Jiajun Zheng, Geng Xu, Wenjie Guo, Yuanyuan Wang, Jianfeng Wu, Dan Zong, Boyang Ding, Li Sun, Xia He
{"title":"Preliminary study of feasibility of surface-guided radiotherapy with concurrent tumor treating fields for glioblastoma: region of interest.","authors":"Jiajun Zheng, Geng Xu, Wenjie Guo, Yuanyuan Wang, Jianfeng Wu, Dan Zong, Boyang Ding, Li Sun, Xia He","doi":"10.1186/s13014-024-02525-3","DOIUrl":"https://doi.org/10.1186/s13014-024-02525-3","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the impact of the residual setup errors from differently shaped region of interest (ROI) and investigate if surface-guided setup can be used in radiotherapy with concurrent tumor treating fields (TTFields) for glioblastoma.</p><p><strong>Methods: </strong>Fifteen patients undergone glioblastoma radiotherapy with concurrent TTFields were involved. Firstly, four shapes of region of interest (ROI) (strip-shaped, T-shaped, <math><mo>⊥</mo></math> -shaped and cross-shaped) with medium size relative to the whole face were defined dedicate for patients wearing TTFields transducer arrays. Then, ROI-shape-dependent residual setup errors in six degrees were evaluated using an anthropomorphic head and neck phantom taking CBCT data as reference. Finally, the four types of residual setup errors were converted into corresponding dosimetry deviations (including the target coverage and the organ at risk sparing) of the fifteen radiotherapy plans using a feasible and robust geometric-transform-based method.</p><p><strong>Results: </strong>The algebraic sum of the average residual setup errors in six degrees (mm in translational directions and ° in rotational directions) of the four types were 6.9, 1.1, 4.1 and 3.5 respectively. In terms of the ROI-shape-dependent dosimetry deviations, the D<sub>98%</sub> of PTV dropped off by (3.4 ± 2.0)% (p < 0.05), (0.3 ± 0.5)% (p < 0.05), (0.9 ± 0.9)% (p < 0.05) and (1.1 ± 0.8)% (p < 0.05). The D<sub>98%</sub> of CTV dropped off by (0.5 ± 0.6)% (p < 0.05) for the strip-shaped ROI while remained unchanged for others.</p><p><strong>Conclusion: </strong>Surface-guided setup is feasible in radiotherapy with concurrent TTFields and a medium-sized T-shaped ROI is appropriate for the surface-based guidance.</p>","PeriodicalId":49639,"journal":{"name":"Radiation Oncology","volume":"19 1","pages":"129"},"PeriodicalIF":3.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11430246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ya Zeng, Xi Su, Tongfang Zhou, Jingyi Jia, Jun Liu, Wen Yu, Qin Zhang, Xinyun Song, Xiaolong Fu, Xuwei Cai
{"title":"Propensity-matched study on locally advanced esophageal cancer: surgery versus post-operative radiotherapy.","authors":"Ya Zeng, Xi Su, Tongfang Zhou, Jingyi Jia, Jun Liu, Wen Yu, Qin Zhang, Xinyun Song, Xiaolong Fu, Xuwei Cai","doi":"10.1186/s13014-024-02528-0","DOIUrl":"10.1186/s13014-024-02528-0","url":null,"abstract":"<p><strong>Background: </strong>This study aims to delineate the long-term outcomes and recurrence patterns of locally advanced thoracic esophageal squamous cell carcinoma (TESCC) patients managed with or without postoperative radiotherapy (PORT).</p><p><strong>Methods: </strong>A retrospective cohort from two academic centers, encompassing patients who initially underwent esophagectomy and were pathologically staged T3-4, was analyzed. Survival outcomes were constructed using Kaplan-Meier method, with survival significance was evaluated using the log-rank test. Propensity score matching (PSM) was utilized to balance potential selection bias.</p><p><strong>Results: </strong>Among the 506 patients, 251 underwent surgery alone and 255 received radiotherapy following radical surgery. With a median follow-up of 49.1 months, PORT significantly improved 5-year overall survival (53.8% vs. 25.3%; p < 0.001) and 5-year disease-free survival rates (45.3% vs. 8.5%; p < 0.001) compared to surgery alone. These differences in survival outcomes persisted even after PSM (p < 0.001 for both). Treatment failure was significantly less frequent in the PORT group (46.7%) compared to the surgery-only group (90.0%; p < 0.001), with corresponding reductions in locoregional recurrence (9.4% vs. 54.1%; p < 0.001). This underscores the significant association between PORT and disease control.