Biological optimization for mediastinal lymphoma radiotherapy - a preliminary study.

Purpose: In current radiotherapy (RT) planning and delivery, population-based dose-volume constraints are used to limit the risk of toxicity from incidental irradiation of organs at risks (OARs). However, weighing tradeoffs between target coverage and doses to OARs (or prioritizing different OARs) in a quantitative way for each patient is challenging. We introduce a novel RT planning approach for patients with mediastinal Hodgkin lymphoma (HL) that aims to maximize overall outcome for each patient by optimizing on tumor control and mortality from late effects simultaneously.Material and Methods: We retrospectively analyzed 34 HL patients treated with conformal RT (3DCRT). We used published data to model recurrence and radiation-induced mortality from coronary heart disease and secondary lung and breast cancers. Patient-specific doses to the heart, lung, breast, and target were incorporated in the models as well as age, sex, and cardiac risk factors (CRFs). A preliminary plan of candidate beams was created for each patient in a commercial treatment planning system. From these candidate beams, outcome-optimized (O-OPT) plans for each patient were created with an in-house optimization code that minimized the individual risk of recurrence and mortality from late effects. O-OPT plans were compared to VMAT plans and clinical 3DCRT plans.Results: O-OPT plans generally had the lowest risk, followed by the clinical 3DCRT plans, then the VMAT plans with the highest risk with median (maximum) total risk values of 4.9 (11.1), 5.1 (17.7), and 7.6 (20.3)%, respectively (no CRFs). Compared to clinical 3DCRT plans, O-OPT planning reduced the total risk by at least 1% for 9/34 cases assuming no CRFs and 11/34 cases assuming presence of CRFs.Conclusions: We developed an individualized, outcome-optimized planning technique for HL. Some of the resulting plans were substantially different from clinical plans. The results varied depending on how risk models were defined or prioritized.

Trends in utilization of hypofractionated whole breast irradiation (HF-WBI) in triple negative breast cancer (TNBC): a national cancer database (NCDB) analysis.

PURPOSE: We sought to identify trends over time with respect to the use of hypofractionated whole breast irradiation (HF-WBI) in women with triple negative breast cancer (TNBC) in the national cancer database (NCDB). METHODS: Trends in utilization of HF-WBI in women diagnosed with T1-2N0 TNBC in the NCDB between 2008 and 2013 were analyzed. Case-matched luminal A women were used for comparison. Variables included age, race, year of diagnosis, insurance status, income quartile, receipt of neoadjuvant chemotherapy, and institution (academic vs. community). Chi square, logistic regression, and multivariate analysis was performed. RESULTS: Utilization of HF-WBI among the 53,269 TNBC women identified steadily increased from 4.7% in 2008 to 14.0% in 2013 for women with TNBC compared to luminal A cancer whose utilization increased from 7.3 to 23.3% over the same time frame (p < 0.001). On univariate analysis, HF-WBI was associated with increasing age (p < 0.001), Medicare insurance (p < 0.001), race (p = 0.041), diagnosis after 2011 (p < 0.001), higher income quartile (p < 0.001), and treatment at academic institutions (p < 0.001). On multivariate analysis, age (p < 0.001, OR 1.038 per year), income quartile (p = 0.002, OR 1.061 per increase in quartile), treatment at an academic institution (p < 0.001, OR 1.78) significantly increased use of HF-WBI. CONCLUSIONS: Treatment at an academic center and year of diagnosis were most correlated with increased HF-WBI in T1-2N0 TNBC women in the NCDB from 2008 to 2013, followed by increasing age and income. Only 14% of T1-2N0 TNBC women received HF-WBI in 2013. Focus on increased utilization is needed for non-academic centers, lower income, and younger women.

Recent advances in radiation oncology: multimodal targeting of high risk and recurrent prostate cancer.

