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Introduction/Background: Second primary lung cancers (SPLC) are common following non-small cell lung cancer (NSCLC) treatment. Development of SPLC following stereotactic ablative radiation therapy (SABR) may differ as compared to surgical cohorts. We report incidence of and outcomes for SPLC detected by surveillance imaging in a cohort of patients treated with SABR. Materials/Methods: Patients treated with SABR for node-negative NSCLC between 02/2007-05/2019 were retrospectively identified. Patient characteristics, frequency of surveillance imaging, development of SPLC, recurrence patterns, and survival were reviewed. Surveillance CT was performed Q3-4 month year one, Q3-6 month year 2, Q6-12 month year 3-5, and Q12 month thereafter. Actuarial estimates of development of SPLC and overall survival (OS) were generated with competing risk analysis. Results: We identified 134 patients treated with SABR with ≥6 months follow up. Eighteen (13.4%) developed a total of 21 SPLC at a median of 28.5 months (range 3.0-84.7 months) following SABR, 19 (90.5%) biopsy-proven. Twenty (95.2%) SPLC were detected by surveillance imaging. Three patients developed 2 metachronous SPLC. Three and 5-year SPLC estimates were 11.7% and 13.1%. Eighteen (85.7%) SPLC were treated with curative intent. Two and 3-year estimate of OS following detection of SPLC was 79.8% and 54.7%. Conclusion: SPLC were more common in our cohort than other published studies. Outcomes following surveillance detected SPLC are similar to those of de novo early stage lung cancers. The high frequency of SPLC in our cohort suggests further studies to refine overall surveillance in very high-risk populations are needed.

IntroductionWe investigated whether adding computed tomography (CT) and/or 18F-fluorodeoxyglucose (18F-FDG) PET radiomics features to conventional prognostic factors (CPFs) improves prognostic value in locally advanced non-small cell lung cancer (NSCLC).Materials and methodsWe retrospectively identified 39 cases with stage III NSCLC who received chemoradiotherapy and underwent planning CT and staging 18F-FDG PET scans. Seven CPFs were recorded. Feature selection was performed on 48 CT and 49 PET extracted radiomics features. A penalized multivariate Cox proportional hazards model was used to generate models for overall survival based on CPFs alone, CPFs with CT features, CPFs with PET features, and CPFs with CT and PET features. Linear predictors generated and categorized into 2 risk groups for which Kaplan-Meier survival curves were calculated. A log-rank test was performed to quantify the discrimination between the groups and calculated the Harrell's C-index to quantify the discriminatory power. A likelihood ratio test was performed to determine whether adding CT and/or PET features to CPFs improved model performance.ResultsAll 4 models significantly discriminated between the 2 risk groups. The discriminatory power was significantly increased when CPFs were combined with PET features (C-index 0.82; likelihood ratio test P < .01) or with both CT and PET features (0.83; P < .01) compared with CPFs alone (0.68). There was no significant improvement when CPFs were combined with CT features (0.68).ConclusionAdding PET radiomics features to CPFs yielded a significant improvement in the prognostic value in locally advanced NSCLC; adding CT features did not.

Background The limited availability of proton beam therapy (PBT) requires individual treatment selection strategies that can be based on normal tissue complication probability (NTCP) models. We developed and externally validated NTCP models for common late side-effects following PBT in brain tumour patients to optimise patients’ quality of life. Methods Cohorts from three PBT centres (216 patients) were investigated for several physician-rated endpoints at 12 and 24 months after PBT: alopecia, dry eye syndrome, fatigue, headache, hearing and memory impairment, and optic neuropathy. Dose-volume parameters of associated normal tissues and clinical factors were used for logistic regression modelling in a development cohort. Statistically significant parameters showing high area under the receiver operating characteristic curve (AUC) values in internal cross-validation were externally validated. In addition, analyses of the pooled cohorts and of time-dependent generalised estimating equations including all patient data were performed. Results In the validation study, mild alopecia was related to high dose parameters to the skin [e.g. the dose to 2% of the volume (D2%)] at 12 and 24 months after PBT. Mild hearing impairment at 24 months after PBT was associated with the mean dose to the ipsilateral cochlea. Additionally, the pooled analyses revealed dose–response relations between memory impairment and intermediate to high doses to the remaining brain as well as D2% of the hippocampi. Mild fatigue at 24 months after PBT was associated with D2% to the brainstem as well as with concurrent chemotherapy. Moreover, in generalised estimating equations analysis, dry eye syndrome was associated with the mean dose to the ipsilateral lacrimal gland. Conclusion We developed and in part validated NTCP models for several common late side-effects following PBT in brain tumour patients. Validation studies are required for further confirmation.

OBJECTIVE To evaluate surfactant protein D (SP-D) concentrations in serum and bronchoalveolar lavage fluid (BALF) from young healthy horses on pasture or housed in a typical barn. ANIMALS 20 young healthy horses. PROCEDURES Horses were randomly assigned to 1 of 2 groups (pasture, n = 10; barn, 10), and serum and BALF samples were collected for SP-D determination at baseline (all horses on pasture) and 2 weeks and 4 weeks after the barn group of horses was relocated from the pasture to the barn. Other evaluations included physical and tracheoscopic examinations. Findings were compared within and between groups. RESULTS Physical and tracheoscopic examinations, CBC, and serum biochemical analysis did not reveal evidence of respiratory disease, and no significant differences were present within and between groups. Serum SP-D concentrations did not significantly differ within and between groups, but BALF SP-D concentrations were significantly lower for the barn group at 2 weeks but not at 4 weeks, compared with baseline. The BALF SP-D concentration-to-BALF total protein concentration ratio was < 1.5 and did not significantly differ within and between groups. CONCLUSIONS AND CLINICAL RELEVANCE A mild decrease was evident in the concentration of SP-D in the BALF collected from young healthy horses after 2 weeks of exposure to a barn environment. The clinical importance of this finding remains to be determined.

PURPOSE: Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) is a standard of care for medically inoperable patients. Our aim was to compare Common Terminology Criteria for Adverse Events (CTCAE) thoracic grade 3 or higher adverse events (AEs) of 30 Gy in one fraction (arm 1) vs. 60 Gy in 3 fractions (arm 2). METHODS: This was a randomized multi-institutional, phase II, two-arm, clinical trial. Medically inoperable patients with biopsy-proven peripheral T1/T2N0M0 NSCLC tumors were enrolled. Patients were randomized to arm 1 or arm 2 and stratified by performance status. The primary endpoint was CTCAE thoracic grade 3 or higher AEs. Secondary end points were local control (LC), progression-free survival (PFS), overall survival (OS), and quality of life (QOL). RESULTS: Between September, 2008 and April, 2015, 98 patients were randomized. Median follow-up was 53.8 months. 10 patients were lost to follow-up; 1 in arm 1 and 9 in arm 2. Thoracic grade 3 AEs were experienced by 8 (16%) patients on arm 1 and 6 (12%) patients on arm 2 there were no grade 4 or 5 AEs.. There were no differences in LC, PFS or OS (p= 0.68, 0.86 and 0.94, respectively). Arm 1 reported better social functioning (p=0.006) with less dyspnea (p=0.016) in follow-up at 6 months. CONCLUSIONS: This randomized phase II study demonstrated 30 Gy in one fraction was equivalent to 60 Gy in three fractions in terms of toxicity, LC, PFS and OS. QOL measures of social functioning and dyspnea favored single fraction SBRT.

The systemic inflammatory response is associated with the loss of lean tissue, anorexia, weakness, fatigue and reduced survival in patients with advanced cancer and therefore is important in the definition of cancer cachexia. The aim of the present study was to carry out a direct comparison of the prognostic value of Eastern Cooperative Oncology Group Performance Status (ECOG-PS), modified Glasgow Prognostic Score (mGPS) and Body Mass Index/Weight Loss Grade (BMI/WL grade) in patients with advanced cancer.All data were collected prospectively across 18 sites in the UK and Ireland. Patient's age, sex, ECOG-PS, mGPS and BMI/WL grade were recorded, as were details of underlying disease including metastases. Survival data were analysed using univariate and multivariate Cox regression.A total of 730 patients were assessed. The majority of patients were male (53%), over 65 years of age (56%), had an ECOG-PS0/1 (56%), mGPS≥1 (56%), BMI≥25 (51%),2.5% weight loss (57%) and had metastatic disease (86%). On multivariate cox regression analysis ECOG-PS (HR 1.61 95%CI 1.42-1.83, p 0.001), mGPS (HR 1.53, 95%CI 1.39-1.69, p 0.001) and BMI/WL grade (HR 1.41, 95%CI 1.25-1.60, p 0.001) remained independently associated with overall survival. In patients with a BMI/WL grade 0/1 both ECOG and mGPS remained independently associated with overall survival.The ECOG/mGPS framework may form the basis of risk stratification of survival in patients with advanced cancer.

