Acute hospitalizations after proton therapy versus intensity-modulated radiotherapy for locally advanced non-small cell lung cancer in the durvalumab era.

INTRODUCTION: It was hypothesized that use of proton beam therapy (PBT) in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiation and consolidative immune checkpoint inhibition is associated with fewer unplanned hospitalizations compared with intensity-modulated radiotherapy (IMRT). METHODS: Patients with locally advanced non-small cell lung cancer treated between October 2017 and December 2021 with concurrent chemoradiation with either IMRT or PBT ± consolidative immune checkpoint inhibition were retrospectively identified. Logistic regression was used to assess the association of radiation therapy technique with 90-day hospitalization and grade 3 (G3+) lymphopenia. Competing risk regression was used to compare G3+ pneumonitis, G3+ esophagitis, and G3+ cardiac events. Kaplan-Meier method was used for progression-free survival and overall survival. Inverse probability treatment weighting was applied to adjust for differences in PBT and IMRT groups. RESULTS: Of 316 patients, 117 (37%) received PBT and 199 (63%) received IMRT. The PBT group was older (p < .001) and had higher Charlson Comorbidity Index scores (p = .02). The PBT group received a lower mean heart dose (p < .0001), left anterior descending artery V15 Gy (p = .001), mean lung dose (p = .008), and effective dose to immune circulating cells (p < .001). On inverse probability treatment weighting analysis, PBT was associated with fewer unplanned hospitalizations (adjusted odds ratio, 0.55; 95% CI, 0.38-0.81; p = .002) and less G3+ lymphopenia (adjusted odds ratio, 0.55; 95% CI, 0.37-0.81; p = .003). There was no difference in other G3+ toxicities, progression-free survival, or overall survival. CONCLUSIONS: PBT is associated with fewer unplanned hospitalizations, lower effective dose to immune circulating cells and less G3+ lymphopenia compared with IMRT. Minimizing dose to lymphocytes may be warranted, but prospective data are needed.

A comprehensive pre-clinical treatment quality assurance program using unique spot patterns for proton pencil beam scanning FLASH radiotherapy.

BACKGROUND: Quality assurance (QA) for ultra-high dose rate (UHDR) irradiation is a crucial aspect in the emerging field of FLASH radiotherapy (FLASH-RT). This innovative treatment approach delivers radiation at UHDR, demanding careful adoption of QA protocols and procedures. A comprehensive understanding of beam properties and dosimetry consistency is vital to ensure the safe and effective delivery of FLASH-RT. PURPOSE: To develop a comprehensive pre-treatment QA program for cyclotron-based proton pencil beam scanning (PBS) FLASH-RT. Establish appropriate tolerances for QA items based on this study's outcomes and TG-224 recommendations. METHODS: A 250 MeV proton spot pattern was designed and implemented using UHDR with a 215nA nozzle beam current. The QA pattern that covers a central uniform field area, various spot spacings, spot delivery modes and scanning directions, and enabling the assessment of absolute, relative and temporal dosimetry QA parameters. A strip ionization chamber array (SICA) and an Advanced Markus chamber were utilized in conjunction with a 2 cm polyethylene slab and a range (R80) verification wedge. The data have been monitored for over 3 months. RESULTS: The relative dosimetries were compliant with TG-224. The variations of temporal dosimetry for scanning speed, spot dwell time, and spot transition time were within ± 1 mm/ms, ± 0.2 ms, and ± 0.2 ms, respectively. While the beam-to-beam absolute output on the same day reached up to 2.14%, the day-to-day variation was as high as 9.69%. High correlation between the absolute dose and dose rate fluctuations were identified. The dose rate of the central 5 × 5 cm2 field exhibited variations within 5% of the baseline value (155 Gy/s) during an experimental session. CONCLUSIONS: A comprehensive QA program for FLASH-RT was developed and effectively assesses the performance of a UHDR delivery system. Establishing tolerances to unify standards and offering direction for future advancements in the evolving FLASH-RT field.

Proton therapy for high-risk prostate cancer: Results from the Proton Collaborative Group PCG 001-09 prospective registry trial.

