C. Marchal

Male breast cancer: Results of the treatments and prognostic factors in 397 cases

From 1960 to 1986, 397 cases of non-metastatic male breast cancer (MBC) treated in 14 French regional cancer centres were reviewed. The median age was 64 years (range 25-93). TNM classification (UICC, 1978) showed seven T0, 79 T1, 162 T2, 31 T3, 74 T4 and 44 unclassified tumours (Tx). Clinical positive lymph nodes were found in 31% of the patients. 24 patients received radiotherapy only, and 373 underwent surgery, 247 of these with postoperative irradiation. Adjuvant chemotherapy and hormonal therapy were used in 71 and 68 patients, respectively. There were 382 infiltrating carcinomas and 15 pure ductal carcinoma in situ. Lymph node involvement was found in 56% of infiltrating carcinoma. The oestrogen (ER) and progesterone (PgR) receptors were positive in 79% and 77%, respectively, of examined cases. Isolated local and regional recurrence were observed in 8.8% and 4.5% of cases, respectively and 40% of patients developed metastases. The crude survival rates by Kaplan-Meier method were 65% and 38% at 5 and 10 years, respectively, and the disease-specific survival rates (without death due to intercurrent disease or second cancer) was 74% at 5 years and 51% at 10 years. The disease-specific survival rate for pN- and pN+ groups were 77% and 39% at 10 years. The prognostic factors were clinical size (T) and histological axillary status (pN-/pN+). The relative risk of death for pN- was 1.0, 2.0 and 3.2 in the T0-T1, T2 and T3-T4 groups, respectively. For pN+, these relative risks increased 1.9, 3.9 and 6.0 in the same groups. The optimal treatment include modified radical mastectomy and irradiation for cases with risk factors of local relapse (nodal invasion, large tumour with cutaneous or muscular involvement). Locoregional failure had unfavourable prognosis. First-line adjuvant treatment seems to be tamoxifen, due to the very high rate of positive hormonal receptors and the old age of the patients, which contraindicate chemotherapy in many cases. The prognosis of patients with breast cancer is the same in male and female patients when disease-specific survival rate, tumour size and axillary involvement are compared.

Nine breast angiosarcomas after conservative treatment for breast carcinoma : a survey from French Comprehensive Cancer Centers

OBJECTIVES To conduct a survey of the angiosarcomas developing after breast conservation for carcinoma in the French Cancer Centers, to study the evolution of these cases in detail, and to review literature in an attempt to propose an optimal treatment scheme. MATERIAL AND METHODS Eleven of the 20 French Cancer Centers agreed to research and retrospectively analyze all angiosarcomas discovered in patients previously treated by conservative treatment. The majority of the patients were node negative, T1N0M0. The mean age of the patients at the time of primary breast cancer treatment was 62.5 years, and 69 years at the diagnosis of the angiosarcoma. RESULTS During the last two decades, nearly 20,000 patients have been treated conservatively in these 11 centers, and only 9 cases of angiosarcoma were found. The median latency period between the treatment of the breast carcinoma and the diagnosis of the breast angiosarcoma was approximately 74 months, with a range of 57-108 months. Mastectomy was performed as the main treatment of this angiosarcoma. All recurrences after mastectomy for the angiosarcoma appeared within 16 months after the mastectomy. A median time of recurrence was found to be 7.5 months, regardless of the treatment. The angiosarcomas appeared to be very aggressive, and chemotherapy, radiotherapy, and sometimes hyperthermia could only palliate the condition for a short time. After the diagnosis of angiosarcoma, the median survival was 15.5 months, showing a particularly poor prognosis. Only 1 patient of 9 is alive without progressive disease at 32 months after salvage mastectomy for the recurrence of the angiosarcoma. Precise data obtained from 11 centers show that, of 18115 breast carcinomas treated conservatively, only 9 breast angiosarcomas are reported, which represents a prevalence of 5 cases of angiosarcoma per 10,000, which is the same prevalence for primary breast angiosarcomas occurring in healthy breasts. CONCLUSION Angiosarcoma developing after breast conserving therapy for carcinoma is a rare event, and induction of it by treatment is controversial. However, early diagnosis is essential and it appears that radical mastectomy gives the highest chance of cure and the best long-term survival.

