Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Trigeminal neuralgia affects approximately 2% of patients with multiple sclerosis (MS) and often shows higher rates of pain recurrence after treatment. Previous studies on the effectiveness of stereotactic radiosurgery (SRS) for trigeminal neuralgia did not consider the different MS subtypes, including remitting relapsing (RRMS), primary progressive (PPMS), and secondary progressive (SPMS). Our objective was to investigate how MS subtypes are related to pain control (PC) rates after SRS. METHODS:We conducted a retrospective multicenter analysis of prospectively collected databases. Pain status was assessed using the Barrow National Institute Pain Intensity Scales. Time to recurrence was estimated through the Kaplan-Meier method and compared groups using log-rank tests. Logistic regression was used to calculate the odds ratio (OR). RESULTS:Two hundred and fifty-eight patients, 135 (52.4%) RRMS, 30 (11.6%) PPMS, and 93 (36%) SPMS, were included from 14 institutions. In total, 84.6% of patients achieved initial pain relief, with a median time of 1 month; 78.7% had some degree of pain recurrence with a median time of 10.2 months for RRMS, 8 months for PPMS, 8.1 months for SPMS (P = .424). Achieving Barrow National Institute-I after SRS was a predictor for longer periods without recurrence (P = .028). Analyzing PC at the last available follow-up and comparing with RRMS, PPMS was less likely to have PC (OR = 0.389; 95% CI 0.153-0.986; P = .047) and SPMS was more likely (OR = 2.0; 95% CI 0.967-4.136; P = .062). A subgroup of 149 patients did not have other procedures apart from SRS. The median times to recurrence in this group were 11.1, 9.8, and 19.6 months for RRMS, PPMS, and SPMS, respectively (log-rank, P = .045). CONCLUSION/CONCLUSIONS:This study is the first to investigate the relationship between MS subtypes and PC after SRS, and our results provide preliminary evidence that subtypes may influence pain outcomes, with PPMS posing the greatest challenge to pain management.

PURPOSE/OBJECTIVE:Our institution was an early adopter of 5-fraction accelerated partial breast irradiation (ABPI) to treat women with early-stage breast cancer. This study reports long-term oncologic and cosmetic outcomes. METHODS:We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Logistic regression models were used to identify factors associated with development of late toxicities, clinician, and patient-rated cosmesis. Kaplan-Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free survival (LR-RFS). RESULTS:442 patients received APBI either daily (56%) or every other day (44%) in the prone position (92%). At a median follow-up of 48 months (range: 5.96-155 months), 12 (2.7%) patients developed a local recurrence (LR). Out of 258 patients with > 3-month toxicity data available, the most common late grade ≥ 2 adverse event was breast fibrosis (6.2%). On multivariate analysis, daily APBI treatment (vs every other day) did not correlate with an increased risk of any late grade ≥ 2 toxicity though it did correlate with a lower risk of any late grade ≥ 2 fibrosis. Overall, at a median follow-up of 80 months, the rates of good-excellent physician and patient-rated cosmesis were 95% and 85%, respectively, with no difference between patients treated on consecutive vs. every other day. On multivariate analysis, patients who did not receive any adjuvant therapy were at increased risk of developing a LR. Five-year OS, LRFS, and DFS were 97.2%, 97.7%, and 89.5%, respectively. CONCLUSIONS:Five-fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity, and excellent cosmesis at long-term follow-up.

