Incidence of hippocampal and perihippocampal brain metastases and impact on hippocampal-avoiding radiotherapy: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: In patients requiring prophylactic cranial irradiation (PCI) or whole-brain radiotherapy (WBRT) for brain metastases (BMs), hippocampal avoidance (HA) has been shown to preserve neurocognitive function and quality of life. Here, we aim to estimate the incidence of hippocampal and perihippocampal BMs and the subsequent risk of local undertreatment in patients undergoing hippocampal sparing radiotherapy. MATERIALS AND METHODS: MEDLINE, Embase, and Scopus were searched with the terms "Hippocampus", "Brain Neoplasms", and related terms. Trials reporting on the incidence of hippocampal and/or perihippocampal BMs or hippocampal failure rate after PCI or WBRT were included. RESULTS: Forty records were included, encompassing a total of 5,374 patients with over 32,570 BMs. Most trials employed a 5 mm margin to define the HA zone. In trials reporting on BM incidence, 4.4 % (range 0 - 27 %) and 9.2 % (3 - 41 %) of patients had hippocampal and perihippocampal BMs, respectively. The most common risk factor for hippocampal BMs was the total number of BMs. The reported failure rate within the HA zone after HA-PCI or HA-WBRT was 4.5 % (0 - 13 %), salvageable with radiosurgery in most cases. SCLC histology was not associated with a higher risk of hippocampal failure (OR = 2.49; p = 0.23). In trials comparing with a conventional (non-HA) PCI or WBRT group, HA did not increase the hippocampal failure rate (OR = 1.90; p = 0.17). CONCLUSION: The overall incidence of hippocampal and perihippocampal BMs is considerably low, with a subsequent low risk of local undertreatment following HA-PCI or HA-WBRT. In patients without involvement, the hippocampus should be spared to preserve neurocognitive function and quality of life.

Image Guided Intraoperative Radiation Therapy After Surgical Resection of Brain Metastases: A First In-Human Feasibility Report.

Purpose: A correct placement of the applicator during intraoperative radiation therapy for brain metastasis is of paramount importance, to deliver a precise and safe treatment. The applicator-to-surface contact assessment cannot be performed under direct observation because the applicator itself limits the visual range. No image guided verification is currently performed intracranially. We hypothesize that image guided intraoperative radiation therapy would assure a more precise delivery in the target area. We describe our workflow in a first in-human experience. Methods and Materials: Phantom-based measurements were performed to reach the best cone beam computed tomography imaging quality possible. Once defined, a clinical feasibility study was initiated. An in-room cone beam computed tomography device is used to acquire intraoperative images after placing the applicator. Repositioning the applicator is thereafter discussed with the surgeon, according to the imaging outcomes, if required. Results: An optimal image quality was achieved with 120-kV voltage, 20-mA current, and a tube current time product of 150 mAs. An additional 0.51 mSv patient exposure was calculated for the entire procedure. The wide dynamic range (-600 HU to +600 HU) of cone beam computed tomography and a 27 HU mean computed tomography values difference between brain tissue and spherical applicator allows distinguishing both structures. In this first in-human experience, the applicator was repositioned after evidencing air gaps, assuring full applicator-to-surface contact. Conclusions: This first in-human procedure confirmed the feasibility of kilovoltage image guided intraoperative radiation therapy in a neurosurgical setting. A prospective study has been initiated and will provide further dosimetric details.

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.

Artificial Intelligence-Based Autosegmentation: Advantages in Delineation, Absorbed Dose-Distribution, and Logistics.

Purpose: The study's purpose was to compare the performance of artificial intelligence (AI) in auto-contouring compared with a human practitioner in terms of precision, differences in dose distribution, and time consumption. Methods and Materials: Datasets of previously irradiated patients in 3 different segments (head and neck, breast, and prostate cancer) were retrospectively collected. An experienced radiation oncologist (MD) performed organs-at-risk (OARs) and standard clinical target volume delineations as baseline structures for comparison. AI-based autocontours were generated in 2 additional CT copies; therefore, 3 groups were assessed: MD alone, AI alone, and AI plus MD corrections (AI+C). Differences in Dice similarity coefficient (DSC) and person-hour burden were assessed. Furthermore, changes in clinically relevant dose-volume parameters were evaluated and compared. Results: Seventy-five previously treated cases were collected (25 per segment) for the analysis. Compared with MD contours, the mean DSC scores were higher than 0.7 for 74% and 80% of AI and AI+C, respectively. After corrections, 17.1% structures presented DSC score deviations higher than 0.1 and 10.4% dose-volume parameters significantly changed in AI-contoured structures. The time consumption assessment yielded mean person-hour reductions of 68%, 51%, and 71% for breast, prostate, and head and neck cancer, respectively. Conclusions: In great extent, AI yielded clinically acceptable OARs and certain clinical target volumes in the explored anatomic segments. Sparse correction and assessment requirements place AI+C as a standard workflow. Minimal clinically relevant differences in OAR exposure were identified. A substantial amount of person-hours could be repurposed with this technology.

