occurred in 24 patients (13%). Five-year actuarial survival rates were 80% for Stage I and 61% for Stage II patients. Prognostic factors were nodal status, histological grading, depth of tumor myometrial invasion, histologic status of the hysterectomy specimen, and peritoneal cytology. Late severe complications occurred for 13 patients (7%). These results are comparable to those published for patients treated with less extensive surgery. We conclude that such an extensive surgery (especially pelvic lymphadenectomy) appears to be useless for all patients with bad prognostic factors requiring pelvic external irradiation. We only still perform external iliac node samples for patients with Stage I grade 1 tumors without deep tumor invasion into the myometrium.

Carcinoma of the uterine cervix stage IB and early stage II. Prognostic value of the histological tumor regression after initial brachytherapy.

In our center limited centro pelvic invasive carcinomas of the uterine cervix (less than 4 cm) are treated with brachytherapy and surgery. With these therapeutic modalities no residual carcinoma was observed for 80% of the patients. The purpose of this study was to evaluate our results with this treatment, and to evaluate the prognostic value of the pathological status of the cervix. From 1976 to 1987 we have treated 115 patients with these modalities. Staging system used was the FIGO classification modified for Stage II (divided in early Stage II and late Stage II). Patients were Stage IB (70 cases) and early Stage II (45 cases); 60 Gy were delivered with utero vaginal brachytherapy before any treatment. Six weeks later a radical hysterectomy with pelvic lymphadenectomy was performed. Twenty-one patients with positive nodes received a pelvic radiotherapy (45 to 55 Gy). Local control rate was 97% (100% for Stage IB and 93% for early Stage II). Uncorrected 10-year actuarial survival rate was 96% for Stage IB and 80% for early Stage II patients. No treatment failure was observed for Stage IB patients. Ninety-two patients (80%) had no residual carcinoma in the cervix (group 1) and 23 patients (20%) had a residual tumor (group 2). The sterilization rate of the cervix was 87% for Stage IB tumors versus 69% for early Stage II, and was 82% for N- patients versus 68% for N+ patients. Ten year actuarial survival rate was 92% for group 1 and 78% for group 2 (p = 0, 1). Grade 3 complications rate was 6%. We conclude that brachytherapy + surgery is a safe treatment for limited centro pelvic carcinomas of the uterine cervix (especially Stage IB) and that pathological status of the cervix after brachytherapy is not a prognostic factor.

Prognostic significance of breast relapse after conservative treatment in node-negative early breast cancer.

The prognostic significance of local relapse after conservative treatment of early stage breast carcinoma has been controversial. To determine the incidence and the prognostic value of a breast relapse, we analyzed the results obtained in a series of patients with pT1pN0 presentation of breast carcinoma treated conservatively without adjuvant medical treatment. From 1976 to 1986, 202 patients with invasive breast carcinoma of less than 2 cm without lymph node involvement were treated with surgery and radiation therapy. The overall survival rate was 97.2% at 5 years. Locoregional relapses occurred in 16 patients (7.9%). In these patients, the overall survival rate was significantly decreased as compared to that of patients without local relapse (87.5% versus 98.3% at 5 years, p less than 0.001). The probability of remaining metastasis-free was also significantly decreased (80.2% vs 91.3%, p less than 0.001). Most relapses (94%) appeared at or close to the primary site. Salvage local treatment was possible in 14/16 patients (87.5%). Age, menopausal status, size and site of primary tumor, histological grade, and boost technique did not influence significantly the risk of local relapse occurrence. We concluded that the occurrence of a breast relapse after a successful local conservative treatment is a pejorative prognostic factor predictive of a high risk of distant metastasis development. There is a need to individualize factors that could allow discrimination of patients with a high probability of local relapse and subsequent metastasis.

Preoperative or postoperative brachytherapy for patients with endometrial carcinoma stage I and II.

