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Purpose Limited evidence is available on the utility of dose-escalated radiation therapy (DE-RT) with or without temozolomide (TMZ) versus standard-of-care radiation therapy (SoC-RT) for patients with newly diagnosed glioblastoma multiforme. We performed a systematic review/meta-analysis to compare overall survival (OS) and progression-free survival (PFS) between DE-RT and SoC-RT. Methods and Materials We used a Population, Intervention, Control, Outcomes, Study Design/Preferred Reporting Items for Systematic Reviews and Meta-analyses/Meta-analysis of Observational Studies in Epidemiology selection criterion to identify studies. The primary and secondary outcomes were 1-year OS and 1-year PFS, respectively. Outcomes and comparisons were subdivided based on receipt of TMZ and MGMT status. DE-RT was defined based on equivalent dose calculations. Random effects meta-analyses using the Knapp-Hartung correction, arcsine transformation, and restricted maximum likelihood method were conducted. Meta-regression was used to compare therapeutic (eg, DE-RT or TMZ) and pathologic characteristics (eg, MGMT methylation status) using the Wald-type test. Results Across 22 published studies, 2198 patients with glioblastoma multiforme were included; 507 received DE-RT. One-year OS after DE-RT alone was higher than SoC-RT alone (46.3% vs 23.4%; P = .02) as was 1-year PFS (17.9% vs 5.3%; P = .02). No significant difference in 1-year OS (73.2% vs 64.4%; P = .23) or 1-year PFS (44.5% vs 44.3%; P = .33) between DE-RT + TMZ and SoC-RT + TMZ was noted. No difference in 1-year OS was noted between DE-RT + TMZ and SoC-RT + TMZ in either MGMT methylated (83.2% vs 73.2%; P = .23) or MGMT unmethylated (72.6% vs 50.6%; P = .16) patients. Conclusions DE-RT alone resulted in superior PFS and OS versus SoC-RT alone. DE-RT + TMZ did not lead to improved outcomes versus SoC-RT + TMZ. No differential benefit based on MGMT status was found. Future studies are warranted to define which subgroups benefit most from DE-RT.

OBJECTIVES: Metastatic cancer has historically been considered fatal; however, there is a paucity of evidence characterizing the epidemiology of incidence, treatment, and outcomes in these patients. MATERIALS AND METHODS: Incidence rates, annual percent change (APC), descriptive epidemiological statistics, and odds ratios for survival were calculated using registry data from the Surveillance, Epidemiology, and End Results (SEER) and the National Cancer Database (NCDB), 1998 to 2015. RESULTS: There were a total of 1,055,860 patients with metastatic cancer. The most frequent primary cancers were lung (42.6%), colorectal (9.5%), and ovarian (5.5%). Metastatic lung and colorectal cancer incidence decreased, APC: -1.57 (P

BACKGROUND Palliative radiation therapy is essential to the care of patients with advanced cancer. Unfortunately, despite their benefits, the principles of palliative radiation therapy and palliative and supportive care are underrepresented in radiation oncology residency curricula. In this study, we attempted to identify areas of emphasis for future palliative radiation therapy curricula by examining the relevant questions posted to theMednet. METHODS Questions tagged with both "Palliation" and "Radiation Oncology" or "General Radiation Oncology" that were posted to theMednet on or before January 7, 2020 were included in this analysis. The questions were grouped thematically, and subthemes within each broader thematic group were identified. Among the thematic groups, variations in social engagement metrics were assessed using the Kruskal-Wallis Test and non-parametric analysis of variance. RESULTS A total of 4,188 questions tagged with the terms "Radiation Oncology," "General Radiation Oncology," or "Palliation" and posed between 2012 and 2020 were identified. Of these, 161 questions satisfied our inclusion criteria. Upon examination of the identified questions, eight thematic groups and several subthemes were identified, representing areas of possible emphasis for future palliative radiation therapy curricula. Among questions in different thematic groups, however, there were no statistically significant differences in any of the examined social engagement metrics. CONCLUSIONS We found many common question themes and subthemes in our examination of the palliative radiation oncology questions posted to theMednet. Our findings suggest that several opportunities for education exist for radiation oncology residents in regards to palliative and supportive care and palliative radiation therapy.

Objective The purpose of this study was to determine the impact of prehabilitation exercise intervention with respect to (1) acceptability, feasibility, and safety; and (2) physical function, measured by 6‐minute‐walk test (6MWT). Data sources PRISMA guidelines were used to systematically search PubMed, Embase, and CINAHL databases evaluating prehabilitation exercise interventions. Study selection The inclusion criteria were studies investigating patients who underwent surgery for their cancer and underwent prehabilitation exercise. Data extraction and synthesis Guidelines were applied by independent extraction by multiple observers. Data were pooled using a random‐effects model. Main outcome(s) and measure(s) Acceptability, feasibility, and safety rates were calculated. 6MWT (maximum distance a person can walk at their own pace on a hard, flat surface, measured in meters, with longer distance indicative of better performance status) was compared using two arms using the DerSimonian and Laird method. Results Objective 1. Across 21 studies included in this review, 1564 patients were enrolled, 1371 (87.7%) accepted the trial; of 1371, 1230 (89.7% feasibility) completed the intervention. There was no grade 3+ toxicities. Objective 2. Meta‐analysis of five studies demonstrated a statistically significant decrease in 6MWT distance postoperatively in the control group (mean difference = +27.9 m; 95% confidence interval (CI): 9.3; 46.6) and a significant improvement postoperatively in the prehabilitation group (mean difference = −24.1 m; 95% CI: −45.7; −2.6). Meta‐analysis demonstrated improvements in 6MWT distance 4–8 weeks postoperatively in the prehabilitation group compared to the control group (mean difference = −58.0 m, 95% CI: −92.8; −23.3). Conclusions and relevance Prehabilitation exercise for cancer patients undergoing surgery was found to be safe, acceptable, and feasible with a statistically significant improvement in the 6MWT, indicating that prehabilitation can improve postoperative functional capacity., Prehabilitation exercise for cancer patients undergoing surgery was found to be safe, acceptable, and feasible.In this meta‐analysis, panel A shows that there is a 27.9 m c post operatively in the control group. Panel B shows that there is a 24.1 m increase in distance walked during the 6MWTpostoperatively in the prehab group. Panel C shows that the two groups (control andprehab) have the same 6MWT distance before randomization. Panel D shows that prehab intervention improved the 6MWT by 58.0 m, suggesting that prehabilitation can improve postoperative functional capacity.

Purpose Multiple efforts have been made in recent years to establish national benchmarks for research productivity among US radiation oncology residents. Morgan et al found a mean of 1.01 first-author, PubMed-searchable articles published by US radiation oncology residents over 4 years of residency between 2002 and 2007, whereas Verma et al found a mean of 1.97 first-author, PubMed-searchable articles published by members of the graduating US radiation oncology residency classes of 2014 and 2015. In this study, we sought to establish new national benchmarks for US radiation oncology resident research productivity and characterize the scholarly work produced by graduating US radiation oncology residents. Methods and Materials We built a database of US radiation oncology residents who graduated between 2015 and 2019 using multiple sources of publicly available data. We subsequently searched the PubMed database to identify all first-author publications for every resident in our database from the start of residency until 3 months after the completion of residency. Publications were categorized by type (original research, review, case report, or commentary) and content. We performed a secondary analysis to identify factors associated with an increased probability of publishing during residency. Results We identified 909 US radiation oncology residency graduates from 89 residency programs between 2015 and 2019. Collectively, these graduates published 2637 first-author, PubMed-searchable articles (mean: 2.90; median: 2.0; range, 0-58; interquartile range, 1-4) in 392 distinct peer-reviewed journals during their residency, and 69.7% of the first-author publications comprised original research. On multivariable analysis, only residency size was predictive of publishing a first-author manuscript during residency. Among residents with at least 1 first-author manuscript, male sex, lack of a doctorate degree, and residency size were all significant predictors of the number of first-author manuscripts published during residency. Conclusions US radiation oncology resident research productivity, as measured by the number of first-author, PubMed-searchable publications, has increased compared with historical data. However, substantial variability exists in resident research productivity nationwide.

Background The optimal extent of surgery and/or radiation to the contralateral lymph node region is unknown in early-stage human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). Methods To investigate the pathologic incidence of and risk factors for contralateral nodal disease (CND) in cT1-T2 HPV-related OPSCC treated with transoral robotic surgery (TORS) and bilateral neck dissection (BND), the records of 120 patients were reviewed. Results Eleven patients displayed pathologic contralateral nodal disease (pCND), including 7.1% of tonsil and 10.9% of base of tongue (BOT) cases. Medial hemistructure involvement and cN2 disease were significantly associated with pCND. Zero cN0 patients had pCND, and on multivariate analysis only cN classification remained significantly associated with pCND. Four percent of BOT patients and 2% of tonsil patients with a well-lateralized primary and cN0/N1 neck demonstrated pCND. Conclusions HPV-related OPSCC that are cN0-N1 have exceedingly low rates of pCND. Well-lateralized HPV-related BOT primaries with limited clinical nodal disease may be candidates for ipsilateral only treatment.

Highlights • Data are limited regarding timing of EBRT initiation in high-risk prostate cancer. • Black race and living in an urban area are assocated with missing > 3 days of EBRT. • Missing >3 days of EBRT was associated with poorer 5-year OS., Introduction High-risk prostate cancer is associated with poorer overall survival (OS) and biochemical control compared to more favorable risk groups. External beam radiation therapy (EBRT) is widely used; however, outcomes data are limited with respect to time elapsed between diagnosis and initiation of EBRT. Methods The National Cancer Database was queried from 2004 to 2015 for patients diagnosed with high-risk adenocarcinoma of the prostate who received androgen deprivation therapy (ADT) and definitive EBRT. Logistic regression was utilized to determine covariates associated with missing EBRT treatments. OS was analyzed using multivariate cox proportional hazards models and propensity score matching. Results 9,610 patients met inclusion criteria with median follow-up of 40.6 months and median age of 72 years. Median PSA was 8.7 and median EBRT dose was 78 Gy. ADT was initiated at a median of 36 days and EBRT at a median of 63 days post-diagnosis. Median number of prolonged treatment days was 2.2. Black race (OR: 1.40; p 74 days (HR: 1.20; p = 0.01) and prolonged treatment>3 days of EBRT (HR: 1.26; p = 0.005) were associated with an increased hazard of death. The 5-year OS was 79.6% and 82.9% for patients with prolonged treatment of 3 days or more of EBRT and those missing 3 days or less, respectively (p = 0.0006). Conclusion In this hypothesis-generating study, prolonged treatment delays and missing three or more EBRT treatments was associated with poorer OS in patients with high-risk adenocarcinoma of the prostate.

