Immunohistochemical subtypes predict the clinical outcome in high-risk node-negative breast cancer patients treated with adjuvant FEC regimen: results of a single-center retrospective study.

BACKGROUND: Anthracycline-based adjuvant chemotherapy improves survival in patients with high-risk node-negative breast cancer (BC). In this setting, prognostic factors predicting for treatment failure might help selecting among the different available cytotoxic combinations. METHODS: Between 1998 and 2008, 757 consecutive patients with node-negative BC treated in our institution with adjuvant FEC (5FU, epirubicin, cyclophosphamide) chemotherapy were identified. Data collection included demographic, clinico-pathological characteristics and treatment information. Molecular subtypes were derived from estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status and Scarff-Bloom-Richardson (SBR) grade. Disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) were estimated using the Kaplan-Meier Method, and prognostic factors were examined by multivariate Cox analysis. RESULTS: After a median follow-up of 70 months, the 5-year DFS, DDFS and OS were 90.6 % (95 % confidence interval (CI): 88.2-93.1), 92.8 % (95 % CI: 90.7-95) and 95.1 % (95 % CI, 93.3-96.9), respectively. In the multivariate analysis including classical clinico-pathological parameters, only grade 3 maintained a significant and independent adverse prognostic impact. In an alternative multivariate model where ER, PR and grade were replaced by molecular subtypes, only luminal B/HER2-negative and triple-negative subtypes were associated with reduced DFS and DDFS. CONCLUSIONS: Node-negative BC patients receiving adjuvant FEC regimen have a favorable outcome. Luminal B/HER2-negative and triple-negative subtypes identify patients with a higher risk of treatment failure, which might warrant more aggressive systemic treatment.

Management and clinical outcome of rectal cancer in patients ≥ 80 years treated in southern France (PACA region) between 2006 and 2008.

BACKGROUND: Rectal cancer is increasingly prevalent in the elderly patients. Their clinical history and outcome after treatment are poorly described. This retrospective study was undertaken to provide more data and to compare therapeutic strategies to the standard of care for younger patients. PATIENTS AND METHODS: Data were retrospectively provided by gastroenterologists, oncologists, and gerontologists of Provence-Alpes-Côte-d'Azur (PACA). Patients concerned were aged 80 years or older, with a rectal cancer diagnosed between 2006 and 2008, irrespective of stage and (the) treatment of the disease. Overall survival (OS) and relapse-free-survival (RFS) were correlated with patient characteristics and treatment. The adopted therapeutic strategy was then compared to the standard-of-care for younger patients. RESULTS: Median follow-up was 36 months. The 3-year OS was 47.4% for the 160 patients analyzed, and 59.2% for the 117 patients treated with curative intent. The 3-year RFS was 76.6% in the "curative" population. In the multivariate analysis, node status and surgery independently influenced OS, while RFS was influenced by age, N status, and gender. For T0-T2 tumors, patients were treated similar to younger patients with an OS of 83.6% and a RFS of 95.2%, respectively. For T3-T4 tumors, 3-year RFS was 65%, even with a less aggressive strategy. CONCLUSION: Surgical resection after evaluation using Comprehensive Geriatric Assessment (CGA) should be the standard treatment for localized rectal cancer (T0-T2) in elderly patients, as it is in younger patients. For locally advanced lesions (T3-T4), results obtained after a conservative approach suggest that a non-surgical strategy can be used in elderly patients.

Is neoadjuvant chemotherapy prior to radio-chemotherapy beneficial in T4 anal carcinoma?

