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Background: Late morbidity after childhood cancer may be mitigated by healthy lifestyle behaviors. We piloted a game-based, parent-child digital intervention to increase activity in sedentary survivors., Methods: Survivors aged 10-16 treated with cardiotoxic therapy and not meeting US physical activity guidelines were enrolled in a single-arm study with a parent. Following a 14-day run-in, participants chose a prespecified step goal and wore an accelerometer daily for 24 weeks (12-week game-based intervention; 12-week follow-up). Participants completed the Acceptability of Intervention Measure (AIM) at 24 weeks; a subset of dyads completed qualitative interviews., Results: Among 129 eligible survivors, 27 enrolled (20.9% participation rate) with a parent. Four dyads were removed during the 14-day run-in period due to noncompliance. Among the 23 dyads who continued to the study, the tracker was worn for 95% of days during the 12-week intervention (95% confidence interval [CI]: 94-96) and 81% during the 12-week follow-up (95% CI: 79-82). Overall, the prespecified step goal was met for 64% (95% CI: 63-66) of days during the intervention and 37% (95% CI: 35-38) during the follow-up. At the end of study, 17/23 dyads responded to AIM; 82% of survivors and 94% of parents reported the intervention as acceptable. During qualitative interviews (n = 5), dyads noted that they liked the accountability of the "buddy system," but would have liked more personalized goal-setting., Conclusions: Despite high ratings of acceptability among participants, difficulties with sustained adherence and retention were encountered in this parent-child gamification intervention. Alternate, tailored designs should be considered in the future., (© 2024 Wiley Periodicals LLC.)

We developed and evaluated the Digital Platform for Exercise (DPEx): a decentralized, patient-centric approach designed to enhance all aspects of clinical investigation of exercise therapy. DPEx integrated provision of a treadmill with telemedicine and remote biospecimen collection permitting all study procedures to be conducted in patient's homes. Linked health biodevices enabled high-resolution monitoring of lifestyle and physiological response. Here we describe the rationale and development of DPEx as well as feasibility evaluation in three different cohorts of patients with cancer: a phase 0a development study among three women with post-treatment primary breast cancer; a phase 0b proof-of-concept trial of neoadjuvant exercise therapy in 13 patients with untreated solid tumors; and a phase 1a level-finding trial of neoadjuvant exercise therapy in 53 men with localized prostate cancer. Collectively, our study demonstrates the utility of a fully digital, decentralized approach to conduct clinical trials of exercise therapy in a clinical population., (© 2024. The Author(s).)

Background: Whether structured exercise therapy improves chemotherapy delivery, tolerability, and tumor response is unclear., Methods: This was a secondary analysis of a phase 2 trial investigating exercise therapy (n = 72) versus usual care (n = 72) in patients with primary breast cancer. Exercise therapy comprised individualized treadmill walking three times weekly for 20-50 minutes per session at 55%-100% of pretreatment exercise capacity. Chemotherapy delivery was assessed according to the relative dose intensity (RDI), tolerability was assessed according to patient-reported outcomes and blood laboratory values, and response was assessed based on the pathologic complete response rate in patients who received neoadjuvant chemotherapy., Results: In the exercise therapy group, 51 patients (71%) reached 100% RDI (median, 100%; interquartile range, 100%-100%) compared with 41 patients (57%) in the usual care group (median, 100%; interquartile range, 95%-100%; p = .08). Tolerability was similar in both groups; the rates of grade 3 or higher neutropenia and anemia were 22% versus 39% and 7% versus 10% in the exercise and usual care groups, respectively. In patients who received anthracyclines (n = 104), 41 (77%) had 100% chemotherapy RDI in the exercise therapy group versus 29 (57%) in the usual care group (p = .026). In the neoadjuvant chemotherapy subgroup (n = 51 tumors), the postneoadjuvant therapy (yp) pathologic complete response (ypT0ypN0) rate was 27% (95% confidence interval, 12%-50%) in the exercise therapy group compared with 28% (95% confidence interval, 13%-47%) in the usual care group (p > .9)., Conclusions: In patients with primary breast cancer, exercise therapy was associated with improved delivery of anthracycline-based chemotherapy. Although exercise therapy was not significantly associated with tumor response, effects varied by tumor subtype (trial registration: Clinicaltrials.gov identifier NCT01943695)., (© 2024 American Cancer Society.)

Purpose: The purpose of this study was to provide updated data on oncologic outcomes following definitive surgical treatment of soft tissue sarcoma of the hand in a cohort of 109 patients, as well as to characterize risk factors for poor oncologic and functional outcomes., Methods: We analyzed data from 109 consecutive patients who had definitive surgical treatment for soft tissue sarcoma of the hand performed between 1996 and 2019 by a single surgeon at a sarcoma center. Primary outcomes included functional outcome (assessed by Musculoskeletal Tumor Society scores), disease-free survival (DFS), and overall survival (OS). We compiled descriptive data and used a multivariable linear model to identify factors associated with functional outcomes. Kaplan-Meier methods were used to estimate 5- and 10-year DFS and OS., Results: Patients had a median age of 36 years at presentation. Median follow-up was 6.1 years among patients alive at the end of follow-up. The median Musculoskeletal Tumor Society score was 29; functional outcome was worse among patients with high-grade tumors or complications. Among the 107 patients who became disease-free, there were four local recurrences (one with metastasis), six distant recurrences, and one death without recurrence. All local recurrences were deep tumors (two myxofibrosarcoma and two myxoinflammatory fibrosarcoma). Estimated 5- and 10-year DFS rates were 89% (95% confidence interval [CI]: 83% to 96%) and 88% (95% CI: 80% to 95%). There were seven deaths, and the estimated 5- and 10-year OS rates were 95% (95% CI: 90% to 100%) and 92% (95% CI: 84% to 100%). Larger tumor size and higher stage at diagnosis were associated with shorter DFS and OS in univariable analyses; low event rates precluded multivariable analysis of survival., Conclusions: Aggressive disease-specific surgical and multidisciplinary treatment can yield long DFS and OS, and good functional outcomes. However, complications and high-grade tumors are associated with worse functional scores., Type of Study/level of Evidence: Prognostic II., Competing Interests: Conflicts of Interest Drs Chapman, Nolan, and Athanasian have nothing to disclose. Ms Lavery reports salary support, unrelated to the submitted work, that was paid to her institution by the American Association of Cancer Research Project Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Importance: Observational data have shown that postdiagnosis exercise is associated with reduced risk of prostate cancer death. The feasibility and tumor biological activity of exercise therapy is not known., Objective: To identify recommended phase 2 dose of exercise therapy for patients with prostate cancer., Design, Setting, and Participants: This single-center, phase 1a dose-finding trial was conducted at a tertiary cancer center using a patientcentric, decentralized platform and included 53 inactive men with treatment-naive localized prostate cancer scheduled to undergo surgical resection between June 2019 and January 2023. Data were analyzed in June 2024., Intervention: Six escalated exercise therapy dose levels ranging from 90 to 450 minutes per week of individualized, moderate-intensity treadmill walking, allocated using adaptive continual reassessment. All exercise therapy sessions were conducted remotely with real-time monitoring., Main Outcomes and Measures: Feasibility was evaluated by relative exercise dose intensity (REDI). A dose level was considered feasible if 70% or more of patients achieved an REDI of 75% or greater. Activity end points were changes in tumor cell proliferation (Ki67) and plasma prostate-specific antigen levels between pretreatment and postintervention. Safety and changes in patient physiology were also assessed., Results: A total of 53 men were enrolled (median [IQR] age, 61 [56-66] years). All dose levels were feasible (≥75% REDI). The mean (95% CI) changes in Ki67 were 5.0% (-4.3% to 14.0%) for 90 minutes per week, 2.4% (-1.3% to 6.2%) for 150 minutes per week, -1.3% (-5.8% to 3.3%) for 225 minutes per week, -0.2% (-4.0% to 3.7%) for 300 minutes per week, -2.6% (-9.2% to 4.1%) for 375 minutes per week, and 2.2% (-0.8% to 5.1%) for 450 minutes per week. Changes in prostate-specific antigen levels were 1.0 ng/mL (-1.8 to 3.8) for 90 minutes per week, 0.2 ng/mL (-1.1 to 1.5) for 150 minutes per week, -0.5 ng/mL (-1.2 to 0.3) for 225 minutes per week, -0.2 (-1.7 to 1.3) for 300 minutes per week, -0.7 ng/mL (-1.7 to 0.4) for 375 minutes per week, and -0.9 ng/mL (-2.4 to 0.7) for 450 minutes per week. No serious adverse events were observed. Overall, 225 minutes per week (approximately 45 minutes per treatment at 5 times weekly) was selected as the recommended phase 2 dose., Conclusions and Relevance: The results of this nonrandomized clinical trial suggest that neoadjuvant exercise therapy is feasible and safe with promising activity in localized prostate cancer., Trial Registration: ClinicalTrials.gov Identifier: NCT03813615.

