Search

Radiation therapy is an effective cancer treatment, although damage to healthy tissues is common. Here we analyzed cell-free, methylated DNA released from dying cells into the circulation to evaluate radiation-induced cellular damage in different tissues. To map the circulating DNA fragments to human and mouse tissues, we established sequencing-based, cell-type-specific reference DNA methylation atlases. We found that cell-type-specific DNA blocks were mostly hypomethylated and located within signature genes of cellular identity. Cell-free DNA fragments were captured from serum samples by hybridization to CpG-rich DNA panels and mapped to the DNA methylation atlases. In a mouse model, thoracic radiation-induced tissue damage was reflected by dose-dependent increases in lung endothelial and cardiomyocyte methylated DNA in serum. The analysis of serum samples from patients with breast cancer undergoing radiation treatment revealed distinct dose-dependent and tissue-specific epithelial and endothelial responses to radiation across multiple organs. Strikingly, patients treated for right-sided breast cancers also showed increased hepatocyte and liver endothelial DNA in the circulation, indicating the impact on liver tissues. Thus, changes in cell-free methylated DNA can uncover cell-type-specific effects of radiation and provide a readout of the biologically effective radiation dose received by healthy tissues.

PurposeSingle extracranial metastases from ovarian and uterine malignancies have historically been treated with surgery or conventional radiation. We report mature local control (LC), overall survival (OS), progression free survival (PFS), and toxicity for patients who completed 5-fraction stereotactic body radiation therapy (SBRT).MethodsPatients with biopsy-proven, single extracranial metastases from primary ovarian and uterine malignancies treated with 5-fraction SBRT were included. Patients were stratified based on tumor volume (small < 50 cc or large ≥ 50 cc) and dose (low dose < 35 Gy or high ≥ 35 Gy). Kaplan–Meier method was used to estimate LC, OS, and PFS.ResultsBetween July 2007 and July 2012, 20 patients underwent SBRT to a single extracranial metastasis. Primary site was divided evenly between ovarian and uterine (n = 10 each). Metastases involved the liver (30%), abdominal lymph nodes (25%), lung (20%), pelvic lymph nodes (10%), spine (10%), and extremity (5%). The median gross tumor volume (GTV) was 42.5 cc (range, 5–273 cc) and the median dose to the GTV was 35 Gy (range, 30–50 Gy). At a median follow-up of 56 months, the 5-year LC and OS estimates were 73 and 46%. When stratified by tumor volume, the 5-year LC and OS for small tumors were significantly better at 100% (p < 0.01) and 65% (p < 0.02). When stratified by dose, the 5-year LC was 87.5% with high dose and 53.6% with low dose (p = 0.035). The 5-year PFS for the entire cohort was 20%. Four patients with small metastases who had complete response remained disease free at study completion and were considered cured (median PFS > 10 years). Treatment was generally well tolerated, and only one patient experienced a late grade III musculoskeletal SBRT related toxicity.ConclusionsSBRT is a versatile, well-tolerated, and effective treatment option for single extracranial metastases from ovarian and uterine primary tumors. 35 Gy in five fractions appears to be a practical minimum effective dose. Four patients with small metastases were disease free at the study completion and considered cured. However, patients with larger metastases (≥50 cc) may require higher SBRT dosing or alternative treatments.

Introduction: Review the early experience with a single-room gantry mounted active scanning proton therapy system.Material and Methods: All patients treated with proton beam radiotherapy (PBT) were enrolled in an institutional review board-approved patient registry. Proton beam radiotherapy was delivered with a 250 MeV gantry mounted synchrocyclotron in a single-room integrated facility within the pre-existing cancer center. Demographic data, cancer diagnoses, treatment technique, and geographic patterns were obtained for all patients. Treatment plans were evaluated for mixed modality therapy. Insurance approval data was collected for all patients treated with PBT.Results: A total of 132 patients were treated with PBT between March 2018 and June 2019. The most common oncologic subsites treated included the central nervous system (22%), gastrointestinal tract (20%), and genitourinary tract (20%). The most common histologies treated included prostate adenocarcinoma (19%), non-small cell lung cancer (10%), primary CNS gliomas (8%), and esophageal cancer (8%). Rationale for PBT treatment included limitation of dose to adjacent critical organs at risk (67%), reirradiation (19%), and patient comorbidities (11%). Patients received at least one x-ray fraction delivered as prescribed (36%) or less commonly due to unplanned machine downtime (34%). Concurrent systemic therapy was administered to 57 patients (43%). Twenty-six patients (20%) were initially denied insurance coverage and required peer-to-peers (65%), written appeals (12%), secondary insurance approval (12%), and comparison x-ray to proton plans (8%) for subsequent approval. Proton beam radiotherapy approval required a median of 17 days from insurance submission.Discussion: Incorporation of PBT into our existing cancer center allowed for multidisciplinary oncologic treatment of a diverse population of patients. Insurance coverage for PBT presents as a significant hurdle and improvements are needed to provide more timely access to necessary oncologic care.

Purpose: Few definitive treatment options exist for elderly patients diagnosed with early stage breast cancer who are medically inoperable or refuse surgery. Historical data suggest very poor local control with hormone therapy alone. We examined the dosimetric feasibility of hypofractionated radiation therapy using stereotactic ablative radiotherapy (SABR) and proton beam therapy (PBT) as a means of definitive treatment for early stage breast cancer. Methods and Materials: Fifteen patients with biopsy-proven early stage breast cancer with a clinically visible tumor on preoperative computed tomography scans were identified. Gross tumor volumes were contoured and correlated with known biopsy-proven malignancy on prior imaging. Treatment margins were created on the basis of set-up uncertainty and image guidance capabilities of the three radiation modalities analyzed (3-dimensional conformal radiation therapy [3D-CRT], SABR, and PBT) to deliver a total dose of 50 Gy in 5 fractions. Dose volume histograms were analyzed and compared between treatment techniques. Results: The median planning target volume (PTV) for SABR, PBT, and 3-dimensional CRT was 11.91, 21.03, and 45.08 cm3, respectively, and were significantly different (P

Introduction: Intraoperative radiation therapy (IORT) is a minimally invasive radiation option for select patients with early stage breast cancer. This prospective, single institution, pilot study summarizes patient-reported quality of life (QoL) outcomes and clinician-reported toxicity following IORT following breast conservation therapy.Methods: Forty-nine patients were enrolled in a prospective study from 2013 until 2015 to assess QoL and toxicity following breast conservation therapy and IORT. Nine patients did not meet criteria for IORT alone on final pathology and required whole breast irradiation afterwards. These patients were evaluated separately. Validated QoL questionnaires were provided to patients at 1-week, 1-month, and subsequent 6-month intervals for 2 years. Radiation-related toxicity symptoms were evaluated by clinicians at the same time intervals. Likert scale responses were converted to continuous variables to depict patient-reported and clinician-reported outcomes.Results: Outcomes were analyzed as weighted averages of the Likert scale for each symptom. Responses for negative QoL symptoms ranged largely from 0 (none) to 2 (moderate). Responses for positive QoL symptoms ranged largely from 3 (quite a bit) to 4 (very much). Seventy-five percent of patients developed a toxicity; however, 99% of the toxicities were grades 1 and 2. All toxicities demonstrated a downward trend over time, with the exception of breast fibrosis and nodularity, which increased over time. There were no local recurrences upon 2-year follow up.Conclusion: Early stage breast cancer treated with IORT yields favorable QoL outcomes and minimal toxicity profiles with adequate short-term local control.