Pub Date : 2024-10-01DOI: 10.1016/j.ijrobp.2024.07.021
Purpose/Objective(s)
As the survival rates of childhood cancer improve, it becomes increasingly important to study the impact of multi-modality therapies on long-term health. Radiotherapy has been implicated as a contributor to late toxicities such as second malignant neoplasms and cardiovascular disease; however, there are still significant gaps in knowledge. Indeed, survivors presenting with late health effects today were treated before the widespread availability of 3D imaging and radiotherapy planning. However, without 3D organ dosimetry, it is difficult to translate the knowledge gained from past treatments into the dose tolerance criteria needed for improving outcomes for patients treated today. The National Wilms Tumor Study (NWTS) provides a unique opportunity to bridge this gap. This paper describes the methods, workflow, and results of a multi-year effort to reconstruct radiotherapy organ doses for the NWTS cohort in support of late effects research.
Materials/Methods
We reconstructed 3D organ doses for 4716 pediatric patients in the NWTS cohort. As CT images were not available for the NWTS patients, computational phantoms were selected from a body-size dependent phantom library to use as surrogate anatomy. Each patient was matched to a phantom in the library based on gender, height, and weight at age of Wilms tumor diagnosis. A DICOM CT image set and structure file for the matched phantom was then imported into a treatment planning system (TPS) for reconstruction of the radiotherapy fields according to paper medical records. The radiotherapy planning was performed by an experienced medical physicist under the supervision of a radiation oncologist familiar with protocols used during the NWTS trials. As the accuracy of the TPS is limited in the out-of-field region, Monte Carlo radiation transport calculations were also performed to improve the organ dose estimates. All calculations were performed on the NIH high-performance computing cluster.
Results
The patients were treated with a variety of photon energies: 4 MV (23%), 6 MV (48%), 10 MV (3%), Co-60 (23%), and other (3%). The most common treatment fields were left and right-flank, abdomen, and chest. The Monte Carlo dose calculations took approximately ~100 CPU hours (wall clock time ~2 hours) for a typical patient, resulting in approximately 0.5 million CPU hours in total for the cohort. Mean organ dose and dose-volume metrics were computed for more than 100 organs or tissues.
Conclusion
This study represents the first time Monte Carlo methods have been directly applied on a large scale to reconstruct organs doses for an epidemiological cohort. The organ doses for the NWTS cohort will provide valuable information for developing dose tolerance criteria for mitigating radiotherapy toxicity.
{"title":"Results of a Dose Reconstruction Effort for a Large-Scale Retrospective Study on Late Health Effects Following Radiotherapy within the National Wilms Tumor Study","authors":"","doi":"10.1016/j.ijrobp.2024.07.021","DOIUrl":"10.1016/j.ijrobp.2024.07.021","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>As the survival rates of childhood cancer improve, it becomes increasingly important to study the impact of multi-modality therapies on long-term health. Radiotherapy has been implicated as a contributor to late toxicities such as second malignant neoplasms and cardiovascular disease; however, there are still significant gaps in knowledge. Indeed, survivors presenting with late health effects today were treated before the widespread availability of 3D imaging and radiotherapy planning. However, without 3D organ dosimetry, it is difficult to translate the knowledge gained from past treatments into the dose tolerance criteria needed for improving outcomes for patients treated today. The National Wilms Tumor Study (NWTS) provides a unique opportunity to bridge this gap. This paper describes the methods, workflow, and results of a multi-year effort to reconstruct radiotherapy organ doses for the NWTS cohort in support of late effects research.</div></div><div><h3>Materials/Methods</h3><div>We reconstructed 3D organ doses for 4716 pediatric patients in the NWTS cohort. As CT images were not available for the NWTS patients, computational phantoms were selected from a body-size dependent phantom library to use as surrogate anatomy. Each patient was matched to a phantom in the library based on gender, height, and weight at age of Wilms tumor diagnosis. A DICOM CT image set and structure file for the matched phantom was then imported into a treatment planning system (TPS) for reconstruction of the radiotherapy fields according to paper medical records. The radiotherapy planning was performed by an experienced medical physicist under the supervision of a radiation oncologist familiar with protocols used during the NWTS trials. As the accuracy of the TPS is limited in the out-of-field region, Monte Carlo radiation transport calculations were also performed to improve the organ dose estimates. All calculations were performed on the NIH high-performance computing cluster.</div></div><div><h3>Results</h3><div>The patients were treated with a variety of photon energies: 4 MV (23%), 6 MV (48%), 10 MV (3%), Co-60 (23%), and other (3%). The most common treatment fields were left and right-flank, abdomen, and chest. The Monte Carlo dose calculations took approximately ~100 CPU hours (wall clock time ~2 hours) for a typical patient, resulting in approximately 0.5 million CPU hours in total for the cohort. Mean organ dose and dose-volume metrics were computed for more than 100 organs or tissues.</div></div><div><h3>Conclusion</h3><div>This study represents the first time Monte Carlo methods have been directly applied on a large scale to reconstruct organs doses for an epidemiological cohort. The organ doses for the NWTS cohort will provide valuable information for developing dose tolerance criteria for mitigating radiotherapy toxicity.</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":"142358947","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.2024.07.051
Purpose/Objective(s)
To report the results of a multi-center phase II trial of using proton re-irradiation (re-RT) for previously irradiated recurrent head/neck cancer (HNC).
