Faculty Bibliography

CONTEXT:Individual goals and values should drive medical decision making for patients with serious illness. Unfortunately, clinicians' existing strategies to encourage reflection and communication regarding patients' personal values are generally time-consuming and limited in scope. OBJECTIVES:Herein, we develop a novel intervention to facilitate at-home reflection and discussion about goals and values. We then conduct a pilot study of our intervention in a small population of patients with metastatic cancer. METHODS:We first engaged former cancer patients and their families to adapt an existing serious illness communication guide to a worksheet format. We then distributed this adapted "Values Worksheet" to 28 patients with metastatic cancer. We surveyed participants about their perceptions of the Worksheet to assess its feasibility. RESULTS:Of 30 patients approached, 28 agreed to participate. Seventeen participants completed the Values Worksheet, and of those 11 (65%) responded to the follow-up survey. Seven of eleven reported that the Values Worksheet was a good use of time, and nine of eleven would be likely to recommend it to other patients with cancer. Eight of ten reported mild distress, two of ten reported moderate to severe distress. CONCLUSION:The Values Worksheet was a feasible way to facilitate at-home discussions of goals and values for select patients with metastatic cancer. Further research should focus on identifying which patients are most likely to benefit from the Values Worksheet, and should employ the Worksheet as one tool to facilitate reflection on the questions that arise around serious illness, as an adjunct to serious illness conversations with a physician.

PURPOSE:Proton craniospinal irradiation (pCSI) is a promising treatment for patients with solid tumor leptomeningeal metastasis (LM). We hypothesize that genetic characteristics before and changes resulting after pCSI will reflect clinical response to pCSI. We analyzed the cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) from patients receiving pCSI for LM and explored genetic variations associated with response. EXPERIMENTAL DESIGN:We subjected CSF from 14 patients with LM before and after pCSI to cell-free DNA sequencing using a targeted-sequencing panel. In parallel, plasma ctDNA and primary tumors were subjected to targeted sequencing. Variant allele frequency (VAF) and cancer cell fraction (CCF) were calculated; clonality of observed mutations was determined. Kaplan-Meier analysis was used to associate genomic changes with survival. RESULTS:The median overall survival (OS) for the cohort was 9 months [interquartile range (IQR), 5-21 months]. We showed clonal evolution between tumor and ctDNA of the CSF and plasma with unique mutations identified by compartment. Higher CSF ctDNA mean VAF before pCSI (VAFpre) had worse OS (6 months for VAFpre ≥ 0.32 vs. 9 months for VAFpre < 0.32; P = 0.05). Similarly, increased VAF after pCSI portended worse survival (6 vs. 18 months; P = 0.008). Higher mean CCF of subclonal mutations appearing after pCSI was associated with worse OS (8 vs. 17 months; P = 0.05). CONCLUSIONS:In patients with solid tumor LM undergoing pCSI, we found unique genomic profiles associated with pCSI through CSF ctDNA analyses. Patients with reduced genomic diversity within the leptomeningeal compartment demonstrated improved OS after pCSI suggesting that CSF ctDNA analysis may have use in predicting pCSI response.

PURPOSE/UNASSIGNED:The management of patients with advanced solid malignancies increasingly uses stereotactic body radiation therapy (SBRT). Advanced cancer patients are at risk for developing leptomeningeal metastasis (LM), a fatal complication of metastatic cancer. Cerebrospinal fluid (CSF) is routinely collected during computed tomography (CT) myelography for spinal SBRT planning, offering an opportunity for early LM detection by CSF cytology in the absence of radiographic LM or LM symptoms (subclinical LM). This study tested the hypothesis that early detection of tumor cells in CSF in patients undergoing spine SBRT portends a similarly poor prognosis compared with clinically overt LM. METHODS AND MATERIALS/UNASSIGNED:We retrospectively analyzed clinical records for 495 patients with metastatic solid tumors who underwent CT myelography for spinal SBRT planning at a single institution from 2014 to 2019. RESULTS/UNASSIGNED: = .02). CONCLUSIONS/UNASSIGNED:LM remains a fatal complication of metastatic cancer. Subclinical LM detected by CSF cytology in spine SBRT patients has a similarly poor prognosis compared with standardly detected LM and warrants consideration of central nervous system-directed therapies. As aggressive local therapies are increasingly used for metastatic patients, more sensitive CSF evaluation may further identify patients with subclinical LM and should be evaluated prospectively.

PURPOSE/UNASSIGNED:Pseudoprogression mimicking recurrent glioblastoma remains a diagnostic challenge that may adversely confound or delay appropriate treatment or clinical trial enrollment. We sought to build a radiomic classifier to predict pseudoprogression in patients with primary isocitrate dehydrogenase wild type glioblastoma. METHODS AND MATERIALS/UNASSIGNED:-methylguanine-DNA methyltransferase status to predict pseudoprogression. RESULTS/UNASSIGNED:-methylguanine-DNA methyltransferase status into the classifier. CONCLUSIONS/UNASSIGNED:Our results suggest that radiomic analysis of contrast T1-weighted images and magnetic resonance imaging perfusion images can assist the prompt diagnosis of pseudoprogression. Validation on external and independent data sets is necessary to verify these advanced analyses, which can be performed on routinely acquired clinical images and may help inform clinical treatment decisions.