Background Weight loss (WL) and sarcopenia are associated with negative oncological outcomes including poor treatment tolerance, decreased quality of life, and reduced survival. The number of patients affected by sarcopenia and WL in Ireland and the UK is unknown. Methods A systematic review was undertaken to determine median rate of WL > 5% and computed tomography‐diagnosed sarcopenia in oncology populations. Gaps in the literature were supplemented using local data, collected as part of a 5 year prospective study. Rates of WL and sarcopenia in the population were extrapolated from these data based on incidence and prevalence of each cancer as per national cancer registries. Results We estimated that across Ireland and the UK, 128 892 cancer patients (34%) are affected by WL > 5% annually (121 641 UK; 7251 Ireland) and there are 133 707 annual cases of sarcopenia in cancer patients (35%) (126 265 UK; 7442 Ireland). Furthermore, we estimate that there are 716 124 and 771 589 cancer survivors with history of WL > 5% or sarcopenia, respectively. Conclusions Large numbers of patients are affected by cancer‐related malnutrition. Given the impact of malnutrition on oncological outcomes and long‐term frailty, there is an urgent need to improve access to cancer nutrition care.

Plasma membranes of animal cells are enriched for cholesterol. Cholesterol-dependent cytolysins (CDCs) are pore-forming toxins secreted by bacteria that target membrane cholesterol for their effector function. Phagocytes are essential for clearance of CDC-producing bacteria; however, the mechanisms by which these cells evade the deleterious effects of CDCs are largely unknown. Here, we report that interferon (IFN) signals convey resistance to CDC-induced pores on macrophages and neutrophils. We traced IFN-mediated resistance to CDCs to the rapid modulation of a specific pool of cholesterol in the plasma membrane of macrophages without changes to total cholesterol levels. Resistance to CDC-induced pore formation requires the production of the oxysterol 25-hydroxycholesterol (25HC), inhibition of cholesterol synthesis and redistribution of cholesterol to an esterified cholesterol pool. Accordingly, blocking the ability of IFN to reprogram cholesterol metabolism abrogates cellular protection and renders mice more susceptible to CDC-induced tissue damage. These studies illuminate targeted regulation of membrane cholesterol content as a host defense strategy.

Background: Optimizing quality of life (QoL) remains the central tenet of care in patients with incurable cancer; however, determinants of QoL are not clear. The objective of the current study was to examine which factors influence QoL in patients with incurable cancer. Methods: A multicenter study of adult patients with advanced cancer was conducted in Ireland and the United Kingdom between 2011 and 2016. Data were collected from patients at study entry and included patient demographics, Eastern Cooperative Oncology Group performance status (ECOG‐PS), nutritional parameters (the percentage weight loss [%WL]), muscle parameters assessed using computed tomography images (skeletal muscle index and skeletal muscle attenuation), inflammatory markers (modified Glasgow Prognostic score [mGPS]), and QoL data (the European Organization for Research and Treatment Quality‐of‐Life Questionnaire C‐30). The relation between clinical, nutritional, and inflammatory parameters with QoL was assessed using the Spearman rank correlation coefficient and multivariate binary logistic regression. Components of the European Organization for Research and Treatment Quality‐of‐Life Questionnaire C‐30 (physical function, fatigue, and appetite loss) and summary QoL scores were mean‐dichotomized for the logistic regression analyses. Results: Data were available for 1027 patients (51% men; median age, 66 years). Gastrointestinal cancer was most prevalent (40%), followed by lung cancer (26%) and breast cancer (9%). Distant metastatic disease was present in 87% of patients. The %WL, ECOG‐PS, and mGPS were significantly correlated with deteriorating QoL functional and symptom scales (all P < .001). On multivariate regression analysis, >10% WL (odds ratio [OR], 2.69; 95% CI, 1.63‐4.42), an ECOG‐PS of 3 or 4 (OR, 14.33; 95% CI, 6.76‐30.37), and an mGPS of 2 (OR, 1.58; 95% CI, 1.09‐2.29) were independently associated with poorer summary QoL scores. These parameters were also independently associated with poorer physical function, fatigue, and appetite loss (all P < .05). Low skeletal muscle attenuation was independently associated with poorer physical functioning (OR, 1.67; 95% CI, 1.09‐2.56), but muscle parameters were not independently associated with fatigue, appetite loss, or QoL summary scores. Conclusions: The current findings indicate that QoL is determined (at least in part) by WL, ECOG‐PS, and the systemic inflammatory response in patients with advanced cancer. Identifying early predictors of poor QoL may allow the identification of patients who may benefit from early referral to palliative and supportive care, which has been shown to improve QoL.

PURPOSE To provide evidence-based recommendations to practicing clinicians on radiographic imaging and biomarker surveillance strategies after definitive curative-intent therapy in patients with stage I-III non–small-cell lung cancer (NSCLC) and SCLC. METHODS ASCO convened an Expert Panel of medical oncology, thoracic surgery, radiation oncology, pulmonary, radiology, primary care, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 2000 through 2019. Outcomes of interest included survival, disease-free or recurrence-free survival, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS The literature search identified 14 relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS Patients should undergo surveillance imaging for recurrence every 6 months for 2 years and then annually for detection of new primary lung cancers. Chest computed tomography imaging is the optimal imaging modality for surveillance. Fluorodeoxyglucose positron emission tomography/computed tomography imaging should not be used as a surveillance tool. Surveillance imaging may not be offered to patients who are clinically unsuitable for or unwilling to accept further treatment. Age should not preclude surveillance imaging. Circulating biomarkers should not be used as a surveillance strategy for detection of recurrence. Brain magnetic resonance imaging should not be used for routine surveillance in stage I-III NSCLC but may be used every 3 months for the first year and every 6 months for the second year in patients with stage I-III small-cell lung cancer who have undergone curative-intent treatment.

Author(s): Yuan, Zilong; Rong, Yi; Benedict, Stanley H; Daly, Megan E; Qiu, Jianfeng; Yamamoto, Tokihiro | Abstract: PURPOSE:Adaptive radiotherapy (ART) has potential to reduce toxicity and facilitate safe dose escalation. Dose calculations with the planning CT deformed to cone beam CT (CBCT) have shown promise for estimating the "dose of the day". The purpose of this study is to investigate the "dose of the day" calculation accuracy based on CBCT and deformable image registration (DIR) for lung cancer radiotherapy. METHODS:A total of 12 lung cancer patients were identified, for which daily CBCT imaging was performed for treatment positioning. A re-planning CT (rCT) was acquired after 20nGy for all patients. A virtual CT (vCT) was created by deforming initial planning CT (pCT) to the simulated CBCT that was generated from deforming CBCT to rCT acquired on the same day. Treatment beams from the initial plan were copied to the vCT and rCT for dose calculation. Dosimetric agreement between vCT-based and rCT-based accumulated doses was evaluated using the Bland-Altman analysis. RESULTS:Mean differences in dose-volume metrics between vCT and rCT were smaller than 1.5%, and most discrepancies fell within the range ofn±n5% for the target volume, lung, esophagus, and heart. For spinal cord Dmax , a large mean difference of -5.55% was observed, which was largely attributed to very limited CBCT image quality (e.g., truncation artifacts). CONCLUSION:This study demonstrated a reasonable agreement in dose-volume metrics between dose accumulation based on vCT and rCT, with the exception for cases with poor CBCT image quality. These findings suggest potential utility of vCT for providing a reasonable estimate of the "dose of the day", and thus facilitating the process of ART for lung cancer.