OBJECTIVES To analyze the association between dosvolume relationships and adverse events in brainstem lesions treated with Gamma Knife radiosurgery (GKRS). METHODS Treatment plans were generated on BrainLab Elements and GammaPlan software. Dosimetric data were analyzed as continuous variables for patients who received GKRS to brain metastases or arteriovenous malformations (AVM) within or abutting the brainstem. Adverse events were classified as clinical and/or radiographic. Logistic and cox regression were used to assess the relationship between dosimetric variables and adverse events. RESULTS Sixty-one patients who underwent single fraction GKRS for brain metastases or AVM were retrospectively analyzed. Median age was 62 years (range: 12-92 years) and the median prescription dose was 18 Gy (range: 13-25 Gy). Median follow-up was 6months. Clinical and radiographic complications were seen in ten (16.4%) and 17 (27.9%) patients, respectively. On logistic regression, increasing D05% was found to be associated with an increased probability of developing a clinical complication post-GKRS (OR: 1.18; 95% CI: 1.01-1.39; p = 0.04). Furthermore, mean brainstem dose (HR: 1.43; 95% CI: 1.05-1.94; p

Hepatocellular carcinoma (HCC) remains a leading cause of cancer death worldwide [1]. While current first line therapy for unresectable HCC consists of molecularly targeted agents including sorafen...

Background and purpose To perform a systematic review/meta-analysis of outcomes for patients with spinal metastases treated with stereotactic radiosurgery (SRS) (either single-fraction (SF-SRS) or multiple-fraction (MF-SRS)) or conventional radiotherapy (RT). Materials and methods Thirty-seven studies were identified. Primary outcomes were 1-year local control (LC) and acute/late grade 3–5 toxicities (including vertebral compression fractures (VCF)). Weighted random effects meta-analyses using the DerSimonian and Laird methods and meta-regressions were conducted to characterize and compare effect sizes. Mixed effects regression models were used in dose analyses. Results A total of 3237 patients with 4911 lesions were included; 43.8%, 19.7%, and 36.5% of lesions received SF-SRS, MF-SRS, or RT, respectively. SF-SRS resulted in improved 1-year LC (92.9% (95% CI: 86.4–97.4%); p = 0.007) compared to RT (81.0% (95% CI: 69.2–90.5%)) with no difference between MF-SRS (82.1%; p = 0.86) and RT. On subgroup analysis of de novo metastases, superior 1-year LC following SF-SRS (95.5% (95% CI: 87.4–99.6%)) was maintained compared to RT (83.6% (95% CI: 70.4–93.5%); p = 0.007). A 4.7% increase in LC was noted for each 10 Gy10 increase in biologically effective dose (BED10, assuming an alpha/beta = 10) with SRS (p Conclusion SF-SRS resulted in superior LC with a roughly 5% LC benefit for every 10 Gy10 increase in BED10 with higher VCF rates compared to MF-SRS. If LC is the goal of treatment, then SRS may be a preferred treatment modality. However, these results are hypothesis-generating, and prospective randomized clinical trials are indicated to definitively address the question of whether SRS results in improved LC compared to RT.

The objectives of this study were to characterize the risk of death (1) from the primary cancer vs competing cause of death; and (2) from various causes of death vs the general poplation. The relative risk of death after a pediatric cancer diagnosis versus the general population and the risk of death from a primary cancer diagnosis versus competing causes of death.This retrospective, population-based study used the Surveillance, Epidemiology, and End Results database (1980-2015) and included patients aged 0 to 19 years at the time of diagnosis. Observed deaths were calculated; the risk of death versus the general population was assessed with standardized mortality ratios (SMRs). Competing risk models for the cause of death were performed.There were 58,356 patients who were diagnosed, and the mortality rate was 22.8%. To assess causes of death, 6996 patients who died during the study period were included (45,580 total person-years at risk): 5128 (73%) died of their primary cancer, and 1868 (27%) died of a competing cause. Among all patients, the rate of death from the index cancer was higher than the rate of death from another cause within the first 5 years after diagnosis. The risk of death from a nonprimary cancer began to supersede the rate of death from the primary cancer 10 years after diagnosis for patients with germ cell tumors, lymphomas, and sarcomas. SMRs for the primary cancer were highest within the first 5 years after diagnosis for all cancers (SMRs, 100-50,000; P .0001). The risk of death from competing causes (heart disease, suicide, and sepsis) was elevated (SMR,100; P .001). The risk of dying of heart disease was high, especially for patients with astrocytomas (SMR, 47.84; 95% confidence interval [CI], 27.87-76.59) and neuroblastomas (SMR, 98.59; 95% CI, 47.28-181.32). The risk of dying of suicide was high in most patients, particularly for those with osteosarcomas (SMR, 111.40; 95% CI, 2.82-620.69), Hodgkin lymphomas (SMR, 62.35; 95% CI, 34.89-102.83), and gonadal germ cell tumors (SMR, 28.97; 95% CI, 12.51-57.09).The cause of death for patients with gonadal germ cell tumors, lymphomas, and sarcomas is more commonly a secondary cancer or noncancerous cause than the primary disease; their risk of death from competing causes (heart disease, suicide, and sepsis) rises throughout life.

To analyze outcomes of non-small cell lung cancer (NSCLC) patients with brain metastases harboring EGFR or ALK mutations and examine for differences between tyrosine kinase inhibitors (TKIs) alone, radiotherapy (RT) alone (either whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS)), or combined TKIs and RT.Thirty studies were identified.with brain metastases from NSCLC.initial TKIs alone with optional salvage RT, RT alone, or TKIs and RT.wild-type NSCLC and TKIs alone for mutational and treatment analysis, respectively.overall survival (OS) and intracranial progression-free survival (PFS).studies with mutation information.A total of 2649 patients were included. Patients with ALK and EGFR mutations had significantly higher median OS (48.5 months, p 0.0001; and 20.9 months; p = 0.0006, respectively) compared to wild-type patients (9.9 months). Similar median OS was noted between TKIs and RT (28.3 months), RT alone (32.2 months; p = 0.22), or TKIs alone (23.9 months; p = 0.2). Patients treated with TKIs and RT had higher median PFS (18.6 months; p = 0.06) compared to TKIs alone (13.6 months) with no difference between TKIs and RT vs. RT alone (16.9 months; p = 0.72). No PFS difference was found between WBRT and TKI (23.2 months; p = 0.72) vs. WBRT alone (24 months) or SRS and TKI (16.7 months; p = 0.56) vs. SRS alone (13.6 months).NSCLC patients with brain metastases harboring EGFR or ALK mutations have superior OS compared to wild-type patients. No PFS or OS benefit was found with the addition of TKIs to RT.

Brain metastases traditionally carried a poor prognosis with treatment being a combination of surgery, whole-brain radiation therapy, and glucocorticoids; however, this treatment paradigm carried a significant amount of morbidity. In recent years, stereotactic radiosurgery (SRS), which involves the delivery of a highly conformal dose of radiation over a single session, has been shown to be an effective alternative to WBRT with excellent rates of local control and improved quality of life; however, a survival benefit has not been demonstrated. Recent developments have challenged the traditional view of the central nervous system being “immunologically privileged” which has led to a greater focus on treating these patients with systemic therapies. Immune checkpoint inhibitors (ICI) have been shown to improve survival in multiple malignancies. As a result, there has been increased utilization in combining these therapies in this setting. We conducted a literature search of medical databases (e.g. PubMed) for articles involving the use of immune checkpoint inhibitors and stereotactic radiosurgery in managing brain metastases. Published evidence utilizing SRS and ICI is largely limited to single institution and retrospective in nature with the most common histology being melanoma. Combination therapy with SRS and ICI appears to improve survival in patients with brain metastases. The available data are largely retrospective; therefore, ongoing and planned prospective studies are needed to further validate these findings.

Background Excellent outcomes and high rates of pathologic complete response (pCR) have been reported in patients with operable esophageal carcinoma using 41.4 Gy of radiation with concurrent carboplatin and paclitaxel. With pCR rates similar to studies using higher doses, it remains unclear whether doses greater than 41.4 Gy result in improved outcomes. This study aims to compare pCR rates and oncologic outcomes in patients treated with neoadjuvant chemoradiation to 50.4 Gy vs 41.4 Gy. Methods We reviewed the charts of patients with operable esophageal carcinoma who were treated with neoadjuvant chemoradiation followed by oncologic resection. Our primary endpoint was the pCR rate. Secondary endpoints were overall survival, progression-free survival (PFS), and toxicity. Results We identified 43 patients meeting inclusion criteria. Nineteen patients were treated with 41.4 Gy and 24 were treated with 50.4 Gy. Cohorts were well-matched, except for a significantly higher percentage of patients with adenocarcinoma (AC) (89.5% vs 54.2%, p = 0.02), usage of intensity-modulated radiation therapy (IMRT) (100% vs 47.6%; p = 0.002), and usage of carboplatin, plus paclitaxel (100% vs 75%; p = 0.003) in the 41.4 Gy group. The pCR rate for the cohort was 44.2%. No differences in the pCR rate (41.7% vs 47.4%), three-year overall survival (OS) (73.7% vs 77.5%), or three-year PFS (52.8% vs 43.7%) were observed. Late toxicity rates also did not vary significantly (p = 0.2). No grade 4 or 5 events were observed. Conclusion In this small series, there were no differences in the pCR rate, PFS, or OS between those treated with 50.4 Gy and 41.4 Gy. Larger, multi-institutional series are needed to validate these findings.

