Citations

The analytical microdosimetric function (AMF) implemented in the Monte Carlo code PHITS is a unique tool that bridges the gap between macro- and microscopic scales of radiation interactions, enabling accurate microdosimetric calculations over macroscopic bodies. The original AMF was published in 2006, based on the results of track structure calculations. Recently, a newer version of the AMF was proposed, incorporating an improved description of the energy loss at the microscopic scale. This study compares the older and the newer AMFs in computing microdosimetric probability distributions, mean values, and the relative biological effectiveness (RBE). To this end, 16000 microdosimetric lineal energy probability density distributions were simulated with PHITS for ions from 1H to 238U over a broad energy range (1–1000 MeV/n). The newer AMF was found to offer superior performance, particularly for very heavy ions, producing results that align more closely with published in vitro clonogenic survival experiments. These findings suggest that the updated AMF provides a more reliable tool for microdosimetric calculations and RBE modeling, essential for ion radiation therapy and space radiation protection.

Abstract T-cell/histiocyte–rich large B-cell lymphoma (THRLBCL) is a rare histologic variant of LBCL. Limited data regarding CD19–directed chimeric antigen receptor T-cell (CART) therapy in relapsed/refractory (R/R) THRLBCL suggest poor efficacy. We investigated CART outcomes for R/R THRLBCL through the Center for International Blood and Marrow Transplant Research registry. A total of 58 adult patients with R/R THRLBCL who received commercial CD19-CART therapy between 2018 and 2022 were identified. Most patients (67%) had early relapse of disease (45% primary refractory) with a median of 3 (range, 1-7) prior therapies and were treated with axicabtagene ciloleucel (69%). At median follow-up of 23 months after CART therapy, 2-year overall and progression-free survival were 42% (95% confidence interval [CI], 27-57) and 29% (95% CI, 17-43), respectively. In univariable analysis, poor performance status before CART therapy was associated with higher mortality (hazard ratio, 2.35; 95%CI, 1.02-5.5). The 2-year cumulative incidences of relapse/progression and nonrelapse mortality were 69% and 2%, respectively. Grade ≥3 cytokine release syndrome and immune effector cell–associated neurologic syndrome occurred in 7% and 15% of patients, respectively. In this largest analysis of CD19-CART therapy for R/R THRLBCL, ∼30% of patients were alive and progression free 2 years after CART therapy. Despite a high incidence of progression (69% at 2 years), these results suggest a subset of patients with R/R THRLBCL may have durable responses with CARTs.

AbstractBackgroundThis was a single‐arm, phase 2 clinical trial of Bavarian Nordic (BN)‐Brachyury vaccine plus radiotherapy (RT) designed to determine the objective response rate (ORR), progression‐free survival (PFS), and safety of the combination in chordoma.MethodsA total of 29 adult patients with advanced chordoma were treated with two subcutaneous priming vaccine doses of modified vaccinia Ankara‐Bavarian Nordic (MVA‐BN)‐Brachyury and one vaccine dose of fowlpox virus (FPV)‐Brachyury before RT. After RT, booster vaccinations were given with FPV‐Brachyury every 4 weeks for 4 doses, then every 12 weeks (week 110). A minimum RT dose of >8 Gy in one fraction for each target was required. Response was evaluated by modified Response Evaluation Criteria in Solid Tumors 1.1 (mRECIST), where only radiated lesions were considered targets, and by standard RECIST 1.1 in a subset of patients.ResultsTwo of 26 evaluable patients experienced durable partial response (PR) (ORR of 7.7%; 90% confidence interval [CI], 2.6–20.8]) by mRECIST 1.1. A total of 21 patients (80.8%; 90% CI, 65.4–90.3) had stable disease, and three patients (11.5%; 90% CI, 4.7–25.6) had progressive disease as best response per mRECIST 1.1. Median PFS was not reached during the study.ConclusionsThis trial confirms the safety of BN‐Brachyury and RT. Although the study did not meet the predefined study goal of four responses in 29 patients, we did observe two PRs and a PFS of greater than 2 years. For a vaccine‐based study in chordoma, an ultra‐rare disease where response rates are low, a randomized study or novel trial designs may be required to confirm activity.

AbstractBackgroundThe management of early breast cancer (BC) has witnessed an uprise in the use of neoadjuvant therapy and a remarkable reshaping of the systemic therapy postneoadjuvant treatment in the last few years, with the evolution of many controversial clinical situations that require consensus.MethodsDuring the 14th Breast‐Gynecological and Immuno‐Oncology International Cancer Conference held in Egypt in 2022, a panel of 44 BC experts from 13 countries voted on statements concerning debatable challenges in the neo/adjuvant treatment setting. The recommendations were subsequently updated based on the most recent data emerging. A modified Delphi approach was used to develop this consensus. A consensus was achieved when ≥75% of voters selected an answer.Results and ConclusionsThe consensus recommendations addressed different escalation and de‐escalation strategies in the setting of neoadjuvant therapy for early BC. The recommendations recapitulate the available clinical evidence and expert opinion to individualize patient management and optimize therapy outcomes. Consensus was reached in 63% of the statements (52/83), and the rationale behind each statement was clarified.

