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Background and Purpose: Radiation pneumonitis (RP) is a common side effect of thoracic radiotherapy and often has a long course characterized by acute exacerbations and progression to permanent lung fibrosis. There are no validated biomarkers of prognosis in patients diagnosed with RP., Materials and Methods: We analyzed a time course of serum chemokines, cytokines, and other proteins from patients with grade 2+ RP in a randomized clinical trial of a steroid taper plus nintedanib, a multiple tyrosine kinase inhibitor, versus placebo plus a steroid taper for the treatment of RP. Weighted gene correlation network analysis (WGCNA) and univariable zero inflated Poisson models were used to identify groups of correlated analytes and their associations with clinical outcomes., Results: Thirty enrolled patients had biomarker data available, and 17 patients had enough analytes tested for network analysis. WGNCA identified ten analytes, including transforming growth factor beta-1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1), and platelet-derived growth factor (PDGF), that in aggregate were correlated with the occurrence of pulmonary exacerbations (p = 0.008), the total number of acute pulmonary exacerbations (p = 0.002), and treatment arm (p = 0.036). By univariable analysis, an increase in rate of change of two components of the RP module were associated with an increased incidence rate of pulmonary exacerbations: interleukin 5 (IL-5, incidence rate ratio (IRR) 1.02, 95% CI 1.01-1.04, p = 0.002), and tumor necrosis factor superfamily 12 (TNFSF12, IRR 1.06, CI 1-1.11, p = 0.036). An increased slope of epidermal growth factor (EGF) was associated with a decreased incidence rate of exacerbations (IRR 0.94, CI 0.89-1, p = 0.036)., Conclusion: We identified a panel of serum biomarkers that showed association with nintedanib treatment and acute pulmonary exacerbations in patients with RP. A confirmatory study will be needed to validate this panel for use as a prognostic tool in patients with RP., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AR previously consulted for Boehringer Ingelheim. CMR has consulted regarding oncology drug development with AbbVie, Amgen, AstraZeneca, Epizyme, Genentech/Roche, Ipsen, Jazz, Lilly, and Syros, and serves on the scientific advisory boards of Bridge Medicines, Earli, and Harpoon Therapeutics. DRJ has consulted for AstraZeneca and serves on the clinical trial steering committee for Merck. All other authors declare no competing interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: The optimal dose and fractionation of stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) have not been defined. Single-fraction SBRT was associated with more gastrointestinal toxicity, so 5-fraction regimens have become more commonly employed. We aimed to determine the safety and maximally tolerated dose of 3-fraction SBRT for LAPC., Methods and Materials: Two parallel phase 1 dose escalation trials were conducted from 2016 to 2019 at Memorial Sloan Kettering Cancer Center and University of Colorado. Patients with histologically confirmed LAPC without distant progression after at least 2 months of induction chemotherapy were eligible. Patients received 3-fraction linear accelerator-based SBRT at 3 dose levels, 27, 30, and 33 Gy, following a modified 3+3 design. Dose-limiting toxicity, defined as grade ≥3 gastrointestinal toxicity within 90 days, was scored by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The secondary endpoints included cumulative incidence of local failure (LF) and distant metastasis (DM), as well as progression-free and overall survival PFS and OS, respectively, toxicity, and quality of life (QoL) using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and the pancreatic cancer-specific QLQ-PAN26 questionnaire., Results: Twenty-four consecutive patients were enrolled (27 Gy: 9, 30 Gy: 8, 33 Gy: 7). The median (range) age was 67 (52-79) years, and 12 (50%) had a head/uncinate tumor location, with a median tumor size of 3.8 (1.1-11) cm and CA19-9 of 60 (1-4880) U/mL. All received chemotherapy for a median of 4 (1.4-10) months. There were no grade ≥3 toxicities. Two-year rates (95% confidence interval) of LF, DM, PFS, and OS were 31.7% (8.6%-54.8%), 70.2% (49.7%-90.8%), 20.8% (4.6%-37.1%), and 29.2% (11.0%-47.4%), respectively. Three- and 6-month QoL assessment showed no detriment., Conclusions: For select patients with LAPC, dose escalation to 33 Gy in 3 fractions resulted in no dose-limiting toxicities, no detriments to QoL, and disease outcomes comparable with conventional RT. Further exploration of SBRT schemes to maximize tumor control while enabling efficient integration with systemic therapy is warranted., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: Radiation pneumonitis (RP) is the most common dose-limiting toxicity for thoracic radiation therapy. Nintedanib is used for the treatment of idiopathic pulmonary fibrosis, which shares pathophysiological pathways with the subacute phase of RP. Our goal was to investigate the efficacy and safety of nintedanib added to a prednisone taper compared with a prednisone taper alone in reducing pulmonary exacerbations in patients with grade 2 or higher (G2+) RP., Methods and Materials: In this phase 2, randomized, double-blinded, placebo-controlled trial, patients with newly diagnosed G2+ RP were randomized 1:1 to nintedanib or placebo in addition to a standard 8-week prednisone taper. The primary endpoint was freedom from pulmonary exacerbations at 1 year. Secondary endpoints included patient-reported outcomes and pulmonary function tests. Kaplan-Meier analysis was used to estimate the probability of freedom from pulmonary exacerbations. The study was closed early due to slow accrual., Results: Thirty-four patients were enrolled between October 2015 and February 2020. Of 30 evaluable patients, 18 were randomized to the experimental Arm A (nintedanib + prednisone taper) and 12 to the