Materials/Methods
Recurrent HNC patients who received >/= 40 Gy of prior head/neck radiation were enrolled. Patients received fractionated re-RT (F-Re-RT to 70 Gy) or QUAD Shot re-RT (QS-Re-RT, 4 cycles to 59.2 Gy) at physician discretion. The primary endpoints (Clopper-Pearson Confidence Intervals method) were to determine the 12-months, 6-months locoregional recurrence-free (LRRF) rates for F-Re-RT and QS-Re-RT, respectively. Secondary endpoints were to determine: overall survival (OS), progression-free survival (PFS) [both estimated using the Kaplan-Meier method]; distant metastasis (DM), locoregional recurrence (LRR) rates [both calculated from using the Cumulative Incidence Function with death as a competing event]. Patient reported outcomes (PROs) included EORTC QLQ-HN35, PRO-CTCAE, Skindex-16, OMWQ-HM mucositis, EQ-5D. Median follow-up was calculated using the Reverse Kaplan-Meier method.
Results
From July 2017 to November 2022, 88 patients were enrolled (85 analyzable): F-Re-RT (n = 57) versus QS-Re-RT (n = 28). F-Re-RT patients were young with better performance status versus QS-Re-RT patients. Median follow-up was 35 months (all patients); F-Re-RT (38 months); QS-Re-RT (23 months). The 1-year LRRF rate for F-Re-RT was 71% (90% CI = 59%, 81%); 6-month LRRF rate for QS-Re-RT was 76% (90% CI = 58%, 89%) [See table for treatment factors, other endpoints] 36% of the patients had acute grade 3-4 toxicities, most notably dermatitis, dysphagia, dysgeusia. Late grade 3 complications were 20% (see the Table below). Nine patients had grade 4 and 3 had grade 5 complications. The Baseline, 1-year post re-RT mean score of EORTC QLQ-HN35 for F-Re-RT versus QS-Re-RT were 31.05 to 39.09 versus 35.43 to 14.85. Other PROs will be presented at the meeting.
Conclusion
In this largest and first multi-center phase II trial for recurrent HNC patients, proton therapy achieved remarkable locoregional control and survival. Although long-term survivors (> 5 years) were observed which compares very favorably to other treatment modalities, especially when multiple therapies were done prior to re-RT with proton, these patients remain at risk for late complications.
{"title":"Phase II Trial of Proton Re-Irradiation+/-Chemotherapy in Previously Irradiated Recurrent Head/Neck Cancer","authors":"","doi":"10.1016/j.ijrobp.2024.07.051","DOIUrl":"10.1016/j.ijrobp.2024.07.051","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>To report the results of a multi-center phase II trial of using proton re-irradiation (re-RT) for previously irradiated recurrent head/neck cancer (HNC).</div></div><div><h3>Materials/Methods</h3><div>Recurrent HNC patients who received >/= 40 Gy of prior head/neck radiation were enrolled. Patients received fractionated re-RT (F-Re-RT to 70 Gy) or QUAD Shot re-RT (QS-Re-RT, 4 cycles to 59.2 Gy) at physician discretion. The primary endpoints (Clopper-Pearson Confidence Intervals method) were to determine the 12-months, 6-months locoregional recurrence-free (LRRF) rates for F-Re-RT and QS-Re-RT, respectively. Secondary endpoints were to determine: overall survival (OS), progression-free survival (PFS) [both estimated using the Kaplan-Meier method]; distant metastasis (DM), locoregional recurrence (LRR) rates [both calculated from using the Cumulative Incidence Function with death as a competing event]. Patient reported outcomes (PROs) included EORTC QLQ-HN35, PRO-CTCAE, Skindex-16, OMWQ-HM mucositis, EQ-5D. Median follow-up was calculated using the Reverse Kaplan-Meier method.</div></div><div><h3>Results</h3><div>From July 2017 to November 2022, 88 patients were enrolled (85 analyzable): F-Re-RT (<em>n</em> = 57) versus QS-Re-RT (<em>n</em> = 28). F-Re-RT patients were young with better performance status versus QS-Re-RT patients. Median follow-up was 35 months (all patients); F-Re-RT (38 months); QS-Re-RT (23 months). The 1-year LRRF rate for F-Re-RT was 71% (90% CI = 59%, 81%); 6-month LRRF rate for QS-Re-RT was 76% (90% CI = 58%, 89%) [See table for treatment factors, other endpoints] 36% of the patients had acute grade 3-4 toxicities, most notably dermatitis, dysphagia, dysgeusia. Late grade 3 complications were 20% (see the Table below). Nine patients had grade 4 and 3 had grade 5 complications. The Baseline, 1-year post re-RT mean score of EORTC QLQ-HN35 for F-Re-RT versus QS-Re-RT were 31.05 to 39.09 versus 35.43 to 14.85. Other PROs will be presented at the meeting.</div></div><div><h3>Conclusion</h3><div>In this largest and first multi-center phase II trial for recurrent HNC patients, proton therapy achieved remarkable locoregional control and survival. Although long-term survivors (> 5 years) were observed which compares very favorably to other treatment modalities, especially when multiple therapies were done prior to re-RT with proton, these patients remain at risk for late complications.</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":"142358542","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.2024.07.053
