Tungsten Filled 3-Dimensional Printed Lung Blocks for Total Body Irradiation.

PURPOSE: Lung blocks for total-body irradiation are commonly used to reduce lung dose and prevent radiation pneumonitis. Currently, molten Cerrobend containing toxic materials, specifically lead and cadmium, is poured into molds to construct blocks. We propose a streamlined method to create 3-dimensional (3D)-printed lung block shells and fill them with tungsten ball bearings to remove lead and improve overall accuracy in the block manufacturing workflow. METHODS AND MATERIALS: 3D-printed lung block shells were automatically generated using an inhouse software, printed, and filled with 2 to 3 mm diameter tungsten ball bearings. Clinical Cerrobend blocks were compared with the physician drawn blocks as well as our proposed tungsten filled 3D-printed blocks. Physical and dosimetric comparisons were performed on a linac. Dose transmission through the Cerrobend and 3D-printed blocks were measured using point dosimetry (ion-chamber) and the on-board Electronic-Portal-Imaging-Device (EPID). Dose profiles from the EPID images were used to compute the full-width-half-maximum and to compare with the treatment-planning-system. Additionally, the coefficient-of-variation in the central 80% of full-width-half-maximum was computed and compared between Cerrobend and 3D-printed blocks. RESULTS: The geometric difference between treatment-planning-system and 3D-printed blocks was significantly lower than Cerrobend blocks (3D: -0.88 ± 2.21 mm, Cerrobend: -2.28 ± 2.40 mm, P = .0002). Dosimetrically, transmission measurements through the 3D-printed and Cerrobend blocks for both ion-chamber and EPID dosimetry were between 42% to 48%, compared with the open field. Additionally, coefficient-of-variation was significantly higher in 3D-printed blocks versus Cerrobend blocks (3D: 4.2% ± 0.6%, Cerrobend: 2.6% ± 0.7%, P < .0001). CONCLUSIONS: We designed and implemented a tungsten filled 3D-printed workflow for constructing total-body-irradiation lung blocks, which serves as an alternative to the traditional Cerrobend based workflow currently used in clinics. This workflow has the capacity of producing clinically useful lung blocks with minimal effort to facilitate the removal of toxic materials from the clinic.

Molecular Features of Resected Melanoma Brain Metastases, Clinical Outcomes, and Responses to Immunotherapy.

Importance: Central nervous system (CNS)-penetrant systemic therapies have significantly advanced care for patients with melanoma brain metastases. However, improved understanding of the molecular landscape and microenvironment of these lesions is needed to both optimize patient selection and advance treatment approaches. Objective: To evaluate how bulk and single-cell genomic features of melanoma brain metastases are associated with clinical outcome and treatment response. Design, Setting, and Participants: This cohort study analyzed bulk DNA sequencing and single nuclear RNA-sequencing data from resected melanoma brain metastases and included 94 consecutive patients with a histopathologically confirmed diagnosis of melanoma brain metastasis who underwent surgical resection at a single National Comprehensive Cancer Network cancer center in San Francisco, California, from January 1, 2009, to December 31, 2022. Exposure: A Clinical Laboratory Improvement Amendments-certified targeted sequencing assay was used to analyze tumor resection specimens, with a focus on BRAF V600E alteration. For frozen pathologic specimens from CNS treatment-naive patients undergoing surgical resection, commercial single nuclear RNA sequencing approaches were used. Main Outcomes and Measures: The primary outcome was overall survival (OS). Secondary outcomes included CNS progression-free survival (PFS), microenvironmental composition with decreased T-cell and macrophage populations, and responses to immunotherapy. Results: To correlate molecular status with clinical outcome, Kaplan-Meier survival analysis of 94 consecutive patients (median age, 64 years [range, 24-82 years]; 70 men [74%]) with targeted BRAF alteration testing showed worse median intracranial PFS (BRAF variant: 3.6 months [IQR, 0.1-30.6 months]; BRAF wildtype: 11.0 months [IQR, 0.8-81.5 months]; P < .001) and OS (BRAF variant: 9.8 months [IQR, 2.5-69.4 months]; BRAF wildtype: 23.2 months [IQR, 1.1-102.5 months]; P = .005; log-rank test) in BRAF V600E variant tumors. Multivariable Cox proportional hazards regression analysis revealed that BRAF V600E status was an independent variable significantly associated with both PFS (hazard ratio [HR], 2.65; 95% CI, 1.54-4.57; P < .001) and OS (HR, 1.96; 95% CI, 1.08-3.55; P = .03). For the 45 patients with resected melanoma brain metastases undergoing targeted DNA sequencing, molecular classification recapitulated The Cancer Genome Atlas groups (NRAS variant, BRAF variant, NF1 variant, and triple wildtype) with no subtype enrichment within the brain metastasis cohort. On a molecular level, BRAF V600E variant lesions were found to have a significantly decreased tumor mutation burden. Moreover, single nuclear RNA sequencing of treatment-naive BRAF V600E variant (n = 3) brain metastases compared with BRAF wildtype (n = 3) brain metastases revealed increased immune cell populations in BRAF wildtype tumors (mean [SD], 11% [4.1%] vs 3% [1.6%] CD45-positive cells; P = .04). Survival analysis of postoperative immunotherapy responses by BRAF status revealed that BRAF wildtype lesions were associated with a response to checkpoint inhibition (median OS: with immunotherapy, undefined; without immunotherapy, 13.0 months [range, 1.1-61.7 months]; P = .001; log-rank test) while BRAF variant lesions (median OS: with immunotherapy, 9.8 months [range, 2.9-39.8 months]; without immunotherapy, 9.5 months [range, 2.5-67.2 months]; P = .81; log-rank test) were not. Conclusions and Relevance: This molecular analysis of patients with resected melanoma brain metastases found that BRAF V600E alteration is an important translational biomarker associated with worse clinical outcomes, differential microenvironmental composition, and benefit from immunotherapy. Patients with BRAF V600E variant melanoma brain metastases may thus benefit from alternative CNS-penetrant systemic regimens.