Lung cancer is the leading cause of death in both men and women in the United States (1). With increasing implementation of low dose computed tomography (CT) screening in high-risk populations, more patients should be diagnosed with early stage disease in the coming years, amenable to curative intent therapy (2). However, no firm consensus yet guides the frequency and modality of surveillance imaging following definitive treatment, with variable guidelines from large national and international oncologic societies.

Purpose: To compare the dosimetric differences in stereotactic radiosurgery between use of passively scattered protons (PSRS) versus photons (XSRS) for pituitary adenomas. Methods and Materials: Nine patients with pituitary adenomas were selected among patients receiving single-fraction proton stereotactic radiosurgery (PSRS) between 2016 and 2017. These cases were replanned with XSRS using volumetric-modulated arc therapy with 2.5 mm and 5 mm multileaf collimators (2.5XSRS and 5XSRS, respectively). PSRS was planned with a dedicated single scattering stereotactic proton unit delivered via 3 equally or unequally weighted isocentric fields. XSRS plans were created with optimization to spare organs at risk. Plans were generated using the original total treatment dose delivered in 1 fraction. Results: Plans were evaluated for target volume dosimetry and estimated clinical toxicity. There was no significant difference in clinical target volume V100%, V95%, V90% or homogeneity index between treatment modalities. PSRS offered lower maximum dose (Dmax) to organs at risk and equivalent uniform dose (EUD) compared with 5XSRS and 2.5XSRS, respectively, for critical structures including optic nerve (right, Dmax 4.18, 5.32, 5.41; EUD 3.35, 4.08, 4.20) and hypothalamus (Dmax 1.71, 3.94, 3.77; EUD 0.94, 2.47, 2.39; P < .05 for PSRS vs 5XSRS and 2.5XSRS). The projected risk of secondary tumors in excess of baseline was lowest for PSRS plans (PSRS 5.28, 5XSRS 12.93, 2.5XSRS 12.66 cases per 10,000 patient-years; P = .008 for PSRS vs 5XSRS, PSRS vs 2.5XSRS, and P = .77 for 5XSRS vs 2.5XSRS). Conclusions: We demonstrate that neither modality has empirically superior dosimetry and identify potential clinical advantages as well as limitations of each technique. PSRS, 5XSRS and 2.5XSRS demonstrate comparable target volume dosimetry for pituitary adenoma. PSRS compared with XSRS modalities offers modestly decreased maximum dose and EUD to critical proximal structures and decreases risk of radiation-induced secondary tumors by more than half.

Medical students have lost invaluable exposure to surgery and research during the COVID-19 pandemic, with the majority of placements being cancelled or converted online 1. As such, they have been denied opportunities and mentorship which have historically influenced a surgical and/or clinical-academic career 2-3.

BackgroundWe conducted a2-part study to evaluate the incorporation of veliparib, a PARP inhibitor, into chemoradiotherapy (CRT) for stage III non-small-cell lung cancer.Patients and methodsIn the phase I part, patients were treated successivelyat3dose levels of veliparib(40,80, and120mg) twice daily during CRT. In the phase II part, patients were randomized to receive veliparib or placebo during thoracic radiotherapy with concurrent weekly carboplatin andpaclitaxel, followed by 2 cycles of consolidation carboplatin and paclitaxel with veliparib or placebo. The study was prematurely discontinued owing to the emergence of adjuvant immunotherapy as standard of care.ResultsOf 21 patients enrolled in phase I, 2 patients developed dose-limiting toxicities (DLTs): 1 grade 3 esophagitis with dysphagia (at 40 mg) and 1 grade 3 esophagitis with dehydration (at 80 mg). No DLTs were seen at veliparib dose of 120 mg twice daily, which was selected for the phase II part that enrolled 31 eligible patients. Progression-free survival (PFS) was not different between the 2 arms (P=.20). For the veliparib and placebo arms, response rates were 56% and 69%, PFS at 1 year 47% and 46%, and overall survival at 1 year 89% and 54%, respectively.ConclusionVeliparib with CRT was feasible and well tolerated. Efficacy could not accurately be determined because of early study closure. Nonetheless, there is enthusiasm for the evaluation of PARP inhibitors in lung cancer as predictive biomarkers are being developed and combinations with immunotherapy are attractive.

PurposeCurrent treatment guidelines for male breast cancer are guided by female-only trials despite data suggesting distinct clinicopathologic differences between sexes. We sought to evaluate whether radiation therapy (RT) after lumpectomy was associated with equivalent survival among men > 70 years of age with stage I, estrogen receptor (ER) positive tumors, as seen in women from the Cancer and Leukemia Group B (CALGB) 9343 trial.MethodsWe performed a retrospective analysis of 752 stage I, ER-positive male breast cancer patients ≥70 years who were treated with hormone therapy and surgery, with or without RT, from the National Cancer Database between 2004 and 2014. Patients were categorized based on surgery and RT (lumpectomy alone, lumpectomy with RT, and mastectomy alone). Multivariable Cox proportional hazards regression analysis was used to compare overall survival between treatment groups.ResultsMost patients underwent total mastectomy, with only 32.6% treated with lumpectomy. Of those who underwent lumpectomy, 72.7% received adjuvant RT. In multivariate analysis, there was no statistical difference in overall survival when comparing lumpectomy alone and lumpectomy with RT (aHR 0.72 [95% CI 0.38-1.37], p=0.31) or when comparing lumpectomy (alone or with RT) and mastectomy (aHR 1.28 [95% CI 0.88-1.87], p=0.20).ConclusionsIn this national sample of elderly men with ER-positive early-stage disease treated with endocrine therapy, there were no significant differences in overall survival when comparing lumpectomy alone and lumpectomy with RT, or lumpectomy (alone or with RT) and mastectomy. These results suggest that less aggressive treatment may be appropriate for a subset of male breast cancer patients.

Purpose Some recent studies have suggested a relationship between cardiac dose and mortality in non-small cell lung cancer (NSCLC), but others have reported conflicting data. The goal of this study was to conduct a systematic review and meta-analysis to provide an evidence-based estimate of the relationship between cardiac dose and mortality in these patients. Methods and Materials A systematic review of MEDLINE (PubMed) and Embase databases (inception to January 2018) was performed according to PRISMA guidelines. Studies that evaluated cardiac dosimetric factors in patients with NSCLC and included outcomes of cardiac events, cardiac mortality, and/or overall survival were identified. Results From 5614 patients across 22 studies, a total of 214 cardiac dosimetric parameters (94 unique) were assessed as possible predictors of cardiac toxicity or death. Assessed predictors included general (eg, mean heart dose [MHD]), threshold-based (eg, heart V5), and anatomic-based (eg, atria, ventricles) dosimetric factors. The most commonly analyzed parameters were MHD, heart V5, and V30. Most studies did not make corrections for multiplicity of testing. For overall survival, V5 was found to be significant on multivariable analysis (MVA) in 1 of 11 studies and V30 in 2 of 12 studies; MHD was not significant in any of 8 studies. For cardiac events, V5 was found to be significant on multivariable analysis in 1 of 2 studies, V30 in 1 of 3 studies, and MHD in 2 of 4 studies. A meta-analysis of the data could not be performed because most negative studies did not report effect estimates. Conclusions Consistent heart dose-volume parameters associated with overall survival of patients with NSCLC were not identified. Multiplicity of testing is a major issue and likely inflates the overall risk of type I errors in the literature. Future studies should specify predictors a priori, correct for multiplicity of testing, and report effect estimates for nonsignificant variables.