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.

Do Barrier Films Impact Long-Term Skin Toxicity following Whole-Breast Irradiation? Objective Follow-Up of Two Randomised Trials.

Purpose: Hydrofilm, a polyurethane-based barrier film, can be used to prevent acute radiation dermatitis (RD) in adjuvant whole-breast irradiation (WBI) for breast cancer. This cost-effective prophylactic measure is currently being recommended to a growing number of patients, yet long-term safety data and its impact on late radiation-induced skin toxicity such as pigmentation changes and fibrosis have not been investigated. Methods: We objectively evaluated patients who were previously enrolled in either of two intrapatient-randomised (lateral versus medial breast halve) controlled trials on the use of Hydrofilm for RD prevention (DRKS00029665; registered on 19 July 2022). Results: Sixty-two patients (47.7% of the initial combined sample size) provided consent for this post-hoc examination, with a median follow-up time (range) of 58 (37-73) months. Following WBI, there was a significant increase in yellow skin tones of the entire breast when compared to baseline measurements before WBI (p < 0.001) and a significant increase of cutis, subcutis, and oedema thickness (p < 0.001, p < 0.001, and p = 0.004, respectively). At follow-up, there were no significant differences in either pigmentation changes or skin fibrosis between the Hydrofilm and standard of care breast halves. Conclusion: These data suggest that Hydrofilm can be safely used in the context of acute RD prevention, without affecting late side effects, supporting its widespread use.

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.

Optimized Conformal Total Body Irradiation with VMAT Using a Linear-Accelerator-Based Radiosurgery Treatment System in Comparison to the Golden Standard Helical TomoTherapy.

Modern irradiation techniques for optimized conformal TBI can be realized by Helical Tomotherapy (HT) or Volumetric Modulated Arc Therapy (VMAT), depending on the availability of suitable specialized equipment. In this dosimetric planning study, we compared both modalities and addressed the question of whether VMAT with small field sizes is also suitable as a backup in case of HT equipment malfunctions. For this purpose, we retrospectively used planning computed tomography (CT) data from 10 patients treated with HT with a total dose of 8 Gy (n = 5) or 12 Gy (n = 5) for treatment planning for VMAT with a small field size (36 × 22 cm). The target volume coverage, dose homogeneity at target volume, and dose reduction in organs at risk (OAR) (lungs, kidneys, lenses) were analyzed and compared. One patient was irradiated with both modalities due to a device failure of the HT equipment during the study, which facilitated a comparison in a real clinical setting. The findings indicate that in addition to a higher mean dose to the lenses in the 12 Gy group for VMAT and a better dose homogeneity in the target volume for HT, comparably good and adequate target dose coverage and dose reduction in the other OAR could be achieved for both modalities, with significantly longer treatment times for VMAT. In conclusion, after appropriate optimization of the treatment times, VMAT using linear accelerator radiosurgery technology can be used both as a backup in addition to HT and in clinical routines to perform optimized conformal TBI.

Opportunities and Alternatives of Modern Radiation Oncology and Surgery for the Management of Resectable Brain Metastases.

Postsurgical radiotherapy (RT) has been early proven to prevent local tumor recurrence, initially performed with whole brain RT (WBRT). Subsequent to disadvantageous cognitive sequalae for the patient and the broad distribution of modern linear accelerators, focal irradiation of the tumor has omitted WBRT in most cases. In many studies, the effectiveness of local RT of the resection cavity, either as single-fraction stereotactic radiosurgery (SRS) or hypo-fractionated stereotactic RT (hFSRT), has been demonstrated to be effective and safe. However, whereas prospective high-level incidence is still lacking on which dose and fractionation scheme is the best choice for the patient, further ablative techniques have come into play. Neoadjuvant SRS (N-SRS) prior to resection combines straightforward target delineation with an accelerated post-surgical phase, allowing an earlier start of systemic treatment or rehabilitation as indicated. In addition, low-energy intraoperative RT (IORT) on the surgical bed has been introduced as another alternative to external beam RT, offering sterilization of the cavity surface with steep dose gradients towards the healthy brain. This consensus paper summarizes current local treatment strategies for resectable brain metastases regarding available data and patient-centered decision-making.

Objective, Clinician- and Patient-Reported Evaluation of Late Toxicity Following Adjuvant Radiation for Early Breast Cancer: Long-Term Follow-Up Results of a Randomised Series.