Purpose: Intravascular tumor emboli in axillary soft tissue (ITE) is a rare pathologic finding in breast cancer and is associated with higher axillary nodal disease burden. The independent prognostic and predictive value of this entity is unknown, as is the role of radiation therapy for ITE., Methods and Materials: We analyzed a prospectively maintained database of breast cancer patients treated from 1992 to 2020. Patients with ITE were matched to those without (1:2) based on propensity scores to control for potential confounding factors. Locoregional (LRR) and distant recurrence (DR) were evaluated using competing risks methods accounting for death as a competing event. Overall survival (OS) and disease-free survival (DFS) were evaluated by Cox regression models. Among patients with ITE, we also evaluated whether RT improved outcomes., Results: Among 2377 total patients, 129 had ITE, of whom 126 were propensity score matched to 252 without ITE. Median follow-up from time of surgery was 5.5 years (IQR 2.3, 9.7). There were no statistically significant differences in the 5-year incidence of LRR between groups (5.4% [95% CI, 1.6%-13%] with ITE vs 10% [95% CI, 6.7%-15%] without, P = .53) or DR (24% [95% CI, 15% 35%] with ITE vs 21% [95% CI, 16%-27%] without, P = .51). Five-year OS and DFS did not differ between groups ( P > .9 for both comparisons, patients with ITE vs without ITE). In analyzing the effect of RT among patients with ITE, receipt of RT was associated with significantly improved DFS (HR, 0.34, 95% CI, 0.12-0.93, P = .04)., Conclusions: Patients with ITE do not exhibit significantly worse LRR, DR, DFS, or OS compared with a propensity-score-matched cohort without ITE. However, among patients with ITE, those who received RT demonstrated significantly improved DFS. Larger studies with longer follow-up are needed to evaluate the prognostic and predictive implications of ITE., (© 2024 The Author(s).)

NK-1 receptor antagonists (NK1-RA) are key agents for chemotherapy-induced nausea and vomiting (CINV) prevention in patients receiving highly emetogenic chemotherapy. Current pediatric practice guidelines recommend the use of intravenous fosaprepitant or oral aprepitant. However, there are reports of hypersensitivity reactions with fosaprepitant due to polysorbate 80. Intravenous aprepitant does not contain polysorbate 80, but its use in pediatric patients has not been described. In this retrospective, single-center study, 106 pediatric patients received either fosaprepitant or intravenous aprepitant as part of their antiemetic regimen. Intravenous aprepitant was well tolerated and did not lead to any instances of hypersensitivity reactions requiring discontinuation., (© 2024 Wiley Periodicals LLC.)

Purpose: Observational clinicogenomic data sets, consisting of tumor next-generation sequencing (NGS) data linked to clinical records, are commonly used for cancer research. However, in real-world practice, oncologists frequently request NGS in search of treatment options for progressive cancer. The extent and impact of this dynamic on analysis of clinicogenomic research data are not well understood., Methods: We analyzed clinicogenomic data for patients with non-small cell lung, colorectal, breast, prostate, pancreatic, or urothelial cancers in the American Association for Cancer Research Biopharmaceutical Consortium cohort. Associations between baseline and time-varying clinical characteristics and time from diagnosis to NGS were measured. To explore the impact of informative cohort entry on biomarker inference, statistical interactions between selected biomarkers and time to NGS with respect to overall survival were calculated., Results: Among 7,182 patients, time from diagnosis to NGS varied significantly by clinical factors, including cancer type, calendar year of sequencing, institution, and age and stage at diagnosis. NGS rates also varied significantly by dynamic clinical status variables; in an adjusted model, compared with patients with stable disease at any given time after diagnosis, patients with progressive disease by imaging or oncologist assessment had higher NGS rates (hazard ratio for NGS, 1.61 [95% CI, 1.45 to 1.78] and 2.32 [95% CI, 2.01 to 2.67], respectively). Statistical interactions between selected biomarkers and time to NGS with respect to survival, potentially indicating biased biomarker inference results, were explored., Conclusion: To evaluate the appropriateness of a data set for a particular research question, it is crucial to measure associations between dynamic cancer status and the timing of NGS, as well as to evaluate interactions involving biomarkers of interest and NGS timing with respect to survival outcomes.

Peritoneal metastases (PM) are common in metastatic colorectal cancer (mCRC). We aimed to characterize patients with mCRC and PM from a clinical and molecular perspective using the American Association of Cancer Research Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative (BPC) registry. Patients' tumor samples underwent targeted next-generation sequencing. Clinical characteristics and treatment outcomes were collected retrospectively. Overall survival (OS) from advanced disease and progression-free survival (PFS) from start of cancer-directed drug regimen were estimated and adjusted for the left truncation bias. A total of 1,281 patients were analyzed, 244 (19%) had PM at time of advanced disease. PM were associated with female sex [OR: 1.67; 95% confidence interval (CI): 1.11-2.54; P = 0.014] and higher histologic grade (OR: 1.72; 95% CI: 1.08-2.71; P = 0.022), while rectal primary tumors were less frequent in patients with PM (OR: 0.51; 95% CI: 0.29-0.88; P < 0.001). APC occurred less frequently in patients with PM (N = 151, 64% vs. N = 788, 79%) while MED12 alterations occurred more frequently in patients with PM (N = 20, 10% vs. N = 32, 4%); differences in MED12 were not significant when restricting to oncogenic and likely oncogenic variants according to OncoKB. Patients with PM had worse OS (HR: 1.45; 95% CI: 1.16-1.81) after adjustment for independently significant clinical and genomic predictors. PFS from initiation of first-line treatment did not differ by presence of PM. In conclusion, PM were more frequent in females and right-sided primary tumors. Differences in frequencies of MED12 and APC alterations were identified between patients with and without PM. PM were associated with shorter OS but not with PFS from first-line treatment., Significance: Utilizing the GENIE BPC registry, this study found that PM in patients with colorectal cancer occur more frequently in females and right-sided primary tumors and are associated with worse OS. In addition, we found a lower frequency of APC alterations and a higher frequency in MED12 alterations in patients with PM., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Objectives: To investigate whether patients with impending or completed fracture of the proximal femur who were treated with bevacizumab in the six weeks prior to surgery are at higher risk of surgical complications than patients given bevacizumab outside of the six-week period., Methods: We retrospectively reviewed cases of hip fracture treated between 1995 and 2020 at our institution. Patients were included if they were age 18 years or older, underwent hip surgery for impending or completed fracture, and received bevacizumab preoperatively but not postoperatively. Charts were reviewed for demographic, surgical, and postoperative details. A Cox model was applied to assess whether the timing of preoperative bevacizumab administration (≤6 weeks vs. >6 weeks) was associated with the risk of a postoperative complication., Results: Two of the 23 patients who received bevacizumab ≤6 weeks before surgery experienced complications (deep vein thrombosis [n=1] and intraoperative fracture related to progression of disease [n=1]). Of the 53 patients who received bevacizumab more than six weeks preoperatively, five experienced complications (wound drainage [n=2] and deep vein thrombosis [n=3]). In the Cox model, timing of bevacizumab was not associated with postoperative complications (univariable hazard ratio, 0.92; 95% confidence interval, 0.18-4.73)., Conclusion: In this cohort of patients who underwent surgery for hip fractures, we did not observe an increased risk of postoperative complications among those who received bevacizumab within six weeks of surgery relative to those who received bevacizumab more than six weeks before surgery. The retrospective nature of the study and small sample size are limiting factors in this study., Competing Interests: Jessica Lavery discloses salary support from the American Association of Cancer Research Project Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative (GENIE BPC). The other authors do not have any potential conflicts of interest for this manuscript., (Copyright © 2024 Mashhad University of Medical Sciences.)

Introduction: Excisional biopsies for soft-tissue sarcoma (STS) of the hand are commonly done outside of sarcoma centers and can compromise incorporation of the biopsy site into standard limb salvage or amputation flaps. We sought to identify risk factors for these suboptimal biopsies., Methods: We analyzed prospective data on all patients (N = 109) who underwent definitive resection of primary STS of the hand between 1995 and 2019 at our institution. Biopsies were classified by type (excisional vs. incisional/needle), whether they were done before referral, and whether the incision could be incorporated into standard limb salvage or amputation flaps (ILS biopsies) or not (NILS biopsies). Analyses examined potential predictors of NILS biopsies and whether outcomes differed by biopsy type., Results: Biopsies done before referral (N = 91) were more likely to be excisional (79% vs. 17%). Excisional biopsies were associated with smaller tumor size (median, 2.0 vs. 3.15 cm; P = 0.025) and longer time to first intervention (1.88 vs. 1.17 months; P = 0.001). Forty-eight percent of excisional and 29% of incisional biopsy sites required soft-tissue coverage at the time of definitive surgery ( P = 0.07). Biopsy type was not associated with Musculoskeletal Tumor Society score or need for amputation. Risk factors for NILS biopsies included larger tumor size, deep tumor, and excisional biopsy. High-risk areas for NILS biopsies included the carpal tunnel, volar wrist, first webspace, radial palm, and proximal thumb. NILS biopsies were associated with positive margins, need for soft-tissue coverage, and lower Musculoskeletal Tumor Society scores., Discussion: This study informs referral guidelines for patients with STS of the hand. Patients with tumors that are deep, large, or in high-risk locations should be referred to a sarcoma center before biopsy. If that is not possible, incisional biopsy in line with standard resection incisions or radiology-guided core needle biopsy is preferable to excisional biopsy., Type of Study: Prognostic study., Level of Evidence: Level II., Competing Interests: Support: This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. Jessica Lavery discloses salary support from the American Association of Cancer Research Project Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative (GENIE BPC). The other authors report no conflicts of interest related to this study., (Copyright © 2023 by the American Academy of Orthopaedic Surgeons.)