Aim: The objective of this study was to compare adverse event (AE) management costs for fruquintinib, regorafenib, trifluridine/tipiracil (T/T) and trifluridine/tipiracil+bevacizumab (T/T+bev) for patients with metastatic colorectal cancer (mCRC) previously treated with at least two prior lines of therapy from the US commercial and Medicare payer perspectives. Materials & methods: A cost-consequence model was developed to calculate the per-patient and per-patient-per-month (PPPM) AE costs using rates of grade 3/4 AEs with incidence ≥5% in clinical trials, event-specific management costs and duration treatment. Anchored comparisons of AE costs were calculated using a difference-in-differences approach with best supportive care (BSC) as a common reference. AE rates and treatment duration were obtained from clinical trials: FRESCO and FRESCO-2 (fruquintinib), RECOURSE (T/T), CORRECT (regorafenib) and SUNLIGHT (T/T, T/T+bev). AE management costs for the commercial and Medicare perspectives were obtained from publicly available sources. Results: From the commercial perspective, the AE costs (presented as per-patient, PPPM) were: $4015, $1091 for fruquintinib (FRESCO); $4253, $1390 for fruquintinib (FRESCO-2); $17,110, $11,104 for T/T (RECOURSE); $9851, $4691 for T/T (SUNLIGHT); $8199, $4823 for regorafenib; and $11,620, $2324 for T/T+bev. These results were consistent in anchored comparisons: the difference-in-difference for fruquintinib based on FRESCO was -$1929 versus regorafenib and -$11,427 versus T/T; for fruquintinib based on FRESCO-2 was -$2257 versus regorafenib and -$11,756 versus T/T. Across all analyses, results were consistent from the Medicare perspective. Conclusion: Fruquintinib was associated with lower AE management costs compared with regorafenib, T/T and T/T+bev for patients with previously treated mCRC. This evidence has direct implications for treatment, formulary and pathways decision-making in this patient population.

Abstract Adrenal cysts are a rare benign adrenal pathology. Although the majority of adrenal cysts are asymptomatic, large cysts may present with debilitating symptoms of mass effect. Surgical adrenalectomy or cyst fenestration has been the primary mode of management for such symptomatic cysts, but these interventions can be associated with excessive morbidity, particularly when considered in the context of benign disease. Here, we present a case of a 34-year-old female with a longstanding, growing, benign left adrenal cyst associated with nonspecific abdominal symptoms. After multidisciplinary discussion, the patient was managed with primary ultrasound/fluoroscopic guided percutaneous sclerotherapy of her adrenal cyst. This technique achieved complete cyst resolution that was durable on 7-month follow-up and was associated with significant improvement of the patient's symptoms. This case illustrates the potential for primary percutaneous sclerotherapy for primary management of benign adrenal cysts.

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IntroductionCervical spine defects result in spinal instability, putting the spinal cord and vertebral arteries at risk of damage and possibly devastating neurological injuries. The fibula free flap can span the spinal defects for stability. There is a paucity of literature on this technique.MethodMulti‐institutional retrospective case series reviewing patients who underwent cervical spine reconstruction with a fibula free flap. Patient demographic information, comorbidities, characteristics of cervical spine defects, and free flap complications were collected.ResultsA total of 1187 fibula free flaps across 10 different institutions were reviewed. Thirteen patients (1.09%) underwent cervical spine reconstruction with a fibula free flap. Average age was 52.3 years old with an age range of 12–79 years. There were six males (46.1%) and seven females (53.8%). The most common defect etiology was infection (n = 6, 46.1%). Most commonly involved cervical spine level of the defect was C5 (n = 10) followed by C6 (n = 9) and C4 (n = 8). The majority of reconstructed defects spanned three or more cervical levels, (n = 9, 69.2%). Facial artery was the most common arterial anastomosis (n = 8). Eight patients (61.5%) required a tracheostomy during their postoperative course. None of the patients had symptomatic or radiographic nonunion.ConclusionThis case series demonstrates that a vascularized fibula flap is a potential reconstructive option for cervical spine defects, especially in defects greater than three cervical levels, in the setting of infection, and previously radiated patients.Level of Evidence4 Laryngoscope, 134:4923–4928, 2024