PURPOSE OF REVIEW: The overview summarizes recent developments in radiation oncology for high risk and recurrent prostate cancer. RECENT FINDINGS: A number of well known phase III prostate hypofractionated radiation therapy (HFxRT) trials were finally published with long-term follow-ups. These trials demonstrate patterns of equivalent tumor control with several showing worse toxicity rates. The ASCENDE-RT randomized trial demonstrated the superiority of brachytherapy boost in intermediate and high-risk prostate cancer. Important randomized trials show a clear benefit to androgen deprivation therapy (ADT) in both intermediate-risk prostate cancer and postprostatectomy patients with rising PSA. Finally, the first randomized trial of metastasis-directed therapy showed a delay in time to ADT and biochemical failures in oligometastatic prostate cancer. SUMMARY: The use of brachytherapy boost in high-risk disease and ADT in locally recurrent cancer after prostatectomy are practice changing given the magnitude of benefit seen in the randomized trials. The benefit of metastasis-directed therapy in oligometastatic prostate cancer must be validated in a larger randomized trial. However, hypofractionated radiation therapy requires further long-term follow-up so that late toxicity risk can be accurately assessed before it becomes a standard of care in prostate cancer.

Prognostic models for patients with brain metastases after stereotactic radiosurgery with or without whole brain radiotherapy: a validation study.

PURPOSE/OBJECTIVE(S): To compare the performance of five prognostic models [RTOG recursive partitioning analysis (RPA), Score Index for Radiosurgery in Brain Metastases (SIR), Barnholtz-Sloan-Kattan nomogram (BSKN), diagnosis-specific Graded Prognostic Assessment (dsGPA), and Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA)] against actual survival in patients with brain metastases treated with SRS +/- WBRT. MATERIALS/METHODS: 100 consecutive patients treated with SRS +/- WBRT between January 2006 and July 2012 were retrospectively analyzed. Patients were binned according to 33 percentiles of the predicted survival distribution for the BSKN and dsGPA models to compare with LungmolGPA, RPA and SIR. Pearson's correlation coefficients between predicted and observed survival were estimated to quantify the proportion of variance in observed survival. RESULTS: Median survival for the entire cohort was 13.5 months, with predicted vs actual MS by BSKN, SIR, dsGPA, RPA, adenocarcinoma Lung-molGPA, and nonadenocarcinoma Lung-molGPA was 3.8 vs 15.6 months, 7 vs 13.5 months, 9.4 vs 13.5 months, 10.3 vs 13.5 months, 13.7 vs 13.7 months, and 9.8 vs 9.7 months, respectively. The BSKN model and adenocarcinoma LungmolGPA created three groups with a statistically significantly different MS (p = 0.002 and p = 0.01, respectively). CONCLUSION: All models under-predicted MS and only the BSKN and Lung-molGPA model stratified patients into three risk groups with statistically significant actual MS. The prognostic groupings of the adenocarcinoma Lung-molGPA group was the best predictor of MS, and showed that we are making improvements in our prognostic ability by utilizing molecular information that is much more widely available in the current treatment era.

Expression of angiopoietin-TIE system components in angiosarcoma.

Angiosarcoma is an aggressive malignancy of endothelial differentiation. Potential roles of the endothelial angiopoietin-tunica interna endothelial cell kinase (ANGPT-TIE) system in angiosarcoma diagnosis, pathogenesis, prognosis and treatment are undefined. To examine the expression and prognostic significance of angiopoietin-1, angiopoietin-2, TIE1 and TEK (TIE2) proteins in angiosarcoma, we immunohistochemically evaluated clinically annotated human angiosarcoma samples. Correlations of protein expression with overall survival and pathological features were explored. The cohort included 51 patients diagnosed with angiosarcoma at the age of 30-86 years (median 67). The 5-year overall survival was 45% with a median of 26 months. Moderate to strong expression of angiopoietin-1, TIE1 and TEK (TIE2) was identified in the majority of angiosarcomas and moderate to strong expression of angiopoietin-2 was observed in 42% of angiosarcomas. Increased angiopoietin-1 expression correlated with improved survival. Non-significant trends toward longer survival were also observed with increased TIE1 and TEK (TIE2) expression. Increased expression of angiopoietin-2, TIE1 and TEK (TIE2) was associated with vasoformative architecture. No differences in expression of these proteins were observed when patients were segregated by age, gender, presence or absence of metastases at diagnosis, primary tumor location, radiation association or the presence of necrosis. We conclude that components of the ANGPT-TIE system are commonly expressed in angiosarcomas. Reduced expression of these proteins is associated with non-vasoformative and clinically more aggressive lesions.

