Mayr, Nina A.

Computations of heterogeneity dose parameters in GRID therapy remain challenging in many treatment planning systems (TPS). To address this difficulty, we developed reference dose tables for a standard GRID collimator and validate their accuracy. The .decimal Inc. GRID collimator was implemented within the Eclipse TPS. The accuracy of the dose calculation was confirmed in the commissioning process. Representative sets of simulated ellipsoidal tumours ranging from 6–20 cm in diameter at a 3-cm depth; 16-cm ellipsoidal tumours at 3, 6, and 10 cm in depth were studied. All were treated with 6MV photons to a 20 Gy prescription dose at the tumour center. From these, the GRID therapy dosimetric parameters (previously recommended by the Radiosurgery Society white paper) were derived. Differences in D5 through D95 and EUD between different tumour sizes at the same depth were within 5% of the prescription dose. PVDR from profile measurements at the tumour center differed from D10/D90, but D10/D90 variations for the same tumour depths were within 11%. Three approximation equations were developed for calculating EUDs of different prescription doses for three radiosensitivity levels for 3-cm deep tumours. Dosimetric parameters were consistent and predictable across tumour sizes and depths. Our study results support the use of the developed tables as a reference tool for GRID therapy.

PURPOSE To develop recommendations for management of patients with breast cancer (BC) with germline mutations in BC susceptibility genes. METHODS The American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology convened an Expert Panel to develop recommendations based on a systematic review of the literature and a formal consensus process. RESULTS Fifty-eight articles met eligibility criteria and formed the evidentiary basis for the local therapy recommendations; six randomized controlled trials of systemic therapy met eligibility criteria. RECOMMENDATIONS Patients with newly diagnosed BC and BRCA1/ 2 mutations may be considered for breast-conserving therapy (BCT), with local control of the index cancer similar to that of noncarriers. The significant risk of a contralateral BC (CBC), especially in young women, and the higher risk of new cancers in the ipsilateral breast warrant discussion of bilateral mastectomy. Patients with mutations in moderate-risk genes should be offered BCT. For women with mutations in BRCA1/ 2 or moderate-penetrance genes who are eligible for mastectomy, nipple-sparing mastectomy is a reasonable approach. There is no evidence of increased toxicity or CBC events from radiation exposure in BRCA1/ 2 carriers. Radiation therapy should not be withheld in ATM carriers. For patients with germline TP53 mutations, mastectomy is advised; radiation therapy is contraindicated except in those with significant risk of locoregional recurrence. Platinum agents are recommended versus taxanes to treat advanced BC in BRCA carriers. In the adjuvant/neoadjuvant setting, data do not support the routine addition of platinum to anthracycline- and taxane-based chemotherapy. Poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and talazoparib) are preferable to nonplatinum single-agent chemotherapy for treatment of advanced BC in BRCA1/ 2 carriers. Data are insufficient to recommend PARP inhibitor use in the early setting or in moderate-penetrance carriers. Additional information available at www.asco.org/breast-cancer-guidelines .