Multicentric Assessment of Safety and Efficacy of Combinatorial Adjuvant Brain Metastasis Treatment by Intraoperative Radiation Therapy and Immunotherapy.

PURPOSE: After surgical resection of brain metastases (BMs), intraoperative radiation therapy (IORT) provides a promising alternative to adjuvant external beam radiation therapy by enabling superior organ-at-risk preservation, reduction of in-hospital times, and timely admission to subsequent systemic treatments, which increasingly comprise novel targeted immunotherapeutic approaches. We sought to assess the safety and efficacy of IORT in combination with immune checkpoint inhibitors (ICIs) and other targeted therapies (TTs). METHODS AND MATERIALS: In a multicentric approach incorporating individual patient data from 6 international IORT centers, all patients with BMs undergoing IORT were retrospectively assessed for combinatorial treatment with ICIs/TTs and evaluated for toxicity and cumulative rates, including wound dehiscence, radiation necrosis, leptomeningeal spread, local control, distant brain progression (DBP), and estimated overall survival. RESULTS: In total, 103 lesions with a median diameter of 34 mm receiving IORT combined with immunomodulatory systemic treatment or other TTs were included. The median follow-up was 13.2 (range, 1.2-102.4) months, and the median IORT dose was 25 (range, 18-30) Gy prescribed to the applicator surface. There was 1 grade 3 adverse event related to IORT recorded (2.2%). A 4.9% cumulative radiation necrosis rate was observed. The 1-year local control rate was 98.0%, and the 1-year DBP-free survival rate was 60.0%. Median time to DBP was 5.5 (range, 1.0-18.5) months in the subgroup of patients experiencing DBP, and the cumulative leptomeningeal spread rate was 4.9%. The median estimated overall survival was 26 (range, 1.2 to not reached) months with a 1-year survival rate of 74.0%. Early initiation of immunotherapy/TTs was associated with a nonsignificant trend toward improved DBP rate and overall survival. CONCLUSIONS: The combination of ICIs/TTs with IORT for resected BMs does not seem to increase toxicity and yields encouraging local control outcomes in the difficult-to-treat subgroup of larger BMs. Time gaps between surgery and systemic treatment could be shortened or avoided. The definitive role of IORT in local control after BM resection will be defined in a prospective trial.

Pharmaceutical management of acute radiation dermatitis in the German speaking radiation oncology community.

BACKGROUND: Radiation dermatitis (RD) remains the most common side effect in radiation therapy (RT) with various pharmaceutical options available for prevention and treatment. We sought to determine pharmaceutical management patterns of radiation dermatitis among radiation oncology professionals. METHODS: We conducted a survey on RD among the German-speaking community of radiation oncologists inquiring for their opinion on preventive and therapeutic pharmaceutical approaches for acute RD. RESULTS: 244 health professionals participated. Dexpanthenol lotion is the agent most widely used both for prevention (53.0%) and treatment (76.9%) of RD, followed by urea (29.8%) for prevention and corticosteroids (46.9%) for treatment. A wide range of substances is used by participants, though the overall experience with them is rather limited. 32.5% of participants do generally not recommend any preventative treatment. 53.4% of participants recommend alternative medicine for RD management. While seldomly used, corticosteroids were considered most effective in RD therapy, followed by dexpanthenol and low-level laser therapy. A majority of participants prefers moist over dry treatment of moist desquamation and 43.8% prescribe antiseptics. CONCLUSIONS: Pharmaceutical management of RD in the German-speaking radiation oncology community remains controversial, inconsistent, and partially not supported by evidence-based medicine. Stronger evidence level and interdisciplinary consensus is required amongst practitioners to improve these care patterns.

Safety and efficacy of helical tomotherapy following lung-sparing surgery in locally advanced malignant pleural mesothelioma.

PURPOSE: To assess the value of radiation therapy (RT) with helical tomotherapy (HT) in the management of locally advanced malignant pleural mesothelioma (MPM) receiving no or lung-sparing surgery. METHODS: Consecutive MPM cases not undergoing extrapleural pneumonectomy and receiving intensity-modulated (IM) HT were retrospectively evaluated for local control, distant control, progression-free survival (PFS), and overall survival (OS). Impact of age, systemic treatment, RT dose, and recurrence patterns was analyzed by univariate and multivariate analysis. As a secondary endpoint, reported toxicity was assessed. RESULTS: A total of 34 localized MPM cases undergoing IMHT were identified, of which follow-up data were available for 31 patients. Grade 3 side effects were experienced by 26.7% of patients and there were no grade 4 or 5 events observed. Median PFS was 19 months. Median OS was 20 months and the rates for 1­ and 2­year OS were 86.2 and 41.4%, respectively. OS was significantly superior for patients receiving adjuvant chemotherapy (p = 0.008). CONCLUSION: IMHT of locally advanced MPM after lung-sparing surgery is safe and feasible, resulting in satisfactory local control and survival. Adjuvant chemotherapy significantly improves OS. Randomized clinical trials incorporating modern RT techniques as a component of trimodal treatment are warranted to establish an evidence-based standard of care pattern for locally advanced MPM.