Clinical outcomes and toxicities of 100 patients treated with proton therapy for chordoma on the proton collaborative group prospective registry.

BACKGROUND: We present efficacy and toxicity outcomes among patients with chordoma treated on the Proton Collaborative Group prospective registry. METHODS: Consecutive chordoma patients treated between 2010-2018 were evaluated. One hundred fifty patients were identified, 100 had adequate follow-up information. Locations included base of skull (61%), spine (23%), and sacrum (16%). Patients had a performance status of ECOG 0-1 (82%) and median age of 58 years. Eighty-five percent of patients underwent surgical resection. The median proton RT dose was 74 Gy (RBE) (range 21-86 Gy (RBE)) using passive scatter proton RT (PS-PBT) (13%), uniform scanning proton RT (US-PBT) (54%) and pencil beam scanning proton RT (PBS-PBT) (33%). Rates of local control (LC), progression-free survival (PFS), overall survival (OS) and acute and late toxicities were assessed. RESULTS: 2/3-year LC, PFS, and OS rates are 97%/94%, 89%/74%, and 89%/83%, respectively. LC did not differ based on surgical resection (p = 0.61), though this is likely limited by most patients having undergone a prior resection. Eight patients experienced acute grade 3 toxicities, most commonly pain (n = 3), radiation dermatitis (n = 2), fatigue (n = 1), insomnia (n = 1) and dizziness (n = 1). No grade ≥ 4 acute toxicities were reported. No grade ≥ 3 late toxicities were reported, and most common grade 2 toxicities were fatigue (n = 5), headache (n = 2), CNS necrosis (n = 1), and pain (n = 1). CONCLUSIONS: In our series, PBT achieved excellent safety and efficacy outcomes with very low rates of treatment failure. CNS necrosis is exceedingly low (<1%) despite the high doses of PBT delivered. Further maturation of data and larger patient numbers are necessary to optimize therapy in chordoma.

Patterns of Failure in Triple Negative Breast Cancer Patients in an Urban, Predominately Black Population.

Triple negative breast cancers (TNBC) behave more aggressively than hormone-receptor positive breast cancers. They are also known preferentially to affect young black women, often leading to poorer outcomes compared with those for white women. We sought to evaluate the comprehensive patterns of failure associated with treatment for TNBC at an urban institution with a predominantly black population and to assess the impact of social determinants of health on treatment failure. A retrospective review of TNBC patients treated from 2005 to 2015 was conducted. Detailed patient, tumor, and treatment characteristics and information on patterns of failure were included. With a median follow-up of 46 months, 32 (16%) documented failures occurred. Locoregional failures comprised 84% of failure patterns whether isolated or in combination with distant failure. Treatment failure was associated with insurance type and smoking status, as well as several tumor characteristics. On multivariate analysis, pathologic nodal staging was the most significant predictor of treatment failure. In contrast to previous studies, we found that black women had higher overall survival than white women, but race was not associated with differences in recurrence patterns or with likelihood of treatment failure. Regardless of race, of the patients who recurred, 53% failed in distant and locoregional sites simultaneously, with an additional 34% failing locally only. These results highlight the need for aggressive local therapies in high-risk patients and suggest a need for improved follow-up focusing on detecting locoregional failures. Multidisciplinary care is essential in the management of these patients at time of failure.

Perceptions and Patterns in Academic Publishing: A Survey of United States Residents in Radiation Oncology.