ACR-ARS Practice Parameter for the Performance of Total Body Irradiation.

OBJECTIVES: This practice parameter was revised collaboratively by the American College of Radiology (ACR) and the American Radium Society (ARS). This practice parameter provides updated reference literature regarding both clinical-based conventional total body irradiation and evolving volumetric modulated total body irradiation. METHODS: This practice parameter was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website ( https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards ) by the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ARS. RESULTS: This practice parameter provides a comprehensive update to the reference literature regarding conventional total body irradiation and modulated total body irradiation. Dependence on dose rate remains an active area of ongoing investigation in both the conventional setting (where instantaneous dose rate can be varied) and in more modern rotational techniques, in which average dose rate is the relevant variable. The role of imaging during patient setup and the role of inhomogeneity corrections due to computer-based treatment planning systems are included as evolving areas of clinical interest notably surrounding the overall dose inhomogeneity. There is increasing emphasis on the importance of evaluating mean lung dose as it relates to toxicity during high-dose total body irradiation regimens. CONCLUSIONS: This practice parameter can be used as an effective tool in designing and evaluating a total body irradiation program that successfully incorporates the close interaction and coordination among the radiation oncologists, medical physicists, dosimetrists, nurses, and radiation therapists.

Adverse radiation effect and freedom from progression following repeat stereotactic radiosurgery for brain metastases.

OBJECTIVE: The authors previously evaluated risk and time course of adverse radiation effects (AREs) following stereotactic radiosurgery (SRS) for brain metastases, excluding lesions treated after prior SRS. In the present analysis they focus specifically on single-fraction salvage SRS to brain metastases previously treated with SRS or hypofractionated SRS (HFSRS), evaluating freedom from progression (FFP) and the risk and time course of AREs. METHODS: Brain metastases treated from September 1998 to May 2019 with single-fraction SRS after prior SRS or HFSRS were analyzed. Serial follow-up magnetic resonance imaging (MRI) and surgical pathology reports were reviewed to score local treatment failure and AREs. The Kaplan-Meier method was used to estimate FFP and risk of ARE measured from the date of repeat SRS with censoring at the last brain MRI. RESULTS: A total of 229 retreated brain metastases in 124 patients were evaluable. The most common primary cancers were breast, lung, and melanoma. The median interval from prior SRS/HFSRS to repeat SRS was 15.4 months, the median prescription dose was 18 Gy, and the median duration of follow-up imaging was 14.5 months. At 1 year after repeat SRS, FFP was 80% and the risk of symptomatic ARE was 11%. The 1-year risk of imaging changes, including asymptomatic RE and symptomatic ARE, was 30%. Among lesions that demonstrated RE, the median time to onset was 6.7 months (IQR 4.7-9.9 months) and the median time to peak imaging changes was 10.1 months (IQR 5.6-13.6 months). Lesion size by quadratic mean diameter (QMD) showed similar results for QMDs ranging from 0.75 to 2.0 cm (1-year FFP 82%, 1-year risk of symptomatic ARE 11%). For QMD < 0.75 cm, the 1-year FFP was 86% and the 1-year risk of symptomatic ARE was only 2%. Outcomes were worse for QMDs 2.01-3.0 cm (1-year FFP 65%, 1-year risk of symptomatic ARE 24%). The risk of symptomatic ARE was not increased with tyrosine kinase inhibitors or immunotherapy before or after repeat SRS. CONCLUSIONS: RE on imaging was common after repeat SRS (30% at 1 year), but the risk of a symptomatic ARE was much less (11% at 1 year). The results of repeat single-fraction SRS were good for brain metastases ≤ 2 cm. The authors recommend an interval ≥ 6 months from prior SRS and a prescription dose ≥ 18 Gy. Alternatives such as HFSRS, laser interstitial thermal therapy, or resection with adjuvant radiation should be considered for recurrent brain metastases > 2 cm.

