Faculty Bibliography

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.

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.

BACKGROUND:Leptomeningeal metastases (LM) are associated with limited survival and treatment options. While involved-field radiotherapy is effective for local palliation, it lacks durability. We evaluated the toxicities of proton craniospinal irradiation (CSI), a treatment encompassing the entire central nervous system (CNS) compartment, for patients with LM from solid tumors. METHODS:We enrolled patients with LM to receive hypofractionated proton CSI in this phase I prospective trial. The primary endpoint was to describe treatment-related toxicity, with dose-limiting toxicity (DLT) defined as any radiation-related grade 3 non-hematologic toxicity or grade 4 hematologic toxicity according to the Common Terminology Criteria for Adverse Events that occurred during or within 4 weeks of completion of proton CSI. Secondary endpoints included CNS progression-free survival (PFS) and overall survival (OS). RESULTS:We enrolled 24 patients between June 2018 and April 2019. Their median follow-up was 11 months. Twenty patients were evaluable for protocol treatment-related toxicities and 21 for CNS PFS and OS. Two patients in the dose expansion cohort experienced DLTs consisted of grade 4 lymphopenia, grade 4 thrombocytopenia, and/or grade 3 fatigue. All DLTs resolved without medical intervention. The median CNS PFS was 7 months (95% CI: 5-13) and the median OS was 8 months (95% CI: 6 to not reached). Four patients (19%) were progression-free in the CNS for more than 12 months. CONCLUSION:Hypofractionated proton CSI using proton therapy is a safe treatment for patients with LM from solid tumors. We saw durable disease control in some patients.

BACKGROUND:), and neuroimaging correlate with outcomes after pCSI for LM. METHODS:), and MRIs were examined. Central nervous system progression-free survival (CNS-PFS) and overall survival (OS) from pCSI were determined using Kaplan Meier analysis, Cox proportional-hazards regression, time-dependent ROC analysis, and joint modeling of time-varying effects and survival outcomes. RESULTS:were found. CONCLUSION/CONCLUSIONS:measurement earlier in the LM treatment paradigm.

The concept of oligometastatic disease has evolved substantially over the past decade. During this time, there has been a transition from retrospective and single-arm prospective studies to randomized evidence suggesting a benefit of local consolidative therapy (LCT) in the setting of limited metastatic non-small cell lung cancer. These trials had constraints and were thus limited in the strength of their conclusions, but led to several other ongoing randomized trials examining the role of LCT. These studies span various disease states (synchronous oligometastatic vs oligoprogressive), the scope of histologies included, and in how they define oligometastases. In addition, parallel biologic work is attempting to integrate relevant biomarkers and molecular classifications, with the ultimate goal of more precisely defining oligometastases and triaging patients to appropriate care. Finally, consensus guidelines have been initiated that provide a framework for designing future studies and for maintaining consistency across analyses that will facilitate the interpretation of results. This review describes the prior randomized data, the limitations therein, and future directions of clinical and preclinical studies that highlight the emerging paradigms for treatment of this select patient cohort.

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.

PURPOSE/OBJECTIVE:For patients with long bone metastases who undergo orthopedic stabilization surgery followed by radiotherapy (RT), it is unclear what extent of hardware coverage by the radiation field is needed for optimal tumor control. METHODS AND MATERIALS/METHODS:Long bone metastases treated with surgical intervention followed by radiation between August 2011 to May 2019 from a single institution were reviewed. Local recurrence, defined as any in-bone recurrence, was identified by chart review. Accompanying demographic and treatment characteristics were recorded. Statistical analysis to evaluate factors associated with tumor recurrence included univariate analysis, multivariate analysis, and propensity score matching. RESULTS: = .026). CONCLUSIONS:In this analysis of mostly patients undergoing conventional radiation, coverage of the whole hardware was associated with reduced local recurrence for patients with long bone metastases, consistent with prior reports. Investigation of approaches to further reduce local recurrence, such as preoperative stereotactic radiation, may be warranted.