Search

Competing Interests: John Lucido receives consulting fees from Varian, paid to his institution, which is not related to this work, however it was related to some equipment (linear accelerator) that was mentioned (but not endorsed or evaluated); receives payment from Global Bridges Oncology Referee for educational travel grant RFA, paid to his institution, which is not related to this work. William Breen receives consulting fees from GE Healthcare, paid to his institution; participates on a data safety monitoring board/advisory board for GE Healthcare, paid to his institution. Nicholas Remmes holds investments in many individual stocks, each valued at <$5000, including some health care stocks. To the best of his knowledge, he has no conflicts of interest between these holdings and his professional responsibilities. Additional details can be made available on request. Justine Dupere declares no conflicts of interest.

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Despite an established standard of care including surgical resection, radiation therapy, and chemotherapy, GBM unfortunately is associated with a dismal prognosis. Therefore, researchers are extensively evaluating avenues to expand GBM therapy and improve outcomes in patients with GBM. In this review, we provide a broad overview of novel GBM therapies that have recently completed or are actively undergoing study in clinical trials. These therapies expand across medical, surgical, and radiation clinical trials. We additionally review methods for improving clinical trial design in GBM.

Abstract: Unirradiated patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) who undergo anti-CD19 chimeric antigen receptor T-cell therapy (CART) have a predominant localized pattern of relapse, the significance of which is heightened in individuals with limited/localized disease before CART. This study reports on the outcomes of patients with R/R NHL and limited (<5 involved sites) disease bridged with or without radiotherapy. A multicenter retrospective review of 150 patients with R/R NHL who received CART with <5 disease sites before leukapheresis was performed. Bridging treatment, if any, was administered between leukapheresis and CART infusion. Study end points included relapse-free survival (RFS), event-free survival (EFS), and overall survival. Before CART infusion, 48 patients (32%) received bridging radiotherapy (BRT), and 102 (68%) did not. The median follow-up was 21 months. After CART infusion, BRT patients had higher objective response (92% vs 78%; P = .046) and sustained complete response rates (54% vs 33%; P = .015). Local relapse in sites present before CART was lower in the BRT group (21% vs 46%; P = .003). BRT patients had improved 2-year RFS (53% vs 44%; P = .023) and 2-year EFS (37% vs 34%; P = .039) compared with patients who did not receive BRT. The impact of BRT was most prominent in patients who had ≤2 pre-CART involved disease sites, with 2-year RFS of 62% in patients who received BRT compared with 42% in those who did not (P = .002). BRT before CART for patients with limited (<5 involved disease sites) R/R NHL improves response rate, local control, RFS, and EFS without causing significant toxicities., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Leptomeningeal disease (LMD) is a devastating sequelae of metastatic spread that affects approximately 5% of cancer patients. The incidence of LMD is increasing due to advancements in systemic therapy and enhanced detection methods. The purpose of this review is to provide a detailed overview of the evidence in the detection, prognostication, and treatment of LMD. A comprehensive literature search of PUBMED was conducted to identify articles reporting on LMD including existing data and ongoing clinical trials. We found a wide array of treatment options available for LMD including chemotherapy, targeted agents, and immunotherapy as well as several choices for radiotherapy including whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and craniospinal irradiation (CSI). Despite treatment, the prognosis for patients with LMD is dismal, typically 2-4 months on average. Novel therapies and combination approaches are actively under investigation with the aim of improving outcomes and quality of life for patients with LMD. Recent prospective data on the use of proton CSI for patients with LMD have demonstrated its potential survival benefit with follow-up investigations underway. There is a need for validated metrics to predict prognosis and improve patient selection for patients with LMD in order to optimize treatment approaches.

Competing Interests: Scott C Lester; royalties from Empyrean Medical Systems.

Objective: To evaluate the completeness and reliability of recurrence data from an institutional cancer registry for patients with head and neck cancer., Patients and Methods: Recurrence information was collected by radiation oncology and otolaryngology researchers. This was compared with the institutional cancer registry for continuous patients treated with radiation therapy for head and neck cancer at a tertiary cancer center. The sensitivity and specificity of institutional cancer registry data was calculated using manual review as the gold standard. False negative recurrences were compared to true positive recurrences to assess for differences in patient characteristics., Results: A total of 1338 patients who were treated from January 1, 2010, through December 31, 2017, were included in a cancer registry and underwent review. Of them, 375 (30%) had confirmed cancer recurrences, 45 (3%) had concern for recurrence without radiologic or pathologic confirmation, and 31 (2%) had persistent disease. Most confirmed recurrences were distant (37%) or distant plus locoregional (29%), whereas few were local (11%), regional (9%), or locoregional (14%) alone. The cancer registry accuracy was 89.4%, sensitivity 61%, and specificity 99%. Time to recurrence was associated with registry accuracy. True positives had recurrences at a median of 414 days vs 1007 days for false negatives., Conclusion: Currently, institutional cancer registry recurrence data lacks the required accuracy for implementation into studies without manual confirmation. Longer follow-up of cancer status will likely improve sensitivity. No identified differences in patients accounted for differences in sensitivity. New, ideally automated, data abstraction tools are needed to improve detection of cancer recurrences and minimize manual chart review., Competing Interests: The spouse of author Roman Kowalchuk, MD, was previously employed by GE Healthcare., (© 2024 The Authors.)

