Pub Date : 2024-10-01DOI: 10.1016/j.ijrobp.2024.07.033
Purpose/Objective(s)
The feasibility of simulation-free radiotherapy (SFRT) has been demonstrated but information regarding its impact on routine care is lacking. The hypothesis was that SFRT is scaleable and beneficial in routine care. Key endpoints of this single institution study were SFRT utilization, impact on consultation-to-RT time and on-couch treatment duration.
Materials/Methods
All patients receiving palliative RT in the study period were eligible for consideration of SFRT unless mask immobilization, a stereotactic technique, or a definitive dose was required. Timing metrics were compared to a contemporary local cohort that received simulation-based palliative RT using unadjusted medians (Wilcoxon rank-sum test) and a propensity score-weighted regression. Electronic patient-reported outcomes (ePROs) captured 2-week toxicity and pain response.
Results
Between April 2018 and February 2024, there were 2845 palliative radiation courses were delivered, of which 1904 were eligible for this study. One thousand of the 1904 courses (52.5% SFRT utilization) were treated using the SFRT protocol, including 668 with IMRT/VMAT. Median patient age was 71 years with 60% being male and 32% being ECOG 2-4. SFRT reduced median consultation-to-RT time from 7.0 to 5.1 days (P < 0.0001) corresponding to an adjusted average treatment effect (aATE) of -2.3 days (95% CI = -2.9 to -1.7). SFRT increased median on-couch treatment duration from 16 min to 18 min (P < 0.0001; aATE 2.0 min, 95% CI = 0.2 to 3.9). SFRT utilization in eligible courses increased from 41% to 54% between the years 2018 and 2019 and 2022 and 2024. PRO-CTCAE grade 3 acute toxicity was 9% and at 4 weeks post RT patients with moderate/severe pain at baseline (≥ 5/10) had had a mean pain reduction of 3.5 points (7.1 to 3.6).
Conclusion
Using widely available technologies the SFRT-1000 cohort demonstrates routine care scalability with patient-centered and workflow benefits. SFRT is an attractive new palliative RT paradigm implementable in most settings.
{"title":"Implementing Simulation-Free Radiotherapy (SFRT) Rapid Access Palliation in Routine Care: A Propensity Score Weight-Adjusted Analysis of the SFRT-1000 Cohort","authors":"","doi":"10.1016/j.ijrobp.2024.07.033","DOIUrl":"10.1016/j.ijrobp.2024.07.033","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>The feasibility of simulation-free radiotherapy (SFRT) has been demonstrated but information regarding its impact on routine care is lacking. The hypothesis was that SFRT is scaleable and beneficial in routine care. Key endpoints of this single institution study were SFRT utilization, impact on consultation-to-RT time and on-couch treatment duration.</div></div><div><h3>Materials/Methods</h3><div>All patients receiving palliative RT in the study period were eligible for consideration of SFRT unless mask immobilization, a stereotactic technique, or a definitive dose was required. Timing metrics were compared to a contemporary local cohort that received simulation-based palliative RT using unadjusted medians (Wilcoxon rank-sum test) and a propensity score-weighted regression. Electronic patient-reported outcomes (ePROs) captured 2-week toxicity and pain response.</div></div><div><h3>Results</h3><div>Between April 2018 and February 2024, there were 2845 palliative radiation courses were delivered, of which 1904 were eligible for this study. One thousand of the 1904 courses (52.5% SFRT utilization) were treated using the SFRT protocol, including 668 with IMRT/VMAT. Median patient age was 71 years with 60% being male and 32% being ECOG 2-4. SFRT reduced median consultation-to-RT time from 7.0 to 5.1 days (<em>P</em> < 0.0001) corresponding to an adjusted average treatment effect (aATE) of -2.3 days (95% CI = -2.9 to -1.7). SFRT increased median on-couch treatment duration from 16 min to 18 min (<em>P</em> < 0.0001; aATE 2.0 min, 95% CI = 0.2 to 3.9). SFRT utilization in eligible courses increased from 41% to 54% between the years 2018 and 2019 and 2022 and 2024. PRO-CTCAE grade 3 acute toxicity was 9% and at 4 weeks post RT patients with moderate/severe pain at baseline (≥ 5/10) had had a mean pain reduction of 3.5 points (7.1 to 3.6).</div></div><div><h3>Conclusion</h3><div>Using widely available technologies the SFRT-1000 cohort demonstrates routine care scalability with patient-centered and workflow benefits. SFRT is an attractive new palliative RT paradigm implementable in most settings.</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ijrobp.2024.07.007
<div><h3>Purpose/Objective(s)</h3><div>Although RNI improves breast cancer survival, it increases risk of upper extremity lymphedema. We hypothesized that hypofractionated RNI may reduce lymphedema risk.</div></div><div><h3>Materials/Methods</h3><div>Patients with a recommendation for RNI for cT0-T3, N0-N2a, N3a invasive breast cancer were randomized between standard RNI (STD-RNI: 50 Gy to breast/chest wall and 45 Gy to RN) or shorter RNI (SH-RNI: 40.05 Gy to breast/chest wall and 37.5 Gy to RN). Patients were stratified by receipt of chemotherapy, body mass index (BMI), type of axillary surgery, and difference in arm volume prior to RNI. RN targets included the internal mammary, infraclavicular, and supraclavicular nodal basins; the level I and II axilla was treated if axillary lymph node dissection was not performed. Boost to the tumor bed or chest wall was permitted. Lymphedema was assessed via standard toxicity grading by the treating physician and by serial perometry measurement prior to surgery, post-operatively and then 6, 12, 18, and 24 months after radiation. The primary outcome was defined as a ≥ 10% relative difference in arm volume on at least one post-radiation perometry assessment, normalized by the pre-operative perometry measurement. Secondary outcomes included comparison of physician-reported toxicities using the NCI CTCAE version 4.0 scale graded weekly during RT, at 6 months, and then annually. Fisher’s exact tests compared groups. Local-regional recurrence (LRR) was calculated using the Kaplan-Meier method and compared using the log-rank test.