Jessika Contreras

The world’s first single-room proton therapy facility: Two-year experience

PURPOSE This is a review of our 2-year experience with the first single-gantry proton therapy (PT) system. METHODS AND MATERIALS All patients were consented to participate on an institutional review board-approved prospective patient registry between December 2013 and December 2015. PT was delivered in a single-room facility using a synchrocyclotron with proton beam energy of 250 MeV. The dataset was interrogated for demographics, diagnosis, treatment modality, and clinical trial involvement. Cases were classified as simple or complex based on fields used and immobilization. The volume of photon patients treated in our department was collected between January 2011 and December 2015 to evaluate the impact of PT on our photon patient volume. RESULTS A total of 278 patients were treated with PT, including 228 (82%) adults and 50 (18%) pediatric cases. PT patients traveled a mean distance of 83.3 miles compared with 47.4 miles for photon patients queried in 2015. Rationale for treatment included reirradiation (20%), involvement in prospective clinical trial (14%), and proximity to critical structures to maximally spare organs at risk (66%). Forty patients were enrolled on 5 adult and 3 pediatric prospective clinical trials. The most common histologies treated were glioma (27%) and non-small cell lung cancer (18%) in adults, and medulloblastoma (22%) and low-grade glioma (24%) in pediatric patients. Prostate cancer composed 6% of PT. Complex cases composed 45% of our volume. Our photon patient volume increased yearly between 2011 and 2015, with 2780 patients completing photon treatment in 2011 and 3385 patients in 2015. PT composed 4% of overall patients treated with external beam radiation. CONCLUSIONS The installation of our single-gantry proton facility has expanded the treatment options within our cancer center, helping to increase the number of patients we see. Patients travel from twice as far away to receive this treatment, many for typical PT indications such as pediatrics or to participate in prospective clinical trials.

Cardiac dose is associated with immunosuppression and poor survival in locally advanced non-small cell lung cancer

PURPOSE Studies have associated increased radiation therapy (RT) heart dose with cardiac toxicity. Others have correlated RT-related immunosuppression with worsened survival. Given the large vascular volumes irradiated during locally advanced non-small cell lung cancer (LA-NSCLC) treatment, we hypothesized an association between increased heart dose and immunosuppression. METHODS We identified 400 LA-NSCLC patients treated with definitive RT ± chemotherapy between 2001 and 2016. Absolute lymphocyte counts (ALC), absolute neutrophil counts (ANC), and neutrophil-to-lymphocyte ratio (NLR = ANC/ALC) were analyzed pre-RT, during RT, and post-RT. Multivariable analysis (MVA) was performed to correlate Clinical factors with both hematologic toxicity and overall survival. An upper tertile threshold to increase specificity of NLR was chosen to dichotomize continuous hematologic variables. RESULTS Median follow up was 17 months (range 0.2-174 months) in all patients and 46 months (range 0.2-161 months) in survivors. A total of 94% of patients had stage III disease and 77% received concurrent chemo radiation. Two-year overall survival (OS), freedom from local recurrence (FFLR), and freedom from distant metastases (FFDM) was 42%, 60% and 45%, respectively. Median survival was 18 months. On MVA for OS (n = 207), male gender (Hazard Ratio [HR] 1.7; 95% CI 1.2-2.3), RT alone (HR 2.1; 95% CI 1.9-4.0), the percentage of heart receiving ≥50 Gy (V50) (HR 1.02; 95% CI 1.01-1.03), and higher NLR at 4 months (HR 1.02, 95% CI 1.01-1.03) were associated with reduced OS. ALC nadir was not associated with treatment outcomes. NLR >10.5 was associated with decreased OS (p < 0.001) and decreased FFDM (p = 0.04). On MVA evaluating factors associated with hematological toxicity (n = 247), adjuvant chemotherapy (HR 2.6; 95% CI 1.3-5.0; p = 0.006), RT alone (HR 3.6; 95% CI 1.1-12; p = 0.04), and heart V50 >25% (HR 2.0; 95% CI 1.1-3.5; p = 0.02) were associated with a NLR >10.5 4 months post-RT. CONCLUSION RT related immunosuppression is associated with worse patient outcomes, and may represent a source of increased mortality beyond cardiac toxicity alone.

Stereotactic MR-guided Online Adaptive Radiation Therapy (SMART) for Ultra-Central Thorax Malignancies: Results of a Phase I Trial

