Pub Date : 2024-10-01DOI: 10.1016/j.ijrobp.2024.07.055
<div><h3>Purpose/Objective(s)</h3><div>Solid tumor leptomeningeal metastasis (LM) is associated with limited survival. We evaluated whether proton craniospinal irradiation (pCSI) would result in improvement in disease control and survival compared to involved-field radiotherapy (IFRT).</div></div><div><h3>Materials/Methods</h3><div>We conducted a randomized phase 2 study comparing pCSI vs. IFRT in patients with non-small cell lung cancer (NSCLC) or breast cancer LM (NCT04343573). Eligibility criteria included radiographic and/or cytologic LM and Karnofsky performance status (KPS) ≥ 60. Patients were stratified by histology and systemic disease and were randomized in a 2:1 ratio favoring pCSI. For all other solid tumor histologies, patients were enrolled on an exploratory cohort and all received pCSI. RT was 3 Gy x 10 fractions. The primary objective was CNS progression-free survival (CNS PFS), defined as time from randomization to CNS progression (POD); secondary objectives included overall survival (OS), treatment-related adverse events (TAEs), patient reported outcomes (PROs), neurocognitive function (NF).</div></div><div><h3>Results</h3><div>From April 2020 to October 2021, there were 42 and 21 patients who were randomized to pCSI and IFRT, respectively. Both cohorts included 57% NSCLC and 52% patients with active systemic disease. In the randomized cohorts, 33 patients had CNS POD and 41 died. Patients followed for CNS PFS without POD had a minimum of 18.5 months follow up (range = 18.5-26.8). At 6 months, 22% (95% CI = 9.5-38) pCSI patients vs. 88% (95% CI = 51-98, <em>P</em> < 0.001) IFRT patients had CNS progression. A significant benefit in CNS PFS was observed with pCSI (median = 8.2 months, 95% CI = 6.6-15.3) vs. IFRT (median = 2.3 months, 95% CI = 1.2-4.0, <em>P</em> < 0.001). OS benefit with pCSI (median = 11.3 months, 95% CI = 7.5-18.3) vs. IFRT (median = 4.9 months, 95% CI = 3.9-15.0, <em>P</em> = 0.04) was also observed. In multivariable analysis, pCSI remained significantly associated with improved CNS PFS (HR = 0.14, 95% CI = 0.06-0.30, <em>P</em> < 0.001) and OS (HR = 0.43, 95% CI = 0.22-0.81, <em>P</em> = 0.009). Grade 3 non-heme and/or Grade 4 heme TAEs occurred in 8 patients with pCSI and 7 with IFRT (<em>P</em> = 0.19). For the exploratory pCSI cohort, 35 patients enrolled, 20 (57%) had active systemic disease, and ovarian (7 [20%]) was the most common histology. In this cohort, 13 had CNS POD and 27 died. Median CNS PFS was 5.8 months (95% CI = 4.4-9.1), OS was 7.0 months (95% CI = 5.4-10.6), and 8 patients had Grade 3 non-heme and/or Grade 4 heme TAEs. There was no Grade 5 toxicity in all cohorts. There was no significant difference in PROs scores between patients who received pCSI or IFRT while on study. In patients who received pCSI and had NF evaluated at baseline (<em>n</em> = 12), decline in verbal memory and executive function but no significant change in working memory and attention was observed at 6 months
{"title":"Proton Craniospinal Irradiation for Patients with Solid Tumor Leptomeningeal Metastasis- Final Analysis of a Phase II Study","authors":"","doi":"10.1016/j.ijrobp.2024.07.055","DOIUrl":"10.1016/j.ijrobp.2024.07.055","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Solid tumor leptomeningeal metastasis (LM) is associated with limited survival. We evaluated whether proton craniospinal irradiation (pCSI) would result in improvement in disease control and survival compared to involved-field radiotherapy (IFRT).</div></div><div><h3>Materials/Methods</h3><div>We conducted a randomized phase 2 study comparing pCSI vs. IFRT in patients with non-small cell lung cancer (NSCLC) or breast cancer LM (NCT04343573). Eligibility criteria included radiographic and/or cytologic LM and Karnofsky performance status (KPS) ≥ 60. Patients were stratified by histology and systemic disease and were randomized in a 2:1 ratio favoring pCSI. For all other solid tumor histologies, patients were enrolled on an exploratory cohort and all received pCSI. RT was 3 Gy x 10 fractions. The primary objective was CNS progression-free survival (CNS PFS), defined as time from randomization to CNS progression (POD); secondary objectives included overall survival (OS), treatment-related adverse events (TAEs), patient reported outcomes (PROs), neurocognitive function (NF).</div></div><div><h3>Results</h3><div>From April 2020 to October 2021, there were 42 and 21 patients who were randomized to pCSI and IFRT, respectively. Both cohorts included 57% NSCLC and 52% patients with active systemic disease. In the randomized cohorts, 33 patients had CNS POD and 41 died. Patients followed for CNS PFS without POD had a minimum of 18.5 months follow up (range = 18.5-26.8). At 6 months, 22% (95% CI = 9.5-38) pCSI patients vs. 88% (95% CI = 51-98, <em>P</em> < 0.001) IFRT patients had CNS progression. A significant benefit in CNS PFS was observed with pCSI (median = 8.2 months, 95% CI = 6.6-15.3) vs. IFRT (median = 2.3 months, 95% CI = 1.2-4.0, <em>P</em> < 0.001). OS benefit with pCSI (median = 11.3 months, 95% CI = 7.5-18.3) vs. IFRT (median = 4.9 months, 95% CI = 3.9-15.0, <em>P</em> = 0.04) was also observed. In multivariable analysis, pCSI remained significantly associated with improved CNS PFS (HR = 0.14, 95% CI = 0.06-0.30, <em>P</em> < 0.001) and OS (HR = 0.43, 95% CI = 0.22-0.81, <em>P</em> = 0.009). Grade 3 non-heme and/or Grade 4 heme TAEs occurred in 8 patients with pCSI and 7 with IFRT (<em>P</em> = 0.19). For the exploratory pCSI cohort, 35 patients enrolled, 20 (57%) had active systemic disease, and ovarian (7 [20%]) was the most common histology. In this cohort, 13 had CNS POD and 27 died. Median CNS PFS was 5.8 months (95% CI = 4.4-9.1), OS was 7.0 months (95% CI = 5.4-10.6), and 8 patients had Grade 3 non-heme and/or Grade 4 heme TAEs. There was no Grade 5 toxicity in all cohorts. There was no significant difference in PROs scores between patients who received pCSI or IFRT while on study. In patients who received pCSI and had NF evaluated at baseline (<em>n</em> = 12), decline in verbal memory and executive function but no significant change in working memory and attention was observed at 6 months","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":"142359569","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.2024.07.050
Purpose/Objective(s)
From 2007 – 2014 our institution accrued to a phase II clinical trial omitting contralateral neck radiation therapy in patients with head and neck (HN) carcinomas with a pN0 contralateral neck following primary surgical treatment and bilateral neck dissection. After that trial’s contralateral neck recurrence rate resulted at only 3%, contralateral neck radiotherapy omission became an institutional practice. In the present study of similar patients treated since the trial’s publication, we hypothesized that contralateral recurrence rates have remained persistently low.