</div></div><div><h3>Results</h3><div>There were three hundred twenty-four patients across 5 treatment centers were enrolled and randomized from 2017 to 2022 with median follow up of 4.75 years. Clinical-pathologic covariates were well-balanced by treatment arm. Median age was 54 years, 64% were non-Hispanic White, and 39% had body mass index (BMI) > 30. 57% underwent mastectomy with or without reconstruction and 42% underwent segmental mastectomy. Sixty-eight percent underwent axillary lymph node dissection and 90% received chemotherapy. Perometry-assessed lymphedema, the primary outcome, was less common after SH-RNI (29%) than STD-RNI (36%), but the difference was not statistically significant (<em>P</em> = 0.24). In contrast, physician-assessed lymphedema was significantly less common with SH-RNI than STD-RNI (15% vs. 27%, <em>P</em> = 0.009). Patients randomized to SH-RNI were less likely to experience any grade ≥ 2 toxicity (52% vs. 78%, <em>P</em> < 0.001). Pneumonitis was uncommon and similar between groups (3% vs 2%, <em>P</em> = 0.46). There were no brachial plexopathy events. Five-year LRR risk was 3% with SH-RNI and 2% with STD-RNI (<em>P</em> = 0.48).</div></div><div><h3>Conclusion</h3><div>In this primary outcome analysis of a multisite phase III randomized clinical trial, SH-RNI did not lower risk of perometry-assessed lymphedema. However, SH-RNI conferred a low risk o
{"title":"Primary Outcome Analysis for Shortening Adjuvant Photon Irradiation to Reduce Edema (SAPHIRE): A Randomized, Phase III Trial of Hypo- vs. Conventionally Fractionated Regional Nodal Irradiation (RNI)","authors":"","doi":"10.1016/j.ijrobp.2024.07.007","DOIUrl":"10.1016/j.ijrobp.2024.07.007","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Although RNI improves breast cancer survival, it increases risk of upper extremity lymphedema. We hypothesized that hypofractionated RNI may reduce lymphedema risk.</div></div><div><h3>Materials/Methods</h3><div>Patients with a recommendation for RNI for cT0-T3, N0-N2a, N3a invasive breast cancer were randomized between standard RNI (STD-RNI: 50 Gy to breast/chest wall and 45 Gy to RN) or shorter RNI (SH-RNI: 40.05 Gy to breast/chest wall and 37.5 Gy to RN). Patients were stratified by receipt of chemotherapy, body mass index (BMI), type of axillary surgery, and difference in arm volume prior to RNI. RN targets included the internal mammary, infraclavicular, and supraclavicular nodal basins; the level I and II axilla was treated if axillary lymph node dissection was not performed. Boost to the tumor bed or chest wall was permitted. Lymphedema was assessed via standard toxicity grading by the treating physician and by serial perometry measurement prior to surgery, post-operatively and then 6, 12, 18, and 24 months after radiation. The primary outcome was defined as a ≥ 10% relative difference in arm volume on at least one post-radiation perometry assessment, normalized by the pre-operative perometry measurement. Secondary outcomes included comparison of physician-reported toxicities using the NCI CTCAE version 4.0 scale graded weekly during RT, at 6 months, and then annually. Fisher’s exact tests compared groups. Local-regional recurrence (LRR) was calculated using the Kaplan-Meier method and compared using the log-rank test.</div></div><div><h3>Results</h3><div>There were three hundred twenty-four patients across 5 treatment centers were enrolled and randomized from 2017 to 2022 with median follow up of 4.75 years. Clinical-pathologic covariates were well-balanced by treatment arm. Median age was 54 years, 64% were non-Hispanic White, and 39% had body mass index (BMI) > 30. 57% underwent mastectomy with or without reconstruction and 42% underwent segmental mastectomy. Sixty-eight percent underwent axillary lymph node dissection and 90% received chemotherapy. Perometry-assessed lymphedema, the primary outcome, was less common after SH-RNI (29%) than STD-RNI (36%), but the difference was not statistically significant (<em>P</em> = 0.24). In contrast, physician-assessed lymphedema was significantly less common with SH-RNI than STD-RNI (15% vs. 27%, <em>P</em> = 0.009). Patients randomized to SH-RNI were less likely to experience any grade ≥ 2 toxicity (52% vs. 78%, <em>P</em> < 0.001). Pneumonitis was uncommon and similar between groups (3% vs 2%, <em>P</em> = 0.46). There were no brachial plexopathy events. Five-year LRR risk was 3% with SH-RNI and 2% with STD-RNI (<em>P</em> = 0.48).</div></div><div><h3>Conclusion</h3><div>In this primary outcome analysis of a multisite phase III randomized clinical trial, SH-RNI did not lower risk of perometry-assessed lymphedema. However, SH-RNI conferred a low risk o","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142359154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ijrobp.2024.07.012
Purpose/Objective(s)
We aimed to determine the maximum tolerable dose (MTD) and dose-limiting toxicity (DLT) of weekly lobaplatin combined with concurrent radiotherapy using image-guided volumetric modulated arc therapy (VMAT) and brachytherapy in locally advanced cervical cancer (LACC) patients.