Purpose: Low-dose total skin electron beam therapy (TSEBT) is a proven treatment for managing cutaneous T-cell lymphoma (CTCL) and Sezary syndrome with skin burden. We performed a retrospective comparison of response rates and time to progression for patients receiving low-dose TSEBT based on dose per fractionation, total dose, and stage., Methods and Materials: One hundred and ten patients with CTCL and Sezary syndrome were treated with 135 courses of low-dose (400-1500 cGy) TSEBT or subtotal skin electron therapy at multiple centers of a single institution between August 2003 and June 2023. Patients were stratified according to total dose, dose per fraction, and stage., Results: The median follow-up was 301 days (IQR, 141, 767). The median age at treatment was 69.9 years (range, 29.7-96.5). T-stage distribution was as follows: 3 (2.7%) T1, 74 (67.3%) T2, 16 (14.5%) T3, and 17 (15.5%) T4. American Joint Committee on Cancer eighth edition stage distribution was as follows: 3 (2.7%) IA, 53 (48.2%) IB, 3 (2.7%) IIA, 16 (14.5%) IIB, 8 (7.3%) IIIA, 19 (17.3%) IVA, and 8 (7.3%) IVB. There was no significant difference in disease distribution between patients treated with different fractionation schemes. The overall response rate was 89.6%. Forty-four courses (32.6%), 34 courses (25.2%), and 43 (31.9%) resulted in a complete, near-complete, and partial response, respectively. Fourteen courses (10.4%) resulted in no clinical response. For all patients, the median time to response was 43.0 days (IQR, 23.0-70). The median time to skin progression for all patients was 107.5 days (IQR, 67.8-233.5)., Conclusions: This analysis demonstrated that CTCL patients treated with low-dose radiation therapy delivered over various fractionation schemes had similar overall response rates and median time to progression., Competing Interests: Aaron Mangold has received funding from Regeneron, Corbus Sun Pharma, Incyte, Pharma, Eli Lilly, Elorac, Novartis, Janssen, Soligenix, Argenx, Palvella, Abbvie, Priovant, and Merck. All other authors have no relevant conflicts of interest to disclose., (© 2024 The Authors.)