Introduction: Lung metastasis is usually associated with poor outcomes in cancer patients. This study was performed to characterize and analyze the population of patients with de novo (synchronous) lung metastases using the Surveillance, Epidemiology and End Results (SEER) database.Materials and Methods: Baseline characteristics of lung metastasis patients were obtained from SEER case listings. Incidence rates and counts of synchronous lung metastasis were also obtained using the SEER*Stat software. Survival outcomes were analyzed using univariate and multivariable Cox regressions, controlling for confounders. An alpha threshold of 0.05 was used for statistical significance and p-values were subject to correction for multiple comparisons.Results: The age-adjusted incidence rate of synchronous lung metastasis was 17.92 per 100,000 between 2010 and 2015. Synchronous lung metastases most commonly arose from primary lung cancers, colorectal cancers, kidney cancers, pancreatic cancers and breast cancers. During this time period, 4% of all cancer cases presented with synchronous lung metastasis. The percentage of patients presenting with synchronous lung metastasis ranged from 0.5% of all prostate cancers to 13% of all primary lung cancers. The percentage of all cancer cases presenting with synchronous lung metastasis increased over time. De novo metastatic patients with lung metastases had worse overall survival [hazard ratio = 1.22 (1.21–1.23), p < 0.001] compared to those with only extrapulmonary metastases, controlling for potential confounders.Conclusions: Synchronous lung metastasis occurs frequently and is an independent predictors of poor patient outcomes. As treatment for lung metastases becomes more complicated, patients with synchronous lung metastasis represent a high-risk population.

Objectives Chemoradiation therapy (CRT) has been established as a standard treatment for locally advanced hypopharynx/larynx squamous cell carcinoma (SCC) but the role of induction chemotherapy (IC) remains unclear. The primary outcome of this study is to determine whether functional larynx-preservation survival (FLPS) is improved with the addition of IC in these patients. Secondary outcomes were overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and laryngectomy rates. Methods Records for patients with AJCC 8th edition clinical stage III-IVB laryngeal and hypopharyngeal SCC treated with CRT +/- IC from 2005-2019 were reviewed. FLPS was defined as time until death, progression, laryngectomy, or non-functional larynx. Kaplan-Meier curves were generated for FLPS, OS, PFS, and DMFS. Outcomes were compared using the stratified log-rank test. Laryngectomy rates were compared using Fisher’s exact test. Results We included 52 patients with laryngeal and 38 with hypopharyngeal SCC (n=90); 19 patients with laryngeal SCC and 19 with hypopharyngeal SCC received IC (median three cycles). There were no differences in the three-year FLPS (61% vs 67.8%; p=0.88), OS (73.9% vs 86.2%; p=0.42), PFS (53.6% vs 62.6%; p=0.44), or DMFS (65.2% vs 71.5%, p= 0.85) between patients who did and did not receive IC all patients. Laryngectomy rates did not differ with and without IC (18.4 % vs 7.7%; p=0.19). Conclusion In this study of advanced laryngeal and hypopharyngeal SCC, IC did not improve three-year FLPS, OS, PFS, or laryngectomy rates compared to CRT alone. A large prospective series would provide a more robust understanding of the role of IC in this group of patients.

Background Chordoma is a rare primary bone tumour with a high propensity for local recurrence. Surgical resection is the mainstay of treatment, but complete resection is often morbid due to tumour location. Similarly, the dose of radiotherapy (RT) that surrounding healthy organs can tolerate is frequently below that required to provide effective tumour control. Therefore, clinicians have investigated different radiation delivery techniques, often in combination with surgery, aimed to improve the therapeutic ratio. Objectives To assess the effects and toxicity of proton and photon adjuvant radiotherapy (RT) in people with biopsy-confirmed chordoma. Search methods We searched CENTRAL (2021, Issue 4); MEDLINE Ovid (1946 to April 2021); Embase Ovid (1980 to April 2021) and online registers of clinical trials, and abstracts of scientific meetings up until April 2021. Selection criteria We included adults with pathologically confirmed primary chordoma, who were irradiated with curative intent, with protons or photons in the form of fractionated RT, SRS (stereotactic radiosurgery), SBRT (stereotactic body radiotherapy), or IMRT (intensity modulated radiation therapy). We limited analysis to studies that included outcomes of participants treated with both protons and photons. Data collection and analysis The primary outcomes were local control, mortality, recurrence, and treatment-related toxicity. We followed current standard Cochrane methodological procedures for data extraction, management, and analysis. We used the ROBINS-I tool to assess risk of bias, and GRADE to assess the certainty of the evidence. Main results We included six observational studies with 187 adult participants. We judged all studies to be at high risk of bias. Four studies were included in meta-analysis. We are uncertain if proton compared to photon therapy worsens or has no effect on local control (hazard ratio (HR) 5.34, 95% confidence interval (CI) 0.66 to 43.43; 2 observational studies, 39 participants; very low-certainty evidence). Median survival time ranged between 45.5 months and 66 months. We are uncertain if proton compared to photon therapy reduces or has no effect on mortality (HR 0.44, 95% CI 0.13 to 1.57; 4 observational studies, 65 participants; very low-certainty evidence). Median recurrence-free survival ranged between 3 and 10 years. We are uncertain whether proton compared to photon therapy reduces or has no effect on recurrence (HR 0.34, 95% CI 0.10 to 1.17; 4 observational studies, 94 participants; very low-certainty evidence). One study assessed treatment-related toxicity and reported that four participants on proton therapy developed radiation-induced necrosis in the temporal bone, radiation-induced damage to the brainstem, and chronic mastoiditis; one participant on photon therapy developed hearing loss, worsening of the seventh cranial nerve paresis, and ulcerative keratitis (risk ratio (RR) 1.28, 95% CI 0.17 to 9.86; 1 observational study, 33 participants; very low-certainty evidence). There is no evidence that protons led to reduced toxicity. There is very low-certainty evidence to show an advantage for proton therapy in comparison to photon therapy with respect to local control, mortality, recurrence, and treatment related toxicity. Authors' conclusions There is a lack of published evidence to confirm a clinical difference in effect with either proton or photon therapy for the treatment of chordoma. As radiation techniques evolve, multi-institutional data should be collected prospectively and published, to help identify persons that would most benefit from the available radiation treatment techniques.

Although cancer is highly heterogeneous, all metastatic cancer is considered American Joint Committee on Cancer (AJCC) Stage IV disease. The purpose of this project was to redefine staging of metastatic cancer. Internal validation of nationally representative patient data from the National Cancer Database (n = 461 357; 2010-2013), and external validation using the Surveillance, Epidemiology and End Results database (n = 106 595; 2014-2015) were assessed using the concordance index for evaluation of survival prediction. A Cox proportional hazards model was used for overall survival by considering identified phenotypes (latent classes) and other confounding variables. Latent class analysis was performed for phenotype identification, where Bayesian information criterion (BIC) and sample-size-adjusted BIC were used to select the optimal number of distinct clusters. Kappa coefficients assessed external cluster validation. Latent class analysis identified five metastatic phenotypes with differences in overall survival (P

Key Points Question What are the sex differences in citation-related publication productivity across academic ranks and specialties in academic medicine? Findings This systematic review and meta-analysis found that women had lower publication productivity than men. When productivity was evaluated separately by specialty, women had lower productivity than men in all analyzed specialties except for plastic surgery; when productivity was organized by rank, women had lower productivity than men at the ranks of assistant professor, associate professor, and professor. Meaning These findings suggest that future investigation should be conducted regarding the causes of women’s decreased citation-related publication productivity within the field and interventions should be developed to provide a more equitable environment for all physicians, regardless of sex., Importance Despite equal numbers of men and women entering medical school, women are underrepresented in the upper echelons of academic medicine and receive less compensation and research funding. Citation-related publication productivity metrics, such as the h-index, are increasingly used for hiring, salary, grants, retention, promotion, and tenure decisions. Exploring sex differences in these metrics across academic medicine provides deeper insight into why differences are observed in career outcomes. Objective To systematically examine the available literature on sex differences in h-index of academic faculty physicians across all medical specialties and all levels of academic rank. Data Sources Medical literature with the term h-index found in PubMed and published between January 1, 2009, and December 31, 2018, was used. Study Selection A PICOS (Population, Intervention, Comparison, and Outcomes), PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses), and MOOSE (Meta-analysis of Observational Studies in Epidemiology) selection protocol was used to find observational studies that published h-indexes for faculty physicians that were stratified by sex. Studies were excluded if they were review articles, retracted, or unavailable online. Ultimately, 14 of 786 studies (1.78%) met the inclusion criteria. Data Extraction and Synthesis Data from 9 studies across 16 specialties were examined using weighted random-effects meta-analyses. Five studies were excluded because of overlapping specialties with another study or because they were missing appropriate statistics for the meta-analysis. Four of these studies were included in qualitative synthesis to bring the total to 13 studies. Main Outcomes and Measures The primary study outcome was the h-index. Results The meta-analysis included 10 665 North American unique academic physicians across 9 different studies from the years 2009 to 2018. Of the 10 665 physicians, 2655 (24.89%) were women. Summary effect sizes for mean h-indexes of men and women and mean h-index difference between men and women were determined for all faculty physicians and at each academic rank. Overall, female faculty had lower h-indexes than male faculty (mean difference, −4.09; 95% CI, −5.44 to −2.73; P, This systematic review and meta-analysis examines the available literature on sex differences in h-index, a measure of citation-related publication productivity, of academic faculty physicians across all medical specialties and all levels of academic rank.

We aim to systematically review and analyze the available literature on "exceptional responders" in oncology. We hypothesize that survival or patients with an exceptional response may be predicted based on clinical factors.A PICOS/PRISMA/MOOSE selection protocol was used to find studies that reported oncology patients with an exceptional response. A total of 333 initial articles were screened, and 76 articles were included, accounting for 85 patients. The primary outcome was survival after exceptional response therapy (ERT). The secondary outcome was survival since diagnosis. Univariate and multivariate analyses were conducted for both outcomes with 17 covariates.The median age was 52 years (interquartile range, 35-66 y), 51.8% were male individuals, 18 (21.2%) had lung cancer, and 1 patient (1%) met all National Cancer Institute criteria for exceptional response. The most common treatment resulting in exceptional response was a form of chemotherapy (49.2%) followed by targeted therapy (26.8%) and radiation therapy (7.7%). The median time from diagnosis to initiation of ERT was 7.92 months (interquartile range, 0-24.72 mo). On multivariate analysis of survival after initiation of ERT, there were no predictors of exceptional response. On multivariate analysis of survival since diagnosis, predictors of prolonged survival included time between diagnosis and ERT initiation (hazard ratio, 0.52; 95% confidence interval, 0.32-0.87; P=0.0124) and single prior surgery versus none (0.08; 95% confidence interval, 0.01-0.98; P=0.04853).There were no clinically apparent patient or treatment factors that predicted favorable survival following ERT; instead, reporting of exceptional response appears to be biased.