Mutational Status and Clinical Outcomes Following Systemic Therapy with or without Focal Radiation for Resected Melanoma Brain Metastases.

BACKGROUND: Brain metastases occur frequently in advanced melanoma and traditionally require surgery and radiation therapy. New evidence demonstrates that systemic therapies are effective for controlling metastatic melanoma brain metastases. This study evaluated outcomes after resection of melanoma brain metastases treated with systemic therapy, with or without focal radiotherapy. METHODS: All patients received immunotherapy or BRAF/MEK inhibitors preoperatively or in the immediate 3 months postoperatively. Resection cavity failure, distant central nervous system progression, and adverse radiation effects were reported in the presence and absence of focal radiotherapy using the Kaplan-Meier method. RESULTS: Between 2011 and 2020, 37 resection cavities in 29 patients met criteria for analysis. Of lesions, 22 (59%) were treated with focal radiotherapy, and 15 (41%) were treated with targeted therapy or immunotherapy alone. The 12- and 24-month freedom from local recurrence was 64.8% (95% confidence interval [CI] 42.1%-99.8%) and 46.3% (95% CI 24.5%-87.5%), respectively, for systemic therapy alone and 93.3% (95% CI 81.5%-100%) at both time points for focal radiotherapy (P = 0.01). On univariate analysis, focal radiotherapy was the only significant factor associated with reduction of local recurrence risk (hazard ratio 0.10, 95% CI 0.01-0.85; P = 0.04). There were no significant differences in central nervous system progression-free survival or overall survival between patients who received systemic therapy plus focal radiotherapy compared with systemic therapy alone. BRAF mutation status was reviewed for either the brain metastasis (n = 9 patients, 31%) or the primary site (n = 20 patients, 69%), and patients harboring BRAFV600E mutations had worse progression-free survival (P = 0.043). CONCLUSIONS: Focal radiotherapy with systemic therapy for resected melanoma brain metastases significantly decreased resection cavity recurrence compared with systemic therapy alone. BRAF mutation status correlated with poorer outcomes.

Resection with intraoperative cesium-131 brachytherapy as salvage therapy for recurrent brain tumors.