In endometrial carcinoma, vaginal vault brachytherapy is performed to improve the local control rate and to decrease vaginal recurrences. To assess the best chronology of this brachytherapy compared to surgery, we have retrospectively analyzed results of treatment of patients treated either with preoperative brachytherapy (60 Gy) and then radical hysterectomy with bilateral salpingo oophorectomy (RH-BSO) (Group 1), or with RH-BSO and then postoperative brachytherapy (60 Gy) (Group 2). There were one hundred twenty-one patients in Group 1 and 63 in Group 2. The mean age was 61.8 years in Group 1 and 64.3 in Group 2. In Group 1, 73% of the patients were Stage I, and 77.6% were in Group 2. The two groups were comparable for histological grading and depth of tumoral invasion into the myometrium. Brachytherapy was delivered with one uterine and two vaginal sources in Group 1 and with three vaginal sources in Group 2. Doses to the reference volume and to reference points were calculated according to ICRU recommendations. Brachytherapy data were similar in the two groups except reference volume, which was smaller in Group 2. Local control rate was 87% in Group 1 and 91% in Group 2. Distant metastasis occurred in 12% of patients in Group 1 and 9% in Group 2. The 5-year actuarial survival rate was 84% in Group 1 and 89% in Group 2. Regarding stage, histological grading, and depth of tumoral invasion, no differences were observed between the two therapeutic groups. The only prognostic factor in the entire population was Stage. The 5-year actuarial survival rate was 91% for Stage I patients and 69% for Stage II (p value less than 0.03). The late severe complication rate was 14% in Group 1 and 7.9% in Group 2, a difference which was not statistically significant. We concluded that since no differences were observed between the two techniques, vaginal brachytherapy should be performed postoperatively when surgery is the first treatment (Stage I or II, grade 1 or 2, and no deep tumoral invasion into the myometrium).

Initial chemotherapy and low-dose radiation in limited fields in childhood Hodgkin's disease: results of a joint cooperative study by the French Society of Pediatric Oncology (SFOP) and Hôpital Saint-Louis, Paris.

To minimize the drawbacks of treatment we had shown in a previous study that it was possible after chemotherapy to limit the radiation fields to the involved areas only. Pursuing our policy of deescalation, we started in January 1982 a study in 29 French pediatric and hematologic centers, with two aims: (1) To compare the efficacy of 4 cycles of two different chemotherapeutic regimens (4 ABVD vs 2 MOPP + ABVD) in early stages (CSIA and II A) while other stages would receive 6 cycles of the same regimen (3 MOPP + 3 ABVD); (2) To evaluate the efficacy of irradiation given at a low dose (20 Gy) in the patients who had a minimum 70% reduction of the size of their nodes (good responders). From January 1982 to March 1987, 174 patients were entered in this study, of whom 157 completed their treatment program at the time of analysis. On completion of chemotherapy, 94% were considered as good responders and were irradiated to 20 Gy. Only 6 patients received a mediastinal boost (up to 40 Gy). Of the 6% (10/157) poor responders a complete remission was obtained in 6 after 40 Gy. Among the good responders, 5 patients relapsed, with only 3 within an area irradiated to 20 Gy. So that 4 nodal relapses occurred among 364 involved lymph areas. The actuarial survival at 42 months (median 30 months) is 95% (IA + IIA = 100%, IB + IIB + III = 94% and IV = 80%) and the disease-free survival 88% (respectively 94, 93 and 54). Until now there is no statistically significant difference between the 2 randomized arms. This study shows that it is possible to achieve a durable remission in most children treated with a less toxic protocol eliminating or reducing Nitrogen Mustard and reducing the dose of irradiation. Less late complications and sequelae are expected with a longer follow-up.

Radiotherapy with high dose rate brachytherapy boost and concomitant chemotherapy for Stages IIB and III esophageal carcinoma: results of a pilot study.