BACKGROUND: This study retrospectively describes the outcome of a series of 38 patients (pts) with T4 anal carcinoma exclusively treated by radio and chemotherapy. PATIENTS AND METHODS: From 1992 to 2007, 38 pts with UST4-N0-2-M0 anal carcinoma were treated with exclusive radiotherapy and chemotherapy. All patients received external beam radiotherapy (EBRT) (median dose 45 Gy) with a concomitant chemotherapy (5-fluorouracil-cisplatin). Eleven patients received neo-adjuvant chemotherapy (5-fluorouracil-cisplatin). After 2-8 weeks, a 15-20 Gy boost was delivered either with EBRT (20 pts) or interstitial (192)Ir brachytherapy (18 pts). Mean follow-up was 66 months. RESULTS: After chemoradiation therapy (CRT), 13 pts (34%) had a complete response, 23 pts (60%) a response >50% (2 pts were not evaluated). The 5-year-disease-free survival was 79.2 ± 6.5%, and the 5-year overall survival was 83.9 ± 6%. Eight patients developed tumor progression (mean delay 8.8 months), six of them requiring a salvage surgery with definitive colostomy for local relapse. Late severe complication requiring colostomy was observed in 2 pts. The 5-year-colostomy-free survival was 78 ± 6.9%. Patients who received primary chemotherapy had a statistically significant better 5-year colostomy-free survival (100% vs. 38 ± 16.4%, P = 0.0006). CONCLUSION: T4 anal carcinoma can be treated with a curative intent using a sphincter-sparing approach of CRT, and neo-adjuvant chemotherapy should be considered prior to radiotherapy.

Immediate post-mastectomy breast reconstruction followed by radiotherapy: risk factors for complications.

The objective is to prospectively determine the factors responsible for reconstruction failure and capsular contracture in mastectomized breast cancer patients who underwent immediate two-stage breast reconstruction with a tissue expander and implant, followed by radiotherapy. This is a multicenter, prospective, non-randomized study. Between February 1998 and September 2006, we prospectively examined 141 consecutive patients, each of which received an implant after mastectomy, followed by chest wall radiotherapy at 46-50 Gy in 23-25 fractions. Radiotherapy was delivered during immediate post-mastectomy reconstruction. Patients were evaluated by both a radiation oncologist and a surgeon 24-36 months after treatment. The median follow-up duration was 37 months. According to Baker's classification, capsular contracture was grade 0, 1, or 2 in 67.5% of cases; it was grade 3 or 4 in 32.5% of cases. In total, 32 breast reconstruction failures required surgery. In univariate analysis, the following factors were associated with Baker grade 3 and 4 capsular contraction: adjuvant hormone therapy (P = 0.02), the surgeon (P = 0.04), and smoking (P = 0.05). Only one factor was significant in multivariate analysis: the surgeon (P = 0.009). Three factors were associated with immediate post-mastectomy breast reconstruction failure in multiple logistic regression analysis: T3 or T4 tumors (P = 0.0005), smoking (P = 0.001), and pN+ axillary status (P = 0.004). Patients with none, 1, 2, or all 3 factors have a probability of failure equal to 7, 15.7, 48.3, and 100%, respectively (P = 3.6 x 10(-6)). The model accurately predicts 80% of failures. Mastectomy, immediate reconstruction (expander followed by implant), and radiotherapy should be considered when conservative surgery is contraindicated. Three factors may be used to select patients likely to benefit from this technique with a low failure rate.

Survival after breast cancer local recurrence according to therapeutic strategies.