BACKGROUND AND OBJECTIVES/OBJECTIVE:To study the clinical, imaging, and survival outcomes in patients with motor cortex brain metastases treated with stereotactic radiosurgery (SRS). METHODS:Imaging and clinical data were obtained from our prospective patient registry. Tumor volumes were obtained from serial imaging data. RESULTS:The outcomes of 208 patients with metastases involving the motor cortex who underwent SRS between 2012 and 2021 were analyzed. A total of 279 metastases (0.01 cm3-12.18 cm3, mean 0.74 cm3) were irradiated. The SRS margin dose varied from 10 to 20 Gy (mean 16.9 Gy). The overall tumor control rate was 97.8%. Perilesional edema was noted in 69 (25%) tumors at presentation. Adverse radiation effects (ARE) were noted in 6% of all tumors but were symptomatic in only 1.4%. Median time to appearance of symptomatic ARE was 8 months. Edema without ARE was observed in 13%. New focal seizures were noted in 5 patients (2%) and new generalized seizures in 1 patient (0.3%). Thirty-six patients (17%) presented with motor deficits. At final follow-up, 32 (85%) were improved or unchanged, 13 (41%) had a normal examination, 10 (31%) had mild deficits, and 9 (28%) still had moderate deficits. New remote brain metastases were found in 31% of patients at a median of 8 months. After treatment, the Karnofsky performance score distribution of the population showed an overall right shift and a median survival of 10 months. Patients with incidentally found brain metastases had significantly better survival than those presenting with deficits (median 13 vs 9 months) (P = .048). Absence of a neurological deficit, recursive partitioning analysis Class I and II, and dose >18 Gy were each associated with a significant survival advantage. CONCLUSION/CONCLUSIONS:SRS for motor cortex metastases is safe in most patients and effective in providing tumor control. Patients treated before neurological deficits develop show better outcomes.

BACKGROUND:There are no effective medical therapies for patients with meningioma who progress beyond surgical and radiotherapeutic interventions. Somatostatin receptor Type 2 (SSTR2) represents a promising treatment target in meningiomas. In this multicenter, single-arm phase II clinical study (NCT03971461), the SSTR2-targeting radiopharmaceutical 177Lu-DOTATATE is evaluated for its feasibility, safety, and therapeutic efficacy in these patients. PATIENTS AND METHODS/METHODS:Adult patients with progressive intracranial meningiomas received 177Lu-DOTATATE at a dose of 7.4 GBq (200 mCi) every eight weeks for four cycles. 68Ga-DOTATATE PET-MRI was performed before and six months after begin of treatment. The primary endpoint was progression-free survival (PFS) at 6 months (PFS-6). Secondary endpoints were safety and tolerability, overall survival (OS) at 12 months (OS-12), median PFS, and median OS. RESULTS:Fourteen patients (F=11, M=3) with progressive meningiomas (WHO 1=3, 2=10, 3=1) were enrolled. Median age was 63.1 (range 49.7-78) years. All patients previously underwent tumor resection and at least one course of radiation. Treatment with 177Lu-DOTATATE was well tolerated. Seven patients (50%) achieved PFS-6. Best radiographic response by modified Macdonald criteria was stable disease (SD) in all seven patients. A >25% reduction in 68Ga-DOTATATE (PET) was observed in five meningiomas and two patients. In one lesion, this corresponded to >50% reduction in bidirectional tumor measurements (MRI). CONCLUSIONS:Treatment with 177Lu-DOTATATE was well tolerated. The predefined PFS-6 threshold was met in this interim analysis, thereby allowing this multicenter clinical trial to continue enrollment. 68Ga-DOTATATE PET may be a useful imaging biomarker to assess therapeutic outcome in patients with meningioma.

PURPOSE/OBJECTIVE:A 3D stereoscopic camera system developed by .decimal was commissioned and implemented into the clinic to improve the efficiency of clinical electron simulations. Capabilities of the camera allowed simulations to be moved from the treatment vault into any room with a flat surface that could accommodate patient positioning devices, eliminating the need for clinical patient setup timeslots on the treatment machine. This work describes the process used for these simulations and compares the treatment parameters determined by the system to those used in delivery. METHODS:The Decimal3D scanner workflow consisted of: scanning the patient surface; contouring the treatment area; determining gantry, couch, collimator, and source-to-surface distance (SSD) parameters for en face entry of the beam with sufficient clearance at the machine; and ordering custom electron cutouts when needed. Transparencies showing the projection of in-house library cutouts at various clinical SSDs were created to assist in choosing an appropriate library cutout. Data from 73 treatment sites were analyzed to evaluate the accuracy of the scanner-determined beam parameters for each treatment delivery. RESULTS:Clinical electron simulations for 73 treatment sites, predominately keloids, were transitioned out of the LINAC vault using the new workflow. For all patients, gantry, collimator, and couch parameters along with SSD and cone size were determined using the Decimal3D scanner with 57% of simulations using library cutouts. Tolerance tables for patient setup were updated to allow differences of 10, 20 and 5 degrees for gantry, collimator and couch, respectively. Approximately 7% of fractions (N=181 total fractions) were setup outside of the tolerance table based on physician-direction during treatment. This reflects physician preference to adjust the LINAC rather than patient position during treatment setup. No scanner-derived plan was untreatable due to cutout shape inaccuracy or clearance issues. CONCLUSION/CONCLUSIONS:Clinical electron simulations were successfully transitioned out of the LINAC vault using the Decimal3D scanner without loss of setup accuracy as measured through machine parameter determination and electron cutout shape.