PURPOSE: Radiotherapy (RT) and concomitant chemotherapy (CT) is the standard treatment for non resectable esophageal cancer. Usual total radiation dose is 50 Gy. In order to enhance local control rate a Phase II study was initiated to evaluate the feasibility of a combined treatment with an external radiation dose of 60 Gy and three cycles of concomitant CT, using the three main active drugs (CDDP, 5 FU and MMC), followed by a high dose rate (HDR) brachytherapy delivering 10 Gy. METHODS AND MATERIALS: Fifty-three patients, 48 men and 5 women, were entered in this study. Stages were evaluated with CT scan and with endoscopic sonography. Fifteen were Stage IIB, 38 Stage III. Treatment consisted of conventional fractionated RT to a total dose of 60 Gy delivered with 2 Gy per fraction, one fraction per day and five fractions per week. The CT regimen was a combination of Cisplatinum (CDDP) 20 mg/m2 and 5 Fluorouracil (5FU) 600 mg/m2 continuous infusion, from days 1-4 Mitomycin C (MMC) was given at 6 mg/m2 on day 1. Three cycles were administered on days 1, 22, and 43. Brachytherapy was delivered one week after the end of external radiation therapy. RESULTS: Full radiation therapy dose was delivered for 94% of the patients. CT compliance, evaluated on the mean relative dose-intensity was 85% for CDDP, 81% for 5FU and 51% for MMC. Overall grade 3 and 4 WHO toxicity rates were 23% and 7%, respectively. Haematologic toxicity was the most limiting factor. One patient died from treatment toxicity. Local control rate at one year was 74%. Three-year actuarial survival rate was 27%. Distant metastasis was the main cause of treatment failure. Swallowing score was good for 75% of the patients. Stage, performance status and weight loss were prognostic factors. CONCLUSION: This regimen with high dose RT, HDR brachytherapy and concomitant CT is feasible; however, a high level of haematologic toxicity was observed with the CDDP, 5FU and MMC regimen. Despite a poor compliance with CT, treatment results are very encouraging for patients with locally advanced disease.

Therapeutic effectiveness of iodine-131 MIBG metastases of a nonsecreting paraganglioma.

This case report describes the treatment of the bone metastases of a nonfunctioning sympathetic paraganglioma, with [131I]MIBG. After primary tumor excision and unsuccessful external radiotherapy, the patient received three therapeutic doses of [131I]MIBG, resulting in a reduction of the number and volume of metastases, and an improvement of the general condition. At 3 yr following [131I]MIBG therapy, the patient remained in remission. [131I]MIBG appears to be an efficient and safe agent for treating malignant sympathetic paraganglioma.

Feasibility study of an alternating schedule of radiotherapy and chemotherapy in advanced uterine cervical carcinoma.

From July 1981 to April 1982, 36 patients with advanced cervical carcinoma stage III (24 patients) and stage IV (12 patients) entered a feasibility study of a radiotherapy and chemotherapy combination. The first three chemotherapy courses consisted of cis-platinum alone (50 mg/m2) and were interdigitated with radiotherapy. Six more courses composed of an association of cis-platinum (50 mg/m2) and cyclophosphamide (400 mg/m2) were given after the completion of radiotherapy. Radiotherapy was delivered in two courses of 25 Gy separated by a gap of 2 weeks. The overall 4-year survival rate was 35% (95% CI: 22%). The 4-year survival rate, cumulative loco-regional failure rate, and cumulative metastasis rate were respectively 44% (95% CI: 20%), 56% (95% CI: 21%), and 30% (95% CI: 21%) in stage III and 28% (95% CI: 27%), 83% (95% CI: 21%) and 74% (95% CI: 30%) in stage IV. The incidence of immediate and late complications was low: no patient had her radiotherapy stopped because of an intolerance and two patients had their chemotherapy stopped because of an haematological intolerance. Only one patient presented a severe late clinical complication (small bowel injury).

Disappearance of the in situ component: a criterion predictive of metastasis in breast cancer after local relapse.