Spheroids in radiobiology and photodynamic therapy

Spheroids are tridimensional aggregates of tumor cells coming from one or several cell clones. This model, which mimics the micro-tumors structure and some of their properties, shows oxygen, pH and nutrient gradients inducing a necrotic area in the center of the spheroid. Analysis of spheroids, cultured under static or stirred conditions, can be performed on whole spheroids or dissociated spheroids. The spheroids sensitivity to ionizing radiation and photodynamic therapy can be altered by oxygen status, damage repair, intercellular commmunications and apoptosis induction, as in experimental tumor models. In radiobiology, the similarity of radiation response between spheroids and tumor xenograft bearing mice makes the spheroids to be a good alternative model to in vivo irradiation studies. In photodynamic therapy, spheroids lead to a better understanding of the own tumor response without interactions with vascular system. Finally, despite the quality of spheroid model, only the use of new technology for analysis of spheroid populations will help to increase their experimental use, particularly in preclinical oncology.

Ductal carcinoma in situ of the male breast. Analysis of 31 cases

From 1970 to 1992, 31 pure ductal carcinoma in situ (DCIS) of the male breast treated in 19 French Regional Cancer Centres were reviewed. They represent 5% of all breast cancers treated in men in the same period. The median age was 58 years, but 6 patients were younger than 40 years. TNM classification (UICC, 1978) showed 12 T0 (discovered only by bloody nipple discharge), 10 T1, 5 T2 and four unclassified tumours (Tx). 11 patients (35.5%) had clinical gynecomastia, and three (10%) had a family history of breast cancer. 6 patients underwent lumpectomy, and 25 mastectomy. Axillary dissection was performed in 19 cases. 6 cases received postoperative irradiation. 15 out of 31 lesions were of the papillary subtype, pure or associated with a cribriform component. The size of the 12 measured lesions varied from 3 to 45 mm. All lymph nodes sampled were negative. With a median follow-up of 83 months, 4 patients (13%) presented a local relapse (LR), respectively, at 12, 27, 36 and 55 months. 3 of these patients had been initially treated by lumpectomy. In one case LR was still in situ, but already infiltrating in the 3 others. Radical salvage surgery was performed in 3 cases, but one patient developed metastases and died 30 months later. The last patient was treated by multiple local excisions and tamoxifen. One 43-year-old patient developed a contralateral DCIS and three others developed a metachronous cancer. The aetiology and risk factors of male breast cancer remain unknown. Gynecomastia, which implies an imbalance between androgen and oestrogen, may be a predisposing factor. As in women, DCIS in the male breast has a good prognosis. Total mastectomy without axillary dissection is the basic treatment. Frequently, the first symptom is a bloody nipple discharge. The age of occurrence is younger than for infiltrating carcinoma, suggesting that DCIS is the first step in the development of breast cancer.

Role of interstitial brachytherapy in oral and oropharyngeal carcinoma: reflection of a series of 1344 patients treated at the time of initial presentation.

Our study focuses on a series of 1344 cases of carcinoma of the oral cavity and oropharynx treated between 1973 and 1992. Brachytherapy was always performed with iridium 192, either alone or in combination with external-beam irradiation or with surgery for the treatment of the primary tumor. For the oral cavity, we studied 565 cases of mobile tongue. The local control and overall survival rates, respectively, at 5 years are as follows: for T1, 92% and 70%; for T2, 62% and 42%; and for T3, 50% and 29%. For the subgroup T1T2NO, there was a better prognosis for treatment by brachytherapy of the primary lesion alone (p < 0.0001). Two hundred seven cases of floor-of-mouth carcinoma have been reported. The T3T4 patients were not considered surgical candidates. The local control and overall survival rates, respectively, at 5 years are as follows: for T1, 97% and 71%; for T2 72% and 42%; and for T3, 51% and 35%. Ninety-seven patients were treated by postoperative brachytherapy. These were patients for whom the margins after surgery were positive or narrow. A technique termed the modified bridge is described for lesions located in the mandible. Carcinomas of the buccal mucosa are rare in our country; only 42 cases were treated in this comparison of two techniques, and the overall survival rate was 48%. Epidermoid carcinomas of the oropharynx have nearly always been treated by a combination of external-beam irradiation and brachytherapy because of the bilateral node risk. Seventy-two patients with epidermoid cancers of the base of the tongue had an overall survival rate of 44%. The tonsil, soft palate, and pillars benefited from the use of the loop technique of brachytherapy combined with external-beam irradiation. Three hundred sixty-one patients were treated. Among these patients were two groups with different prognoses. Patients with tonsil, soft palate, and posterior pillar carcinomas had a local control rate of 84% and an overall survival rate of 57%. Conversely, the anterior pillar and the pharyngoglossal sulcus have a local control rate of only 65% and an overall survival rate of 38%. Statistical analysis revealed the prognostic factors for local control. The complications were classified into four grades: minor (20%), moderate (9%), major (4%), or inducing death (0.2%). The bone complications of grade 2 or 3 are more frequent for the floor of the mouth than for other locations.