Abstract: Immune checkpoint inhibitors (ICIs) have demonstrated remarkable response rates in relapsed or refractory Hodgkin lymphoma (HL). Still, most patients eventually progress. Patterns of progression after ICIs are not well described and are essential to defining the role of local therapies in combination with ICIs. We identified patients who received ICIs for HL between 2013 and 2022. Fludeoxyglucose-18 positron emission tomography (FDG-PET) before initiating ICI and at progression on/after ICI were reviewed, and areas of active HL were recorded. An exploratory analysis of treatable progression included patients with ≤5 sites of disease on pre-ICI FDG-PET and progression only at pre-ICI sites. Ninety patients were identified; 69 had complete records, and of these, 32 (52%) had relapsed at ICI initiation, 17 (25%) were refractory, and 16 (23%) received ICI as first-line therapy. Forty-five of 69 patients had ≤5 sites of disease (limited) on pre-ICI FDG-PET. Patients with >5 sites of disease had a higher risk of progression, and every site of disease >5 sites conferred an additional 1.2x higher chance of progression. At a median follow-up of 4.0 years, 41 of 69 patients had progressed on/after ICIs (cumulative incidence 66.4%), and of these, 22 of 41 patients progressed only at pre-ICI sites (cumulative incidence 39.4%). In an exploratory analysis, the cumulative incidence of a treatable progression among 45 patients with limited disease was 34%. The cumulative incidence of any progression among this cohort was 58.9%. More than one-third of patients with limited disease before ICIs experienced progression only at pre-ICI sites of disease. These patients could be candidates for radiation during or after ICIs., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: This study aimed to determine whether proton craniospinal irradiation (CSI) decreased the dose to normal tissue and resulted in less toxicity than photon CSI for adult patients., Methods: This single-institution retrospective analyzed differences in radiation doses, acute toxicity, and cost between proton and CSI for adult medulloblastoma patients., Results: Of 39 total patients, 20 were treated with photon CSI prior to 2015, and 19 were treated with proton CSI thereafter. Median age was 28 years (range 18-66). The molecular subtype was most commonly sonic hedgehog (68%). Patients most commonly received 36 Gy CSI in 20 fractions with a boost to 54-55.8 Gy (92%). Proton CSI delivered significantly lower mean doses to cochleae, lacrimal glands, lens, parotid glands, pharyngeal constrictors, esophagus, lungs, liver, and skin (all P  < .001). Patients receiving proton CSI had significantly lower rates of acute dysphagia of any grade (5% versus 35%, P  = .044) and decreased median weight loss during radiation (+1.0 versus -2.8 kg, P  = .011). Weight loss was associated with acute hospitalization ( P  = .009). Median follow-up was 2.9 and 12.9 years for proton and photon patients, respectively, limiting late toxicity and outcome comparisons. At the last follow-up, 5 photon patients had died (2 of progressive disease, 3 without recurrence ages 41-63) and 21% had experienced major cardiovascular events. At 10 years, 89% were alive and 82% were recurrence free., Conclusions: This study demonstrates dosimetric improvements with proton CSI, potentially leading to decreased acute toxicity including dysphagia and weight loss during treatment., Competing Interests: None of the authors reported conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Introduction: Proton craniospinal irradiation (pCSI) is a treatment option for leptomeningeal disease (LMD), which permits whole neuroaxis treatment while minimizing toxicity. Despite this, patients inevitably experience progression. Adding systemic therapy to pCSI may improve outcomes., Methods: In this single-institution retrospective case series, we present the feasibility of treatment with pCSI (30Gy, 10 fractions) and an immune checkpoint inhibitor (ICI) in two sequential patients with LMD from melanoma., Results: The first patient developed LMD related to BRAF V600E-mutant melanoma after prior ICI and BRAF -targeted therapy. After pCSI with concurrent nivolumab, the addition of relatlimab, and BRAF -targeted therapy, he remained alive 7 months after LMD diagnosis despite central nervous system progression. The second patient developed LMD related to BRAF -wildtype melanoma after up-front ICI. He received pCSI with concurrent ipilimumab and nivolumab, then nivolumab maintenance. Though therapy was held for ICI hepatitis, the patient remained progression-free 5 months after LMD diagnosis., Conclusion: Adding an ICI to pCSI is feasible for patients with LMD and demonstrates a tolerable toxicity profile. While prospective evaluation is ultimately warranted, pCSI with ICI may confer survival benefits, even after prior ICI., Competing Interests: Conflicts of Interest: None.

Anti-CD19 chimeric antigen receptor T-cell therapy (CART) has revolutionized the outcomes of relapsed and/or refractory B-cell non-Hodgkin lymphoma. However, CART is still limited by its availability, toxicity, and response durability. Not all patients make it to the CART infusion phase due to disease progression. Among those who receive CART, a significant number of patients experience life-threatening cytokine release syndrome toxicity, and less than half maintain a durable response with the majority relapsing in pre-existing sites of disease present pre-CART. Radiation therapy stands as a promising peri-CART and salvage treatment that can improve the outcomes of these patients. Evidence suggests that bridging radiotherapy prior to CART controls the disease during the manufacturing period, augments response rates and local control, cytoreduces/debulks the disease and decreases the severity of cytokine release syndrome, and may prolong disease-free intervals and survival especially in patients with bulky disease. Consolidative radiotherapy for residual post-CART disease alters the pattern of relapse and improves local recurrence-free and progression-free survivals. Salvage radiotherapy for relapsed post-CART disease has favorable survival outcomes when delivered comprehensively for patients with limited relapsed disease and palliates symptoms for patients with diffuse relapsed disease. The biology of the disease during the peri-CART period is poorly understood, and further studies investigating the optimal timing and dosing of radiation therapy (RT) are needed. In this review, we tackle the most significant challenges of CART, review and propose how RT can help mitigate these challenges, and provide The Mayo Clinic experts' approach on incorporating RT with CART., (© 2023 Wiley Periodicals LLC.)

Most patients with solitary bone plasmacytomas (SBP) progress to multiple myeloma (MM) after definitive radiation therapy as their primary treatment. Whether the presence of high-risk (HR) cytogenetic abnormalities by fluorescence in situ hybridization (FISH) in the clonal plasma cells, obtained either directly from the diagnostic SBP tissue or the corresponding bone marrow examination at the time of diagnosis, is associated with a shorter time to progression (TTP) to MM is unknown. This study evaluated all patients diagnosed with SBP at the Mayo Clinic from January 2012 to July 2022. The presence of del(17p), t(14;16), t(4;14), or +1q (gain or amplification) by FISH in clonal plasma cells was defined as HR. A total of 114 patients were included in this cohort, and baseline FISH was available for 55 patients (48%), of which 22 were classified as HR (40%). The median TTP to MM for patients with SBP and HR FISH was 8 months (95% confidence interval [CI], 6.3-26) compared with 42 months (95% CI, 25-not reached [NR]) in patients with SBP without HR FISH (P < .001). In a multivariate analysis, only HR FISH was a significant predictor for shorter TTP to MM, independent of minimal marrow involvement and an abnormal serum free light chain ratio at diagnosis. Deletion (17p) and gain 1q abnormalities were the most common FISH abnormalities responsible for the short TTP to MM. Thus, assessing for HR FISH abnormalities in clonal plasma cells derived from either the diagnostic SBP tissue or the staging bone marrow examination of patients with newly diagnosed SBP is feasible and prognostic for a shorter TTP to MM., (© 2023 by The American Society of Hematology.)