Materials/Methods
Patients with clinical stage IB3-IVA cervical cancer were enrolled and received image-guided volume-modulated arc radiation therapy and brachytherapy combined with concurrent weekly lobaplatin following a standard 3+3 dose escalation design. Patients received 45 Gy in 25 fractions to the pelvis and 60 Gy in 25 fractions to the involved pelvic and para-aortic lymph nodes. High-dose-rate intracavitary brachytherapy was conducted weekly during the fourth or fifth week of radiation at a dose of 28 Gy in 4 fractions. The starting weekly dose of lobaplatin 8 mg/m2, which was subsequently successively increased by 2 mg/m2 for a total of 5 levels. The primary endpoints were the MTD and DLT of weekly lobaplatin. DLTs were defined as follows: (1) grade 4 hematologic toxicity, febrile neutropenia, or grade 3 or higher thrombocytopenia with bleeding; (2) grade 3 or higher nonhematologic toxicity (except nausea, vomiting, or alopecia); and (3) less than 3 cycles of lobaplatin due to treatment-related toxicity.
Results
Between December 30 and October 19, there were 21 patients who were enrolled in this study. All patients completed image-guided volume-modulated arc radiotherapy and brachytherapy per protocol. Three patients experienced DLTs: grade 3 fatigue at 14 mg/m2, two cycles of chemotherapy at 16 mg/m2, and grade 3 fatigue at 16 mg/m2. Grade 3 hematologic toxicities were observed only at 14 mg/m2 and 16 mg/m2, with 7 patients (33.3%) having leukopenia and 1 (4.8%) having neutropenia. The only severe and dose-limiting nonhematologic toxicity was Grade 3 fatigue. The MTD of weekly lobaplatin was 14 mg/m2.
Conclusion
In this phase I clinical trial, the MTD of weekly lobaplatin combined with image-guided volume-modulated arc radiation therapy and brachytherapy for LACC was found to be 14 mg/m2.
{"title":"Phase I Clinical Trial of Lobaplatin Combined with Image-Guided Volume-Modulated Arc Radiation Therapy in Locally Advanced Cervical Cancer","authors":"","doi":"10.1016/j.ijrobp.2024.07.012","DOIUrl":"10.1016/j.ijrobp.2024.07.012","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>We aimed to determine the maximum tolerable dose (MTD) and dose-limiting toxicity (DLT) of weekly lobaplatin combined with concurrent radiotherapy using image-guided volumetric modulated arc therapy (VMAT) and brachytherapy in locally advanced cervical cancer (LACC) patients.</div></div><div><h3>Materials/Methods</h3><div>Patients with clinical stage IB3-IVA cervical cancer were enrolled and received image-guided volume-modulated arc radiation therapy and brachytherapy combined with concurrent weekly lobaplatin following a standard 3+3 dose escalation design. Patients received 45 Gy in 25 fractions to the pelvis and 60 Gy in 25 fractions to the involved pelvic and para-aortic lymph nodes. High-dose-rate intracavitary brachytherapy was conducted weekly during the fourth or fifth week of radiation at a dose of 28 Gy in 4 fractions. The starting weekly dose of lobaplatin 8 mg/m<sup>2</sup>, which was subsequently successively increased by 2 mg/m<sup>2</sup> for a total of 5 levels. The primary endpoints were the MTD and DLT of weekly lobaplatin. DLTs were defined as follows: (1) grade 4 hematologic toxicity, febrile neutropenia, or grade 3 or higher thrombocytopenia with bleeding; (2) grade 3 or higher nonhematologic toxicity (except nausea, vomiting, or alopecia); and (3) less than 3 cycles of lobaplatin due to treatment-related toxicity.</div></div><div><h3>Results</h3><div>Between December 30 and October 19, there were 21 patients who were enrolled in this study. All patients completed image-guided volume-modulated arc radiotherapy and brachytherapy per protocol. Three patients experienced DLTs: grade 3 fatigue at 14 mg/m<sup>2</sup>, two cycles of chemotherapy at 16 mg/m<sup>2</sup>, and grade 3 fatigue at 16 mg/m<sup>2</sup>. Grade 3 hematologic toxicities were observed only at 14 mg/m<sup>2</sup> and 16 mg/m<sup>2</sup>, with 7 patients (33.3%) having leukopenia and 1 (4.8%) having neutropenia. The only severe and dose-limiting nonhematologic toxicity was Grade 3 fatigue. The MTD of weekly lobaplatin was 14 mg/m<sup>2</sup>.</div></div><div><h3>Conclusion</h3><div>In this phase I clinical trial, the MTD of weekly lobaplatin combined with image-guided volume-modulated arc radiation therapy and brachytherapy for LACC was found to be 14 mg/m<sup>2</sup>.</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142359556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ijrobp.2024.07.006
<div><h3>Purpose/Objective(s)</h3><div>Radiation-induced lung injury (RILI) can reduce survival time and lowering the quality of life of patients. However, the current standard therapy does not target its pathophysiologic process. Pirfenidone is indicated for idiopathic pulmonary fibrosis, and our experiments have shown that it ameliorates alveolar inflammation and fibrosis in mice after radiation, and its mechanism of action is similar to the pathophysiological process of RILI. Therefore, the aim of this trial was to investigate the efficacy and safety of pirfenidone in combination with standard therapy versus standard therapy alone for the treatment of grade 2 or 3 RILI.</div></div><div><h3>Materials/Methods</h3><div>This randomized, controlled, open-label phase II clinical trial enrolled patients diagnosed with grade 2 or 3 RILI at 10 centers who were randomly assigned in a 1:1 ratio to the pirfenidone group (pirfenidone plus standard therapy) and the control group (standard therapy). They were followed up once each at weeks 4, 8, 16, and 24 after randomization. Primary endpoint was change from baseline in DLCO% at week 24. Secondary endpoints were change from baseline in FVC%, FEV1%, CT score, symptom score, RILI classification score and acute pulmonary exacerbation free survival at week 24. Exploratory endpoints were progression free survival (PFS) and overall survival (OS). Repeated-measures data were analyzed using a linear mixed effects model. This was an exploratory trial and did not adjust alpha for multiple comparisons, so alpha was set to 0.05 (two-sided) for all endpoints.