<div><h3>Purpose/Objective(s)</h3><div>Radiation-induced mucositis (RIM) pain confers substantial morbidity for head and neck cancer (HNC) patients undergoing radiotherapy (RT) or chemoradiotherapy (CRT). With no established standard treatment, OPTIMAL-HN aimed to demonstrate the non-inferiority of multimodal analgesia (MMA; analgesic medications with different mechanisms of action) to the institutional standard of opioid analgesia alone.</div></div><div><h3>Materials/Methods</h3><div>OPTIMAL-HN (NCT04221165) was an open label, single-institution, non-inferiority, randomized clinical trial. HNC patients receiving curative-intent RT/CRT and experiencing moderate 4 of 10 RIM pain were randomized 1:1, stratified by RT vs. CRT, to opioids alone per institutional standard or MMA (Pregabalin, Acetaminophen, Naproxen, and opioids if required). The primary endpoint was mean pain score (range = 0-10) during the last week of RT. Secondary endpoints included mean weekly opioid use, duration of opioid requirement, mean daily pain score, quality of life, hospitalizations for analgesic medication-related complications, time to feeding tube insertion, weight loss, toxicity, RT interruptions, and death. Assuming a non-inferiority margin of 1 point, a standard deviation of 1.5 in both arms (80% power, 1-sided alpha 0.05, dropout rate 6%), 62 patients were required. All analyses were pre-specified, including testing for superiority if non-inferiority was demonstrated, and intention-to-treat.</div></div><div><h3>Results</h3><div>Forty-nine patients were enrolled, 25 in the opioid analgesia alone arm and 24 in the MMA arm. The trial was prematurely closed due to slow accrual. Baseline characteristics were well-balanced between arms; median age was 61 (IQR = 53-70) years; 36 male (73.5%) and 13 female (26.5%); baseline median pain score was 5 (IQR = 4-6) in the opioid arm and 4 (IQR = 4-6) in the MMA arm (<em>P</em> = 0.161). Median follow-up was 4.24 (IQR = 3.75-4.73) months. The primary endpoint, mean pain score during the last 7 days of RT, was 5.10 (95% CI = 4.11-6.09) in the opioid arm and 4.85 (95% CI = 3.81-5.90) in the MMA arm (non-inferiority <em>P</em> = 0.039, superiority <em>P</em> = 0.724). Analyzing all pain scores from enrollment to 6 weeks post-RT using linear mixed models, MMA demonstrated significantly lower pain scores compared to opioids alone (non-inferiority <em>P</em> = 0.002, superiority <em>P</em> < 0.001). Median weekly opioid use was numerically higher in the opioid arm (99.2 mg oral morphine equivalent dose [OMED], IQR = 16.3-173.1) compared to the MMA arm (50.5 mg OMED; IQR = 8.4-126.3), although nonsignificant (<em>P</em> = 0.435). One patient in the MMA arm was admitted with grade 3 acute kidney injury, possibly related to the analgesic regimen. There was no grade ≥ 3 toxicity in the opioid arm. Arms were similar for all other secondary endpoints.</div></div><div><h3>Conclusion</h3><div>MMA demonstrates non-inferiority to opioid anal
目的/目标：对于接受放射治疗（RT）或化学放疗（CRT）的头颈部癌症（HNC）患者来说，放射诱导的粘膜炎（RIM）疼痛会导致严重的发病率。由于没有既定的标准治疗方法，OPTIMAL-HN旨在证明多模式镇痛（MMA；具有不同作用机制的镇痛药物）的效果不劣于仅使用阿片类镇痛的机构标准。材料/方法OPTIMAL-HN（NCT04221165）是一项开放标签、单一机构、非劣效随机临床试验。按照机构标准或 MMA（普瑞巴林、对乙酰氨基酚、萘普生，必要时加阿片类药物），对接受治愈性 RT/CRT 且出现中度 4 of 10 RIM 疼痛的 HNC 患者进行 1:1 随机分组，按 RT vs. CRT 进行分层。主要终点是 RT 最后一周的平均疼痛评分（范围 = 0-10）。次要终点包括每周阿片类药物平均用量、阿片类药物需求持续时间、每日平均疼痛评分、生活质量、镇痛药物相关并发症住院情况、插入喂食管时间、体重下降、毒性、RT中断和死亡。假设两组的非劣效差为 1 分，标准差为 1.5（功率为 80%，单侧α为 0.05，辍学率为 6%），则需要 62 名患者。所有分析都是预先指定的，包括在证明非劣效性的情况下进行优效性测试，以及意向治疗。由于招募缓慢，试验提前结束。两组患者的基线特征非常均衡；中位年龄为 61（IQR = 53-70）岁；36 名男性（73.5%），13 名女性（26.5%）；阿片类药物治疗组的基线中位疼痛评分为 5（IQR = 4-6）分，MMA 治疗组的基线中位疼痛评分为 4（IQR = 4-6）分（P = 0.161）。中位随访时间为 4.24 (IQR = 3.75-4.73) 个月。主要终点是 RT 最后 7 天的平均疼痛评分，阿片类药物治疗组为 5.10（95% CI = 4.11-6.09），MMA 治疗组为 4.85（95% CI = 3.81-5.90）（非劣效 P = 0.039，优效 P = 0.724）。使用线性混合模型分析从入院到靶向治疗后 6 周的所有疼痛评分，与单独使用阿片类药物相比，MMA 的疼痛评分显著降低（非劣效 P = 0.002，优效 P < 0.001）。阿片类药物治疗组（99.2 毫克口服吗啡当量剂量 [OMED]，IQR = 16.3-173.1）与 MMA 治疗组（50.5 毫克口服吗啡当量剂量；IQR = 8.4-126.3）相比，阿片类药物治疗组的每周阿片类药物使用量中位数更高，但无显著性差异（P = 0.435）。MMA治疗组有一名患者因3级急性肾损伤入院，可能与镇痛方案有关。阿片类药物治疗组未出现≥3级毒性反应。结论MMA在治疗RT最后一周的RIM疼痛方面不劣于单独使用阿片类镇痛药，在分析RT后时间段的疼痛时具有优势。因此，MMA 是一种有效的镇痛方案，应考虑用于 HNC 患者。