BACKGROUND: Data for proton therapy in high-risk prostate cancer (HRPC) are limited. Using the Proton Collaborative Group prospective registry, we evaluated outcomes for HRPC patients treated with proton therapy. METHODS: A totsl of 605 men with localized HRPC treated with proton therapy from 8/2009 to 3/2019 at nine institutions were selected. Outcomes examined included freedom from progression (FFP), metastasis free survival (MFS), overall survival (OS), and toxicity. Multivariable cox/binomial regression models were used to assess predictors of FFP and toxicity. RESULTS: Median age was 71 years. Gleason grade groups 4 (49.4%) and 5 (31.7%) were most common, as were clinical stage T1c (46.1%) and cT2 (41.3%). The median pretreatment prostate specific antigen (PSA) was 9.18 and median International Prostate Symptom Score (IPSS) was 6. Androgen deprivation therapy was given in 63.6%. Median dose was 79.2 GyE in 44 fractions. Pelvic lymph nodes were treated in 58.2% of cases. Pencil beam scanning was used in 54.5%, uniform scanning in 38.8%, and a rectal spacer in 14.2%. At a median followup of 22 months, the 3- and 5-year FFP were 90.7% and 81.4%, respectively. Five-year MFS and OS were 92.8% and 95.9%, respectively. Independent correlates of FFP included Gleason ≥8, PSA > 10, and cT2 (all p < 0.05). No grade 4 or 5 adverse events were reported. There were 23 (5%) grade 2 and 0 grade 3 gastrointestinal events. Prevalence of late grade 3, late grade 2, acute grade 3, and acute grade 2 genitourinary toxicity was 1.7%, 5.8%, 0%, and 21.8%, respectively. Prevalence of grade 2 and 3 erectile dysfunction at 2 years was 48.4% and 8.4%, respectively. CONCLUSIONS: In the largest series published to date, our results suggest early outcomes using proton therapy for HRPC are encouraging for both safety and efficacy. Further evaluation is needed to determine if an advantage exists to use protons over other radiation techniques in this population.

Radiofrequency ablation versus stereotactic body radiation therapy for hepatocellular carcinoma: a meta-regression.

Aim: The aim of this meta-regression was to assess the impact of mean/median age, mean/median tumor size, percentage of males in total sample, and total sample size on the comparative effectiveness of radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT). Methods: Ten studies reporting on the composite outcome of overall survival and local control were included. Results: A significant relationship was found between age and overall survival at 1 and 2 for both RFA and SBRT. A significant relationship was noted also between age and local control at 1 and 2 years for RFA. Conclusion: Patients treated with SBRT had a wider range of tumor sizes and larger tumor sizes; no relationship was observed between tumor size and overall survival or local control by SBRT.

Expert-augmented machine learning.

Machine learning is proving invaluable across disciplines. However, its success is often limited by the quality and quantity of available data, while its adoption is limited by the level of trust afforded by given models. Human vs. machine performance is commonly compared empirically to decide whether a certain task should be performed by a computer or an expert. In reality, the optimal learning strategy may involve combining the complementary strengths of humans and machines. Here, we present expert-augmented machine learning (EAML), an automated method that guides the extraction of expert knowledge and its integration into machine-learned models. We used a large dataset of intensive-care patient data to derive 126 decision rules that predict hospital mortality. Using an online platform, we asked 15 clinicians to assess the relative risk of the subpopulation defined by each rule compared to the total sample. We compared the clinician-assessed risk to the empirical risk and found that, while clinicians agreed with the data in most cases, there were notable exceptions where they overestimated or underestimated the true risk. Studying the rules with greatest disagreement, we identified problems with the training data, including one miscoded variable and one hidden confounder. Filtering the rules based on the extent of disagreement between clinician-assessed risk and empirical risk, we improved performance on out-of-sample data and were able to train with less data. EAML provides a platform for automated creation of problem-specific priors, which help build robust and dependable machine-learning models in critical applications.

Radiofrequency ablation vs radiation therapy vs transarterial chemoembolization vs yttrium 90 for local treatment of liver cancer - a systematic review and network meta-analysis of survival data.