PURPOSE: We aimed to assess perceptions of, and training regarding, the publishing process among US radiation oncology (RO) residents, focusing on awareness and understanding of criteria for selecting appropriate and legitimate peer-reviewed journals for academic publishing. The growing challenge of predatory publication in the broader scientific realm and its relevancy to resident training is also briefly discussed. METHODS AND MATERIALS: A survey was opened to residents of all Accreditation Council for Graduate Medical Education-accredited RO programs in the United States, focusing on 3 categories: (1) demographics; (2) submission, peer review, and publication of academic research; and (3) subjective ranking of factors for choosing an appropriate publisher/journal. Results were stratified by level of training and number of publications. RESULTS: Overall, 150 of 690 residents (19.8%) responded, with a 98% (147 of 150) completion rate. Twenty of 150 residents (13.3%) reported formal training in manuscript preparation and choosing academic journals. Only 3.4% of residents reported departmental guidelines regarding publication in "predatory" journals; 57.7% were unsure. The 3 most important factors influencing publisher and journal choice were impact factor (ranked first for 59.0%), whether a journal is found in a major index (ranked first for 18.0%), and association with a reputable organization (ranked first for 17.0%). Importance of impact factor increased with number of publications (50% with 0 publications, 48.3% with 1-5, 63.9% with 5-10, 76.2% with 10-15, and 70.6% with >15). Cost considerations influenced journal choice at least once for 79 (52.7%) residents. CONCLUSIONS: Impact factor was the most important consideration for residents when choosing an appropriate publisher, with increased emphasis with increasing number of publications. A minority had formal training in choosing appropriate academic journals and knowing how to identify so-called predatory journals or were aware if their department has proscriptions regarding publication in such journals. Additional emphasis on formal training for RO residents in manuscript preparation and choosing academic journals is warranted.

The Utility of PET/Computed Tomography for Radiation Oncology Planning, Surveillance, and Prognosis Prediction of Gastrointestinal Tumors.

At present, the strongest evidence for the use of PET/computed tomography (CT) in gastrointestinal (GI) malignancies is to rule out distant metastatic disease at diagnosis, radiation treatment planning for anal malignancies, and disease recurrence monitoring in colorectal and anal malignancies. Use of PET/CT for GI malignancies continues to evolve over time, with new studies evaluating prognostic abilities of PET/CT and with increasing sensitivity and spatial resolution of more modern PET/CT scanners. The authors encourage future applications and prospective evaluation of the use of PET/CT in the staging, prognostication, and recurrence prediction for GI malignancies.

Insurance Status is an Independent Predictor of Overall Survival in Patients With Stage III Non-small-cell Lung Cancer Treated With Curative Intent.

INTRODUCTION: Population studies suggest an impact of insurance status on oncologic outcomes. We sought to explore this in a large single-institution cohort of patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively analyzed 342 consecutive patients (January 2000 to December 2013) curatively treated for stage III NSCLC. Patients were categorized by insurance status as uninsured (U), Medicare/Medicaid + Veterans Affairs (M/M + VA), or Private (P). The χ2 test was utilized to compare categorical variables. The Kaplan-Meier approach and the Cox proportional hazard models were used to analyze overall survival (OS) and freedom from recurrence (FFR). RESULTS: Compared with M/M + VA patients, P insurance patients were more likely to be younger (P < .001), married (P < .001), Caucasian (P = .001), reside in higher median income zip codes (P < .001), have higher performance status (P < .001), and undergo consolidation chemotherapy (P < .001) and trimodality therapy (P < .001). Diagnosis to treatment was delayed > 30 days in U (67.3%), M/M + VA (68.1%), and P (52.6%) patients (P = .017). Compared with the M/M + VA and U cohorts, P insurance patients had improved OS (median/5-year: 30.7 months/34.2%, 19 months/17%, and 16.9 months/3.8%; P < .001) and FFR (median/5-year: 18.4 months/27.3%, 15.2 months/23.2%, and 11.4 months/4.8%; P = .012), respectively. On multivariate analysis, insurance status was an independent predictor for OS (P = .017) but not FFR. CONCLUSION: Compared with U or M/M + VA patients, P insurance patients with stage III NSCLC were more likely to be optimally diagnosed and treated, resulting in a doubling of median OS for P versus U patients. Improved access to affordable health insurance is critical to combat inequities in access to care and has potential for improvements in cancer outcomes.

A Phase II Study Evaluating Bone Marrow-Sparing, Image-guided Pelvic Intensity-Modulated Radiotherapy (IMRT) With Cesium-131 Brachytherapy Boost, Adjuvant Chemotherapy, and Long-Term Hormonal Ablation in Patients With High Risk, Nonmetastatic Prostate Cancer.

