Prospective Study of Intensity-Modulated Radiation Therapy for Locally Advanced Breast Cancer.

The objective of this study was to evaluate the acute and medium-term toxicities, the quality of life, and aesthetic results of patients with breast cancer (BC) treated with tomotherapy. This was a prospective study, including patients with BC treated by tomotherapy. Radiation therapy delivered 50 Gy in 25 fractions to the breast or chest wall and to lymph node areas, with a simultaneous integrated boost at a dose of 60 Gy at the tumor bed in cases of breast conservative surgery. We included 288 patients, 168 and 120 treated with breast-conserving surgery and mastectomy respectively. Two hundred sixty patients (90.3%) received lymph node irradiation. Median follow-up was 25 months (6-48). Acute dermatitis was observed in 278 patients (96.5%), mostly grade 1 (59.7%). The aesthetic aspect of the breast at one year was reported as "good" or "excellent" in 84.6% of patients. The patients' quality of life improved over time, especially those treated with chemotherapy. The two-year overall survival and disease-free survival were 97.8% (95% confidence interval (CI): 94.1-99.2%), and 93.4% (95% CI: 89.2-96.0%) respectively. Tomotherapy for locally advanced BC has acceptable toxicity, supporting its use in this indication; however, longer follow-up is needed to assess long-term outcomes.

Chest Magnetic Resonance Imaging Decreases Inter-observer Variability of Gross Target Volume for Lung Tumors.

Purpose: PET/CT is a standard medical imaging used in the delineation of gross tumor volume (GTV) in case of radiation therapy for lung tumors. However, PET/CT could present some limitations such as resolution and standardized uptake value threshold. Moreover, chest MRI has shown good potential in diagnosis for thoracic oncology. Therefore, we investigated the influence of chest MRI on inter-observer variability of GTV delineation. Methods and Materials: Five observers contoured the GTV on CT for 14 poorly defined lung tumors during three contouring phases based on true daily clinical routine and acquisition: CT phase, with only CT images; PET phase, with PET/CT; and MRI phase, with both PET/CT and MRI. Observers waited at least 1 week between each phases to decrease memory bias. Contours were compared using descriptive statistics of volume, coefficient of variation (COV), and Dice similarity coefficient (DSC). Results: MRI phase volumes (median 4.8 cm3) were significantly smaller than PET phase volumes (median 6.4 cm3, p = 0.015), but not different from CT phase volumes (median 5.7 cm3, p = 0.30). The mean COV was improved for the MRI phase (0.38) compared to the CT (0.58, p = 0.024) and PET (0.53, p = 0.060) phases. The mean DSC of the MRI phase (0.67) was superior to those of the CT and PET phases (0.56 and 0.60, respectively; p < 0.001 for both). Conclusions: The addition of chest MRI seems to decrease inter-observer variability of GTV delineation for poorly defined lung tumors compared to PET/CT alone and should be explored in further prospective studies.

Efficacy and Tolerance of Post-operative Hypo-Fractionated Stereotactic Radiotherapy in a Large Series of Patients With Brain Metastases.

Purpose: The aim of this study was to assess, in a large series, the efficacy and tolerance of post-operative adjuvant hypofractionated stereotactic radiation therapy (HFSRT) for brain metastases (BMs). Materials and Methods: Between July 2012 and January 2017, 160 patients from 2 centers were operated for BM and treated by HFSRT. Patients had between 1 and 3 BMs, no brainstem lesions or carcinomatous meningitis. The primary endpoint was local control. Secondary endpoints were distant brain control, overall survival (OS) and tolerance to HFSRT. Results: 73 patients (46%) presented with non-small cell lung cancer (NSCLC), 23 (14%) had melanoma and 21 (13%) breast cancer. Median age was 58 years (range, 22-83 years). BMs were synchronous in 50% of the cases. The most frequent prescription regimens were 24 Gy in 3 fractions (n = 52, 33%) and 30 Gy in 5 fractions (n = 37, 23%). Local control rates at 1 and 2 years were 88% [95%CI, 81-93%] and 81% [95%CI, 70-88%], respectively. Distant control rate at 1 year was 48% [95%CI, 81-93%]. In multivariate analysis, primary NSCLC was associated with a significant reduction in the risk of death compared to other primary sites (HR = 0.57, p = 0.007), the number of extra-cerebral metastatic sites (HR = 1.26, p = 0.003) and planning target volumes (HR = 1.15, p = 0.012) were associated with a lower OS. There was no prognostic factor of time to local progression. Median OS was 15.2 months [95%CI, 12.0-17.9 months] and the OS rate at 1 year was 58% [95% CI, 50-65%]. Salvage radiotherapy was administered to 72 patients (45%), of which 49 received new HFSRT. Ten (7%) patients presented late grade 2 and 4 (3%) patients late grade 3 toxicities. Thirteen (8.9%) patients developed radiation necrosis. Conclusions: This large multicenter retrospective study shows that HFSRT allows for good local control of metastasectomy tumor beds and that this technique is well-tolerated by patients.