PURPOSE/OBJECTIVE:Radiation myelitis (RM) is a rare complication of radiation therapy (RT). The Pediatric Normal Tissue Effects in the Clinic spinal cord task force aimed to identify RT dose effects and assess risk factors for RM in children. Through systematic review, we analyzed RT dose, fraction size, latency between completion of RT and toxicity, chemotherapy use, age when irradiated, and sex. METHODS AND MATERIALS/METHODS:We conducted literature searches of peer-reviewed manuscripts published from 1964 to June 2017 evaluating RM among children. Normality of variables was assessed with Kolmogorov-Smirnov or Shapiro-Wilk tests. Spearman's rank correlation coefficients were used to test correlations between RT dose/fraction size and latency between RT and development of toxicity. RESULTS:Of 1329 identified and screened reports, 144 reports were fully reviewed and determined to have adequate data for analysis; 16 of these reports had a total of 33 cases of RM with a median age of 13 years (range, 0.2-18) at the time of RT. The most common primary tumor histologies were rhabdomyosarcoma (n = 9), medulloblastoma (n = 5), and Hodgkin lymphoma (n = 2); the most common chemotherapy agents given were vincristine (n = 15), intrathecal methotrexate (n = 12), and intrathecal cytarabine (n = 10). The median RT dose and fraction size were 40 Gy (range, 24-57.4 Gy) and 1.8 Gy (range, 1.3-2.6 Gy), respectively. RT dose resulting in RM in patients who also received chemotherapy was lower than in those not receiving chemotherapy (mean 39.6 vs 49.7 Gy; P = .04). There was no association of age with RT dose. The median latency period was 7 months (range, 1-29). Higher RT dose was correlated with longer latency periods (P = .03) to RM whereas sex, age, fraction size, and chemotherapy use were not. Two of 17 patients with adequate follow-up recovered from RM; unfortunately, it was fatal in 6 of 15 evaluable patients. Complication probability modeling was not possible because of the rarity of events. CONCLUSIONS:This report demonstrates a relatively short latency from RT (with or without chemotherapy) to RM and a wide range of doses (including fraction sizes) associated with RM. No apparent association with age at the time of RT could be discerned. Chemotherapy appears to reduce spinal cord tolerance. Recovery from RM is rare, and it is often fatal.

PURPOSE/OBJECTIVE:The American Association of Physicists in Medicine Radiation Oncology Medical Physics Education Subcommittee (ROMPES) has updated the radiation oncology physics core curriculum for medical residents in the radiation oncology specialty. METHODS AND MATERIALS/METHODS:Thirteen physicists from the United States and Canada involved in radiation oncology resident education were recruited to ROMPES. The group included doctorates and master's of physicists with a range of clinical or academic roles. Radiation oncology physician and resident representatives were also consulted in the development of this curriculum. In addition to modernizing the material to include new technology, the updated curriculum is consistent with the format of the American Board of Radiology Physics Study Guide Working Group to promote concordance between current resident educational guidelines and examination preparation guidelines. RESULTS:The revised core curriculum recommends 56 hours of didactic education like the 2015 curriculum but was restructured to provide resident education that facilitates best clinical practice and scientific advancement in radiation oncology. The reference list, glossary, and practical modules were reviewed and updated to include recent literature and clinical practice examples. CONCLUSIONS:ROMPES has updated the core physics curriculum for radiation oncology residents. In addition to providing a comprehensive curriculum to promote best practice for radiation oncology practitioners, the updated curriculum aligns with recommendations from the American Board of Radiology Physics Study Guide Working Group. New technology has been integrated into the curriculum. The updated curriculum provides a framework to appropriately cover the educational topics for radiation oncology residents in preparation for their subsequent career development.