Complications following definitive irradiation for cancers of the oral cavity and the oropharynx (in a series of 1134 patients)

PURPOSE To study the rate and severity of complications in a series of 1134 patients treated by definitive irradiation for tumors of the oral cavity (772 cases) or the oropharynx (361 cases). METHODS AND MATERIALS Patients were staged as 29.5% T1, 42% T2, 26% T3, 2.5% T4-Tx, and 74.5% N0 tumors. We treated 364 patients with brachytherapy only (192Ir) for the primary lesion. External irradiation and brachytherapy were combined for 770 patients. RESULTS The results included local control and survival. Out of 1134 patients, 330 had 376 complications. Grade 1 complications occurred in 20% of the patients, Grade 2 in 9%; Grade 3 in 4%; and Grade 4 in 0.2%. Of the Grade 1 complications, 78% were soft tissue and only 24% were bone complications. For the more severe grades (2, 3, and 4), there were 56 soft tissue complications and 90 bone complications out of 1340 patients. The statistical analysis included tumor-related factors and treatment-related factors. For the first two factors, only tumor location was significant. The treatment-related factors significant for complications were studied in univariate and multivariate study. This multivariate study confirmed that for soft tissue complications dose rate and volume treated were important (p < 0.001). It also confirmed that for bone complications, total dose > 80 Gy, dose rate > 0.7 Gy/h, and the absence of leaded protection of the mandible were all important factors. CONCLUSION This statistical study should allow future reduction of severe complications (Grades 2, 3, 4), if treatment factors inducing them can be taken into account. This is not always possible for very large tumors.

Phase III Trial of Protracted Compared With Split-Course Chemoradiation for Esophageal Carcinoma: Fédération Francophone de Cancérologie Digestive 9102

PURPOSE Chemoradiotherapy (CRT) is an alternative to surgery for resectable locally advanced esophageal carcinoma (RLA-EC). We investigated the heterogeneity of the treatment benefits across subgroups of patients, defined according to the radiation scheme. PATIENTS AND METHODS Between February 1993 and December 2000, 451 patients were enrolled. The following two schemes were allowed: protracted radiotherapy (P-RT), which scheduled 46 Gy over 4.5 weeks or split-course radiotherapy (SC-RT) with two 1-week courses of 15 Gy. Two courses of cisplatin and fluorouracil were delivered concomitantly. In case of exclusive CRT, a further course of 20 Gy over 2 weeks in the P-RT group and one 1-week course of 15 Gy in the SC-RT group were delivered with three courses of chemotherapy. SC-RT and P-RT were administered to 285 patients (64%) and 161 patients (36%), respectively. RESULTS For P-RT versus SC-RT, the response rate to induction CRT was 67% v 68%, respectively (P = .09), and 2-year local relapse-free survival rate was 76.7% v 56.8%, respectively (P = .002). Shorter tumor length and P-RT were associated with better local control in multivariate analysis (P = .002 for both). After a median follow-up time of 47.4 months, 2-year overall survival rate was 37.1% for P-RT compared with 30.5% for SC-RT (P = .25). Independent prognostic factors on survival were tumor diameter (P = .02), weight loss of 10% or less (P = .05), and response to induction CRT (P = .002). CONCLUSION Patients with RLA-EC treated with P-RT had better local control than patients treated with SC-RT. Response to induction CRT is a determinant prognostic factor on survival.

Treatment duration as a prognostic factor for local control and survival in epidermoid carcinomas of the tonsillar region treated by combined external beam irradiation and brachytherapy