</p><p><strong>Conclusion: </strong>The absence of neoadjuvant chemoradiotherapy highlights the importance of PORT in improving survival and reducing recurrence in advanced T3-4 TESCC patients. This study underscores the importance of PORT as a salvage treatment for locally advanced TESCC patients without neoadjuvant chemoradiotherapy.</p>","PeriodicalId":49639,"journal":{"name":"Radiation Oncology","volume":"19 1","pages":"130"},"PeriodicalIF":3.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dose escalation in radical radio(chemo)therapy for cervical and upper thoracic esophageal cancer with 3DCRT/IMRT (ChC&UES): a multicenter retrospective study.","authors":"Xiao-Han Zhao, Wen-Cheng Zhang, Xin Wang, Jun-Qiang Chen, Yuan-Ji Xu, Kuai-Le Zhao, Wei Huang, Pu-Dong Qian, Ya-Tian Liu, Xiao-Lin Ge, Xiao-Jie Xia, Chen-Gang Weng, Chun-Yue Gai, He-Song Wang, Hong-Mei Gao, Wen-Bin Shen, Shu-Chai Zhu","doi":"10.1186/s13014-024-02521-7","DOIUrl":"https://doi.org/10.1186/s13014-024-02521-7","url":null,"abstract":"<p><strong>Background: </strong>Cervical and upper thoracic esophageal cancer (ESCA) presents treatment challenges due to limited clinical evidence. This multi-center study (ChC&UES) explores radical radio(chemo)therapy efficacy and safety, especially focusing on radiation dose.</p><p><strong>Method: </strong>We retrospectively analyzed clinical data from 1,422 cases across 8 medical centers. According to the radiation dose for primary gross tumor, patients were divided into standard dose radiotherapy (SD, 50-55 Gy) or high dose (HD, > 55 Gy) radiotherapy. HD was further subdivided into conventional- high-dose group (HD-conventional, 55-63 Gy) and ultra-high-dose group (HD-ultra, ≥ 63 Gy). Primary outcome was Overall Survival (OS).</p><p><strong>Results: </strong>The median OS was 33.0 months (95% CI: 29.401-36.521) in the whole cohort. Compared with SD, HD shown significant improved survival in cervical ESCA in Kaplan-Meier (P = 0.029) and cox multivariate regression analysis (P = 0.024) while shown comparable survival in upper thoracic ESCA (P = 0.735). No significant difference existed between HD-conventional and HD-ultra in cervical (P = 0.976) and upper thoracic (P = 0.610) ESCA. Incidences of radiation esophagitis and pneumonia from HD were comparable to SD (P = 0.097, 0.240), while myosuppression risk was higher(P = 0.039). The Bonferroni method revealed that, for both cervical and upper thoracic ESCA, HD-ultra enhance the objective response rate (ORR) compared to SD (P < 0.05).</p><p><strong>Conclusion: </strong>HD radiotherapy benefits cervical but not upper thoracic ESCA, while increasing bone marrow suppression risk. Further dose escalating (≥ 63 Gy) doesn't improve survival but enhances ORR.</p>","PeriodicalId":49639,"journal":{"name":"Radiation Oncology","volume":"19 1","pages":"126"},"PeriodicalIF":3.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chao Li, You-Ping Xiao, Lin Huang, Wang Jing, Bin Zhang, Song-Hua Huang, Li-Bao Yang, Su-Fang Qiu
{"title":"High buttocks supine position to reduce small bowel exposure in gynecological radiotherapy.","authors":"Chao Li, You-Ping Xiao, Lin Huang, Wang Jing, Bin Zhang, Song-Hua Huang, Li-Bao Yang, Su-Fang Qiu","doi":"10.1186/s13014-024-02522-6","DOIUrl":"https://doi.org/10.1186/s13014-024-02522-6","url":null,"abstract":"<p><strong>Purpose: </strong>To minimize radiation exposure to the small bowel (SB) in patients undergoing treatment for gynecological tumors by adopting a comfortable positioning method.</p><p><strong>Methods and patients: </strong>All 76 women undergoing Intensity-Modulated Radiation Therapy (IMRT) were included in this study. Patients were immobilized in a supine position using a vacuum bag and thermoplastic cast formation. In the trial group (n = 36), patients raised their buttocks and a solid foam pad was placed under the sacral tail before immobilization. The control group (n = 40) received treatment in the standard supine position. The SB was delineated from the pubic symphysis to the total iliac bifurcation in computed tomography (CT) scans.