AIMS: To compare survival outcomes after mastectomy (Mt) and lumpectomy plus interstitial brachytherapy (LpIB) in the treatment of breast cancer local recurrence (LR) occurring after conservative surgery. METHODS: Medical records of patients treated for an isolated LR from January 1, 1981 to December 31, 2009 were reviewed. To overcome the bias due to the fact that treatment choice (Mt or LpIB) was based on prognostic factors with LpIB proposed preferentially to women with good prognosis, Mt and LpIB populations were matched and compared with regard to overall survival (OS) and metastasis free survival (MFS). RESULTS: Among 348 patients analyzed, 66.7% underwent Mt, 17.8% LpIB and 15.5% Lp alone. After a median follow-up of 73.3 months, 65 patients had died (42/232 Mt, 8/62 LpIB, 15/54 Lp). Before matching, OS and MFS at 5 years were significantly better in the LpIB compared to the Mt group, due to significantly more frequent poor prognostic factors in the latter (p = 0,07 and p = 0,09 respectively, log-rank significance limit of 10%). After matching, the benefits of LpIB disappeared since MFS and OS rates were not significantly different in both groups (p = 0.68 and 0.88 respectively). After LpIB, the second LR rate was 17% at 5 years and 30% at 10 years. CONCLUSION: A second conservative breast cancer treatment associating lumpectomy and interstitial brachytherapy is possible for selected patients with LR, without decrease in neither OS nor MFS compared to mastectomy.

[Observance and results of concurrent chemoradiotherapy after induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil for locally advanced head and neck cancers]. / Observance et résultats de la chimioradiothérapie concomitante après chimiothérapie d'induction par docétaxel, cisplatine et 5-fluoro-uracile pour les cancers de la tête et du cou localement évolués.

PURPOSE: Retrospectively evaluate the safety, feasibility and efficacy of concomitant chemoradiotherapy after induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil for locally advanced head and neck cancers. PATIENTS AND METHODS: Patients' data from three radiotherapy centres in South of France, with locally advanced head and neck cancers, and treated between December 2007 and July 2013 by concomitant chemoradiotherapy, after induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil, were analysed. Adverse effects were graduated according to CTCAE v3.0 criteria. Overall survival and disease-free survival were calculated according to Kaplan-Meier method. RESULTS: One hundred and sixty-eight patients, mostly oropharynx (38%) T4 (46%) N2 (54%) tumors, received, after induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil, a concomitant chemoradiotherapy with platin or cetuximab, which delivered 66 to 70Gy. Grade 3-4 adverse effects were less frequent in the group of patients who received cisplatin (with or withour 5-fluoro-uracil) at 100mg/m(2) each 21 days compared to cetuximab (radiomucositis: 32.5% vs 61%, P=0.018; radioepithelitis: 13% vs 61 %, P<0.0001). Chemopotentiation was incomplete for 21% of patients without impacting survival. Two years overall survival and disease-free survival were respectively of 81% and 64%. Lymph nodes status and WHO status significantly influenced these survivals (overall survival 84% if N<3 vs 56% if N3, P=0.017 and 85 % if WHO status ≤ 1 vs 50% if WHO status>1, P=0.006; disease-free survival 66% if N<3 vs 47% if N3, P=0.046). CONCLUSION: The association of induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil and concomitant chemoradiotherapy shows satisfying results with an acceptable toxicity. The terms of the chemopotentiation and its superiority to a single concomitant chemoradiotherapy treatment still remain to be clarified.

Early stage cervical cancer: Brachytherapy followed by type a hysterectomy versus type B radical hysterectomy alone, a retrospective evaluation.

BACKGROUND: Two options are possible for the management of early stage cervical cancer, without lymph node involvement: radical surgery or brachytherapy followed by surgery. The aim of this study was to compare overall survival (OS) and disease-free survival (DFS) of early stage cervical cancers managed by uterovaginale brachytherapy followed by extrafasciale hysterectomy (group 1) or by radical hysterectomy alone (group 2). The secondary objectives were to compare the morbidity of these two different approaches and to evaluate the parametrial involvement rate in patients managed by radical hysterectomy. MATERIALS AND METHODS: It is a retrospective and collaborative study between the Paoli Calmettes Institute (Marseille) and the Oscar Lambret Center (Lille) from 2001 to 2013, in patients with tumors FIGO stages IA1, IA2, IB1 and IIA less than 2 cm of diameter, without pelvic lymph node involvement. RESULTS: One hundred and fifty-one patients were included (74 in group 1 and 77 in group 2). The demographic characteristics of the two groups were comparable. OS and DFS were respectively 92.3% versus 100% (p = 0.046) and 92.3% and 98.7% (p = 0.18). Complication rates were 12.2% and 44.2%, respectively (p < 0.0001). In group 2, the parametrial invasion rate in this study was 1.30%. CONCLUSION: In our study, the two strategies are comparable in terms of DFS. Complications seem more frequent in the group 2, but more severe in the group 1. Finally, the low rate of parametrial invasion in group 2 confirms the interest of a less radical surgical treatment in these stages with good prognosis.

