Background: 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.
Method: 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).
Results: 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).
Conclusion: 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.
{"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}
Pub Date : 2024-09-27DOI: 10.1186/s13014-024-02522-6
Chao Li, You-Ping Xiao, Lin Huang, Wang Jing, Bin Zhang, Song-Hua Huang, Li-Bao Yang, Su-Fang Qiu
Purpose: To minimize radiation exposure to the small bowel (SB) in patients undergoing treatment for gynecological tumors by adopting a comfortable positioning method.
Methods and patients: 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.
Result: 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.
Conclusion: 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.
{"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}
Pub Date : 2024-09-27DOI: 10.1186/s13014-024-02519-1
D Dudas, T J Dilling, I El Naqa
Purpose: 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.
Materials and methods: 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.
Results: Treatment technique, tumor features, and dosiomic features in a 3 cm wide ring around the PTV (PTV3cm) were identified as the strongest predictors of DM. The Hazard Ratio (HR) for Dmean,PTV3cm was significantly above 1 (p < 0.001). There was no significance of the PTV3cm dose after treatment technique stratification. However, the dose in PTV3cm 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).
Conclusions: 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 PTV3cm 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).
{"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}
Background: 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).
Methods: 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.
Results: 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.
Conclusion: 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.
{"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}
Pub Date : 2024-09-18DOI: 10.1186/s13014-024-02502-w
Brittney Chau, Tariq Abuali, Shervin M. Shirvani, David Leung, Karine A. Al Feghali, Susanta Hui, Heather McGee, Chunhui Han, An Liu, Arya Amini
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.
{"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}
Pub Date : 2024-09-17DOI: 10.1186/s13014-024-02517-3
Jenna Dean, Nigel Anderson, Georgia K. B. Halkett, Jessica Lye, Mark Tacey, Farshad Foroudi, Michael Chao, Caroline Wright
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
{"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}
Pub Date : 2024-09-17DOI: 10.1186/s13014-024-02520-8
Isabella Gruber, Daniel Wolff, Oliver Koelbl
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.
{"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}
Pub Date : 2024-09-13DOI: 10.1186/s13014-024-02514-6
Rebecca A. Bekker, Nina Obertopp, Gage Redler, José Penagaricano, Jimmy J. Caudell, Kosj Yamoah, Shari Pilon-Thomas, Eduardo G. Moros, Heiko Enderling
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.
肿瘤与免疫之间的相互作用塑造了发育中的肿瘤及其肿瘤免疫微环境（TIME），从而形成了浸润良好、免疫发炎的肿瘤床或浸润水平较低的免疫荒漠。治疗前 TIME 的免疫构成与治疗效果有关；免疫发炎的肿瘤通常比未发炎的肿瘤对放射治疗和免疫治疗的反应更好。然而，众所周知，放疗会引起相反的免疫后果，导致免疫刺激和抑制两种反应。事实上，人们认为辐射诱导的杀瘤免疫反应会被随后的辐射应用所抑制。因此可以想象，通过GRID区块（SFRT-GRID）或格状放疗来创建低剂量或高剂量照射区域的空间分割放疗（SFRT），可能会创建肿瘤免疫微环境的保护库，从而保留对放疗成功至关重要的抗肿瘤免疫反应。我们建立了一个基于代理的肿瘤-免疫相互作用模型（ABM），以研究2,text{Gy}times 35＄＄全幅放疗后的免疫学后果和临床结果。times35$$全肿瘤放疗（WTRT）和SFRT-GRID后的免疫后果和临床疗效。ABM 从概念上进行了校准，使未经治疗的肿瘤逃避免疫监视并生长至临床检测。单个 ABM 模拟由四张不同的多重免疫组化（mIHC）切片初始化，并使用拉丁超立方采样生成与免疫相关的参数率。硅学模拟表明，仅靠辐射诱导的癌细胞死亡不足以清除 WTRT 肿瘤。然而，明确考虑辐射诱导的抗肿瘤免疫与辐射细胞毒性协同作用，可以根除肿瘤。同样，SFRT-GRID 在辐射诱导抗肿瘤免疫方面也取得了成功，而且对于某些治疗前 TIME 成分和建模参数，SFRT-GRID 在控制肿瘤方面可能优于 WTRT。这项研究证明了辐射诱导的抗肿瘤免疫的关键作用。延长的分次治疗计划可能会抵消早期免疫招募，而SFRT促进的免疫库可能会保护早期免疫招募。根据治疗前 TIME 的组成和模型参数，可以观察到不同的生物反应和治疗结果。在得出临床转化结论之前，需要针对不同肿瘤类型和免疫浸润状态进行严格的分析和模型校准。
{"title":"Spatially fractionated GRID radiation potentiates immune-mediated tumor control","authors":"Rebecca A. Bekker, Nina Obertopp, Gage Redler, José Penagaricano, Jimmy J. Caudell, Kosj Yamoah, Shari Pilon-Thomas, Eduardo G. Moros, Heiko Enderling","doi":"10.1186/s13014-024-02514-6","DOIUrl":"https://doi.org/10.1186/s13014-024-02514-6","url":null,"abstract":"Tumor-immune interactions shape a developing tumor and its tumor immune microenvironment (TIME) resulting in either well-infiltrated, immunologically inflamed tumor beds, or immune deserts with low levels of infiltration. The pre-treatment immune make-up of the TIME is associated with treatment outcome; immunologically inflamed tumors generally exhibit better responses to radio- and immunotherapy than non-inflamed tumors. However, radiotherapy is known to induce opposing immunological consequences, resulting in both immunostimulatory and inhibitory responses. In fact, it is thought that the radiation-induced tumoricidal immune response is curtailed by subsequent applications of radiation. It is thus conceivable that spatially fractionated radiotherapy (SFRT), administered through GRID blocks (SFRT-GRID) or lattice radiotherapy to create areas of low or high dose exposure, may create protective reservoirs of the tumor immune microenvironment, thereby preserving anti-tumor immune responses that are pivotal for radiation success. We have developed an agent-based model (ABM) of tumor-immune interactions to investigate the immunological consequences and clinical outcomes after $$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}