{"title":"Opioid Therapy vs. Multimodal Analgesia in Head and Neck Cancer (OPTIMAL-HN): Results of a Randomized Clinical Trial","authors":"","doi":"10.1016/j.ijrobp.2024.07.053","DOIUrl":"10.1016/j.ijrobp.2024.07.053","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Radiation-induced mucositis (RIM) pain confers substantial morbidity for head and neck cancer (HNC) patients undergoing radiotherapy (RT) or chemoradiotherapy (CRT). With no established standard treatment, OPTIMAL-HN aimed to demonstrate the non-inferiority of multimodal analgesia (MMA; analgesic medications with different mechanisms of action) to the institutional standard of opioid analgesia alone.</div></div><div><h3>Materials/Methods</h3><div>OPTIMAL-HN (NCT04221165) was an open label, single-institution, non-inferiority, randomized clinical trial. HNC patients receiving curative-intent RT/CRT and experiencing moderate 4 of 10 RIM pain were randomized 1:1, stratified by RT vs. CRT, to opioids alone per institutional standard or MMA (Pregabalin, Acetaminophen, Naproxen, and opioids if required). The primary endpoint was mean pain score (range = 0-10) during the last week of RT. Secondary endpoints included mean weekly opioid use, duration of opioid requirement, mean daily pain score, quality of life, hospitalizations for analgesic medication-related complications, time to feeding tube insertion, weight loss, toxicity, RT interruptions, and death. Assuming a non-inferiority margin of 1 point, a standard deviation of 1.5 in both arms (80% power, 1-sided alpha 0.05, dropout rate 6%), 62 patients were required. All analyses were pre-specified, including testing for superiority if non-inferiority was demonstrated, and intention-to-treat.</div></div><div><h3>Results</h3><div>Forty-nine patients were enrolled, 25 in the opioid analgesia alone arm and 24 in the MMA arm. The trial was prematurely closed due to slow accrual. Baseline characteristics were well-balanced between arms; median age was 61 (IQR = 53-70) years; 36 male (73.5%) and 13 female (26.5%); baseline median pain score was 5 (IQR = 4-6) in the opioid arm and 4 (IQR = 4-6) in the MMA arm (<em>P</em> = 0.161). Median follow-up was 4.24 (IQR = 3.75-4.73) months. The primary endpoint, mean pain score during the last 7 days of RT, was 5.10 (95% CI = 4.11-6.09) in the opioid arm and 4.85 (95% CI = 3.81-5.90) in the MMA arm (non-inferiority <em>P</em> = 0.039, superiority <em>P</em> = 0.724). Analyzing all pain scores from enrollment to 6 weeks post-RT using linear mixed models, MMA demonstrated significantly lower pain scores compared to opioids alone (non-inferiority <em>P</em> = 0.002, superiority <em>P</em> < 0.001). Median weekly opioid use was numerically higher in the opioid arm (99.2 mg oral morphine equivalent dose [OMED], IQR = 16.3-173.1) compared to the MMA arm (50.5 mg OMED; IQR = 8.4-126.3), although nonsignificant (<em>P</em> = 0.435). One patient in the MMA arm was admitted with grade 3 acute kidney injury, possibly related to the analgesic regimen. There was no grade ≥ 3 toxicity in the opioid arm. Arms were similar for all other secondary endpoints.</div></div><div><h3>Conclusion</h3><div>MMA demonstrates non-inferiority to opioid anal","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":"142358605","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.2024.07.031
Purpose/Objective(s)
While SABR is known for its overall low toxicity and safety, there remains a research gap regarding its combined use with specific systemic therapies. This study aims to evaluate the toxicity of SABR in combination with various systemic therapies. The hypothesis is that certain systemic therapies would significantly increase the risk of Grade 2+ and Grade 3+ radiation therapy-related toxicities when used concurrently with Stereotactic Ablative Radiotherapy (SABR).
Materials/Methods
A secondary analysis of the SABR-5 trial compared grade 2+ and 3+ toxicities associated with SABR until the last follow-up in patients receiving high-risk or non-high-risk systemic therapy at intervals of 3 months, 2 weeks, 1 week, and concurrently with SABR. High-risk systemic therapy was a priori defined, based on previous literature, as drugs that, when given close to SABR, may increase treatment toxicity. This category encompasses cytotoxic chemotherapy drugs, multi-targeted tyrosine kinase inhibitors, cyclin-dependent kinase 4/6 inhibitors, epidermal growth factor receptor inhibitors, anti-vascular endothelial growth factor agents, and anti-cytotoxic T-lymphocyte-associated protein 4 agents.