Background The objective of this study was to compare the cosmesis and recurrence rates of conventional excision (CE), Mohs micrographic surgery (MMS), external-beam radiation therapy (EBRT), or brachytherapy (BT), for basal cell carcinoma and squamous cell carcinoma of the skin. Methods Population, Intervention, Control, Outcome, Study Design (PICOS), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and Meta-Analyses of Observational Studies in Epidemiology (MOOSE) methods were used to identify studies on PubMed (from 1985 to 2018), including patients with American Joint Committee on Cancer (AJCC) T1-T2N0 basal cell carcinomas and squamous cell carcinomas and ≥10 months follow-up who received CE, MMS, EBRT, or BT. The primary endpoint was cosmesis, classified as "good," "fair," or "poor." The secondary endpoint was 1-year recurrence. Fixed-effects and random-effects meta-analyses were performed to evaluate primary and secondary outcomes with respect to treatment modality. Results In total, 18,095 studies met initial search criteria. There were 24 CE, 13 MMS, 19 EBRT, and 7 BT studies included with a total of 21,371 patients. The summary effect size for "good" cosmesis was 81% (95% CI, 70.6%-89.6%), 74.6% (95% CI, 63%-84.6%), and 97.6% (95% CI, 91.3%-100%) for CE, EBRT, and BT, respectively. Good cosmesis was 96.0% in the only MMS study that reported cosmesis. BT had improved "good" cosmesis over EBRT (P = .0025) and was similar to CE and MMS. No significant differences were seen for "fair" or "poor" cosmesis. One-year recurrence rates were low throughout at 0.8% (95% CI, 0.3%-1.6%), 0.2% (95% CI, 0%-0.6%), 2% (95% CI, 1.3%-2.7%), and 0% (95% CI, 0%-0.5%) for CE, MMS, EBRT, and BT, respectively. Conclusions For T1-T2N0 skin cancers, BT and MMS have improved cosmesis over EBRT and CE. It is unclear whether this is because of treatment superiority or selection and reporting bias. Local control is similar among all modalities at 1 year.

While the combination of stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) is becoming more widely used in the treatment of brain metastases (BM), there is a paucity of prospective data to validate both the safety and efficacy, as well as the optimal timing of these two therapies relative to one another.A PICOS/PRISMA/MOOSE selection protocol was used to identify 17 studies across 15 institutions in 3 countries. Inclusion criteria were patients: diagnosed with BM; treated with SRS/ICI, either concurrently or non-concurrently; with at least one of the primary or secondary outcome measures reported. Weighted random effects meta-analyses using the DerSimonian and Laird method were performed. The primary outcome was 1-year overall survival (OS). Secondary outcomes were 1-year local control (LC), 1-year regional brain control (RBC), and radionecrosis incidence.A total of 534 patients with 1,570 BM were included. The 1-year OS was 64.6% and 51.6% for concurrent and non-concurrent therapy, respectively (p 0.001). Local control at 1-year was 89.2% and 67.8% for concurrent and non-concurrent therapy, respectively (p = 0.09). The RBC at 1-year was 38.1% and 12.3% for concurrent and ICI administration prior to SRS, respectively (p = 0.049). The overall incidence of radionecrosis for all studies was 5.3%.Concurrent administration of SRS/ICI may be associated with improved safety and efficacy versus sequential therapy. These findings, however, are hypothesis-generating and require further validation by ongoing and planned prospective trials.

BackgroundImmunotherapy for GBM is an emerging field which is increasingly being investigated in combination with standard of care treatment options with variable reported success rates.ObjectiveTo perform a systematic review of the available data to evaluate the safety and efficacy of combining immunotherapy with standard of care chemo-radiotherapy following surgical resection for the treatment of newly diagnosed GBM.MethodsA literature search was performed for published clinical trials evaluating immunotherapy for GBM from January 1, 2000, to October 1, 2020, in PubMed and Cochrane using PICOS/PRISMA/MOOSE guidelines. Only clinical trials with two arms (combined therapy vs. control therapy) were included. Outcomes were then pooled using weighted random effects model for meta-analysis and compared using the Wald-type test. Primary outcomes included 1-year overall survival (OS) and progression-free survival (PFS), secondary outcomes included severe adverse events (SAE) grade 3 or higher.ResultsNine randomized phase II and/or III clinical trials were included in the analysis, totaling 1,239 patients. The meta-analysis revealed no statistically significant differences in group’s 1-year OS [80.6% (95% CI: 68.6%–90.2%) vs. 72.6% (95% CI: 65.7%–78.9%), p = 0.15] or in 1-year PFS [37% (95% CI: 26.4%–48.2%) vs. 30.4% (95% CI: 25.4%–35.6%) p = 0.17] when the immunotherapy in combination with the standard of care group (combined therapy) was compared to the standard of care group alone (control). Severe adverse events grade 3 to 5 were more common in the immunotherapy and standard of care group than in the standard of care group (47.3%, 95% CI: 20.8–74.6%, vs 43.8%, 95% CI: 8.7–83.1, p = 0.81), but this effect also failed to reach statistical significance.ConclusionOur results suggests that immunotherapy can be safely combined with standard of care chemo-radiotherapy without significant increase in grade 3 to 5 SAE; however, there is no statistically significant increase in overall survival or progression free survival with the combination therapy.

There has not been an assessment of the Holman Research Pathway (HRP) in radiation oncology (RO) in nearly 10 years. In this study, we sought to review the demographic characteristics, research productivity during and after residency, job placements, and National Institutes of Health (NIH) grant funding of RO residents who completed the HRP in the modern era.We created a comprehensive database of RO residents who completed the HRP between 2010 and 2019. Using a variety of data sources, we obtained demographic information, first-author manuscripts published in residency, and first- and last-author manuscripts published in the first 30 months after residency for each resident. In addition, we identified the first and current job and NIH grant funding for each resident.Ninety-seven RO residents who graduated from 50 medical schools and 25 residency programs were included. The majority were male (82.5%), had a PhD (92.8%), and identified as white (64.9%). Collectively, these residents published 212 first-author, PubMed-searchable manuscripts during residency (mean: 2.2) and 142 first- or last-author, PubMed-searchable manuscripts in the first 30 months after completion of residency (mean: 1.5). The number of first-author publications authored by HRP graduates during residency was highly correlated (r = 0.62; P.01) with the number of first- and last-author publications they authored during the first 30 months after completing residency. Ninety-six of the 97 residents (99.0%) were employed in full-time clinical positions after completing residency. Seventy-six HRP residents (78.4%) obtained an academic position as their first job after residency, only 4 of whom have since left academia, and 20 (20.6%) obtained a nonacademic position. Of the 75 HRP graduates currently employed in an academic position, 39 (52.0%) have their own laboratories. Twenty-three of the 96 HRP residents (24.0%) who secured employment in full-time clinical positions after residency switched jobs over the study period. Lastly, 33 of the 97 HRP residents (34.0%) have thus far received 47 extramural NIH research grants, 15 of which were R-01 grants.Over the past decade, the HRP has proven successful in training a new cohort of physician investigators in RO. Although productive, HRP residents have had relatively homogenous sex, educational, and racial backgrounds. Ensuring sufficient representation of residents from a variety of backgrounds in the HRP in the future will be crucial.

Introduction Patients with hepatocellular carcinoma (HCC) involving the inferior vena cava (IVC) and/or right atrium (RA) often experience debilitating symptoms, including lower extremity edema, dyspnea on exertion, shortness of breath at rest, chest pain, and ascites, that impact quality of life. The efficacy of external beam radiation therapy (EBRT) in palliating these symptoms is unclear. Thus, we sought to assess the effectiveness of EBRT in the palliation of symptoms and treatment outcomes in this patient population. Materials and methods All patients with HCC that compressed or invaded the IVC, received EBRT, and had a two-month follow-up visit to assess clinical response at our institution between 2010 and 2018 were analyzed. Patient demographics and clinical features were retrieved from the electronic medical record. Local control, local progression-free survival, and overall survival (OS) were measured from the last day of EBRT and calculated using the Kaplan-Meier method. Results Twenty-six patients with invasion or compression of the IVC were identified, 11 of whom (42%) had involvement of the RA. The median follow-up was 3.6 months. Five patients (19%) were treated with stereotactic body radiation therapy (SBRT) (all with five fractions) and 21 patients (81%) were treated with fractionated radiation therapy (range 10-16 fractions), both to a median dose of 3,000 cGy (range 2500-4000 cGy for SBRT, 2500-3750 cGy for fractionated radiation therapy). Significant proportions of patients experienced symptomatic relief from peripheral edema (54%), dyspnea on exertion (57%), shortness of breath (83%), chest pain (67%), and ascites (25%) after receiving EBRT. Additionally, they experienced few toxicities, with zero experiencing grade three or higher toxicities. One-year and two-year local control rates were 11.5% and 7.7%, respectively, and the median local progression-free survival was 4.8 months. One-year and two-year OS rates were 38.4% and 38.4%, respectively. Conclusions Our results suggest that EBRT should be considered as a potential treatment option for patients with HCC invading or compressing the IVC with or without involvement of the RA. EBRT was very well-tolerated and effectively palliated a variety of symptoms in patients with advanced disease.

PURPOSE/OBJECTIVE(S) Chest wall rib fractures are frequent complications after thoracic stereotactic body radiation therapy (SBRT). While well described for lung SBRT, limited data exists on the frequency and predictors for chest wall toxicity with SBRT to the liver for primary or metastatic lesions. We aimed to characterize the clinical, demographic and dosimetric factors of rib fractures. MATERIALS/METHODS A chart review identified 283 patients (204 male and 79 female) who received liver SBRT from 2014-2019. Univariate logistic regression models were used to identify demographic, clinical, and dosimetric factors associated with the development of rib fractures post liver SBRT. All statistical tests were two-sided and the null hypothesis was rejected for P 30 (P = 0.36) were not associated with the development of rib fractures. CONCLUSION Rib fractures after liver SBRT are a rare event and were observed in 8% of patients. Clinicians should continue to utilize well-established dose constraints and minimize radiation dose delivery to the chest wall.