Pub Date : 2024-09-13DOI: 10.1186/s13014-024-02510-w
Chao Wei, Jie Kong, Huina Han, Xue Wang, Zimeng Gao, Danyang Wang, Andu Zhang, Jun Zhang, Zhikun Liu
To explore the high-risk factors affecting the prognosis of pT1 − 2N1M0 patients after mastectomy, establish a nomogram prediction model, and screen the radiotherapy benefit population. The clinical data of 936 patients with pT1 − 2N1M0 who underwent mastectomy in the fourth hospital of Hebei Medical University from 2010 to 2016 were retrospectively analyzed. There were 583 patients received postmastectomy radiotherapy(PMRT), and 325 patients without PMRT. Group imbalances were mitigated using the propensity score matching (PSM) method, and the log-rank test was employed to compare overall survival (OS) and disease-free survival (DFS) between the cohorts. The efficacy of PMRT across various risk groups was evaluated using a nomogram model. The median follow-up period was 98 months, Patients who received PMRT demonstrated significantly improved 5-year and 8-year OS and DFS compared to those who did not (P < 0.001). Multivariate analysis revealed that age, primary tumor site, positive lymph node, stage, and Ki-67 level independently influenced OS, while age, primary tumor site, and stage independently affected DFS. PMRT drastically enhanced OS in the high-risk group (P = 0.001), but did not confer benefits in the low-risk and intermediate risk groups (P = 0.057, P = 0.099). PMRT led to a significant improvement in disease-free survival (DFS) among patients in the intermediate and high-risk groups (P = 0.036, P = 0.001), whereas the low-risk group did not experience a significant benefit (P = 0.475). Age ≤ 40 years, tumor located in the inner quadrant or central area, T2 stage, 2–3 lymph nodes metastasis, and Ki67 > 30% were the high-risk factors affecting the prognosis of this cohort of patients. In OS nomogram, patients with a risk score of 149 or higher who received PMRT exhibited improved OS. Similarly, in DFS nomogram, patients with a risk score of 123 or higher who received PMRT demonstrated enhanced DFS.
{"title":"The significance of risk stratification through nomogram-based assessment in determining postmastectomy radiotherapy for patients diagnosed with pT1 − 2N1M0 breast cancer","authors":"Chao Wei, Jie Kong, Huina Han, Xue Wang, Zimeng Gao, Danyang Wang, Andu Zhang, Jun Zhang, Zhikun Liu","doi":"10.1186/s13014-024-02510-w","DOIUrl":"https://doi.org/10.1186/s13014-024-02510-w","url":null,"abstract":"To explore the high-risk factors affecting the prognosis of pT1 − 2N1M0 patients after mastectomy, establish a nomogram prediction model, and screen the radiotherapy benefit population. The clinical data of 936 patients with pT1 − 2N1M0 who underwent mastectomy in the fourth hospital of Hebei Medical University from 2010 to 2016 were retrospectively analyzed. There were 583 patients received postmastectomy radiotherapy(PMRT), and 325 patients without PMRT. Group imbalances were mitigated using the propensity score matching (PSM) method, and the log-rank test was employed to compare overall survival (OS) and disease-free survival (DFS) between the cohorts. The efficacy of PMRT across various risk groups was evaluated using a nomogram model. The median follow-up period was 98 months, Patients who received PMRT demonstrated significantly improved 5-year and 8-year OS and DFS compared to those who did not (P < 0.001). Multivariate analysis revealed that age, primary tumor site, positive lymph node, stage, and Ki-67 level independently influenced OS, while age, primary tumor site, and stage independently affected DFS. PMRT drastically enhanced OS in the high-risk group (P = 0.001), but did not confer benefits in the low-risk and intermediate risk groups (P = 0.057, P = 0.099). PMRT led to a significant improvement in disease-free survival (DFS) among patients in the intermediate and high-risk groups (P = 0.036, P = 0.001), whereas the low-risk group did not experience a significant benefit (P = 0.475). Age ≤ 40 years, tumor located in the inner quadrant or central area, T2 stage, 2–3 lymph nodes metastasis, and Ki67 > 30% were the high-risk factors affecting the prognosis of this cohort of patients. In OS nomogram, patients with a risk score of 149 or higher who received PMRT exhibited improved OS. Similarly, in DFS nomogram, patients with a risk score of 123 or higher who received PMRT demonstrated enhanced DFS.","PeriodicalId":49639,"journal":{"name":"Radiation Oncology","volume":"11 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142193505","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}
