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Cancer progression is driven in part by genomic alterations

PURPOSE To describe the quality assurance (QA) program and early toxicities in the phase III randomized trial BONBIS (NCT00907868) on the role of a localized radiation boost in ductal carcinoma in situ (DCIS). MATERIALS AND METHODS From November 2008 to July 2014, 2004 patients were randomized in arm A (only whole breast radiotherapy, WBRT) and arm B (WBRT + boost). The QA program involved 44 participant centers that performed the dummy run (DR). Compliance and uniformity of clinical target volume (CTV) delineations, and dose prescription and delivery according to the BONBIS trial radiotherapy guidelines were analyzed. Acute toxicities (during and up to 3 months after radiotherapy completion, NCI-CTCAE v3.0 classification) were evaluated in 1929 patients. RESULTS The differences in whole breast CTV (CTV1) and planning target volume (PTV1) were ≤10%, and the differences in boost CTV (CTV2) and PTV (PTV2) were ≥20% compared with the reference DR values; 95% of the prescribed dose encompassed 98.7% and 100% of the median CTV1 and CTV2. Grade ≥2 breast erythema (38.3% vs. 22.4% of grade 2 and 5.4% vs. 2.1% of grade 3, p

The impact of single-agent antibodies against programmed death-ligand 1 (PD-L1) as maintenance therapy is unknown in patients with metastatic breast cancer. The SAFIR02-BREAST IMMUNO substudy included patients with human epidermal growth factor receptor type 2 (Her2)-negative metastatic breast cancer whose disease did not progress after six to eight cycles of chemotherapy. Patients (n = 199) were randomized to either durvalumab (10 mg kg−1 every 2 weeks) or maintenance chemotherapy. In the overall population, durvalumab did not improve progression-free survival (adjusted hazard ratio (HR): 1.40, 95% confidence interval (CI): 1.00–1.96; P = 0.047) or overall survival (OS; adjusted HR: 0.84, 95% CI: 0.54–1.29; P = 0.423). In an exploratory subgroup analysis, durvalumab improved OS in patients with triple-negative breast cancer (TNBC; n = 82; HR: 0.54, 95% CI: 0.30–0.97, P = 0.0377). Exploratory analysis showed that the HR of death was 0.37 (95% CI: 0.12–1.13) for patients with PD-L1+ TNBC (n = 32) and 0.49 (95% CI: 0.18–1.34) for those with PD-L1− TNBC (n = 29). In patients with TNBC, exploratory analyses showed that the HR for durvalumab efficacy (OS) was 0.18 (95% CI: 0.05–0.71; log-rank test, P = 0.0059) in patients with CD274 gain/amplification (n = 23) and 1.12 (95% CI: 0.42–2.99; log-rank test, P = 0.8139) in patients with CD274 normal/loss (n = 32). Tumor infiltration by lymphocytes (CD8, FoxP3 and CD103 expressions) and homologous recombination deficiency did not predict sensitivity to durvalumab in exploratory analyses. This latter finding should be interpreted with caution since only one patient presented a germline BRCA mutation. The present study provides a rationale to evaluate single-agent durvalumab in maintenance therapy in patients with TNBC. Exploratory analyses identified CD274 amplification as a potential biomarker of sensitivity. Maintenance chemotherapy was more effective than durvalumab in patients with hormone receptor-positive and Her2-negative disease. Exploratory analyses from the phase 2 randomized SAFIR02-IMMUNO trial identify biomarkers associated with improved outcomes to durvalumab as compared to maintenance chemotherapy in patients with triple-negative breast cancer.

Background Ductal carcinoma in situ (DCIS) represents 15% of all breast cancers in France. The first national survey was conducted in 2003. The present multi-center real-life practice survey aimed at assessing possible changes in demographic, clinical, pathologic, and treatment features. Material and Methods From March 2014 to September 2015, patients diagnosed with DCIS from 71 centers with complete information about age, diagnostic features, and treatment modalities were prospectively included. Results A total of 2125 patients with a median age of 58.6 years from 71 centers were studied. DCIS was diagnosed by mammography in 87.5% of cases. Preoperative biopsy was performed in 96% of cases. The median tumor size was 15 mm. Nuclear grade was low, intermediate, and high in 12%, 36%, and 47% of cases, respectively. Margins were considered to be negative in 83% of cases. Overall mastectomy and lumpectomy rates were 25% and 75%, respectively. The immediate breast reconstruction rate was 50%. Sentinel node biopsy and axillary dissection rates were 41% and 2.6%, respectively. After lumpectomy, 97% of patients underwent radiotherapy, and 32% received a boost dose. Only 1% of patients received endocrine therapy. Compared with our previous survey, the median tumor size remained the same, and the proportion of high-grade lesions increased by 9%. The mastectomy rate decreased by 4%. Conclusions The clinical practice identified in this survey complies with French DCIS guidelines. About 10% of patients with low-grade DCIS may be eligible to participate in treatment de-escalation trials.