</div></div><div><h3>Results</h3><div>A total of 134 patients were enrolled, with 121 completing follow-up by February 16, 2024, there were 60 randomized to the pirfenidone group and 61 to the control group. Compared with the control group, the adjusted least squares mean changes from baseline to week 24 in DLCO%, FVC%, and FEV1% in the pirfenidone group increased by 10.6%, 9.4%, and 6.8%, respectively (<em>P</em> = 0.002, <em>P</em> = 0.004, and <em>P</em> = 0.051), and the proportion of improvement in CT ground-glass, reticulation, and honeycombing scores at week 24 compared to baseline increased by 28.0%, 50.8%, and 7.6%, respectively (<em>P</em> = 0.030, <em>P</em> = 0.002, and <em>P</em> = 0.358), and the 24-week survival rate without acute pulmonary exacerbation increased by 20.1% (<em>P</em> = 0.026). Cough, fever, dyspnea, radiation pneumonitis, and radiation pulmonary fibrosis scores at week 24 were not statistically different between the two groups, nor were PFS and OS (<em>P</em> = 0.056, <em>P</em> = 0.932, <em>P</em> = 0.897, <em>P</em> = 0.076, <em>P</em> = 0.152, <em>P</em> = 0.339, and <em>P</em> = 0.345). The incidence of grade 3, 4, and 5 adverse events was similar in the pirfenidone and control groups (11.7% vs 11.5%, 1.7% vs 3.3%, and 8.3% vs 6.6%), and no pirfenidone related grade ≥ 4 adverse events were observed.</div></div><div><h3>Conclusion<
{"title":"Pirfenidone in the Treatment of Radiation-Induced Lung Injury: A Randomized, Controlled, Multicenter Clinical Trial","authors":"","doi":"10.1016/j.ijrobp.2024.07.006","DOIUrl":"10.1016/j.ijrobp.2024.07.006","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Radiation-induced lung injury (RILI) can reduce survival time and lowering the quality of life of patients. However, the current standard therapy does not target its pathophysiologic process. Pirfenidone is indicated for idiopathic pulmonary fibrosis, and our experiments have shown that it ameliorates alveolar inflammation and fibrosis in mice after radiation, and its mechanism of action is similar to the pathophysiological process of RILI. Therefore, the aim of this trial was to investigate the efficacy and safety of pirfenidone in combination with standard therapy versus standard therapy alone for the treatment of grade 2 or 3 RILI.</div></div><div><h3>Materials/Methods</h3><div>This randomized, controlled, open-label phase II clinical trial enrolled patients diagnosed with grade 2 or 3 RILI at 10 centers who were randomly assigned in a 1:1 ratio to the pirfenidone group (pirfenidone plus standard therapy) and the control group (standard therapy). They were followed up once each at weeks 4, 8, 16, and 24 after randomization. Primary endpoint was change from baseline in DLCO% at week 24. Secondary endpoints were change from baseline in FVC%, FEV1%, CT score, symptom score, RILI classification score and acute pulmonary exacerbation free survival at week 24. Exploratory endpoints were progression free survival (PFS) and overall survival (OS). Repeated-measures data were analyzed using a linear mixed effects model. This was an exploratory trial and did not adjust alpha for multiple comparisons, so alpha was set to 0.05 (two-sided) for all endpoints.</div></div><div><h3>Results</h3><div>A total of 134 patients were enrolled, with 121 completing follow-up by February 16, 2024, there were 60 randomized to the pirfenidone group and 61 to the control group. Compared with the control group, the adjusted least squares mean changes from baseline to week 24 in DLCO%, FVC%, and FEV1% in the pirfenidone group increased by 10.6%, 9.4%, and 6.8%, respectively (<em>P</em> = 0.002, <em>P</em> = 0.004, and <em>P</em> = 0.051), and the proportion of improvement in CT ground-glass, reticulation, and honeycombing scores at week 24 compared to baseline increased by 28.0%, 50.8%, and 7.6%, respectively (<em>P</em> = 0.030, <em>P</em> = 0.002, and <em>P</em> = 0.358), and the 24-week survival rate without acute pulmonary exacerbation increased by 20.1% (<em>P</em> = 0.026). Cough, fever, dyspnea, radiation pneumonitis, and radiation pulmonary fibrosis scores at week 24 were not statistically different between the two groups, nor were PFS and OS (<em>P</em> = 0.056, <em>P</em> = 0.932, <em>P</em> = 0.897, <em>P</em> = 0.076, <em>P</em> = 0.152, <em>P</em> = 0.339, and <em>P</em> = 0.345). The incidence of grade 3, 4, and 5 adverse events was similar in the pirfenidone and control groups (11.7% vs 11.5%, 1.7% vs 3.3%, and 8.3% vs 6.6%), and no pirfenidone related grade ≥ 4 adverse events were observed.</div></div><div><h3>Conclusion<","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142359153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ijrobp.2024.07.017
Purpose/Objective(s)
Machine learning (ML) radiotherapy (RT) treatment planning has shown improved efficiency while maintaining quality. However, there has been no prospective evaluation of patient outcomes when using ML as standard-of-care for RT planning, thereby limiting the assessment of its value proposition. We hypothesized that minimal clinical differences in genitourinary (GU) and gastrointestinal (GI) toxicities exist between ML- and human-generated RT plans during prospective application.