Glioblastoma (GBM), the most common primary brain malignancy in adults, is notoriously difficult to treat due to several factors: tendency to be radiation resistant, the presence of the blood brain barrier (BBB) which limits drug delivery and immune-privileged status which hampers effective immune responses. Traditionally, high-dose irradiation (8 Gy) is known to effectively enhance anti-tumor immune responses, but its application is limited by the risk of severe brain damage. Currently, conventional dose segmentation (2 Gy) is the standard radiotherapy method, which does not fully exploit the potential of high-dose irradiation for immune activation. The hypothesis of our study posits that instead of directly applying high doses of radiation, which is risky, a strategy could be developed to harness the immune-stimulating benefits of high-dose irradiation indirectly. This involves using nanoparticles to enhance antigen presentation and immune responses in a safer manner. Angiopep-2 (A2) was proved a satisfactory BBB and brain targeting and Dbait is a small molecule that hijack DNA double strand break damage (DSB) repair proteins to make cancer cells more sensitive to radiation. In view of that, the following two nanoparticles were designed to combine immunity of GBM, radiation resistance and BBB innovatively. One is cationic liposome nanoparticle interacting with Dbait (A2-CL/Dbait NPs) for radiosensitization effect; the other is PLGA-PEG-Mal nanoparticle conjugated with OX40 antibody (A2-PLGA-PEG-Mal/anti-OX40 NPs) for tumor-derived protein antigens capture and optimistic immunoregulatory effect of anti-OX40 (which is known to enhance the activation and proliferation T cells). Both types of nanoparticles showed favorable targeting and low toxicity in experimental models. Specifically, the combination of A2-CL/Dbait NPs and A2-PLGA-PEG-Mal/anti-OX40 NPs led to a significant extension in the survival time and a significant tumor shrinkage of mice with GBM. The study demonstrates that combining these innovative nanoparticles with conventional radiotherapy can effectively address key challenges in GBM treatment. It represents a significant step toward more effective and safer therapeutic options for GBM patients.
{"title":"A multifunctional targeted nano-delivery system with radiosensitization and immune activation in glioblastoma","authors":"Xin Wen, Zhiying Shao, Xueting Chen, Hongmei Liu, Hui Qiu, Xin Ding, Debao Qu, Hui Wang, Andrew Z. Wang, Longzhen Zhang","doi":"10.1186/s13014-024-02511-9","DOIUrl":"https://doi.org/10.1186/s13014-024-02511-9","url":null,"abstract":"Glioblastoma (GBM), the most common primary brain malignancy in adults, is notoriously difficult to treat due to several factors: tendency to be radiation resistant, the presence of the blood brain barrier (BBB) which limits drug delivery and immune-privileged status which hampers effective immune responses. Traditionally, high-dose irradiation (8 Gy) is known to effectively enhance anti-tumor immune responses, but its application is limited by the risk of severe brain damage. Currently, conventional dose segmentation (2 Gy) is the standard radiotherapy method, which does not fully exploit the potential of high-dose irradiation for immune activation. The hypothesis of our study posits that instead of directly applying high doses of radiation, which is risky, a strategy could be developed to harness the immune-stimulating benefits of high-dose irradiation indirectly. This involves using nanoparticles to enhance antigen presentation and immune responses in a safer manner. Angiopep-2 (A2) was proved a satisfactory BBB and brain targeting and Dbait is a small molecule that hijack DNA double strand break damage (DSB) repair proteins to make cancer cells more sensitive to radiation. In view of that, the following two nanoparticles were designed to combine immunity of GBM, radiation resistance and BBB innovatively. One is cationic liposome nanoparticle interacting with Dbait (A2-CL/Dbait NPs) for radiosensitization effect; the other is PLGA-PEG-Mal nanoparticle conjugated with OX40 antibody (A2-PLGA-PEG-Mal/anti-OX40 NPs) for tumor-derived protein antigens capture and optimistic immunoregulatory effect of anti-OX40 (which is known to enhance the activation and proliferation T cells). Both types of nanoparticles showed favorable targeting and low toxicity in experimental models. Specifically, the combination of A2-CL/Dbait NPs and A2-PLGA-PEG-Mal/anti-OX40 NPs led to a significant extension in the survival time and a significant tumor shrinkage of mice with GBM. The study demonstrates that combining these innovative nanoparticles with conventional radiotherapy can effectively address key challenges in GBM treatment. It represents a significant step toward more effective and safer therapeutic options for GBM patients.","PeriodicalId":49639,"journal":{"name":"Radiation Oncology","volume":"25 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142193506","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}
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