PURPOSE/OBJECTIVE(S): Management of localized high-risk prostate cancer remains challenging. At our institution we performed a prospective phase II study of 2 years of androgen deprivation therapy (ADT), pelvic radiation, Cesium (Cs)-131 brachytherapy boost, and adjuvant docetaxel in high risk, localized prostate cancer with a primary endpoint of 3-year disease-free survival. MATERIALS/METHODS: Acute/chronic hematologic, gastrointestinal (GI) and genitourinary (GU) toxicities were scored based on the CTCAE v3.0/RTOG-EORTC criteria, respectively. Actuarial biochemical recurrence free survival (bRFS), bRFSdisease free survival (DFS) and overall survival (OS) were calculated. Patients had a median age of 62 years (range, 45 to 82), median Gleason score 8 (74% Gleason 8-10), median PSA of 11.2 (range, 2.8 to 96), and 47% cT2-T3a stage disease. Androgen deprivation was given for 2 years, 45 Gy whole-pelvis IMRT was followed by an 85 Gy Cs-131 boost to the prostate gland, and adjuvant docetaxel was given for 4 cycles. RESULTS: In total 38 patients enrolled from 2006 to 2014, with 82% completing protocol specified treatment, and 84.2% completing 4 cycles of docetaxel. Median follow-up for the entire and alive cohorts were 44 months and 58 months (range, 3.4 to 118), respectively. Acute grade ≥2 GI and GU toxicity rates were 18.4% and 23.7%, respectively. Chronic grade ≥2 GI and GU toxicity rates were 2.6% and 2.6%, respectively. Twelve patients (31.6%) developed grade 4 hematologic toxicity, with no grade 5 toxicity. The 5-year DFS, bRFS and OS rates were 74.1%, 86.0%, and 80.3%, respectively. CONCLUSIONS: This aggressive pilot multimodal approach appears to be safe and well-tolerated, providing disease control in a significant proportion of patients with particularly high-risk prostate cancer.

Quantification of Acute Skin Toxicities in Patients With Breast Cancer Undergoing Adjuvant Proton versus Photon Radiation Therapy: A Single Institutional Experience.

PURPOSE: Acute skin toxicity in the form of radiation dermatitis (RD) or skin hyperpigmentation (SH) is a common problem experienced by patients undergoing breast irradiation. Proton radiation has been thought to deliver higher doses to skin compared with photon radiation because of differences in the physical properties between photons and protons; however, limited literature exists directly comparing toxicity outcomes. METHODS AND MATERIALS: The highest recorded grades of acute RD and SH were analyzed in 86 patients undergoing adjuvant radiation therapy to the breast with or without regional lymph nodes after lumpectomy (breast-conserving surgery) or mastectomy with either proton pencil-beam scanning (n = 39) or photon (n = 47) radiation therapy within a single institution to analyze differences in severity of acute skin reactions. For 34 of 47 photon and 33 of 39 proton patients, a "skin" contour was retroactively created in our treatment planning systems, and multiple dosimetric parameters were calculated to quantify objective radiation doses received by skin. RESULTS: On χ2 analysis, the highest reported grade of RD was significantly higher in women undergoing proton radiation compared with photon radiation; grade ≥2 RD was present in 69.2% versus 29.8% of patients receiving proton and photon therapy, respectively (P = .002). Rates of grade 3 RD were 5.1% versus 4.3% for proton versus photon radiation, respectively (P = .848). Overall, there were no significant differences in rates of SH between modalities. There were no grade 4 to 5 toxicities in either cohort. CONCLUSIONS: In a comparison with patients receiving photon radiation, a significantly higher rate of grade ≥2 RD was observed in patients undergoing proton radiation, with very low rates of grade 3 toxicity in both groups. Rates of SH did not differ significantly between modalities. Women should be counseled regarding the possibility of increased grade 2 toxicities, although this might present a dosimetric advantage for physicians when treating patients in the postmastectomy setting or when skin was involved on presentation.

Long-term biochemical outcomes using cesium-131 in prostate brachytherapy.