control Arm B (placebo + prednisone taper). Freedom from exacerbation at 1 year was 72% (confidence interval, 54%-96%) in Arm A and 40% (confidence interval, 20%-82%) in Arm B (1-sided, P = .037). In Arm A, there were 16 G2+ adverse events possibly or probably related to treatment compared with 5 in the placebo arm. There were 3 deaths during the study period in Arm A due to cardiac failure, progressive respiratory failure, and pulmonary embolism., Conclusions: There was an improvement in pulmonary exacerbations by the addition of nintedanib to a prednisone taper. Further investigation is warranted for the use of nintedanib for the treatment of RP., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: A positive post-treatment prostate biopsy following definitive radiotherapy carries significant prognostic implications., Objective: To determine whether local recurrences after prostate stereotactic body radiation therapy (SBRT) are associated with the presence of and occur more commonly within the region of a PI-RADS 4 or 5 dominant intra-prostatic lesion (DIL) identified on pre-treatment multi-parametric magnetic resonance imaging (MRI)., Design, Setting, and Participants: 247 patients with localized prostate cancer treated with SBRT at our institution from 2009-2018 underwent post-treatment biopsies (median time to biopsy: 2.2 years) to evaluate local control., Interventions: Prostate SBRT (median 40 Gy in 5 fractions)., Outcome Measurements and Statistical Analysis: MRIs were read by a single diagnostic radiologist blinded to other patient characteristics and treatment outcomes. The DIL presence, size, location, and extent were then analyzed to determine associations with the post-treatment biopsy outcomes., Results and Limitations: Among patients who underwent post-treatment biopsies, 39/247 (15.8%) were positive for Gleason-gradable prostate adenocarcinoma, of which 35/39 (90%) had a DIL initially present and 29/39 (74.4%) had a positive biopsy within the DIL. Factors independently associated with post-treatment biopsy outcomes included the presence of a DIL (OR 6.95; p = 0.001), radiographic T3 disease (OR 5.23, p < 0.001), SBRT dose ≥40 Gy (OR 0.26, p = 0.003), and use of androgen deprivation therapy (ADT; OR 0.28, p = 0.027). Among patients with a DIL (N = 149), the only factors associated with post-treatment biopsy outcomes included ≥50% percent cores positive (OR 2.4, p = 0.037), radiographic T3 disease (OR 4.04, p = 0.001), SBRT dose ≥40 Gy (OR 0.22, p < 0.001), and use of ADT (OR 0.21, p = 0.014)., Conclusions: Our results suggest that men with PI-RADS 4 or 5 DILs have a higher risk of local recurrence after prostate SBRT and that most recurrences are located within the DIL., Patient Summary: We found the presence of a dominant tumor on pre-treatment MRI was strongly associated with residual cancer within the prostate after SBRT and that most recurrences were within the dominant tumor., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Older patients with hematologic malignancies are increasingly considered for allogeneic hematopoietic cell transplant (allo-HCT). However, older patients often have increased comorbidities and thus may require an increased level of post-transplant care. These factors can contribute to increased caregiver distress, which has been associated with worsened health outcomes for caregivers and patients. To examine predictors of caregiver distress and support group participation in caregivers of older allo-HCT patients, we retrospectively reviewed charts of 208 patients aged 60 and older who underwent their first allo-HCT at our institution from 2014 through 2016. We systematically characterized and identified the incidence of caregiver distress and attendance in a caregiver support group from the start of conditioning through 1 year post allo-HCT. Evidence of caregiver distress and support group participation was recorded by reviewing clinical and/or social work documentation. We found that 20 caregivers (10%) endorsed stress and 44 caregivers (21%) attended our support group at least once. A patient's prior history of psychiatric diagnosis ( p = .046) or the use of potentially inappropriate medications for older adults ( p = .046) was found to be associated with caregiver stress. Caregivers who were spouses or partners of patients ( p = .048) or caregivers of married patients were more likely to attend the support group ( p = .007). While limited by retrospective design and likely underreporting, this study reveals factors associated with caregiver distress in the older allo-HCT caregiver population. This information can help providers identify caregivers at risk for distress and improve caregiver resources, which may improve both caregiver and patient outcomes., Competing Interests: Dr. Perales reports honoraria from Abbvie, Astellas, Bristol-Myers Squibb, Celgene, Equilium, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Novartis, Nektar Therapeutics, Omeros, Takeda, VectivBio AG, and Vor Biopharma. He serves on DSMBs for Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier, and the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros. He has received research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, and Novartis. He serves in a volunteer capacity as a member of the Board of Directors of the American Society for Transplantation and Cellular Therapy (ASTCT) and Be The Match (National Marrow Donor Program, NMDP), as well as on the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Executive Committee. Dr. Giralt serves on the scientific advisory board of Actinium, Celgene, Bristol-Myers Squibb, Sanofi, Amgen, Pfizer, GlaxoSmithKline, JAZZ, Janssen, and Omeros. He reports research consultancy for Kite. He has received research support for clinical trials from Actinium, Bristol-Myers Squibb, Celgene, Pfizer, Takeda, Janssen, Amgen, and Sanofi. Dr. Jakubowski reports ownership interest in Novartis. The other authors have no conflicts of interest to disclose., (© 2023 Harborside™.)