Materials/Methods
We prospectively evaluated ML- and human-generated plans for curative-intent prostate RT (60 Gy in 20 fractions) in a cohort of 113 consecutive patients treated between November 2019 and June 2022. We employed a previously institutionally developed, validated, and clinically implemented dose prediction ML model functioning within a commercial RT planning system. ML planning, without any manual adjustments, was the default planning method used in all cases. Radiation oncologists either approved the ML plan or requested an alternative human-generated plan for direct comparison, and then selected the preferred plan for treatment. GU and GI toxicities with minimum follow-up of 180 days were collected for all patients. We performed a toxicity-free survival Kaplan-Meier analysis for grade 2+ GU and grade 2+ GI toxicities between ML- and human-generated plans, and comparisons were based on log-rank tests.
Results
In the prospective standard of care ML deployment study, radiation oncologists selected ML plans for clinical treatment in 86 cases (76%) and selected human plans in 27 cases (24%). For cases in which a human-generated plan was requested, the ML plan was selected for treatment in only one case. In terms of treatment outcomes, there were no treatment-related grade 2+ GI toxicities observed and no significant differences in toxicity-free survival were observed for GU grade 2+ toxicities between ML- and human-generated plans (P = 0.39).
Conclusion
This is the first study demonstrating that dose prediction ML planning maintains low levels of toxicity in curative-intent prostate cancer and encourages the clinical translation of this technology into practice. When appropriately validated and deployed, ML planning can retain good clinical outcomes while improving efficiencies and can be safely used as standard of care applicable to the majority of patients, with a human-in-loop strategy.
目的/目标 机器学习（ML）放疗（RT）治疗规划在保证质量的同时提高了效率。然而，目前还没有将机器学习作为标准治疗方法来制定放疗计划的前瞻性患者疗效评估，因此限制了对其价值主张的评估。我们假设，在前瞻性应用过程中，ML 和人工生成的 RT 计划在泌尿生殖系统（GU）和胃肠道（GI）毒性方面的临床差异极小。材料/方法我们在 2019 年 11 月至 2022 年 6 月期间接受治疗的 113 例连续患者队列中，对 ML 和人工生成的治疗性前列腺 RT（60 Gy，20 次分次）计划进行了前瞻性评估。我们采用了此前由本机构开发、验证并在临床上实施的剂量预测 ML 模型，该模型在商用 RT 计划系统中运行。ML计划是所有病例的默认计划方法，无需任何手动调整。放射肿瘤专家要么批准 ML 计划，要么要求提供人类生成的替代计划进行直接比较，然后选择首选计划进行治疗。我们收集了所有患者至少 180 天的泌尿系统和消化系统毒性随访结果。我们对 ML 计划和人类生成计划的 2 级以上 GU 和 2 级以上 GI 毒性进行了无毒生存期 Kaplan-Meier 分析，并根据 log-rank 检验进行比较。在要求使用人工生成计划的病例中，只有一个病例选择了 ML 计划进行治疗。在治疗结果方面，没有观察到与治疗相关的 2+ 级消化道毒性，在无毒生存率方面，ML 计划与人类生成计划之间没有观察到 2+ 级 GU 毒性的显著差异（P = 0.39）。如果经过适当的验证和部署，ML 计划可以在提高效率的同时保持良好的临床效果，并且可以安全地用作适用于大多数患者的标准治疗方法，同时采用人工环路策略。
{"title":"Clinical Outcomes for Standard of Care Machine Learning Prostate Radiotherapy Treatment Planning","authors":"","doi":"10.1016/j.ijrobp.2024.07.017","DOIUrl":"10.1016/j.ijrobp.2024.07.017","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Machine learning (ML) radiotherapy (RT) treatment planning has shown improved efficiency while maintaining quality. However, there has been no prospective evaluation of patient outcomes when using ML as standard-of-care for RT planning, thereby limiting the assessment of its value proposition. We hypothesized that minimal clinical differences in genitourinary (GU) and gastrointestinal (GI) toxicities exist between ML- and human-generated RT plans during prospective application.</div></div><div><h3>Materials/Methods</h3><div>We prospectively evaluated ML- and human-generated plans for curative-intent prostate RT (60 Gy in 20 fractions) in a cohort of 113 consecutive patients treated between November 2019 and June 2022. We employed a previously institutionally developed, validated, and clinically implemented dose prediction ML model functioning within a commercial RT planning system. ML planning, without any manual adjustments, was the default planning method used in all cases. Radiation oncologists either approved the ML plan or requested an alternative human-generated plan for direct comparison, and then selected the preferred plan for treatment. GU and GI toxicities with minimum follow-up of 180 days were collected for all patients. We performed a toxicity-free survival Kaplan-Meier analysis for grade 2+ GU and grade 2+ GI toxicities between ML- and human-generated plans, and comparisons were based on log-rank tests.</div></div><div><h3>Results</h3><div>In the prospective standard of care ML deployment study, radiation oncologists selected ML plans for clinical treatment in 86 cases (76%) and selected human plans in 27 cases (24%). For cases in which a human-generated plan was requested, the ML plan was selected for treatment in only one case. In terms of treatment outcomes, there were no treatment-related grade 2+ GI toxicities observed and no significant differences in toxicity-free survival were observed for GU grade 2+ toxicities between ML- and human-generated plans (<em>P</em> = 0.39).</div></div><div><h3>Conclusion</h3><div>This is the first study demonstrating that dose prediction ML planning maintains low levels of toxicity in curative-intent prostate cancer and encourages the clinical translation of this technology into practice. When appropriately validated and deployed, ML planning can retain good clinical outcomes while improving efficiencies and can be safely used as standard of care applicable to the majority of patients, with a human-in-loop strategy.</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ijrobp.2024.07.038
Purpose/Objective(s)
Heterotopic ossification (HO) is the formation of extra-skeletal bone in abnormal areas including muscle and soft tissue. Once HO forms, surgical excision is the only option which unfortunately frequently leads to recurrence. Radiation has been one of the most effective prophylactic treatments for HO, however, the mechanism remains unknown despite multiple randomized controlled trials demonstrating radiation efficacy. The purpose of this study is to recapitulate the use of radiation in preventing heterotopic ossification in an animal model to thereby mechanistically investigate radiation-induced changes in gene and protein expression changes at the single cell level.