Purpose: Our institution was an early adopter of 5-fraction accelerated partial breast irradiation (ABPI) to treat women with early-stage breast cancer. This study reports long-term oncologic and cosmetic outcomes. Methods: We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Logistic regression models were used to identify factors associated with development of late toxicities, clinician, and patient-rated cosmesis. Kaplan"“Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free survival (LR-RFS). Results: 442 patients received APBI either daily (56%) or every other day (44%) in the prone position (92%). At a median follow-up of 48 months (range: 5.96"“155 months), 12 (2.7%) patients developed a local recurrence (LR). Out of 258 patients with > 3-month toxicity data available, the most common late grade ≥ 2 adverse event was breast fibrosis (6.2%). On multivariate analysis, daily APBI treatment (vs every other day) did not correlate with an increased risk of any late grade ≥ 2 toxicity though it did correlate with a lower risk of any late grade ≥ 2 fibrosis. Overall, at a median follow-up of 80 months, the rates of good"“excellent physician and patient-rated cosmesis were 95% and 85%, respectively, with no difference between patients treated on consecutive vs. every other day. On multivariate analysis, patients who did not receive any adjuvant therapy were at increased risk of developing a LR. Five-year OS, LRFS, and DFS were 97.2%, 97.7%, and 89.5%, respectively. Conclusions: Five-fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity, and excellent cosmesis at long-term follow-up.

Introduction:As overall survival in prostate cancer increases due to advances in early detection and management, there is a growing need to understand the long-Term morbidity associated with treatment, including secondary tumors. The significance of developing radiation-Associated secondary cancers in an elderly population remains unknown.Methods:Patients diagnosed with prostate cancer between 1975 and 2016 in one of 9 Surveillance, Epidemiology, and End Results registries were included in this study. Risk of second primary pelvic malignancies (SPPMs) were assessed with death as a competing risk using the Fine-Gray model. Time-varying Cox proportional hazard models were employed to analyze risk to overall mortality based on secondary tumor status.Results:A total of 569,167 primary prostate cancers were included in analysis with an average follow-up of 89 months. Among all prostate cancer patients, 4956 SPPMs were identified. After controlling for differences in age, year of diagnosis, and surgery at time of prostate cancer treatment, radiation receipt was associated with a significantly higher incidence of SPPMs (1.1% vs 1.8% at 25 years). Among those who received radiation during initial prostate cancer treatment (n = 195,415), developing an SPPM is significantly associated with worse survival (adjusted hazard ratio = 1.76), especially among younger patients (under age 63, adjusted hazard ratio = 2.36).Conclusions:While developing a secondary malignancy carries a detrimental effect on overall survival, the absolute risk of developing such tumors is exceedingly low regardless of radiation treatment.

Purpose: The expression of PD-L1 in high-grade meningiomas made it a potential target for immunotherapy research in refractory cases. Several prospective studies in this field are still on going. We sought to retrospectively investigate the effects of check-point inhibitors (CI) on meningiomas that had been naïve to either surgical or radiation approaches by following incidental meningiomas found during treatment with CI for various primary metastatic cancers. Methods: We used the NYU Perlmutter Cancer Center Data Hub to find patients treated by CI for various cancers, who also had serial computerized-tomography (CT) or magnetic-resonance imaging (MRI) reports of intracranial meningiomas. Meningioma volumetric measurements were compared between the beginning and end of the CI treatment period. Patients treated with chemotherapy during this period were excluded. Results: Twenty-five patients were included in our study, of which 14 (56%) were on CI for melanoma, 5 (20%) for non-small-cell lung cancer and others. CI therapies included nivolumab (n = 15, 60%), ipilimumab (n = 11, 44%) and pembrolizumab (n = 9, %36), while 9 (36%) were on ipilimumab/nivolumab combination. We did not find any significant difference between tumor volumes before and after treatment with CI (1.31 ± 0.46 vs. 1.34 ± 0.46, p=0.8, respectively). Among patients beyond 1 year of follow-up (n = 13), annual growth was 0.011 ± 0.011 cm³/year. Five patients showed minor volume reduction of 0.12 ± 0.10 cm³ (21 ± 6% from baseline). We did not find significant predictors of tumor volume reduction. Conclusion: Check-point inhibitors may impact the natural history of meningiomas. Additional research is needed to define potential clinical indications and treatment goals.