PURPOSE/OBJECTIVE(S) Multiple single institution retrospective studies have suggested that managing melanoma brain metastases (MBM) with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) is associated with improved overall survival (OS) when administered concurrently (within 4 weeks) rather than sequentially (ICI and SRS administered more than 4 weeks apart). However, there is a paucity of data quantifying the risk of developing radiation necrosis (RN) in this setting. MATERIALS/METHODS The International Radiosurgery Research Foundation approved the analysis. The Kaplan Meier method and log-rank test were used to compare OS and local control (LC) at 1- and 2-years post SRS. Factors associated with the development of RN and OS were further analyzed using logistic and Cox proportional hazards regression models. The null hypothesis was rejected for P < 0.05. RESULTS There were 254 patients with 1,322 MBM treated across 10 international institutions. The median follow-up was 12.9 months, median age was 63 years (interquartile range [IQR]: 51-73 years), BRAF mutation was present in 46.6% of patients, active extracranial disease was present in 70% of patients, and the median Karnofsky Performance Status (KPS) was 90. SRS/ICI was administered concurrently in 46.5% of patients. All patients were treated on the stereotactic radiosurgery platform. The median margin dose was 20 Gy (IQR: 18-21 Gy), median number of fractions was 1 (range: 1-4), mean total brain metastasis volume was 3.4 cc and the mean V12 Gy was 8.7 cc. Radiation necrosis occurred in 14.2% of patients (5.9% Grade 1; 5.1% Grade 2; 2.8% Grade 3; 0.4% Grade 4). Overall survival at 1-year was 77.4% vs. 72.1%, and at 2-years was 63.1% vs. 46.1% (P = 0.048) for concurrent and sequential therapy, respectively. Local control at 1-year was 91.5% vs. 84.6%, and at 2-years was 84.9% vs. 75.6% (P = 0.12) for concurrent and sequential therapy, respectively. On multivariate logistic regression total treated brain metastasis volume (odds radio [OR]: 1.11; 95% confidence interval [CI]: 1.03-1.20; P = 0.008) was associated with a higher risk of development of RN; however, sequential therapy (OR: 0.97; 95% CI: 0.46-2.06; P = 0.94), and V12 (OR: 0.98; 95% CI: 0.95-1.01; P = 0.22) were not statistically significant. On multivariate cox regression, sequential therapy (hazard ratio [HR]: 1.58; 95% CI: 1.05-2.42; P = 0.03) and KPS (HR: 0.96; 95% CI: 0.94-0.98; P < 0.001) were prognostic factors for OS, while the presence of extracranial disease (HR: 1.03; 95% CI: 0.66-1.59; P = 0.90) and age (HR: 1.01; 95% CI: 1.00-1.02; P = 0.25) were not prognostic. CONCLUSION In appropriately selected patients with MBM, concurrent administration of SRS/ICI may be associated with improved OS without an increased risk of RN when compared to sequential therapy. The risk of RN appears to increase with irradiated brain volume; therefore, hypofractionated SRS may be considered in patients with high volume disease. Prospective data are needed to further evaluate these findings. AUTHOR DISCLOSURE E.J. Lehrer: None. J. Gurewitz: None. T.D. Malouff: ASTRO Bylaws Committee. K. Bernstein: None. D. Kondziolka: None. P. Bonney: None. S.I. Patel: Independent Contractor; Alberta Health Services. Research Grant; Alberta Cancer Foundation. Travel Expenses; University Hospital Foundation. Chair; Alberta Health Services. Co-Director; Alberta Health Services. Manage and screen wish applications; Make-A-Wish Foundation (Northern Alberta Chapter). J.D. Palmer: Research Grant; Varian Medical Systems, The Kroger Company. Consultant; Huron Consulting. Speaker's Bureau; Varian Medical Systems, Depuy Synthes. Advisory Board; Novocure. Member of panel; NCCN.K. Fakhoury: None. C.G. Rusthoven: Employee; SURVIVEiT (nonprofit cancer patient advocacy). Research Grant; Takeda. Advise regarding patient-facing medical content; SURVIVEiT.D. Mathieu: None. C. Deibert: None. P. Picozzi: None. B. Jones: None. C. Lee: None. S. Sharma: None. A. Niranjan: None. J.P. Sheehan: Neuropoint Alliance. M. Ahluwalia: None. D.M. Trifiletti: None.

CONTEXT: Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and gastrointestinal (GI) toxicity associated with any local salvage modality. OBJECTIVE: To quantitatively compare the efficacy and toxicity of salvage radical prostatectomy (RP), high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low–dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy. EVIDENCE ACQUISITION: We performed a systematic review of PubMed, EMBASE, and MEDLINE. Two- and 5-yr recurrence-free survival (RFS) rates and crude incidences of severe GU and GI toxicity were extracted as endpoints of interest. Random-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Estimates for each modality were then compared with RP after adjusting for individual study-level covariates using mixed-effect regression models, while allowing for differences in between-study variance across treatment modalities. EVIDENCE SYNTHESIS: A total of 150 studies were included for analysis. There was significant heterogeneity between studies within each modality, and covariates differed between modalities, necessitating adjustment. Adjusted 5-yr RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and RP. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with RP (adjusted rates of 20% after RP vs 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with RP (adjusted rates 1.8% vs 0.0%, p < 0.01), with no other differences identified. CONCLUSIONS: Large differences in 5-yr outcomes were not uncovered when comparing all salvage treatment modalities against RP. Reirradiation with SBRT, HDR brachytherapy, or LDR brachytherapy appears to result in less severe GU toxicity than RP, and reirradiation with HDR brachytherapy yields less severe GI toxicity than RP. Prospective studies of local salvage for radiorecurrent disease are warranted. PATIENT SUMMARY: In a large study-level meta-analysis, we looked at treatment outcomes and toxicity for men treated with a number of salvage treatments for radiorecurrent prostate cancer. We conclude that relapse-free survival at 5 years is equivalent among salvage modalities, but reirradiation may lead to lower toxicity.

BACKGROUND: For malignant pleural mesothelioma (MPM), the benefit of resection, as well as the optimal surgical technique, remain controversial. In efforts to better refine patient selection, this retrospective observational cohort study queried the National Cancer Database in an effort to quantify and evaluate predictors of 30- and 90-day mortality between extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D), as well as nonoperative management. METHODS: After applying selection criteria, cumulative incidences of mortality by treatment paradigm were graphed for the unadjusted and propensity-matched populations, as well as for six a priori age-based intervals (≤60, 61–65, 66–70, 71–75, 76–80, and ≥81 years). The interaction between age and hazard ratio (HR) for mortality between treatment paradigms was also graphed. Cox multivariable analysis ascertained factors independently associated with 30- and 90-day mortality. RESULTS: Of 10,723 patients, 2,125 (19.8%) received resection (n=438 EPP, n=1,687 P/D) and 8,598 (80.2%) underwent nonoperative management. The unadjusted 30/90-day mortality for EPP, P/D, and all operated cases was 3.0%/8.0%, 5.4%/14.1%, and 4.9%/12.8%, respectively. There were no short-term mortality differences between EPP and P/D following propensity-matching, within each age interval, or between age subgroups on interaction testing (P>0.05 for all). Nonoperative patients had a crude 30- and 90-day mortality of 9.9% and 24.6%, respectively. Several variables were identified as predictors of short-term mortality, notably patient age (HR 1.022, P

This cross-sectional population-based study characterizes the epidemiology of cancer in US adolescents and young adults aged 15 to 39 years with respect to (1) patient demographic characteristics, (2) cancer type frequencies, and (3) cancer incidence trends over time., Key Points Question What are the epidemiological characteristics and trends of cancers in US adolescents and young adults (AYAs) from 1973 to 2015? Findings In this serial cross-sectional, US population-based study using cancer registry data from 497 452 AYAs, the rate of cancer increased by 29.6% from 1973 to 2015, with kidney carcinoma increasing at the greatest rate. Breast carcinoma and testicular cancer were the most common cancer diagnoses for female and male AYAs, respectively. Meaning The results of this study provide further understanding of the distinct characteristics of cancer in AYAs, including incidence trends of cancer subtypes, which is valuable to guide more targeted research and interventions specifically to AYAs., Importance Previous studies have demonstrated that adolescents and young adults (AYAs) with cancer are a distinct cancer population; however, research on long-term epidemiological trends and characteristics of cancers in AYAs is lacking. Objective To characterize the epidemiology of cancer in AYAs aged 15 to 39 years with respect to (1) patient demographic characteristics, (2) frequencies of cancer types, and (3) cancer incidence trends over time. Design, Setting, and Participants This retrospective, serial cross-sectional, population-based study used registry data from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 1973, to December 31, 2015 (SEER 9 and SEER 18). The study population was from geographically distinct US regions, chosen to represent the racial and ethnic heterogeneity of the country. Initial analyses were performed from January 1 to August 31, 2019. Main Outcomes and Measures Incidence rates and descriptive epidemiological statistics for patients aged 15 to 39 years with invasive cancer. Results A total of 497 452 AYAs diagnosed from 1973 to 2015 were included in this study, with 293 848 (59.1%) female and 397 295 (79.9%) White participants. As AYAs aged, an increase in the relative incidence of carcinomas and decrease in the relative incidence of leukemias, lymphomas, germ cell and trophoblastic neoplasms, and neoplasms of the central nervous system occurred. Among the female AYAs, 72 564 (24.7%) were diagnosed with breast carcinoma; 48 865 (16.6%), thyroid carcinoma; and 33 828 (11.5%), cervix and uterus carcinoma. Among the male AYAs, 37 597 (18.5%) were diagnosed with testicular cancer; 20 850 (10.2%), melanoma; and 19 532 (9.6%), non-Hodgkin lymphoma. The rate of cancer in AYAs increased by 29.6% from 1973 to 2015, with a mean annual percentage change (APC) per 100 000 persons of 0.537 (95% CI, 0.426-0.648; P