OBJECTIVE: The authors' objective was to examine the safety and efficacy of salvage intracranial cesium-131 brachytherapy in combination with resection of recurrent brain tumors. METHODS: The authors conducted a retrospective chart review of consecutive patients treated with intraoperative intracranial cesium-131 brachytherapy at a single institution. Permanent suture-stranded cesium-131 seeds were implanted in the resection cavity after maximal safe tumor resection. The primary outcomes of interest were local, locoregional (within 1 cm), and intracranial control, as well as rates of overall survival (OS), neurological death, symptomatic adverse radiation effects (AREs), and surgical complication rate graded according to Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Between 2016 and 2020, 36 patients received 40 consecutive cesium-131 implants for 42 recurrent brain tumors and received imaging follow-up for a median (interquartile range [IQR]) of 17.0 (12.7-25.9) months. Twenty patients (55.6%) with 22 implants were treated for recurrent brain metastasis, 12 patients (33.3%) with 16 implants were treated for recurrent atypical (n = 7) or anaplastic (n = 5) meningioma, and 4 patients (11.1%) were treated for other recurrent primary brain neoplasms. All except 1 tumor (97.6%) had received prior radiotherapy, including 20 (47.6%) that underwent 2 or more prior radiotherapy treatments and 23 (54.8%) that underwent prior resection. The median (IQR) tumor size was 3.0 (2.3-3.7) cm, and 17 lesions (40.5%) had radiographic evidence of ARE prior to salvage therapy. Actuarial 1-year local/locoregional/intracranial control rates for the whole cohort and patients with metastases and meningiomas were 91.6%/83.4%/47.9%, 88.8%/84.4%/45.4%, and 100%/83.9%/46.4%, respectively. No cases of local recurrence of any histology (0 of 27) occurred after gross-total resection (p = 0.012, log-rank test). The 1-year OS rates for the whole cohort and patients with metastases and meningiomas were 82.7%, 79.1%, and 91.7%, respectively, and the median (IQR) survival of all patients was 26.7 (15.6-36.4) months. Seven patients (19.4%) experienced neurological death from progressive intracranial disease (7 of 14 total deaths [50%]), 5 (13.9%) of whom died of leptomeningeal disease. Symptomatic AREs were observed in 9.5% of resection cavities (n = 4), of which 1 (2.4%) was grade 3 in severity. The surgical complication rate was 16.7% (n = 7); 4 (9.5%) of these patients had grade 3 or higher complications, including 1 patient (2.4%) who died perioperatively. CONCLUSIONS: Cesium-131 brachytherapy resulted in good local control and acceptable rates of symptomatic AREs and surgical complications in this heavily pretreated cohort, and it may be a reasonable salvage adjuvant treatment for this patient population.

Redistributing Central Target Dose Hot Spots for Hypofractionated Radiosurgery of Large Brain Tumors: A Proof-of-Principle Study.

OBJECTIVE: The present proof-of-principle study investigated radiobiological effects of redistributing central target dose hot spots across different treatment fractions during hypofractionated stereotactic radiosurgery (HSRS) of large intracranial tumors. METHODS: Redistribution of central target dose hot spots during HSRS was simulated, and its effects were evaluated in eight cases of brain metastases. To assess dose variations in the target across N number of treatment fractions, a generalized biologically effective dose (gBED) was formulated. The gBED enhancement ratio was defined as the ratio of gBED in the tested treatment plan (with central target dose hot spot redistributions across fractions) to gBED in the conventional treatment plan (without central target dose hot spot redistributions). RESULTS: At a median α value of 0.3/Gy, the tested treatment plans resulted in average gBED increases of 15.6 ± 3.5% and 8.3 ± 1.8% for α/ß ratios of 2 and 10 Gy, respectively. In comparison with conventional treatment plans, the differences in the Paddick conformity index and gradient index did not exceed 2%. CONCLUSION: Redistributing central target dose hot spots across different treatment fractions during HSRS may be considered promising for enhancing gBED in the target. It may be beneficial for management of large intracranial neoplasms; thus, it warrants further clinical testing.

Impact of the Skull Size on the Normal Brain Radiation Dose During Gamma Knife Radiosurgery: Results of a Pilot Study.

OBJECTIVE: The objective of the present study was evaluation of the interrelationships between changes in the skull size and variations in the normal brain radiation dose during Gamma Knife surgery (GKS). METHODS: With use of systematic modeling within Leksell GammaPlan® (Elekta AB; Stockholm, Sweden) in each of 15 analyzed cases, the skull was "expanded" and "contracted" by variation of its measurement values from 0 to ±3 cm. The mean normal brain radiation dose was then computed for each variant of the adjusted skull size and compared with the original treatment plan. Variations in the maximum point dose delivered to selected critical anatomical structures were also investigated. RESULTS: With changes in the skull radius within ±3 cm, the maximum absolute deviation in the mean normal brain radiation dose was 0.8%. As the skull radius increased, the mean normal brain radiation dose also increased linearly (confidence level >99%) with a positive slope of 0.2% per centimeter of radius length change. The maximum point dose deviations in all evaluated critical anatomical structures did not exceed 0.5%, with an overall trend toward a dose increase in parallel with an increase in the skull radius. CONCLUSION: The small skull size of pediatric patients may be associated with dosimetric advantages in terms of normal brain sparing during GKS.

Lessons From Learners: Adapting Medical Student Education During and Post COVID-19.