PurposeIncreased rates of toxicity have been described after stereotactic body radiation therapy (SBRT) for central lung tumors within 2cm of the proximal bronchial tree (PBT). Recent studies have defined a new class of ultracentral tumors. We report our experience treating ultracentral, central, and paramediastinal tumors with SBRT and compare toxicity, disease control, and survival rates.Methods and materialsWe reviewed the records of patients with central lung tumors treated with SBRT between September 2009 and July 2017. Tumors were classified as central if within 2cm of the PBT, ultracentral if the planning target volume touched the PBT or esophagus, and paramediastinal if touching mediastinal pleura. Actuarial rates of grades 2+and 3+toxicity, local control (LC), and overall survival were assessed using the Kaplan-Meier method and compared using a log-rank test. Toxicity was scored with the Common Terminology Criteria for Adverse Events, version 4.03.ResultsWe identified 68 patients with 69 central lung tumors, including 14 ultracentral, 15 paramediastinal, and 39 central tumors. Fifty-three patients were treated for early stage lung cancer and 15 for lung metastases. The prescribed dose ranged from 40Gy to 60Gy over 3 to 8 fractions. Most patients were treated using 5 fractions (83%), followed by 8 fractions (10%). Median follow-up was 19.7months (range, 3.3-78.3months). The 2-year estimates of LC (89%, 85%, and 93%, respectively; P=.72) and overall survival (76%, 73%, and 72%, respectively; P=.75) for ultracentral, central, and paramediastinal tumors were similar. Ultracentral tumors had an increased risk of grade 2+toxicity (57.6% vs 14.2% vs 7.1%; P=.007) at 2years. One patient with an ultracentral tumor developed grade 5 respiratory failure.ConclusionsThe oncologic outcomes after SBRT for ultracentral, central, and paramediastinal lung tumors were similar, with LC exceeding 85% at 2years using predominantly 5-fraction schedules. Ultracentral lung tumors were associated with an increased risk of toxicity in our patient cohort. Additional studies are needed to minimize toxicity for ultracentral tumors.

Background: Current consensus guidelines for the treatment of male breast cancer are driven by female-only clinical trials despite data suggesting distinct biologic, clinicopathologic, and prognostic differences between male and female breast cancer patients. This includes a recent retrospective multicenter analysis showing greater overall survival among male breast cancer patients who underwent lumpectomy with radiation therapy (RT), compared to total mastectomy or lumpectomy alone. In light of these findings and the CALGB 9343 trial performed in women, we sought to evaluate if survival was also equivalent in men ≥70 years old with early stage breast cancer treated with hormone therapy and lumpectomy with or without radiation therapy (RT), as shown in women. Methods: We performed a retrospective analysis of 752 stage I (T1N0M0), estrogen receptor (ER) positive male breast cancer patients ≥70 years of age who were treated with hormone therapy and underwent lumpectomy with or without RT or total mastectomy (without RT) from the National Cancer Database (NCDB) between the years 2004 to 2014. Chi-squared, Kruskal-Wallis, and analysis of variance tests were used to compare demographic and clinicopathologic differences between groups. Multivariable Cox proportional hazards regression analysis was used to compare overall survival between treatment groups, controlling for demographic and clinicopathologic differences. Results: Most patients underwent total mastectomy (67.4%), with only 32.6% treated with lumpectomy. Of those who underwent lumpectomy, 72.6% (n=178) underwent adjuvant RT. There were significant differences in age, tumor size, histology, grade, surgical margins, nodal surgery, and chemotherapy between patients who underwent lumpectomy without RT, lumpectomy with RT, and total mastectomy (p Conclusion: In this national sample of elderly ER positive male breast cancer patients with early disease on hormone therapy, lumpectomy alone was associated with equivalent survival compared to lumpectomy with RT and total mastectomy alone. These results suggest that breast conserving surgery without radiation therapy is appropriate for this subset of male breast cancer patients and greater adoption by breast surgeons should be considered. Citation Format: Bateni SB, Arora M, Daly ME, Bold RJ, Canter RJ, Sauder CA. The role of lumpectomy and radiation therapy in men 70 years of age and older with early breast cancer on hormone therapy: A NCDB analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-19-03.

Purpose Prone positioning has been used as a viable alternative to conventional supine position for patients receiving breast radiation therapy. However, little research has been done exploring the axial rotation of patients toward the treated breast when “sinking” into the opening of the breast board and its potentially negative effects on dosimetric outcomes, which may include increased heart and lung dose. The physician may need to move the posterior border away from the chest wall to reduce heart and lung dose. Methodology 49 consecutive female patients with left sided early stage breast cancer treated at University of California Davis Medical Center were assessed from 2015 to 2018 (age range: 42-84 years, median age: 62 years). All patients underwent prone whole breast therapy with conventional external beam radiation therapy (EBRT) at doses of 50 Gy (n = 12) or hypofractionated at 42.56 Gy (n = 37). Treatment plans and dose volumes were retrospectively analyzed for each patient. Standard tangents were designed for each patient using clinical landmarks of the midaxillary line and midsternal line, which were then compared to the delivered tangent beams. The angle created between a vertical line centered on center sternum and a line drawn from center sternum to center spinal cord served to define degree of axial rotation. Breast depth was defined by the longest horizontal length from outer rib to edge of breast on sagittal view. Patients were divided into subgroups by degree of rotation and absolute breast depth. A two tailed paired Student's t-test was used for analysis. Results Overall mean heart and lung dose were 82.2 cGy and 50.43 cGy for the entire cohort, respectively. For standard tangents, patients with degree of rotation < 5 degrees in the prone position (n = 23) had significant lung sparing as compared to patients with degree of rotation > 5 cm (n = 26) (mean lung dose: 61.8 cGy vs 129.6 cGy, p = 0.00329). This was also seen for cardiac sparing (mean heart dose: 105.9 cGy vs 183.9 cGy, p = 0.000235). Even with reduction of posterior border for treatment delivery, there remained a significant increase in mean heart and lung dose with increased rotation (p = 0.038, p = 0.046). Although not statistically significant, for patients with > 5 degrees of rotation there was a trend toward increased reduction of the posterior border of the tangent (13 mm vs. 7.5 mm, p = 0.13). A significant predictor of increased rotation was breast depth > 10 cm (p = 0.01). Patients with absolute breast depth > 10 cm (n = 23) in the prone position had significant lung sparing as compared to patients with absolute breast depth < 10 cm (n = 26) (mean lung dose: 58.6 cGy vs 40.8 cGy, p = 0.042). Conclusion To our knowledge, this is the first dosimetric comparison of prone breast therapy exploring the degree of patient roll into the prone-breast setup cavity. This study demonstrates a significant increase in mean lung and heart dose when patient rotation is greater than 5 degrees. Given this, the posterior border may have to be reduced to prevent a higher than intended dose to the heart and lung. Proper attention during simulation is important to allow for optimal dose distribution and special attention should be paid to women with smaller breast size. Citation Format: Cheng K, Hoopingarner S, Wright C, Daly M, Fragoso R, Zhao X. Dosimetric impact of patient rotation during prone breast radiotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-25.

BackgroundCurrent treatment guidelines for male breast cancer are predominantly guided by female-only clinical trials. With scarce research, it is unclear whether breast-conserving therapy (BCT) is equivalent to mastectomy in men. We sought to compare overall survival (OS) among male breast cancer patients who underwent BCT versus mastectomy.MethodsWe performed a retrospective analysis of 8445 stage I-II (T1-2 N0-1 M0) male breast cancer patients from the National Cancer Database (2004-2014). Patients were grouped according to surgical and radiation therapy (RT). BCT was defined as partial mastectomy followed by RT. Multivariable and inverse probability of treatment-weighted (IPTW) Cox proportional hazards models were used to compare OS between treatment groups, controlling for demographic and clinicopathologic characteristics.ResultsMost patients underwent total mastectomy (61.2%), whereas 18.2% underwent BCT, 12.4% underwent total mastectomy with RT, and 8.2% underwent partial mastectomy alone. In multivariable and IPTW models, partial mastectomy alone, total mastectomy alone, and total mastectomy with RT were associated with worse OS compared with BCT (p

Background The limited availability of proton beam therapy (PBT) requires individual treatment selection strategies, such as based on normal tissue complication probability (NTCP). We developed and externally validated NTCP models for common acute side-effects following PBT in brain tumour patients in effort to provide guidance on optimising patient quality of life. Methods An exploration cohort including 113 adult brain tumour patients who underwent PBT was investigated for the following endpoints: alopecia, scalp erythema, headache, fatigue and nausea. Dose–volume parameters of associated normal tissues were used for logistic regression modelling. Statistically significant parameters showing high area under the receiver operating characteristic curve (AUC) values in internal cross-validation were externally validated on two cohorts of 71 and 96 patients, respectively. Results Statistically significant correlations of dose–volume parameters of the skin for erythema and alopecia were found. In internal cross-validation, the following prognostic parameters were selected: V35Gy (absolute volume receiving 35 Gy) for erythema grade ≥1, D2% (dose to 2% of the volume) for alopecia grade ≥1 and D5% for alopecia grade ≥2. Validation was successful for both cohorts with AUC >0.75. A bivariable model for fatigue grade ≥1 could not be validated externally. No correlations of dose–volume parameters of the brain were seen for headache or nausea. Conclusion We developed and successfully validated NTCP models for scalp erythema and alopecia in primary brain tumour patients treated with PBT.