Local recurrence after conservative treatment of breast cancer is associated with a significant risk for metastasis. In order to identify criteria predictive of metastasis in this subset of women, we analyzed a series of 35 patients with local relapse among 512 consecutive patients treated with tumorectomy and radiotherapy. When relapse occurred within 2 years of initial treatment, overall 2-year survival from the time of local relapse was 39.5%. When local relapse occurred more than 2 years from initial therapy, 2-year survival was 80.5% (p < 0.001). Pathological slides of both initial and recurrent tumors were reviewed and compared. In 17 patients, local relapse and initial tumor had the same morphological features, with an in-situ component either absent or present in the same proportion. Metastasis occurred in two of these patients. In contrast, 9 of 12 patients in whom the proportion of non-invasive carcinoma had decreased at the time of local recurrence developed metastasis. Overall 2-year survival from the time of relapse was significantly better in the former group of patients (93.3% versus 52.5%, p < 0.05). We concluded that early relapses have a poor prognostic significance and that disappearance of the in-situ component or increase of the invasive component at the time of relapse is a feature predictive of tumor-related death and that more intensive therapy might benefit to this subset of women.

Squamous cell carcinoma of the base of the tongue: results of treatment in 115 cases.

Between 1976 and 1986, we treated 115 patients (mean age 53.8 years) with base of tongue carcinomas. The staging system used was the UICC TNM classification of 1979. Seventy per cent of the tumours were T3 or T4 and 42% had N2 or N3 lymph node. Locoregional treatment was irradiation alone (98/115) or surgery and post-operative radiotherapy (17/115). Sixty-seven patients received induction chemotherapy. Actuarial survival of the entire group at 3 and 5 years was 25 and 23%, respectively, and 3-year actuarial survival rates for T1, T2, T3 and T4 lesions were 42, 48, 20 and 17%, respectively. The local control rate at the primary site was 55% and 78% in the neck. Distant metastases occurred in 10% of patients and 8% had a second primary. Nodal status was the only other prognostic factor. The local control rate obtained with irradiation alone was not good. For limited T1 and T2 tumours, interstitial therapy or surgery should improve the local control rate.

Oropharynx carcinoma: irradiation alone versus induction chemotherapy plus irradiation--5 year results.

Induction chemotherapy (CT) has demonstrated overall response rates of 80% for oropharynx carcinomas, but no overall survival benefit has been reported. In order to determine the value of induction CT for such patients, we conducted a retrospective study: 121 patients were treated with CT and radiotherapy (RT) (Group 1). This group was compared with a historical group of 84 patients treated by RT alone (Group 2). The CT used was Cisplatinum associated with Bleomycin and Vincristin or Vindesin and with 5 Fluoro-uracil. An objective response to CT was observed for 41% of patients. The 5 year actuarial survival rate was 19% for Group 1 and 24% for Group 2. Patterns of failure were identical in the two groups. The only difference observed was for patients with N3 nodes (26% of 5 year survival rate in Group 1 versus 9% in Group 2) (p = 0.05). The results did not depend on the histological differentiation, the tumour site or the type of CT. We conclude that this retrospective study failed to demonstrate an advantage for induction CT in oropharynx carcinoma except for patients with N3 nodes.

Lymphadenectomy in the management of endometrial carcinoma stage I and II. Retrospective study of 155 cases.

In our institution endometrial carcinomas Stage I and II were treated with initial uterovaginal brachytherapy 60 Gy followed by modified radical hysterectomy with pelvic lymphadenectomy. We have studied the results in order to assess the value of lymphadenectomy in the treatment strategy. Between 1976 and 1986, 155 patients were treated (107 Stage I, 48 Stage II mean age 60.2 years). Twenty-six patients also received postoperative pelvic external beam irradiation on account of lymph node involvement and/or deep tumour invasion into the myometrium. Fourteen patients (9%) had lymph node involvement. External iliac lymph nodes were involved in 78.5% of these cases. Lymph node involvement rate was higher for stage II, grade 3 tumours and when there was deep tumour invasion of the myometrium. The rate of local (pelvic) treatment failure was 12% for node-negative patients and 36% for node-positive patients and the 5-year actuarial survival rates for the two groups were 83% and 41% respectively. As a consequence of our interpretation of the findings and influenced by the high complication rate which we attribute to lymphadenectomy and the information given by other prognostic indicators, we have changed to a policy of carrying out pelvic external radiotherapy for all Stage II, grade 2 or 3 cases and those with deep myometrial invasion. Lymphadenectomy is not performed in these cases. For patients with Stage I grade 1 tumours without deep tumour invasion only external iliac node sampling is performed. If this shows tumour, external irradiation is given in addition to vaginal vault brachytherapy.