INTRODUCTION: The comparative effectiveness of radiofrequency ablation (RFA), radiation therapy (RT), transarterial chemoembolization (TACE) and transarterial radioembolization with Yttrium-90 (Y90) relative to one another for the treatment of hepatocellular carcinoma (HCC) is unclear. The aim of this systematic review and network meta-analysis is to compare RFA to RT to TACE to Y90 in the treatment of HCC. METHODS: Pubmed, Embase and Cochrane CENTRAL were searched up until April 19, 2021. Observational analyses with propensity score matched (PSM) cohort analyses and randomized controlled trials (RCT) reporting on two or more treatments relative to one another with respect to overall survival (OS) and/or progression free survival (PFS) were included. Survival data were extracted from Kaplan-Meier survival curves, and meta-analyzed using a multivariate network meta-analysis. RESULTS: After exclusions, 24 RCTs or PSM observational studies reporting on 5549 patients were included. While 1-year OS was greater for Y90 than TACE (RR 0.85, 95% CI: 0.72-0.99), all other 1-year OS comparisons across the 4 modalities yielded similar OS, and there were no differences across any modalities in 2-year and 3-year OS. TACE had a modest PFS advantage relative to RFA (RR 0.81, 95% CI: 0.68-0.95) and RT (RR 0.65, 95% CI: 0.51-0.83) at 2 years. CONCLUSION: All modalities assessed resulted in similar OS, which explains the current heterogenous practice patterns. This conclusion may assist in decision making based on administrative and patient costs, and implementation of these modalities. Other factors such as toxicity rate specific to individual patients could not be assessed using network meta-analysis and may also play a role in selection of modality. Further studies, ideally using PSM cohort analyses or RCT study design, reporting on OS, PFS, local control, complete response and toxicity are needed prior to drawing definitive conclusions.

Building more accurate decision trees with the additive tree.

The expansion of machine learning to high-stakes application domains such as medicine, finance, and criminal justice, where making informed decisions requires clear understanding of the model, has increased the interest in interpretable machine learning. The widely used Classification and Regression Trees (CART) have played a major role in health sciences, due to their simple and intuitive explanation of predictions. Ensemble methods like gradient boosting can improve the accuracy of decision trees, but at the expense of the interpretability of the generated model. Additive models, such as those produced by gradient boosting, and full interaction models, such as CART, have been investigated largely in isolation. We show that these models exist along a spectrum, revealing previously unseen connections between these approaches. This paper introduces a rigorous formalization for the additive tree, an empirically validated learning technique for creating a single decision tree, and shows that this method can produce models equivalent to CART or gradient boosted stumps at the extremes by varying a single parameter. Although the additive tree is designed primarily to provide both the model interpretability and predictive performance needed for high-stakes applications like medicine, it also can produce decision trees represented by hybrid models between CART and boosted stumps that can outperform either of these approaches.

Prophylaxis and treatment of cancer-related dyspnea with pharmacologic agents: A systematic review and network meta-analysis.

INTRODUCTION: Cancer-related dyspnea is a common symptom in patients with cancer. It has also been reported to be a predictor of poorer prognosis, which can then change clinical treatment and advance care planning. Currently, no definitive recommendation for pharmacologic agents for cancer-related dyspnea exists. The aim of this systematic review and network meta-analysis is to compare pharmacologic agents for the prophylaxis and treatment of cancer-related dyspnea. METHODS: A search was conducted in the databases of PubMed, Embase, and Cochrane CENTRAL through May 2021. Standardized mean differences (SMDs), as reported by studies or calculated from baseline and follow-up dyspnea scores, were amalgamated into a summary SMD and 95% confidence interval (CI) using a restricted maximum likelihood multivariate network meta-analysis. RESULTS: Twelve studies were included in this review; six reported on prophylaxis of exertional dyspnea, five on treatment of everyday dyspnea, and one on treatment of episodic dyspnea. Morphine sulfate was better at controlling everyday dyspnea than placebo (SMD 1.210; 95% CI: 0.415-2.005). Heterogeneity in study design and comparisons, however, led to some concerns with the underlying consistency assumption in network meta-analysis design. CONCLUSION: Optimal pharmacologic interventions for cancer-related dyspnea could not be determined based on this analysis. Further trials are needed to report on the efficacy of pharmacologic interventions for the prophylaxis and treatment of cancer-related dyspnea.