International cancer registries make real-world genomic and clinical data available, but their joint analysis remains a challenge. AACR Project GENIE, an international cancer registry collecting data from 19 cancer centers, makes data from >130,000 patients publicly available through the cBioPortal for Cancer Genomics (https://genie.cbioportal.org). For 25,000 patients, additional real-world longitudinal clinical data, including treatment and outcome data, are being collected by the AACR Project GENIE Biopharma Collaborative using the PRISSMM data curation model. Several thousand of these cases are now also available in cBioPortal. We have significantly enhanced the functionalities of cBioPortal to support the visualization and analysis of this rich clinico-genomic linked dataset, as well as datasets generated by other centers and consortia. Examples of these enhancements include (i) visualization of the longitudinal clinical and genomic data at the patient level, including timelines for diagnoses, treatments, and outcomes; (ii) the ability to select samples based on treatment status, facilitating a comparison of molecular and clinical attributes between samples before and after a specific treatment; and (iii) survival analysis estimates based on individual treatment regimens received. Together, these features provide cBioPortal users with a toolkit to interactively investigate complex clinico-genomic data to generate hypotheses and make discoveries about the impact of specific genomic variants on prognosis and therapeutic sensitivities in cancer., Significance: Enhanced cBioPortal features allow clinicians and researchers to effectively investigate longitudinal clinico-genomic data from patients with cancer, which will improve exploration of data from the AACR Project GENIE Biopharma Collaborative and similar datasets., (©2023 The Authors; Published by the American Association for Cancer Research.)

Purpose: The impact of postdiagnosis exercise on cause-specific mortality in cancer survivors and whether this differs on the basis of cancer site is unclear., Methods: We performed an analysis of 11,480 patients with cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial. Patients with a confirmed diagnosis of cancer completing a standardized survey quantifying exercise after diagnosis were included. The primary outcome was all-cause mortality (ACM); secondary end points were cancer mortality and mortality from other causes. Cox models were used to estimate the cause-specific hazard ratios (HRs) for ACM, cancer, and noncancer mortality as a function of meeting exercise guidelines versus not meeting guidelines with adjustment for important clinical covariates., Results: After a median follow-up of 16 years from diagnosis, 4,665 deaths were documented (1,940 due to cancer and 2,725 due to other causes). In multivariable analyses, exercise consistent with guidelines was associated with a 25% reduced risk of ACM compared with nonexercise (HR, 0.75; 95% CI, 0.70 to 0.80). Compared with nonexercise, exercise consistent with guidelines was associated with a significant reduction in cancer mortality (HR, 0.79; 95% CI, 0.72 to 0.88) and mortality from other causes (HR, 0.72; 95% CI, 0.66 to 0.78). The inverse relationship between exercise and cause-specific mortality varied by exercise dose. Exercise consistent with guidelines was associated with a reduced hazard of ACM for multiple cancer sites. Reduction in cancer mortality for exercisers was only observed in head and neck and renal cancer., Conclusion: In this pan-cancer sample of long-term cancer survivors, exercise consistent with guidelines was associated with substantial ACM benefit driven by both reductions in cancer and noncancer mortality. The cause-specific impact of exercise differed as a function of cancer site.

Objectives: To compare outcomes of patients with high-grade epithelial ovarian cancer (EOC) who underwent secondary cytoreduction surgery (SCS) after up-front treatment with neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) versus primary debulking surgery (PDS)., Methods: Patients with high-grade EOC who underwent SCS from 2/1/2004-10/31/2021 were classified by up-front treatment. Clinical and treatment characteristics were compared between cohorts. Progression-free survival (PFS2) and overall survival (OS2) following SCS were compared using a Cox model adjusted for stage, age at SCS, and number of years between end of chemotherapy and SCS., Results: Of 374 patients, 62 (17%) underwent NACT-IDS and 312 (83%) PDS. Justification for NACT was disease extent (n = 57, 92%), comorbidities (n = 3, 5%), and thromboembolism (n = 2, 3%). The NACT-IDS cohort had a higher median age at SCS (64 years [IQR: 56-70] vs 59 years [IQR: 53-66]; P = .03), higher proportion of stage III/IV disease (100% vs 81%; P < .001), and shorter median interval between end of chemotherapy and SCS (1.5 years [IQR: 1.1-2.3] vs 1.9 years [IQR: 1.3-3.1]; P = .01). Achievement of complete gross resection at SCS did not differ between NACT-IDS and PDS (84% vs 88%; P = .18). PFS2 (HR: 1.19, 95% CI: 0.83-1.71) and OS2 (HR: 0.96, 95% CI: 0.57-1.63) did not vary by primary treatment modality after adjusting for clinically relevant covariates., Conclusions: Despite more extensive disease at presentation, patients with high-grade EOC who recur after NACT-IDS seem to have similar surgical and survival outcomes after SCS compared to patients who recur after PDS, suggesting that prior NACT-IDS should not preclude SCS., Competing Interests: Conflict of interest Outside the submitted work, D. Chi reports personal fees from Apyx Medical, Verthermia Inc., Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE. A. Iasonos reports consulting fees from Mylan. J. Lavery discloses salary support from the American Association of Cancer Research Project Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative (GENIE BPC). Y.L. Liu reports research funding from AstraZeneca, GSK, and Repare Therapeutics. R.N. Grisham reports honoraria from GSK, AstraZeneca, Natera, Springworks, Corcept, MJH, and PER. The other authors do not have potential conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: We describe the clinical and genomic landscape of the non-small cell lung cancer (NSCLC) cohort of the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative (BPC)., Experimental Design: A total of 1,846 patients with NSCLC whose tumors were sequenced from 2014 to 2018 at four institutions participating in AACR GENIE were randomly chosen for curation using the PRISSMM data model. Progression-free survival (PFS) and overall survival (OS) were estimated for patients treated with standard therapies., Results: In this cohort, 44% of tumors harbored a targetable oncogenic alteration, with EGFR (20%), KRAS G12C (13%), and oncogenic fusions (ALK, RET, and ROS1; 5%) as the most frequent. Median OS (mOS) on first-line platinum-based therapy without immunotherapy was 17.4 months [95% confidence interval (CI), 14.9-19.5 months]. For second-line therapies, mOS was 9.2 months (95% CI, 7.5-11.3 months) for immune checkpoint inhibitors (ICI) and 6.4 months (95% CI, 5.1-8.1 months) for docetaxel ± ramucirumab. In a subset of patients treated with ICI in the second-line or later setting, median RECIST PFS (2.5 months; 95% CI, 2.2-2.8) and median real-world PFS based on imaging reports (2.2 months; 95% CI, 1.7-2.6) were similar. In exploratory analysis of the impact of tumor mutational burden (TMB) on survival on ICI treatment in the second-line or higher setting, TMB z-score harmonized across gene panels was associated with improved OS (univariable HR, 0.85; P = 0.03; n = 247 patients)., Conclusions: The GENIE BPC cohort provides comprehensive clinicogenomic data for patients with NSCLC, which can improve understanding of real-world patient outcomes., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Extramural venous invasion (EMVI) on baseline MRI is associated with poor prognosis in patients with locally advanced rectal cancer. This study investigated the association of persistent EMVI after total neoadjuvant therapy (TNT) (chemoradiotherapy and systemic chemotherapy) with survival., Methods: Baseline MRI, post-TNT MRI, and surgical pathology data from 175 patients with locally advanced rectal cancer who underwent TNT and total mesorectal excision between 2010 and 2017 were retrospectively analyzed for evidence of EMVI. Two radiologists assessed EMVI status with disagreement adjudicated by a third. Pathologic EMVI status was assessed per departmental standards. Cox regression models evaluated the associations between EMVI and disease-free and overall survival., Results: EMVI regression on both post-TNT MRI and surgical pathology was associated with disease-free survival (hazard ratio, 0.17; 95% confidence interval (CI), 0.04-0.64) and overall survival (hazard ratio, 0.11; 95% CI, 0.02-0.68). In an exploratory analysis of 35 patients with EMVI on baseline MRI, only six had EMVI on pathology compared with 18 on post-TNT MRI; these findings were not associated (p = 0.2). Longer disease-free survival was seen with regression on both modalities compared with remaining positive. Regression on pathology alone, independent of MRI EMVI status, was associated with similar improvements in survival., Conclusions: Baseline EMVI is associated with poor prognosis even after TNT. EMVI regression on surgical pathology is common even with persistent EMVI on post-TNT MRI. EMVI regression on surgical pathology is associated with improved DFS, while the utility of post-TNT MRI EMVI persistence for decision-making and prognosis remains unclear., (© 2023. Society of Surgical Oncology.)