Results
Among the 381 patients, the actuarial rates of grade 2+ and 3+ toxic effects were as follows: for patients not on systemic therapy 3 months prior to SABR (n = 202), the rates were 17.3% and 3.5%, respectively; for patients on non-high-risk systemic therapy concurrent with SABR (n = 102), the rates were 18.6% and 3.9%, respectively; and for patients on high-risk systemic therapy concurrent with SABR (n = 5), the rates were notably higher at 60% and 40%, respectively. On multivariable analysis, concurrent use of high-risk systemic therapy was associated with a higher risk of grade 2+ (OR = 7.15, P = 0.043) or 3+ toxic effects (OR = 13.9, P = 0.015). Significance was not observed when high-risk drugs were used only within 1 week, 2 weeks, or 3 months of SABR, nor with the use of any non-high-risk drugs. A second adverse factor included increased tumor diameter (per 1 cm increment; G2+ OR = 1.25, P < 0.001; G3+ OR = 1.27, P = 0.015).
Conclusion
High-risk drugs have demonstrated a potential of increased SABR-related toxicity, warranting caution in their concurrent use with SABR. In contrast, the combination of non-high-risk drugs with SABR may be safe. Ongoing efforts are essential to identify potential risks and uncertainties associated with this therapeutic combination.
{"title":"Evaluating Toxicity and Interaction Outcomes of Systemic Therapy and Stereotactic Ablative Radiotherapy for Oligometastatic Disease: A Secondary Analysis of the Phase II SABR-5 Trial","authors":"","doi":"10.1016/j.ijrobp.2024.07.031","DOIUrl":"10.1016/j.ijrobp.2024.07.031","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>While SABR is known for its overall low toxicity and safety, there remains a research gap regarding its combined use with specific systemic therapies. This study aims to evaluate the toxicity of SABR in combination with various systemic therapies. The hypothesis is that certain systemic therapies would significantly increase the risk of Grade 2+ and Grade 3+ radiation therapy-related toxicities when used concurrently with Stereotactic Ablative Radiotherapy (SABR).</div></div><div><h3>Materials/Methods</h3><div>A secondary analysis of the SABR-5 trial compared grade 2+ and 3+ toxicities associated with SABR until the last follow-up in patients receiving high-risk or non-high-risk systemic therapy at intervals of 3 months, 2 weeks, 1 week, and concurrently with SABR. High-risk systemic therapy was a priori defined, based on previous literature, as drugs that, when given close to SABR, may increase treatment toxicity. This category encompasses cytotoxic chemotherapy drugs, multi-targeted tyrosine kinase inhibitors, cyclin-dependent kinase 4/6 inhibitors, epidermal growth factor receptor inhibitors, anti-vascular endothelial growth factor agents, and anti-cytotoxic T-lymphocyte-associated protein 4 agents.</div></div><div><h3>Results</h3><div>Among the 381 patients, the actuarial rates of grade 2+ and 3+ toxic effects were as follows: for patients not on systemic therapy 3 months prior to SABR (<em>n</em> = 202), the rates were 17.3% and 3.5%, respectively; for patients on non-high-risk systemic therapy concurrent with SABR (<em>n</em> = 102), the rates were 18.6% and 3.9%, respectively; and for patients on high-risk systemic therapy concurrent with SABR (<em>n</em> = 5), the rates were notably higher at 60% and 40%, respectively. On multivariable analysis, concurrent use of high-risk systemic therapy was associated with a higher risk of grade 2+ (OR = 7.15, <em>P</em> = 0.043) or 3+ toxic effects (OR = 13.9, <em>P</em> = 0.015). Significance was not observed when high-risk drugs were used only within 1 week, 2 weeks, or 3 months of SABR, nor with the use of any non-high-risk drugs. A second adverse factor included increased tumor diameter (per 1 cm increment; G2+ OR = 1.25, <em>P</em> < 0.001; G3+ OR = 1.27, <em>P</em> = 0.015).</div></div><div><h3>Conclusion</h3><div>High-risk drugs have demonstrated a potential of increased SABR-related toxicity, warranting caution in their concurrent use with SABR. In contrast, the combination of non-high-risk drugs with SABR may be safe. Ongoing efforts are essential to identify potential risks and uncertainties associated with this therapeutic combination.</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":"142358675","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.2024.07.011
Purpose/Objective(s)
Proton postmastectomy radiation therapy (PMRT) is under investigation and increasingly used in clinical practice. However, limited prospective health related quality of life data have been reported to assist patients and physicians with treatment decisions. To date studies involving proton PMRT have primarily used conventional fractionation (CF). We evaluated patient reported outcomes from a randomized trial comparing CF and hypofractionation (HF) proton PMRT, including those with immediate breast reconstruction.
Materials/Methods
We conducted a randomized phase 2 trial (MC1631) comparing CF (50 Gy in 25 fractions [relative biological effectiveness (RBE) 1.1]) and HF (40.05 Gy in 15 fractions [RBE 1.1]) proton PMRT. Patients were randomly assigned (1:1) to either CF or HF, with presence of immediate reconstruction (yes vs no) as a stratification factor. All patients were treated with pencil-beam scanning. Eligibility criteria included age 18 years or older with breast cancer resected by mastectomy with or without immediate reconstruction with indications for PMRT. Psychosocial well-being, physical well-being, sexual well-being, satisfaction with breasts, and satisfaction with outcomes scores were measured using the condition-specific validated BREAST-Q patient-reported outcome instrument during annual follow-up. Data were analyzed using linear mixed-effects modeling. This trial is registered with ClinicalTrials.gov, NCT02783690.