Materials/Methods
We established a traumatic HO burn/tenotomy mouse model demonstrating decreased HO formation with radiation therapy. Single-cell RNA sequencing (scRNA-seq) of the Achilles tenotomy injury site at 7 days post-injury with and without radiation treatment was performed as an unbiased approach to determine radiation effects on gene expression at the single cell level. Further scRNA-seq analyses revealed distinct cell type clustering as well as differentially expressed genes and enriched pathways. Immunofluorescent histology of the injury site at 7 days post-injury was performed to confirm protein expression changes and scRNA-seq analyses.
Results
There was 7 Gy in one fraction delivered 72 hours perioperatively to the injury site decreased HO formation by approximately 50% compared to control group in a burn/tenotomy traumatic HO mouse model (P < 0.05, n = 10/group). Tendon-associated HO superior to the radiation field demonstrated no difference in HO volume between control and radiated groups (P = ns, n = 10/group). ScRNA-seq identified 10 distinct cell clusters in both control and radiated groups. Further analyses revealed decreased major transcription factors for osteogenic (Runx2) and chondrogenic (Sox9) gene expression in irradiated HO progenitor cells. Immunofluorescence of the injured hindlimb also reveal decreased RUNX2 and SOX9 signaling with radiation treatment (P < 0.05, n = 9/group). Our scRNA-seq analyses also demonstrated downregulated Alk4 and BMP HO signaling pathways with radiation treatment, leading to decreased HO formation.
Conclusion
Our study is the first to explore the mechanism of radiotherapy prophylaxis in the prevention of traumatic HO. Our findings reveal that radiation reduces aberrant osteochondral differentiation of HO progenitor cells, thereby decreasing overall HO and improving joint function. Future studies will further elucidate the key pathways and optimize the timing and dosage of radiation prophylaxis to mitigate HO.
{"title":"Unraveling the Mechanism behind Prophylactic Radiotherapy to Prevent Traumatic Heterotopic Ossification","authors":"","doi":"10.1016/j.ijrobp.2024.07.038","DOIUrl":"10.1016/j.ijrobp.2024.07.038","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Heterotopic ossification (HO) is the formation of extra-skeletal bone in abnormal areas including muscle and soft tissue. Once HO forms, surgical excision is the only option which unfortunately frequently leads to recurrence. Radiation has been one of the most effective prophylactic treatments for HO, however, the mechanism remains unknown despite multiple randomized controlled trials demonstrating radiation efficacy. The purpose of this study is to recapitulate the use of radiation in preventing heterotopic ossification in an animal model to thereby mechanistically investigate radiation-induced changes in gene and protein expression changes at the single cell level.</div></div><div><h3>Materials/Methods</h3><div>We established a traumatic HO burn/tenotomy mouse model demonstrating decreased HO formation with radiation therapy. Single-cell RNA sequencing (scRNA-seq) of the Achilles tenotomy injury site at 7 days post-injury with and without radiation treatment was performed as an unbiased approach to determine radiation effects on gene expression at the single cell level. Further scRNA-seq analyses revealed distinct cell type clustering as well as differentially expressed genes and enriched pathways. Immunofluorescent histology of the injury site at 7 days post-injury was performed to confirm protein expression changes and scRNA-seq analyses.</div></div><div><h3>Results</h3><div>There was 7 Gy in one fraction delivered 72 hours perioperatively to the injury site decreased HO formation by approximately 50% compared to control group in a burn/tenotomy traumatic HO mouse model (<em>P</em> < 0.05, <em>n</em> = 10/group). Tendon-associated HO superior to the radiation field demonstrated no difference in HO volume between control and radiated groups (<em>P</em> = ns, <em>n</em> = 10/group). ScRNA-seq identified 10 distinct cell clusters in both control and radiated groups. Further analyses revealed decreased major transcription factors for osteogenic (<em>Runx2</em>) and chondrogenic (<em>Sox9</em>) gene expression in irradiated HO progenitor cells. Immunofluorescence of the injured hindlimb also reveal decreased RUNX2 and SOX9 signaling with radiation treatment (<em>P</em> < 0.05, <em>n</em> = 9/group). Our scRNA-seq analyses also demonstrated downregulated Alk4 and BMP HO signaling pathways with radiation treatment, leading to decreased HO formation.</div></div><div><h3>Conclusion</h3><div>Our study is the first to explore the mechanism of radiotherapy prophylaxis in the prevention of traumatic HO. Our findings reveal that radiation reduces aberrant osteochondral differentiation of HO progenitor cells, thereby decreasing overall HO and improving joint function. Future studies will further elucidate the key pathways and optimize the timing and dosage of radiation prophylaxis to mitigate HO.</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ijrobp.2024.08.016
<div><h3>Purpose/Objective(s)</h3><div>To assess the feasibility and safety of weekly on-line MR-Linac (MRL) adaptive radiotherapy with concurrent temozolomide (chemoRT), with a reduced 5 mm clinical target volume (CTV) margin, for patients with HGG (grade 4 astrocytoma or IDH-wildtype glioblastoma).