PURPOSE: Long-term outcomes reveal equivalent biochemical outcomes with low-dose-rate (LDR) brachytherapy (BT) compared with radical prostatectomy and external-beam radiotherapy for the management of prostate cancer. Iodine-125, the most commonly used isotope, may be associated with long-term urinary consequences. Cesium-131 (131Cs) has a higher dose rate and shorter dose delivery time, predicting a shorter duration of urinary morbidity. We report our institution's high-volume experience and the most mature data to date on outcomes with 131Cs prostate BT. METHODS AND MATERIALS: 571 men (median age: 65.38 years) with low (55%)-, intermediate (36%)-, and high-risk disease (9%) received monobrachytherapy, dual-modality, or trimodality using 131Cs at a single institution. Risk groups were defined according to the National Comprehensive Cancer Network definition. Median prescription dose for definitive LDR-BT and LDR-BT boost was 115 Gy and 70 Gy, respectively. Median initial PSA was 6.1 ng/mL (IQR: 4.6-8.7). RESULTS: Median followup time was 5 years. 5/7-year overall survival for low-, intermediate-, and high-risk patients was 96.9%/96/9%, 92.8%/89.7%, and 95.8%/87.1%, respectively (p = 0.02). 5/7-year freedom from biochemical failure for low-, intermediate-, and high-risk patients was 98.5%/96.3%, 94.1%/86.4%, and 93.2%/74.5%, respectively (p < 0.01). 5/7-year prostate cancer -specific survival was 100%/100%, 99.3%/99.3%, and 98.0%/98.0% for low-, intermediate-, and high-risk patients, respectively (p < 0.01). CONCLUSIONS: 131Cs is a viable alternative isotope for prostate brachytherapy for organ-confined disease. Long-term biochemical control and survival outcomes are excellent and on par with those attained with the use of 125I or 103Pd. This report therefore supports the continued use of 131Cs as an effective and comparable alternative isotope.

Proton Therapy Delivery and Its Clinical Application in Select Solid Tumor Malignancies.

Radiation therapy is a frequently used modality for the treatment of solid cancers. Although the mechanisms of cell kill are similar for all forms of radiation, the in vivo properties of photon and proton beams differ greatly and maybe exploited to optimize clinical outcomes. In particular, proton particles lose energy in a predictable manner as they pass through the body. This property is used clinically to control the depth at which the proton beam is terminated, and to limit radiation dose beyond the target region. This strategy can allow for substantial reductions in radiation dose to normal tissues located just beyond a tumor target. However, the degradation of proton energy in the body remains highly sensitive to tissue density. As a consequence, any changes in tissue density during the course of treatment may significantly alter proton dosimetry. Such changes may occur through alterations in body weight, respiration, or bowel filling/gas, and may result in unfavorable dose deposition. In this manuscript, we provide a detailed method for the delivery of proton therapy using both passive scatter and pencil beam scanning techniques for prostate cancer. Although the described procedure directly pertains to prostate cancer patients, the method may be adapted and applied for the treatment of virtually all solid tumors. Our aim is to equip readers with a better understanding of proton therapy delivery and outcomes in order to facilitate the appropriate integration of this modality during cancer therapy.

A Novel Prospective Study Assessing the Combination of Photodynamic Therapy and Proton Radiation Therapy: Safety and Outcomes When Treating Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma remains difficult to treat, with high failure rates despite optimal therapy. We present a novel prospective trial combining proton therapy (PT) and photodynamic therapy (PDT) and the largest-ever mesothelioma PT experience (n = 10). PDT photosensitizers included porfimer sodium (2 mg·kg-1 ; 24 h drug-light interval) or 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) (4 mg·m-2 ;48 h) with wavelengths of 630 nm to 60J·cm-2 and 665 nm to 15-45J·cm-2 , respectively. With a median age of 69 years, patients were predominantly male (90%) with epithelioid histology (100%) and stage III-IV disease (100%). PT was delivered to a median of 55.0 CGE/1.8-2.0 CGE (range 50-75 CGE) adjuvantly (n = 8) or as salvage therapy (n = 2) following extended pleurectomy/decortication (ePD)/PDT. Two-year local control was 90%, with distant and regional failure rates of 50% and 30%, respectively. All patients received chemotherapy, and four received immunotherapy. Surgical complications included atrial fibrillation (n = 3), pneumonia (n = 2), and deep vein thrombosis (n = 2). Median survival from PT completion was 19.5 months (30.3 months from diagnosis), and 1- and 2-year survival rates were 58% and 29%. No patient experienced CTCAEv4 grade ≥2 acute or late toxicity. Our prolonged survival in very advanced-stage patients compares favorably to survival for PT without PDT and photon therapy with PDT, suggesting possible spatial or systemic cooperativity and immune effect.