Majority of non-Hodgkin lymphoma (NHL) patients who achieve partial response (PR) or stable disease (SD) to CAR T-cell therapy (CAR T) on day +30 progress and only 30% achieve spontaneous complete response (CR). This study is the first to evaluate the role of consolidative radiotherapy (cRT) for residual fluorodeoxyglucose (FDG) activity on day +30 post- CAR T in NHL. We retrospectively reviewed 61 patients with NHL who received CAR T and achieved PR or SD on day +30. Progression-free survival (PFS), overall survival (OS), and local relapse-free survival (LRFS) were assessed from CAR T infusion. cRT was defined as comprehensive - treated all FDG-avid sites - or focal. Following day +30 positron emission tomography scan, 45 patients were observed and 16 received cRT. Fifteen (33%) observed patients achieved spontaneous CR, and 27 (60%) progressed with all relapses involving initial sites of residual FDG activity. Ten (63%) cRT patients achieved CR, and four (25%) progressed with no relapses in the irradiated sites. The 2-year LRFS was 100% in the cRT sites and 31% in the observed sites (P<0.001). The 2-year PFS was 73% and 37% (P=0.025) and the 2-year OS was 78% and 43% (P=0.12) in the cRT and observation groups, respectively. Patients receiving comprehensive cRT (n=13) had superior 2- year PFS (83% vs. 37%; P=0.008) and 2-year OS (86% vs. 43%; P=0.047) compared to observed or focal cRT patients (n=48). NHL patients with residual FDG activity following CAR T are at high risk of local progression. cRT for residual FDG activity on day +30 post-CAR T appears to alter the pattern of relapse and improve LRFS and PFS.

Leptomeningeal disease (LMD) remains a challenging condition with a dismal prognosis. In this case study, we report partial response of LMD in a patient with metastatic large cell neuroendocrine carcinoma following treatment with proton craniospinal irradiation (CSI), bevacizumab, and pembrolizumab. Two years after the initial diagnosis, he presented with LMD. He underwent proton CSI with bevacizumab followed by combination therapy with pembrolizumab and bevacizumab. He had a partial disease response with progression-free survival after LMD diagnosis of 4.6 months. He unfortunately developed pembrolizumab induced hypophysitis, after which he experienced rapid neurologic clinical progression. Overall, this novel combination led to a durable partial response which warrants prospective evaluation.

PET/CT is used to evaluate relapsed/refractory non-Hodgkin lymphoma (NHL) prior to chimeric antigen receptor T-cell (CAR-T) infusion at two time points: pre-leukapheresis (pre-leuk) and pre-lymphodepletion chemotherapy (pre-LD). We hypothesized that changes in PET/CT between these time points predict outcomes after CAR-T. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and other metrics were calculated from pre-leuk and pre-LD PET/CT scans in patients with NHL who received axicabtagene ciloleucel, and assessed for association with outcomes. Sixty-nine patients were analyzed. While single time point PET/CT characteristics were not associated with risk of PD or death, increases from pre-leuk to pre-LD in parenchymal MTV, nodal MTV, TLG of the largest lesion, and total number of lesions were associated with increased risk of death (p < 0.05 for all). LASSO analysis identified increasing extranodal MTV and increasing TLG of the largest lesion as strong predictors of death (AUC 0.74). Greater pre-LD total MTV was associated with higher risk of grade 3+ immune effector cell-associated neurotoxicity syndrome (ICANS) (p = 0.042). Increasing metabolic disease burden during CAR-T manufacturing is associated with increased risk of progression and death. A two variable risk score stratifies prognosis prior to CAR-T infusion and may inform risk-adapted strategies., (© 2023. Springer Nature Limited.)