Materials/Methods
Clinical records and radiation plans of HN radiotherapy patients at a single institution were reviewed, and a cohort of patients was identified with oral cavity, oropharynx, hypopharynx, larynx, or unknown primary HN carcinomas treated with adjuvant ipsilateral radiation therapy after surgical treatment including a bilateral neck dissection with pN0 contralateral lymph nodes. Clinical variables for these patients were abstracted and tested for associations with recurrence events using nonparametric statistical tests.
Results
Records for 858 patients treated with HN radiotherapy from 2020 – 2023 were reviewed, and 58 patients met cohort inclusion criteria. The cohort median age was 60.5 years, 79% were male, and 53% were or had been smokers with a median 24 pack-year history. Carcinomas arose in the oropharynx (71%), oral cavity (21%) hypopharynx (5%) or from an unknown primary (3%), and most (71%) were p16+. Eighteen patients (31%) had stage IVA or IVB disease. With a median follow-up of 16 months the rates of any recurrence, contralateral recurrence, and contralateral recurrence as a first recurrent site (isolated or synchronous) were 19% (11 events), 12% (7 events), and 10% (6 events), respectively. Contralateral recurrence was associated with pathologic stage IVA and IVB disease (P < 0.001) and oral cavity primary (P = 0.02). Among 38 patients with p16+ oropharyngeal primaries, no contralateral recurrences were observed. In contrast, among 20 patients with p16- oropharynx primaries (3) or another primary site (17), seven contralateral recurrences (35%; two oropharynx, five oral cavity) were observed.
Conclusion
Despite a relatively short median follow-up, contralateral recurrences after ipsilateral neck radiotherapy were overall more frequent than hypothesized. Most were a site of first recurrence. However, contralateral recurrences were primarily driven by oral cavity primaries and stage IVA and IVB disease, for whom treatment intensification with adjuvant bilateral neck radiotherapy may be warranted. In the subset of patients with p16+ oropharyngeal primaries, the contralateral recurrence rate remained low.
{"title":"Contralateral Neck Recurrence Rates in Head and Neck Carcinomas after Primary Surgery, Bilateral Neck Dissection, a Pathologically Negative Contralateral Neck, and Adjuvant Ipsilateral Neck Radiation","authors":"","doi":"10.1016/j.ijrobp.2024.07.050","DOIUrl":"10.1016/j.ijrobp.2024.07.050","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>From 2007 – 2014 our institution accrued to a phase II clinical trial omitting contralateral neck radiation therapy in patients with head and neck (HN) carcinomas with a pN0 contralateral neck following primary surgical treatment and bilateral neck dissection. After that trial’s contralateral neck recurrence rate resulted at only 3%, contralateral neck radiotherapy omission became an institutional practice. In the present study of similar patients treated since the trial’s publication, we hypothesized that contralateral recurrence rates have remained persistently low.</div></div><div><h3>Materials/Methods</h3><div>Clinical records and radiation plans of HN radiotherapy patients at a single institution were reviewed, and a cohort of patients was identified with oral cavity, oropharynx, hypopharynx, larynx, or unknown primary HN carcinomas treated with adjuvant ipsilateral radiation therapy after surgical treatment including a bilateral neck dissection with pN0 contralateral lymph nodes. Clinical variables for these patients were abstracted and tested for associations with recurrence events using nonparametric statistical tests.</div></div><div><h3>Results</h3><div>Records for 858 patients treated with HN radiotherapy from 2020 – 2023 were reviewed, and 58 patients met cohort inclusion criteria. The cohort median age was 60.5 years, 79% were male, and 53% were or had been smokers with a median 24 pack-year history. Carcinomas arose in the oropharynx (71%), oral cavity (21%) hypopharynx (5%) or from an unknown primary (3%), and most (71%) were p16+. Eighteen patients (31%) had stage IVA or IVB disease. With a median follow-up of 16 months the rates of any recurrence, contralateral recurrence, and contralateral recurrence as a first recurrent site (isolated or synchronous) were 19% (11 events), 12% (7 events), and 10% (6 events), respectively. Contralateral recurrence was associated with pathologic stage IVA and IVB disease (<em>P</em> < 0.001) and oral cavity primary (<em>P</em> = 0.02). Among 38 patients with p16+ oropharyngeal primaries, no contralateral recurrences were observed. In contrast, among 20 patients with p16- oropharynx primaries (3) or another primary site (17), seven contralateral recurrences (35%; two oropharynx, five oral cavity) were observed.</div></div><div><h3>Conclusion</h3><div>Despite a relatively short median follow-up, contralateral recurrences after ipsilateral neck radiotherapy were overall more frequent than hypothesized. Most were a site of first recurrence. However, contralateral recurrences were primarily driven by oral cavity primaries and stage IVA and IVB disease, for whom treatment intensification with adjuvant bilateral neck radiotherapy may be warranted. In the subset of patients with p16+ oropharyngeal primaries, the contralateral recurrence rate remained low.</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":"142358541","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.2024.08.020