Quantification of global lung inflammation using volumetric 18F-FDG PET/CT parameters in locally advanced non-small-cell lung cancer patients treated with concurrent chemoradiotherapy: a comparison of photon and proton radiation therapy.

INTRODUCTION: Radiation pneumonitis is a major dose-limiting complication in thoracic radiation therapy (RT) and presents clinically in the first few months after RT. We evaluated the feasibility of quantifying pulmonary parenchymal glycolysis (PG) as a surrogate of global lung inflammation and radiation-induced pulmonary toxicity using a novel semiautomatic lung segmentation technique in non-small-cell lung cancer (NSCLC) patients and compared PG in patients treated with photon or proton RT. PATIENTS AND METHODS: We evaluated 18 consecutive locally advanced NSCLC patients who underwent pretreatment and post-treatment F-FDG PET/CT treated with definitive (median: 66.6 Gy; 1.8 Gy fractions) photon or proton RT between 2010 and 2014. Lung volume segmentation was conducted using 3D Slicer by performing simple thresholding. Pulmonary PG was calculated by summing F-FDG uptake in the whole lung. RESULTS: In nine patients treated with photon RT, significant increases in PG in both ipsilateral (mean difference: 1400±510; P=0.02) and contralateral (mean difference: 1200±450; P=0.03) lungs were noted. In nine patients treated with proton therapy, no increase in pulmonary PG was observed in either the ipsilateral (P=0.30) or contralateral lung (P=0.98). CONCLUSION: We observed a significant increase in global lung inflammation bilaterally as measured by quantification of PG. However, no significant change in global lung inflammation was noted after proton therapy. Future larger studies are needed to determine whether this difference correlates with lower risks of radiation pneumonitis in NSCLC patients treated with proton therapy.

Lymph Node Size Predicts for Asymptomatic Brain Metastases in Patients With Non-small-cell Lung Cancer at Diagnosis.

BACKGROUND: We questioned whether the National Comprehensive Cancer Network recommendations for brain magnetic resonance imaging (MRI) for patients with stage ≥ IB non-small-cell lung cancer (NSCLC) was high-yield compared with American College of Clinical Pharmacy and National Institute for Health and Care Excellence guidelines recommending stage III and above NSCLC. We present the prevalence and factors predictive of asymptomatic brain metastases at diagnosis in patients with NSCLC without extracranial metastases. MATERIALS AND METHODS: A retrospective analysis of 193 consecutive, treatment-naïve patients with NSCLC diagnosed between January 2010 and August 2015 was performed. Exclusion criteria included no brain MRI staging, symptomatic brain metastases, or stage IV based on extracranial disease. Univariate and multivariate logistic regression was performed. RESULTS: The patient characteristics include median age of 65 years (range, 36-90 years), 51% adenocarcinoma/36% squamous carcinoma, and pre-MRI stage grouping of 31% I, 22% II, 34% IIIA, and 13% IIIB. The overall prevalence of brain metastases was 5.7% (n = 11). One (2.4%) stage IA and 1 (5.6%) stage IB patient had asymptomatic brain metastases at diagnosis, both were adenocarcinomas. On univariate analysis, increasing lymph nodal stage (P = .02), lymph nodal size > 2 cm (P = .009), multi-lymph nodal N1/N2 station involvement (P = .027), and overall stage (P = .005) were associated with asymptomatic brain metastases. On multivariate analysis, increasing lymph nodal size remained significant (odds ratio, 1.545; P = .009). CONCLUSION: Our series shows a 5.7% rate of asymptomatic brain metastasis for patients with stage I to III NSCLC. Increasing lymph nodal size was the only predictor of asymptomatic brain metastases, suggesting over-utilization of MRI in early-stage disease, especially in lymph node-negative patients with NSCLC. Future efforts will explore the utility of baseline MRI in lymph node-positive stage II and all stage IIIA patients.