Patients with limited English proficiency receive worse care due to communication barriers. Little is known about which cancer hospitals have written language access policies addressing bilingual clinicians. We conducted a cross-sectional survey of healthcare organizations, matching survey data to American Hospital Association Survey and American Community Survey data. We analyzed characteristics associated with hospitals having bilingual clinician policies. The response rate was 71% (127/178). Many hospitals (53 [42%]) did not have written policies on bilingual clinicians. Having bilingual clinicians available at the hospital was associated with having a written policy on bilingual clinicians, while being an NCORP site was associated with not having a written policy on bilingual clinicians. Patient demographic characteristics were not associated with hospitals having written policies on bilingual clinicians. A substantial proportion of cancer hospitals do not have policies that cover language use by bilingual clinicians, particularly at NCORP sites. Having written policies on bilingual clinicians has the potential to mitigate cancer disparities by facilitating accountability, improving communication, and reducing errors., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Oncologists often order genomic testing to inform treatment for worsening cancer. The resulting correlation between genomic testing timing and prognosis, or "informative entry," can bias observational clinico-genomic research. The efficacy of existing approaches to this problem in clinico-genomic cohorts is poorly understood., Methods: We simulated clinico-genomic cohorts followed from an index date to death. Subgroups in each cohort who underwent genomic testing before death were "observed." We varied data generation parameters under four scenarios: (i) independent testing and survival times; (ii) correlated testing and survival times for all patients; (iii) correlated testing and survival times for a subset of patients; and (iv) testing and mortality exclusively following progression events. We examined the behavior of conditional Kendall tau (Tc) statistics, Cox entry time coefficients, and biases in overall survival (OS) estimation and biomarker inference across scenarios., Results: Scenario #1 yielded null Tc and Cox entry time coefficients and unbiased OS inference. Scenario #2 yielded positive Tc, negative Cox entry time coefficients, underestimated OS, and biomarker associations biased toward the null. Scenario #3 yielded negative Tc, positive Cox entry time coefficients, and underestimated OS, but biomarker estimates were less biased. Scenario #4 yielded null Tc and Cox entry time coefficients, underestimated OS, and biased biomarker estimates. Transformation and copula modeling did not provide unbiased results., Conclusions: Approaches to informative clinico-genomic cohort entry, including Tc and Cox entry time statistics, are sensitive to heterogeneity in genotyping and survival time distributions., Impact: Novel methods are needed for unbiased inference using observational clinico-genomic data., (©2023 American Association for Cancer Research.)

Motivation: Data from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative (GENIE BPC) represent comprehensive clinical data linked to high-throughput sequencing data, providing a multi-institution, pan-cancer, publicly available data repository. GENIE BPC data provide detailed demographic, clinical, treatment, genomic and outcome data for patients with cancer. These data result in a unique observational database of molecularly characterized tumors with comprehensive clinical annotation that can be used for health outcomes and precision medicine research in oncology. Due to the inherently complex structure of the multiple phenomic and genomic datasets, the use of these data requires a robust process for data integration and preparation in order to build analytic models., Results: We present the {genieBPC} package, a user-friendly data processing pipeline to facilitate the creation of analytic cohorts from the GENIE BPC data that are ready for clinico-genomic modeling and analyses., Availability and Implementation: {genieBPC} is available on CRAN and GitHub., (© The Author(s) 2022. Published by Oxford University Press.)

Background: Estimated peak oxygen consumption (Vo 2 peak) is widely used in oncology; however, estimated Vo 2 peak equations were developed in noncancer settings., Objectives: The aim of this study was to evaluate the validity of estimated Vo 2 peak in women with primary breast cancer and to develop oncology-specific estimated Vo 2 peak equations., Methods: Vo 2 peak was directly measured (TrueOne 2400, Parvo Medics) during 380 cardiopulmonary exercise tests in women previously treated for breast cancer (mean age: 59 ± 10 years; 3.1 ± 1.2 years post-therapy). The American College of Sports Medicine (ACSM), the Fitness Registry and the Importance of Exercise National Database (FRIEND), and heart failure (HF)-FRIEND equations were used to estimate Vo 2 peak. New equations were developed using patient and peak (Onc peak ) or submaximal (Onc sub ) exercise test characteristics., Results: The median differences between measured and estimated Vo 2 peak were 7.0 mL O 2 ·kg -1 ·min -1 , 3.9 mL O 2 ·kg -1 ·min -1 , and -0.2 mL O 2 ·kg -1 ·min -1 for ACSM, FRIEND, and HF-FRIEND, respectively. The number of estimated Vo 2 peak values within ±3.5 mL O 2 ·kg -1 ·min -1 of the measured values was 70 (18%), 164 (43%), and 306 (81%) for ACSM, FRIEND, and HF-FRIEND, respectively. The Onc peak and Onc Sub models included body mass index, age, a history of chemotherapy or radiation, the peak measured heart rate, and the treadmill grade and/or speed. The median differences between measured and estimated Vo 2 peak were 0.02 mL O 2 ·kg -1 ·min -1 (Onc peak ) and -0.2 mL O 2 ·kg -1 ·min -1 (Onc sub ). Eighty-six percent (n = 325) and 76% (n = 283) estimated Vo 2 peak values were within ±3.5 mL O 2 ·kg -1 ·min -1 of the measured Vo 2 peak values for Onc peak and Onc sub , respectively., Conclusions: HF-FRIEND or oncology-specific equations could be applied to estimate Vo 2 peak in patients previously treated for breast cancer in settings where cardiopulmonary exercise tests are not available. (Trial Comparing the Effects of Linear Versus Nonlinear Aerobic Training in Women With Operable Breast Cancer [EXCITE]; NCT01186367., Competing Interests: This study was supported by a research grant from the National Cancer Institute (R01-CA142566) awarded to Dr Jones and grants from AKTIV Against Cancer and the Memorial Sloan Kettering Cancer Center Support Grant/Core Grant (P30 CA008748). Dr Jones has stock ownership in Pacylex, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Aims: Our objective was to determine if preoperative patient-reported assessments are associated with survival after surgery for stabilization of skeletal metastases., Patients and Methods: All patients with metastatic cancer to bone and indications for skeletal stabilization surgery were approached to participate in a prospective cohort study at a tertiary care center from 2012 to 2017. Of the 208 patients who were eligible, 195 (94%) completed the 36-item Short Form Health Survey (SF-36) preoperatively and underwent surgical treatment of skeletal metastases with complete or impending fractures; the sample encompassed a range of cancer diagnoses and included cases of both internal fixation and endoprosthetic replacement. Cox proportional hazards models were used to identify associations between SF-36 scores and survival., Results: In a model adjusted for clinical factors, patients' mental and physical SF-36 component summary scores were significantly associated with survival, as was their SF-36 composite score ( P  = 0.004, P  = 0.015, and P  < 0.001, respectively). Scores in the general health, vitality, and mental health domains were each strongly associated with survival ( P  < 0.001)., Conclusions: Patients' preoperative assessments of their health status are associated with their survival after surgery for skeletal metastases. Patient-reported assessments have the potential to contribute unique information to models that estimate patient survival, as part of efforts to provide optimal, individualized care and make informed decisions about the type and magnitude of surgery for metastatic bone disease that will last the patient's lifetime., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Modifiable lifestyle-related factors heighten the risk and severity of coronavirus disease 2019 (COVID-19) in patients with cancer. Whether exercise lowers susceptibility or severity is not known., Methods: We identified 944 cancer patients from Memorial Sloan Kettering Cancer Center (mean age: 64; 85% female; 78% White) completing an exercise survey before receiving a confirmed positive or negative SARS-CoV-2 test. Exercise was defined as reporting moderate-intensity ≥5 days per week, ≥30 minutes/session or strenuous-intensity ≥3 days per week, ≥20 minutes/session. Multivariable logistic regression was used to determine the relationship between exercise and COVID-19 susceptibility and severity (i.e., composite of hospital admission or death events) with adjustment for clinical-epidemiologic covariates., Results: Twenty-four percent (230/944) of the overall cohort were diagnosed with COVID-19 and 35% (333/944) were exercisers. During a median follow-up of 10 months, 26% (156/611) of nonexercising patients were diagnosed with COVID-19 compared with 22% (74/333) of exercising patients. The adjusted OR for risk of COVID-19 was 0.65 [95% confidence interval (CI), 0.44-0.96, P = 0.03] for exercisers compared with nonexercisers. A total of 20% (47/230) of COVID-19 positive patients were hospitalized or died. No difference in the risk of severe COVID-19 as a function of exercise status was observed (P > 0.9)., Conclusions: Exercise may reduce the risk of COVID-19 infection in patients with a history of cancer, but not its severity., Impact: This study provides the first data showing that exercise might lower the risk of COVID-19 in cancer patients, but further research is required., (©2022 American Association for Cancer Research.)

Background: It is unclear how intensity-modulated radiation therapy (IMRT) impacts long-term risk of second malignant neoplasms (SMNs) in childhood cancer patients., Procedure: Patients aged ≤21 years treated with IMRT between 1998 and 2009 and who survived ≥5 years after IMRT were included. SMN site in relation to isodose level (IDL) of IMRT was evaluated. Standardized incidence ratios (SIR) and excess absolute risks (EAR) were calculated. Cumulative incidences were estimated with death as a competing risk., Results: Three-hundred twenty-five patients were included with median follow-up of 11.2 years from IMRT (interquartile range: 9.4-14.0) among patients alive at the end of follow-up. Two hundred (62%) patients had ≥10 years of follow-up and 284 (87%) patients were alive at the time of analysis. Fifteen patients developed SMNs (11 solid, four hematologic). Median time from IMRT to solid SMN was 11.0 years (range: 6.8-19.2) with 10- and 15-year cumulative incidences 1.8% (95% CI: 0.7-3.9) and 3.5% (95% CI: 1.4-7.5), respectively; SIR was 13.7 (95% CI: 6.9-24.6) and EAR was 2.8 per 1000 person-years (95% CI: 1.0-4.6). Eight solid SMNs developed within the IMRT field (100% IDL [n = 5], 80% IDL [n = 1], 50% IDL [n = 1], 40% IDL [n = 1]), one within the 70%-80% IDL of a conventional field, one was out-of-field, and one could not be determined., Conclusions: With median follow-up of >10 years, many solid SMNs after IMRT in childhood cancer survivors develop in the high-dose region. These data serve as a foundation for comparison with other modalities of radiation treatment (e.g., proton therapy)., (© 2022 Wiley Periodicals LLC.)