Purpose: Purpose: Subtotal skin electron beam therapy may be an option for patients with cutaneous lymphoma receiving radiation therapy to treat large areas of their skin but may benefit from sparing specific areas that may have had previous radiation therapy, are of specific cosmetic concern, and/or show no evidence of disease. We report here on the design, implementation, and dosimetric characteristics of a reusable and transparent customizable shield for use with the large fields used to deliver total skin electron beam therapy at extended distance with a conventional linear accelerator., Methods and Materials: A shield was designed and manufactured consisting of acrylic blocks that can be mounted on a steel frame to allow patient-specific shielding. The dosimetry of the device was measured using radiochromic film., Results: The shield is easy to use and well-tolerated for patient treatment, providing minimal electron transmission through the shield with a sharp penumbra at the field edge, with no increase in x-ray dose. We report on the dosimetry of a commercial device that has been used to treat more than 30 patients to date., Conclusions: The customizable shield is well suited to providing patient-specific shielding for subtotal skin electron beam therapy., Competing Interests: William Breen reports being on the scientific advisory board for GE Healthcare, with all payments made to his institution. John Lucido reports receiving an honorarium paid to his institution for work as grant referee for Global Bridges Oncology and consulting fees paid to his institution by Varian Medical Systems. Aaron Mangold reports currently receiving research grants paid to his institution by Regeneron, Corbus, Incyte, Pfizer, Eli Lilly, Argenyx, Palvella, Abbview, Priovant, and Merck and previous research grants in the past 36 months for Kyowa Kirin, Miragen, Sun Pharma, Elorac, Janssen, and Novartis. He also is currently receiving consulting fees paid to him from Janssen and Boehringer Ingelheim and paid to his institution from Argenyx, Incyte, Regeneron, Clarivate, and Pfizer, previously received consulting fees paid to him from Kyowa Kirin, Clarivate, Soligenix, Phlecs, Incyte, Eli Lilly, Momenta, UCB, and Bristol Myers Squibb, and is currently receiving payment for manuscript writing (for a separate manuscript) from Janssen. He holds a patent for “Topical Ruxolitinib for Treating Lichen Planus” (PCT/US2021/053149; 63/086,898) and has filed for a patent for “Methods and Materials for Assessing and Treating Cutaneous Squamous Cell Carcinoma” (63/423,254). Aaron Mangold is also currently on the Advisory Board for Bristol Myers Squibb currently the President of Pacific Dermatology Society, the Chair of the Community Outreach Committee for the American Academy of Dermatology, on the Board of Directors for the US Cutaneous Lymphoma Consortium, was previously the President of the Arizona Dermatology and Dermatological Society and a Board Member for the Arizona Medical Association (all unpaid), has personal stock ownership of Intellia Therapeutics and Editas, and is receiving medical writing support from Pfizer and Janssen. Chris Deufel reports being a board member of the American Brachytherapy Society., (© 2023 The Author(s).)

Purpose: Concurrent chemoradiation therapy is a curative treatment for squamous cell carcinoma of the anus, but patients can suffer from significant treatment-related toxicities. This study was undertaken to determine whether intensity modulated proton therapy (IMPT) is associated with less acute toxicity than intensity modulated radiation therapy (IMRT) using photons., Materials and Methods: We performed a multi-institutional retrospective study comparing toxicity and oncologic outcomes of IMRT versus IMPT. Patients with stage I-IV (for positive infrarenal para-aortic or common iliac nodes only) squamous cell carcinoma of the anus, as defined by the American Joint Committee on Cancer's AJCC Staging Manual , eighth edition, were included. Patients with nonsquamous histology or mixed IMPT and IMRT treatment courses were excluded. Acute nonhematologic toxicities, per the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 4, were recorded prospectively at all sites. Acute and late toxicities, dose metrics, and oncologic outcomes were compared between IMRT and IMPT using univariable and multivariable statistical methods. To improve the robustness of our analysis, we also analyzed the data using propensity score weighting methods., Results: A total of 208 patients were treated with either IMPT (58 patients) or IMRT (150 patients). Of the 208 total patients, 13% had stage I disease, 36% stage II, 50% stage III, and 1% stage IV. IMPT reduced the volume of normal tissue receiving low-dose radiation but not high-dose radiation to bladder and bowel. There was no significant difference between treatment groups in overall grade 3 or greater acute toxicity (IMRT, 68%; IMPT, 67%; P  = .96) or 2-year overall grade 3 or greater late toxicity (IMRT, 3.5%; IMPT, 1.8%; P  = .88). There was no significant difference in 2-year progression-free survival (hazard ratio, 0.8; 95% CI, 0.3-2.0)., Conclusions: Despite reducing the volume of normal tissue receiving low-dose radiation, IMPT was not associated with decreased grade 3 or greater acute toxicity as measured by CTCAE. Additional follow-up is needed to assess whether important differences arise in late toxicities and if further prospective evaluation is warranted., (© 2021 The Author(s).)