Purpose Stereotactic body radiation therapy (SBRT) is an effective treatment for oligometastatic or unresectable primary malignancies, although target proximity to organs at risk (OARs) within the ultracentral thorax (UCT) limits safe delivery of an ablative dose. Stereotactic magnetic resonance (MR)–guided online adaptive radiation therapy (SMART) may improve the therapeutic ratio using reoptimization to account for daily variation in target and OAR anatomy. This study assessed the feasibility of UCT SMART and characterized dosimetric and clinical outcomes in patients treated for UCT lesions on a prospective phase 1 trial. Methods and Materials Five patients with oligometastatic (n = 4) or unresectable primary (n = 1) UCT malignancies underwent SMART. Initial plans prescribed 50 Gy in 5 fractions with goal 95% planning target volume (PTV) coverage by 95% of prescription, subject to strict OAR constraints. Daily real-time online adaptive plans were created as needed to preserve hard OAR constraints, escalate PTV dose, or both, based on daily setup MR image set anatomy. Treatment times, patient outcomes, and dosimetric comparisons were prospectively recorded. Results All initial and daily adaptive plans met strict OAR constraints based on simulation and daily setup MR imaging anatomy, respectively. Four of the 5 patients received ≥1 adapted fraction. Ten of the 25 total delivered fractions were adapted. A total of 30% of plan adaptations were performed to improve PTV coverage; 70% were for reversal of ≥1 OAR violation. Local control by Response Evaluation Criteria in Solid Tumors was 100% at 3 and 6 months. No grade ≥3 acute (within 6 months of radiation completion) treatment-related toxicities were identified. Conclusions SMART may allow PTV coverage improvement and/or OAR sparing compared with nonadaptive SBRT and may widen the therapeutic index of UCT SBRT. In this small prospective cohort, we found that SMART was clinically deliverable to 100% of patients, although treatment delivery times surpassed our predefined, timing-based feasibility endpoint. This technique is well tolerated, offering excellent local control with no identified acute grade ≥3 toxicity.

Magnetic Resonance Image-Guided Radiotherapy (MRIgRT): A 4.5-Year Clinical Experience

AIMS Magnetic resonance image-guided radiotherapy (MRIgRT) has been clinically implemented since 2014. This technology offers improved soft-tissue visualisation, daily imaging, and intra-fraction real-time imaging without added radiation exposure, and the opportunity for adaptive radiotherapy (ART) to adjust for anatomical changes. Here we share the longest single-institution experience with MRIgRT, focusing on trends and changes in use over the past 4.5 years. MATERIALS AND METHODS We analysed clinical information, including patient demographics, treatment dates, disease sites, dose/fractionation, and clinical trial enrolment for all patients treated at our institution using MRIgRT on a commercially available, integrated 0.35 T MRI, tri-cobalt-60 device from 2014 to 2018. For each patient, factors including disease site, clinical rationale for MRIgRT use, use of ART, and proportion of fractions adapted were summated and compared between individual years of use (2014-2018) to identify shifts in institutional practice patterns. RESULTS Six hundred and forty-two patients were treated with 666 unique treatment courses using MRIgRT at our institution between 2014 and 2018. Breast cancer was the most common disease, with use of cine MRI gating being a particularly important indication, followed by abdominal sites, where the need for cine gating and use of ART drove MRIgRT use. One hundred and ninety patients were treated using ART in 1550 fractions, 67.6% (1050) of which were adapted. ART was primarily used in cancers of the abdomen. Over time, breast and gastrointestinal cancers became increasingly dominant for MRIgRT use, hypofractionated treatment courses became more popular, and gastrointestinal cancers became the principal focus of ART. DISCUSSION MRIgRT is widely applicable within the field of radiation oncology and new clinical uses continue to emerge. At our institution to date, applications such as ART for gastrointestinal cancers and accelerated partial breast irradiation (APBI) for breast cancer have become dominant indications, although this is likely to continue to evolve.

Palliative radiation therapy (RT) for prostate cancer patients with bone metastases at diagnosis: A hospital-based analysis of patterns of care, RT fractionation scheme, and overall survival

Prostate cancer (PCa) is one of the most common malignancies associated with bone metastases, and palliative radiation therapy (RT) is an effective treatment option. A total of 2641 patients were identified with PCa and bone metastases at diagnosis from 2010 to 2014 in the NCDB. Fractionation scheme was designated as short course ([SC‐RT]: 8 Gy in 1 fraction and 20 Gy in 5 fractions) vs long course ([LC‐RT]: 30 Gy in 10 fractions and 37.5 Gy in 15 fractions). Patient characteristics were correlated with fractionation scheme using logistic regression. Overall survival was analyzed using the Kaplan‐Meier method, log‐rank test, Cox proportional hazards models, and propensity score‐matched analyses. A total of 2255 (85.4%) patients were included in the LC‐RT group and 386 (14.6%) patients in the SC‐RT group. SC‐RT was more common in patients over 75 years age (odds ratio [OR]: 1.70, 95% confidence interval [CI] 1.32‐2.20), treatment at an academic center (OR: 1.76, 1.20‐2.57), living greater than 15 miles distance to treatment facility (OR: 1.38, 1.05‐1.83), treatment to the rib (OR: 2.99, 1.36‐6.60), and in 2014 (OR: 1.73, 1.19‐2.51). RT to the spine was more commonly long course (P < .0001). In the propensity‐matched cohort, LC‐RT was associated with improved OS (P < .0001), but no OS difference was observed between 37.5 Gy and either 8 Gy in one fraction or 20 Gy in 5 fractions (P > .5). LC‐RT remains the most common treatment fractionation scheme for palliative bone metastases in PCa patients. Use of palliative SC‐RT is increasing, particularly in more recent years, for older patients, treatment at academic centers, and with increasing distance from a treatment center.