Purpose: Although hydrogel spacer placement (HSP) minimizes rectal dose during prostate cancer radiation therapy, its potential benefit for modulating rectal toxicity could depend on the achieved prostate-rectal separation. We therefore developed a quality metric associated with rectal dose reduction and late rectal toxicity among patients treated with prostate stereotactic body radiation therapy (SBRT)., Methods and Materials: A quality metric consisting of prostate-rectal interspace measurements from axial T2-weighted magnetic resonance imaging simulation images was applied to 42 men enrolled in a multi-institutional phase 2 study using HSP with prostate SBRT (45 Gy in 5 fractions). A score of 0, 1, or 2 was assigned to a prostate-rectal interspace measurement of <0.3 cm, 0.3 to 0.9 cm, or ≥1 cm, respectively. An overall spacer quality score (SQS) was computed from individual scores at rectal midline and ±1 cm laterally, located at the prostate base, midgland, and apex. Associations of SQS with rectal dosimetry and late toxicity were evaluated., Results: The majority of the analyzed cohort had an SQS of 1 (n = 17; 41%) or 2 (n = 18; 43%). SQS was associated with maximum rectal point dose (rectal Dmax; P  = .002), maximum dose to 1 cc of rectum (D1cc; P  = .004), and volume of rectum receiving ≥100% of prescription dose (V45; P  = .046) and ≥40 Gy (V40; P  = .005). SQS was also associated with a higher incidence of ( P  = .01) and highest-graded late rectal toxicity ( P  = .01). Among the 20 men who developed late grade ≥1 rectal toxicity, 57%, 71%, and 22% had an SQS of 0, 1, and 2, respectively. Men with an SQS of 0 or 1 compared with 2 had 4.67-fold (95% CI, 0.72-30.11) or 8.40-fold (95% CI, 1.83-38.57) greater odds, respectively, of developing late rectal toxicity., Conclusions: We developed a reliable and informative metric for assessing HSP, which appears to be associated with rectal dosimetry and late rectal toxicity after prostate SBRT., (© 2023 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.)

Objective: To characterize patterns of failure using prostate-specific membrane antigen positron emission tomography (PSMA PET) after radical prostatectomy (RP) and salvage radiotherapy (SRT)., Methods: Patients with rising PSA post-RP+SRT underwent 68 Ga-HBED-iPSMA PET/CT on a single-arm, prospective imaging trial (NCT03204123). Scans were centrally reviewed with pattern-of-failure analysis by involved site. Positive scans were classified using 3 failure categories: pelvic nodal, extra-pelvic nodal or distant non-nodal. Associations with failure categories were analyzed using cumulative incidence and generalized logits regression., Results: We included 133 men who received SRT a median of 20 months post-RP; 56% received SRT to the prostatic fossa alone, while 44% received pelvic SRT. PSMA PET/CT was performed a median of 48 months post-SRT. Overall, 31% of PSMA PET/CT scans were negative, 2% equivocal and 67% had at least 1 positive site. Scan detection was significantly associated with PSA level prior to PSMA PET/CT. Analysis of 89 positive scans demonstrated pelvic nodal (53%) was the most common relapse and fossa relapse was low (9%). Overall, positive scans were pelvic (n = 35, 26%), extra-pelvic nodal (n = 26, 20%) or distant non-nodal failure (n = 28, 21%), and 70% of positive scans were oligorecurrent. We observed similar cumulative incidence for all failure categories and relatively few clinicodemographic associations. Men treated with pelvic SRT had reduced odds of pelvic failure versus exclusive fossa treatment., Conclusion: Pelvic, extra-pelvic nodal, and distant non-nodal failures occur with similar incidence post-SRT. Regional nodal relapse is relatively common, especially with fossa-only SRT. A high oligorecurrence rate suggests a potentially important role for PSMA-guided focal therapies., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To determine prevalence and frequency of malignancy among bone lesions detected on breast MRI and to identify clinical and imaging features associated with bone metastases from breast cancer (BC), as bone lesions are suboptimally evaluated on breast imaging protocols and can present a diagnostic challenge., Methods: This IRB-approved retrospective review of breast MRIs performed from June 2009 to June 2018 identified patients with bone lesions. Demographic, clinical, and MRI features were reviewed. Clinical outcome of bone lesions was determined based on pathology and/or additional diagnostic imaging. All benign lesions had ≥ 2 years of imaging follow-up. Statistics were computed with Fisher's exact and Wilcoxon rank sum tests., Results: Among all patients with breast MRI, 1.2% (340/29 461) had bone lesions. Of these, 224 were confirmed benign or metastatic BC by pathology or imaging follow-up, with 70.1% (157/224) be- nign and 29.9% (67/224) metastatic. Bone metastases were associated with BC history (P < 0.001), with metastases occurring in 58.2% (53/91) of patients with current BC, 17.9% (14/78) patients with prior BC, and 0.0% (0/55) without BC. Bone metastases were associated with invasive and ad- vanced stage BC and, on MRI, with location in sternum, ribs, or clavicles, larger size, multiplicity, andT1 hypointensity (all P < 0.01 in tests of overall association)., Conclusion: Of clinically confirmed breast MRI-detected bone lesions, 30% were bone metastases; all were detected in patients with current or prior BC. Metastases were associated with advanced stage, invasive carcinoma, larger lesion size, multiplicity, low T1 signal, and non-spine location., Competing Interests: CONFLICT OF INTEREST STATEMENT Dr. Kimberly Feigin reports that she is an advisor to Covera Health. The remaining authors have nothing to disclose.