</p><p><strong>Result: </strong>In the trial group, a significant reduction in SB volume within the pelvic cavity was observed (mean 399.17 ± 158.7 cc) compared to the control group (mean 547.48 ± 166.9 cc), with a p-value less than 0.001. The trial group showed a statistically significant reduction in the absolute volume of irradiated SB at each dose, ranging from the low dose (10 Gy) to the high dose (45 Gy). In the control group, a negative correlation was found between SB and bladder volumes (R = -0.411, P = 0.008), whereas in the trial group, this correlation was weaker (R = -0.286, P = 0.091), with no significant relationship observed between bladder volume and SB.</p><p><strong>Conclusion: </strong>The high buttocks supine position effectively reduces SB radiation exposure without the need for bladder distension. This positioning method holds promise for reducing SB irradiation in various pelvic tumors.</p>","PeriodicalId":49639,"journal":{"name":"Radiation Oncology","volume":"19 1","pages":"131"},"PeriodicalIF":3.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A deep learning-informed interpretation of why and when dose metrics outside the PTV can affect the risk of distant metastasis in SBRT NSCLC patients.","authors":"D Dudas, T J Dilling, I El Naqa","doi":"10.1186/s13014-024-02519-1","DOIUrl":"https://doi.org/10.1186/s13014-024-02519-1","url":null,"abstract":"<p><strong>Purpose: </strong>Recent papers suggested a correlation between the risk of distant metastasis (DM) and dose outside the PTV, though conclusions in different publications conflicted. This study resolves these conflicts and provides a compelling explanation of prognostic factors.</p><p><strong>Materials and methods: </strong>A dataset of 478 NSCLC patients treated with SBRT (IMRT or VMAT) was analyzed. We developed a deep learning model for DM prediction and explainable AI was used to identify the most significant prognostic factors. Subsequently, the prognostic power of the extracted features and clinical details were analyzed using conventional statistical methods.</p><p><strong>Results: </strong>Treatment technique, tumor features, and dosiomic features in a 3 cm wide ring around the PTV (PTV<sub>3cm</sub>) were identified as the strongest predictors of DM. The Hazard Ratio (HR) for D<sub>mean,PTV3cm</sub> was significantly above 1 (p < 0.001). There was no significance of the PTV<sub>3cm</sub> dose after treatment technique stratification. However, the dose in PTV<sub>3cm</sub> was found to be a highly significant DM predictor (HR > 1, p = 0.004) when analyzing only VMAT patients with small and spherical tumors (i.e., sphericity > 0.5).</p><p><strong>Conclusions: </strong>The main reason for conflicting conclusions in previous papers was inconsistent datasets and insufficient consideration of confounding variables. No causal correlation between the risk of DM and dose outside the PTV was found. However, the mean dose to PTV<sub>3cm</sub> can be a significant predictor of DM in small spherical targets treated with VMAT, which might clinically imply considering larger PTV margins for smaller, more spherical tumors (e.g., if IGTV > 2 cm, then margin ≤ 7 mm, else margin > 7 mm).</p>","PeriodicalId":49639,"journal":{"name":"Radiation Oncology","volume":"19 1","pages":"127"},"PeriodicalIF":3.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11430131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Joint modeling of longitudinal health-related quality of life during concurrent chemoradiotherapy period and long-term survival among patients with advanced nasopharyngeal carcinoma.","authors":"Ji-Bin Li, Shan-Shan Guo, Ting Liu, Zhuo-Chen Lin, Wei-Jie Gong, Lin-Quan Tang, Ling Guo, Hao-Yuan Mo, Hai-Qiang Mai, Qiu-Yan Chen","doi":"10.1186/s13014-024-02473-y","DOIUrl":"https://doi.org/10.1186/s13014-024-02473-y","url":null,"abstract":"<p><strong>Background: </strong>To investigate the prognosis of longitudinal health-related quality of life (HRQOL) during concurrent chemoradiotherapy (CCRT) on survival outcomes in patients with advanced nasopharyngeal carcinoma (NPC).</p><p><strong>Methods: </strong>During 2012-2014, 145 adult NPC patients with stage II-IVb NPC were investigated weekly using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORCT QLQ-C30) during their CCRT period. The effects of longitudinal trends of HRQOL on survival outcomes were estimated using joint modeling, and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were reported as a 10-point increase in HRQOL scores.