Background and Purpose: This study aimed to differentially assess the frequency and severity of late radiation-induced toxicity following adjuvant whole-breast irradiation for early breast cancer with conventional fractionation (CF) and moderate hypofractionation (mHF). Materials and Methods: Patients recruited in a previous randomised controlled trial comparing acute toxicity between CF and mHF without disease recurrence were included in a post hoc analysis. Spectrophotometric and ultrasonographic examinations were performed for an objective evaluation and subsequent comparison of long-term skin toxicity. Furthermore, patient- and clinician-reported outcomes were recorded. Results: Sixty-four patients with a median age of 58 (37-81) years were included. The median follow-up was 57 (37-73) months. A total of 55% underwent CF and 45% mHF. A total of 52% received a sequential boost to the tumour bed. A significant decrease in mean L* (p = 0.011) and an increase in a* (p = 0.040) and b* values (p < 0.001) were observed, indicating hyperpigmentation. In comparison with the non-irradiated breast, there was a significant increase in both cutis (+14%; p < 0.001) and subcutis (+17%; p = 0.011) thickness, significantly more pronounced in CF patients (p = 0.049). In CF patients only, a sequential boost significantly increased the local cutis thickness and oedema compared to non-boost regions in the same breast (p = 0.001 and p < 0.001, respectively). Conclusions: mHF objectively resulted in reduced long-term skin toxicity compared to CF. A sequential boost increased the local fibrosis rate in CF, but not in mHF. This might explain the subjectively reported better cosmetic outcomes in patients receiving mHF and reinforces the rationale for favouring mHF as the standard of care.

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.

Barrier films for the prevention of acute radiation dermatitis in breast cancer: A systematic review and meta-analysis of randomised controlled trials.

PURPOSE: Radiation dermatitis (RD) is the most common side effect of adjuvant whole-breast or chest wall irradiation, majorly impacting quality of life in numerous patients. The use of barrier films (polyurethane dressings such as Hydrofilm® and Mepitel® film remaining on the skin for the duration of the radiation treatment) has been investigated as a prophylactic measure in several prospective trials. Here, we critically appraise the available evidence behind preventive barrier film application in the context of breast cancer treatment. METHODS: International literature was reviewed and high-quality randomised controlled trials (RCTs) were included in this meta-analysis. RESULTS: The results of 5 RCTs (663 patients; >90% Caucasian) were analysed. Overall, barrier films lead to improved clinician- and patient-reported outcomes: fewer grade ≥2 RD (11% vs. 42%; OR = 0.16; p < 0.001) and moist desquamation (2% vs. 16%; OR = 0.12; p = 0.006), as well as less patient-reported pain (standardised mean difference [SMD] -0.51; p < 0.001), itching (SMD -0.52; p = 0.001), burning (SMD -0.41; p = 0.011), and limitations in daily activities (SMD -0.20; p = 0.007). Furthermore, barrier films have a high acceptance rate among patients, as well as a favourable cost-benefit ratio. Possible side effects due to its application are mild and mostly self-limiting. Overall, there was a lack of information on the radiation treatment techniques used. CONCLUSION: The evidence presented in this meta-analysis suggests that barrier films are an excellent tool in the prevention of RD among Caucasian patients receiving whole-breast or chest wall irradiation. Its use should therefore be considered routinely in these patients.

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.

Long-term characterization of MRI-morphologic alterations after active motion-compensated liver SBRT: a multi-institutional pooled analysis.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an effective therapeutic approach in patients with liver metastases. However, long-term changes in hepatic normal tissue have to be taken into account in multimodal treatment regimes. Magnetic-resonance-imaging (MRI) based morphologic liver alterations (MMA) after liver SBRT have been analyzed longitudinally. MATERIAL AND METHODS: 57 patients treated with gantry-based or robotic-based SBRT of 69 treatment volumes of liver metastases, who had long-term follow-up (FU) ≥6 months were included in this retrospective analysis. Post-SBRT MMAs were contoured on each contrast-enhanced-T1-weighted (T1w) MRI-sequence. Morphologic/volumetric data of the liver and MMAs were evaluated longitudinally, including the dependency on treatment-related factors of the planning target volume (PTV) and liver. RESULTS: The median FU time was 1 year [6-48 months]. 66 of 69 treatment volumes developed MMAs (mean 143.8 ± 135.1 ccm at first appearance). 31.8% of MMAs resolved completely during FU. Of the persisting MMAs 82.2%/13.3% decreased/increased in size until last available FU. Morphological characterization of the MMAs at first appearance included 75% hypointense and 25% hyperintense T1w-MRI-based appearances. Hypointense as compared to hyperintense appearance was significantly associated with a higher mean liver dose EQD2α/ß=3 Gy (p = 0.0212) and non-significantly greater MMA size. Variance analysis demonstrated a significant reduction of MMA and total liver volume after SBRT (p < 0.0001). The volume reduction decelerated longitudinally for both MMA (p < 0.0001) and liver size (p = 0.0033). Radiation doses (PTV-BEDα/ß=3 Gy and 10 Gy) were not significantly associated with MMA volume reduction. SBRT of liver metastases with mean liver dose EQD2α/ß=3 Gy > 18 Gy were characterized by greater MMA volumes (p = 0.0826) and steeper MMA reduction gradients during FU than those with EQD2α/ß=3 Gy ≤ 18 Gy (p < 0.0001). CONCLUSION: Radiogenic MMAs either completely resolve or usually decrease in volume with pronounced reduction during short-term FU. This course was independent of the MMA's morphological appearance. Further, increased mean liver dose was associated with greater MMA size and a greater gradient of MMA size reduction during FU.