</div></div><div><h3>Materials/Methods</h3><div>In this single arm Phase 2 trial (NCT04726397), patients with newly diagnosed HGG planned for chemoRT with either 60 Gy/30 fractions (long course) or 40 Gy/15 fractions (short course) were eligible. Gross tumor volume (GTV) was defined as the surgical cavity and residual tumor; the CTV was a 5 mm uniform expansion plus involved T2-hyperintense FLAIR signal at the discretion of the oncologist; PTV was 3 mm. All patients were treated using a 1.5T integrated MRL. At fraction 1, and each subsequent fifth fraction, an on-line contrast-enhanced MR was acquired, volumes were re-contoured and treatment was re-planned. For the remaining fractions an on-line workflow used non-enhanced MR images to account for positional shifts. The primary endpoint was the risk of a marginal failure (MF) defined as 20-80% of the recurrent GTV (at the time of failure) within the 95% treatment isodose line and/or within a standard 15 mm CTV envelope. Using a historical 11.1% MF event risk from previously reported series using non-adaptive chemoRT with standard (15-20 mm) CTV margins, non-inferiority would be demonstrated if 13 or fewer MF events were observed within a sample size of 98, assuming a 11.9% non-inferiority margin (95% upper boundary of historical outcomes). Secondary endpoints included progression-free survival (PFS) and overall survival (OS) according to treatment schedule (long versus short course).</div></div><div><h3>Results</h3><div>A total of 108 patients were consented between April 2021 and May 2023 of which 98 completed the treatment protocol (59 long course and 39 short course). All tumors were IDH-wt, and 52/98 (53%) were MGMT methylated (MGMT-m), 41/98 (42%) unmethylated (MGMT-um) and 5/98 (5%) indeterminate. Median follow up was 23.3 months (mo). MF events were observed in 4/98 (4.1%, 95% CI: 1.6-10%) patients, establishing non-inferiority (p<0.001); the most common pattern of failure was central (52%). Median PFS was 11.6 mo for a long course (14.1 mo for MGMT-m and 8.5 mo for MGMT-um), and 6.8 mo for those treated with a short course (9.4 mo for MGMT-m and 5.1 mo for MGMT-um). Median OS was 18.5 mo after a long course (31.9 mo for MGMT-m and 13.0 mo for MGMT-um) and 10.6 mo after short course (15.3 mo for MGMT-m and 8.9 mo for MGMT-um).</div></div><div><h3>Conclusion</h3><div>We present the first trial evaluating on-line MRL weekly adaptive chemoRT for HGG with a limited CTV. Safety and feasibility was demonstrated with a low risk of MF (4%) without compromising PFS or OS. Further trials are required to test whether the reduction in irradiated normal brain tissue using this approach results in neurocog
{"title":"MR-Linac On-Line Weekly Adaptive Radiotherapy for High Grade Glioma (HGG): Results from the UNITED Single Arm Phase II Trial","authors":"","doi":"10.1016/j.ijrobp.2024.08.016","DOIUrl":"10.1016/j.ijrobp.2024.08.016","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>To assess the feasibility and safety of weekly on-line MR-Linac (MRL) adaptive radiotherapy with concurrent temozolomide (chemoRT), with a reduced 5 mm clinical target volume (CTV) margin, for patients with HGG (grade 4 astrocytoma or IDH-wildtype glioblastoma).</div></div><div><h3>Materials/Methods</h3><div>In this single arm Phase 2 trial (NCT04726397), patients with newly diagnosed HGG planned for chemoRT with either 60 Gy/30 fractions (long course) or 40 Gy/15 fractions (short course) were eligible. Gross tumor volume (GTV) was defined as the surgical cavity and residual tumor; the CTV was a 5 mm uniform expansion plus involved T2-hyperintense FLAIR signal at the discretion of the oncologist; PTV was 3 mm. All patients were treated using a 1.5T integrated MRL. At fraction 1, and each subsequent fifth fraction, an on-line contrast-enhanced MR was acquired, volumes were re-contoured and treatment was re-planned. For the remaining fractions an on-line workflow used non-enhanced MR images to account for positional shifts. The primary endpoint was the risk of a marginal failure (MF) defined as 20-80% of the recurrent GTV (at the time of failure) within the 95% treatment isodose line and/or within a standard 15 mm CTV envelope. Using a historical 11.1% MF event risk from previously reported series using non-adaptive chemoRT with standard (15-20 mm) CTV margins, non-inferiority would be demonstrated if 13 or fewer MF events were observed within a sample size of 98, assuming a 11.9% non-inferiority margin (95% upper boundary of historical outcomes). Secondary endpoints included progression-free survival (PFS) and overall survival (OS) according to treatment schedule (long versus short course).</div></div><div><h3>Results</h3><div>A total of 108 patients were consented between April 2021 and May 2023 of which 98 completed the treatment protocol (59 long course and 39 short course). All tumors were IDH-wt, and 52/98 (53%) were MGMT methylated (MGMT-m), 41/98 (42%) unmethylated (MGMT-um) and 5/98 (5%) indeterminate. Median follow up was 23.3 months (mo). MF events were observed in 4/98 (4.1%, 95% CI: 1.6-10%) patients, establishing non-inferiority (p<0.001); the most common pattern of failure was central (52%). Median PFS was 11.6 mo for a long course (14.1 mo for MGMT-m and 8.5 mo for MGMT-um), and 6.8 mo for those treated with a short course (9.4 mo for MGMT-m and 5.1 mo for MGMT-um). Median OS was 18.5 mo after a long course (31.9 mo for MGMT-m and 13.0 mo for MGMT-um) and 10.6 mo after short course (15.3 mo for MGMT-m and 8.9 mo for MGMT-um).</div></div><div><h3>Conclusion</h3><div>We present the first trial evaluating on-line MRL weekly adaptive chemoRT for HGG with a limited CTV. Safety and feasibility was demonstrated with a low risk of MF (4%) without compromising PFS or OS. Further trials are required to test whether the reduction in irradiated normal brain tissue using this approach results in neurocog","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ijrobp.2024.07.036
Purpose/Objective(s)
Partial tumor irradiation (PTI) is a novel immunomodulatory concept which adds to the direct cell-killing radiation effects an additional component of immune-mediated tumor cell-killing. PTI consists of 3 key principles: (1) neutralizing the immunosuppressive, central hypovascularized, and hypometabolic tumor segment, (2) preserving the peritumoral immune microenvironment (PIM) as OAR, and (3) delivering the treatment at precisely planned times, individually tailored for each patient based on homeostatic oscillations of immune activity (time-synchronized immune-guided radiotherapy). We hypothesized that PTI would generate radio-immunogenic effects thereby enhancing patient prognosis. The primary endpoint: bystander and abscopal responses rate.