<div><h3>Purpose/Objective(s)</h3><div>When designing the ESOPEC trial, the CROSS (C) regimen provided the highest level of evidence of neoadjuvant therapy for both, squamous cell (ESCC) and EAC. During recruitment into ESOPEC, the FLOT(F)-4 trial identified perioperative 5-fluorouracil, leucovorin (L), oxaliplatin (O) and docetaxel (T) as best evidence of chemotherapy. The ESOPEC trial aimed to compare the two protocols exclusively in EAC and hypothesized F to be superior to C.</div></div><div><h3>Materials/Methods</h3><div>Included were patients with cM0 EAC staged cT1 N+ or cT2-4a, cN0/+. C was the control arm with 41.4 Gy in 23 fractions and 5 weekly simultaneous doses of carboplatin (2 mg/ml/min AUC) and paclitaxel [(50 mg/m²); CP]. GTV and PTV were defined as described by Matzinger et al. (doi: 10.1016/j.radonc.2009.03.018). F was the experimental arm with 5-fluorouracil 2600 mg/m² (24 hours), d1 L 200 mg/m², d1 O 85 mg/m², d1 T 50mg/m2, d1 every two weeks (q2w); 4 neoadjuvant cycles (8 weeks) prior to surgery and 4 adjuvant cycles (8 weeks) postoperatively. Esophagectomy was done 4-6 weeks after neoadjuvant therapies. Primary endpoint was overall survival (OS), secondary endpoints were progression free survival (PFS), ypTNM stage, tumor regression grading, recurrence free survival (RFS) in patients with R0/R1 resection, site of tumor recurrence, postoperative complications, adverse events, and quality of life. Sample size calculation was based on 1-sided significance level of 2.5% and 90% power assuming a hazard ratio (HR) of 0.645 with respect to OS, and required 218 death events (438 patients). Prospectively documented chemoradiotherapy specific variables consisted in administered percentage of planned chemo- and radiotherapy, adherence to target volume definitions, doses to organs at risk, specifically heart and lungs.</div></div><div><h3>Results</h3><div>From 2/16 to 4/20, 438 patients were randomized to C (217) and F (221), intention-to-treat population (ITT). Characteristics were well balanced with mean age of 63 years, 89.3% males, 73.9% cT3, 6.7% cT4, 79.7% cN+. Neoadjuvant treatment was started in 90.3% (196) vs 93.7% (207) in C vs F (per-protocol-population (PP)). In PP, full RT dose was given in 98.0% (192); 75.0% (147), 18.9% (37) and 6.1% (12) had 5, 4 or <4 cycles of CP. In ITT, surgery rates were C 82.9% (180) vs F 86.4% (191). In 371 patients with surgery, local pCR rates were 13.3% (C) vs 18.3% (F), and near CR rates 39.4% (C) vs 25.1% (F). In 368 patients with R0/R1 resection, 3-year RFS after surgery was 36.5% (C) and 52.8% (F), median RFS was 17 (C) vs 43 (F) months (HR 0.68 [0.51 – 0.90]; p = 0.0076). Postoperative morbidity was comparable. In ITT, 3-year-OS was 50.7% (C) and 57.4% (F), and median OS was 37 (C) vs 66 (F) months (HR 0.70 [0.53 – 0.92]; p = 0.012).</div></div><div><h3>Conclusion</h3><div>Both C and F were well tolerated. OS was superior after F vs C, and F should be preferred over C. Posthoc limitatio
目的/目标在设计 ESOPEC 试验时，CROSS (C) 方案为鳞状细胞 (ESCC) 和 EAC 的新辅助治疗提供了最高水平的证据。在 ESOPEC 的招募过程中，FLOT(F)-4 试验确定围手术期 5-氟尿嘧啶、亮氨醇 (L)、奥沙利铂 (O) 和多西他赛 (T) 为最佳化疗证据。ESOPEC试验旨在比较这两种方案对EAC的治疗效果，并假设F优于C.材料/方法包括分期为cT1 N+或cT2-4a、cN0/+的cM0 EAC患者。C为对照组，剂量为41.4 Gy，分23次进行，每周同时使用5次卡铂（2 mg/ml/min AUC）和紫杉醇[（50 mg/m²）；CP]。GTV和PTV的定义如Matzinger等人（doi: 10.1016/j.radonc.2009.03.018）所述。F为实验组，5-氟尿嘧啶2600毫克/平方米（24小时），d1 L 200毫克/平方米，d1 O 85毫克/平方米，d1 T 50毫克/平方米，d1每两周一次（q2w）；术前4个新辅助周期（8周），术后4个辅助周期（8周）。食管切除术在新辅助疗法后4-6周进行。主要终点是总生存期（OS），次要终点是无进展生存期（PFS）、ypTNM分期、肿瘤消退分级、R0/R1切除患者的无复发生存期（RFS）、肿瘤复发部位、术后并发症、不良事件和生活质量。样本量的计算基于2.5%的单侧显著性水平和90%的功率，假设OS的危险比（HR）为0.645，且需要218例死亡事件（438例患者）。结果从2/16到4/20，438名患者被随机分配到C组（217人）和F组（221人），意向治疗人群（ITT）。患者特征非常均衡，平均年龄为63岁，89.3%为男性，73.9%为cT3，6.7%为cT4，79.7%为cN+。C组与F组（按方案人群（PP））中，90.3%（196人）与93.7%（207人）开始了新辅助治疗。在 PP 组中，98.0%（192 例）接受了全 RT 剂量治疗；75.0%（147 例）、18.9%（37 例）和 6.1%（12 例）接受了 5、4 或 4 个周期的 CP 治疗。在 ITT 中，手术率为 C 82.9% (180) vs F 86.4% (191)。在371例手术患者中，局部pCR率为13.3%（C）vs 18.3%（F），近CR率为39.4%（C）vs 25.1%（F）。在368名接受R0/R1切除术的患者中，术后3年RFS分别为36.5%（C）和52.8%（F），中位RFS分别为17个月（C）和43个月（F）（HR 0.68 [0.51 - 0.90]；P = 0.0076）。术后发病率相当。在 ITT 中，3 年 OS 为 50.7%（C）和 57.4%（F），中位 OS 为 37（C）个月 vs 66（F）个月（HR 0.70 [0.53 - 0.92]；P = 0.012）。F 与 C 相比，OS 更优，应首选 F，而不是 C。C 的事后限制是：基线 FDG-PET/CT 不是强制性的，而且没有附加免疫疗法。
{"title":"Neoadjuvant Chemoradiation (CROSS) vs. Perioperative Chemotherapy (FLOT) in Esophageal Adenocarcinoma (EAC): ESOPEC – a Randomised Controlled Prospective Multicentre Phase III Trial","authors":"","doi":"10.1016/j.ijrobp.2024.08.020","DOIUrl":"10.1016/j.ijrobp.2024.08.020","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>When designing the ESOPEC trial, the CROSS (C) regimen provided the highest level of evidence of neoadjuvant therapy for both, squamous cell (ESCC) and EAC. During recruitment into ESOPEC, the FLOT(F)-4 trial identified perioperative 5-fluorouracil, leucovorin (L), oxaliplatin (O) and docetaxel (T) as best evidence of chemotherapy. The ESOPEC trial aimed to compare the two protocols exclusively in EAC and hypothesized F to be superior to C.</div></div><div><h3>Materials/Methods</h3><div>Included were patients with cM0 EAC staged cT1 N+ or cT2-4a, cN0/+. C was the control arm with 41.4 Gy in 23 fractions and 5 weekly simultaneous doses of carboplatin (2 mg/ml/min AUC) and paclitaxel [(50 mg/m²); CP]. GTV and PTV were defined as described by Matzinger et al. (doi: 10.1016/j.radonc.2009.03.018). F was the experimental arm with 5-fluorouracil 2600 mg/m² (24 hours), d1 L 200 mg/m², d1 O 85 mg/m², d1 T 50mg/m2, d1 every two weeks (q2w); 4 neoadjuvant cycles (8 weeks) prior to surgery and 4 adjuvant cycles (8 weeks) postoperatively. Esophagectomy was done 4-6 weeks after neoadjuvant therapies. Primary endpoint was overall survival (OS), secondary endpoints were progression free survival (PFS), ypTNM stage, tumor regression grading, recurrence free survival (RFS) in patients with R0/R1 resection, site of tumor recurrence, postoperative complications, adverse events, and quality of life. Sample size calculation was based on 1-sided significance level of 2.5% and 90% power assuming a hazard ratio (HR) of 0.645 with respect to OS, and required 218 death events (438 patients). Prospectively documented chemoradiotherapy specific variables consisted in administered percentage of planned chemo- and radiotherapy, adherence to target volume definitions, doses to organs at risk, specifically heart and lungs.