Results
Seventy-four of 82 randomized patients (90%) completed at least one BREAST-Q questionnaire (36 CF, 38 HF). Median age was 53 years (range = 32-78). Fifty-two (70%) had immediate breast reconstruction with tissue expanders (83%), implants (13%), or autologous reconstruction (4%) at the time of PMRT. Fifty-seven (77%) received neoadjuvant and/or adjuvant chemotherapy. At 36 months, mean score (95% CI) of patient-reported satisfaction (mastectomy) was 59.5 (51.2-67.8) for CF and 61.0 (95% CI = 52.5-69.5) for HF. Amongst patients with reconstruction, similar satisfaction with breasts (63.9 [95% CI = 55.9-71.9] vs 59.0 [95% CI = 51.1-66.8]) and satisfaction with outcome (70.3 [95% CI = 60.0-80.7] vs 70.5 [95% CI = 60.0-81.0]) scores were observed for the CF and HF arms, respectively. No significant differences were also observed for psychosocial well-being, physical well-being, and sexual well-being.
Conclusion
CF and HF proton PMRT yield similar patient reported satisfaction and well-being at 3 years of follow up.
目的/目标：质子乳房切除术后放射治疗（PMRT）正在接受研究，并越来越多地应用于临床实践。然而，用于帮助患者和医生做出治疗决定的前瞻性健康相关生活质量数据却十分有限。迄今为止，涉及质子 PMRT 的研究主要使用常规分次法（CF）。材料/方法 我们进行了一项随机 2 期试验（MC1631），比较了 CF（50 Gy，25 次分次[相对生物效应（RBE）1.1]）和 HF（40.05 Gy，15 次分次[RBE 1.1]）质子 PMRT。患者被随机分配（1:1）至CF或HF，并将是否立即重建（是与否）作为分层因素。所有患者均接受铅笔束扫描治疗。资格标准包括年龄在18岁或18岁以上，乳房切除术切除的乳腺癌，有或没有立即重建，有PMRT适应症。在年度随访期间，使用针对特定情况的有效 BREAST-Q 患者报告结果工具测量了患者的社会心理健康、身体健康、性健康、对乳房的满意度以及对结果的满意度。数据采用线性混合效应模型进行分析。该试验已在 ClinicalTrials.gov 登记，编号为 NCT02783690。结果82 名随机患者中有 74 名（90%）至少完成了一份 BREAST-Q 问卷（36 名 CF，38 名 HF）。中位年龄为 53 岁（范围 = 32-78）。52名患者（70%）在接受PMRT时立即进行了乳房重建，包括组织扩张器（83%）、植入物（13%）或自体重建（4%）。57人（77%）接受了新辅助和/或辅助化疗。在36个月时，患者报告的满意度（乳房切除术）平均得分（95% CI）为：CF为59.5（51.2-67.8），HF为61.0（95% CI = 52.5-69.5）。在接受乳房再造的患者中，CF 和 HF 两组的乳房满意度（63.9 [95% CI = 55.9-71.9] vs 59.0 [95% CI = 51.1-66.8]）和结果满意度（70.3 [95% CI = 60.0-80.7] vs 70.5 [95% CI = 60.0-81.0]）评分相似。结论CF和HF质子PMRT在随访3年后患者报告的满意度和幸福感相似。
{"title":"Conventional vs. Hypofractionated Proton Postmastectomy Radiotherapy: Patient Reported Outcomes from a Randomized Phase 2 Trial","authors":"","doi":"10.1016/j.ijrobp.2024.07.011","DOIUrl":"10.1016/j.ijrobp.2024.07.011","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Proton postmastectomy radiation therapy (PMRT) is under investigation and increasingly used in clinical practice. However, limited prospective health related quality of life data have been reported to assist patients and physicians with treatment decisions. To date studies involving proton PMRT have primarily used conventional fractionation (CF). We evaluated patient reported outcomes from a randomized trial comparing CF and hypofractionation (HF) proton PMRT, including those with immediate breast reconstruction.</div></div><div><h3>Materials/Methods</h3><div>We conducted a randomized phase 2 trial (MC1631) comparing CF (50 Gy in 25 fractions [relative biological effectiveness (RBE) 1.1]) and HF (40.05 Gy in 15 fractions [RBE 1.1]) proton PMRT. Patients were randomly assigned (1:1) to either CF or HF, with presence of immediate reconstruction (yes vs no) as a stratification factor. All patients were treated with pencil-beam scanning. Eligibility criteria included age 18 years or older with breast cancer resected by mastectomy with or without immediate reconstruction with indications for PMRT. Psychosocial well-being, physical well-being, sexual well-being, satisfaction with breasts, and satisfaction with outcomes scores were measured using the condition-specific validated BREAST-Q patient-reported outcome instrument during annual follow-up. Data were analyzed using linear mixed-effects modeling. This trial is registered with ClinicalTrials.gov, NCT02783690.</div></div><div><h3>Results</h3><div>Seventy-four of 82 randomized patients (90%) completed at least one BREAST-Q questionnaire (36 CF, 38 HF). Median age was 53 years (range = 32-78). Fifty-two (70%) had immediate breast reconstruction with tissue expanders (83%), implants (13%), or autologous reconstruction (4%) at the time of PMRT. Fifty-seven (77%) received neoadjuvant and/or adjuvant chemotherapy. At 36 months, mean score (95% CI) of patient-reported satisfaction (mastectomy) was 59.5 (51.2-67.8) for CF and 61.0 (95% CI = 52.5-69.5) for HF. Amongst patients with reconstruction, similar satisfaction with breasts (63.9 [95% CI = 55.9-71.9] vs 59.0 [95% CI = 51.1-66.8]) and satisfaction with outcome (70.3 [95% CI = 60.0-80.7] vs 70.5 [95% CI = 60.0-81.0]) scores were observed for the CF and HF arms, respectively. No significant differences were also observed for psychosocial well-being, physical well-being, and sexual well-being.</div></div><div><h3>Conclusion</h3><div>CF and HF proton PMRT yield similar patient reported satisfaction and well-being at 3 years of follow up.</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":"142359555","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.2024.07.061