PURPOSE:Photon involved-field radiotherapy (IFRT) is the standard-of-care radiotherapy for patients with leptomeningeal metastasis (LM) from solid tumors. We tested whether proton craniospinal irradiation (pCSI) encompassing the entire CNS would result in superior CNS progression-free survival (PFS) compared with IFRT. PATIENTS AND METHODS:We conducted a randomized, phase II trial of pCSI versus IFRT in patients with non-small-cell lung cancer and breast cancers with LM. We enrolled patients with other solid tumors to an exploratory pCSI group. For the randomized groups, patients were assigned (2:1), stratified by histology and systemic disease status, to pCSI or IFRT. The primary end point was CNS PFS. Secondary end points included overall survival (OS) and treatment-related adverse events (TAEs). RESULTS:= .19). In the exploratory pCSI group, 35 patients enrolled, the median CNS PFS was 5.8 months (95% CI, 4.4 to 9.1 months) and OS was 6.6 months (95% CI, 5.4 to 11 months). CONCLUSION:Compared with photon IFRT, we found pCSI improved CNS PFS and OS for patients with non-small-cell lung cancer and breast cancer with LM with no increase in serious TAEs.

BACKGROUND:Salvage of recurrent previously irradiated brain metastases (rBrM) is a significant challenge. Resection without adjuvant re-irradiation is associated with a high local failure rate, while reirradiation only partially reduces failure but is associated with greater radiation necrosis risk. Salvage resection plus Cs131 brachytherapy may offer dosimetric and biologic advantages including improved local control versus observation, with reduced normal brain dose versus re-irradiation, however data are limited. METHODS:A prospective registry of consecutive patients with post-stereotactic radiosurgery (SRS) rBrM undergoing resection plus implantation of collagen-matrix embedded Cs131 seeds (GammaTile, GT Medical Technologies) prescribed to 60 Gy at 5 mm from the cavity was analyzed. RESULTS:Twenty patients underwent 24 operations with Cs131 implantation in 25 tumor cavities. Median maximum preoperative diameter was 3.0 cm (range 1.1-6.3). Gross- or near-total resection was achieved in 80% of lesions. A median of 16 Cs131 seeds (range 6-30), with a median air-kerma strength of 3.5 U/seed were implanted. There was one postoperative wound dehiscence. With median follow-up of 1.6 years for survivors, two tumors recurred (one in-field, one marginal) resulting in 8.4% 1-year progression incidence (95%CI = 0.0-19.9). Radiographic seed settling was identified in 7/25 cavities (28%) 1.9-11.7 months post-implantation, with 1 case of distant migration (4%), without clinical sequelae. There were 8 cases of radiation necrosis, of which 4 were symptomatic. CONCLUSIONS:With > 1.5 years of follow-up, intraoperative brachytherapy with commercially available Cs131 implants was associated with favorable local control and toxicity profiles. Weak correlation between preoperative tumor geometry and implanted tiles highlights a need to optimize planning criteria.

PURPOSE/UNASSIGNED:Local treatment for bone metastases is becoming increasingly complex. National guidelines traditionally focus only on radiation therapy (RT), leaving a gap in clinical decision support resources available to clinicians. The objective of this study was to reach expert consensus regarding multidisciplinary management of non-spine bone metastases, which would facilitate standardizing treatment within an academic-community partnership. METHODS AND MATERIALS/UNASSIGNED:A multidisciplinary panel of physicians treating metastatic disease across the Memorial Sloan Kettering (MSK) Cancer Alliance, including community-based partner sites, was convened. Clinical questions rated of high importance in the management of non-spine bone metastases were identified via survey. A literature review was conducted, and panel physicians drafted initial recommendation statements. Consensus was gathered on recommendation statements through a modified Delphi process from a full panel of 17 physicians from radiation oncology, orthopaedic surgery, medical oncology, interventional radiology, and anesthesia pain. Consensus was defined a priori as 75% of respondents indicating "agree" or "strongly agree" with the consensus statement. Strength of Recommendation Taxonomy was employed to assign evidence strength for each statement. RESULTS/UNASSIGNED:Seventeen clinical questions were identified, of which 11 (65%) were selected for the consensus process. Consensus was reached for 16 of 17 answer statements (94%), of which 12 were approved after Round 1 and additional 4 approved after Round 2 of the modified Delphi voting process. Topics included indications for referral to surgery or interventional radiology, radiation fractionation and appropriate use of stereotactic approaches, and the handling of systemic therapies during radiation. Evidence strength was most commonly C (n = 7), followed by B (n = 5) and A (n = 3). CONCLUSIONS/UNASSIGNED:Consensus among a multidisciplinary panel of community and academic physicians treating non-spine bone metastases was feasible. Recommendations will assist clinicians and potentially provide measures to reduce variation across diverse practice settings. Findings highlight areas for further research such as pathologic fracture risk estimation, pre-operative radiation, and percutaneous ablation.

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.

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.