Importance: Real-world data sets that combine clinical and genomic data may be subject to left truncation (when potential study participants are not included because they have already passed the milestone of interest at the time of study recruitment). The lapse between diagnosis and molecular testing can present analytic challenges and threaten the validity and interpretation of survival analyses., Observations: Effects of ignoring left truncation when estimating overall survival are illustrated using data from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative (GENIE BPC), and a straightforward risk-set adjustment approach is described. Ignoring left truncation results in overestimation of overall survival: unadjusted median survival estimates from diagnosis among patients with stage IV non-small cell lung cancer or stage IV colorectal cancer were overestimated by more than 1 year., Conclusions and Relevance: Clinicogenomic data are a valuable resource for evaluation of real-world cancer outcomes and should be analyzed using appropriate methods to maximize their potential. Analysts must become adept at application of appropriate statistical methods to ensure valid, meaningful, and generalizable research findings.

Purpose: The American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative is a multi-institution effort to build a pan-cancer repository of genomic and clinical data curated from the electronic health record. For the research community to be confident that data extracted from electronic health record text are reliable, transparency of the approach used to ensure data quality is essential., Materials and Methods: Four institutions participating in AACR's Project GENIE created an observational cohort of patients with cancer for whom tumor molecular profiling data, therapeutic exposures, and treatment outcomes are available and will be shared publicly with the research community. A comprehensive approach to quality assurance included assessments of (1) feasibility of the curation model through pressure test cases; (2) accuracy through programmatic queries and comparison with source data; and (3) reproducibility via double curation and code review., Results: Assessments of feasibility resulted in critical modifications to the curation directives. Queries and comparison with source data identified errors that were rectified via data correction and curator retraining. Assessment of intercurator reliability indicated a reliable curation model., Conclusion: The transparent quality assurance processes for the GENIE BPC data ensure that the data can be used for analyses that support clinical decision making and advances in precision oncology., Competing Interests: Jessica A. LaveryResearch Funding: AACR Project GENIE (Inst) Eva M. LepistoEmployment: Kiniksa Pharmaceuticals (I)Stock and Other Ownership Interests: Kiniksa Pharmaceuticals (I) Samantha BrownResearch Funding: AACR Michele LeNoue-NewtonEmployment: DaVita (I)Stock and Other Ownership Interests: DaVita (I)Research Funding: GE Healthcare (Inst) Shawn SweeneyEmployment: ConcertAI (I)Research Funding: Amgen, AstraZeneca, Bristol Myers Squibb, Genentech, Bayer, Boehringer Ingelheim, Janssen, Merck, Novartis, Analysis Group Ben Ho ParkLeadership: LoxoStock and Other Ownership Interests: Loxo, CelcuityConsulting or Advisory Role: Horizon Discovery, Loxo, Casdin Capital, Jackson Laboratory for Genomic Medicine, Celcuity, Sermonix Pharmaceuticals, Hologic, EQRxResearch Funding: AbbVie, Pfizer, GE Healthcare, LillyPatents, Royalties, Other Intellectual Property: Royalties paid through inventions at Johns Hopkins University by Horizon Discovery LtdTravel, Accommodations, Expenses: Lilly, LoxoUncompensated Relationships: Tempus Jeremy L. WarnerThis author is an Associate Editor for JCO Clinical Cancer Informatics. Journal policy recused the author from having any role in the peer review of this manuscript.Stock and Other Ownership Interests: HemOnc.orgConsulting or Advisory Role: Westat, IBM, Roche, Flatiron HealthTravel, Accommodations, Expenses: IBM Philippe L. BedardConsulting or Advisory Role: BMS (Inst), Pfizer (Inst), Seattle Genetics, Lilly, Amgen, MerckResearch Funding: Bristol Myers Squibb (Inst), Sanofi (Inst), AstraZeneca (Inst), Genentech/Roche (Inst), Servier (Inst), GlaxoSmithKline (Inst), Novartis (Inst), PTC Therapeutics (Inst), Nektar (Inst), Merck (Inst), Seattle Genetics (Inst), Mersana (Inst), Immunomedics (Inst), Lilly (Inst), Amgen (Inst), Bicara Therapeutics (Inst) Gregory RielyResearch Funding: Novartis (Inst), Roche/Genentech (Inst), GlaxoSmithKline (Inst), Pfizer (Inst), Infinity Pharmaceuticals (Inst), Mirati Therapeutics (Inst), Merck (Inst), Takeda (Inst)Patents, Royalties, Other Intellectual Property: Patent application submitted covering pulsatile use of erlotinib to treat or prevent brain metastases (Inst)Travel, Accommodations, Expenses: Merck Sharp & DohmeOther Relationship: Pfizer, Roche/Genentech, Takeda Deborah SchragStock and Other Ownership Interests: Merck (I)Honoraria: PfizerConsulting or Advisory Role: JAMA-Journal of the American Medical AssociationResearch Funding: AACR (Inst), GRAIL (Inst)Patents, Royalties, Other Intellectual Property: PRISSMM model is trademarked and curation tools are available to academic medical centers and government under creative commons licenseOther Relationship: JAMA-Journal of the American Medical Association Katherine S. PanageasStock and Other Ownership Interests: AstraZeneca, Pfizer, Sunesis PharmaceuticalsNo other potential conflicts of interest were reported.

Importance: Contemporary observational cancer research requires associating genomic biomarkers with reproducible end points; overall survival (OS) is a key end point, but interpretation can be challenging when multiple lines of therapy and prolonged survival are common. Progression-free survival (PFS), time to treatment discontinuation (TTD), and time to next treatment (TTNT) are alternative end points, but their utility as surrogates for OS in real-world clinicogenomic data sets has not been well characterized., Objective: To measure correlations between candidate surrogate end points and OS in a multi-institutional clinicogenomic data set., Design, Setting, and Participants: A retrospective cohort study was conducted of patients with non-small cell lung cancer (NSCLC) or colorectal cancer (CRC) whose tumors were genotyped at 4 academic centers from January 1, 2014, to December 31, 2017, and who initiated systemic therapy for advanced disease. Patients were followed up through August 31, 2020 (NSCLC), and October 31, 2020 (CRC). Statistical analyses were conducted on January 5, 2021., Exposures: Candidate surrogate end points included TTD; TTNT; PFS based on imaging reports only; PFS based on medical oncologist ascertainment only; PFS based on either imaging or medical oncologist ascertainment, whichever came first; and PFS defined by a requirement that both imaging and medical oncologist ascertainment have indicated progression., Main Outcomes and Measures: The primary outcome was the correlation between candidate surrogate end points and OS., Results: There were 1161 patients with NSCLC (648 women [55.8%]; mean [SD] age, 63 [11] years) and 1150 with CRC (647 men [56.3%]; mean [SD] age, 54 [12] years) identified for analysis. Progression-free survival based on both imaging and medical oncologist documentation was most correlated with OS (NSCLC: ρ = 0.76; 95% CI, 0.73-0.79; CRC: ρ = 0.73; 95% CI, 0.69-0.75). Time to treatment discontinuation was least associated with OS (NSCLC: ρ = 0.45; 95% CI, 0.40-0.50; CRC: ρ = 0.13; 95% CI, 0.06-0.19). Time to next treatment was modestly associated with OS (NSCLC: ρ = 0.60; 0.55-0.64; CRC: ρ = 0.39; 95% CI, 0.32-0.46)., Conclusions and Relevance: This cohort study suggests that PFS based on both a radiologist and a treating oncologist determining that a progression event has occurred was the surrogate end point most highly correlated with OS for analysis of observational clinicogenomic data.

We investigated whether a novel, real-time fluoroscopybased navigation system optimized component positioning and leg length in fluoroscopically aided direct anterior approach total hip arthroplasty (DAA-THA). We retrospectively reviewed 75 fluoroscopically assisted DAA-THA performed by a single surgeon: 37 procedures used the software intraoperatively to overlay anteversion, inclination, and leg length information over the existing fluoroscopic radiograph with the aim of enhancing component positioning. The control group consisted of 38 procedures from the single surgeon's patient pool who had undergone non-navigated fluoroscopic assisted DAA-THA 1 month prior to the system's trial. Our results demonstrate that the navigation group measurements were significantly closer to the target numbers with less variation. The mean difference from target value were as follows: for anteversion (control: -4.68°, navigated: -01.0°), inclination (control: -1.87°, navigated: 0.8°), and leg length discrepancy (control: -2.59°, navigated: -0.98°). In addition, surgical time was shorter in the navigation group (75.7 vs. 74 minutes; p = 0.001). The real-time feedback and calculations provided by the navigation software provided a reproducible precision for component positioning and leg length measurement during DAA-THA.

This retrospective study aimed to better define the characteristics and outcomes of extranodal stage I diffuse large B-cell lymphoma (DLBCL) in the rituximab era. Patients diagnosed with stage I DLBCL from 2001 to 2015 treated with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) or R-CHOP-like regimens with or without radiation (RT) were included. We identified 1955 patients with newly diagnosed DLBCL, of whom 341 had stage I and were eligible for this analysis. Extranodal presentation was observed in 224 (66%) patients, whereas 117 (34%) had nodal involvement. The most common extranodal sites were as follows: bone, 21%; stomach, 19%; testis, 9%; intestine, 8%; breast, 8%. Overall, 69% extranodal patients and 68% nodal patients received RT. Median follow-up was 5.5 years (interquartile range, 4.3-8.2). Ten-year overall survival (OS) and disease-free survival were 77% (95% confidence interval [CI], 67%-83%) and 77% (95% CI, 68%-85%). In the multivariable analyses, extranodal involvement was associated with worse OS (hazard ratio [HR], 3.44; 95% CI, 1.05-11.30) and progression-free survival (PFS; HR, 3.25; 95% CI, 1.08-9.72) compared with nodal involvement. Consolidation RT was associated with better OS (HR, 0.26; 95% CI, 0.12-0.49) and PFS (HR, 0.35; 95% CI, 0.18-0.69) in the extranodal population; however, the benefit was no longer observed in patients that were positron emission tomography (PET) negative at the end of immunochemotherapy. Relapses occurred usually late (median, 37 months), and the most common sites were the lymph nodes (31%) and the central nervous system (27%). Extranodal stage I DLBCL had a worse outcome than nodal stage 1 DLBCL. End of immunochemotherapy PET results may help select extranodal patients for consolidation RT., (© 2021 by The American Society of Hematology.)

