Faculty Bibliography

PURPOSE/UNASSIGNED:Community-academic partnerships have the potential to improve access to clinical trials for under-represented minority patients who more often receive cancer treatment in community settings. In 2017, the Memorial Sloan Kettering (MSK) Cancer Center began opening investigator-initiated clinical trials in radiation oncology in targeted community-based partner sites with a high potential to improve diverse population accrual. This study evaluates the effectiveness of a set of implementation strategies for increasing overall community-based enrollment and the resulting proportional enrollment of Hispanic patients on trials on the basis of availability in community-based partner sites. METHODS/UNASSIGNED:An interrupted time series analysis evaluating implementation strategies was conducted from April 2018 to September 2021. Descriptive analysis ofHispanic enrollment on investigator-initiated randomized therapeutic radiation trials open at community-based sites was compared with those open only at themain academic center. RESULTS/UNASSIGNED:Overall, 84 patients were enrolled in clinical trials in the MSK Alliance, of which 48 (56%) identified as Hispanic. The quarterly patient enrollment pre- vs postimplementation increased from 1.39 (95% CI, -3.67 to 6.46) to 9.42 (95% CI, 2.05 to 16.78; P5 .017). In the investigator-initiated randomized therapeutic radiation trials open in the MSK Alliance, Hispanic representation was 11.5% and 35.9% in twometastatic trials and 14.2% in a proton versus photon trial. Inmatched trials open only at the main academic center, Hispanic representation was 5.6%, 6.0%, and 4.0%, respectively. CONCLUSION/UNASSIGNED:A combination of practice-level and physician-level strategies implemented at community-based partner sites was associated with increased clinical trial enrollment, which translated to improved Hispanic representation. This supports the role Q:2 of strategic community-academic partnerships in addressing disparities in clinical trial enrollment.

For patients with oligometastatic cancer, radiotherapy presents a promising avenue for achieving meaningful symptom relief and durable disease control. Data from recently published and ongoing randomized studies are helping to define the appropriate contexts for effective intervention with stereotactic ablative body radiotherapy (SABR) in the oligometastatic setting. Importantly, older adults represent a significant portion of patients with oligometastatic disease, yet often comprise a minority of patients in clinical trials. Moreover, older adults of the same chronologic age may have variable degrees of fitness and frailty. In this review, we highlight the specific challenges and considerations for the use of radiotherapy for older adults with oligometastatic disease-noting the importance of geriatric assessments in clinical decision-making about the appropriateness of SABR and other metastasis-directed therapies in this population. We then review data from existing trials, including a subset analysis of adverse events and survival estimates among older adults enrolled in the landmark SABR-COMET trial. Finally, we discuss future directions for research, including the need for focused clinical trials in older adult cohorts. Ultimately, a multidisciplinary approach is critical when carefully balancing the potential risks and benefits of this emerging treatment paradigm in the older adult population.

Background Artificial intelligence (AI) applications for cancer imaging conceptually begin with automated tumor detection, which can provide the foundation for downstream AI tasks. However, supervised training requires many image annotations, and performing dedicated post hoc image labeling is burdensome and costly. Purpose To investigate whether clinically generated image annotations can be data mined from the picture archiving and communication system (PACS), automatically curated, and used for semisupervised training of a brain MRI tumor detection model. Materials and Methods In this retrospective study, the cancer center PACS was mined for brain MRI scans acquired between January 2012 and December 2017 and included all annotated axial T1 postcontrast images. Line annotations were converted to boxes, excluding boxes shorter than 1 cm or longer than 7 cm. The resulting boxes were used for supervised training of object detection models using RetinaNet and Mask region-based convolutional neural network (R-CNN) architectures. The best-performing model trained from the mined data set was used to detect unannotated tumors on training images themselves (self-labeling), automatically correcting many of the missing labels. After self-labeling, new models were trained using this expanded data set. Models were scored for precision, recall, and F₁ using a held-out test data set comprising 754 manually labeled images from 100 patients (403 intra-axial and 56 extra-axial enhancing tumors). Model F₁ scores were compared using bootstrap resampling. Results The PACS query extracted 31 150 line annotations, yielding 11 880 boxes that met inclusion criteria. This mined data set was used to train models, yielding F₁ scores of 0.886 for RetinaNet and 0.908 for Mask R-CNN. Self-labeling added 18 562 training boxes, improving model F₁ scores to 0.935 (P < .001) and 0.954 (P < .001), respectively. Conclusion The application of semisupervised learning to mined image annotations significantly improved tumor detection performance, achieving an excellent F₁ score of 0.954. This development pipeline can be extended for other imaging modalities, repurposing unused data silos to potentially enable automated tumor detection across radiologic modalities. © RSNA, 2022 Online supplemental material is available for this article.

