Prognostic value of sarcopenia in patients treated by Radiochemotherapy for locally advanced oesophageal cancer.

BACKGROUND: Sarcopenia is defined by a loss of skeletal muscle mass with or without loss of fat mass. Sarcopenia has been associated to reduced tolerance to treatment and worse prognosis in cancer patients, including patients undergoing surgery for limited oesophageal cancer. Concomitant chemo-radiotherapy is the standard treatment for locally-advanced tumour, not accessible to surgical resection. Using automated delineation of the skeletal muscle, we have investigated the prognostic value of sarcopenia in locally advanced oesophageal cancer (LAOC) patients treated by curative-intent chemo-radiotherapy. METHODS: The clinical, nutritional, anthropometric, and functional-imaging (18FDG-PET/CT) data were collected in 97 patients treated between 2006 and 2012 in our institution. The skeletal muscle area was automatically delineated on cross-sectional CT images acquired at the 3rd. lumbar vertebra level and divided by the patient's squared height (SML3/h2) to obtain the Skeletal Muscle Index (SMI). The primary endpoint was overall survival probability. RESULTS: Seventy-six deaths were reported. The median survival time was 27 [95% Confidence Interval 23-40] months for the whole population. Univariate analyses (Cox Proportional Hazard Model) showed decreased survival probabilities in patients with reduced SMI, WHO > 0, Body Mass Index ≤21, and Nutritional Risk Index ≤97.5. Multivariate analyses showed that sarcopenia was the only significant prognostic factor (HR 2.32 [1.24-4.34], p = 0.008). Using Receiver Operating Characteristics curves, the Area Under the Curve (AUC) was 0.73 in males (p = 0.0002], the optimal threshold being 51.5 cm2/m2. In women, the AUC was 0.65 (p = 0.19). CONCLUSION: Sarcopenia is a powerful independent prognostic factor, associated with a rise of the overall mortality in patients treated exclusively by radiochemotherapy for a locally advanced oesophageal cancer. L3 CT images are easily gathered from 18FDG-PET/CT acquisitions.

Lobular carcinoma in situ (LCIS) of the breast: is long-term outcome similar to ductal carcinoma in situ (DCIS)? Analysis of 200 cases.

BACKGROUND: Lobular carcinomas in situ (LCIS) represent 1-2% of all breast cancers. Both significance and treatment remain widely debated, as well as the possible similarities with DCIS. MATERIALS AND METHODS: Two hundred patients with pure LCIS were retrospectively analyzed in seven centres from 1990 to 2008. Median age was 52 years; 176 patients underwent breast-conserving surgery (BCS) and 24 mastectomy. Seventeen patients received whole breast irradiation (WBRT) after BCS and 20 hormonal treatment (15 by tamoxifen). RESULTS: With a 144-month median follow-up (FU), there were no local recurrences (LR) among 24 patients treated by mastectomy. With the same FU, 3 late LR out of 17 (17%) occurred in patients treated by BCS and WBRT (with no LR at 10 years). Among 159 patients treated by BCS alone, 20 developed LR (13%), but with only a 72-month FU (17.5% at 10 years). No specific LR risk factors were identified. Three patients developed metastases, two after invasive LR; 22 patients (11%) developed contralateral BC (59% invasive) and another five had second cancer. CONCLUSIONS: LCIS is not always an indolent disease. The long-term outcome is quite similar to most ductal carcinomas in situ (DCIS). The main problems are the accuracy of pathological definition and a clear identification of more aggressive subtypes, in order to avoid further invasive LR. BCS + WBRT should be discussed in some selected cases, and the long-term results seem comparable to DCIS.

Radiotherapy with concomitant weekly docetaxel for Stages III/IV oropharynx carcinoma. Results of the 98-02 GORTEC Phase II trial.

PURPOSE: We designed a prospective Phase II clinical trial to evaluate the addition of weekly chemotherapy using Docetaxel during standard radiation therapy in patients with Stages III and IV oropharynx carcinoma. METHODS: A total of 63 patients have been entered in a Phase II multicenter trial. Radiotherapy delivered, with conventional fractionation, 70 Gy in 35 fractions. Patients received during the period of radiotherapy seven cycles of Docetaxel (20 mg/m2 each week). RESULTS: Radiotherapy compliance was good in respect to total dose, treatment duration, and treatment interruption. The rate of Grade 3 and 4 mucositis was 84%. Grade 3 and 4 skin toxicity occurred in 53% of the patients. Hematologic toxicity was infrequent, with only a 5% rate of Grade 3 or 4 neutropenia. Three-year overall actuarial survival and disease-free survival rates were, respectively, 47% (95% CI = 39-68%) and 39% (95% CI = 30-57%). The local and regional control rate was 64%. CONCLUSION: The adjunction of weekly Docetaxel to conventional radiotherapy is feasible. Mucositis and skin toxicity were the major acute toxic effects. Therapeutic results were similar to those observed with concomitant chemotherapy using platinum and/or 5-FU. Further trials using Docetaxel in combination with other cytotoxic agents are needed.

Breast-conserving therapy for ductal carcinoma in situ of the breast: the French Cancer Centers' experience.

PURPOSE: To assess the long-term outcome for women with ductal carcinoma in situ of the breast treated in current clinical practice by conservative surgery with or without definitive breast irradiation. METHODS AND MATERIALS: We analyzed 705 cases of ductal carcinoma in situ treated between 1985 and 1995 in nine French regional cancer centers; 515 underwent conservative surgery and radiotherapy (CS+RT) and 190 CS alone. The median follow-up was 7 years. RESULTS: The 7-year crude local recurrence (LR) rate was 12.6% (95% confidence interval [CI] 9.4-15.8) and 32.4% (95% CI 25-39.7) for the CS+RT and CS groups, respectively (p <0.0001). The respective 10-year results were 18.2% (95% CI 13.3-23) and 43.8% (95% CI 30-57.7). A total of 125 LRs occurred, 66 and 59 in the CS+RT and CS groups, respectively. Invasive or microinvasive LRs occurred in 60.6% and 52% of the cases in the same respective groups. The median time to LR development was 55 and 41 months. Nine (1.7%) and 6 (3.1%) nodal recurrences occurred in the CS+RT and CS groups, respectively. Distant metastases occurred in 1.4% and 3% of the respective groups. Patient age and excision quality (final margin status) were both significantly associated with LR risk in the CS+RT group: the LR rate was 29%, 13%, and 8% among women aged < or =40, 41-60, and > or =61 years (p <0.001). Even in the case of complete excision, we observed a 24% rate of LR (6 of 25) in women <40 years. Patients with negative, positive, or uncertain margins had a 7-year crude LR rate of 9.7%, 25.2%, and 12.2%, respectively (p = 0.008). RT reduced the LR rate in all subgroups, especially in those with comedocarcinoma (17% vs. 59% in the CS+RT and CS groups, respectively, p <0.0001) and mixed cribriform/papillary tumors (9% vs. 31%, p <0.0001). In the multivariate Cox regression model, young age and positive margins remained significant in the CS+RT group (p = 0.00012 and p = 0.016). Finally, the relative LR risk in the CS+RT group compared with the CS group was 0.35 (95% CI 0.25-0.51, p = 0.0001). Subsequent contralateral breast cancer occurred in 7.1% and 7.5% of the patients in the CS+RT and CS groups, respectively. CONCLUSION: Despite the absence of randomization, our results are extremely consistent with the updated National Surgical Adjuvant Breast Project B17 and European Organization for Research and Treatment of Cancer 10853 trials. We also noted that the LR risk was very high in women <40 years and/or in the case of incomplete excision.