Highly favorable outcome in BRCA-mutated metastatic breast cancer patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation.

Breast cancer carrying BRCA mutation may be highly sensitive to DNA-damaging agents. We hypothesized a better outcome for BRCA-mutated (BRCA(mut)) metastatic breast cancer (MBC) patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDC AHSCT) versus unaffected BRCA (BRCA wild type; (BRCA(wt))) or patients without documented BRCA mutation (BRCA untested (BRCA(ut))). All female patients treated for MBC with AHSCT at Institut Paoli-Calmettes between 2003 and 2012 were included. BRCA(mut) and BRCA(wt) patients were identified from our institutional genetic database. Overall survival (OS) was the primary end point. A total of 235 patients were included. In all, 15 patients were BRCA(mut), 62 BRCA(wt) and 149 BRCA(ut). In multivariate analyses, the BRCA(mut) status was an independent prognostic factor for OS (hazard ratio (HR): 3.08, 95% confidence interval (CI): 1.10-8.64, P=0.0326) and PFS (HR: 2.52, 95% CI :1.29-4.91, P=0.0069). In this large series of MBC receiving HDC AHSCT, we report a highly favorable survival outcome in the subset of patients with documented germline BRCA mutations.

Intensive sequential chemotherapy with repeated blood stem-cell support for untreated poor-prognosis non-Hodgkin's lymphoma.

PURPOSE: To demonstrate the feasibility and efficacy of six ambulatory high-dose sequential chemotherapy courses that include three intensified cycles supported by stem-cell infusion in high-risk and high-intermediate-risk untreated non-Hodgkin's lymphoma (NHL) patients. PATIENTS AND METHODS: A pilot nonrandomized study included 20 untreated patients aged less than 60 years with aggressive histologically identified NHL and two or three adverse-prognosis criteria (International Index). Patients received an ambulatory regimen with high-dose chemotherapy supported by granulocyte colony-stimulating factor (G-CSF) and repeated peripheral-blood stem-cell (PBSC) infusion. The median age was 39 years (range, 20 to 59), with 13 men and seven women. Chemotherapy consisted of one cycle every 21 days for a total of six cycles. The first three cycles (A1, A2, and A3) consisted of cyclophosphamide (Cy) 3,000 mg/m2, doxorubicin (Doxo) 75 mg/m2, and vincristine 2 mg (plus corticosteroids). The last three cycles (B4, B5, and B6) consisted of the same drug combination plus etoposide 300 mg/m2 and cisplatin 100 mg/m2. For an expected duration of 18 weeks, the projected dose-intensity was 25 mg/m2/wk for Doxo and 1,000 mg/m2/wk for Cy. G-CSF 300 micrograms was administered from day 6 following each cycle until neutrophil reconstitution. Two aphereses were performed at approximately day 13 after each A cycle, and PBSCs were injected at day 4 of each B cycle. Radiotherapy on tumor masses > or = 5 cm was scheduled after completion of the last cycle. RESULTS: The median duration of grade 4 neutropenia was 1 day (range, 0 to 7) for each A cycle and 4 days (range, 1 to 10) for each B cycle (P = .02). The median duration of grade 4 thrombopenia was 0 days (range, 0 to 8) for each A cycle and 6 days (range, 1 to 21) for each B cycle (P < .001). Hospitalization for febrile neutropenia was required for 18% and 44% of patients during cycles A and B, respectively (P < .01). Only three patients did not complete the protocol: one due to emergency surgery after cycle B4, one who died after cycle B5 from interstitial pneumonia, and one with delayed hematologic reconstitution after cycle B4. Chemotherapy delivery was optimal (median actual relative dose-intensity, 97%; range, 66 to 100). The median total dose administered over 18 weeks was 18,000 mg Cy (range, 12,000 to 18,000), 450 mg Doxo (range, 300 to 450), 900 mg etoposide (range, 300 to 900), and 300 mg cisplatin (range, 100 to 300). Evaluation of response after six courses showed 13 complete remissions ([CRs] 65%), four partial remissions (PRs), two nonresponses (NRs), and one toxic death. With a median follow-up period of 25 months (range, 16 to 43), 15 patients are alive, with 12 in continuous first CR; five patients relapsed (four of four PRs and one of 13 CRs). Two-year survival and failure-free survival (FFS) rates are 73% and 56%, respectively. The disease-free survival (DFS) rate for the CRs is 86%. CONCLUSION: PBSC support contributes to the feasibility of first-line, very-high-dose, ambulatory chemotherapy delivery in poor-risk NHL and is associated with a high rate of remission and FFS.

