We compared two intensity-modulated radiotherapy techniques for left-sided breast treatment, involving lymph node irradiation including the internal mammary chain. Inverse planned arc-therapy (VMAT) was compared with a forward-planned multi-segment technique with a mono-isocenter (MONOISO). Ten files were planned per technique, delivering a 50-Gy dose to the breast and 46.95 Gy to nodes, within 25 fractions. Comparative endpoints were planning target volume (PTV) coverage, dose to surrounding structures, and treatment delivery time. PTV coverage, homogeneity and conformality were better for two arc VMAT plans; V95%PTV-T was 96% for VMAT vs 89.2% for MONOISO. Homogeneity index (HI)PTV-T was 0.1 and HIPTV-N was 0.1 for VMAT vs 0.6 and 0.5 for MONOISO. Treatment delivery time was reduced by a factor of two using VMAT relative to MONOISO (84 s vs 180 s). High doses to organs at risk were reduced (V30left lung = 14% using VMAT vs 24.4% with MONOISO; dose to 2% of the volume (D2%)heart = 26.1 Gy vs 32 Gy), especially to the left coronary artery (LCA) (D2%LCA = 34.4 Gy vs 40.3 Gy). However, VMAT delivered low doses to a larger volume, including contralateral organs (mean dose [Dmean]right lung = 4 Gy and Dmeanright breast = 3.2 Gy). These were better protected using MONOISO plans (Dmeanright lung = 0.8 Gy and Dmeanright breast = 0.4 Gy). VMAT improved PTV coverage and dose homogeneity, but clinical benefits remain unclear. Decreased dose exposure to the LCA may be clinically relevant. VMAT could be used for complex treatments that are difficult with conventional techniques. Patient age should be considered because of uncertainties concerning secondary malignancies.

Purpose: EGFR is frequently overexpressed in cervical cancer, suggesting EGFR blockade as a promising treatment approach. Cetuximab, an anti EGFR antibody, used conjointly with radiochemotherapy, was feasible in first-line treatment of cervix carcinoma limited to the pelvis.Experimental Design: This randomized phase II trial enrolled 78 FIGO stage IB2-IIIB cervical cancer patients to either cisplatinbased radiochemotherapy alone (arm B, n ¼ 38) or conjointly with a 6-week course of weekly cetuximab (arm A, n ¼ 40). Brachytherapy was given to the pelvic mass. Primary endpoint was disease-free survival (DFS) at 2 years. EGFR expression and targeted sequencing were performed in 54 of 78 patients.Results: Cetuximab over a 6-week period did not improve DFS at 24 months. At 31 months median follow-up, DFS was not significantly different (P ¼ 0.18). Complete response at 4 to 6 months was strongly predictive for excellent DFS (log-rank test; P < 0.001). PIK3CA, KRAS, and STK11 mutations were observed in 22%, 4%, and 2% of patients, respectively. No tumor with a PI3K pathway mutation showed complete response (0/8 in arm A and 0/6 in arm B), whereas 14 of 52 (27%) tumors without mutations did (P ¼ 0.021). PI3K pathway-mutated tumors showed a trend toward poorer DFS (P ¼ 0.06) following cetuximab (8/22) as compared with those following standard treatment only (6/18).Conclusions: Similar to patients with head and neck cancer, patients with cervical cancer showed no gain in DFS at 2 years following a combined treatment of cetuximab with radiochemotherapy. Although treatment tolerance and compliance were satisfactory, it remains to be demonstrated whether maintenance therapy with cetuximab could be beneficial in selected patient groups.