PURPOSE OF REVIEW:Radiation therapy (RT) is a mainstay of treatment for brain metastases from solid tumors. Treatment of these patients is complex and should focus on minimizing symptoms, preserving functional status, and prolonging survival. RECENT FINDINGS:Whole-brain radiotherapy (WBRT) can lead to toxicity, and while it does reduce recurrence in the CNS, this has not been shown to provide a survival benefit. Recent advances focus on reducing the toxicity of WBRT or using more targeted radiation therapy. New paradigms including the use of proton RT for leptomeningeal metastases (LM) and stereotactic radiosurgery (SRS) before craniotomy hold promise in improving treatment efficacy and reducing toxicity. Omission or replacement of WBRT is often safe and the use of SRS is expanding to include patients with more lesions and preoperative RT. Proton RT holds promise for LM. Progress is being made in improving patient-centered outcomes and reducing toxicity for patients with brain metastases.

PURPOSE:Local therapy for patients with nonspine bone metastases is evolving, with data supporting the use of single-fraction treatments, and more recently, showing possible benefit from stereotactic body radiation therapy (SBRT). However, the rate of local salvage therapy (LST) after each technique has not been characterized in real-world clinic settings where patients are selected at physician discretion. We examined rates of LST in patients with nonspine bone metastases. METHODS AND MATERIALS:We reviewed records of RT for nonspine bone metastases at our institution from January 1, 2016, to December 31, 2018. We defined LST as the first occurrence of RT or surgery for oncologic progression to a bone metastasis after initial RT. Cumulative incidence functions for retreatment were generated. We conducted multivariate analysis to identify variables associated with LST. RESULTS:A total of 1754 patients were analyzed, with median follow-up of 16.2 months (range, 0-36.8 months). Of all episodes of RT, 51.5% were multifraction external beam radiation therapy (EBRT), 7.0% were single-fraction EBRT, and 41.4% were SBRT. Altogether, 88 patients (5.0%) required LST, with an incidence at 6 months of 2.5%. Incidence of LST at 6 months was 2.1% for SBRT, 5.3% for single-fraction conventional regimens, and 2.4% for multifraction conventional regimens (P = .26). Patients of younger age, who had a higher Karnofsky performance status, and/or who had lesions in the pelvis had a higher risk of retreatment. CONCLUSIONS:In this large institutional cohort, the rate of LST was low, with no difference between RT techniques. The findings indicated that SBRT for patients at high risk for treatment failure may reduce the rate of retreatment overall. When treatment modality was selected based on patient characteristics, rates of LST were lower than when treatment was randomly selected.

Although cancer is highly heterogeneous, all metastatic cancer is considered American Joint Committee on Cancer (AJCC) Stage IV disease. The purpose of this project was to redefine staging of metastatic cancer. Internal validation of nationally representative patient data from the National Cancer Database (n = 461 357; 2010-2013), and external validation using the Surveillance, Epidemiology and End Results database (n = 106 595; 2014-2015) were assessed using the concordance index for evaluation of survival prediction. A Cox proportional hazards model was used for overall survival by considering identified phenotypes (latent classes) and other confounding variables. Latent class analysis was performed for phenotype identification, where Bayesian information criterion (BIC) and sample-size-adjusted BIC were used to select the optimal number of distinct clusters. Kappa coefficients assessed external cluster validation. Latent class analysis identified five metastatic phenotypes with differences in overall survival (P < .0001): (Stage IVA) nearly exclusive bone-only metastases (n = 59 049, 12.8%; median survival 12.7 months; common in lung, breast and prostate cancers); (IVB) predominant lung metastases (n = 62 491, 13.5%; 11.4 months; common in breast, stomach, kidney, ovary, uterus, thyroid, cervix and soft tissue cancers); (IVC) predominant liver/lung metastases (n = 130 014, 28.2%; 7.0 months; common in colorectum, pancreatic, lung, esophagus and stomach cancers); (IVD) bone/liver/lung metastases predominant over brain (n = 61 004, 13.2%; 5.9 months; common in lung and breast cancers); and (IVE) brain/lung metastases predominant over bone/liver (n = 148 799, 32.3%; 5.7 months; lung cancer and melanoma). Long-term survivors were identified, particularly in Stages IVA-B. A pan-cancer nomogram model to predict survival (STARS: site, tumor, age, race, sex) was created, validated and provides 13% better prognostication than AJCC: 1-month concordance index of 0.67 (95% confidence interval [CI]: 0.66-0.67) vs 0.61 (95% CI: 0.60-0.61). STARS is simple, uses easily accessible variables, better prognosticates survival outcomes and provides a platform to develop novel metastasis-directed clinical trials.