[Is there a rationale for regional node irradiation in pN1mi and pN0(i+) breast tumours?]. / Y a-t-il un rationnel pour irradier les aires ganglionnaires des tumeurs du sein de stades pN1mi et pN0(i+)?

The advent of sentinel lymph node technique has led to a shift in lymph node staging, due to the emergence of new entities, namely micrometastases and isolated tumour cells. In addition, the therapeutic role of axillary lymph node dissection is more and more questioned and radiotherapy has been shown to be equivalent to complementary axillary lymph node dissection in patients without clinical node involvement. This article looks at the literature in favour of performing axillary irradiation in patients with pN1mi stage breast cancer who have undergone a mastectomy without a complementary axillary lymph node dissection, and in favour of abstention of any further treatment of the axilla in patients with pN0(i+) or pN1mi tumours who have undergone breast conserving surgery and a sentinel lymph node procedure followed by systemic treatment. The impact of regional lymph nodes irradiation in case of axillary involvement 2mm or less is also discussed.

[Management and clinical outcome in patients over 80 years with rectal cancer treated between 2006 and 2008 in Southern France (PACA region)]. / Prise en charge et devenir des patients de plus de 80ans atteints d'un cancer du rectum, en région Provence-Alpes-Côte-d'Azur de 2006 à 2008.

PURPOSE: Rectal cancer is increasingly prevalent in elderly patients. Their clinical history and outcome after treatment are poorly described. This retrospective study was undertaken to provide more data and to compare therapeutic strategies to the standard of care for younger patients. PATIENTS AND METHODS: Patients concerned were aged 80 years or older, with a rectal cancer diagnosed between 2006 and 2008 and treated in Provence-Alpes-Côte-d'Azur (PACA), irrespective of stage and treatment of the disease. Overall survival and relapse-free-survival were correlated with patients' characteristics and treatment. The adopted therapeutic strategy was then compared to the standard-of-care for younger patients. RESULTS: With a median follow-up of 36 months, among the 160 patients included, the 3-year overall survival and relapse-free survival were 59.2% and 76.6%, respectively for the 117 patients who received a treatment with curative intent. In the multivariate analysis, node status and surgery independently influenced overall survival, while relapse-free survival was influenced by age, N status, and gender. For T0-T2 tumours, patients were treated similarly to younger patients with an overall survival of 83.6% and a relapse-free survival of 95.2%. For T3-T4 tumours, the 3-year relapse-free survival was 65%, even with a less aggressive strategy. CONCLUSION: Surgical resection after evaluation using the Comprehensive Geriatric Assessment (CGA) test should be the standard treatment for localized rectal cancer (T0-T2) in elderly patients, as it is in younger patients. For locally advanced lesions (T3-T4), results obtained after a conservative approach suggest that a non-surgical strategy can be used in elderly patients.