Intraoperative or postoperative stereotactic radiotherapy for brain metastases: time to systemic treatment onset and other patient-relevant outcomes.

PURPOSE: Intraoperative radiotherapy (IORT) has become a viable treatment option for resectable brain metastases (BMs). As data on local control and radiation necrosis rates are maturing, we focus on meaningful secondary endpoints such as time to next treatment (TTNT), duration of postoperative corticosteroid treatment, and in-hospital time. METHODS: Patients prospectively recruited within an IORT study registry between November 2020 and June 2023 were compared with consecutive patients receiving adjuvant stereotactic radiotherapy (SRT) of the resection cavity within the same time frame. TTNT was defined as the number of days between BM resection and start of the next extracranial oncological therapy (systemic treatment, surgery, or radiotherapy) for each of the groups. RESULTS: Of 95 BM patients screened, IORT was feasible in 84 cases (88%) and ultimately performed in 64 (67%). The control collective consisted of 53 SRT patients. There were no relevant differences in clinical baseline features. Mean TTNT (range) was 36 (9 - 94) days for IORT patients versus 52 (11 - 126) days for SRT patients (p = 0.01). Mean duration of postoperative corticosteroid treatment was similar (8 days; p = 0.83), as was mean postoperative in-hospital time (11 versus 12 days; p = 0.97). Mean total in-hospital time for BM treatment (in- and out-patient days) was 11 days for IORT versus 19 days for SRT patients (p < 0.001). CONCLUSION: IORT for BMs results in faster completion of interdisciplinary treatment when compared to adjuvant SRT, without increasing corticosteroid intake or prolonging in-hospital times. A randomised phase III trial will determine the clinical effects of shorter TTNT.

Outcome assessment of intraoperative radiotherapy for brain metastases: results of a prospective observational study with comparative matched-pair analysis.

PURPOSE: Intraoperative radiation therapy (IORT) is an emerging alternative to adjuvant stereotactic external beam radiation therapy (EBRT) following resection of brain metastases (BM). Advantages of IORT include an instant prevention of tumor regrowth, optimized dose-sparing of adjacent healthy brain tissue and immediate completion of BM treatment, allowing an earlier admission to subsequent systemic treatments. However, prospective outcome data are limited. We sought to assess long-term outcome of IORT in comparison to EBRT. METHODS: A total of 35 consecutive patients, prospectively recruited within a study registry, who received IORT following BM resection at a single neuro-oncological center were evaluated for radiation necrosis (RN) incidence rates, local control rates (LCR), distant brain progression (DBP) and overall survival (OS) as long-term outcome parameters. The 1 year-estimated OS and survival rates were compared in a balanced comparative matched-pair analysis to those of our institutional database, encompassing 388 consecutive patients who underwent adjuvant EBRT after BM resection. RESULTS: The median IORT dose was 30 Gy prescribed to the applicator surface. A 2.9% RN rate was observed. The estimated 1 year-LCR was 97.1% and the 1 year-DBP-free survival 73.5%. Median time to DBP was 6.4 (range 1.7-24) months in the subgroup of patients experiencing intracerebral progression. The median OS was 17.5 (0.5-not reached) months with a 1 year-survival rate of 61.3%, which did not not significantly differ from the comparative cohort (p = 0.55 and p = 0.82, respectively). CONCLUSION: IORT is a safe and effective fast-track approach following BM resection, with comparable long-term outcomes as adjuvant EBRT.

Risk assessment, surveillance, and nonpharmaceutical prevention of acute radiation dermatitis: results of a multicentric survey among the German-speaking radiation oncology community.