Geospatial Disparities in Access to Proton Therapy in the Continental United States.

Proton therapy (PT) is an important component of therapy for select cancers, but no formal study of geospatial access to PT has been conducted to date. Population data for 320.7 million people in 32,644 zip codes were analyzed. Median travel time was 1.61 (IQR 0.67-3.36) hours for children and 1.64 (IQR 0.69-3.33) hours for adults. Significant variation in travel time to nearest PT center was observed between states. The West has a longer median travel time of 3.51 (IQR 1.15-7.13) hours when compared to the Midwest (1.70, IQR 0.79-2.69), South (1.60, IQR 0.61-3.12) and Northeast (1.04, IQR 0.57-2.01).

Using patient-specific bolus for pencil beam scanning proton treatment of periorbital disease.

PURPOSE: A unique mantle cell lymphoma case with bilateral periorbital disease unresponsive to chemotherapy and with dosimetry not conducive to electron therapy was treated with pencil beam scanning (PBS) proton therapy. This patient presented treatment planning challenges due to the thin target, immediately adjacent organs at risk (OAR), and nonconformal orbital surface anatomy. Therefore, we developed a patient-specific bolus and hypothesized that it would provide superior setup robustness, dose uniformity and dose conformity. MATERIALS/METHODS: A blue-wax patient-specific bolus was generated from the patient's face contour to conform to his face and eliminate air gaps. A relative stopping power ratio (RSP) of 0.972 was measured for the blue-wax, and the HUs were overridden accordingly in the treatment planning system (TPS). Orthogonal kV images were used for bony alignment and then to ensure positioning of the bolus through fiducial markers attached to the bolus and their contours in TPS. Daily CBCT was used to confirm the position of the bolus in relation to the patient's surface. Dosimetric characteristics were compared between (a) nonbolus, (b) conventional gel bolus and (c) patient-specific bolus plans. An in-house developed workflow for assessment of daily treatment dose based on CBCT images was used to evaluate inter-fraction dose accumulation. RESULTS: The patient was treated to 24 cobalt gray equivalent (CGE) in 2 CGE daily fractions to the bilateral periorbital skin, constraining at least 50% of each lacrimal gland to under 20 Gy. The bolus increased proton beam range by adding 2-3 energy layers of different fields to help achieve better dose uniformity and adequate dose coverage. In contrast to the plan with conventional gel bolus, dose uniformity was significantly improved with patient-specific bolus. The global maximum dose was reduced by 7% (from 116% to 109%). The max and mean doses were reduced by 6.0% and 7.7%, respectively, for bilateral retinas, and 3.0% and 13.9% for bilateral lacrimal glands. The max dose of the lens was reduced by 2.1%. The rigid shape, along with lightweight, and smooth fit to the patient face was well tolerated and reported as "very comfortable" by the patient. The daily position accuracy of the bolus was within 1 mm based on IGRT marker alignment. The daily dose accumulation indicates that the target coverage and OAR doses were highly consistent with the planning intention. CONCLUSION: Our patient-specific blue-wax bolus significantly increased dose uniformity, reduced OAR doses, and maintained consistent setup accuracy compared to conventional bolus. Quality PBS proton treatment for periorbital tumors and similar challenging thin and shallow targets can be achieved using such patient-specific bolus with robustness on both setup and dosimetry.

Treatment planning and outcomes effects of reducing the preferred mean esophagus dose for conventionally fractionated non-small cell lung cancer radiotherapy.

Based on an analysis of published literature, our department recently lowered the preferred mean esophagus dose (MED) constraint for conventionally fractionated (2 Gy/fraction in approximately 30 fractions) treatment of locally advanced non-small cell lung cancer (LA-NSCLC) with the goal of reducing the incidence of symptomatic acute esophagitis (AE). The goal of the change was to encourage treatment planners to achieve a MED close to 21 Gy while still permitting MED to go up to the previous guideline of 34 Gy in difficult cases. We compared all our suitable LA-NSCLC patients treated with plans from one year before through one year after the constraint change. The primary endpoint for this study was achievability of the new constraint by the planners; the secondary endpoint was reduction in symptomatic AE. Planners were able to achieve the new constraint in statistically significantly more cases during the year following its explicit implementation than in the year before (P = 0.0025). Furthermore, 38% of patients treated after the new constraint developed symptomatic AE during their treatment as opposed to 48% of the patients treated before. This is a clinically desirable endpoint although the observed difference was not statistically significant. A subsequent power calculation suggests that this is due to the relatively small number of patients in the study.

