Outcomes of non-angiosarcoma radiation-associated soft tissue sarcomas of the chest.

BACKGROUND: Radiation-associated soft tissue sarcomas (RA-STS) are rare complications of patients receiving radiation therapy (RT) and are generally associated with a poor prognosis. Most of the literature surrounding RA-STS of the chest is centered on angiosarcoma. Therefore, we aim to document the management and outcome of patients with non-angiosarcoma RA-STS of the chest. METHODS: We reviewed 17 patients (all female, median age 65 years) diagnosed with RA-STS. The most common primary malignancy was breast carcinoma (n = 15), with a median RT dose of 57.9 Gy. All patients underwent surgical resection; five patients (29%) received radiotherapy; and five patients (29%) received peri-operative chemotherapy. RESULTS: The 5-year local recurrence and metastatic-free survival were 61% and 60%, while the 5-year disease-specific survival was 53%. Local recurrence was associated with death due to disease (HR 9.06, p = 0.01). Complications occurred in nine of patients, most commonly due to a wound complication (n = 7). At the most recent follow-up, the median Musculoskeletal Tumor Society Score was 63%. CONCLUSION: RA-STS involving the chest wall are aggressive tumors with a high risk of local relapse and death due to disease. Local recurrence was associated with death due to disease; as such, we recommend aggressive surgical management with evaluation for adjuvant therapies.

The Role of an Integrated Multidisciplinary Clinic in the Management of Patients with Cutaneous Lymphoma.

The clinical benefit of a multidisciplinary clinic practice model has been well described in a variety of medical specialties and cancer types. It proves particularly valuable when an integrated team is needed to optimally manage patients with rare or complex neoplasms. However, the ideal implementation of an integrated multidisciplinary care program for translational research and education has not been well reported. Herein, we propose how a multimodality cutaneous lymphoma (CL) clinic model can optimally manage CL patients. We offer our perspective on this model as an efficient means for delivering patient care, a continuing education resource for referring physicians, a conduit for translational and clinical research, and an educational tool for medical students, house staff, and fellows.

Improving intra-fractional target position accuracy using a 3D surface surrogate for left breast irradiation using the respiratory-gated deep-inspiration breath-hold technique.

PURPOSE: To evaluate the use of 3D optical surface imaging as a surrogate for respiratory gated deep-inspiration breath-hold (DIBH) for left breast irradiation. MATERIAL AND METHODS: Patients with left-sided breast cancer treated with lumpectomy or mastectomy were selected as candidates for DIBH treatment for their external beam radiation therapy. Treatment plans were created on both free breathing (FB) and DIBH computed tomography (CT) simulation scans to determine dosimetric benefits from DIBH. The Real-time Position Management (RPM) system was used to acquire patient's breathing trace during DIBH CT acquisition and treatment delivery. The reference 3D surface models from FB and DIBH CT scans were generated and transferred to the "AlignRT" system for patient positioning and real-time treatment monitoring. MV Cine images were acquired during treatment for each beam as quality assurance for intra-fractional position verification. The chest wall excursions measured on these images were used to define the actual target position during treatment, and to investigate the accuracy and reproducibility of RPM and AlignRT. RESULTS: Reduction in heart dose can be achieved using DIBH for left breast/chest wall radiation. RPM was shown to have inferior correlation with the actual target position, as determined by the MV Cine imaging. Therefore, RPM alone may not be an adequate surrogate in defining the breath-hold level. Alternatively, the AlignRT surface imaging demonstrated a superior correlation with the actual target positioning during DIBH. Both the vertical and magnitude real-time deltas (RTDs) reported by AlignRT can be used as the gating parameter, with a recommended threshold of ±3 mm and 5 mm, respectively. CONCLUSION: The RPM system alone may not be sufficient for the required level of accuracy in left-sided breast/CW DIBH treatments. The 3D surface imaging can be used to ensure patient setup and monitor inter- and intra- fractional motions. Furthermore, the target position accuracy during DIBH treatment can be improved by AlignRT as a superior surrogate, in addition to the RPM system.

The B55α subunit of PP2A drives a p53-dependent metabolic adaptation to glutamine deprivation.

Glutamine is an essential nutrient for cancer cell survival and proliferation, yet the signaling pathways that sense glutamine levels remain uncharacterized. Here, we report that the protein phosphatase 2A (PP2A)-associated protein, α4, plays a conserved role in glutamine sensing. α4 promotes assembly of an adaptive PP2A complex containing the B55α regulatory subunit via providing the catalytic subunit upon glutamine deprivation. Moreover, B55α is specifically induced upon glutamine deprivation in a ROS-dependent manner to activate p53 and promote cell survival. B55α activates p53 through direct interaction and dephosphorylation of EDD, a negative regulator of p53. Importantly, the B55α-EDD-p53 pathway is essential for cancer cell survival and tumor growth under low glutamine conditions in vitro and in vivo. This study delineates a previously unidentified signaling pathway that senses glutamine levels as well as provides important evidence that protein phosphatase complexes are actively involved in signal transduction.