Combining immunotherapy with radiation therapy in thoracic oncology.

Thoracic malignancies comprise some of the most common and deadly cancers. Immunotherapies have been proven to improve survival outcomes for patients with advanced non-small cell lung cancer (NSCLC) and show great potential for patients with other thoracic malignancies. Radiation therapy (RT), an established and effective treatment for thoracic cancers, has acted synergistically with immunotherapies in preclinical studies. Ongoing clinical trials are exploring the clinical benefits of combining RT with immunotherapies and the optimal manner in which to deliver these complementary treatments.

Context for Protons as Adjunctive Therapy in Neovascular Age-Related Macular Degeneration: A Review.

In the last few years we have witnessed increasing availability of proton therapy in the United States and worldwide. As a result, proton therapy is considered as either a primary or adjunctive approach for numerous indications where conventional radiation therapy shows promise but is accompanied by toxicities. Age-related macular degeneration (AMD) remains the leading cause of adult blindness in industrialized nations, and third worldwide, following cataract and glaucoma. Current standard therapy is intravitreal injection of anti-vascular endothelial growth factor agents. While this treatment shows improvement and stabilization in visual acuity for 40% of patients, 60% still experience disease progression. These injections are costly, necessitate repeated office visits, and carry the risk of endophthalmitis. The pathophysiology underlying neovascular AMD (nAMD) underscores the need to simultaneously target multiple pathways to retain useful vision. Radiation can be antiangiogenic, anti-inflammatory, and antiproliferative. Early photon therapy clinical trials were heterogeneous, and a Cochrane review of data demonstrated usefulness in treatment of nAMD but recommended further studies. Advantages of proton therapy over photon therapy include the ability to deliver a focal dose to the target while minimizing dose to normal structures, which is enhanced by unique treatment planning software that uses fluorescein angiography to verify target location and allows conformation of dose to the irregular shape and thickness characteristic of choroidal neovascular membranes, the pathognomonic finding in nAMD. Preliminary data suggest a potential role for proton therapy in the treatment of nAMD. In this article we review previous treatments for AMD, including those with both photon and proton radiation, and recommend future directions for clinical investigations to evaluate the role of proton therapy as an adjunct to antiangiogenic therapy, the current standard of care in this challenging setting.

What Are Medical Students in the United States Learning About Radiation Oncology? Results of a Multi-Institutional Survey.

PURPOSE: The purposes of this study were to assess the exposure that medical students (MSs) have to radiation oncology (RO) during the course of their medical school career, as evidenced by 2 time points in current medical training (ie, first vs fourth year; MS1s and MS4s, respectively) and to assess the knowledge of MS1s, MS4s, and primary care physicians (PCPs) about the appropriateness of RT in cancer management in comparison with RO attendings. METHODS: We developed and beta tested an electronic survey divided into 3 parts: RO job descriptions, appropriateness of RT, and toxicities of RT. The surveys were distributed to 7 medical schools in the United States. A concordance of >90% (either yes or no) among RO attendings in an answer was necessary to determine the correct answer and to compare with other subgroups using a χ(2) test (P<.05 was significant). RESULTS: The overall response rate for ROs, MS1s, MS4s, and PCPs was 26%; n (22 + 315 + 404 + 43)/3004. RT misconceptions decreased with increasing level of training. More than 1 of 10 MSs did not believe that RT alone could cure cancer. Emergent oncologic conditions for RT (eg, spinal cord compression, superior vena cava syndrome) could not be identified by >1 of 5 respondents. Multiple nontoxicities of RT (eg, emitting low-level radiation from the treatment site) were incorrectly identified as toxicities by >1 of 5 respondents. MS4s/PCPs with an RO rotation in medical school had improved scores in all prompts. CONCLUSIONS: Although MS knowledge of general RT principles improves from the first to the fourth year, a large knowledge gap still exists between MSs, current PCPs, and ROs. Some basic misconceptions of RT persist among a minority of MSs and PCPs. We recommend implementing formal education in RO fundamentals during the core curriculum of medical school.