<div><h3>Purpose/Objective(s)</h3><div>Artificial intelligence (AI) normal tissue contouring tools are now widely available and used in many treatment planning systems. However, few studies have prospectively demonstrated the value of such tools when employed in clinical workflows. We conducted a randomized controlled trial to assess the benefit of using an AI heart contouring algorithm to assist breast radiotherapy (RT) planning.</div></div><div><h3>Materials/Methods</h3><div>A single institution, 2-arm randomized controlled crossover trial was undertaken between December 2021 and October 2023. A convolutional neural network for heart auto-contouring, which had median Dice 0.95 compared to gold standard contours and reduced contouring time by 50% in pre-clinical studies, was implemented as a scripted tool within a treatment planning system. Eligible patients had breast cancer planned for RT, with hearts contoured according to the randomization of the dosimetrist assigned to their plan. Dosimetrists were stratified by experience and randomized to (1) manual heart contouring first or (2) AI-assisted heart contouring first. AI-assisted contouring consisted of running the model within the treatment planning system and editing the contour as needed. After completing 5 cases on the initial contour strategy, dosimetrists crossed to the other strategy. Co-primary outcomes were feasibility and efficacy, defined as heart contouring time (measured by recording screen during contouring). Secondary endpoints included dosimetrist and treating physician contour assessments. The trial had 90% power to detect a 30% reduction in contour time with 2-sided type I error of 5%.</div></div><div><h3>Results</h3><div>One hundred eighteen patients enrolled; 60 patients’ hearts were contoured manually and 58 with AI assistance. Eleven dosimetrists enrolled; 5 were randomized to manual first arm and 6 to AI-assisted first arm. There was no difference in manual vs. AI-assisted contour time overall (mean 277.3 ± 151.2 vs. 267.2 ± 199.0 seconds, <em>P</em> = 0.76), on the manual first arm only (<em>P</em> = 0.15), or on the AI first arm only (<em>P</em> = 0.67). There was no difference in contour time among only dosimetrists with ⩽2 yr experience (mean = 374.4 ± 174.2 vs. 403.3 ± 275.9 secs, <em>P</em> = 0.72), nor among dosimetrists with > 3 yr experience (mean = 241.9 ± 126.4 vs. 210.8 ± 121.9 secs, <em>P</em> = 0.25). Dosimetrists considered AI contours acceptable with minor/no modification in 13 of 47 (27.6%) cases and unacceptable in 34 of 47 (72.4%) cases; but considered the AI helpful in 35 of 47 (74.5%) cases and to improve subjective efficiency in 29 of 47 (61.7%) cases. Physicians, blinded to randomization, thought contours presented for review were unacceptable in 6 of 56 (10.7%) AI-assisted and 3 of 56 (5.4%) manual cases.</div></div><div><h3>Conclusion</h3><div>Despite improving efficiency pre-clinically, AI assistance did not reduce heart contour time compare
{"title":"A Randomized Controlled Crossover Trial to Evaluate the Efficacy of AI-Assisted Heart Contouring","authors":"","doi":"10.1016/j.ijrobp.2024.07.061","DOIUrl":"10.1016/j.ijrobp.2024.07.061","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Artificial intelligence (AI) normal tissue contouring tools are now widely available and used in many treatment planning systems. However, few studies have prospectively demonstrated the value of such tools when employed in clinical workflows. We conducted a randomized controlled trial to assess the benefit of using an AI heart contouring algorithm to assist breast radiotherapy (RT) planning.</div></div><div><h3>Materials/Methods</h3><div>A single institution, 2-arm randomized controlled crossover trial was undertaken between December 2021 and October 2023. A convolutional neural network for heart auto-contouring, which had median Dice 0.95 compared to gold standard contours and reduced contouring time by 50% in pre-clinical studies, was implemented as a scripted tool within a treatment planning system. Eligible patients had breast cancer planned for RT, with hearts contoured according to the randomization of the dosimetrist assigned to their plan. Dosimetrists were stratified by experience and randomized to (1) manual heart contouring first or (2) AI-assisted heart contouring first. AI-assisted contouring consisted of running the model within the treatment planning system and editing the contour as needed. After completing 5 cases on the initial contour strategy, dosimetrists crossed to the other strategy. Co-primary outcomes were feasibility and efficacy, defined as heart contouring time (measured by recording screen during contouring). Secondary endpoints included dosimetrist and treating physician contour assessments. The trial had 90% power to detect a 30% reduction in contour time with 2-sided type I error of 5%.</div></div><div><h3>Results</h3><div>One hundred eighteen patients enrolled; 60 patients’ hearts were contoured manually and 58 with AI assistance. Eleven dosimetrists enrolled; 5 were randomized to manual first arm and 6 to AI-assisted first arm. There was no difference in manual vs. AI-assisted contour time overall (mean 277.3 ± 151.2 vs. 267.2 ± 199.0 seconds, <em>P</em> = 0.76), on the manual first arm only (<em>P</em> = 0.15), or on the AI first arm only (<em>P</em> = 0.67). There was no difference in contour time among only dosimetrists with ⩽2 yr experience (mean = 374.4 ± 174.2 vs. 403.3 ± 275.9 secs, <em>P</em> = 0.72), nor among dosimetrists with > 3 yr experience (mean = 241.9 ± 126.4 vs. 210.8 ± 121.9 secs, <em>P</em> = 0.25). Dosimetrists considered AI contours acceptable with minor/no modification in 13 of 47 (27.6%) cases and unacceptable in 34 of 47 (72.4%) cases; but considered the AI helpful in 35 of 47 (74.5%) cases and to improve subjective efficiency in 29 of 47 (61.7%) cases. Physicians, blinded to randomization, thought contours presented for review were unacceptable in 6 of 56 (10.7%) AI-assisted and 3 of 56 (5.4%) manual cases.</div></div><div><h3>Conclusion</h3><div>Despite improving efficiency pre-clinically, AI assistance did not reduce heart contour time compare","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":"142359159","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.2024.09.051
Giuseppe Sanguineti, Pasqualina D'Urso, Marta Bottero, Alessia Farneti, Lucia Goanta, Diana Giannarelli, Valeria Landoni
Purpose/objective(s): To report the results of a phase I-II study on SBRT for early glottic cancer.