Calcifications and tungsten deposits after breast-conserving surgery and intraoperative radiotherapy for breast cancer.

AIM: To describe the presence of atypical calcifications on post-operative mammography after breast-conserving surgery (BCS) and intraoperative radiotherapy (IORT). MATERIALS AND METHODS: We retrospectively include all patients followed after BCS and IORT for breast cancer (n=271). All follow-up mammograms at 6 months after surgery were retrospectively evaluated by two board-certified radiologists. The radiologists had to notify the presence or the absence of atypical calcifications. RESULTS: Five patients had on follow-up mammography the presence of atypical calcifications. Two patients had a stereotactic breast biopsy. The pathologic examination showed the presence of small tungsten particles located in the breast parenchyma. CONCLUSION: The presence of atypical calcifications after BCS and IORT, presenting as multiple, scattered, round calcifications, should be rated as BIRADS 2 and do not require biopsy. They corresponded on tungsten deposits.

Interleukin-2 in association with increasing doses of interferon-gamma in patients with advanced cancer.

Twenty-seven patients with evaluable metastatic cancer were treated with recombinant interleukin-2 (rIL-2) and escalating doses of interferon gamma (IFN-gamma). rIL-2 was infused over a 15 min period at a constant dose (8 x 10(6) IU/m2/8 h x 5 days first cycle, and 8 x 10(6) IU/m2/12 h x 5 days second and third cycles, with 9 days rest between each cycle). IFN-gamma was started 4 days before each cycle of rIL-2 and was given every other day at a dosage of 1 x 10(6) U/m2 x 3/cycle (four patients), 5 x 10(6) U/m2 x 3/cycle (four patients), 5 x 10(6) U/m2 x 5/cycle (four patients) and 10 x 10(6) U/m2 x 5/cycle (15 patients). Common side effects were fluid retention and hepatic toxicity (27 and 15% grade greater than or equal to 2); one ischemic chest pains and one acute respiratory distress occurred. Toxicities were not greater than those described with high dose rIL-2 alone and were similar in each dose level of IFN-gamma. No patient died from the procedure. Four patients responded, one complete response and three partial responses; all were treated with 25 or 50 x 10(6) U/m2/cycle of IFN-gamma (melanoma, two patients; renal cell carcinoma, one patient; lymphoma, one patient). Further phase II studies at these dosages are justified to precisely define the antitumoral efficacy of this association.

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.

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.

Low energy Helium-Neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant: results of a double blind randomized trial.

PURPOSE: To evaluate the efficiency of Helium-Neon (He-Ne) laser in the prevention of oral mucositis induced by high dose chemoradiotherapy before autologous bone marrow transplantation (BMT). METHODS AND MATERIALS: Between 1993 and 1995, 30 consecutive patients receiving an autologous peripheral stem-cell or bone marrow transplant (BMT) after high dose chemoradiotherapy were randomized to possibly receive prophylactic laser to the oral mucosa after giving informed consent. Chemotherapy consisted of cyclophosphamide, 60 mg/kg intravenously (I.V.) on day (d)-5 and d-4 in 27 cases, or melphalan 140 mg/kg I.V. on d-4 in three cases. Total body irradiation (TBI) consisted of 12 Gy midplane dose in six fractions (4 Gy/day for three days). He-Ne laser (632.8 nm wavelength, power 60 mW) applications were performed daily from d-5 to d-1 on five anatomic sites of the oral mucosa. Oral examination was performed daily from d0 to d + 20. Mucositis was scored according to an oral exam guide with a 16 item scale of which four were assessed by the patients themselves. Mean daily self assessment scores for oral pain, ability to swallow and oral dryness were measured. A daily mucositis index (DMI) and a cumulative oral mucositis score (COMS) were established. Requirement for narcotics and parenteral nutrition was recorded. RESULTS: The COMS was significantly reduced among laser treated (L+) patients (p = 0.04). The improvement of DMI in L+ patients was also statistically significant (p < 0.05) from d + 2 to d + 7. Occurrence and duration of grade III oral mucositis were reduced in L+ patients (p = 0.01). Laser applications reduced oral pain as assessed by patients (p = 0.05) and L+ patients required less morphine (p = 0.05). Xerostomia and ability to swallow were improved among the L+ patients (p = 0.005 and p = 0.01, respectively). Requirement for parenteral nutrition was not reduced (p = NS). CONCLUSION: Helium-Neon laser treatment was well tolerated, feasible in all cases, and reduced high dose chemoradiotherapy-induced oral mucositis. Optimal laser treatment schedules still needs to be defined.