Introduction: To report long-term efficacy and adverse events (AEs) associated with intensity modulated radiotherapy (IMRT) for patients with anal canal squamous cell carcinoma (ASCC)., Materials and Methods: This was a retrospective review of patients with ASCC who received curative-intent IMRT and concurrent chemotherapy (98%) between 2003 and 2019. Overall survival (OS), colostomy-free survival (CFS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method. The cumulative incidence of local recurrence (LR), locoregional recurrence (LRR), and distant metastasis (DM) were reported. Acute and late AEs were recorded per National Cancer Institute Common Terminology Criteria for AEs., Results: 127 patients were included. The median patient age was 63 years (interquartile range [IQR] 55-69) and 79% of patients were female. 33% of patients had T3-4 disease and 68% had clinically involved pelvic or inguinal lymph nodes (LNs).The median patient follow-up was 47 months (IQR: 28-89 months). The estimated 4-year OS, CFS, and PFS were 81% (95% confidence interval [CI]: 73%-89%), 77% (95% CI: 68%-86%), and 78% (95% CI: 70%-86%), respectively. The 4-year cumulative incidences of LR, LRR, and DM were 3% (95% CI: 1%-9%), 9% (95% CI: 5%-17%), and 10% (95% CI: 6%-18%), respectively. Overall treatment duration greater than 39 days was associated with an increased risk of LRR (Hazard Ratio [HR]: 5.2, 95% CI: 1.4-19.5, p = 0.015). The most common grade 3+ acute AEs included hematologic (31%), gastrointestinal (GI) (17%), dermatologic (16%), and pain (15%). Grade 3+ late AEs included: GI (3%), genitourinary (GU) (2%), and pain (1%). Current smokers were more likely to experience grade 3+ acute dermatologic toxicity compared to former or never smokers (34% vs. 7%, p < 0.001)., Conclusions: IMRT was associated with favorable toxicity rates and long-term efficacy. These data support the continued utilization of IMRT as the preferred treatment technique for patients with ASCC., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Jethwa report honoraria from RadOncQuestions.com, LLC., (© 2021 The Author(s).)

Purpose: Postoperative stereotactic radiosurgery (SRS) is associated with up to 30% risk of subsequent leptomeningeal disease (LMD). Radiographic patterns of LMD (classical sugarcoating [cLMD] vs. nodular [nLMD]) in this setting has been shown to be prognostic. However, the association of these findings with neurologic death (ND) is not well described., Methods and Materials: The records for patients with brain metastases who underwent surgical resection and adjunctive SRS to 1 lesion (SRS to other intact lesions was allowed) and subsequently developed LMD were combined from 7 tertiary care centers. Salvage radiation therapy (RT) for LMD was categorized according to use of whole-brain versus focal cranial RT., Results: The study cohort included 125 patients with known cause of death. The ND rate in these patients was 79%, and the rate in patients who underwent LMD salvage treatment (n = 107) was 76%. Univariate logistic regression demonstrated radiographic pattern of LMD (cLMD vs. nLMD, odds ratio: 2.9; P = .04) and second LMD failure after salvage treatment (odds ratio: 3.9; P = .02) as significantly associated with ND. The ND rate was 86% for cLMD versus 68% for nLMD. Whole-brain RT was used in 95% of patients with cLMD and 52% with nLMD. In the nLMD cohort (n = 58), there was no difference in ND rate based on type of salvage RT (whole-brain RT: 67% vs. focal cranial RT: 68%, P = .92)., Conclusions: LMD after surgery and SRS for brain metastases is a clinically significant event with high rates of ND. Classical LMD pattern (vs. nodular) and second LMD failure after salvage treatment were significantly associated with a higher risk of ND. Patients with nLMD treated with salvage focal cranial RT did not have higher ND rates compared with WBRT. Methods to decrease LMD and the subsequent high risk of ND in this setting warrant further investigation., (© 2021 The Authors.)