PURPOSE: Radiation dermatitis (RD) represents one of the most frequent side effects in radiotherapy (RT). Despite technical progress, mild and moderate RD still affects major subsets of patients and identification and management of patients with a high risk of severe RD is essential. We sought to characterize surveillance and nonpharmaceutical preventive management of RD in German-speaking hospitals and private centers. METHODS: We conducted a survey on RD among German-speaking radiation oncologists inquiring for their evaluation of risk factors, assessment methods, and nonpharmaceutical preventive management of RD. RESULTS: A total of 244 health professionals from public and private institutions in Germany, Austria, and Switzerland participated in the survey. RT-dependent factors were deemed most relevant for RD onset followed by lifestyle factors, emphasizing the impact of treatment conceptualization and patient education. While a broad majority of 92.8% assess RD at least once during RT, 59.0% of participants report RD at least partially arbitrarily and 17.4% stated to classify RD severity solely arbitrarily. 83.7% of all participants were unaware of patient-reported outcomes (PROs). Consensus exists on some lifestyle recommendations like avoidance of sun exposure (98.7%), hot baths (95.1%), and mechanical irritation (91.8%) under RT, while deodorant use (63.4% not at all, 22.1% with restrictions) or application of skin lotion (15.1% disapproval) remain controversial and are not recommended by guidelines or evidence-based practices. CONCLUSION: Identification of patients at an increased risk of RD and subsequent implementation of adequate preventive measures remain relevant and challenging aspects of clinical routines. Consensus exists on several risk factors and nonpharmaceutical prevention recommendations, while RT-dependent risk factors, e.g., the fractionation scheme, or hygienic measures like deodorant use remain controversial. Surveillance is widely lacking methodology and objectivity. Intensifying outreach in the radiation oncology community is needed to improve practice patterns.

Five-Fraction Stereotactic Radiotherapy for Brain Metastases-A Retrospective Analysis.

PURPOSE: To determine the safety and outcome profile of five-fraction stereotactic radiotherapy (FSRT) for brain metastases (BM), either as a definitive or adjuvant treatment. METHODS: We assessed clinical data of patients receiving five fractions of 7 Gy each (cumulative physical dose of 35 Gy) to BM or surgical cavities. The primary endpoints were toxicity and radiation necrosis (RN) rates. Secondary endpoints were 1-year cumulative local control rate (LCR) and estimated overall survival (OS). RESULTS: A total of 36 eligible patients receiving FSRT to a total of 49 targets were identified and included. The median follow up was 9 (1.1-56.2) months. The median age was 64.5 (34-92) years, the median ECOG score was 1, and the median Diagnostic-Specific Graded Prognostic Assessment (DS-GPA) score was 2. Treatment was well tolerated and there were no grade 3 adverse events or higher. The overall RN rate was 14.3% and the median time to RN was 12.9 (1.8-23.8) months. RN occurrence was associated with immunotherapy, young age (≤45 years), and large PTV. The cumulative 1-year local control rate was 83.1% and the estimated median local progression free-survival was 18.8 months. The estimated median overall survival was 11 (1.1-56.2) months and significantly superior in those patients presenting with RN. CONCLUSIONS: FSRT with 5 × 7 Gy represents a feasible, safe, and efficient fast track approach of intensified FSRT with acceptable LC and comparable RN rates for both the adjuvant and definitive RT settings.

Peripheral blood kinetics following total body irradiation and allogeneic hematopoietic stem cell transplantation: Timing matters.

Total body irradiation (TBI) remains an important component in many conditioning regimens before allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because of its frequent toxicity, patient selection is crucial, making it of interest to identify factors improving engraftment. In this retrospective single center analysis, the characteristics of 48 adult such patients were studied. Mean overall survival (OS) was 22.2 months after allo-HSCT. Interestingly, people with an interval ≥3 days between TBI completion and allo-HSCT showed improved OS, when compared to a shorter interval (p = 0.10). Peripheral blood kinetics after successful engraftment also differed, with a longer interval resulting in a higher platelet count and lower leukocyte and neutrophil (p < 0.05) count. These data suggest that the exact timing of TBI before allo-HSCT might directly impact a patient's survival and could help single out those at higher risk of graft failure who might benefit from an altered conditioning regimen.

Chasing a rarity: a retrospective single-center evaluation of prognostic factors in primary gliosarcoma.

BACKGROUND AND PURPOSE: Primary gliosarcoma (GS) is a rare variant of IDH-wildtype glioblastoma multiforme. We performed a single-center analysis to identify prognostic factors. PATIENTS AND METHODS: We analyzed the records of 26 patients newly diagnosed with primary WHO grade IV GS. Factors of interest were clinical and treatment data, as well as molecular markers, time to recurrence, and time to death. RESULTS: Median follow-up was 9 months (range 5-21 months). Gross total resection did not lead to improved survival, most likely due to the relatively small sample size. Low symptom burden at the time of diagnosis was associated with longer PFS (P = 0.023) and OS (P = 0.018). Median OS in the entire cohort was 12 months. Neither MGMT promoter hypermethylation nor adjuvant temozolomide therapy influenced survival, consistent with some previous reports. CONCLUSION: In this retrospective study, patients exhibiting low symptom burden at diagnosis showed improved survival. None of the other factors analyzed were associated with an altered outcome.