Each year, approximately 18 million new cancer cases are diagnosed worldwide, and about half must be treated with radiotherapy. A successful treatment requires treatment planning with the customization of penetrating radiation beams to sterilize cancerous cells without harming nearby normal organs and tissues. This process currently involves extensive manual tuning of parameters by an expert planner, making it a time-consuming and labor-intensive process, with quality and immediacy of critical care dependent on the planner's expertise. To improve the speed, quality, and availability of this highly specialized care, Memorial Sloan Kettering Cancer Center developed and applied advanced optimization tools to this problem (e.g., using hierarchical constrained optimization, convex approximations, and Lagrangian methods). This resulted in both a greatly improved radiotherapy treatment planning process and the generation of reliable and consistent high-quality plans that reflect clinical priorities. These improved techniques have been the foundation of high-quality treatments and have positively impacted over 4,000 patients to date, including numerous patients in severe pain and in urgent need of treatment who might have otherwise required longer hospital stays or undergone unnecessary surgery to control the progression of their disease. We expect that the wide distribution of the system we developed will ultimately impact patient care more broadly, including in resource-constrained countries.

ABSTRACTPURPOSE/UNASSIGNED:Systemic, immune, and target therapies are growing in use in the management of metastatic cancers. The aim of this review was to describe up-to-date published data on the safety and tolerability of metastasis-directed hypofractionated radiation therapy (RT) when combined with newer systemic, immune, and targeted therapies and to provide suggested strategies to mitigate potential toxicities in the clinical setting. METHODS AND MATERIALS/UNASSIGNED:A comprehensive search was performed for the time period between 1946 and August 2021 using predetermined keywords describing the use of noncentral nervous system palliative RT with commonly used targeted systemic therapies on PubMed and Medline databases. A total of 1022 articles were screened, and 130 met prespecified criteria to be included in this review. RESULTS/UNASSIGNED:BRAF and MEK inhibitors are reported to be toxic when given concurrently with RT; suspension 3 days and 1 to 2 days, respectively, prior and post-RT is suggested. Cetuximab, erlotinib/gefitinib, and osimertinib were generally safe to use concomitantly with conventional radiation. But in a palliative/hypofractionated RT setting, suspending cetuximab during radiation week, erlotinib/gefitinib 1 to 2 days, and osimertinib ≥2 days pre- and post-RT is suggested. Vascular endothelial growth factor inhibitors such as bevacizumab reported substantial toxicities, and the suggestion is to suspend 4 weeks before and after radiation. Less data exist on sorafenib and sunitinib; 5 to 10 days suspension before and after RT should be considered. As a precaution, until further data are available, for cyclin-dependent kinase 4-6 inhibitors, consideration of suspending treatment 1 to 2 days before and after RT should be given. Ipilimumab should be suspended 2 days before and after RT, and insufficient data exist for other immunotherapy agents. Trastuzumab and pertuzumab are generally safe to use in combination with RT, but insufficient data exist for other HER2 target therapy. CONCLUSIONS/UNASSIGNED:Suggested approaches are described, using up-to-date literature, to aid clinicians in navigating the integration of newer targeted agents with hypofractionated palliative and/or ablative metastatic RT. Further prospective studies are required.

PURPOSE/UNASSIGNED:The objective of this study was to determine the toxicities and outcomes of patients with spinal metastasis treated with external beam radiation therapy (EBRT) to 25 Gy in 5 fractions. METHODS AND MATERIALS/UNASSIGNED:Data were extracted from an institutional tumor registry for patients with spinal metastasis who were treated with EBRT to 25 Gy in 5 fractions to their spinal lesion(s). Cox regression and Kaplan-Meier analyses to determine local control and overall survival (OS) were employed. RESULTS/UNASSIGNED: = .014) were significant predictors for better OS. CONCLUSIONS/UNASSIGNED:Our single-institutional retrospective analysis of patients with spinal metastasis suggested that palliative EBRT to 25 Gy in 5 fractions is safe, with a low toxicity profile and minimal risk for myelopathy with an achievable dose maximum to the spinal cord and cauda equina ≤27 Gy (equivalent total dose in 2-Gy fractions ≤50 Gy), and it may provide durable palliation and local control in cases where stereotactic body radiation therapy may not be indicated.

Palliative care and radiation therapy have played an expanding role in the management of patients with advanced cancers. Recent advances in our understanding of oligometastatic disease have led to increasing demand for familiarity with ablative techniques. Recognizing the demands of hospitalized patients for rapid access to care, we created an inpatient radiation oncology consult service (IROC) with consolidated expertise in palliative radiation and ablative techniques. In this quality improvement cohort study, we analyzed inpatient radiation oncology consults placed before and after IROC implementation and found that IROC led to increased delivery of specialty care and decreased hospital length of stay (median 8 days v 7 days, P = .005). This difference was most pronounced for patients for whom radiation therapy was indicated (14.5 v 11 days, P = .007). Our institutional experience demonstrates the value of recognizing metastatic disease as a distinct discipline and providing rapid access to palliative treatments for patients with advanced malignancies.