</p><p><strong>Results: </strong>After a median follow-up of 83.4 months, the multivariable models showed significant associations of longitudinal increasing scores in fatigue and appetite loss during the CCRT period with distant metastasis-free survival: 10-point increases in scores of fatigue and appetite loss domains during CCRT period were significantly associated with 75% (HR: 1.75, 95% CI: 1.01, 3.02; p = 0.047) and 59% (HR: 1.59, 95% CI: 1.09, 2.59; p = 0.018) increase in the risk of distant metastasis, respectively. The prognostic effects of the longitudinal HRQOL trend on overall survival and progress-free survival were statistically non-significant.</p><p><strong>Conclusion: </strong>Increases in fatigue and appetite loss of HRQOL during the CCRT period are significantly associated with high risks of distant metastasis in advanced NPC patients. Nutritional support and psychological intervention are warranted for NPC patients during the treatment period.</p>","PeriodicalId":49639,"journal":{"name":"Radiation Oncology","volume":"19 1","pages":"125"},"PeriodicalIF":3.3,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brittney Chau, Tariq Abuali, Shervin M. Shirvani, David Leung, Karine A. Al Feghali, Susanta Hui, Heather McGee, Chunhui Han, An Liu, Arya Amini
{"title":"Feasibility of Biology-guided Radiotherapy (BgRT) Targeting Fluorodeoxyglucose (FDG) avid liver metastases","authors":"Brittney Chau, Tariq Abuali, Shervin M. Shirvani, David Leung, Karine A. Al Feghali, Susanta Hui, Heather McGee, Chunhui Han, An Liu, Arya Amini","doi":"10.1186/s13014-024-02502-w","DOIUrl":"https://doi.org/10.1186/s13014-024-02502-w","url":null,"abstract":"Biology-guided radiotherapy (BgRT) is a novel radiation delivery approach utilizing fluorodeoxyglucose (FDG) activity on positron emission tomography (PET) imaging performed in real-time to track and direct RT. Our institution recently acquired the RefleXion X1 BgRT system and sought to assess the feasibility of targeting metastatic sites in various organs, including the liver. However, in order for BgRT to function appropriate, adequate contrast in FDG activity between the tumor and the background tissue, referred to as the normalized SUV (NSUV), is necessary for optimal functioning of BgRT. We reviewed the charts of 50 lung adenocarcinoma patients with liver metastases. The following variables were collected: SUVmax and SUVmean for each liver metastasis, SUVmean and SUVmax at 5 and 10 mm radially from the lesion, and NSUV at 5 mm and 10 mm (SUVmax of the liver metastasis divided by SUV mean at 5 mm at 10 mm respectively). 82 measurable liver metastases were included in the final analysis. The average SUVbackground of liver was 2.26 (95% confidence interval [CI] 2.17–2.35); average SUVmean for liver metastases was 5.31 (95% CI 4.87–5.75), and average SUVmax of liver metastases was 9.19 (95% CI 7.59–10.78). The average SUVmean at 5 mm and 10 mm radially from each lesion were 3.08 (95% CI 3.00-2.16) and 2.60 (95% CI 2.52–2.68), respectively. The mean NSUV at 5 mm and 10 mm were 3.13 (95% CI 2.53–3.73) and 3.69 (95% CI 3.00-4.41) respectively. Furthermore, 90% of lesions had NSUV greater than 1.45 at 5 mm and greater than 1.77 at 10 mm. This is the first study to comprehensively characterize FDG contrast between the liver tumor and background, referred to as NSUV. Due to the high background SUV normally found in the liver, this work will be valuable for guiding optimization of BgRT for treating liver metastases in the future using the RefleXion® X1 and potentially other similar BgRT platforms.","PeriodicalId":49639,"journal":{"name":"Radiation Oncology","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jenna Dean, Nigel Anderson, Georgia K. B. Halkett, Jessica Lye, Mark Tacey, Farshad Foroudi, Michael Chao, Caroline Wright