PurposeThis study evaluates the benefit of a virtual bolus method for volumetric modulated arc therapy (VMAT) plan optimization to compensate breast modifications that may occur during breast treatment.MethodsTen files were replanned with VMAT giving 50 Gy to the breast and 47 Gy to the nodes within 25 fractions. The planning process used a virtual bolus for the first optimization, then the monitors units were reoptimized without bolus, after fixing the segments shapes. Structures and treatment planning were exported on a second scanner (CT) performed during treatment as a consequence to modifications in patient's anatomy. The comparative end‐point was clinical target volume's coverage. The first analysis compared the VMAT plans made using the virtual bolus method (VB‐VMAT) to the plans without using it (NoVB‐VMAT) on the first simulation CT. Then, the same analysis was performed on the second CT. Finally, the level of degradation of target volume coverage between the two CT using VB‐VMAT was compared to results using a standard technique of forward‐planned multisegment technique (Tan‐IMRT).ResultsUsing a virtual bolus for VMAT does not degrade dosimetric results on the first CT. No significant result in favor of the NoVB‐VMAT plans was noted. The VB‐VMAT method led to significant better dose distribution on a second CT with modified anatomies compared to NoVB‐VMAT. The clinical target volume's coverage by 95% (V95%) of the prescribed dose was 98.9% [96.1–99.6] on the second CT for VB‐VMAT compared to 92.6% [85.2–97.7] for NoVB‐VMAT (P = 0.0002). The degradation of the target volume coverage for VB‐VMAT is not worse than for Tan‐IMRT: the median differential of V95% between the two CT was 0.9% for VMAT and 0.7% for Tan‐IMRT (P = 1).ConclusionThis study confirms the safety and benefit of using a virtual bolus during the VMAT planning process to compensate potential breast shape modifications.

Refractory chronic GVHD (cGVHD) remains a major cause of morbidity after transplantation. Many drugs are used but there is no consensus on the standard of care. We investigated the efficacy of TLI in corticosteroid-refractory cGVHD. We analyzed retrospectively 31 patients receiving one or more TLI session for refractory cGVHD from 2000 to 2007. The main objective was to evaluate the response rate after TLI. Decreased corticosteroid doses and/or discontinued immunosuppressive agents were considered to be surrogate markers of response. All but one patient presented with severe cGVHD at the time of TLI. The median number of previous immunosuppressive treatment lines was 3 (range: 2-4). Fourteen patients (45%) achieved an objective response after TLI and 8 (25%) were cGVHD free at long-term follow-up. In all, 5 (29%) of the 17 nonresponsive patients did not show the features of progressive cGVHD and could decrease the amount of immunosuppressive drugs taken. Response after TLI significantly improved 5-year GVHD-related mortality (14% vs 42%, P ¼ 0.038) but not OS (58%vs 64% P ¼ 0.27). Regarding the promising response rate in this heavily pretreated population, we reasoned that TLI could be an alternative treatment for corticosteroid-refractory cGVHD.

The spread of systematic screening and the emergence of oncoplastic techniques allow more breast conservative treatment associating lumpectomy and external beam radiation therapy. In order to furthermore facilitate the patient's treatment, intraoperative radiation therapy (IORT) has been developed. The oncological safety of this technique has been studied, and is considered acceptable. Many questions remain unsolved in regard of the toxicity of this procedure as well as the patient's selection criteria. In this study, we present the first results and complications rate of patients treated by IORT in a single French institution. Between 2012 and 2015, all patients with breast cancer treated in a one‐step procedure associating lumpectomy and IORT were retrospectively included in a monocentric cohort. Acute and long‐term toxicities were evaluated using CTCAE v4.0 classification. 280 breast cancers were treated using IORT procedure. Additional external beam radiation therapy was requested for 45.7% patients. The acute complications rate was 14.6%, with 5 surgical revisions needed (1.78%). With a median follow up of 911 days, the long‐term grade‐3 toxicity rate was 1.1%. The only risk factor for local fibrosis was external beam radiation therapy (EBRT) (OR = 1.99; IC95 [1.05–3.81], P = 0.036). Three patients (1.07%) were diagnosed with local recurrence. The results from this cohort confirm the low complication and recurrence rate of IORT procedure. A good selection of patients is necessary in order to lower the EBRT rate and allow therapeutic de‐escalation. The classification of tumors into IHC subsets seems a good selection gate. Intraoperative radiation therapy appears to have a low toxicity rate with an acceptable local recurrence risk, and should therefore be considered as an option in the treatment of early breast cancer.