</div></div><div><h3>Results</h3><div>From 2/16 to 4/20, 438 patients were randomized to C (217) and F (221), intention-to-treat population (ITT). Characteristics were well balanced with mean age of 63 years, 89.3% males, 73.9% cT3, 6.7% cT4, 79.7% cN+. Neoadjuvant treatment was started in 90.3% (196) vs 93.7% (207) in C vs F (per-protocol-population (PP)). In PP, full RT dose was given in 98.0% (192); 75.0% (147), 18.9% (37) and 6.1% (12) had 5, 4 or <4 cycles of CP. In ITT, surgery rates were C 82.9% (180) vs F 86.4% (191). In 371 patients with surgery, local pCR rates were 13.3% (C) vs 18.3% (F), and near CR rates 39.4% (C) vs 25.1% (F). In 368 patients with R0/R1 resection, 3-year RFS after surgery was 36.5% (C) and 52.8% (F), median RFS was 17 (C) vs 43 (F) months (HR 0.68 [0.51 – 0.90]; p = 0.0076). Postoperative morbidity was comparable. In ITT, 3-year-OS was 50.7% (C) and 57.4% (F), and median OS was 37 (C) vs 66 (F) months (HR 0.70 [0.53 – 0.92]; p = 0.012).</div></div><div><h3>Conclusion</h3><div>Both C and F were well tolerated. OS was superior after F vs C, and F should be preferred over C. Posthoc limitatio","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":"142359494","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.2024.07.002
Purpose/Objective(s)
A 5-week course of conventionally fractionated radiation after mastectomy remains standard of care for women with intermediate- and high-risk breast cancer (BC), despite widespread adoption of shorter schedules in other BC patients (pts). To fill the evidence gap of shorter PMRT schedules, we conducted a non-inferiority, multi-institutional, prospective randomized trial of hypofractionated radiation after mastectomy in pts with completed or in-progress breast reconstruction, comparing 25 vs 16 fractions (fx) of daily radiation. Primary outcome was composite reconstruction complication (wound healing, readmission, capsular contracture, unplanned re-operation, reconstruction failure).
Materials/Methods
Women enrolled with unilateral invasive BC, pT0-2 pN1-2 or pT3N0, or clinically staged before neoadjuvant chemotherapy (NAC), who were planning delayed or immediate breast reconstruction and PMRT. Pts were randomized 1:1 to 50.0 Gy in 25 fx or 42.56 Gy in 16 fx, delivered 5 days/week using photon techniques. The study was designed to test non-inferiority of hypofractionated to conventional PMRT with non-inferiority margin of 10%, assuming a complication rate of 25% in the conventional arm. Accounting for 10% ineligibility, a sample size of 880 pts provided 90% power at one-sided type I error of 0.025 with 1 interim analysis. Randomization was stratified by planned immediate vs delayed and autologous vs implant-only reconstruction.
Results
From 2018 to 2021, 898 pts enrolled from 209 centers in United States and Canada; median follow-up was 4.5 years. Seventy-three women came off study before the primary event could be analyzed. Pt characteristics were well balanced with median age 49 years, 14% known genetic predisposition gene, 6% diabetes, and 67% with body mass index > 25. Tumor characteristics were well balanced. 51% of pts received NAC; 37% received adjuvant chemotherapy. Among 572 pts who completed reconstruction, 45% had immediate and 55% delayed (average 265-day delay), 57% had implant alone and 43% autologous +/- implant. The 24-month month incidence of reconstruction complications was 14% (59/422) with hypofractionation vs 11.7% (47/403) with conventional PMRT, estimated difference 2.3%, 95% CI = 2.2% to 6.9%, P = 0.0005. Complication rate was decreased (regardless of arm) with autologous vs implant only reconstruction, odds ratio 0.504, P = 0.0059. Acute and late toxicity rates were not statistically different between arms. Thirty-six month local or regional recurrences occurred in 1.5%, 95% CI = (0.7-3.3% of hypofractionated and 2.3%, 95% CI = 1.1-4.6% of conventional pts.
Conclusion
A 16-fraction course of hypofractionated PMRT appears safe and effective for pts undergoing breast reconstruction and is non-inferior to traditional 25-fraction course of PMRT. (NCT03414970)
目的/目标：尽管在其他乳腺癌患者（pts）中广泛采用了更短的计划，但乳房切除术后进行为期 5 周的常规分次放射治疗仍是中危和高危乳腺癌（BC）女性患者的标准治疗方法。为了填补缩短 PMRT 计划的证据空白，我们在乳房切除术后进行了一项非劣效性、多机构、前瞻性随机试验，对已完成或正在进行乳房重建的患者进行低分次放射治疗，比较每日放射 25 次与 16 次。主要结果是重建并发症（伤口愈合、再次入院、乳房囊性挛缩、计划外再次手术、重建失败）。材料/方法入组妇女均为单侧浸润性乳腺癌，pT0-2 pN1-2 或 pT3N0，或新辅助化疗 (NAC) 前临床分期，计划延迟或立即进行乳房重建和 PMRT。患者按 1:1 随机分配到 50.0 Gy（25 个 X 光点）或 42.56 Gy（16 个 X 光点）的治疗方案中，使用光子技术进行治疗，治疗时间为 5 天/周。该研究的目的是测试低分射PMRT与传统PMRT的非劣效性，假定传统治疗组的并发症发生率为25%，非劣效性差值为10%。考虑到10%的患者不符合条件，880名患者的样本量在单侧I型误差为0.025的情况下可提供90%的功率，并进行一次中期分析。随机化按照计划的立即与延迟、自体与纯植入物重建进行了分层。结果从2018年到2021年，美国和加拿大的209个中心共有898名患者入组；中位随访时间为4.5年。73名女性在分析主要事件前退出了研究。患者特征非常均衡，中位年龄为49岁，14%有已知遗传易感基因，6%有糖尿病，67%体重指数为25。肿瘤特征非常均衡。51%的患者接受了NAC治疗，37%接受了辅助化疗。在完成重建的572名患者中，45%的患者接受了即刻重建，55%的患者接受了延迟重建（平均延迟265天），57%的患者仅接受了植入物重建，43%的患者接受了自体+/-植入物重建。重建并发症在24个月内的发生率为：低分量治疗14%（59/422），传统PMRT 11.7%（47/403），估计差异为2.3%，95% CI = 2.2%至6.9%，P = 0.0005。自体重建与仅植入物重建相比，并发症发生率均有所下降（与手术臂无关），几率比为 0.504，P = 0.0059。不同手术组的急性和晚期毒性率没有统计学差异。36个月的局部或区域复发率为：低分量治疗1.5%，95% CI = 0.7-3.3%；传统治疗2.3%，95% CI = 1.1-4.6%。(NCT03414970)