Purpose: To compare retinal toxicity as measured by electroretinogram, ocular, and patient survival in retinoblastoma treated with intravitreal melphalan at two concentrations (25 vs. 30 µg)., Methods: Single-center, retrospective analysis of retinoblastoma eyes receiving 25-µg or 30-µg intravitreal melphalan from September 2012 to January 2019. Ocular toxicity was measured by electroretinogram of evaluable injections in 449 injections in 136 eyes. A repeated-measures linear mixed model with a random intercept and slope was applied to account for repeated measures for each eye., Results: Average decline in electroretinogram after each additional injection was -4.9 µV (95% confidence interval -6.3 to -3.4); electroretinogram declined by -4.6 µV (95% confidence interval -7.0 to -2.2) after 25-µg injections and -5.2 µV (95% confidence interval -6.6 to -3.8) after 30-µg injections (P = 0.66). Injection at a new clock site hour was associated with a -3.91-µV lower average (95% confidence interval -7.8 to -0.04)., Conclusion: Electroretinogram-measured toxicity in retinoblastoma eyes treated with intravitreal injections was not found to be different across 25-µg and 30-µg injections. There were no cases of extraocular extension or metastatic deaths in our patient population.

Background: Survivors of head and neck cancer (HNC) have increased risk of opioid misuse., Methods: Using Surveillance, Epidemiology and End-Results-Medicare data, we matched adults ≥66 years diagnosed with HNC 2008-2015 with cancer-free controls. We computed odds ratios (OR) for receipt of chronic opioid therapy (COT, claims for ≥90 consecutive days) for HNC survivors compared to controls each year after matching through 2016., Results: The cohort of HNC survivors declined from 5107 in the first year after diagnosis to 604 in the sixth year after diagnosis. For 5 years, rates of COT among HNC survivors exceeded that of controls. Differences between survivors and controls declined each year (ORs: year 1, 4.36; year 2, 2.60; year 3, 2.18; year 4, 1.85; and year 5, 1.35; all P-values <.05)., Conclusions: Among older HNC survivors, cancer-associated opioid use in the first years after diagnosis suggests that the benefit of opioids must balance the risk of opioid misuse., (© 2020 Wiley Periodicals LLC.)

Pegaspargase is a modified version of asparaginase with prolonged asparagine depletion. It appears to be safe in adults <40 years old, but has a unique spectrum of toxicities, the risks of which appear to increase with age. The primary objective of this study was to evaluate pegaspargase tolerability and toxicity as assessed by evaluation of incidence and severity of adverse events. Secondary objectives included characterization of the reasons underlying pegaspargase discontinuation, when applicable. Grade 3/4 asparaginase-related toxicities with ≥10% incidence included: hyperbilirubinemia, hyperglycemia, hypertriglyceridemia, hypoalbuminemia, hypofibrinogenemia, and transaminitis. 63% of patients (38 of 60) received all intended doses of pegaspargase, with the most common reasons for discontinuation noted as hypersensitivity (12%), hyperbilirubinemia/transaminitis (8%), and hematopoietic transplantation in complete remission (10%). This study suggests that while hepatotoxicity and other known adverse effects are common, with careful monitoring, pegaspargase can safely be administered to adults with ALL age ≥40 years old.

Purpose To measure financial toxicity and explore its association with quality of life (QOL) in an emerging population of survivors: advanced melanoma patients treated with immunotherapy. Design Cross-sectional survey and medical record review. Sample 106 survivors (39% response). Median time since start of immunotherapy was 36.4 months (range: 14.2-133.9). Methods The Comprehensive Score for Financial Toxicity measured financial toxicity, and the EORTC-QLQ30 assessed QOL and functioning across five domains. Data were collected online, by phone, or in clinic. Findings : Younger patients (<65 years) reported higher financial toxicity ( p  < .001) than older patients. Controlling for age, financial toxicity was correlated with QOL ( p  < .001), financial difficulties ( p  < .001), and EORTC-QLQ30 functioning subscales. Conclusions Given the demonstrated association between financial toxicity and QOL, our study highlights the importance of addressing financial toxicity, particularly among patients receiving high-cost treatments. Implications for Psychosocial Providers : Providers should educate patients and their caregivers about cost-management techniques, link them with available resources, and provide psychosocial counseling to alleviate related distress.

BACKGROUNDUnderstanding outcomes and immunologic characteristics of cellular therapy recipients with SARS-CoV-2 is critical to performing these potentially life-saving therapies in the COVID-19 era. In this study of recipients of allogeneic (Allo) and autologous (Auto) hematopoietic cell transplant and CD19-directed chimeric antigen receptor T cell (CAR T) therapy at Memorial Sloan Kettering Cancer Center, we aimed to identify clinical variables associated with COVID-19 severity and assess lymphocyte populations.METHODSWe retrospectively investigated patients diagnosed between March 15, 2020, and May 7, 2020. In a subset of patients, lymphocyte immunophenotyping, quantitative real-time PCR from nasopharyngeal swabs, and SARS-CoV-2 antibody status were available.RESULTSWe identified 77 patients with SARS-CoV-2 who were recipients of cellular therapy (Allo, 35; Auto, 37; CAR T, 5; median time from cellular therapy, 782 days; IQR, 354-1611 days). Overall survival at 30 days was 78%. Clinical variables significantly associated with the composite endpoint of nonrebreather or higher oxygen requirement and death (n events = 25 of 77) included number of comorbidities (HR 5.41, P = 0.004), infiltrates (HR 3.08, P = 0.032), and neutropenia (HR 1.15, P = 0.04). Worsening graft-versus-host disease was not identified among Allo recipients. Immune profiling revealed reductions and rapid recovery in lymphocyte populations across lymphocyte subsets. Antibody responses were seen in a subset of patients.CONCLUSIONIn this series of Allo, Auto, and CAR T recipients, we report overall favorable clinical outcomes for patients with COVID-19 without active malignancy and provide preliminary insights into the lymphocyte populations that are key for the antiviral response and immune reconstitution.FUNDINGNIH grant P01 CA23766 and NIH/National Cancer Institute grant P30 CA008748.

Purpose: SMARCA4 mutations are among the most common recurrent alterations in non-small cell lung cancer (NSCLC), but the relationship to other genomic abnormalities and clinical impact has not been established., Experimental Design: To characterize SMARCA4 alterations in NSCLC, we analyzed the genomic, protein expression, and clinical outcome data of patients with SMARCA4 alterations treated at Memorial Sloan Kettering., Results: In 4,813 tumors from patients with NSCLC, we identified 8% ( n = 407) of patients with SMARCA4 -mutant lung cancer. We describe two categories of SMARCA4 mutations: class 1 mutations (truncating mutations, fusions, and homozygous deletion) and class 2 mutations (missense mutations). Protein expression loss was associated with class 1 mutation (81% vs. 0%, P < 0.001). Both classes of mutation co-occurred more frequently with KRAS, STK11 , and KEAP1 mutations compared with SMARCA4 wild-type tumors ( P < 0.001). In patients with metastatic NSCLC, SMARCA4 alterations were associated with shorter overall survival, with class 1 alterations associated with shortest survival times ( P < 0.001). Conversely, we found that treatment with immune checkpoint inhibitors (ICI) was associated with improved outcomes in patients with SMARCA4 -mutant tumors ( P = 0.01), with class 1 mutations having the best response to ICIs ( P = 0.027)., Conclusions: SMARCA4 alterations can be divided into two clinically relevant genomic classes associated with differential protein expression as well as distinct prognostic and treatment implications. Both classes co-occur with KEAP1, STK11 , and KRAS mutations, but individually represent independent predictors of poor prognosis. Despite association with poor outcomes, SMARCA4 -mutant lung cancers may be more sensitive to immunotherapy., (©2020 American Association for Cancer Research.)