Materials/Methods
This is a mono-centric, prospective, two-arm, phase 1 proof of principle trial including 22 patients with complex unresectable bulky tumors and at least 1 untreated metastatic site, deemed unsuitable for standard radiotherapy experiencing disease progression despite systemic therapies. Hypovascularized and hypometabolic tumor segment, delineated using the c.e. CT and FDG-PET-CT, was targeted with 10 Gy x 3 at 70% sparing the PIM. 2 weeks prior PTI, each patient had 7 serial blood draws assessing CRP, LDH and lymphocyte/monocyte ratio to determine each patient´s idiosyncratic immune activity cycle. First 11 patients (arm 1) PTI was delivered at an estimated “less reactive day” and to last 11 patients (arm 2) at “most reactive day.” In selected patients, residual tumors, radiation-spared PIM and unirradiated abscopal tumor sites were surgically removed for immunohistochemistry (IHC) and cell-death inducing genes (CDIG) analysis.
Results
PTI exhibited significant radio-immunogenic effect (Tab. 1). Arm 2 demonstrated superior outcomes across nearly all treatment aspects. A higher proportion of long-term survivors were from arm 2 (55%, median follow-up of 54 months) compared to arm 1 (27%, median follow-up of 43 months). IHC and CDIG revealed significant anti-tumor-directed-activation of the immune system.
Conclusion
PTI was safe and effective. This study highlights the profound impact PTI can have on a highly palliative patient cohort previously deemed beyond therapeutic hope. It revealed the critical impact of treatment timing on clinical outcomes which has significant implications for optimizing individualized cancer treatment.
{"title":"Time-Synchronized Immune-Guided Partial Tumor Irradiation: Proof-of-Principle Trial (NCT04168320)","authors":"","doi":"10.1016/j.ijrobp.2024.07.036","DOIUrl":"10.1016/j.ijrobp.2024.07.036","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Partial tumor irradiation (PTI) is a novel immunomodulatory concept which adds to the direct cell-killing radiation effects an additional component of immune-mediated tumor cell-killing. PTI consists of 3 key principles: (1) neutralizing the immunosuppressive, central hypovascularized, and hypometabolic tumor segment, (2) preserving the peritumoral immune microenvironment (PIM) as OAR, and (3) delivering the treatment at precisely planned times, individually tailored for each patient based on homeostatic oscillations of immune activity (time-synchronized immune-guided radiotherapy). We hypothesized that PTI would generate radio-immunogenic effects thereby enhancing patient prognosis. The primary endpoint: bystander and abscopal responses rate.</div></div><div><h3>Materials/Methods</h3><div>This is a mono-centric, prospective, two-arm, phase 1 proof of principle trial including 22 patients with complex unresectable bulky tumors and at least 1 untreated metastatic site, deemed unsuitable for standard radiotherapy experiencing disease progression despite systemic therapies. Hypovascularized and hypometabolic tumor segment, delineated using the c.e. CT and FDG-PET-CT, was targeted with 10 Gy x 3 at 70% sparing the PIM. 2 weeks prior PTI, each patient had 7 serial blood draws assessing CRP, LDH and lymphocyte/monocyte ratio to determine each patient´s idiosyncratic immune activity cycle. First 11 patients (arm 1) PTI was delivered at an estimated “less reactive day” and to last 11 patients (arm 2) at “most reactive day.” In selected patients, residual tumors, radiation-spared PIM and unirradiated abscopal tumor sites were surgically removed for immunohistochemistry (IHC) and cell-death inducing genes (CDIG) analysis.</div></div><div><h3>Results</h3><div>PTI exhibited significant radio-immunogenic effect (Tab. 1). Arm 2 demonstrated superior outcomes across nearly all treatment aspects. A higher proportion of long-term survivors were from arm 2 (55%, median follow-up of 54 months) compared to arm 1 (27%, median follow-up of 43 months). IHC and CDIG revealed significant anti-tumor-directed-activation of the immune system.</div></div><div><h3>Conclusion</h3><div>PTI was safe and effective. This study highlights the profound impact PTI can have on a highly palliative patient cohort previously deemed beyond therapeutic hope. It revealed the critical impact of treatment timing on clinical outcomes which has significant implications for optimizing individualized cancer treatment.</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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