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.

[Advanced carcinoma of the oropharynx: the value of induction chemotherapy before locoregional treatment. A retrospective study of 138 cases]. / Carcinomes avancés de l'oropharynx: valeur d'une chimiothérapie d'induction précédant le traitement locorégional. Etude retrospective de 138 cas.

Induction chemotherapy in oropharynx carcinomas had demonstrated overall response rates of 80%, but no overall survival benefit have been reported. In order to determine the value of induction chemotherapy for these patients, we conducted a retrospective study: 86 patients were treated with chemotherapy (CT) and RT (group 1) and 52 patients were treated by radiotherapy (RT) alone (group 2). All patients had T3 or T4 tumors. CT used was cisplatinum based associated with bleomycin and vincristine or vindesine and actually with 5 fluoro-uracil. Objective response to the CT was observed for 34% patients. Five years actuarial survival rate was 18% for group 1 and 17% for group 2. Patterns of failure were identical in the 2 groups. A difference was observed only for patients with N3 nodes (24% 5 years survival rate in group 1 versus 6% in group 2) (P = 0.05). According to the histologic differentiation, the tumor site or the type of CT, no difference was observed. We concluded that this study failed to demonstrate an advantage for induction chemotherapy in advanced oropharynx carcinoma excepted for patients with N3 nodes.

[Carcinomas of the base of tongue: analysis of treatment results in 115 patients]. / Carcinomes de la base de la langue: analyse des résultats du traitement de 115 patients.

Between 1976 and 1986, we have treated 115 patients with base of the tongue carcinomas. The mean age was 53.8 years. Staging system used was the UICC TNM classification of 1979. 70% of the tumors were T3 or T4 and 42% had N2 or N3 lymph nodes. Loco-regional treatment was irradiation alone (98/115) or surgery and post-operative radiotherapy (17/115). 67 patients received an induction chemotherapy. 3 and 5 years actuarial survival was 25% and 23%, and 42, 48, 20 and 17% at 3 years for T1, T2, T3 and T4 lesions respectively. Local control rate at the primary sites was 55%, local control rate in the neck was 78%. Distant metastases occurred for 10% and 8% had a second primary. Nodal status was the only other prognostic factor. Local control rate obtained with irradiation alone was not good. For limited tumors T1 and T2, a better local control rate can be obtained with interstitial therapy or surgery.

[Carcinoma of the cervical stump. Retrospective analysis of 43 cases]. / Carcinomes sur col restant. Analyse retrospective de 43 cas.

Seven to eight percent of cervix carcinomas are carcinomas of the cervical stump. The prognosis for these tumors has sometimes been considered more unfavourable than that for carcinomas on intact uterus. From 1976 to 1986 we treated 43 patients with carcinoma of the cervical stump. The mean age was 63.6 years. Staging system used was FIGO classification modified according to the criteria of Institut Gustave Roussy in Villejuif. There were 12 stage IB, 12 early stage II, 5 late stage II and 14 stage III. Twenty-four centropelvic tumors (IB and early stage II) were treated with radiotherapy and surgery, 2 with surgery alone and one with radiotherapy alone. Late stage II and stage III tumors were treated with radiotherapy alone (+ hysterectomy for two patients). Local control rate was 83% for centropelvic tumors and 53% for late stage II and stage III. Seven patients developed distant metastases. Uncorrected 5-year actuarial survival rate was 78% for centro-pelvic tumors and 46% for late stage II and stage III. Three patients developed severe complications (grade 3). Prognostic factors were: stage, nodal status and pathological status of the cervix after radiotherapy. For the same stage the results were similar to those observed for carcinomas on intact uterus treated at our institution during the same time period.