Fractionated total body irradiation and bone marrow transplantation in acute lymphoblastic leukemia.

From March 1982 to September 1988, 108 patients with acute lymphoblastic leukemia (ALL) were conditioned before allogeneic (57 patients of whom 16 T-depleted) or before autologous (51 patients) bone marrow transplantation (BMT). BMT was realized in 66 patients (31 allogeneic and 35 autologous) in first complete remission (CR) and in 42 patients (26 allogeneic and 16 autologous) in second CR or greater or in relapse. All patients received high doses of alkylating agents prior to a low-dose fractionated total body irradiation of 11 Gy in 5 fractions and 5 days. Rejection and relapse rate are described in relation to the three BMT types, allogeneic non T-depleted, allogeneic T-depleted, and autologous, and to the status of the patient at the time of the transplantation. Leukemic deaths are detailed according to the same parameters. Non-leukemic deaths and complications are determined. For the allogeneic population, the 4-year disease-free survival (DFS) is 47%; it is 68.5% in first CR patients, 23.5% in second or subsequent CR patients, and 50% in T-depleted BMT. For the autologous population, 4-year DFS is 35.7%; it is 52% in first CR patients and 30% in patients in second CR or greater. The conditioning regimen appears to be efficient in terms of disease control with a low rate of complications for the non T-depleted population, transplanted in first CR, but has to be improved for the other patients.

Radiotherapy and chemotherapy for invasive thymomas: a multicentric retrospective review of 90 cases. The FNCLCC trialists. Fédération Nationale des Centres de Lutte Contre le Cancer.

PURPOSE: Thymoma is a rare disease. The treatment of patients with invasive thymoma remains controversial. The prognosis of such patients is poor, even with the use of postoperative radiation therapy and chemotherapy. We retrospectively reviewed the outcome and prognostic factors in a series of 90 patients presenting with an invasive thymoma treated by partial resection or biopsy and radiation therapy. METHODS AND MATERIALS: From 1979-1990, 163 patients with the diagnosis of lymphoepithelial thymoma were treated in 10 French cancer centers. Patients were staged using the postoperative "GETT" classification derived from that of Masaoka. Ninety patients who presented with an invasive thymoma, 58 Stage III (21 IIIA: partial resection and 37 IIIB: biopsy) and 32 Stage IVA (intrathoracic thymoma spread), are the subject of this report. Treatment combined surgery and radiation therapy (+/- chemotherapy), with curative intent. Surgery consisted of partial resection in 31 patients (21 Stage III), and biopsy in 55 patients (37 Stage III). The median radiation dose to the tumor was 50 Gy (30-70 Gy). Supraclavicular radiation was performed in 59 patients (median dose 40 Gy). Chemotherapy, combined with radiation in 59 patients, consisted of multidrug regimens, mainly platinum based. RESULTS: The median follow-up is 105 months (20-165 months). The 5- and 10-year overall survival rates are 51 and 39%, respectively. There is a great impact of the extent of surgery on survival: the 5- and 10-year survival rates were 64% and 43%, respectively, after partial resection, compared to 39% and 31% after biopsy (p < 0.02). Local control at 8.5 years was obtained in 59 of 90 patients (66%): 40 Stage III, 19 Stage IVA. There is a significant relationship between the extent of surgery and the local control (16% of relapse after partial resection vs. 45% after biopsy, p < 0.05). Seven patients developed significant (grades 3-4 WHO grading system) treatment-induced side effects. Stage, histologic type, and chemotherapy were not prognostic factors. CONCLUSION: In this large multicentric retrospective study of invasive thymomas (Stage III-IVA) treated by surgery and radiation, results show the importance of loco-regional treatments, such as surgery and radiation therapy. There is also a great impact of radiation on local control. However, the rate of local recurrence (34%) justifies recommending a higher dose of radiation (> 50 Gy) than doses used in this study, for incompletely resected patients. The role of chemotherapy needs to be further assessed.