Purpose: : Guidelines for early-stage breast cancer allow for radiation therapy (RT) omission after breast conserving surgery among older women, though high utilization of RT persists. This study explored surgeon referral and the effect of a productivity-based bonus metric for radiation oncologists in an academic institution with centralized quality assurance review., Methods and Materials: : We evaluated patients ≥70 years of age treated with breast conserving surgery for estrogen receptor (ER)+ pT1N0 breast cancer at a single tertiary cancer network between 2015 and 2018. The primary outcomes were radiation oncology referral and RT receipt. Covariables included patient and physician characteristics and treatment decisions before versus after productivity metric implementation. Univariable generalized linear effects models explored associations between these outcomes and covariables., Results: : Of 703 patients included, 483 (69%) were referred to radiation oncology and 273 (39%) received RT (among those referred, 57% received RT). No difference in RT receipt pre- versus post-productivity metric implementation was observed ( P  = .57). RT receipt was associated with younger patient age (70-74 years; odds ratio [OR], 2.66; 95% confidence interval [CI], 1.54-4.57) and higher grade (grade 3; OR, 7.75; 95% CI, 3.33-18.07). Initial referral was associated with younger age (70-74; OR, 5.64; 95% CI, 3.37-0.45) and higher performance status (Karnofsky performance status ≥90; OR, 5.34; 95% CI, 2.63-10.83)., Conclusions: : Nonreferral to radiation oncology accounted for half of RT omission but was based on age and Karnofsky performance status, in accordance with guidelines. Lack of radiation oncologist practice change in response to misaligned financial incentives is reassuring, potentially reflecting incentive design and/or centralized quality assurance review. Multi-institutional studies are needed to confirm these findings., (© 2022 The Authors.)

Background: A complex relationship between adipose tissue and malignancy, involving an inflammatory response, has been reported. The goal of this work was to assess the prevalence of white adipose tissue (WAT) inflammation in patients with endometrial cancer (EC), and the association with circulating inflammation markers. Furthermore, the aim was to characterize the pathways activated in and the cell type composition of adipose tissue in patients with EC., Methods: Adipose tissue and blood samples were prospectively collected from 101 patients with EC at initial surgery. WAT inflammation was determined based on adipocytes surrounded by macrophages forming crown-like structures. Circulating levels of metabolic syndrome-associated and inflammatory markers were quantified. RNA-sequencing was performed on adipose samples (n = 55); differential gene expression, pathway, and cellular decomposition analyses were performed using state-of-the-art bioinformatics methods., Results: WAT inflammation was identified in 46 (45.5%) of 101 EC patients. Dyslipidemia, hypertension, and diabetes mellitus were significantly associated with WAT inflammation (p < .05). WAT inflammation was associated with greater body mass index (p < .001) and higher circulating levels of leptin, high-sensitivity C-reactive protein, and interleukin-6, as well as lower levels of adiponectin and sex hormone-binding globulin (p < .05). Transcriptomic analysis demonstrated increased levels of proinflammatory and pro-neoplastic-related gene expression in inflamed omental adipose tissue., Conclusions: WAT inflammation is associated with metabolic syndrome, obesity, and inflammatory markers, as well as increased expression of proinflammatory and proneoplastic genes., (© 2022 American Cancer Society.)