{"title":"A Randomized Trial of Hypofractionated Post-Mastectomy Radiation Therapy (PMRT) in Women with Breast Reconstruction (RT CHARM, Alliance A221505)","authors":"","doi":"10.1016/j.ijrobp.2024.07.002","DOIUrl":"10.1016/j.ijrobp.2024.07.002","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>A 5-week course of conventionally fractionated radiation after mastectomy remains standard of care for women with intermediate- and high-risk breast cancer (BC), despite widespread adoption of shorter schedules in other BC patients (pts). To fill the evidence gap of shorter PMRT schedules, we conducted a non-inferiority, multi-institutional, prospective randomized trial of hypofractionated radiation after mastectomy in pts with completed or in-progress breast reconstruction, comparing 25 vs 16 fractions (fx) of daily radiation. Primary outcome was composite reconstruction complication (wound healing, readmission, capsular contracture, unplanned re-operation, reconstruction failure).</div></div><div><h3>Materials/Methods</h3><div>Women enrolled with unilateral invasive BC, pT0-2 pN1-2 or pT3N0, or clinically staged before neoadjuvant chemotherapy (NAC), who were planning delayed or immediate breast reconstruction and PMRT. Pts were randomized 1:1 to 50.0 Gy in 25 fx or 42.56 Gy in 16 fx, delivered 5 days/week using photon techniques. The study was designed to test non-inferiority of hypofractionated to conventional PMRT with non-inferiority margin of 10%, assuming a complication rate of 25% in the conventional arm. Accounting for 10% ineligibility, a sample size of 880 pts provided 90% power at one-sided type I error of 0.025 with 1 interim analysis. Randomization was stratified by planned immediate vs delayed and autologous vs implant-only reconstruction.</div></div><div><h3>Results</h3><div>From 2018 to 2021, 898 pts enrolled from 209 centers in United States and Canada; median follow-up was 4.5 years. Seventy-three women came off study before the primary event could be analyzed. Pt characteristics were well balanced with median age 49 years, 14% known genetic predisposition gene, 6% diabetes, and 67% with body mass index > 25. Tumor characteristics were well balanced. 51% of pts received NAC; 37% received adjuvant chemotherapy. Among 572 pts who completed reconstruction, 45% had immediate and 55% delayed (average 265-day delay), 57% had implant alone and 43% autologous +/- implant. The 24-month month incidence of reconstruction complications was 14% (59/422) with hypofractionation vs 11.7% (47/403) with conventional PMRT, estimated difference 2.3%, 95% CI = 2.2% to 6.9%, <em>P</em> = 0.0005. Complication rate was decreased (regardless of arm) with autologous vs implant only reconstruction, odds ratio 0.504, <em>P</em> = 0.0059. Acute and late toxicity rates were not statistically different between arms. Thirty-six month local or regional recurrences occurred in 1.5%, 95% CI = (0.7-3.3% of hypofractionated and 2.3%, 95% CI = 1.1-4.6% of conventional pts.</div></div><div><h3>Conclusion</h3><div>A 16-fraction course of hypofractionated PMRT appears safe and effective for pts undergoing breast reconstruction and is non-inferior to traditional 25-fraction course of PMRT. (NCT03414970)</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":"142359139","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.2024.08.022
Purpose/Objective(s)
Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is effectively treated with radiotherapy (RT) with or without concurrent chemotherapy (CRT). These treatments are highly efficacious but can cause significant toxicities. Reducing the volume of elective nodal irradiation (ENI) to uninvolved cervical nodal levels is one strategy for limiting toxicity. CCTG HN.10 (NCT03822897) evaluated whether volume-reduced ENI would result in acceptable disease control and survival rates in patients with HPV-related OPSCC.
Materials/Methods
In this multi-center prospective phase II single arm trial, eligible patients had stage T1-3 N0-1 M0 (8th Ed. TNM) HPV-related OPSCC treated with definitive RT or CRT. Patients received 70 Gy over 7 weeks if eligible for concurrent cisplatin or over 6 weeks if treated with RT alone. For all patients, volume-reduced ENI was tailored to primary location, T-category, and distribution of involved nodes. RT contours underwent central quality assurance prior to treatment. Primary endpoint was 2-year event-free survival (EFS), and secondary endpoints included locoregional control (LRC), out-of-field regional control, overall survival (OS), toxicity, and quality of life. With an expected 2-year EFS of 91% in this population, 100 eligible patients would provide 80% power to detect a clinically meaningful 6% EFS decrement with one-sided alpha of 0.1. The null hypothesis would be rejected if 2-year EFS exceeded 88.85%.
Results
CCTG HN.10 accrued 103 patients from 2/2019 through 12/2021. As of the data cut-off date for this final analysis (May 31, 2024), median follow-up was 37 (0-56) months, and total person-years follow-up was 304.7. Median age was 62.8 years, 82.5% were male, 87.4% were T1-2, 89.3% were N1, 26.2% had smoked >10 pack-years. Among 100 treated patients, all completed RT, with 50 also receiving cisplatin. Grade 3 and 4 toxicities were observed in 46% and 1%, respectively. In 99 eligible patients, 2-year EFS was 91.8% (95% CI: 86.6%-97.4%), surpassing the protocol-specified threshold. In secondary analysis, there were 5 LRC events including 1 out-of-field regional control event; 2-year OS was 94.7% (95% CI: 90.2%-99.3%). Subgroup analysis showed identical 2-year EFS among patients treated with RT or CRT. By 24 months post-RT, quality of life measurements approximated baseline whereby FACT-HN overall scores and MDADI composite scores improved by mean of 0.41 (N=85, SD=14.8) and declined by mean of 3.58 (N=85, SD=16.2), respectively.
Conclusion
For patients with HPV-related OPSCC treated with radical RT, volume-reduced ENI as defined in this study can be safely performed while maintaining high efficacy with rare out-of-field regional failures. This de-escalation strategy should continue to be evaluated in rigorously conducted trials.