In response to the COVID-19 pandemic, many medical schools suspended clinical clerkships and implemented newly adapted curricula to facilitate continued educational progress. While the implementation of these new curricula has been described, an understanding of the impact on student learning outcomes is lacking. In 2020, the authors followed Kern's 6-step approach to curricular development to create and evaluate a novel COVID-19 curriculum for medical students at the University of California San Francisco School of Medicine and evaluate its learning outcomes. The primary goal of the curriculum was to provide third- and fourth-year medical students an opportunity for workplace learning in the absence of clinical clerkships, specifically for students to develop clerkship-level milestones in the competency domains of practice-based learning and improvement, professionalism, and systems-based practice. The curriculum was designed to match students with faculty-mentored projects occurring primarily in virtual formats. A total of 126 students enrolled in the curriculum and completed a survey about their learning outcomes (100% response rate). Of 35 possible clerkship-level milestones, there were 12 milestones for which over half of students reported development in competency domains including practice-based learning and improvement, professionalism, and interpersonal and communication skills. Thematic analysis of students' qualitative survey responses demonstrated 2 central motivations for participating in the curriculum: identity as physicians-in-training and patient engagement. Six central learning areas were developed during the curriculum: interprofessional teamwork, community resources, technology in medicine, skill-building, quality improvement, and specialty-specific learning. This analysis demonstrates that students can develop competencies and achieve rich workplace learning through project-based experiential learning, even in virtual clinical workplaces. Furthermore, knowledge of community resources, technology in medicine, and quality improvement was developed through the curriculum more readily than in traditional clerkships. These could be considered as integral learning objectives in future curricular design.

Neuro-Oncology Practice Clinical Debate: Early treatment or observation for patients with newly diagnosed oligodendroglioma and small-volume residual disease.

Advances in treatment of oligodendroglioma represent arguably the most significant recent development in the treatment of brain tumors, with multiple clinical trials demonstrating that median survival is approximately doubled in patients with World Health Organization grade II and III 1p/19q codeleted gliomas (ie, oligodendrogliomas) treated with procarbazine, lomustine, vincristine chemotherapy and radiation vs radiation alone. However, chemoradiotherapy itself is not without morbidity, including both short-term toxicities primarily related to chemotherapy and longer-term cognitive issues likely due to radiation. Patients and physicians both desire maximally effective therapy with minimal toxicity, and it remains unclear whether some patients with macroscopic residual disease after surgery can safely delay therapy, to avoid or delay toxicity, while simultaneously preserving the full benefits of treatment. In this article, experts in the field discuss the rationale for the approaches of up-front treatment with chemoradiotherapy and initial observation, respectively.

Germline MUTYH Mutation in a Pediatric Cancer Survivor Developing a Secondary Malignancy.

Radiotherapy-induced second malignant neoplasms (SMNs) are a severe late complication in pediatric cancer survivors. Germline mutations in tumor suppressor genes contribute to SMNs; however, the most relevant germline variants mediating susceptibility are not fully defined. The authors performed matched whole-exome sequencing analyses of germline and tumor DNA from 4 pediatric solid tumor survivors who subsequently developed radiation-associated SMNs. Pathogenic and predicted deleterious germline variants were identified for each patient and validated with Sanger sequencing. These germline variants were compared with germline variants in a cohort of 59 pediatric patients diagnosed with primary sarcomas. Pathway analysis was performed to test for similarities in the germline variant profiles between individuals diagnosed with SMNs or primary sarcomas. One index patient was found to have a pathogenic germline monoallelic mutation in the MUTYH gene, which encodes the base excision repair enzyme adenine DNA glycosylase. This specific germline mutation is associated with a form of familial adenomatous polyposis, a new diagnosis in the patient. Germline-level genetic similarity exists between SMN-developing patients and patients developing primary sarcomas, with relevant genes involved in signal transduction and DNA repair mechanisms. The authors identify a germline MUTYH mutation in a pediatric cancer survivor developing an SMN. Germline mutations involving specific pathways such as base excision repair may identify individuals at risk for developing SMNs. The composition of germline variants in individual patients may enable estimates of patient-specific risk for developing SMNs. The authors anticipate that further analyses of germline genomes and epigenomes will reveal diverse genes and mechanisms influencing cancer risk.

High-risk Meningioma: Initial Outcomes From NRG Oncology/RTOG 0539.