IMPORTANCE: The oligometastatic paradigm postulates that patients with a limited number of metastases can be treated with ablative local therapy to each site of disease with curative intent. Stereotactic ablative radiotherapy (SABR) is a radiation technique that has become widely used in this setting. However, prospective data are limited and are mainly from single institutional studies. OBJECTIVE: To conduct a meta-analysis to characterize the safety and clinical benefit of SABR in oligometastatic cancer. DATA SOURCES: A comprehensive search was conducted in PubMed/MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cumulative Index to Nursing and Allied Health Literature on December 23, 2019, that included prospective clinical trials and review articles that were published within the past 15 years. STUDY SELECTION: Inclusion criteria were single-arm or multiarm prospective trials including patients with oligometastatic cancer (ie, ≤5 sites of extracranial disease), and SABR was administered in less than or equal to 8 fractions with greater than or equal to 5 Gy/fraction. DATA EXTRACTION AND SYNTHESIS: The Population, Intervention, Control, Outcomes and Study Design; Preferred Reporting Items for Systematic Reviews and Meta-analyses; and Meta-analysis of Observational Studies in Epidemiology methods were used to identify eligible studies. Study eligibility and data extraction were reviewed by 3 authors independently. Random-effects meta-analyses using the Knapp-Hartung correction, arcsine transformation, and restricted maximum likelihood method were conducted. MAIN OUTCOMES AND MEASURES: Safety (acute and late grade 3-5 toxic effects) and clinical benefit (1-year local control, 1-year overall survival, and 1-year progression-free survival). RESULTS: Twenty-one studies comprising 943 patients and 1290 oligometastases were included. Median age was 63.8 years (interquartile range, 59.6-66.1 years) and median follow-up was 16.9 months (interquartile range, 13.7-24.5 months). The most common primary sites were prostate (22.9%), colorectal (16.6%), breast (13.1%), and lung (12.8%). The estimate for acute grade 3 to 5 toxic effect rates under the random-effects models was 1.2% (95% CI, 0%-3.8%; I(2) = 50%; 95% CI, 3%-74%; and τ = 0.20%; 95% CI, 0.00%-1.43%), and the estimate for late grade 3 to 5 toxic effects was 1.7% (95% CI, 0.2%-4.6%; I(2) = 54%; 95% CI, 11%-76%; and τ = 0.25%; 0.01%-1.00%). The random-effects estimate for 1-year local control was 94.7% (95% CI, 88.6%-98.6%; I(2) = 90%; 95% CI, 86%-94%; and τ = 0.81%; 95% CI, 0.36%-2.38%]). The estimate for 1-year overall survival was 85.4% (95% CI, 77.1%-92.0%; I(2) = 82%; 95% CI, 71%-88%; and τ = 0.72%; 95% CI, 0.30%-2.09%) and 51.4% (95% CI, 42.7%-60.1%; I(2) = 58%; 95% CI, 17%-78%; and τ = 0.20%; 95% CI, 0.02%-1.21%) for 1-year progression-free survival. CONCLUSIONS AND RELEVANCE: In this meta-analysis, SABR appears to be relatively safe in patients with oligometastatic cancer with clinically acceptable rates of acute and late grade 3 to 5 toxic effects less than 13% and with clinically acceptable rates of 1-year local control overall survival, and progression-free survival. These findings are hypothesis generating and require validation by ongoing and planned prospective clinical trials.

Background and purpose Immune checkpoint inhibitor with radiation therapy (ICI + RT) is under investigation for improved patient outcome, so we performed a systematic review/meta-analysis of toxicities for ICI + RT compared to immune checkpoint inhibitor (ICI) therapy alone. Materials and methods A PRISMA-compliant systematic review of studies in MEDLINE (PubMed) and in the National Comprehensive Cancer Network guidelines was conducted, with primary outcome grade 3 + toxicity. Criteria for ICI alone were: phase III/IV trials that compared immunotherapy to placebo, chemotherapy, or alternative immunotherapy; and for ICI + RT: prospective/retrospective studies with an arm treated with ICI + RT. Meta-analysis was performed by random effects models using the DerSimonian and Laird method. The I2 statistic and Cochran’s Q test were used to assess heterogeneity, while funnel plots and Egger’s test assessed publication bias. Results This meta-analysis included 51 studies (n = 15,398), with 35 ICI alone (n = 13,956) and 16 ICI + RT studies (n = 1,442). Our models showed comparable grade 3–4 toxicities in ICI + RT (16.3%; 95% CI, 11.1–22.3%) and ICI alone (22.3%; 95% CI, 18.1–26.9%). Stratification by timing of radiation and irradiated site showed no significant differences, but anti-CTLA-4 therapy and melanoma showed increased toxicity. The grade 5 toxicities were 1.1% and 1.9% for ICI alone and ICI + RT respectively. There was significant heterogeneity, but not publication bias. Conclusions The random effects model showed comparable grade 3–4 toxicity in using ICI + RT compared to ICI alone in CNS melanoma metastases, NSCLC, and prostate cancer. ICI + RT is safe for future clinical trials in these cancers.

Stereotactic body radiation therapy (SBRT), low dose rate brachytherapy (LDR-BT) and high dose rate brachytherapy (HDR-BT) are ablative-intent radiotherapy options for prostate cancer (PCa). These vary considerably in dose delivery, which may impact post-treatment prostate-specific antigen (PSA) patterns and biochemical control. We compared PSA kinetics between SBRT, HDR-BT, and LDR-BT, and assessed their relationships to biochemical recurrence-free survival (BCRFS).Retrospective PSA data were analyzed for 3502 men with low-risk (n = 2223; 63.5%), favorable intermediate-risk (n = 869; 24.8%), and unfavorable intermediate-risk (n = 410; 11.7%) PCa treated with SBRT (n = 1716; 49.0%), HDR-BT (n = 512; 14.6%), or LDR-BT (n = 1274; 36.4%) without upfront androgen deprivation therapy at 10 institutions from 1990 to 2017. We compared nadir PSA (nPSA), time to nPSA, achievement of nPSA0.2 ng/mL and0.5 ng/mL, rates of nPSA0.4 ng/mL at 4 years, and BCRFS.Median follow-up was 72 months. Median nPSA and nPSA0.2 ng/mL were stratified by risk group (interaction p ≤ 0.001). Median nPSA and time to nPSA were 0.2 ng/mL at 44 months after SBRT, 0.1-0.2 ng/mL at 37 months after HDR-BT, and 0.01-0.2 ng/mL at 51 months after LDR-BT (mean log nPSA p ≤ 0.009 for LDR-BT vs. SBRT or HDR-BT for low/favorable intermediate-risk). There were no differences in nPSA0.4 ng/mL at 4 years (p ≥ 0.51). BCRFS was similar for all three modalities (p ≥ 0.27). Continued PSA decay beyond 4 years was predictive of durable biochemical control.LDR-BT led to lower nPSAs with longer continued decay compared to SBRT and HDR-BT, but no differences in BCRFS.

Background Human papilloma virus (HPV) has been implicated in the pathology of oropharyngeal head and neck cancers, but its role in sinonasal squamous cell carcinoma (SNSCC) has not been well established. Methods Thirty‐two patients with SNSCC diagnosed between 2011 and 2018 were identified and stratified by HPV status and viral serotype, as determined by PCR. Endpoints including recurrence, metastases and survival were analyzed using the Kaplan‐Meier method. Results Seventeen (53%) patients were HPV‐positive and 15 (47%) were HPV‐negative. The median follow‐up time of living patients was 30.7 months (range 4‐123 months). Survival did not differ by HPV status, but HPV+ tumors were more likely to locally recur and metastasize. When stratifying by treatment type, the lowest rate of recurrence occurred in patients receiving surgery and chemoradiation. Conclusion A significant proportion of sinonasal tumors appear to be associated with HPV. Testing for HPV might be justified in all cases of sinonasal cancers. Further investigation is warranted to better understand the role of HPV in SNSCC.

Intraoperative stimulation (IS) mapping has become the preferred standard treatment for eloquent tumors as it permits a more accurate identification of functional areas, allowing surgeons to achieve higher extents of resection (EOR) and decrease postoperative morbidity. For lesions adjacent to the perirolandic area and descending motor tracts, mapping can be done with both awake craniotomy (AC) and under general anesthesia (GA). We aimed to determine which anesthetic protocol—AC vs. GA—provides better patient outcomes by comparing EOR and postoperative morbidity for surgeries using IS mapping in gliomas located near or in motor areas of the brain. A systematic literature search was carried out to identify relevant studies from 1983 to 2019. Seven databases were screened. A total of 2351 glioma patients from 17 studies were analyzed. A random-effects meta-analysis revealed a trend towards a higher mean EOR in AC [90.1% (95% C.I. 85.8–93.8)] than with GA [81.7% (95% C.I. 72.4–89.7)] (p = 0.06). Neurological deficits were divided by timing and severity for analysis. There was no significant difference in early neurological deficits [20.9% (95% C.I. 4.1–45.0) vs. 25.4% (95% C.I. 13.6–39.2)] (p = 0.74), late neurological deficits [17.1% (95% C.I. 0.0–50.0) vs. 3.8% (95% C.I. 1.1–7.6)] (p = 0.06), or in non-severe [28.4% (95% C.I. 0.0–88.5) vs. 20.1% (95% C.I. 7.1–32.2)] (p = 0.72), and severe morbidity [2.6% (95% C.I. 0.0–15.5) vs. 4.5% (95% C.I. 1.1–9.6)] (p = 0.89) between patients who underwent AC versus GA, respectively. Mapping during resection of gliomas located in or near the perirolandic area and descending motor tracts can be safely carried out with both AC and GA.