{"title":"A Phase II Single Arm Trial of Elective Volume Adjusted De-Escalation Radiotherapy (EVADER) in Patients with Low-risk HPV-related Oropharyngeal Squamous Cell Carcinoma","authors":"","doi":"10.1016/j.ijrobp.2024.08.022","DOIUrl":"10.1016/j.ijrobp.2024.08.022","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is effectively treated with radiotherapy (RT) with or without concurrent chemotherapy (CRT). These treatments are highly efficacious but can cause significant toxicities. Reducing the volume of elective nodal irradiation (ENI) to uninvolved cervical nodal levels is one strategy for limiting toxicity. CCTG HN.10 (NCT03822897) evaluated whether volume-reduced ENI would result in acceptable disease control and survival rates in patients with HPV-related OPSCC.</div></div><div><h3>Materials/Methods</h3><div>In this multi-center prospective phase II single arm trial, eligible patients had stage T1-3 N0-1 M0 (8th Ed. TNM) HPV-related OPSCC treated with definitive RT or CRT. Patients received 70 Gy over 7 weeks if eligible for concurrent cisplatin or over 6 weeks if treated with RT alone. For all patients, volume-reduced ENI was tailored to primary location, T-category, and distribution of involved nodes. RT contours underwent central quality assurance prior to treatment. Primary endpoint was 2-year event-free survival (EFS), and secondary endpoints included locoregional control (LRC), out-of-field regional control, overall survival (OS), toxicity, and quality of life. With an expected 2-year EFS of 91% in this population, 100 eligible patients would provide 80% power to detect a clinically meaningful 6% EFS decrement with one-sided alpha of 0.1. The null hypothesis would be rejected if 2-year EFS exceeded 88.85%.</div></div><div><h3>Results</h3><div>CCTG HN.10 accrued 103 patients from 2/2019 through 12/2021. As of the data cut-off date for this final analysis (May 31, 2024), median follow-up was 37 (0-56) months, and total person-years follow-up was 304.7. Median age was 62.8 years, 82.5% were male, 87.4% were T1-2, 89.3% were N1, 26.2% had smoked >10 pack-years. Among 100 treated patients, all completed RT, with 50 also receiving cisplatin. Grade 3 and 4 toxicities were observed in 46% and 1%, respectively. In 99 eligible patients, 2-year EFS was 91.8% (95% CI: 86.6%-97.4%), surpassing the protocol-specified threshold. In secondary analysis, there were 5 LRC events including 1 out-of-field regional control event; 2-year OS was 94.7% (95% CI: 90.2%-99.3%). Subgroup analysis showed identical 2-year EFS among patients treated with RT or CRT. By 24 months post-RT, quality of life measurements approximated baseline whereby FACT-HN overall scores and MDADI composite scores improved by mean of 0.41 (N=85, SD=14.8) and declined by mean of 3.58 (N=85, SD=16.2), respectively.</div></div><div><h3>Conclusion</h3><div>For patients with HPV-related OPSCC treated with radical RT, volume-reduced ENI as defined in this study can be safely performed while maintaining high efficacy with rare out-of-field regional failures. This de-escalation strategy should continue to be evaluated in rigorously conducted trials.</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":"142358945","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.2024.07.035
<div><h3>Purpose/Objective(s)</h3><div>Patients with cancer who use cannabis frequently note pain as a reason for their cannabis use. Available data do support cannabis use for management of pain in some settings, though the effectiveness of cannabis for cancer-associated pain is less clear. Based on limited data, some have suggested that cannabis might be used as an alternative to opiates for management of cancer-related pain. We sought to determine the relationship between cannabis use and opioid use in a multicenter cohort of patients undergoing radiotherapy for bone metastases.</div></div><div><h3>Materials/Methods</h3><div>On January 1, 2021, questions about cannabis use were added to Michigan Radiation Oncology Quality Consortium (MROQC) questionnaires for bone metastasis patients. Pain scores, opioid use, social, demographic, and disease characteristics were also prospectively collected. A multivariable model using logistic regression identified associations between recent cannabis use and opioid use, accounting for relevant patient and disease characteristics.</div></div><div><h3>Results</h3><div>Since questions on cannabis were introduced, 2,096 patients have been enrolled. A total of 1143 of 2096 (54.5%) completed questionnaires about recent cannabis use; 1912 of 2096 (91%) completed questionnaires about current opioid use; and 1064 of 2096 (51%) completed both. Among those who completed both, 132 of 1064 (12%) reported recent opioid and cannabis use, 320 of 1064 (30%) reported recent opioid but not cannabis use, 57 of 1064 (5%) reported no recent opioid but recent cannabis use, 281 of 1064 (26%) reported no recent opioid or cannabis use, and the remaining individuals (274/1064 [26%]) declined to answer cannabis use questions by selecting “decline to answer”. In a multivariable model, cannabis use [OR = 2.11 (95% CI = 1.37, 3.26) <em>P</em> = 0.001], along with pain score [Score 1-3 vs 0, OR = 2.32 (95% CI = 1.36, 3.94); Score 4-7 vs 0, OR = 6.55 (95% CI = 4.06, 10.6); Score 8-10 vs 0, OR = 11.20 (95% CI = 6.32, 19.8), <em>P</em> < 0.001], NSAID use [OR = 1.66 (95% CI = 1.17, 2.37) <em>P</em> = 0.005], prior systemic therapy [OR = 0.54 (95% CI = 0.37, 0.78) <em>P</em> = 0.005], and number of metastatic lesions [3-5 vs 1-2, OR = 1.57 (95% CI = 0.95, 2.26); 5-10 vs 1-2, OR = 1.54 (95% CI = 0.91, 2.59); 11+ vs 1-2, OR = 3.26 (95% CI = 2.06, 5.15) <em>P</em> < 0.001] predicted opiate use while age, gender, and race did not.</div></div><div><h3>Conclusion</h3><div>Patients with bone metastases frequently use cannabis, opioids, or both. Though it has been suggested that cannabis availability might reduce opioid use among patients with cancer, our finding that cannabis use predicts opioid use does not support this hypothesis. These data suggest a more complex relationship between cannabis use and opioid use in this population. Further study is needed to assess risks of concurrent cannabis and opioid use and to explore patient rationale f