BACKGROUND: Phase 2 cooperative group meningioma trial assessing the safety and efficacy of risk-adaptive management strategies. This is the initial analysis of the high-risk cohort. METHODS AND MATERIALS: High-risk patients were those with a new or recurrent World Health Organization (WHO) grade III meningioma of any resection extent, recurrent WHO grade II of any resection extent, or new WHO grade II after subtotal resection. Patients received intensity-modulated radiotherapy (IMRT) using a simultaneous integrated boost technique (60 Gy high dose and 54 Gy low dose in 30 fractions). Three-year progression-free survival (PFS) was the primary endpoint. Adverse events (AEs) were scored per NCI Common Terminology Criteria for Adverse Events version 3. RESULTS: Of 57 enrolled patients, 53 received protocol treatment. Median follow-up was 4.0 years (4.8 years for living patients). Two patients withdrew without progression before year 3; for the remaining 51 patients, 3-year PFS was 58.8%. Among all 53 protocol-treated patients, 3-year PFS was 59.2%. Three-year local control was 68.9%, and overall survival was 78.6%. Of 51 patients, 1 patient (1.9%) experienced a late grade-5 necrosis-related AE. All other acute (23 of 53 patients) and late (21 of 51 patients) AEs were grades 1 to 3. CONCLUSIONS: Patients with high-risk meningioma treated with IMRT (60 Gy/30) experienced 3-year PFS of 58.8%. Combined acute and late AEs were limited to grades 1 to 3, except for a single necrosis-related grade 5 event. These results support postoperative IMRT for high-risk meningioma and invite ongoing investigations to improve outcomes further.

Stereotactic Radiosurgery to More Than 10 Brain Metastases: Evidence to Support the Role of Radiosurgery for Ideal Hippocampal Sparing in the Treatment of Multiple Brain Metastases.

BACKGROUND: Brain metastases are a common occurrence, with literature supporting the treatment of a limited number of brain metastases with stereotactic radiosurgery (SRS), as opposed to whole brain radiotherapy (WBRT). Less well understood is the role of SRS in patients with ≥10 brain metastases. METHODS: Patients treated with SRS to ≥10 brain metastases without concurrent WBRT between March 1999 and December 2016 were reviewed. Analysis was performed for overall survival, treated lesion freedom from progression (FFP), freedom from new metastases (FFNMs), and adverse radiation effect. Hippocampal volumes were retrospectively generated in patients treated with up-front SRS for evaluation of dose volume metrics. RESULTS: A total of 143 patients were identified with 75 patients having up-front SRS and 68 patients being treated as salvage therapy after prior WBRT. The median number of lesions per patient was 13 (interquartile range [IQR], 11-17). Median total volume of treatment was 4.1 cm3 (IQR, 2.0-9.9 cm3). The median 12-month FFP for up-front and salvage treatment was 96.8% (95% confidence interval [CI], 95.5-98.1) and 83.6% (95% CI, 79.9-87.5), respectively (P < 0.001). Twelve-month FFNMs for up-front and salvage SRS was 18.8% (95% CI, 10.9-32.3) versus 19.2% (95% CI, 9.7-37.8), respectively (P = 0.90). The mean hippocampal dose was 150 cGy (IQR, 100-202 cGy). CONCLUSIONS: Excellent rates of local control can be achieved when treating patients with >10 intracranial metastases either in the up-front or salvage setting. Hippocampal sparing is readily achievable with expected high rates of new metastatic lesions in treated patients.

Jump-Starting Faculty Development in Quality Improvement and Patient Safety Education: A Team-Based Approach.

PROBLEM: Quality improvement (QI) and patient safety (PS) are cornerstones of health care delivery. Accreditation organizations increasingly require that learners engage in QIPS. For many faculty, these are new domains. Additional faculty development is needed for them to teach and mentor trainees. Existing programs, such as the Association of American Medical Colleges Teaching for Quality (Te4Q) program, target individual faculty and thus accommodate only limited participants at a time, which is problematic for institutions that need to train many faculty to support their learners. APPROACH: The authors invited diverse stakeholders from across the University of California, San Francisco (UCSF) School of Medicine and related health systems to participate in a team-based adaptation of the Te4Q program. The teams completed 5 projects based on previously identified priority areas to increase local capacity for QIPS teaching: (1) online modules for faculty new to QIPS, (2) a tool kit for graduate medical education programs, (3) a module for medical school clerkship directors, (4) guidelines for faculty to integrate early learners into QI projects, and (5) a "Teach-for-UCSF" certificate program in teaching QIPS. OUTCOMES: Thirty-five faculty members participated in the initial Te4Q workshop in January 2015, and by fall 2016, all projects were implemented. These projects led to additional faculty development initiatives and a rapidly expanding number of faculty across campus with expertise in teaching QIPS. NEXT STEPS: Further collaborations between faculty focused on QIPS in care delivery and those focused on QIPS education to promote QIPS teaching have resulted from these initial projects.