Introduction To characterize the efficacy (5-year disease-free survival [DFS]) and safety (incidence of grade 2+ late gastrointestinal or genitourinary toxicity) of ultrahypofractionated radiation therapy (UHRT) versus hypofractionated radiation therapy (HFRT) and conventionally fractionated radiation therapy (CFRT) by comparing patients treated on phase III protocols. Methods A PICOS/PRISMA/MOOSE protocol was used to identify eligible studies. Weighted random effects meta-analyses were conducted using the DerSimonian and Laird method. Wald-type tests were used to compare treatment modalities for each outcome, where the null hypothesis was rejected for p Results Seven studies were included that consisted of 6795 patients (2849 CFRT, 3357 HFRT, and 589 UHRT). Median age was 68 years. Summary effect sizes for 5-year DFS were 85.1% (95% CI: 82.1%-87.8%) for CFRT, 86% (95% CI: 83%-88.7%) for HFRT, and 85% (95% CI: 80%-87%) for UHRT (p = 0.66 and p = 0.8 for CFRT vs. HFRT and CFRT versus UHRT, respectively). Summary effect sizes for late grade 2+ gastrointestinal toxicity were 12.1% (95% CI: 9.2%-15.4%) for CFRT, 14.6% (95% CI: 9.9%-20%) for HFRT, and 10% (95% CI: 7%-13%) for UHRT (p = 0.41 and p = 0.09 for CFRT versus HFRT and CFRT versusus UHRT, respectively). Summary effect sizes for late grade 2+ genitourinary toxicity were 19.4% (95% CI: 10.7-29.9%) for CFRT, 20.4% (95% CI: 10.2%-32.9%) for HFRT, and 18% (95% CI: 15%-22%) for UHRT (p = 0.89 and p = 0.92 for CFRT versus HFRT and CFRT versus UHRT, respectively). Conclusion Ultrahypofrationated regimens appear to offer similar levels of safety and efficacy to CFRT and HFRT. These findings are hypothesis-generating and require further validation by ongoing prospective trials.

To assess the impact of RTOG-9601 and GETUG-AFU-16 on the routine use of combination androgen deprivation therapy (ADT) with postoperative radiotherapy (PORT) for prostate cancer (CaP).Patients with localized CaP treated with radical prostatectomy (RP) and PORT with or without ADT at a comprehensive cancer center from January 2006 to June 2007 (Period 1 = P1), July 2011 to December 2012 (Period 2 = P2), and January 2017 to June 2018 (Period 3 = P3) were included. Clinicopathologic features and treatment characteristics were analyzed and compared. Multivariable logistic regression was used to assess prognostic factors and association with ADT use. Statistical tests were two-sided and a P value0.05 was considered significant. To validate the findings, United States National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results (SEER) data were collected to assess rates of combined ADT and PORT from 2004 to 2015.Five hundred and two patients were included: 152 (P1), 185 (P2), and 165 (P3). PORT was most commonly delivered as early SRT (delivered1 year post-RP with undetectable PSA or PSA0.05 and ≤0.5 ng/ml) in all periods. The use of combination PORT and ADT increased over time: 14.5% (P1), 32% (P2), and 41% (P3) (P0.001). The proportion of patients that met eligibility criteria for either GETUG-AFU-16 or RTOG-9601 decreased from 47% (P1) to 35% (P3) (P = 0.04). International Society of Urological Pathology grade ≥4 (P0.002) and pre-PORT PSA0.5 ng/ml (P0.001) were associated with use of ADT. Positive surgical margin status had a negative association (RR 0.5, P0.002). The NCDB demonstrated similar trends for use of combined ADT with PORT, increasing from 37% to 49% from 2004 to 2015.The use of combined ADT with PORT increased over time. However, only a third of contemporary patients undergoing PORT are represented in the major trials supporting the evidence for combination treatment, highlighting the need to characterize the modern impact of this intensification strategy.

Aims The objectives of this study were to (1) characterize the epidemiology of liver metastases at the time of primary cancer diagnosis (synchronous liver metastases), (2) characterize the incidence trends of synchronous liver metastases from 2010−2015 and (3) assess survival of patients with synchronous liver metastases. Methods The Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 was queried to obtain cases of patients with liver metastases at the time of primary cancer diagnosis. The primary cancers with an incidence rate of liver metastasis >0.1 are presented in this analysis. Results Among 2.4 million cancer patients, 5.14 % of cancer patients presented with synchronous liver metastases. The most common primary site was breast cancers for younger women (ages 20–50), and colorectal cancers for younger men. As patients get older, a more heterogenous population of the top cancers with liver metastases emerges including esophageal, stomach, small intestine, melanoma, and bladder cancer in addition to the large proportion of lung, pancreatic, and colorectal cancers. The 1-year survival of all patients with liver metastases was 15.1 %, compared to 24.0 % in those with non-hepatic metastases. Regression analysis showed that the presence of liver metastasis was associated with reduced survival, particularly in patients with cancers of the testis, prostate, breast, and anus, and in those with melanoma. Conclusions The most common primary sites for patients with liver metastases varied based on age at diagnosis. Survival for patients with liver metastasis was significantly decreased as compared to patients without liver metastasis.

Background: This study evaluated the incidence of de novo bone metastasis across all primary cancer sites and their impact on survival by primary cancer site, age, race, and sex. Questions/purposes: Our objectives were (I) characterize the epidemiology of de novo bone metastasis with respect to patient demographics, (II) characterize the incidence by primary site, age, and sex (2010–2015), and (III) compare survival of de novo metastatic cancer patients with and without bone metastasis. Methods: This is a retrospective, population-based study using nationally representative data from the Surveillance, Epidemiology, and End Results program, 2010–2015. Incidence rates by year of diagnosis, annual percentage changes, Kaplan-Meier, univariate and multiple Cox regression models are included in the analysis. Results: Of patients with cancer in the SEER database, 5.1% were diagnosed with metastasis to bone, equaling ~18.8 per 100,000 bone metastasis diagnoses in the US per year (2010–2015). For adults >25, lung cancer is the most common primary site (2015 rate: 8.7 per 100,000) with de novo bone metastases, then prostate and breast primaries (2015 rates: 3.19 and 2.38 per 100,000, respectively). For patients

Background The objectives of this study were to characterize (1) epidemiology of brain metastases at the time of primary cancer diagnosis, (2) incidence and trends of synchronous brain metastases from 2010 to 2015, and (3) overall survival (OS) of patients with synchronous brain metastases. Methods A total of 42 047 patients with synchronous brain metastases from 2010 to 2015 were identified from the Surveillance, Epidemiology, and End Results database. Descriptive analysis was utilized to analyze demographics and incidence. The Kaplan–Meier method and a Cox proportional hazards model were utilized to evaluate potential prognostic factors for OS. Results The majority of patients were diagnosed from age older than 50 (91.9%). Common primary sites included lung (80%), melanoma (3.8%), breast (3.7%), and kidney/renal pelvis (3.0%). Among pediatric patients, common primaries included kidney/renal pelvis and melanomas. The incidence was roughly 7.3 persons/100 000. Synchronous brain metastases were associated with significantly poorer OS compared to extracranial metastases alone (hazard ratio [HR] =1.56; 95% CI: 1.54–1.58; P < .001). Among patients with brain metastases, male gender (HR = 1.60 vs 1.52), age older than 65 years (HR = 1.60 vs 1.46), synchronous liver, bone, or lung metastases (HR = 1.61 vs 1.49), and earlier year of diagnosis (HR = 0.98 for each year following 2010) were associated with significantly poorer OS. Conclusions The vast majority of brain metastases are from lung primaries. Synchronous brain metastases are associated with poorer OS compared to extracranial metastases alone.

The health care industry has many stakeholders who seek relationships within government to ensure certain interests are considered in the legislative process. This study characterized the federal political contributions of US radiation oncologists (ROs).Public finance data from the Federal Election Commission (FEC) containing self-identified ROs' contributions to a federal candidate or committee were obtained from 2003 to 2018. Contribution recipients were classified as a political action committee (PAC) or a presidential, Senate, or House candidate. Political parties of recipients were based on FEC designations. For PACs, political parties of recipients were based on spending patterns to political parties in each 2-year election cycle or, when unavailable, overall spending patterns of greater than 50% to 1 political party, as detailed by the Center for Responsive Politics. Data were analyzed temporally, and Spearman's rho was used to assess trends.From 2003 to 2018, the FEC reported a total of 31,646,000 federal political contributions. Exactly 4617 federal political contributions were made from 1021 unique self-identified ROs, totaling $3,350,747. The number of ROs making contributions ranged from 56 in 2005 to 600 in 2016 (mean, 289 ± 191.4 ROs yearly), with a mean annual contribution of $209,422. Of all RO dollars, 61.5% went to Democrats, 37.5% to Republicans, and 1.0% to third-party candidates. Most RO dollars (81.0%) went to PACs rather than candidates, with the majority of those PAC dollars (50.2%) directed toward the American Society for Radiation Oncology Political Action Committee. There was a positive annual trend in number of donors by year (ρ = 0.83, P.0001) as well as RO contributions to the House (ρ = 0.58, P.02), Senate (ρ = 0.58, P.02), Democrats (ρ = 0.81, P.001), Republicans (ρ = 0.66, P.006), third-parties (ρ = 0.87, P.001), PACs (ρ = 0.85, P.0001), and overall (ρ = 0.8, P.001). There was not a significant trend in contributions to presidential candidates (ρ = 0.71, P = .06).ROs' federal political contributions have significantly increased over the last decade and a half. This growth overwhelmingly represents contributions to specialty-focused PACs and both Democratic and Republican congressional candidates.

Background The goal of this study was to characterize the efficacy and safety of stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation therapy with concurrent chemotherapy (CFRT) for the definitive treatment of locally advanced pancreatic cancer. The primary outcome measure was efficacy, defined by 2-year overall survival (OS). Secondary outcomes were incidence of any grade 3/4 toxicity and 1-year OS. Methods A PICOS/PRISMA/MOOSE selection protocol was used to identify eligible studies. Inclusion criteria were: 1) patients diagnosed with locally advanced N0-1 M0 pancreatic cancer; 2) CFRT 1.8 to 2.0 Gy/fraction with chemotherapy per protocol or SBRT ≥5 Gy/fraction in ≤5 fractions; 3) either no control group or another definitive chemotherapy or radiation therapy arm; 4) at least 1 of the outcome measures reported; and 5) single or multi-arm phase 2/3 prospective study for CFRT and/or phase 1/2 or retrospective study for SBRT. Neoadjuvant and/or adjuvant chemotherapy was prescribed per protocol specifications. Weighted random effects meta-analyses were conducted using the DerSimonian and Laird method to characterize summary effect sizes for each outcome. Results A total of 470 studies were initially screened; of these, 9 studies assessed SBRT and 11 studies assessed CFRT. For SBRT, the median dose was 30 Gy, and the most common regimen was 30 Gy/5 fractions. For CFRT, doses ranged from 45 to 54 Gy in 1.8- to 2.0-Gy fractions, with the majority of studies delivering 50.4 Gy in 28 fractions with concurrent gemcitabine. The random effects estimate for 2-year OS was 26.9% (95% CI, 20.6%-33.6%) for SBRT versus 13.7% (95% CI, 8.9%-19.3%) for CFRT and was statistically significant in favor of SBRT. The random effects estimate for 1-year OS was 53.7% (95% CI, 39.3%-67.9%) for SBRT versus 49.3% (95% CI, 39.3%-59.4%) for CFRT, and was not statistically significant. The random effects estimate for acute grade 3/4 toxicity was 5.6% (95% CI, 0.0%-20.0%) for SBRT versus 37.7% (95% CI, 24.0%-52.5%) for CFRT and was statistically significant in favor of SBRT. The random effects estimate for late grade 3/4 toxicity was 9.0% for SBRT (95% CI, 3.3%-17.1%) versus 10.1% (95% CI, 1.8%-23.8%) for CFRT, which was not statistically significant. Conclusion These results suggest that SBRT for LAPC may result in a modest improvement in 2-year OS with decreased rates of acute grade 3/4 toxicity and no change in 1-year-OS or late toxicity. Further study into the use of stereotactic body radiation therapy for these patients is needed.