Immunotherapy (IO) has become a standard treatment in patients with metastatic and locally advanced non-small cell lung cancer (NSCLC), and is now being tested in patients with early stage disease. IO agents currently in use for lung cancer target PD-1, PD-L1, and CTLA-4. While survival and tumor control have improved with IO, many patients have limited or short responses to IO. Therefore, methods to improve the systemic response to IO are needed. Radiation therapy (RT) is an integral component of lung cancer treatment, and may improve systemic response to IO by increasing antigen presentation, increasing co-stimulatory signaling, increasing T-cells recruitment, upregulating PD-L1, increasing tumor stromal lymphocyte infiltration, and altering the microenvironment. IO after definitive chemoradiation is now standard treatment in unresectable stage III NSCLC following publication of the PACIFIC clinical trial. For early stage NSCLC, IO is being investigated in conjunction with stereotactic body radiotherapy (SBRT). The benefit of adding RT to IO in patients with metastatic disease may be especially pronounced in patients with low baseline PD-L1 expression, potentially when delivered as a short course of SBRT, as supported by the PEMBRO-RT clinical trial. Current and ongoing clinical trials are evaluating the optimal radiation dose, timing, and sequencing of RT with IO., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form, available at: http://dx.doi.org/10.21037/jtd-2019-cptn-07. The series “Contemporary Practice in Thoracic Neoplasm Diagnosis, Evaluation and Treatment” was commissioned by the editorial office without any funding or sponsorship. KL reports honoraria for the institution from OncLive, other from Takeda, outside the submitted work. KWM reports grants from Astra Zeneca, grants from Advanced Accelerator Applications, and grants from Pfizer, outside the submitted work. The other authors have no other conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Background: The optimal radiation dose for adult supratentorial low-grade glioma is unknown. The aim of this study was to provide a final update on oncologic and cognitive outcomes of high-dose versus low-dose radiation for low-grade glioma., Methods: Between 1986 and 1994, 203 patients with supratentorial low-grade glioma were randomized (1:1) to 50.4 Gy in 28 fractions versus 64.8 Gy in 36 fractions after any degree of resection., Results: For all patients, median overall survival (OS) was 8.4 years (95% CI: 7.2-10.8). Median progression-free survival (PFS) was 5.2 years (95% CI: 4.3-6.6). Median follow-up is 17.2 years for the 33 patients still alive. High-dose radiation did not improve 15-year OS (22.4%) versus low-dose radiation (24.9%, log-rank P = 0.978) or 15-year PFS (high dose, 15.2% vs low dose, 9.5%; P = 0.7142). OS was significantly better for patients with preoperative tumor diameter <5 cm and baseline Mini-Mental State Examination (MMSE) >27 and who underwent gross total resection. PFS was improved for patients with oligodendroglioma versus astrocytoma, preoperative tumor diameter <5 cm, patients who had gross total resection, and patients with baseline MMSE >27. For patients who had normal MMSE at baseline, at 7 years only 1 patient (5%) had a clinically significant decrease in MMSE from the previous time point, with the remainder (95%) stable. None had decrease in MMSE at 10, 12, or 15 years., Conclusions: Long-term follow-up indicates no benefit to high-dose over low-dose radiation for low-grade gliomas. Cognitive function appeared to be stable after radiation as measured by MMSE., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The optimal treatment sequence for localized malignant pleural mesothelioma (MPM) is controversial. We aimed to assess outcomes and toxicities of treating localized MPM with neoadjuvant radiation therapy (RT) followed by extrapleural pneumonectomy (EPP). Methods: Patients were enrolled on an institutional protocol of surgery for mesothelioma after radiation therapy (SMART) between June 2016 and May 2017. Eligible patients were adults with MPM localized to the ipsilateral pleura. Patients underwent staging with PET/CT, pleuroscopy, bronchoscopy/EBUS, mediastinoscopy, and laparoscopy. Five fractions of RT were delivered using intensity modulated radiation therapy (IMRT), with 30 Gy delivered to gross disease and 25 Gy to the entire pleura. EPP was performed 4-10 days following completion of RT. Results: Five patients were treated on protocol. Median age was 62 years (range 36-66). Histology was epithelioid on initial biopsy in all patients, but one was found to have biphasic histology after surgery. Three patients had surgeon-assessed gross total resection, and two had gross residual disease. While all patients were clinically node negative by pretreatment staging, three had positive nodal disease at surgery. Patients were hospitalized for a median 24 days (range 5-69) following surgery. Two patients developed empyema, one of whom developed respiratory failure and subsequently renal failure requiring dialysis, while the other required multiple surgical debridements. Two patients developed atrial fibrillation with rapid ventricular response after surgery, one of whom developed acute respiratory distress requiring intubation and tracheostomy. At last follow-up, one patient died at 1.4 years after local and distant progression, two were alive with local and distant progression, and the remaining two were alive without evidence of disease at 0.1 and 2.7 years. Median time to progression was 9 months. Three patients received salvage chemotherapy. Conclusions: SMART provided promising oncologic outcomes at the cost of significant treatment related morbidity. Due to the significant treatment associated morbidity and favorable treatment alternatives, we have not broadly adopted SMART at our institution., (Copyright © 2020 Breen, Garces, Olivier, Park, Merrell, Nichols, Peikert, Molina, Mansfield, Roden, Blackmon and Wigle.)