The impact of single-agent antibodies against programmed death-ligand 1 (PD-L1) as maintenance therapy is unknown in patients with metastatic breast cancer. The SAFIR02-BREAST IMMUNO substudy included patients with human epidermal growth factor receptor type 2 (Her2)-negative metastatic breast cancer whose disease did not progress after six to eight cycles of chemotherapy. Patients (n = 199) were randomized to either durvalumab (10 mg kg

To assess the benefit of intensity-modulated radiotherapy (IMRT) compared with conventional RT for the quality of life (QOL) of head and neck cancer survivors.Cross-sectional QOL measures (European Organization for Research and Treatment of Cancer QOL questionnaire C30 and head and neck cancer module) were used with a French multicenter cohort of patients cured of head and neck cancer (follow-upor = 1 year) who had received bilateral neck RT (or = 45 Gy) as a part of their initial treatment. We compared the QOL mean scores regarding RT modality (conventional RT vs. IMRT). The patients of the two groups were matched (one to one) according to the delay between the end of RT and the timing of the QOL evaluation and the T stage. Each QOL item was divided into two relevant levels of severity: "not severe" (responses, "not at all" and "a little") vs. "severe" (responses "quite a bit" and "very much"). The association between the type of RT and the prevalence of severe symptoms was approximated, through multivariate analysis using the prevalence odds ratio.Two comparable groups (67 pairs) were available. Better scores were observed on the head and neck cancer module QOL questionnaire for the IMRT group, especially for dry mouth and sticky saliva (p0.0001). Severe symptoms were more frequent with conventional RT concerning saliva modifications and oral discomfort. The adjusted prevalence odds ratios were 3.17 (p = 0.04) for dry mouth, 3.16 (p = 0.02) for sticky saliva, 3.58 (p = 0.02) for pain in the mouth, 3.35 (p = 0.04) for pain in the jaw, 2.60 (p = 0.02) for difficulties opening the mouth, 2.76 (p = 0.02) for difficulties with swallowing, and 2.68 (p = 0.03) for trouble with eating.The QOL assessment of head and neck cancer survivors demonstrated the benefit of IMRT, particularly in the areas of salivary dysfunction and oral discomfort.

Secondary tumours (ST) represent a major concern in survivors of Hodgkin's disease (HD). Breast cancer (BC) is the most frequent ST among young treated women.One hundred and eighty-nine women treated for HD by radiotherapy (RT) and/or chemotherapy (CT) subsequently developed 214 BCs.Median age at HD diagnosis was 25 years (34% were less than 20). Median interval between HD and BC was 18.6 years, with a 42-year median age at first BC. According to the TNM classification, there were 30 (14%) T0 (non palbable lesions), 86 (40%) T1, 56 (26%) T2, 13 (6%) T3T4 and 29 (14%) Tx. There were 25 (13.2%) contralateral BC. 160 (75%) and 15 (7%) tumours were infiltrating ductal and lobular carcinomas, 7 (3.3%) were other subtypes and 27 (22%) DCIS. The rate of axillary nodal involvement was 32%. Among 203 operated tumours, 79 (39%) were treated by breast conserving surgery (BCS), with RT in 56 (71%) cases. CT and hormonal treatment were delivered in 51% and 45% of the patients. With a 50-month median follow-up, local recurrence occurred in 12% of the tumours (9% after mastectomy, 21% after lumpectomy alone and 13.7% after lumpectomy with RT). Metastasis occurred in 47 (26%) patients. The risk factors were pN+, pT, high SBR grade and young age (50 years). The ten-year overall and specific survival rates were 53% and 63.5%, respectively. The ten-year specific survival rates were 79% for pT0T1T2, 48% for pT3T4 (p = 0.0002) and 79% for pN0 versus 38.5% for pN+ (p = 0.00026). Among 67 deaths, 43 (73%) were due to BC.Patients and physicians should be aware that BC is the most frequent secondary tumour in young women treated for HD. The new RT modalities (lower doses and involved fields) may decrease the risk in the future. However, these women require a careful monitoring as from 8 to 10 years after HD treatment, combining mammography, ultrasound and MRI according to several ongoing studies. BC with whole breast irradiation is feasible in some selected cases.