Local and distant recurrence after conservative management of "very low-risk" breast cancer are dependent events: a 10-year follow-up.

PURPOSE: To determine the risk factors associated with recurrence after breast-conserving treatments, and the relationship between occurrence of a local recurrence and subsequent distant metastases. METHODS AND MATERIALS: Among the 3697 patients with primary breast cancer treated at Institut Paoli-Calmettes Cancer Center, Marseille, between 1980 and 1995, we retrospectively analyzed 756 patients who had been treated with conservative surgery with uninvolved margins of excision, were node-negative, and had received uniform radiotherapy and no chemotherapy. One third of the patients received hormonal therapy via tamoxifen or surgical castration. The endpoints considered were local failures and distant metastases. All tumors were reviewed by our pathologists. The median follow-up for the 700 survivors was 62 months. RESULTS: In the multivariate analysis, histological multifocality (p = 0.0076), peritumoral vessel invasion (p = 0.0215), and young age (p = 0.0245) were associated with an increased risk of local recurrences, whereas tumor size (p = 0.0013), young age (p = 0.003), and histological multifocality (p = 0.0414) were associated with an increased risk of distant metastases. Local recurrences and distant metastases had similar yearly-event probabilities. Median time to distant metastases was shorter after a local recurrence. Early timing of local recurrences did not mark a higher risk of distant metastases. Hazard of relapsing from distant metastases was 4.4 times higher after a local recurrence. CONCLUSION: our results support the hypothesis that, in this subset of patients, local recurrences favor further dissemination of cancer cells. We are unable to clearly identify a group who would benefit from more aggressive local therapy.

Thallium-201 perfusion scintigraphy in the evaluation of late myocardial damage in left-side breast cancer treated with adjuvant radiotherapy.

PURPOSE: To evaluate late myocardial damage after adjuvant radiotherapy using a mixed-beam (photons plus electrons) technique to treat the internal mammary lymph nodes in left-side breast cancer. METHODS AND MATERIALS: A bicycle ergometer stress test coupled with thallium-201 perfusion scintigraphy and analysis by single-photon computed tomography (CT) was performed on 19 patients treated with left-side breast/chest wall and internal mammary radiation for breast cancer between 1987 and 1993. To be sure that we would evaluate late toxicity caused by the irradiation, patients had to fulfill the following eligibility criteria: left-side breast cancer, treatment between 1987 and 1993 and no recurrence during follow-up, age < or = 75 years, no known risk for coronary artery disease, no previous chemotherapy, internal mammary field treated with an association of photons and electrons, and CT scan-based treatment planning. RESULTS: Median age at scintigraphy was 59 years. Two patients did not reach optimal exercise level and were not evaluable. Among the 17 evaluable patients representing 91.6 patient years of follow-up, there were no perfusion defects by visual or quantitative analysis. CONCLUSION: The mixed-beam technique seemed to spare the heart from harmful irradiation and to protect the myocardium. Results need to be confirmed on the long-term use of this technique.