PURPOSE/OBJECTIVE(S) For women with left-sided breast cancer, the most relevant side effect is collateral damage to the heart with radiation therapy. Prone treatment techniques have helped reduce heart dose, but is more unstable and difficult to replicate. Setup uncertainties can lead to higher than expected heart doses or under-dosing of breast tissue. Our objective was to investigate the potential dosimetric benefit of utilizing a low dose cone beam CT (CBCT) in the daily setup of prone left breast radiation. MATERIALS/METHODS We performed a retrospective review patients treated at our institution between April 2019 and February 2020 in the prone position for left sided early-stage breast cancer. Patients were set up to clinical marks and a custom low dose partial arc CBCT was acquired with each fraction. Using the daily shifts, we calculated the delivered dose if these shifts were not performed. Differences between planned and pre-CBCT shift doses were recorded for the heart and breast tissue. Patients were grouped into 3 outcomes: (A) Significantly high heart dose: More than 10% increase in delivered heart dose from planned; (B) Poor Breast Coverage: More than 5% decrease in the volume receiving 90% of the prescription dose; or (C) Minimal Variation: No significant increase in heart dose or decrease in breast coverage. Patient factors were also collected. Statistical comparisons were made using t-tests. RESULTS 18 patients were included, with 283 daily CBCT shifts and an average of 15.8 CBCT's per patient (range 13-25). The mean age of the patients was 61.6 (39-80) and average BMI 28.3 (20.3 - 45). Breast and heart dose were available for 196 scans, of which 47 (24%) had high heart dose (A), 55 (28%) had poor breast coverage and only 98 (50%) had no more than minimal variation in either. Patients with breast size < 1000 cc had a 64.5% chance of a delivery with poor breast coverage or increased heart dose as opposed to 40% for women with larger breast (P < 0.01). The same relationship was seen for weight (P < 0.01), refer to Table 1. When combining the total dose for each patient, 3 (17%) patients were in group A (increased heart dose), 9 patients (50%) were in group B (poor breast coverage) and 6 patients (33%) were in group C. Patients with minimal variation had significantly higher weight (84 kg vs 66 kg, P = 0.038), BMI (33 vs 26, P = 0.03) and breast volumes (1716 cc vs 992 cc, P = 0.01). CONCLUSION Overall, our study demonstrated significant variation in daily setup for patients receiving prone breast radiation. Only half of treatments would have been delivered with minimal variation and a majority of patients would have either received significantly increased heart dose or suboptimal breast coverage if setup errors were not corrected. Likelihood of a significant setup error was seen most in women with smaller breasts or lower weight.

OBJECTIVE: To study genetic variants and their function within genes coding for complement receptors in pre-eclampsia. DESIGN: A case-control study. SETTING: Pre-eclampsia is a common vascular disease of pregnancy. The clearance of placenta-derived material is one of the functions of the complement system in pregnancy. POPULATION: We genotyped 500 women with pre-eclamptic pregnancies and 190 pregnant women without pre-eclampsia, as controls, from the FINNPEC cohort, and 122 women with pre-eclamptic pregnancies and 1905 controls from the national FINRISK cohort. METHODS: The functional consequences of genotypes discovered by targeted exomic sequencing were explored by analysing the binding of the main ligand iC3b to mutated CR3 or CR4, which were transiently expressed on the surface of COS-1 cells. MAIN OUTCOME MEASURES: Allele frequencies were compared between pre-eclamptic pregnancies and controls in genetic studies. The functional consequences of selected variants were measured by binding assays. RESULTS: The most significantly pre-eclampsia-linked CR3 variant M441K (P = 4.27E-4, OR = 1.401, 95% CI = 1.167-1.682) displayed a trend of increased adhesion to iC3b (P = 0.051). The CR4 variant A251T was found to enhance the adhesion of CR4 to iC3b, whereas W48R resulted in a decrease of the binding of CR4 to iC3b. CONCLUSIONS: Results suggest that changes in complement-facilitated phagocytosis are associated with pre-eclampsia. Further studies are needed to ascertain whether aberrant CR3 and CR4 activity leads to altered pro- and anti-inflammatory cytokine responses in individuals carrying the associated variants, and the role of these receptors in pre-eclampsia pathogenesis. TWEETABLE ABSTRACT: Genetic variants of complement receptors CR3 and CR4 have functional consequences that are associated with pre-eclampsia. publishedVersion

Purpose Taste and smell alterations (TAs and SAs) are often reported by patients with cancer receiving systemic antitumor therapy and can negatively impact food intake and quality of life. This study aimed to examine the occurrence of TAs and SAs and investigate the impact of TAs on overall liking of oral nutritional supplements (ONS) with warming and cooling sensations. Methods Patients receiving systemic antitumor therapy completed a questionnaire on sensory alterations and evaluated overall liking of 5 prototype flavors of Nutridrink® Compact Protein (hot tropical ginger (HTG), hot mango (HM), cool red fruits (CRF), cool lemon (CL), and neutral (N)) on a 10-point scale via a sip test. Differences between patients with and without TAs were investigated using permutation analysis. Results Fifty patients with various cancer types and treatments were included. Thirty patients (60%) reported TAs and 13 (26%) experienced SAs. Three flavors were rated highly with a liking score > 6 (CRF 6.8 ± 1.7; N 6.5 ± 1.9; HTG 6.0 ± 2.0). Larger variation in ONS liking scores was observed in patients with TAs with or without SAs (4.5–6.9 and 4.6–7.2, respectively) vs. patients without TAs (5.9–6.5). TAs were associated with increased liking of CRF (Δ = + 0.9) and N (Δ = + 1.0) flavors. Conclusions TAs and SAs are common in patients with cancer undergoing systemic antitumor therapy. Patients with TAs were more discriminant in liking of ONS flavors compared to patients without TAs, and sensory-adapted flavors appeared to be appreciated. The presence of TAs should be considered when developing or selecting ONS for patients with cancer. Trial registration Registration at ClinicalTrials.gov (NCT03525236) on 26 April 2018.

PURPOSE The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline on radiation therapy (RT) for small-cell lung cancer (SCLC). Because of the relevance of this topic to ASCO membership, ASCO reviewed the guideline, applying a set of procedures and policies used to critically examine guidelines developed by other organizations. METHODS The ASTRO guideline on RT for SCLC was reviewed for developmental rigor by methodologists. Then, an ASCO Expert Panel reviewed the content and the recommendations. RESULTS The ASCO Expert Panel determined that the recommendations from ASTRO guideline on RT for SCLC, published in June 2020, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed ASTRO guideline on RT for SCLC with a few discussion points. RECOMMENDATIONS Recommendations addressed thoracic radiotherapy for limited-stage SCLC, role of stereotactic body radiotherapy in stage I or II node-negative SCLC, prophylactic cranial radiotherapy, and thoracic consolidation for extensive-stage SCLC. Additional information is available at www.asco.org/thoracic-cancer-guidelines .

Background Pleural infection (PI) is a common and complicated disease. Empirical antibiotic usage has been correlated to poor clinical outcomes. Although the identification of the pathogen is essential for successful treatment, conventional culture-based pathogen detection techniques fail in approximately 40% of cases. Therefore, the bacteriology of PI remains incomplete. Next generation sequencing (NGS) is a molecular-based methodology which could be applied to metagenomics studies and improve pathogen recognition. Aim To investigate and characterise the bacterial patterns of PI. Methods Pleural fluid specimens from the ‘Pleural Infection Longitudinal Outcome Study’1 (PILOT, n=243) were subjected to bacterial DNA extraction followed by 16S rRNA NGS. The DADA2 and Phyloseq R packages were used for the analysis of the data. Results We identified 363 distinct species of bacteria, with various abundances among the samples. Diverse patterns between monomicrobial and polymicrobial PI were detected. 131 (54%) samples had one pathogen with abundance over 50% and 89 (36%) samples had at least three pathogens with relative abundance over 10%, suggesting a polymicrobial infection. Discussion We developed a methodology to extract bacterial DNA from pleural fluid specimens derived from patients with PI and the quality was satisfactory to be used for NGS. 16S rRNA gene NGS has the potential to detect the total microbiome of pleural fluid samples1 from complex PI. Funding National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). Reference Corcoran, J.P., et al. Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study. Eur Respir J ( 2020).