Objectives: Describe the cumulative incidence (CUIN) of peritoneal carcinomatosis (PC) and survival in patients presenting with advanced rectal cancer at staging pelvic MRI., Methods: From 2013 to 2018, clinicopathologic records of patients with pretreatment rectal MRI clinical (c)T3c, cT3d, cT4a, and cT4b primary rectal adenocarcinoma were retrospectively reviewed by two radiologists. Standard MRI descriptors and pathologic stages were recorded. Recurrence-free (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Development of PC was explored using competing risk analysis. Differences in survival were compared using the log-rank test. Gray's test was used to test for differences in CUIN of PC., Results: Three hundred forty-three patients (147 women; median age, 56 years) had MRI stages cT3cd, n = 170; cT4a, n = 40; and cT4b, n = 133. Median follow-up among survivors was 27 months (0.36-70 months). For M1 patients, OS differed only by cT stage (2-year OS: cT3 88.1%, cT4a 79.1%, cT4b 64.7%, p = 0.045). For M0 patients, OS and RFS differed only by pathological (p)T stage. We observed a statistically significant difference in the cumulative incidence of PC by cT stage (2-year CUIN: cT3 3.2%, cT4a 8.5%, cT4b 1.6%, p = 0.01), but not by pT stage. Seventy-nine patients (23%) presented with metastatic disease (M1), eight with PC (2.3%). Overall, eight patients presented with PC (cT4a: n = 4, other stages: n = 4) and 22 developed PC (cT4a: n = 5, other stages: n = 17)., Conclusions: PC is uncommon in rectal cancer. MRI-based T stage exhibited an overall association with the cumulative incidence of PC, and descriptively, cT4a stage appears to have the highest CUIN., Key Points: • In a retrospective study of 343 patients with rectal cancer undergoing baseline MRI and clinical follow-up, we found that peritoneal carcinomatosis was rare. • We observed a significant overall association between PC at presentation and cT stage that appeared to be driven by the higher proportion of cT4a patients presenting with PC. • Among patients that did not present with PC, we observed a significant overall association between time to PC and cT stage that may be driven by the higher cumulative incidence of PC in cT4a patients., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

This cross-sectional study uses data from the Centers for Medicare & Medicaid Services to assess the use of professional society guideline-nonconcordant radiotherapy in patients at the end of life., Competing Interests: Conflict of Interest Disclosures: Dr Mathis reported being in a research fellowship funded by eContour.org, a nonprofit educational website, during the conduct of the study. Dr Bekelman reported receiving grants from UnitedHealth Group, Pfizer, North Carolina BCBS, Embedded Healthcare, and personal fees from UnitedHealthcare, NCCN, New England Life Care, and Reimagine Care outside the submitted work. Dr Gillespie reported being co-founder of an educational website for radiation oncology professionals (eContour.org). No other disclosures were reported., (Copyright 2022 Santos PMG et al. JAMA Health Forum.)

Purpose: The LI-RADS Treatment Response (LR-TR) algorithm was introduced in 2017 to assist radiologists in assessing hepatocellular carcinoma (HCC) response following locoregional therapy. The objective of this study was to evaluate the associations between pre-treatment LI-RADS diagnostic categories, post-treatment LR-TR categories, and mRECIST response categories with overall survival (OS) of patients with HCC., Methods: This retrospective study included untreated patients with one or two lesions who underwent transarterial embolization with or without concomitant ablation from December 2003 to December 2017. Two radiologists (R1 and R2) reviewed pre- and post-treatment CT imaging. Associations between pre- and post-treatment variables, including post-treatment LR-TR categories (Viable, Equivocal, Nonviable), with OS were assessed using the Kaplan-Meier method and Cox proportional hazards regression., Results: Eighty-five patients were included (median age = 71 years, range 50-87; 17 women). The median OS from first embolization was 43.92 months. Pre- and post-treatment tumor size, pre-treatment LR-TIV (compared with LR-5), and post-treatment LR-TR Viable (compared with LR-TR Nonviable) were associated with OS (p < 0.05 for all). Median OS was shorter for LR-TR Viable patients (R1, 25.64 months, 95% CI 18.58-35.70; R2, 26.43 months 95% CI 20.68-43.92) than for LR-TR Nonviable patients (64.21 months R1 and R2, 95% CI 42.71-92.45 and 36.30-94.09, respectively). mRECIST categories showed similar associations with OS. Inter-reader agreement was moderate for LI-RADS categories (κ = 0.57, 95% CI 0.35-0.78) and substantial for LR-TR categories (κ = 0.68, 95% CI 0.55-0.81)., Conclusions: LR-TR categories show a strong association with OS in HCC patients treated with transarterial embolization., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

The purpose of this study was to examine associations between screen time (ST) parenting practices and 2-5-year-old children's TV viewing and weight status. Data were collected from 252 parent-child dyads enrolled in a randomized parent-focused childhood obesity prevention trial from 2009-2012. ST parenting practices were assessed at baseline using a validated parent-reported survey. Parent-reported child TV viewing and objectively measured anthropometrics were assessed at baseline, post-intervention (35 weeks), and follow-up (59 weeks). Marginal effect models were developed to test the association between baseline ST parenting practices and children's TV viewing, BMI z-score, and waist circumference across all time points. Limiting/monitoring ST was associated with decreased weekly TV viewing (β = -1.79, 95% CI: -2.61; -0.95), while exposure to TV was associated with more weekly TV viewing over 59 weeks (β = 1.23, 95% CI: 0.71; 1.75). Greater parent use of ST as a reward was associated with increased child BMI z-score (β = 0.15, 95% CI: 0.03; 0.27), while limiting/monitoring ST was associated with decreased BMI z-score (β = -0.16, 95% CI: -0.30; -0.01) and smaller waist circumference (β = -0.55, 95% CI: -1.04; -0.06) over the study period. These findings suggest that modifying parent ST practices may be an important strategy to reduce ST and promote healthy weight in young children.