Whole body irradiation with intensity-modulated helical tomotherapy prior to haematopoietic stem cell transplantation: analysis of organs at risk by dose and its effect on blood kinetics.

BACKGROUND: Intensity-modulated helical tomotherapy (HT) is a promising technique in preparation for bone marrow transplantation. Nevertheless, radiation-sensitive organs can be substantially compromised due to suboptimal delivery techniques of total body irradiation (TBI). To reduce the potential burden of radiation toxicity to organs at risk (OAR), high-quality coverage and homogeneity are essential. We investigated dosimetric data from kidney, lung and thorax, liver, and spleen in relation to peripheral blood kinetics. To further advance intensity-modulated total body irradiation (TBI), the potential for dose reduction to lung and kidney was considered in the analysis. PATIENTS AND METHODS: 46 patients undergoing TBI were included in this analysis, partially divided into dose groups (2, 4, 8, and 12 Gy). HT was performed using a rotating gantry to ensuring optimal reduction of radiation to the lungs and kidneys and to provide optimal coverage of other OAR. Common dosimetric parameters, such as D05, D95, and D50, were calculated and analysed. Leukocytes, neutrophils, platelets, creatinine, GFR, haemoglobin, overall survival, and graft-versus-host disease were related to the dosimetric evaluation using statistical tests. RESULTS: The mean D95 of the lung is 48.23%, less than half the prescribed and unreduced dose. The D95 of the chest is almost twice as high at 84.95%. Overall liver coverage values ranged from 96.79% for D95 to 107% for D05. The average dose sparing of all patients analysed resulted in an average D95 of 68.64% in the right kidney and 69.31% in the left kidney. Average D95 in the spleen was 94.28% and D05 was 107.05%. Homogeneity indexes ranged from 1.12 for liver to 2.28 for lung. The additional significance analyses conducted on these blood kinetics showed a significant difference between the 2 Gray group and the other three groups for leukocyte counts. Further statistical comparisons of the dose groups showed no significant differences. However, there were significant changes in the dose of OAR prescribed with dose sparing (e.g., lung vs. rib and kidney). CONCLUSION: Using intensity-modulated helical tomotherapy to deliver TBI is a feasible method in preparation for haematopoietic stem cell transplantation. Significant dose sparing in radiosensitive organs such as the lungs and kidneys is achievable with good overall quality of coverage. Peripheral blood kinetics support the positive impact of HT and its advantages strongly encourage its implementation within clinical routine.

Perioperative therapy with FLOT4 significantly increases survival in patients with gastroesophageal and gastric cancer in a large real-world cohort.

In 2019, the FLOT4 protocol was established as the new standard for perioperative therapy in patients with locally advanced gastroesophageal and gastric cancer. Whether this protocol is beneficial in a real-world setting remains a question with limited answers to date. In our study, a large cohort of unselected patients treated with FLOT4 was analyzed and compared to protocols based on 5-FU/platinum derivative. This retrospective analysis included patients with locally advanced gastroesophageal and gastric cancer treated with perioperative FLOT or 5-FU/platinum derivative at University Hospital, Bonn between 2010 and 2022 in a curative setting (n = 99). Overall survival, disease-free survival, therapy response and therapy complications were analyzed. Patients treated with FLOT showed a statistically significant longer median overall survival of 57.8 vs 28.9 months (HR: 0.554, 95% CI: 0.317-0.969, P = .036). Moreover, pathological tumor regression (pTR) was significantly higher in the FLOT group compared to the 5-FU/platinum group (P = .001). Subgroup analysis showed a favorable survival benefit for the FLOT vs 5-FU/platinum derivate in patients with AEG and non-signet cell carcinoma. Overall, FLOT was tolerated well but CTCAE ≥3 grade neutropenia and diarrhea occurred more often within the FLOT group. Similar to the prospective phase II/III trials, FLOT4 was the best protocol for patients with locally advanced gastroesophageal and gastric cancer as perioperative therapy in terms of overall survival and pathological response rate compared to 5-FU/platinum derivative protocols. Interestingly, patients with gastroesophageal cancer benefitted more from this therapy. In contrast, patients with signet ring cells appear not to benefit from addition of docetaxel.

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.