Purpose: We sought to evaluate whether provider volume or other factors are associated with chemotherapy guideline compliance in elderly patients with epithelial ovarian cancer (EOC)., Methods: We queried the SEER-Medicare database for patients ≥66 years, diagnosed with FIGO stage II-IV EOC from 2004 to 2013 who underwent surgery and received chemotherapy within 7 months of diagnosis. We compared NCCN guideline compliance (6 cycles of platinum-based doublet) and chemotherapy-related toxicities across provider volume tertiles. Factors associated with guideline compliance and chemotherapy-related toxicities were assessed using logistic regression. Overall survival (OS) was compared across volume tertiles and Cox proportional-hazards model was created to adjust for case-mix., Results: 1924 patients met inclusion criteria. The overall rate of guideline compliance was 70.3% with a significant association between provider volume and compliance (64.5% for low-volume, 72.2% for medium-volume, 71.7% for high-volume, p = .02). In the multivariate model, treatment by low-volume providers and patient age ≥ 80 years were independently associated with worse chemotherapy-guideline compliance. In the survival analysis, there was a significant difference in median OS across provider volume tertiles with median survival of 32.8 months (95%CI 29.6, 36.4) low-volume, 41.9 months (95%CI 37.5, 46.7) medium-volume, 42.1 months (95%CI 38.8, 44.2) high-volume providers, respectively (p < .01). After adjusting for case-mix, low-volume providers were independently associated with higher rates of mortality (aHR 1.25, 95%CI: 1.08, 1.43)., Conclusions: In a modern cohort of elderly Medicare patients with advanced EOC, we found higher rates of non-compliant care and worse survival associated with treatment by low-volume Medicare providers. Urgent efforts are needed to address this volume-outcomes disparity., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The value of testing for folate deficiency has been scrutinized recently given low prevalence of deficiency with widespread dietary fortification. Numerous studies have shown folate testing to be low yield overall. However, the value of such testing in the inpatient cancer population has not been defined., Methods: We queried all folate tests performed during 2017 at our center on admitted cancer patients. We used diagnosis codes and manual chart review to assess risk factors for folate deficiency. Descriptive statistics were used to summarize characteristics of patients undergoing folate testing, the frequency of vitamin B12 co-testing, and repeat folate testing. Fisher's exact test was used to compare the proportion of deficient vs. not deficient tests based on the presence of risk factors. A Cox proportional hazards model was fit to examine the association between folate deficiency and survival., Results: In total, 937 patients had 1065 tests performed during 2017. Among all tests, 7.0% indicated folate deficiency. In patients who underwent two folate tests in a single hospitalization, 89% were deficient neither instance. Risk factors for folate deficiency were equally common in instances with deficient compared with replete testing (25.3 vs. 20.4%, P = 0.334). Folate deficiency was associated with higher risk for death (HR 1.49, 95% CI 1.10-2.03, P = 0.01)., Conclusion: Folate deficiency was present in 7% of hospitalized cancer patients and associated with shorter overall survival. Repeat testing in the same patient over time was low yield. Traditional risk factors for folate deficiency do not appear to apply in this patient population.

Purpose: As data-sharing projects become increasingly frequent, so does the need to map data elements between multiple classification systems. A generic, robust, shareable architecture will result in increased efficiency and transparency of the mapping process, while upholding the integrity of the data., Materials and Methods: The American Association for Cancer Research's Genomics Evidence Neoplasia Information Exchange (GENIE) collects clinical and genomic data for precision cancer medicine. As part of its commitment to open science, GENIE has partnered with the National Cancer Institute's Genomic Data Commons (GDC) as a secondary repository. After initial efforts to submit data from GENIE to GDC failed, we realized the need for a solution to allow for the iterative mapping of data elements between dynamic classification systems. We developed the Linked Entity Attribute Pair (LEAP) database framework to store and manage the term mappings used to submit data from GENIE to GDC., Results: After creating and populating the LEAP framework, we identified 195 mappings from GENIE to GDC requiring remediation and observed a 28% reduction in effort to resolve these issues, as well as a reduction in inadvertent errors. These results led to a decrease in the time to map between OncoTree, the cancer type ontology used by GENIE, and International Classification of Disease for Oncology, 3rd Edition, used by GDC, from several months to less than 1 week., Conclusion: The LEAP framework provides a streamlined mapping process among various classification systems and allows for reusability so that efforts to create or adjust mappings are straightforward. The ability of the framework to track changes over time streamlines the process to map data elements across various dynamic classification systems.

High-grade B-cell lymphoma (HGBL) with translocations involving MYC and BCL2 or BCL6 comprises ∼10% of cases of diffuse large B-cell lymphoma (DLBCL) and carries a poor prognosis. The incidence, prognosis, and optimal therapy for DLBCL harboring extra copies of the genes MYC, BCL2, and BCL6, rather than their genetic translocations, are unknown. In this retrospective, single-center study we identified 144 DLBCL cases including 46 patients with classic HGBL with double-hit or triple-hit chromosomal translocations (DHL), 55 with extra copies of MYC in addition to aberrations (extra copies or translocations) of BCL2 and/or BCL6 but did not meet the criteria for HGBL (EC group), and 43 without any aberrations of MYC, BCL2, or BCL6 (wild type [WT]). Unfavorable baseline characteristics had similar frequency in the EC and WT groups, but were significantly more prevalent in the DHL group. With a median follow-up of 36 months, the 2-year event-free survival (EFS) was similar between the WT and EC groups at 77% (95% confidence interval [CI], 65-90) and 82% (95% CI, 72-93), respectively. In contrast, the 2-year EFS of the DHL group was 63% (95% CI, 51-79). The 2-year overall survival in the WT, EC, and DHL groups was 86% (95% CI, 76-97), 89% (95% CI, 81-98), and 74% (95% CI, 62-88), respectively. Among patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the EC group had outcomes similar to those of the WT group. Our results indicate that patients with DLBCL with extra gene copies of MYC, BCL2, and BCL6 fare differently from those with HGBL and respond well to standard R-CHOP therapy., (© 2020 by The American Society of Hematology.)

Objective: Intravitreal melphalan injections are commonly used in the treatment for intraocular retinoblastoma. This study compares retinal toxicity and ocular survival between two formulations, with and without propylene glycol (Alkeran vs. Evomela, respectively)., Methods: A retrospective cohort study of retinoblastoma patients who received intravitreal injections of Alkeran and Evomela at 30 μg from September 2012 to January 2019 at a single tertiary care center were enrolled. Retinal toxicity was measured using electroretinogram (ERG) and compared using a multivariate analysis of 338 injections in 101 eyes of 96 patients. Ocular survival of 163 eyes in 150 patients was compared across formulations using Cox proportional hazards model. Eyes were censored at the time a patient received a dose other than 30 μg., Results: Overall, ERG decline (mean, 95% CI) for each injection was -5.58 μV (-7.17, -3.99). No significant differences in ERG decrement were found between Alkeran (with alcohol) -5.52uV (-6.99, -4.05). and Evomela (without alcohol) -5.65uV (-8.31 to -2.98) formulations (p = 0.93). Ocular survival at 24 months was 93.6% (95% CI 86.2, 97.1) with alcohol and 91.7% (95% CI 53.9, 98.8) without alcohol. The hazard ratio (HR) for without vs with alcohol was 0.50 (95% CI 0.06 to 4.07); no significant difference in ocular survival was found between formulations (p = 0.52)., Conclusions and Relevance: No differences were found in retinal toxicity and ocular survival between 30 μg intravitreal injections of Alkeran or Evomela for intraocular retinoblastoma. Given the increased stability of Evomela, intravitreal treatment could be expanded to centers without the ability to supply Alkeran due to its shorter safety window; however, Alkeran is less expensive. For those with existing infrastructure, Alkeran is a comparable, cost-effective alternative., Competing Interests: The authors have declared that no competing interests exist.