Materials/methods: This a prospective study at a single Institution enrolling patients with T1 glottic cancer. The true vocal cords (TVC) were divided into thirds and the third(s) containing disease prescribed 36 Gy in 3 fractions. The portions of the TVCs next to the involved one were planned to receive 30 Gy in 3 fxs. SBRT was delivered by a LINAC-based approach using multiple arcs. Toxicity was scored by CTCAE and late events were considered those occurring 3 months after SBRT. Voice quality was investigated by the voice handicap index (VHI) at regular intervals. The planned sample size was 75 patients.
Results: Accrual was discontinued after 33 patients due to concerns for late toxicity. T stage was as follows: T1a: 23 pts (69.7%); T1b: 10 pts (30.3%). All patients received the planned treatment and the median follow-up time is 51.5 months (IQR: 47.9-61.0 months). At last follow up, all patients are alive and without evidence of disease but two patients who died for intercurrent causes. The local control rate is 100% at 4 yrs. Six patients (18.2%) developed soft tissue necrosis (N=4) or cartilage necrosis (N=2) after a median time of 14.9 months from SBRT. Five out of 6 necrotic events were observed in patients who kept smoking and/or had a recent COVID infection. All 4 soft tissue events healed with conservative therapy. After an initial deterioration the average VHI score significantly improved at 6 months over baseline.
Conclusion: SBRT to 36 Gy in 3 fractions is highly effective in controlling T1 TVC carcinoma, but necrosis, though mostly transient, is a concern. Based on the present results, a reduction in total dose as well as a more accurate patient selection are warranted.
{"title":"Stereotactic Radiotherapy in 3 fractions for T1 Glottic Cancer: SBRT in 3 fractions for early glottic cancer.","authors":"Giuseppe Sanguineti, Pasqualina D'Urso, Marta Bottero, Alessia Farneti, Lucia Goanta, Diana Giannarelli, Valeria Landoni","doi":"10.1016/j.ijrobp.2024.09.051","DOIUrl":"https://doi.org/10.1016/j.ijrobp.2024.09.051","url":null,"abstract":"<p><strong>Purpose/objective(s): </strong>To report the results of a phase I-II study on SBRT for early glottic cancer.</p><p><strong>Materials/methods: </strong>This a prospective study at a single Institution enrolling patients with T1 glottic cancer. The true vocal cords (TVC) were divided into thirds and the third(s) containing disease prescribed 36 Gy in 3 fractions. The portions of the TVCs next to the involved one were planned to receive 30 Gy in 3 fxs. SBRT was delivered by a LINAC-based approach using multiple arcs. Toxicity was scored by CTCAE and late events were considered those occurring 3 months after SBRT. Voice quality was investigated by the voice handicap index (VHI) at regular intervals. The planned sample size was 75 patients.</p><p><strong>Results: </strong>Accrual was discontinued after 33 patients due to concerns for late toxicity. T stage was as follows: T1a: 23 pts (69.7%); T1b: 10 pts (30.3%). All patients received the planned treatment and the median follow-up time is 51.5 months (IQR: 47.9-61.0 months). At last follow up, all patients are alive and without evidence of disease but two patients who died for intercurrent causes. The local control rate is 100% at 4 yrs. Six patients (18.2%) developed soft tissue necrosis (N=4) or cartilage necrosis (N=2) after a median time of 14.9 months from SBRT. Five out of 6 necrotic events were observed in patients who kept smoking and/or had a recent COVID infection. All 4 soft tissue events healed with conservative therapy. After an initial deterioration the average VHI score significantly improved at 6 months over baseline.</p><p><strong>Conclusion: </strong>SBRT to 36 Gy in 3 fractions is highly effective in controlling T1 TVC carcinoma, but necrosis, though mostly transient, is a concern. Based on the present results, a reduction in total dose as well as a more accurate patient selection are warranted.</p>","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":"142371821","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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