Multi-institutional analysis of stereotactic body radiotherapy for sarcoma pulmonary metastases: High rates of local control with favorable toxicity.

BACKGROUND/OBJECTIVES: Oligometastatic sarcoma pulmonary metastases (PM's) are traditionally treated with resection and/or chemotherapy. We hypothesize that stereotactic body radiotherapy (SBRT) is an effective, safe alternative to surgery that can achieve excellent local control (LC) with a favorable toxicity profile. METHODS: Patients treated with SBRT for sarcoma PM's from 2011 to 2016 at Massachusetts General Hospital and the University of Pennsylvania were included. Median dose was 50 Gy. Patients underwent computed tomography (CT) or positron emission tomography/CT Q3 months post-SBRT. RESULTS: 44 patients with 56 separate PM's were treated with SBRT. Median age was 59 (range 19-82). 82% received prior chemotherapy, 66% had prior pulmonary resections (range, 1-5 resections), and 32% received prior thoracic radiotherapy. Median lesion size was 2.0 cm (range, 0.5-8.1 cm). Median follow-up was 16 months and 25 months for patients alive at last follow-up. Overall survival at 12 and 24 months was 74% (95% confidence interval [CI], 67%-81%) and 46% (95% CI, 38%-55%). LC at 12 and 24 months was 96% (95% CI, 93%-98%) and 90% (95% CI, 84%-96%). LC and overall survival did not differ based on age, gender, histology, fractionation, lesion location, or size (P > .05). Three developed Common Terminology Criteria for Adverse Events version 4 grade-2 chest-wall toxicities; one had grade-2 pneumonitis. CONCLUSIONS: In the first multi-institutional series on SBRT for sarcoma PM's, SBRT has excellent LC and is well-tolerated. SBRT should be considered as an alternative/complement to resection.

Hypofractionated vs. conventional radiation therapy for stage III non-small cell lung cancer treated without chemotherapy.

Background: Patients with unresectable locally advanced NSCLC who refuse or are not candidates for chemotherapy often receive radiation therapy (RT) alone. Hypofractionated RT (HFRT) regimens are becoming increasingly common. An analysis of the National Cancer Database (NCDB) was performed to evaluate the practice patterns and outcomes of HFRT vs. conventionally fractionated RT (CFRT) in patients with stage III NSCLC undergoing definitive RT alone.Material and methods: The NCDB was queried for all patients with stage III NSCLC diagnosed between 2004 and 2014 who received RT alone. CFRT was defined as patients treated to a total dose of 60-80 Gy in 1.8-2 Gy daily fractions. HFRT was defined as patients treated to a total dose of 50-80 Gy in 2.25-4 Gy fractions. Logistic regression, univariable and multivariable analyses (MVAs) for overall survival (OS) and propensity score matched analyses (PSMAs) were performed.Results: A total of 6490 patients were evaluated: 5378 received CFRT and 1112 received HFRT. Median CFRT dose was 66 Gy in 2 Gy fractions vs. 58.5 Gy in 2.5 Gy fractions for HFRT. HFRT was associated with older age, lower biological effective dose (BED10), academic facility type, higher T-stage and lower N-stage. On initial analysis, HFRT was associated with inferior OS (median 9.9 vs. 11.1 months, p<.001), but after adjusting for the imbalance in covariates such as age, BED10, T-stage and N-stage using PSMA, the difference in survival was no longer significant (p=.1).Conclusions: In the appropriate clinical context, HFRT can be an option for patients with locally advanced NSCLC who are not candidates for chemotherapy or surgical resection. HFRT needs to be further studied in prospective trials to evaluate toxicity and tumor control.

Management of Malignant Pleural Mesothelioma in the Elderly Population.