Background: While public reporting of surgical outcomes for noncancer conditions is common, cancer surgeries have generally been excluded. This is true despite numerous studies showing outcomes to differ between hospitals based on their characteristics. Our objective was to assess whether three prerequisites for quality assessment and reporting are present for 30-day mortality after cancer surgery: low burden for timely reporting, hospital variation, and potential for public health gains., Study Design: We used Fee-for-Service (FFS) Medicare claims to examine the extent of variation in 30-day cancer surgical mortality between 3860 US hospitals. We included 340 489 surgeries for 12 cancer types for FFS Medicare beneficiaries aged ≥66 years, 2011-2013. Hierarchical mixed-effects logistic regression models adjusted for patient and hospital characteristics and with a random hospital effect were fit to obtain hospital-specific risk-standardized mortality rates (RSMRs) and 99% confidence intervals (CI). We calculated a hospital odds ratio to describe the difference in mortality risk for a hospital above vs below average quality and estimated the potential mortality reduction., Results: The median number of cancer surgeries per hospital was 34. The median RSMR overall was 2.41% (99% CI 2.28%, 2.66%). In aggregate and for most cancers, variation between hospitals exceeded that due to differences in patient and hospital characteristics. For individual cancers, relative differences exceeded 20% in mortality risk between patients undergoing surgery at a hospital below vs above average quality, with the potential for an estimated 500 deaths prevented annually given hypothetical improvements., Conclusion: Quality measurement and reporting of 30-day mortality for cancer surgery is worthy of consideration., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Immune checkpoint inhibitors (CIs) have revolutionized treatment of advanced melanoma, leading to an emerging population of long-term survivors. Survivors' quality of life (QOL) and symptom burden are poorly understood. We set out to evaluate symptom burden and QOL in patients with advanced melanoma alive more than 1 year after initiating CI therapy., Methods: Cross-sectional surveys, accompanied by chart review of patients with advanced melanoma treated with CIs at Memorial Sloan Kettering Cancer Center, completed therapy, and were alive >1 year after treatment initiation. Surveys were administered between February and August 2018. Surveys included: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, EuroQOL, items from Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events and Fatigue Severity Scale., Results: We included 90 patients. The most common CI regimens were ipilimumab plus nivolumab (53%) and pembrolizumab (41%); most patients (71%) were not treated in clinical trials. Median time from CI therapy initiation was 40 months and from last dose was 28 months. Fatigue was reported by 28%, with higher fatigue scores in women than men; 12% reported difficulty sleeping. Aching joints (17%) and muscles (12%) were fairly common. Level of functioning was generally high. Overall QOL was excellent though 40% reported 'some or moderate' problems with anxiety/depression and 31% with pain/discomfort., Conclusions: After CI therapy, long-surviving advanced melanoma patients commonly report fatigue but otherwise have moderate symptom burden and good QOL. Ensuring appropriate symptom management will optimize clinical outcomes for these patients., Competing Interests: Competing interests: SSB is an employee of Flatiron Health which is a subsidiary of Roche. JW is a consultant for: Adaptive Biotech; Advaxis; Amgen; Apricity; Array BioPharma; Ascentage Pharma; Astellas; Bayer; Beigene; Bristol Myers Squibb; Celgene; Chugai; Elucida; Eli Lilly; F Star; Genentech; Imvaq; Janssen; Kleo Pharma; Kyowa Hakko Kirin; Linneaus; MedImmune; Merck; Neon Therapuetics; Northern Biologics; Ono; Polaris Pharma; Polynoma; Psioxus; Puretech; Recepta; Takara Bio; Trieza; Sellas Life Sciences; Serametrix; Surface Oncology; Syndax; Syntalogic. Research support: Bristol Myers Squibb; Medimmune; Merck Pharmaceuticals; Genentech. Equity in: Potenza Therapeutics; Tizona Pharmaceuticals; Adaptive Biotechnologies; Elucida; Imvaq; Beigene; Trieza; Linneaus; Honoraium: EsanexMP is a consultant for: BMS; Merck; Array BioPharma; Novartis; Aduro; Incyte; NewLink Genetics. Institutional support for: BMS; Merck; RGenix; Infinity; AstraZeneca; Novartis; Array BioPharma. Honoraria: BMS and Merck. DK’s spouse serves on the scientific advisory board of Vedanta Biosciences and is a consultant for Takeda. JAL discloses salary support for Project Genomics Evidence Neoplasia Information Exchange (GENIE) through the American Association for Cancer Research., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rational, Aims, and Objectives: While public reports of hospital-level surgical quality measures are becoming increasingly common in health care, a comprehensive national assessment of surgical quality across multiple cancer sites has yet to be developed. Fee-for-service (FFS) Medicare claims present a potential resource from which to measure outcomes following cancer surgery given the national scope of patients and providers. However, due to the administrative nature of the data, clinical cancer information such as stage is not recorded. Leveraging the Surveillance, Epidemiology, and End Results (SEER) registry linked to FFS Medicare claims to analyse outcomes for patients whom we ultimately know stage information, we determined whether Medicare claims are suitable for measuring provider quality following cancer surgery by assessing the extent to which the lack of stage information modifies assessments of provider performance., Methods: We identified patients aged 66 and older undergoing cancer surgery between 2011 and 2013 from SEER-Medicare. We compared the changes in the risk-standardized rates (RSRs), decile rankings, and c-statistics with and without risk adjustment for cancer stage for three measures of hospital performance: 30-day mortality, surgical complications, and unplanned readmissions., Results: The RSR changed by at most 11.4% for mortality and by less than 4% for complications and readmissions, indicating that measures of hospital performance were stable with and without adjustment for stage. The relative performance of hospitals was also stable, as demonstrated by fewer than 20% of hospitals changing decile rank. The c-statistic declined by less than 2% across all measures, indicating that model fit was not substantially worsened without this information., Conclusion: These findings support the use of FFS Medicare claims for hospital-level analyses of short-term outcomes following cancer surgery. Quality reporting based on these analyses can be used to help patients choose among hospitals and for evaluating policies to improve surgical cancer care., (© 2019 John Wiley & Sons, Ltd.)

Quality of immune reconstitution after cord blood transplantation (CBT) without antithymocyte globulin (ATG) in adults is not established. We analyzed immune recovery in 106 engrafted adult CBT recipients (median age 50 years [range 22-70]) transplanted for hematologic malignancies with cyclosporine/mycophenolate mofetil immunoprophylaxis and no ATG. Patients were treated predominantly for acute leukemia (66%), and almost all (96%) underwent myeloablation. Recovery of CD4+ T cells was faster than CD8+ T cells with median CD4+ T-cell counts exceeding 200/mm3 at 4 months. Early post-CBT, effector memory (EM), and central memory cells were the most common CD4+ subsets, whereas effector and EM were the most common CD8+ T-cell subsets. Naive T-cell subsets increased gradually after 6 to 9 months post-CBT. A higher engrafting CB unit infused viable CD3+ cell dose was associated with improved CD4+ and CD4+CD45RA+ T-cell recovery. Cytomegalovirus reactivation by day 60 was associated with an expansion of total, EM, and effector CD8+ T cells, but lower CD4+ T-cell counts. Acute graft-versus-host disease (aGVHD) did not significantly compromise T-cell reconstitution. In serial landmark analyses, higher CD4+ T-cell counts and phytohemagglutinin responses were associated with reduced overall mortality. In contrast, CD8+ T-cell counts were not significant. Recovery of natural killer and B cells was prompt, reaching medians of 252/mm3 and 150/mm3 by 4 months, respectively, although B-cell recovery was delayed by aGVHD. Neither subset was significantly associated with mortality. ATG-free adult CBT is associated with robust thymus-independent CD4+ T-cell recovery, and CD4+ recovery reduced mortality risk., (© 2020 by The American Society of Hematology.)

Objective: To determine the effects of the Safe Motherhood Initiative's (SMI) obstetric hemorrhage bundle in New York State (NYS)., Study Design: In 2013, the SMI convened interprofessional workgroups on hemorrhage, venous thromboembolism, and hypertension tasked with developing evidence-based care bundles. Participating hospitals submitted data measured before, during, and after implementation of the hemorrhage bundle: maternal mortality, intensive care unit (ICU) admission, cardiovascular collapse, hysterectomy, and transfusion of ≥4 units of red blood cells (RBCs). Data were analyzed for trends stratified by implementation status., Results: Of the 123 maternity hospitals in NYS, 117 participated, of which 113 submitted data. Of 250,719 births, transfusion of ≥4 units RBCs (1.8 per 1,000) and ICU admissions (1.1 per 1,000) were the most common morbidities. Four hemorrhage-related maternal deaths (1.6 per 100,000) and 10 cases of cardiovascular collapse requiring cardiopulmonary resuscitation (4.0 per 100,000) occurred. Hemorrhage morbidity did not change over the five quarters studied. Risks were similar across hospital level of care and implementation status., Conclusion: Statewide implementation of bundles is feasible with resources critical to success. The low hemorrhage-related maternal death rate makes changes in mortality risk difficult to detect over short time intervals. Long-term and timely data collection with individual expert case review will be required., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Purpose: Pediatric fingertip injuries are most commonly reported in the setting of an accidental occurrence. The purpose of this study was to determine whether there is an association of child abuse and neglect with pediatric fingertip injuries., Methods: The New York Statewide Planning and Research Cooperative System (2004 to 2013) administrative database was used to identify children aged 0 to 12 years who presented in the inpatient or outpatient (emergency department or ambulatory surgery) setting. International Classification of Diseases, Ninth Revision diagnosis codes were used to identify fingertip injuries (amputation, avulsion, or crushed finger) and abuse. Cohort demographics of children presenting with fingertip injuries were described. We analyzed the association between fingertip injuries and child abuse using multivariable logistic regression, with variables for insurance status, race, ethnicity, sex, and behavioral risks including depression, attention-deficit hyperactivity disorder, aggressive behavior, and autism., Results: Of the 4,870,299 children aged 0 to 12 years in the cohort, 79,108 patients (1.62%) during the study period (2004 to 2013) presented with fingertip injuries. Of those with a fingertip injury, 0.27% (n = 216) presented either at that visit or in other visits with a code for child abuse, compared with 0.22% of pediatric patients without a fingertip injury (n = 10,483). In an adjusted analysis, the odds of a fingertip injury were 23% higher (odds ratio [OR] = 1.23; 95% confidence interval [CI], 1.07-1.41) for children who had been abused, compared with those who had not. Patients were more likely to present with fingertip injuries if they had ever had Medicaid insurance (OR = 1.40; 95% CI, 1.37-1.42) or had a behavioral risk factor (OR = 1.35; 95% CI, 1.30-1.40)., Conclusions: Patients presenting with abuse are significantly more likely to have fingertip injuries during childhood compared with those without recorded abuse, which suggests that these injuries may be ones of abuse or neglect. Medicaid insurance, white race, and behavioral diagnoses of depression, attention-deficit hyperactivity disorder, aggressive behavior, and autism were also associated with increased odds of presenting with fingertip injuries., Type of Study/level of Evidence: Prognostic III., (© 2019 THE AUTHORS. Published by Elsevier Inc. on behalf of The American Society for Surgery of the Hand.)

Rectal cancer (RC) is a challenging disease to treat that requires chemotherapy, radiation and surgery to optimize outcomes for individual patients. No accurate model of RC exists to answer fundamental research questions relevant to patients. We established a biorepository of 65 patient-derived RC organoid cultures (tumoroids) from patients with primary, metastatic or recurrent disease. RC tumoroids retained molecular features of the tumors from which they were derived, and their ex vivo responses to clinically relevant chemotherapy and radiation treatment correlated with the clinical responses noted in individual patients' tumors. Upon engraftment into murine rectal mucosa, human RC tumoroids gave rise to invasive RC followed by metastasis to lung and liver. Importantly, engrafted tumors displayed the heterogenous sensitivity to chemotherapy observed clinically. Thus, the biology and drug sensitivity of RC clinical isolates can be efficiently interrogated using an organoid-based, ex vivo platform coupled with in vivo endoluminal propagation in animals.