Purpose: This prospective phase 3 randomized trial was designed to test whether ultra high single-dose radiation therapy (24 Gy SDRT) improves local control of oligometastatic lesions compared to a standard hypofractionated stereotactic body radiation therapy regimen (3 × 9 Gy SBRT). The secondary endpoint was to assess the associated toxicity and the impact of ablation on clinical patterns of metastatic progression., Methods and Materials: Between November 2010 and September 2015, 117 patients with 154 oligometastatic lesions (≤5/patient) were randomized in a 1:1 ratio to receive 24 Gy SDRT or 3 × 9 Gy SBRT. Local control within the irradiated field and the state of metastatic spread were assessed by periodic whole-body positron emission tomography/computed tomography and/or magnetic resonance imaging. Median follow-up was 52 months., Results: A total of 59 patients with 77 lesions were randomized to 24 Gy SDRT and 58 patients with 77 lesions to 3 × 9 Gy SBRT. The cumulative incidence of local recurrence for SDRT-treated lesions was 2.7% (95% confidence interval [CI], 0%-6.5%) and 5.8% (95% CI, 0.2%-11.5%) at years 2 and 3, respectively, compared with 9.1% (95% CI, 2.6%-15.6%) and 22% (95% CI, 11.9%-32.1%) for SBRT-treated lesions (P = .0048). The 2- and 3-year cumulative incidences of distant metastatic progression in the SDRT patients were 5.3% (95% CI, 0%-11.1%), compared with 10.7% (95% CI, 2.5%-18.8%) and 22.5% (95% CI, 11.1%-33.9%), respectively, for the SBRT patients (P = .010). No differences in toxicity were observed., Conclusions: The study confirms SDRT as a superior ablative treatment, indicating that effective ablation of oligometastatic lesions is associated with significant mitigation of distant metastatic progression., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Treatment options for Helicobacter pylori-independent gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML) include surgery, immunotherapy, chemotherapy, and radiation therapy (RT). The purpose of this study was to investigate the efficacy and safety of RT and routine endoscopic surveillance, hypothesizing that most patients are curable with RT alone. We queried a single institution database at a tertiary referral cancer center for patients with H pylori-independent GML treated with RT between 1991 and 2017. Response was assessed by follow-up endoscopies (EGDs) starting 10 to 12 weeks post-RT. Computed tomography scans were also part of the follow-up program, and positron emission tomography was added when clinically appropriate. We identified 178 patients (median age, 63 years; range, 25-89 years); 86% had stage I disease, 7% had stage II disease, and 7% had stage IV disease. Median RT dose was 3000 cGy over 20 fractions. Ninety-five percent of patients exhibited complete pathologic response on posttreatment EGD. Two patients experienced grade 3 toxicity, and 2 patients experienced in-field secondary malignancies. Over a median follow-up of 6.2 years, 9.6% experienced local failures, and 11.8% developed distant sites of disease. Five-year and 10-year overall survival were 94% and 79%, respectively, from last date of RT. RT is a highly effective and safe treatment for GML with excellent overall survival and very rare acute or late treatment-related toxicities. Favorable outcomes from this large retrospective sample of patients provide credible and compelling support for RT as standard of care for H pylori-independent GML., (© 2021 by The American Society of Hematology.)