目的/目标：使用大麻的癌症患者经常将疼痛作为使用大麻的一个原因。现有数据确实支持在某些情况下使用大麻来控制疼痛，但大麻对癌症相关疼痛的疗效并不明确。基于有限的数据，一些人建议使用大麻替代阿片类药物来治疗癌症相关疼痛。材料/方法 2021 年 1 月 1 日，密歇根放射肿瘤质量联合会（MROQC）针对骨转移患者的调查问卷中增加了有关大麻使用情况的问题。此外，还对疼痛评分、阿片类药物使用情况、社会、人口和疾病特征进行了前瞻性收集。使用逻辑回归建立的多变量模型确定了近期大麻使用与阿片类药物使用之间的关联，并考虑了相关的患者和疾病特征。在 2096 名患者中，共有 1143 人（54.5%）完成了关于近期使用大麻情况的问卷调查；2096 名患者中有 1912 人（91%）完成了关于目前使用阿片类药物情况的问卷调查；2096 名患者中有 1064 人（51%）完成了这两项问卷调查。在同时完成这两项调查的人中，1064 人中有 132 人（12%）报告近期使用过阿片类药物和大麻，1064 人中有 320 人（30%）报告近期使用过阿片类药物但未使用过大麻，1064 人中有 57 人（5%）报告近期未使用过阿片类药物但使用过大麻，1064 人中有 281 人（26%）报告近期未使用过阿片类药物或大麻，其余的人（274/1064 [26%]）通过选择 "拒绝回答 "来拒绝回答大麻使用问题。在多变量模型中，使用大麻[OR = 2.11 (95% CI = 1.37, 3.26) P = 0.001]以及疼痛评分[评分 1-3 vs 0, OR = 2.32 (95% CI = 1.36, 3.94); 评分 4-7 vs 0, OR = 6.55 (95% CI = 4.06, 10.6); Score 8-10 vs 0, OR = 11.20 (95% CI = 6.32, 19.8), P < 0.001]、非甾体抗炎药使用[OR = 1.66 (95% CI = 1.17, 2.37) P = 0.005]、既往系统治疗[OR = 0.54 (95% CI = 0.37, 0.78) P = 0.005]、转移病灶数量[3-5 vs 1-2，OR = 1.57 (95% CI = 0.95, 2.26)；5-10 vs 1-2，OR = 1.54 (95% CI = 0.91, 2.59)；11+ vs 1-2，OR = 3.26 (95% CI = 2.06, 5.15) P < 0.001]可预测阿片类药物的使用，而年龄、性别和种族则无法预测。虽然有人认为大麻的供应可能会减少癌症患者对阿片类药物的使用，但我们发现大麻的使用会预测阿片类药物的使用，这并不支持这一假设。这些数据表明，在这一人群中，大麻使用与阿片类药物使用之间的关系更为复杂。需要进一步研究评估同时使用大麻和阿片类药物的风险，并探讨患者同时使用大麻和阿片类药物的理由。
{"title":"Relationship between Cannabis Use and Opioid Use in Patients with Cancer Metastatic to Bone in a Large Multicenter Cohort from a State with Legalized Adult Non-Medical Cannabis","authors":"","doi":"10.1016/j.ijrobp.2024.07.035","DOIUrl":"10.1016/j.ijrobp.2024.07.035","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Patients with cancer who use cannabis frequently note pain as a reason for their cannabis use. Available data do support cannabis use for management of pain in some settings, though the effectiveness of cannabis for cancer-associated pain is less clear. Based on limited data, some have suggested that cannabis might be used as an alternative to opiates for management of cancer-related pain. We sought to determine the relationship between cannabis use and opioid use in a multicenter cohort of patients undergoing radiotherapy for bone metastases.</div></div><div><h3>Materials/Methods</h3><div>On January 1, 2021, questions about cannabis use were added to Michigan Radiation Oncology Quality Consortium (MROQC) questionnaires for bone metastasis patients. Pain scores, opioid use, social, demographic, and disease characteristics were also prospectively collected. A multivariable model using logistic regression identified associations between recent cannabis use and opioid use, accounting for relevant patient and disease characteristics.</div></div><div><h3>Results</h3><div>Since questions on cannabis were introduced, 2,096 patients have been enrolled. A total of 1143 of 2096 (54.5%) completed questionnaires about recent cannabis use; 1912 of 2096 (91%) completed questionnaires about current opioid use; and 1064 of 2096 (51%) completed both. Among those who completed both, 132 of 1064 (12%) reported recent opioid and cannabis use, 320 of 1064 (30%) reported recent opioid but not cannabis use, 57 of 1064 (5%) reported no recent opioid but recent cannabis use, 281 of 1064 (26%) reported no recent opioid or cannabis use, and the remaining individuals (274/1064 [26%]) declined to answer cannabis use questions by selecting “decline to answer”. In a multivariable model, cannabis use [OR = 2.11 (95% CI = 1.37, 3.26) <em>P</em> = 0.001], along with pain score [Score 1-3 vs 0, OR = 2.32 (95% CI = 1.36, 3.94); Score 4-7 vs 0, OR = 6.55 (95% CI = 4.06, 10.6); Score 8-10 vs 0, OR = 11.20 (95% CI = 6.32, 19.8), <em>P</em> < 0.001], NSAID use [OR = 1.66 (95% CI = 1.17, 2.37) <em>P</em> = 0.005], prior systemic therapy [OR = 0.54 (95% CI = 0.37, 0.78) <em>P</em> = 0.005], and number of metastatic lesions [3-5 vs 1-2, OR = 1.57 (95% CI = 0.95, 2.26); 5-10 vs 1-2, OR = 1.54 (95% CI = 0.91, 2.59); 11+ vs 1-2, OR = 3.26 (95% CI = 2.06, 5.15) <em>P</em> < 0.001] predicted opiate use while age, gender, and race did not.</div></div><div><h3>Conclusion</h3><div>Patients with bone metastases frequently use cannabis, opioids, or both. Though it has been suggested that cannabis availability might reduce opioid use among patients with cancer, our finding that cannabis use predicts opioid use does not support this hypothesis. These data suggest a more complex relationship between cannabis use and opioid use in this population. Further study is needed to assess risks of concurrent cannabis and opioid use and to explore patient rationale f","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":"142358604","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.2024.08.021
<div><h3>Purpose/Objective(s)</h3><div>The STOMP and ORIOLE randomized clinical trials (RCTs) showed progression-free survival (PFS) benefits of metastasis-directed therapy (MDT) alone without androgen-deprivation therapy (ADT) for oligometastatic hormone-sensitive prostate cancer (omHSPC). However, most patients with bone metastatic (BM) omHSPC recur with additional BM following MDT alone. We hypothesized the addition of BM-targeting alpha-emitter radium-223 (Ra223), approved for treatment of BM castration-resistant prostate cancer (mCRPC), could delay progression of disease. In addition, biomarkers to determine patients who benefit most from MDT are still poorly defined. We report on the first RCT to examine Ra223 and evaluate novel biomarkers in BM omHSPC.</div></div><div><h3>Materials/Methods</h3><div>In this phase 2 multi-institutional RCT (NCT04037358), men with recurrent omHSPC (≥1 BM & ≤5 radiation fields) were: i) stratified by institution, primary management (radiotherapy vs surgery), PSA doubling time and prior ADT, and ii) randomized 1:1 to stereotactic ablative radiation (SABR) MDT or SABR and 6 monthly cycles of Ra223. The primary endpoint was composite PFS [(PSA ≥ 25% increase and ≥ nadir + 2 ng/mL) and/or (RECIST 1.1 or new lesion on bone scan) and/or (ADT initiation or symptomatic decline)]. Tissue, liquid and imaging correlative studies were obtained and analyzed as biomarkers.</div></div><div><h3>Results</h3><div>From 8/2019-3/2023, 64 patients were randomized (33 to SABR and 31 to SABR/Ra223). Arms were balanced for key covariates. 26 (87%) patients received the full 6 planned cycles of Ra223. Median PFS was 10.2 months with SABR and 10.4 months with SABR/Ra223 (stratified HR 1.7, 95% CI, 0.78-3.69, p = 0.18). 