BACKGROUND: The median age at diagnosis for malignant pleural mesothelioma (MPM) is approximately 72 years. Elderly patients pose unique management challenges because of the increased risk of therapy-related toxicities and mortality. Because there are no high-volume retrospective studies, prospective trials, or dedicated treatment recommendations for this population, this investigation addresses a major knowledge gap by examining national practice patterns and postoperative/survival outcomes in elderly MPM patients. METHODS: The National Cancer Database was queried for patients aged ≥ 80 years with newly diagnosed nonmetastatic MPM. Multivariable logistic regression ascertained factors associated with observation and surgery. Kaplan-Meier analysis assessed overall survival (OS), and multivariable Cox proportional hazards modeling examined factors associated with OS. Survival was also calculated following propensity matching. Additionally, postoperative outcomes were evaluated in surgical patients. RESULTS: Of 4526 patients, 2% received surgery and chemotherapy, 22% underwent chemotherapy alone, and 63% were observed. Respective median OS was 12.2, 9.5, and 4.1 months (p < 0.001). Differences between all groups persisted following propensity matching (all comparisons p < 0.05). For the 8% of patients who underwent specified definitive surgery (95% of whom received pleurectomy/decortication), 30- and 90-day mortality rates were 11.0% and 28.5%, respectively. The median length of postoperative hospitalization was 6 days, with 30-day readmission occurring in 7.5% of patients. CONCLUSIONS: The majority of elderly MPM patients in the US are observed, which was associated with poorer OS than chemotherapy and/or surgery. Although highly selected surgery/chemotherapy patients were associated with the longest OS, given the high biases in database studies and high perioperative mortality rates, careful patient selection for combined modality approaches in this population is imperative.

A prospective study of the feasibility of FDG-PET/CT imaging to quantify radiation-induced lung inflammation in locally advanced non-small cell lung cancer patients receiving proton or photon radiotherapy.

PURPOSE: This prospective study assessed the feasibility of 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) to quantify radiation-induced lung inflammation in patients with locally advanced non-small cell lung cancer (NSCLC) who received radiotherapy (RT), and compared the differences in inflammation in the ipsilateral and contralateral lungs following proton and photon RT. METHODS: Thirty-nine consecutive patients with NSCLC underwent FDG-PET/CT imaging before and after RT on a prospective study. A novel quantitative approach utilized regions of interest placed around the anatomical boundaries of the lung parenchyma and provided lung mean standardized uptake value (SUVmean), global lung glycolysis (GLG), global lung parenchymal glycolysis (GLPG) and total lung volume (LV). To quantify primary tumor metabolic response to RT, an adaptive contrast-oriented thresholding algorithm was applied to measure metabolically active tumor volume (MTV), tumor uncorrected SUVmean, tumor partial volume corrected SUVmean (tumor-PVC-SUVmean), and total lesion glycolysis (TLG). Parameters of FDG-PET/CT scans before and after RT were compared using two-tailed paired t-tests. RESULTS: All tumor parameters after either proton or photon RT decreased significantly (p < 0.001). Among the 21 patients treated exclusively with proton RT, no significant increase in PVC-SUVmean or PVC-GLPG was observed in ipsilateral lungs after the PVC parameters of primary tumor were subtracted (p = 0.114 and p = 0.453, respectively). Also, there were no significant increases in SUVmean or GLG of contralateral lungs of patients who received proton RT (p = 0.841, p = 0.241, respectively). In contrast, among the nine patients who received photon RT, there was a statistically significant increase in PVC-GLPG of ipsilateral lung (p < 0.001) and in GLG of contralateral (p = 0.036) lung. In the subset of nine patients who received a combined proton and photon RT, there was a statistically significant increase in PVC-GLPG of ipsilateral lung (p < 0.001). CONCLUSION: Our data suggest less induction of inflammatory response in both the ipsilateral and contralateral lungs of patients treated with proton compared to photon or combined proton-photon RT.

Proton therapy for thymic malignancies: multi-institutional patterns-of-care and early clinical outcomes from the proton collaborative group and the university of Florida prospective registries.