Purpose: Guidelines recommend short-course (≤10 fractions) external-beam radiation therapy (EBRT) for bone metastases. Stereotactic body radiation therapy (SBRT) may also improve outcomes; however, routine use is not recommended outside clinical trials. We assessed national radiation therapy trends in complex techniques for bone metastases and associated expenditures., Methods and Materials: Using a claims-based Medicare data set covering 84% of beneficiaries, we assessed the relative proportion of all radiation episodes represented by bone metastases. We then evaluated use of short-course and long-course (>10 fractions) EBRT, intensity modulated radiation therapy (IMRT), and SBRT for bone metastases in hospital-affiliated outpatient (OPD) or freestanding (FREE) facilities. We assessed differences using χ 2 d or Wilcoxon rank sum tests for categorical and continuous variables, respectively. We identified associations with modality, fractionation, and expenditures using multivariable logistic/linear regression., Results: Among 467,781 radiation episodes for 17 cancer diagnoses, the overall proportion of episodes dedicated to bone metastases (9.4%) was stable from 2015 to 2017, although treatments were increasing in the hospital-affiliated outpatient setting (P < .005). We identified 40,993 episodes for bone metastases, of which 63% were short-course EBRT, 24% were long-course EBRT, 7% were SBRT, and 6% were IMRT. Techniques more common in the hospital-affiliated outpatient setting included short-course EBRT (OPD, 69%, vs FREE, 56%) and SBRT (OPD, 9%, vs FREE, 5%). Techniques more common among free-standing centers included long-course EBRT (OPD, 19%, vs FREE, 31%) and IMRT (OPD, 4%, vs FREE, 9%). From 2015 to 2017, long-course EBRT decreased by an absolute 8%; short-course EBRT, SBRT, and IMRT increased by 4%, 2.5%, and 1%, respectively. The SBRT/IMRT uptake did not differ by setting (P = .4). Differences in expenditures between SBRT and short-course EBRT decreased by a relative 8% in professional and 12% in technical fees., Conclusions: Approximately 1 in 4 patients received long-course EBRT, with small reductions in use largely replaced by complex treatment modalities. However, expenditures for complex modalities also decreased over time. As alternative payment models take effect, quality metrics are needed to ensure appropriate, effective, and safe delivery of complex technologies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Distinguishing separate primary lung carcinomas (SPLCs) from intrapulmonary metastases (IPMs) in non-small cell lung cancer (NSCLC) patients is a challenging dilemma in clinical practice. Next-generation sequencing (NGS) was recently shown to represent a robust molecular method for clonal discrimination in this setting. In this study, using clonal relationships established by comprehensive NGS as the ground truth, we investigated whether NSCLC patients with SPLCs versus IPMs exhibit distinct imaging characteristics., Material and Methods: This retrospective study included patients who underwent pre-treatment computed tomography (CT) and/or positron emission tomography/CT (PET/CT) imaging followed by surgical resection for >1 NSCLC. Nodular, parenchymal, pleural, and ancillary CT features, as well as maximum standardized uptake values (SUVs) on PET/CT were recorded. Rao-Scott chi-square, Wilcoxon rank-sum, and Fisher's exact tests were used in patient- and lesion-level comparisons., Results: This study included 60 patients (median age = 69 years, 68 % female) with 127 individual tumors comprising 51 SPLC vs 23 IPM tumor pairs based on NGS profiling. SPLCs were associated with subsolid consistency (P = 0.005) and spiculated contours (P <  0.001), while IPMs were associated with greater difference of size between lesions (P = 0.017) or pure solid consistency of the smaller lesion (P = 0.011). Lymph node involvement was more frequent in IPMs than SPLCs (P = 0.036). SUV measurements were not useful for differentiation (P > 0.05)., Conclusion: Selected preoperative CT features are distributed differentially in SPLCs and IPMs, suggesting that imaging may have a role in distinguishing clonal relationships of tumors in patients with >1 NSCLC., (Copyright © 2021. Published by Elsevier B.V.)

Background and Purpose: Concurrent chemoradiation (cCRT) and durvalumab is standard therapy for patients with unresectable stage III non-small-cell lung cancers (NSCLC). Data is limited on outcomes with this regimen outside of clinical trials. Local-regional control rates remain undefined., Materials and Methods: We reviewed patients with stage III unresectable NSCLCs treated between November 2017 and February 2019 with cCRT and ≥1 dose of durvalumab. We examined 12-month progression-free-survival (PFS), overall-survival (OS), toxicities, and the incidence and pattern of local-regional and metastatic failures., Results: Sixty-two patients (median follow-up 12 months) with median age of 66 years of which 73% had stage IIIB (n = 33) or IIIC (n = 12) disease started durvalumab a median of 1.5 months from the end of cCRT and were treated with a median of 8 months of durvalumab. Common reasons for stopping durvalumab included disease progression (32%, 20/62) and toxicity (24%, 15/62). The estimated 12-month PFS and OS were 65% (95% CI: 51-79%) and 85% (95% CI: 75-95%), respectively. The cumulative 12-month incidence of local-regional and distant failures were 18% (95% CI: 5.9-30%) and 30% (95% CI: 16.3-44.5%), respectively. Among patients with distant metastatic disease (n = 17), 47% had oligometastatic disease. High tumor mutation burden (≥8.8 mt/Mb) or PD-L1 (≥1% or PD-L1 ≥ 50%) did not predict improved PFS., Conclusions: Outcomes with cCRT and durvalumab in practice align with the PACIFIC trial. A substantial minority of patients are candidates for metastasis-directed therapies at progression. Local regional outcomes appear improved to historical data of cCRT alone., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To characterize the clinical outcomes when stereotactic body radiation therapy (SBRT) alone is used to treat high-grade epidural disease without prior surgical decompression, the authors conducted a retrospective cohort study of patients treated at the Memorial Sloan Kettering Cancer Center between 2014 and 2018. The authors report locoregional failure (LRF) for a cohort of 31 cases treated with hypofractionated SBRT alone for grade 2 epidural spinal cord compression (ESCC) with radioresistant primary cancer histology., Methods: High-grade epidural disease was defined as grade 2 ESCC, which is notable for radiographic deformation of the spinal cord by metastatic disease. Kaplan-Meier survival curves and cumulative incidence functions were generated to examine the survival and incidence experiences of the sample level with respect to overall survival, LRF, and subsequent requirement of vertebral same-level surgery (SLS) due to tumor progression or fracture. Associations with dosimetric analysis were also examined., Results: Twenty-nine patients undergoing 31 episodes of hypofractionated SBRT alone for grade 2 ESCC between 2014 and 2018 were identified. The 1-year and 2-year cumulative incidences of LRF were 10.4% (95% CI 0-21.9) and 22.0% (95% CI 5.5-38.4), respectively. The median survival was 9.81 months (95% CI 8.12-18.54). The 1-year cumulative incidence of SLS was 6.8% (95% CI 0-16.0) and the 2-year incidence of SLS was 14.5% (95% CI 0.6-28.4). All patients who progressed to requiring surgery had index lesions at the thoracic apex (T5-7)., Conclusions: In carefully selected patients, treatment of grade 2 ESCC disease with hypofractionated SBRT alone offers a 1-year cumulative incidence of LRF similar to that in low-grade ESCC and postseparation surgery adjuvant hypofractionated SBRT. Use of SBRT alone has a favorable safety profile and a low cumulative incidence of progressive disease requiring open surgical intervention (14.5%).