{"title":"Study protocol: Optimising patient positioning for the planning of accelerated partial breast radiotherapy for the integrated magnetic resonance linear accelerator: OPRAH MRL","authors":"Jenna Dean, Nigel Anderson, Georgia K. B. Halkett, Jessica Lye, Mark Tacey, Farshad Foroudi, Michael Chao, Caroline Wright","doi":"10.1186/s13014-024-02517-3","DOIUrl":"https://doi.org/10.1186/s13014-024-02517-3","url":null,"abstract":"Accelerated partial breast irradiation (APBI) is an accepted treatment option for early breast cancer. Treatment delivered on the Magnetic Resonance integrated Linear Accelerator (MRL) provides the added assurance of improved soft tissue visibility, important in the delivery of APBI. This technique can be delivered in both the supine and prone positions, however current literature suggests that prone treatment on the MRL is infeasible due to physical limitations with bore size. This study aims to investigate the feasibility of positioning patients on a custom designed prone breast board compared with supine positioning on a personalised vacuum bag. Geometric distortion, the relative position of Organs at Risk (OAR) to the tumour bed and breathing motion (intrafraction motion) will be compared between the supine and prone positions. The study will also investigate the positional impact on dosimetry, patient experience, and position preference. Up to 30 patients will be recruited over a 12-month period for participation in this Human Research Ethics Committee approved exploratory cohort study. Patients will be scanned on the magnetic resonance imaging (MRI) Simulator in both the supine and prone positions as per current standard of care for APBI simulation. Supine and prone positioning comparisons will all be assessed on de-identified MRI image pairs, acquired using appropriate software. Patient experience will be explored through completion of a short, anonymous electronic survey. Descriptive statistics will be used for reporting of results with categorical, parametric/non-parametric tests applied (data format dependent). Survey results will be interpreted by comparison of percentage frequencies across the Likert scales. Thematic content analysis will be used to interpret qualitative data from the open-ended survey questions. The results of this study will be used to assess the feasibility of treating patients with APBI in the prone position on a custom designed board on the MRL. It may also be used to assist with identification of patients who would benefit from this position over supine without the need to perform both scans. Patient experience and technical considerations will be utilised to develop a tool to assist in this process. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN1262400067583. Registered 28th of May 2024. https://www.anzctr.org.au/ACTRN12624000679583.aspx ","PeriodicalId":49639,"journal":{"name":"Radiation Oncology","volume":"4 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Secondary solid malignancies in long-term survivors after total body irradiation","authors":"Isabella Gruber, Daniel Wolff, Oliver Koelbl","doi":"10.1186/s13014-024-02520-8","DOIUrl":"https://doi.org/10.1186/s13014-024-02520-8","url":null,"abstract":"Total body irradiation (TBI)-based allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for selected patients with acute myeloid leukemia (AML). Yet, secondary malignancies contribute to long-term morbidity and mortality with TBI potentially influencing these risks. This retrospective study analyzed the cumulative incidences of secondary solid malignancies and precancerous lesions of 89 consecutive AML patients after TBI-based conditioning before 1st allo-HSCT between 2000 and 2016. TBI was performed with an average dose rate of 4 cGy/min and a twice-daily fractionation. Cause-specific hazard models analyzed risk factors for secondary malignancies/precancerous lesions and the competing risks of dying before developing secondary malignancies/precancerous lesions. The median patient age at TBI was 42.5 years (interquartile range, 32.5–51.2), while the median follow-up was 15.2 years (interquartile range, 13.0-18.2). Most patients received a myeloablative conditioning (MAC) containing 8 Gy (n = 47) and 12 Gy TBI (n = 11). Reduced-intensity regimens (RIC, 4 Gy TBI) were applied in 31 patients. Of note, patients receiving RIC were older than patients receiving MAC. The most common cancer types were non-squamous cell carcinomas (n = 14) after exclusion of a patient diagnosed with sarcoma within less than a year after TBI. The cumulative incidences of secondary malignancies and precancerous lesions were 8% (95%CI, 4–16), 14% (95%CI, 7–23), and 17% (95%CI, 9–27) at 10, 15 and 20 years, while the cumulative incidences of