Stereotactic Re-irradiation for Local Recurrence in the Prostatic Bed After Prostatectomy: Preliminary Results.

Objectives: To report the preliminary results of salvage re-irradiation in the prostatic bed after radical prostatectomy and salvage external beam radiation therapy (EBRT) using robotic stereotactic body radiation therapy (SBRT) with Cyberknife® for local recurrence of prostate cancer. Materials and Methods: Retrospective monocentric analysis was performed on patients treated with SBRT for isolated macroscopic recurrence in the prostatic bed. All patients had radical prostatectomy and salvage or adjuvant EBRT. Local recurrence was documented using magnetic resonance imaging (MRI) and positron emission tomography (PET). Biochemical recurrence was defined as 2 rises in prostate-specific antigen (PSA) of ≥ 0.2 ng/mL above nadir. Internal gold fiducials were used for the tracking of tumor motion during SBRT. The prescription dose was 36 Gy in 6 fractions for all patients. Toxicity was scored according to the CTCAE v4.0. Results: Between July 2011 and November 2017, 12 patients were treated with SBRT for prostatic bed recurrence with a median follow-up of 34.2 (range, 3.5-64.4) months. Isolated non-metastatic recurrence in the prostatic bed was seen at MRI and PET imaging. Two patients were treated with 6 months androgen deprivation therapy (ADT) concomitant with re-irradiation. The median planning target volume was 4.5 cm3 (range, 1.2-13.3). A PSA decrease after SBRT was found in 10 (83%) patients. The 1 and 2 years biochemical recurrence-free survival rates were 79 and 56%, respectively. Biochemical recurrence was observed for 6 patients (50%) after a median time of 18 (4-42) months. Toxicity showed: 3 patients (25%) with grade 1 cystitis and 1 patient (8%) with acute grade 2 proctitis at 4 months. One patient (13%) had grade 1 cystitis at 12 months. Conclusion: Re-irradiation for local recurrence in the prostatic bed using Cyberknife® after surgery and salvage or adjuvant EBRT is well-tolerated and associated with 2 years biochemical recurrence-free survival rates of 56%. Longer follow-up and larger series are necessary.

REGOSARC: Regorafenib versus placebo in doxorubicin-refractory soft-tissue sarcoma-A quality-adjusted time without symptoms of progression or toxicity analysis.

BACKGROUND: In a placebo-controlled, randomized phase 2 trial (ClinicalTrials.gov identifier NCT01900743), regorafenib improved progression-free survival (PFS) for patients with doxorubicin-pretreated advanced nonadipocytic sarcoma. A quality-adjusted time without symptoms of progression or toxicity (Q-TWiST) post hoc exploratory analysis was applied to provide an integrated measure of its clinical benefit. METHODS: In the base-case analysis, each patient's overall survival (OS) was partitioned into 3 mutually exclusive health states: the time with a grade 3 or 4 adverse event (TOX), the time without symptoms of disease or grade 3 or 4 toxicity from treatment, and the time after tumor progression or relapse. The time spent in each state was weighted with a health-state utility associated with that state and was summed to calculate the Q-TWiST. The stability of the base-case analysis was explored with several sensitivity analyses. RESULTS: In nonadipocytic sarcoma, the PFS was (4.0 months [2.6-5.5 months] with regorafenib vs 1.0 month [0.9-1.8 months] with a placebo; hazard ratio, 0.36 [0.25-0.53]; P < .0001); the OS was 13.4 months (8.6-17.3 months) with regorafenib and 9.0 months (6.8-12.5 months) with a placebo (hazard ratio, 0.67 [0.44-1.02]). With the classic definition of TOX (including all grade 3 and 4 clinical adverse events), the Q-TWiSTs were 8.0 months (7.0-9.0 months) with regorafenib and 5.7 months (4.9-6.4 months) with a placebo (P < .001). CONCLUSIONS: For patients with doxorubicin-pretreated soft-tissue sarcoma, regorafenib significantly improved quality-adjusted survival in comparison with a placebo. Cancer 2017;123:2294-2302. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.