Introduction: Evidence-based recommendations on duration of multiagent systemic therapy for LAPC are lacking. Herein, we assess the impact of duration of combination systemic therapy on survival of patients with LAPC., Methods: The National Cancer Database was interrogated to identify patients with untreated LAPC diagnosed from 2004 to 2014. Patients treated with ≥ 1 month of multiagent chemotherapy (MAC) and ≥ 6 months of follow-up were included. Kaplan-Meier survival curves were generated to examine OS of each MAC duration group. Univariable and multivariable Cox proportional hazards regression was used to examine the association between OS with demographic and clinical variables. Statistical computations were performed using SAS Software Version 9.4., Results: Of the 3410 patients, 1114 met inclusion criteria. Median age was 64 years. Median treatment duration was 3.2 months (range 1-19.8). Median follow-up was 23.5 months (range 3-120). Median OS of all patients was 9.4 months (95% CI: 8.7-10.1). Median OS of patients receiving ≥ 1-4 months, >4-6 months and > 6 months of MAC was 8.4 months (95% CI: 7.7-9), 10.2 months (95% CI: 9-11.8), and 12.8 months (95% CI 11.6-16). Twelve-month survival was 37% for patients receiving ≥ 1-4 months, 43% for > 4-6 months, and 56% for > 6 months. Female sex (P = .02), higher median household income (P = .03), and longer duration of MAC (P < .001) were independently associated with improved OS following multivariable analysis., Conclusion: This analysis in LAPC patients suggests that combination systemic therapy regimens of 6 months or more may optimize survival outcomes. Further investigation on the duration of systemic therapy question in LAPC is needed., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: To evaluate the role of diffusion kurtosis and diffusivity as potential imaging biomarkers to predict response to neoadjuvant chemoradiation therapy (CRT) from baseline staging magnetic resonance imaging (MRI) in locally advanced rectal cancer (LARC)., Materials and Methods: This retrospective study included 45 consecutive patients (31 male/14 female) who underwent baseline MRI with high b-value sequences (up to 1500 mm/s 2 ) for LARC followed by neoadjuvant chemoradiation and surgical resection. The mean age was 57.4 years (range 34.2-72.9). An abdominal radiologist using open source software manually segmented T2-weighted images. Segmentations were used to derive diffusion kurtosis and diffusivity from diffusion-weighted images as well as volumetric data. These data were analyzed with regard to tumor regression grade (TRG) using the four-tier American Joint Committee on Cancer (AJCC) classification, TRG 0-3. Proportional odds regression was used to analyze the four-level ordinal outcome. A sensitivity analysis was performed using univariable logistic regression for binary TRG groups, TRG 0/1 (> 90% response), or TRG 2/3 (< 90% response). p < 0.05 was considered significant throughout., Results: In the univariable proportional odds regression analysis, higher diffusivity summary (D sum ) values were observed to be significantly associated with higher odds of being in one or more favorable TRG group (TRG 0 or 1). In other words, on average, patients with higher D sum values were more likely to be in a more favorable TRG group. These results are mostly consistent with the sensitivity analysis, in which higher values for most D sum values [all but region of interest (ROI)-max D median (p = 0.08)] were observed to be significantly associated with higher odds of being TRG 0 or 1. Tumor volume of interest (VOI) and ROI volume, ROI kurtosis mean and median, and VOI kurtosis mean and median were not significantly associated with TRG., Conclusion: Diffusivity derived from the baseline staging MRI, but not diffusion kurtosis or volumetric data, is associated with TRG and therefore shows promise as a potential imaging biomarker to predict the response to neoadjuvant chemotherapy in LARC., Clinical Relevance Statement: Diffusivity shows promise as a potential imaging biomarker to predict AJCC TRG following neoadjuvant CRT, which has implications for risk stratification. Patients with TRG 0/1 have 5-year disease-free survival (DFS) of 90-98%, as opposed to those who are TRG 2/3 with 5-year DFS of 68-73%.