Purpose: Our aim was to determine the dose to the clinical target volume (CTV) required for solitary extramedullary plasmacytoma (EMP) in the head and neck (HN). Methods and Materials: Seventeen patients (15 Stage I and 2 Stage II) were treated for HN EMP at our institution between 1979 and 2003. The mean International Commission on Radiation Units (ICRU) dose prescribed to the CTV was 52.6 Gy (range, 40–65 Gy) over 24 fractions (range: 20–30). The Stage II patients received neck irradiation doses of 40 and 60 Gy. A mean dose of 36.4 Gy was used for 5 Stage I patients who received elective neck irradiation. Dose administrated to the CTV was evaluated from dosimetric data or from planning films when dosimetric data were not available. Two groups of patients were distinguished: CTV covered with a dose greater than 40 Gy and CTV covered with a dose greater than 45 Gy. Results: The 5-year local control was 72.8%. It was 100% for patients who received dose to the CTV ≤ 45 Gy vs. 50% for dose to the CTV p = 0.034). The prognostic factor for 5-year disease-specific survival (81.6%) was local control ( p = 0.058). The prognostic factors for disease-free survival (64.1%) were monoclonal immunoglobulin secretion ( p = 0.008) and a CTV dose ≤ 45 Gy ( p = 0.056) Conclusions: Local control of EMP in the HN seems to be improved when the dose to the CTV is ≤ 45 Gy. A minimum dose of 45 Gy should be recommended to the CTV.

Abstract #6153 Background Breast cancer (BC) is the most frequent second malignancy in women treated for Hodgkin's disease (HD), but there are few specific data on these tumors. This study assesses histopathological features, locoregional and systemic treatments as well as prognostic factors of these secondary BC. Material and methods: 127 women treated for HD in 9 centers subsequently developed 143 BC. Median age at HD diagnosis was 25 years. HD stages were I, II, III and IV in 28%, 49%, 16% and 7%. Radiotherapy (RT) alone was used in 44 cases and chemotherapy (CT) + RT in 83 cases. Twelve patients relapsed and had a new treatment by RT (3), CT (5) or both (4). Results: First BC occurred after 18-year median interval (20 years: 40%). TNM classification (126/143) showed 23 mammographically detected T0 (18%), 54 T1 (43%, 40 T2 (32%) and 9 T3T4 (7%). 129 tumors were infiltrating carcinoma (IC) and 14 (10%) DCIS. Twenty-four (17%) tumors were multifocal. Five patients had metastasis at diagnosis; 135 tumors were operated (121 IC and 14 DCIS): 57 (42%) by conservative surgery (40 with RT) and 78 (58%) by mastectomy (5 with RT). Axillary dissection (AD) and SNB were performed in 74% and 23% of the cases. Median tumor size for IC was 19 mm. Axillary nodal involvement (ANI) was found in 28% of IC (pN1-3 : 22%; pN>3 : 6%). ER and PgR were positive in 57% and 49%. 43 (39%) tumors were SBR III (high grade). Chemotherapy (CT) and hormonotherapy (HT) were performed in 47% and 42% of IC. With a 5-year median FU, 17 patients (12%) developed local recurrences (LR) and 35 (30%) had metastases. Significant metastasis predictive factors were ANI and SBR III; 12 (10%) women developed a third cancer. 5 and 10-year overall survival (OS) rates were 69% and 53%, and disease-specific survival (DSS) rates 72% and 62%. 5-year DSS rates were 79% for T0T1 versus 44% for pT2T3T4 (p=0.0068) and 81% for pN0 versus 65% for pN+ (p=0.0012). Conclusion Young women (especially 15-25 years) treated for HD should be carefully monitored by mammography, ultrasound and maybe MRI in order to detect early occurrence of BC. The prognosis of small lesions (pTis/pT1) is excellent and conservative treatment often feasible. This study is still ongoing, with 200 planned cases. Optimal adjuvant treatment options will be discussed and compared with a former series including 133 cases (Radiotherapy and Oncology, 2001, 59: 247-255). Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6153.