Objective: To assess familiarity with sarcoma guidelines among primary care practitioners (PCPs) in Minnesota., Participants and Methods: Surveys were distributed at 2 educational conferences held in Minnesota on April 16-17, 2015, and October 24, 2015. The PCPs were asked a series of questions about their current practice, past experience with sarcoma, and familiarity with sarcoma guidelines. They were then given a series of case presentations and asked to indicate if they would pursue a sarcoma work-up given the information provided., Results: The study group included 80 physicians and 32 nurse practitioners (NPs). Over their careers (median, 14 years), physicians reported seeing a mean of 2.2 cases of soft tissue sarcoma and 0.7 cases of bone sarcoma. The NPs reported seeing a mean of 0.7 and 0.2 cases, respectfully, over their careers (median, 8 years). Both physicians and NPs reported low familiarity with sarcoma guidelines. When challenged with case presentations for which urgent referral to a sarcoma specialist is recommended, more than 50% of PCPs did not indicate that they would refer patients. The PCPs who had previous experience with soft tissue sarcoma and bone sarcoma estimated that only 17% and 23% of their patients, respectively, were diagnosed within 1 month of presentation. The most reported reason for a delayed diagnosis was the PCP advising the patient to "watch and wait.", Conclusion: Minnesota PCPs have seen very few cases of sarcoma and report low familiarity with sarcoma guidelines. When challenged with case presentations, PCPs made decisions inconsistent with established guidelines. This study supports ongoing efforts to increase sarcoma awareness., (© 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

Background: Radiographic leptomeningeal disease (LMD) develops in up to 30% of patients following postoperative stereotactic radiosurgery (SRS) for brain metastases. However, the clinical relevancy of this finding and outcomes after various salvage treatments are not known., Methods: Patients with brain metastases, of which 1 was resected and treated with adjunctive SRS, and who subsequently developed LMD were combined from 7 tertiary care centers. LMD pattern was categorized as nodular (nLMD) or classical ("sugarcoating," cLMD)., Results: The study cohort was 147 patients. Most patients (60%) were symptomatic at LMD presentation, with cLMD more likely to be symptomatic than nLMD (71% vs. 51%, P = 0.01). Salvage therapy was whole brain radiotherapy (WBRT) alone (47%), SRS (27%), craniospinal radiotherapy (RT) (10%), and other (16%), with 58% receiving a WBRT-containing regimen. WBRT was associated with lower second LMD recurrence compared with focal RT (40% vs 68%, P = 0.02). Patients with nLMD had longer median overall survival (OS) than those with cLMD (8.2 vs 3.3 mo, P < 0.001). On multivariable analysis for OS, pattern of initial LMD (nodular vs classical) was significant, but type of salvage RT (WBRT vs focal) was not., Conclusions: Nodular LMD is a distinct pattern of LMD associated with postoperative SRS that is less likely to be symptomatic and has better OS outcomes than classical "sugarcoating" LMD. Although focal RT demonstrated increased second LMD recurrence compared with WBRT, there was no associated OS detriment. Focal cranial RT for nLMD recurrence after surgery and SRS for brain metastases may be a reasonable alternative to WBRT., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: For patients with stage III (N2) non-small cell lung cancer (NSCLC) treated with surgical resection, postoperative chemotherapy improves overall survival (OS), but the role of postoperative radiation therapy (PORT) is controversial. The purpose of this study was to evaluate risk factors for local-regional recurrence and to evaluate the impact of PORT on local-regional control (LRC) and OS in a modern series of patients with surgically resected stage III (N2) NSCLC., Methods and Materials: A retrospective review was performed of patients with Stage III (N2) NSCLC who underwent curative intent resection at our institution between February 1999 and January 2012. OS, LRC, and metastasis-free survival were estimated from the date of surgery using the Kaplan Meier method., Results: A total of 71 patients were included in the study. Patient median age was 63 years. Histology was adenocarcinoma in 69% of patients. Pretreatment positron emission tomography/computed tomography staging was performed for 90% of patients, and preoperative chemotherapy was administered in 23%. The rate of R0 resection was 96%. Forty-one patients (58%) received PORT and the median PORT dose was 50 Gy (range, 41.4-60 Gy). The median follow-up time for living patients was 5.0 years. Five-year OS for all patients was 66%. OS at 5 years for patients who received PORT compared with patients who did not receive PORT was 71% versus 60%, respectively (hazard ratio [HR], 0.61; 95% CI, 0.30-1.44; P = .28). LRC at 5 years for patients who received PORT compared with patients who did not receive PORT was 89% versus 76%, respectively (HR, 0.44; 95% CI, 0.13-1.45; P = .17). Factors associated with decreased LRC were male sex ( P = .011) and primary tumor (pT) stage (pT3/4 vs. pT1/2, P = .006). Metastasis-free survival at 5 years for patients who received PORT compared with those who did not receive PORT was 62% versus 63%, respectively (HR, 1.07; 95% CI, 0.51-2.40; P = .86)., Conclusions: In this modern series of patients with resected stage III (N2) NSCLC, patients who received PORT had higher rates of OS and LRC, but these differences were not statistically significant.