The internist plays a vital role in managing the elderly patient undergoing emergency surgery. Internists are involved in each stage of care, not only as primary care physicians but also as hospitalists. As the primary care provider (PCP), the internist develops a relationship with the patient, is familiar with the medical history, and understands the patient’s preferences for treatment. When a patient suffers an acute event requiring hospitalization, it is often the internist who is charged with the management of care. Before pursuing surgery, the internist conducts a medical evaluation, including a risk assessment, to determine whether the benefits of surgery will outweigh the potential risks. Elderly patients often have comorbidities that may complicate postsurgical outcomes. The internist determines if the patient is too frail for surgery.

Highlights • Recommendations for risk-mitigation pandemic scenario: • Do not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. • Postponement or interruption of radiotherapy of COVID-19 positive patients is generally recommended Severe pandemic scenario characterized by reduced resources: • Factors for patient triage include potential for cure, relative benefit of radiation, life expectancy, and performance status., Background The COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic. Methods For this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk–benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC. Results In a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided. Conclusion This joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic.

Urethral bulking agents (UBA) have traditionally been offered as salvage procedures for recurrent stress urinary incontinence (SUI). We compare the success of UBA in patients that had undergone a previous procedure for SUI (Salvage-UBA) to the SUI surgery naive (Primary-UBA). We hypothesised a positive effect in both Primary and Salvage-UBA with potentially poorer rates of response in the salvage group. Retrospective case series of patients having their first UBA (2010–2018). Primary outcome was to assess any difference in patient reported success between groups. Patient-reported improvement was assessed on a 4-point scale: ‘cured, improved, no change, worse’ and treatment ‘success’ defined as ‘cured’ or ‘improved’. A multivariate analysis, adjusting for plausible differences between groups, was undertaken in IBM SPSS Statistics (2016). 135 Primary-UBA and 38 Salvage-UBA were performed. Complete follow-up was obtained for 114 patients (66%): 86 Primary and 28 Salvage. Median follow-up time: 33 months. In 2012, 47% (8/17) of all UBA were Salvage-UBA, whilst in 2018, the majority were Primary-UBA (92%, 46/50). Success was not significantly different between Salvage-UBA 75% (21/28) versus Primary-UBA 67% (58/86) (Wald χ2 = 0.687, df = 1, p = 0.407). Top-up rates were similar: 14% (n = 4/28, Salvage-UBA) versus 15% (n = 13/86, Primary-UBA) (χ2 = 0.011, df = 1, p = 0.914). The number of women opting for UBA has increased substantially. No significant differences were noted for success with Salvage-UBA compared to Primary-UBA.

Cancer remains one of the leading causes of mortality worldwide and the associated reduction in physical function has a marked impact on both quality of life and survival. The aim of the present study was to examine the relationship between Eastern Cooperative Oncology Group-Performance status (ECOG-PS), modified Glasgow Prognostic Score (mGPS), Body Mass Index/ Weight Loss grade (BMI/WL grade), and Computerised Tomography (CT)-derived body composition measurement and physical function in patients with advanced cancer. Nine sites contributed prospective data on patient demographics, ECOG-PS, mGPS, physical function tests, and CT-derived body composition. Categorical variables were analysed using &chi, 2 test for linear-by-linear association, or &chi, 2 test for 2-by-2 tables. Associations were analysed using binary logistic regression. A total of 523 cancer patients (266 males, 257 females) were included in the final analysis and most had metastatic disease (83.2%). The median overall survival was 5.6 months. On multivariate binary logistic regression analysis, a high ECOG-PS remained independently associated with a low skeletal muscle index (p &lt, 0.001), low skeletal muscle density (p &lt, 0.05), and timed up and go test failure (p &lt, 0.001). A high mGPS remained independently associated with a low skeletal muscle density (p &lt, 0.05) and hand grip strength test failure (p &lt, 0.01). A high BMI/WL grade remained independently associated with a low subcutaneous fat index (p &lt, 0.05), low visceral obesity (p &lt, 0.01), and low skeletal muscle density (p &lt, 0.05). In conclusion, a high ECOG-PS and a high mGPS as outlined in the ECOG-PS/mGPS framework were consistently associated with poorer body composition and physical function in patients with advanced cancer.

Non-small cell lung cancer (NSCLC) is a common and lethal malignancy. The recent development of immune checkpoint inhibitors has afforded a durable, dramatic treatment response for a subset of patients, but strategies to expand these benefits to a broader swath of patients are needed. Preliminary evidence suggests radiotherapy may modulate a patient's immune system, particularly when delivered in high doses over few fractions with conformal techniques, as with stereotactic ablative radiotherapy (SABR). Radiotherapy for advanced stage NSCLC has traditionally been administered with palliative intent. However, an emergence of data from retrospective studies and, more recently, prospective trials has indicated the potential of using stereotactic ablative radiotherapy (SABR), in combination with systemic immunotherapy agents have synergistic effect and may enhance survival. We review current evidence for synergy between radiation and immunotherapy in metastatic, locally advanced, and localized NSCLC and discuss ongoing studies.

Objectives Proton beam therapy (PBT) is a type of radiation therapy (RT) used for certain cancer types because it minimizes collateral tissue damage. The high cost and limited availability of PBT have constrained its utilization. This study examined patterns and determinants of PBT use in California. Study design Persons with diagnoses of all cancer types from 2003 to 2016 inclusive who had any type of RT were identified in the California Cancer Registry in this retrospective analysis. Methods Cross-tabulations were performed to summarize the demographic characteristics of the study population, both for individuals who received PBT and for those who received other RT modalities. PBT use patterns over time were assessed. Multivariate logistic regression models assessed the effects of demographics and health insurance type on receipt of PBT. Results Of the 2,499,510 people with a cancer diagnosis during the study period, 578,632 (23%) received some type of RT, and of these, 8609 received PBT (1.5%). PBT was most often used to treat cancers of the prostate (41.3%), breast (14.0%), eye (11.7%), lung (6.1%), and brain (6.0%). PBT use was highest in 2003-2004 and then declined over time. PBT use was significantly associated with being white or male, younger age, higher socioeconomic status, Medicare or dual Medicare-Medicaid insurance, uninsured/self-pay status, and proximity to treatment. Conclusions Significant differences exist in PBT use by demographics and health insurance type. The identified racial and socioeconomic disparities merit further investigation. More granular studies on both use patterns and effectiveness of PBT for specific cancers are needed to draw stronger conclusions about its cost-benefit ratio.

Purpose Several sentinel phase III randomized trials have recently been published challenging traditional radiation therapy (RT) practices for small cell lung cancer (SCLC). This American Society for Radiation Oncology guideline reviews the evidence for thoracic RT and prophylactic cranial irradiation (PCI) for both limited-stage (LS) and extensive-stage (ES) SCLC. Methods The American Society for Radiation Oncology convened a task force to address 4 key questions focused on indications, dose fractionation, techniques and timing of thoracic RT for LS-SCLC, the role of stereotactic body radiation therapy (SBRT) compared with conventional RT in stage I or II node negative SCLC, PCI for LS-SCLC and ES-SCLC, and thoracic consolidation for ES-SCLC. Recommendations were based on a systematic literature review and created using a consensus-building methodology and system for grading evidence quality and recommendation strength. Results The task force strongly recommends definitive thoracic RT administered once or twice daily early in the course of treatment for LS-SCLC. Adjuvant RT is conditionally recommended in surgically resected patients with positive margins or nodal metastases. Involved field RT delivered using conformal advanced treatment modalities to postchemotherapy volumes is also strongly recommended. For patients with stage I or II node negative disease, SBRT or conventional fractionation is strongly recommended, and chemotherapy should be delivered before or after SBRT. In LS-SCLC, PCI is strongly recommended for stage II or III patients who responded to chemoradiation, conditionally not recommended for stage I patients, and should be a shared decision for patients at higher risk of neurocognitive toxicities. In ES-SCLC, radiation oncologist consultation for consideration of PCI versus magnetic resonance surveillance is strongly recommended. Lastly, the use of thoracic RT is strongly recommended in select patients with ES-SCLC after chemotherapy treatment, including a conditional recommendation in those responding to chemotherapy and immunotherapy. Conclusions RT plays a vital role in both LS-SCLC and ES-SCLC. These guidelines inform best clinical practices for local therapy in SCLC.