Objective: Thymic malignancies (TM) are rare tumors with long-term survivorship, causing concerns for radiotherapy-related late side effects. Proton therapy (PT) reduces the radiation dose to organs at risk, potentially decreasing long-term toxicities while preserving disease control. We report patterns-of-care and early clinical outcomes after PT for thymoma and thymic carcinoma. Methods: Between January 2008 and March 2017, 30 patients with TMs enrolled on one of two IRB-approved prospective protocols and received postoperative or definitive PT. Clinical outcomes, pathology, treatment dose, toxicities, and follow-up information were analyzed. Results: Twenty-two thymoma patients with a median age of 52.1 years (range, 23-72) received a median RT dose of 54 Gy (RBE) (range, 45-70) either postoperatively (91%) or definitively (9%); 23% received adjuvant chemotherapy. Among eight thymic carcinoma patients, the median age was 65.5 years (range, 38-88) and median RT dose was 60 Gy (RBE) (range, 42-70) delivered postoperatively (75%) or definitively (25%); 50% received chemotherapy. Median follow-up for all patients was 13 months (range, 2-59 months). Five patients relapsed, one locally (3%). Three patients died of disease progression, including two thymomas and one thymic carcinoma patient; a fourth died of intercurrent disease. One patient with thymic carcinoma and 1 with thymoma are alive with disease. No patients treated with PT for their initial disease (de novo) experienced grade ≥3 toxicities. The most common grade 2 toxicities were dermatitis (37%), cough (13%), and esophagitis (10%). Conclusion: Adjuvant and definitive PT are being used in the treatment of TMs. Early results of the largest such cohort reported to date demonstrates an acceptable rate of recurrence with a favorable toxicity profile. Longer follow-up and a larger patient cohort are needed to confirm these findings.

Malignant Peritoneal Mesothelioma: National Practice Patterns, Outcomes, and Predictors of Survival.

PURPOSE: This study of a large, contemporary national database evaluated management patterns, outcomes, and prognostic factors of malignant peritoneal mesothelioma (MPM) in the USA. METHODS: The National Cancer Data Base was queried for newly diagnosed nonmetastatic MPM. Patients were divided into five cohorts: observation, chemotherapy alone, cytoreductive surgery (CRS) alone, CRS/chemo [referring to any non-hyperthermic intraperitoneal chemotherapy (HIPEC) chemotherapy], and CRS/HIPEC. Statistics included multivariable logistic regression, Kaplan-Meier analysis, and Cox proportional hazards modeling. RESULTS: Of 1514 patients, 379 (25%) underwent observation, 370 (24%) received chemotherapy only, 197 (13%) CRS alone, 352 (23%) CRS/chemo, and 216 (14%) CRS/HIPEC. No major temporal trends in management were noted. Factors predictive of CRS administration included younger age, female gender, insurance status, residence in educated areas, living farther from treating institutions, and treatment at academic centers (p < 0.05 for all). Compared with epithelioid histology, those with sarcomatoid and biphasic histology were less and more likely to undergo CRS, respectively (p < 0.05 for both). In all CRS patients, 30- and 90-day mortality rates were 0.8 and 1.2%, respectively. At median follow-up of 50 months, median OS in the respective groups was 6, 17, 21, 52, and 61 months (p < 0.001). Poor prognostic factors included advanced age, male gender, uninsured/Medicaid insurance, and sarcomatoid/biphasic histology (p < 0.05 for all). CONCLUSIONS: In the USA, MPM is treated using a wide variety of strategies. Many factors impact the type of treatment delivered, including age, sociodemographics, geography, histology, and facility type. Although these data do not imply causation, combined-modality management seems associated with the longest OS.

Chemoradiotherapy Versus Chemotherapy Alone for Unresected Nonmetastatic Gallbladder Cancer: National Practice Patterns and Outcomes.

