Faculty Bibliography

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.

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.

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.

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.

CONTEXT/BACKGROUND:Aggressive pituitary tumors that have progressed following temozolomide have limited treatment options. Peptide receptor radionuclide therapy and immunotherapy may have a complementary role in the management of these tumors. METHODS:We provide follow-up data on a previously reported patient with a hypermutated recurrent tumor. The patient in this report provided written informed consent for tumor sequencing and review of medical records on an institutional review board-approved research protocol (NCT01775072). RESULTS:Lu-DOTATATE, the patient had a partial response with a 61% reduction in volume of the target lesion. CONCLUSION/CONCLUSIONS:Ga-DOTATATE positron emission tomography.

PURPOSE:We examined the characteristics of breast cancer patients with oligometastases (OM) treated with stereotactic ablative body radiotherapy (SABR) to identify factors associated with local progression, distant metastasis progression, time to subsequent therapy, progression-free survival (PFS), and overall survival (OS). METHODS:We retrospectively reviewed a single-institution database of patients treated with radiotherapy between 2008 and 2018 and identified 79 patients who received SABR to OM. Twenty-seven patients had genetic testing of metastatic tumors using an institutional targeted sequencing platform. Kaplan-Meier analysis, Cox regression, and competing risk models were used to compare clinical and genetic correlates with outcomes. RESULTS:Median follow-up was 50 months (IQR: 29-66) with 67% of patients alive at the last follow-up. Of the 65% of patients who progressed, 82% progressed outside of the radiation field, 18% experienced local failure, and 80% had oligoprogression. Median OS was 86 months (IQR: 29-66), and PFS was 33 months (IQR: 10-38). Less than 5 years from diagnosis to SABR and triple-negative breast cancer (TNBC) were associated with worse OS. Advanced T stage, any prior chemotherapy, and TNBC were associated with worse PFS. Alterations in CEBPB, RB1, TBX3, PTEN, and CDK4 were associated with worse survival outcomes. CONCLUSION:Long-term systemic disease control and survival can be achieved with SABR for oligometastatic breast cancer. Hormone receptor-positive patients with a long disease interval from initial diagnosis and limited systemic progression history may be ideal for SABR to all sites of disease.