Spontaneous cancer regression is rare, and particularly rare for non-small cell lung cancer (NSCLC). The pathogenesis of spontaneous regressions is poorly understood, but of interest to many patients and providers. The infrequency of spontaneous regression makes it a challenging phenomenon to understand and study. We present a case of biopsy-proven NSCLC in a 73-year-old man that regressed without treatment.

Methods to stimulate appetite in the sick or elderly remains a challenge with few safe therapeutic options. Ghrelin is an orexigenic hormone, increasing appetite and subsequent food intake. It has received considerable attention as a therapeutic target to stimulate food intake in patients with anorexia. The identification of food-grade bioactives with proven orexigenic effects would mark significant progress in the treatment of disease-related malnutrition. This study therefore investigated the effects of two milk-derived ghrelinergic peptides on appetite and energy intake in healthy humans.A single-blind, placebo-controlled, 3-arm (placebo, casein bioactive MF1145 and whey bioactive UL-2-141) cross-over trial was conducted in healthy male volunteers. Participants received 26 mg/kg of both the bioactives and placebo. The main outcome measures were energy & protein intake from a set breakfast and ad libitum lunch and subjective appetite sensations as assessed by visual analogue scale (VAS). Basal and postprandial levels of active ghrelin (AG) were measured. Dietary intakes were analysed using Nutritics software. Statistical analyses were performed in R.Overall, 22 male participants (mean age 27 years) were included, average BMI was 24.6 kg/m2, (19.8 to 30.2 kg/m2). Mean energy and protein intakes at lunch when treated with placebo were 1343 kcal (95% CI: 1215–1471 kcal) and 74 g (95% CI: 66–81 g), respectively. Energy and protein intakes were not significantly different from placebo for either treatment (p = 0.918, p = 0.319 for UL-2-141 and p = 0.889, p = 0.959 for MF1145, respectively). Similarly, appetite, hunger and satiety responses on VAS were not significantly different from placebo for either treatment. AG peak post-lunch on placebo was 653 pg/ml (95% CI: 511–794 pg/ml). Treatment with UL-2-141 resulted in 139 pg/ml reduction in post-prandial AG compared to placebo and treatment with MF1145 resulted in 114 pg/ml reduction compared to placebo. This pattern was significant for both treatments (p = 0.021 and p = 0.045, respectively) however when controlling for fasting-AG, the pattern was no longer significant (p = 0.590 and p = 0.877 respectively). Pre-prandial AG peaks were not significantly different across treatments.While these peptides have previously demonstrated ghrelinergic effects in rats, no effect on appetite or food intake in humans was identified by this study. This may be attributable to the small sample size or low dose. However, since healthy adults are often not in tune with their own physiological hunger, they may not respond strongly to simple physiological modulators and repeating the study in subjects with established anorexia may be prudent.

Obesity is an established risk factor for colorectal cancer (CRC), however little is known about changes in body composition during chemotherapy and its impact on survival. The aim of this study was to examine in patients with CRC: (1) The prevalence of abnormal body composition phenotypes, (2) The impact of baseline body composition on overall survival, (3) Changes in body composition throughout treatment and its impact on overall survival.A prospective study of adult CRC patients undergoing chemotherapy between 2012–2016 was conducted. Longitudinal changes in body composition were examined using computed tomography (CT) images at two timepoints (interval 7 months, IQR: 5–9 months) using paired t-tests. Sarcopenia and low muscle attenuation (MA) were defined using published cut-offs. Cox proportional-hazards models were used to estimate mortality hazard ratios, adjusted for known prognostic covariates – stage, age, sex, performance status & systemic inflammation.In total, 268 patients were recruited (66% male, mean age 63 years) and 51% were undergoing chemotherapy with a palliative intent. At baseline, 4% were underweight (BMI < 20 kg/m2), 38% had a normal BMI, and 58% were overweight/obese. Despite this, 38% had cancer cachexia, 34% were sarcopenic and 43% had low MA. Neither sarcopenia, sarcopenic obesity nor cachexia at baseline predicted survival. Over 100 days, 68% were muscle stable (± 1 kg), while 25% lost > 1 kg and 7% gained > 1 kg. Fat mass remained stable ± 1 kg in 49%, while 28% lost > 1 kg and 23% gained > 1 kg. When adjusted for known prognostic covariates, baseline BMI (20–25 kg/m2) in those having palliative chemotherapy was independently associated with reduced survival compared to those with BMI indicating overweight (BMI 25–30 kg/m2) [HR: 1.80 (95% CI: 1.04–3.14), p = 0.037]. In those undergoing chemotherapy with palliative intent, a loss of > 6.4% subcutaneous fat (Q1 SAT) over 100 days was predictive of poor survival versus those with small losses, remaining stable or gaining SAT (Q2-4), independent of changes in muscle mass [HR: 2.22 (95% CI: 1.07–4.62), p = 0.033].Patients with CRC, particularly those treated with a palliative intent, experience significant losses in muscle and fat mass during chemotherapy. Loss of SAT mass during palliative chemotherapy is prognostic of poor survival, independent of changes in muscle mass. Baseline BMI in the overweight range confers a survival advantage. Nutritional strategies to prevent or attenuate weight loss during chemotherapy are advisable especially in the context of advanced CRC.

PurposeDespite the strong interest in combining stereotactic ablative radiation therapy (SAR) with immunotherapy, limited data characterizing the systemic immune response after SAR are available. We hypothesized that the systemic immune responseto SAR would differ by irradiated site owing to inherent differences in the microenvironment of various organs.Methods and materialsPatients receiving SAR to any organ underwent prospective blood banking before and 1 to 2weeks after SAR. Peripheral blood mononuclear cells (PBMCs) and serum were isolated. PBMCs were stained with fluorophore-conjugated antibodies against T and natural killer (NK) cell markers. Cells were interrogated by flow cytometry, and the results were analyzed using FlowJo software. Serum cytokine and chemokine levels were measured using Luminex. We analyzed the changes from before to after therapy using paired t tests or 1-way analysis of variance (ANOVA) with Bonferroni's post-test.ResultsA total of 31 patients had evaluable PBMCs for flow cytometry and 37 had evaluable serum samples for Luminex analysis. The total number of NK cells andcytotoxic (CD56dimCD16+) NK cells decreased (P=.02) and T-cell immunoglobulin- and mucin domain-containing molecule-3-positive (TIM3+) NK cells increased (P=.04) after SAR to parenchymal sites (lung and liver) but not tobone or brain. The total memory CD4+ T cells, activated inducible co-stimulator-positive and CD25+CD4+ memory T cells, and activated CD25+CD8+ memory Tcells increased after SAR to parenchymal sites but not bone or brain. The circulating levels of tumor necrosis factor-α (P=.04) and multiple chemokines, including RANTES (P=.04), decreased after SAR to parenchymal sites but not bone or brain.ConclusionsOur data suggest SAR to parenchymal sites induces systemic immune changes, including a decrease in total and cytotoxic NK cells, an increase in TIM3+ NK cells, and an increase in activated memory CD4+ and CD8+ T cells. SAR to nonparenchymal sites did not induce these changes. By comparing the immune response after radiation to different organs, our data suggest SAR induces systemic immunologic changes that are dependent on the irradiated site.