Reirradiation of recurrent high-grade glioma and development of prognostic scores for progression and survival.

BACKGROUND: Optimal techniques and patient selection for salvage reirradiation of high-grade glioma (HGG) are unclear. In this study, we identify prognostic factors for freedom from progression (FFP) and overall survival (OS) after reirradiation, risk factors for high-grade toxicity, and validate clinical prognostic scores. METHODS: A total of 116 patients evaluated between 2000 and 2018 received reirradiation for HGG (99 WHO grade IV, 17 WHO grade III). Median time to first progression after initial therapy was 10.6 months. Salvage therapies before reirradiation included surgery (31%) and systemic therapy (41%). Sixty-five patients (56%) received single-fraction stereotactic radiosurgery (SRS) as reirradiation. The median biologically effective dose (BED) was 47.25 Gy, and the median planning target volume (PTV) was 4.8 cc for SRS and 95.0 cc for non-SRS treatments. Systemic therapy was given concurrently to 52% and adjuvantly to 74% of patients. RESULTS: Median FFP was 4.9 months, and median OS was 11.0 months. Significant multivariable prognostic factors for FFP were performance status, time to initial progression, and BED; for OS they were age, time to initial progression, and PTV volume at recurrence. High-grade toxicity was correlated to PTV size at recurrence. Three-level prognostic scores were generated for FFP and OS, with cross-validated receiver operating characteristic area under the curve (AUC) of 0.640 and 0.687, respectively. CONCLUSIONS: Clinical variables at the time of reirradiation for HGG can be used to prognosticate FFP and OS.

Preoperative Dural Contact and Recurrence Risk After Surgical Cavity Stereotactic Radiosurgery for Brain Metastases: New Evidence in Support of Consensus Guidelines.

PURPOSE: The incidence of brain metastases is increasing as a result of more routine diagnostic imaging and improved extracranial systemic treatment strategies. As noted in recent consensus guidelines, postoperative stereotactic radiosurgery (SRS) to the resection cavity has lower rates of local control than whole brain radiation therapy but improved cognitive outcomes. Further analyses are needed to improve local control and minimize toxicity. METHODS AND MATERIALS: Patients receiving SRS to a resection cavity between 2006 and 2016 were retrospectively analyzed. Presurgical variables, including tumor location, diameter, dural/meningeal contact, and histology, were collected, as were SRS treatment parameters. Patients had routine follow-up with magnetic resonance imaging, and those noted to have local failure were further assessed for the recurrence location, distance from the target volume, and dosimetric characteristics. RESULTS: Overall, 82 patients and 85 resection cavities underwent postoperative SRS during the study period. Of these, 58 patients with 60 resection cavities with available follow-up magnetic resonance imaging scans were included in this analysis. With a median follow-up of 19.8 months, local recurrence occurred in 12 of the resection cavities for a 15% 1-year and 18% 2-year local recurrence rate. Pretreatment tumor volume contacted the dura/meninges in 100% of cavities with recurrence versus 67% of controlled cavities (P = .025). A total of 5 infield, 5 marginal, and 4 out-of-field recurrences were found, with a median distance to the centroid from the target volume of 3 mm. The addition of a 10-mm dural margin increased the target volume overlap with the recurrence contours for 10 of the 14 recurrences. CONCLUSIONS: Dural contact was associated with an increased rate of recurrence for patients who received SRS to a surgical cavity, and the median distance of marginal recurrences from the target volume was 3 mm. These results provide evidence in support of recent consensus guidelines suggesting that additional dural margin on SRS volumes may benefit local control.

Peer support: A needs assessment for social support from trained peers in response to stress among medical physicists.