Purpose: Current guidelines recommend chemotherapy (CT) with or without radiotherapy for unresected nonmetastatic gallbladder cancer (GC), with little consensus. However, several small-volume, single-institution studies have documented the efficacy of local therapy for this population. This is the largest study to date evaluating outcomes of chemoradiotherapy (CRT) versus CT alone in unresected nonmetastatic GC. Methods: The National Cancer Database was queried for primary GC cases (2004-2013) receiving CT alone or CRT. Patients receiving resection or lack of CT were excluded, as were those with metastatic disease or unknown M classification. Logistic regression analysis ascertained factors associated with CRT delivery. Kaplan-Meier analysis evaluated overall survival (OS) between both cohorts. Cox proportional hazards modeling determined variables associated with OS. Results: In total, 1,199 patients were analyzed (CRT: n=327, 27%; CT: n=872, 73%). Groups were evenly balanced, with no factor on multivariate logistic regression analysis statistically predicting for receipt of a particular paradigm. Median OS in the CRT and CT groups was 12.9 versus 7.8 months, respectively (P=.001). On multivariate analysis, OS was associated with age and years of treatment (P=.001 each). Notably, receipt of CRT independently predicted for improved OS (P=.001). Conclusions: CRT, compared with CT alone, was independently associated with improved survival in unresected nonmetastatic GC. Although causation is not implied, these results support the necessity for prospective CRT evaluation.

Patterns of care and outcomes with the addition of chemotherapy to radiation therapy for stage I nasopharyngeal cancer.

PURPOSE: The standard of care for stage I (T1N0) nasopharyngeal cancer (NPC) is definitive radiotherapy (RT). Given the phase III evidence supporting combined chemoradiotherapy (CRT) for stage II NPC, we investigated practice patterns and outcomes associated with administration of chemotherapy to RT alone for stage I NPC. METHODS: The National Cancer Data Base (NCDB) was queried for clinical T1N0 primary NPC cases (2004-2013) receiving curative-intent RT. Patients with unknown RT/chemotherapy status were excluded, as were benign/sarcomatous histologies and receipt of pharyngectomy. Patient, tumor, and treatment parameters were extracted. Logistic regression analysis ascertained factors associated with receipt of additional chemotherapy. Kaplan-Meier analysis was used to evaluate overall survival (OS) between patients receiving RT versus CRT. Cox proportional hazards modeling determined variables associated with receipt of OS. RESULTS: In total, 396 patients were analyzed. Chemotherapy was delivered in 147 patients (37%). On multivariate analysis, patients treated at academic/integrated centers were less likely to receive chemotherapy (p = .008); a racial predilection was noted, as non-black/non-white patients were also less likely to receive chemotherapy (p = .006). Respective 5-year OS in patients receiving RT alone versus CRT were 77% and 75% (p = .428). Receipt of chemotherapy did not independently predict for greater OS (p = .447). CONCLUSIONS: These data do not support the routine addition of chemotherapy to definitive RT for T1N0 NPC.

Dosimetric comparison of advanced radiotherapy approaches using photon techniques and particle therapy in the postoperative management of thymoma.

BACKGROUND: The purpose of this study was to compare dosimetric differences related to target volume and organs-at-risk (OAR) using 3D-conformal radiotherapy (3DCRT), volumetric modulated arc therapy (VMAT), TomoTherapy (Tomo), proton radiotherapy (PRT), and carbon ion radiotherapy (CIRT) as part of postoperative thymoma irradiation. MATERIAL AND METHODS: This single-institutional analysis included 10 consecutive patients treated with adjuvant radiotherapy between December 2013 and September 2016. CT-datasets and respective RT-structures were anonymized and plans for all investigated RT modalities (3DCRT, VMAT, Tomo, PRT, CIRT) were optimized for a total dose of 50 Gy in 25 fractions. Comparisons between target volume and OAR dosimetric parameters were performed using the Wilcoxon rank-sum test. RESULTS: The best target volume coverage (mean PTV V95% for all patients) was observed for Tomo (97.9%), PRT (97.6%), and CIRT (96.6%) followed by VMAT (85.4%) and 3DCRT (74.7%). PRT and CIRT both significantly reduced mean doses to the lungs, breasts, heart, and esophagus, as well as the spinal cord maximum dose compared with photon modalities. Among photon-based techniques, VMAT showed improved OAR sparing over 3DCRT. Tomo was associated with considerable low-dose exposure to the lungs, breasts, and heart. CONCLUSIONS: Particle radiotherapy (PRT, CIRT) showed superior OAR sparing and optimal target volume coverage. The observed dosimetric advantages are expected to reduce toxicity rates. However, their clinical impact must be investigated prospectively.