PURPOSE/OBJECTIVE(S) The optimal treatment for unresectable pancreatic cancer remains unclear, as patients with locally advanced pancreatic cancer (LAPC) have poor outcomes despite aggressive therapies. Due to these poor outcomes, there has been interest in advanced techniques for definitive radiation, and robust literature has emerged for the definitive irradiation of LAPC, including photon-based techniques such as SBRT and IMRT/VMAT, proton, and carbon-ion irradiation. Despite promising early results, there are few advanced-stage clinical trials comparing these modalities. MATERIALS/METHODS A systematic review was performed in December 2020 on PubMed/Medline using the following search terms: "pancreas" and "carbon ion radiotherapy," "proton," "stereotactic body radiation therapy," "SBRT," "IMRT," or "VMAT," which yielded 860 results. Retrospective or prospective studies using either SBRT, IMRT, VMAT, proton, or carbon ion radiotherapy for definitive radiation with or without concurrent chemotherapy were included. Resectable/borderline resectable, adjuvant radiation, and trials using older radiation techniques (3D conformal, 2D planning) were excluded from analysis. The primary outcomes were grade 3-5 acute and late toxicity, with secondary outcomes including 1-year overall survival (OS) and 1-year local control (LC). Random effects meta-analyses were conducted for each primary and secondary outcome using the restricted maximum likelihood method. The Wald-type test was used to compare treatment modalities, where the null hypothesis was rejected for P < 0.05. RESULTS A total of 6 particle studies (proton and carbon ion) and 11 photon studies (IMRT/VMAT and SBRT) were included in the final analysis. The summary effect size for acute grade 3-5 toxicity was 4.9% for photon irradiation compared to 2.7% with particles (P = 0.46). The summary effect size for late grade 3-5 toxicities were 3.7% and 1.0% for photons and particles, respectively (P = 0.13). At 1 year, LC was 71.6% with photons and 86.7% with particles (P = 0.07), with OS of 59.3% and 74.4%, respectively (P = 0.09). CONCLUSION Particle therapy with protons or carbon appears to be at least equally efficacious and safe compared to advanced photon-based treatment techniques in the treatment of unresectable pancreatic cancer. These findings are hypothesis generating and should be validated in well-designed prospective trials.

PURPOSE/OBJECTIVE(S): The COVID-19 pandemic has resulted in over 2 million deaths worldwide and numerous studies demonstrate cancer patients are at increased risk of mortality. In this current study, the authors seek to investigate patient characteristics, clinical course, and predictors of COVID-19 diagnosis, severity and mortality in patients with active cancer at Elmhurst Hospital. MATERIALS/METHODS: A retrospective analysis of patients presenting to our institution with an active cancer diagnosis between January-June 2020 was performed. Inclusion criteria consisted of diagnosis of cancer or active cancer-directed treatment including surgery, radiation, and systemic therapy during this time period. Demographic, clinical characteristics, treatment, SARS-CoV-2 laboratory results, and outcomes were evaluated. Statistical analysis was performed using students t-test, chi-square, and Fisher's exact test. COVID-confirmed death required confirmatory laboratory evidence for SARS-CoV-2 using RT-PCR testing. Severe events were defined as patients requiring hospitalization, oxygen supplementation, mechanical ventilation, or death. RESULTS: 266 patients met inclusion criteria for this study. 108 patients were tested for COVID-19 with 21 testing positive. Only 7.9% of cancer patients tested positive for SARS-CoV-2 with a test-positive rate of 19.4%. Median age of entire cohort was 61 years old (IQR 52-69) and 55 years old (IQR 46-70) in COVID positive cohort. There was a male preponderance in COVID positive cohort (66.7%, P = 0.07) and COVID-confirmed deaths (83.3%, P = 0.09) that trended toward statistical significance. A higher proportion of COVID positive patients (66.7%) and COVID-confirmed deaths (83.3%) were of Hispanic ethnicity compared to patients without COVID diagnosis (53.0%, P = 0.23) and patients who died without COVID (31.6%, P = 0.06); however, this was not statistically significant. Furthermore, there was a statistically significant higher proportion of COVID positive patients that were receiving cytotoxic chemotherapy compared non-COVID patients (P = 0.02). The overall 30-day mortality in this cohort of cancer patients was 2.3%, with 3% of patients having severe events. Of the cancer patients who tested positive, 9 had severe events (42.9%) and 6 had confirmed COVID-related deaths (28.6%). There were no significant predictors for diagnosis of COVID nor were there significant predictors of severity or mortality. CONCLUSION: The incidence of laboratory confirmed SARS-CoV-2 infection in cancer patients during the height of the COVID-19 pandemic in New York City was low suggesting safety procedures implemented were effective. Patients receiving radiation treatment were not at increased risk of COVID diagnosis but patients receiving cytotoxic chemotherapy were. Based on our analysis, patients with cancer seem to be at increased risk for mortality (case-fatality rate of 29%) and severe events (43%) due to the SARS-CoV-2 infection compared to general population.

PURPOSE/OBJECTIVE(S) Staging for metastatic disease is unreliable; there is usually only one category of Stage IV in the American Joint Commission on Cancer (AJCC) 8th edition, but survival can range from weeks to years. We hypothesize that prognostication can be improved for metastatic disease by using common clinical covariates in a pan-cancer phenotype staging system. MATERIALS/METHODS Latent class analysis was performed to explore the phenotypes using nationally representative patient data from the National Cancer Database (NCDB; n = 461,357, years 2010-2013, for the training cohort) and the Surveillance, Epidemiology, and End Results database (SEER; n = 106,595, years 2014-2015, for the validation cohort). The optimal number of clusters was determined based on Bayesian information criterion (BIC) and sample-size-adjusted BIC. Kappa coefficients were used to assess external validation. In addition, we used a Cox proportional hazards model with latent classification for survival prediction. Internal validation of the NCDB and the external validation of the training set of SEER were assessed using the concordance (C)-index. RESULTS Of the 461,357 patients included from the NCDB (median age 65), latent class analysis identified five metastatic phenotypes: (Stage IVA) nearly-exclusive bone-only metastases, commonly seen in lung, breast, and prostate cancer (n = 59,049, 12.8%; median survival = 12.7 months); (IVB) predominant lung metastases, commonly seen in breast, stomach, kidney, ovary, uterus, thyroid, cervix, and soft tissue cancer (n = 62,491, 13.6%; median survival = 11.4 months); (IVC) predominant liver/lung metastases, commonly seen in colon, rectum, pancreas, lung, esophagus, and stomach cancer (n = 130,014, 28.2%; median survival = 7.0 months); (IVD) bone/liver/lung metastases predominant over brain, commonly seen in lung and breast cancer (n = 61,004, 13.2%; median survival = 5.9 months); (IVE) brain/lung metastases predominant over bone/liver, commonly seen in lung cancer and melanoma (n = 148,799, 32.3%; median survival = 5.7 months). These phenotypes had differences in overall survival, and long-term survivors were identified in Stages IVA-B (P < 0.0001). A pan-cancer nomogram model to predict survival (STARS; based on Site, Tumor, Age, Race, Sex) was created and validated. STARS has 13% better prognostication than AJCC: C-index at 1 month of 0.69 (95% CI 0.68-0.69) vs 0.61 (95% CI 0.60-0.61). CONCLUSION We created and validated a novel pan-cancer staging system for metastatic disease, termed STARS, which is significantly more prognostic than AJCC staging. STARS is innovative because: (1) it takes a global approach, not just focusing on primary tumor, (2) it can be used in all communities, since it relies on readily available, inexpensive predictors; (3) it is simple and allows for rapid validation.

PURPOSE/OBJECTIVE(S) We aimed to examine how the rise of open access (OA) journals in biomedicine has impacted resident research in radiation oncology. MATERIALS/METHODS We built a comprehensive database of first-author, PubMed-searchable articles published by US radiation oncology residents who graduated between 2015 and 2019. We then classified each journal in which these manuscripts appeared as either OA or non-OA, and obtained the current article processing charge (APC) for every publication that appeared in an OA journal. Lastly, we performed a secondary analysis to identify the factors associated with publishing an article in an OA journal. RESULTS The US radiation oncology residents in this study published 2,637 first-author, PubMed-searchable manuscripts, 555 (21.0%) of which appeared in 138 OA journals. The number of publications in OA journals increased from 0.47 per resident for the class of 2015 to 0.79 per resident for the class of 2019. Likewise, the number of publications in OA journals with a 2019 impact factor of zero increased from 0.14 per resident for the class of 2015 to 0.43 per resident for the class of 2019. Publications in OA journals garnered fewer citations than those in non-OA journals (8.9 versus 14.9, P < 0.01). 90.6% of OA journals levy an APC for original research reports (median $1,896), which is positively correlated with their 2019 impact factor (r = 0.63, P < 0.01). Aggregate APCs totaled $900,319.21 for all US radiation oncology residency programs and appeared to increase over the study period. CONCLUSION The number of first-author, PubMed-searchable manuscripts published by graduating US radiation oncology residents in OA journals rose significantly over the study period. US radiation oncology residency programs appear to be investing increasing and significant sums of money to publish the work of their residents in these journals. A more substantive discussion about the proper role of OA journals in resident research is needed.