PURPOSE: Previous studies suggest that within radiation oncology, medical physicists (MP) experience high workloads. Little is known about how MPs use social support (SS) in times of stress. METHODS: In collaboration with the Workgroup on Prevention of Medical Error, the American Association of Physicists in Medicine administered this Human Investigation Committee (HIC) approved email survey to 8566 members. Respondents were considered likely to seek SS if they answered (probably/definitely would) and unlikely to seek support if they answered (probably/definitely would not). Logistic regression was applied to determine associations between demographic factors and willingness to seek support as well as perception of barriers. RESULTS: One thousand two hundred and ninety-seven members (15.1%) accessed and gave consent for the survey. One thousand and one (11.7%) respondents answered all relevant questions. Respondents were predominantly male (69.1%), MP in radiation oncology (81.8%), private practice (51.6%), with practice duration> 10 yr (60.2%). MPs were likely to seek SS for personal physical illness (78.63%), involvement in a medical error (73.94%) or adverse patient outcome (75.17%). MPs sought SS in the setting of personal fatigue (33.2%) or burnout (44.3%). Barriers to seeking SS were lack of time (80.3%), and uncertainty about whom to access (70.7%). MPs responded that they would be most likely to seek support from an equally experienced medical physicist colleague (81.0%). Most MPs (67.0%) identified as having experienced stressors, with serious family illness (35.2%), or burnout (32.8%) being most common. Factors associated with MPs unwillingness to seek SS for medical error included> 20 yr in practice (vs still in training - OR 0.30, P = 0.015), and male gender (OR 0.60, P = 0.003). Male gender was associated with the lowest willingness to seek support (OR 2.10, P = 0.0001), but also with fewer perceived barriers (OR 1.60, P = 0.0075). CONCLUSION: Willingness to seek SS is demonstrated, and MPs want colleagues to provide support. Given these results, peer support could be considered among MPs.

Quality Improvement Initiative to Improve Tobacco Cessation Efforts in Radiation Oncology.

PURPOSE: Although continued tobacco use in patients who are treated with radiation therapy is associated with inferior outcomes and increased treatment-related toxicity, multiple studies have shown that current tobacco cessation efforts in oncology are insufficient. A quality improvement (QI) initiative was developed with the goal of improving tobacco cessation efforts in radiation oncology. METHODS: Using iterative plan-do-study-act cycles, barriers to tobacco cessation were identified and then addressed with a single-institutional QI initiative designed to improve physician assessment of patient readiness to quit tobacco by 50% or more. Residents assessed readiness to quit tobacco during new patient consultations and recorded this assessment in prespecified fields within the electronic health record. Feedback on assessment efforts was provided to our department via an automated search of the electronic health record. RESULTS: From December 2014 to February 2015, before the initiation of the QI initiative, 4% of patients were assessed for their readiness to quit tobacco. After implementing the initiative, 67% of patients were assessed for their readiness to quit. CONCLUSION: After instituting a QI initiative at our institution, significantly more patients were assessed for readiness to quit tobacco before treatment with radiation therapy. Ongoing efforts in our department are aimed at improving the efficacy of this intervention.

Palliative radiotherapy near the end of life.

BACKGROUND: A significant proportion of patients with advanced cancer undergo palliative radiotherapy (RT) within their last 30 days of life. This study characterizes palliative RT at our institution and aims to identify patients who may experience limited benefit from RT due to imminent mortality. METHODS: Five hundred and-eighteen patients treated with external beam RT to a site of metastatic disease between 2012 and 2016 were included. Mann-Whitney U and chi-squared tests were used to identify factors associated with RT within 30 days of death (D30RT). RESULTS: Median age at RT was 63 years (IQR 54-71). Median time from RT to death was 74 days (IQR 33-174). One hundred and twenty-five patients (24%) died within 30 days of RT. D30RT was associated with older age at RT (64 vs. 62 years, p = 0.04), shorter interval since diagnosis (14 vs. 31 months, p <  0.001), liver metastasis (p = 0.02), lower KPS (50 vs. 70, p <  0.001), lower BMI (22 vs. 24, p = 0.001), and inpatient status at consult (56% vs. 26%, p < 0.001). Patients who died within 30 days of RT were less likely to have hospice involved in their care (44% vs. 71%, p = 0.001). D30RT was associated with higher Chow and TEACHH scores at consult (p < 0.001 for both). CONCLUSIONS: Twenty-four percent of patients received palliative RT within 30 days of death. Additional tools are necessary to help physicians identify patients who would benefit from short treatment courses or alternative interventions to maximize quality at the end of life.