PURPOSE We wanted to study the influence of the time factor in a combination of external irradiation and brachytherapy from a retrospective study of 370 squamous cell carcinomas of soft palate and tonsil. PATIENTS AND METHODS From 1977 to 1993, 370 soft palate and tonsillar carcinomas were treated at the Centre Alexis Vautrin. All patients received external irradiation (ERT) with a minimum dose to the tumour of 45 Gy, followed by low dose rate brachytherapy by Iridium 192 using the technique of plastic tubes; 22 patients received neo-adjuvant chemotherapy. We treated 85 T1, 159 T2, 117 T3 and nine T4 or TX carcinomas; 128 of these had palpable nodes. There were 267 men and 24 women. The median age was 55 years (range 33-81 years). RESULTS The median duration of the total treatment was 57 days. The rate of local control was 88% at 5 years when the treatment time was 7 weeks and 74% when it was 9 weeks (P = 0.001). The rates of overall survival at 5 years were 63 and 44%, respectively (P < 0.0001). For the interval between external irradiation and brachytherapy the series was divided into three groups, i.e. patients treated with a delay inferior or equal to 16 days (2 weeks), patients for which the interval was between 16 and 20 days and patients treated with a delay greater than 20 days (3 weeks). The rates of local control and overall survival at 5 years were not significantly different in the two first groups so we amalgamated these two groups and compared them with the third group. In this way the time cut-off for the delay between external irradiation and brachytherapy was 20 days. At 5 years, the rate of local control was 85% for the group for which the interval was inferior to 3 weeks and 73% when the delay was greater (P = 0.01). The rates of overall survival at 5 years were 59 and 38%, respectively (P < 0.001). Multivariate analysis confirmed that protraction of treatment was a factor for poorer local control. This factor was independent of the other prognostic factors. CONCLUSION The total duration of irradiation and the delay between external irradiation and brachytherapy were significant prognostic factors for local control and overall survival of soft palate and tonsil carcinomas. The overall duration should not be greater than 7 weeks (external irradiation, 5 weeks plus a delay of 12-15 days between ERT and brachytherapy). The delay should never be greater than 20 days, but a boost should be considered to make up for the loss of local control.

Conservative treatment by irradiation of epidermoid carcinomas of the anal margin

PURPOSE Few series have described treatment results of anal margin tumors as defined in the UICC 87 classification. The purpose of this article is to describe experience with an uncommon condition in a single cancer center. METHODS AND MATERIALS From 1971 to 1995, 32 patients with carcinoma of the anal margin were irradiated with a curative intent, and 31 were followed-up for more than 6 months (mean = 4.5 years). There were 9 T1, 15 T2, 7 T3, and 1 T4 (vulvar), with 26 N0 and 6 N1. There was a minor invasion of the lower canal in 17 patients. The histological types were 24 squamous cell and 7 basocellular carcinomas, and 1 Pagets disease. The treatment was a combined External Beam Irradiation (EBI) and Brachytherapy (BT) in 16 patients, an exclusive BT in 12 patients, and an exclusive EBI in 4 patients. No prophylactic inguinal irradiation was delivered. RESULTS The 5-year actuarial results are as follows: overall survival = 67%, specific survival = 89%. The only prognostic factor was nodal involvement (p < 0.001). T-stage, T-size, age, sex, and treatment schedule were not significant. The overall local control was 77%, and 93.5% after salvage. Two N0 patients relapsed in inguinal areas (one was salvaged). Twenty-six percent presented a Grade 3 or 4 late complication, necessitating a temporary colostomy in only one patient. The sphincter conservation reached 84% for the whole series, 80% for patients followed-up 5 years or more, and 89% for cured patients. CONCLUSION Results are similar to other series, and seem better than for anal canal cancer. We recommend exclusive irradiation. There is no data recommending concomitant chemotherapy. Depending on the tumor size and localization, the tumor boost can be applied by EBI or BT. Surgery is reserved for small tumors far from the canal or for salvage. An inguinal prophylactic bilateral irradiation should be recommended for N0, with tumors over 4 cm.

Indications, techniques and results of postoperative brachytherapy in cancer of the oral cavity

Abstract Purpose/objective : We tried to reduce the number of local recurrences after surgery and external beam irradiation (EBI) in carcinoma of the oral cavity, when margins were positive or close. Material and methods : From 1980 to 1992, we treated 97 cases of carcinomas of the oral cavity by postoperative brachytherapy. Surgery was combined with EBI + brachytherapy in 51 cases and with brachytherapy alone in 46 cases. We treated 29 T1, 34 T2, 30 T3T4 and four Tx (73% were N0 at first examination and 23% had positive nodes). The type of surgery is analysed. Brachytherapy was performed in one or two planes along the surgical scar. If the mandibular rim was resected, especially when the tongue or the remaining floor were sutured to the internal face of the inferior lip or to the buccal mucosa, the bridge technique was used. To decrease the dose to the inferior part of the mandible, the bridge was modified thanks to experimental dosimetry. Results : At 5 years, the local control (LC) is 89%, the locoregional control (LRC) 82%, the specific survival (SS) 74% and the overall survival (OS) 67%. Complications : We noted 19% of grade 1 (minor), 12% of grade 2 (moderate) and 6% of grade 3 (major) complications. Conclusion : Compared with the results of the literature, we think that postoperative brachytherapy can improve classical radiosurgical results in selected cases with a risk of local recurrence.