premature deaths were 59% (95%CI, 48–69), 59% (95%CI, 48–69), and 64% (95%CI, 49–76). In multivariate analyses, higher patient age at TBI was associated with lower rates of secondary malignancies/precancerous lesions, while higher patient age translated into a trend towards premature deaths (before patients could develop malignancies). Higher TBI doses, mainly applied in younger patients, translated into lower rates of secondary malignancies/precancerous lesions while lacking associations with mortality. Chronic GVHD requiring systemic immunosuppression was associated with premature deaths. Although this study indicates an inverse relationship between TBI doses applied and treatment-related malignancies, confounding by competing risks is present. The age dependency may be explained by the fact that older patients had a lower life expectancy independent of malignancies, illustrating the pitfalls of competing risks. The study was retrospectively registered.","PeriodicalId":49639,"journal":{"name":"Radiation Oncology","volume":"76 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rebecca A. Bekker, Nina Obertopp, Gage Redler, José Penagaricano, Jimmy J. Caudell, Kosj Yamoah, Shari Pilon-Thomas, Eduardo G. Moros, Heiko Enderling
{"title":"Spatially fractionated GRID radiation potentiates immune-mediated tumor control","authors":"Rebecca A. Bekker, Nina Obertopp, Gage Redler, José Penagaricano, Jimmy J. Caudell, Kosj Yamoah, Shari Pilon-Thomas, Eduardo G. Moros, Heiko Enderling","doi":"10.1186/s13014-024-02514-6","DOIUrl":"https://doi.org/10.1186/s13014-024-02514-6","url":null,"abstract":"Tumor-immune interactions shape a developing tumor and its tumor immune microenvironment (TIME) resulting in either well-infiltrated, immunologically inflamed tumor beds, or immune deserts with low levels of infiltration. The pre-treatment immune make-up of the TIME is associated with treatment outcome; immunologically inflamed tumors generally exhibit better responses to radio- and immunotherapy than non-inflamed tumors. However, radiotherapy is known to induce opposing immunological consequences, resulting in both immunostimulatory and inhibitory responses. In fact, it is thought that the radiation-induced tumoricidal immune response is curtailed by subsequent applications of radiation. It is thus conceivable that spatially fractionated radiotherapy (SFRT), administered through GRID blocks (SFRT-GRID) or lattice radiotherapy to create areas of low or high dose exposure, may create protective reservoirs of the tumor immune microenvironment, thereby preserving anti-tumor immune responses that are pivotal for radiation success. We have developed an agent-based model (ABM) of tumor-immune interactions to investigate the immunological consequences and clinical outcomes after $$2,text{Gy} times 35$$ whole tumor radiation therapy (WTRT) and SFRT-GRID. The ABM is conceptually calibrated such that untreated tumors escape immune surveillance and grow to clinical detection. Individual ABM simulations are initialized from four distinct multiplex immunohistochemistry (mIHC) slides, and immune related parameter rates are generated using Latin Hypercube Sampling. In silico simulations suggest that radiation-induced cancer cell death alone is insufficient to clear a tumor with WTRT. However, explicit consideration of radiation-induced anti-tumor immunity synergizes with radiation cytotoxicity to eradicate tumors. Similarly, SFRT-GRID is successful with radiation-induced anti-tumor immunity, and, for some pre-treatment TIME compositions and modeling parameters, SFRT-GRID might be superior to WTRT in providing tumor control. This study demonstrates the pivotal role of the radiation-induced anti-tumor immunity. Prolonged fractionated treatment schedules may counteract early immune recruitment, which may be protected by SFRT-facilitated immune reservoirs. Different biological responses and treatment outcomes are observed based on pre-treatment TIME composition and model parameters. A rigorous analysis and model calibration for different tumor types and immune infiltration states is required before any conclusions can be drawn for clinical translation.","PeriodicalId":49639,"journal":{"name":"Radiation Oncology","volume":"4 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}