Background Weight loss (WL) has long been recognized as an important factor associated with reduced quality of life (QoL) and reduced survival in patients with cancer. The body mass index (BMI)‐adjusted weight loss grading system (WLGS) has been shown to be associated with reduced survival. However, its impact on QoL has not been established. The aim of this study was to assess the relationship between this WLGS and QoL in patients with advanced cancer. Methods A biobank analysis was undertaken of adult patients with advanced cancer. Data collected included patient demographics, Eastern Cooperative Oncology Group performance status, and anthropometric parameters (BMI and %WL). Patients were categorized according to the BMI‐adjusted WLGS into one of five distinct WL grades (grades 0–4). QoL was collected using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐C30. The Kruskal–Wallis test and multivariate logistic regression analyses were used to assess the relationship between the WLGS and QoL scores. Overall survival was assessed using Kaplan–Meier curve and Cox proportional hazard models. Results A total of 1027 patients were assessed (51% male, median age: 66 years). Gastrointestinal cancer was most prevalent (40%), and 87% of patients had metastatic disease. Half (58%) of patients had a WL grade of 0–1, while 12%, 20%, and 10% had WL grades of 2, 3, and 4, respectively. Increasing WL grades were significantly associated with poorer QoL functioning and symptoms scales (all P < 0.05). Physical, role, and emotional functioning decreased by a median of >20 points between WL grade 0 and WL grade 4, while appetite loss, pain, dyspnoea, and fatigue increased by a median score >20 points, indicative of a large clinical significant difference. Increasing WL grades were associated with deteriorating QoL summary score. WL grades 2, 3, and 4 were independently associated with a QoL summary score below the median (

Purpose To report the first series of proton stereotactic radiosurgery (SRS) for the treatment of patients with single or multiple brain metastases, including failure patterns, survival outcomes, and toxicity analysis. Methods and Materials This was a single-institution, retrospective study of 815 metastases from 370 patients treated with proton SRS between April 1991 and November 2016. Cumulative incidence estimates of local failure, distant brain failure, and pathologically confirmed radionecrosis and Kaplan-Meier estimates of overall survival were calculated. Fine and Gray and Cox regressions were performed to ascertain whether clinical and treatment factors were associated with the described endpoints. Results The median follow-up from proton SRS was 9.2 months. The 6- and 12-month estimates of local failure, distant brain failure, and overall survival were 4.3% (95% confidence interval [CI] 3.0%-5.9%) and 8.5% (95% CI 6.7%-10.6%), 39.1% (95% CI 34.1%-44.0%) and 48.2% (95% CI 43.0%-53.2%), and 76.0% (95% CI 71.3%-80.0%) and 51.5% (95% CI 46.3%-56.5%), respectively. The median survival was 12.4 months (95% CI 10.8-14.0 months) after proton SRS. The most common symptoms were low-grade fatigue (12.5%), headache (10.0%), motor weakness (6.2%), seizure (5.8%), and dizziness (5.4%). The rate of pathologically confirmed radionecrosis at 12 months was 3.6% (95% CI 2.0%-5.8%), and only target volume was associated on multivariate analysis (subdistribution hazard ratio 1.13, 95% CI 1.0-1.20). Conclusions To the best of our knowledge, this is the first reported series of proton SRS for the management of brain metastases. Moderate-dose proton SRS is well tolerated and can achieve good local control outcomes, comparable to those obtained with conventional photon SRS strategies. Although proton SRS remains resource-intensive, future strategies evaluating its selective utility in patients who would benefit most from integral dose reduction should be explored.

The landscape of care for early-stage non-small cell lung cancer continues to evolve. While some of the developments do not seem as dramatic as what has occurred in advanced disease in recent years, there is a continuous improvement in our ability to diagnose disease earlier and more accurately. We have an increased understanding of the diversity of early-stage disease and how to better tailor treatments to make them more tolerable without impacting efficacy. The International Association for the Study of Lung Cancer and the Journal of Thoracic Oncology publish this annual update to help readers keep pace with these important developments. Experts in the care of early-stage lung cancer patients have provided focused updates across multiple areas including screening, pathology, staging, surgical techniques and novel technologies, adjuvant therapy, radiotherapy, surveillance, disparities, and quality of life. The source for information includes large academic meetings, the published literature, or novel unpublished data from other international oncology assemblies. (C) 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Advancements in image-based technologies and body composition research over the past decade has led to increased understanding of the importance of muscle abnormalities, such as low muscle mass (sarcopenia), and more recently low muscle attenuation (MA), as important prognostic indicators of unfavourable outcomes in patients with cancer. Muscle abnormalities can be highly prevalent in patients with cancer (ranging between 10 and 90 %), depending on the cohort under investigation and diagnostic criteria used. Importantly, both low muscle mass and low MA have been associated with poorer tolerance to chemotherapy, increased risk of post-operative infectious and non-infectious complications, increased length of hospital stay and poorer survival in patients with cancer. Studies have shown that systemic antineoplastic treatment can exacerbate losses in muscle mass and MA, with reported loss of skeletal muscle between 3 and 5 % per 100 d, which are increased exponentially with progressive disease and proximity to death. At present, no effective medical intervention to improve muscle mass and MA exists. Most research to date has focused on treating muscle depletion as part of the cachexia syndrome using nutritional, exercise and pharmacological interventions; however, these single-agent therapies have not provided promising results. Rehabilitation care to modify body composition, either increasing muscle mass and/or MA should be conducted, and its respective impact on oncology outcomes explored. Although the optimal timing and treatment strategy for preventing or delaying the development of muscle abnormalities are yet to be determined, multimodal interventions initiated early in the disease trajectory appear to hold the most promise.

Purpose To analyze functional outcomes for patients treated on a phase 2 trial of de-escalated chemoradiation therapy for human papillomavirus–positive oropharyngeal cancer. Methods and Materials Patient eligibility included p16-positive, stage III or IV oropharyngeal squamous cell carcinoma and a Zubrod performance status of 0 to 1. Treatment was induction chemotherapy with paclitaxel, 175 mg/m2, and carboplatin, area under the curve (AUC) of 6 mg/ml/min, for 2 cycles every 21 days, followed by concurrent paclitaxel, 30 mg/m2, every 7 days with dose-reduced radiation therapy of 54 or 60 Gy. Trends in body weight and body mass index (BMI) were analyzed with gastrostomy tube and narcotic use rates. Functional outcomes were assessed using the University of Washington Quality of Life Scale and the Functional Assessment of Cancer Therapy–Head and Neck Scale. Results Forty-five patients were registered, of whom 40 were evaluable. Only 1 patient had a BMI deemed unhealthy at the completion of treatment. For the 15 patients (38%) with a normal BMI (18-25 kg/m2) before treatment, recovery back to baseline occurred at approximately 18 months (average BMI, 23.2 kg/m2 vs 22.3 kg/m2; P=.09). In 2 patients (5%), gastrostomy tubes were placed during treatment. No patient was enteral feeding tube-dependent at 6 months after treatment. Ninety-five percent of patients tolerated a normal regular diet at last follow-up. Conclusions De-escalated chemoradiation therapy may improve functional outcomes as indicated by the relatively low incidence of gastrostomy tube placement and long-term dysphagia. In patients with a normal BMI prior to chemoradiation therapy, BMI recovered to baseline levels.

Purpose The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline on treatment with stereotactic body radiotherapy (SBRT) for patients with early-stage non–small-cell lung cancer. ASCO has a policy and set of procedures for endorsing and/or adapting clinical practice guidelines that have been developed by other professional organizations. Methods The ASTRO Evidence-Based Guideline for Stereotactic Body Radiotherapy for Early-Stage Non–Small-Cell Lung Cancer was reviewed for developmental rigor by methodologists. An ASCO Expert Panel updated the literature search and reviewed the guideline content and recommendations. Results The ASCO Expert Panel determined that the recommendations from the ASTRO guideline, published in 2017, are clear, thorough, and based on the most relevant scientific evidence. ASCO statements and minor modifications were added to enhance the applicability of the ASTRO guideline for the broader ASCO audience. Recommendations For standard operative risk patients with stage I NSCLC, SBRT is not recommended outside of a clinical trial. Lobectomy with systematic lymph node evaluation remains the recommended treatment, although a sublobar resection may be considered in select clinical scenarios. Recommendations are provided regarding the use of SBRT in high operative risk patients and for inoperative patients, including in challenging scenarios where tumors are: centrally located, > 5 cm in diameter, lacking tissue diagnosis, synchronous primary or multifocal, second primary after pneumonectomy, proximal to or involved with mediastinal structures, abutting the chest wall, or recurring after previous treatment. Qualifying statements are included to provide further guidance for implementation, and the importance of a discussion of treatment options among members of the multidisciplinary cancer care team is emphasized. Additional information is available at: www.asco.org/thoracic-cancer-guidelines and www.asco.org/guidelineswiki .