13 patients (20%) experienced grade 3 toxicity (no grade 4 or 5), of which 6 were non-treatment-related, 2 related to SABR, and 5 related to SABR/Ra223 (lymphopenia, back pain). Baseline circulating tumor cells (CTCs) were detected in 55% of patients, and prostate-specific membrane antigen (PSMA)+ CTCs at baseline were prognostic for PFS (p = 0.029). Compared with the observation arm from the ORIOLE RCT, T-cell receptor deep sequencing (TCR-seq) identified significantly more clonotypic expansions between baseline and day 90 with SABR (p = 0.009) and SABR/Ra223 (p = 0.0007). Greater unique productive TCR rearrangements (UPRs) were prognostic for PFS independent of treatment arm (aHR, 0.45; 95% CI, 0.21-0.96; p = 0.04). UPRs were also associated with PFS in the ORIOLE RCT (HR, 0.46; 95% CI, 0.19-1.05; p = 0.07).</div></div><div><h3>Conclusion</h3><div>SABR alone for omHSPC affords PFS benefits, but emergence of additional BM in most patients remains a challenge. We report for the first time that the addition of Ra223 to SABR MDT in this low volume BM state does not delay progression of disease. CTCs are present in omHSPC, and SABR MDT induces a systemic adaptive immune response. We validate the TCR repertoire as a prog
{"title":"Outcomes of RAdium-223 and SABR vs. SABR for oligomEtastatic prostate caNcerS – The RAVENS Phase II Randomized Trial","authors":"","doi":"10.1016/j.ijrobp.2024.08.021","DOIUrl":"10.1016/j.ijrobp.2024.08.021","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>The STOMP and ORIOLE randomized clinical trials (RCTs) showed progression-free survival (PFS) benefits of metastasis-directed therapy (MDT) alone without androgen-deprivation therapy (ADT) for oligometastatic hormone-sensitive prostate cancer (omHSPC). However, most patients with bone metastatic (BM) omHSPC recur with additional BM following MDT alone. We hypothesized the addition of BM-targeting alpha-emitter radium-223 (Ra223), approved for treatment of BM castration-resistant prostate cancer (mCRPC), could delay progression of disease. In addition, biomarkers to determine patients who benefit most from MDT are still poorly defined. We report on the first RCT to examine Ra223 and evaluate novel biomarkers in BM omHSPC.</div></div><div><h3>Materials/Methods</h3><div>In this phase 2 multi-institutional RCT (NCT04037358), men with recurrent omHSPC (≥1 BM & ≤5 radiation fields) were: i) stratified by institution, primary management (radiotherapy vs surgery), PSA doubling time and prior ADT, and ii) randomized 1:1 to stereotactic ablative radiation (SABR) MDT or SABR and 6 monthly cycles of Ra223. The primary endpoint was composite PFS [(PSA ≥ 25% increase and ≥ nadir + 2 ng/mL) and/or (RECIST 1.1 or new lesion on bone scan) and/or (ADT initiation or symptomatic decline)]. Tissue, liquid and imaging correlative studies were obtained and analyzed as biomarkers.</div></div><div><h3>Results</h3><div>From 8/2019-3/2023, 64 patients were randomized (33 to SABR and 31 to SABR/Ra223). Arms were balanced for key covariates. 26 (87%) patients received the full 6 planned cycles of Ra223. Median PFS was 10.2 months with SABR and 10.4 months with SABR/Ra223 (stratified HR 1.7, 95% CI, 0.78-3.69, p = 0.18). 13 patients (20%) experienced grade 3 toxicity (no grade 4 or 5), of which 6 were non-treatment-related, 2 related to SABR, and 5 related to SABR/Ra223 (lymphopenia, back pain). Baseline circulating tumor cells (CTCs) were detected in 55% of patients, and prostate-specific membrane antigen (PSMA)+ CTCs at baseline were prognostic for PFS (p = 0.029). Compared with the observation arm from the ORIOLE RCT, T-cell receptor deep sequencing (TCR-seq) identified significantly more clonotypic expansions between baseline and day 90 with SABR (p = 0.009) and SABR/Ra223 (p = 0.0007). Greater unique productive TCR rearrangements (UPRs) were prognostic for PFS independent of treatment arm (aHR, 0.45; 95% CI, 0.21-0.96; p = 0.04). UPRs were also associated with PFS in the ORIOLE RCT (HR, 0.46; 95% CI, 0.19-1.05; p = 0.07).</div></div><div><h3>Conclusion</h3><div>SABR alone for omHSPC affords PFS benefits, but emergence of additional BM in most patients remains a challenge. We report for the first time that the addition of Ra223 to SABR MDT in this low volume BM state does not delay progression of disease. CTCs are present in omHSPC, and SABR MDT induces a systemic adaptive immune response. We validate the TCR repertoire as a prog","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":"142358944","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.2024.07.027
<div><h3>Purpose/Objective(s)</h3><div>A cloud-based bidirectional app (ePRO) communicating real-time patient-reported cancer treatment symptom(s) and clinical care team (CCT) recommendation(s) can lessen treatment burden. However, symptoms manifest differently for radiation therapy (RT) and systemic therapies (ST) and CCTs require one solution to be effective for both groups across time. This study tests whether there is a longitudinal difference in app satisfaction scores, a proxy for overall app utility, between these two groups.</div></div><div><h3>Materials/Methods</h3><div>The study focuses on a subgroup of Noona users who have reported app satisfaction 2 or more times (<em>n</em> = 7,202). They, and all other patients, have access to three primary features. In the first, the CCT uses the software to administer CTCAE-derived items at a cadence based on the treatment regimen (e.g., weekly for radiation therapy). Patients can also complete it ad hoc. When patients report moderate or severe symptoms, they receive programmed recommendations and the software triages patient in order of urgency on a clinic-facing dashboard so that a team member can efficiently follow-up with additional questions or instructions. The app also includes a diary patients can use to record any personal information, as well as a secure communication feature which facilitates exchange of additional medical and non-medical information with the CCT. Data used for this study include passively collected, anonymized information and a patient satisfaction item that randomly asked those with active accounts > 30 days, “How likely are you to recommend (software name) to another patient” using an 11-point scale. Data are reported descriptively and analyzed using a linear mixed model with patient as a random effect and repeated measurements with an autoregressive covariance structure.</div></div><div><h3>Results</h3><div>Most patients were from the United States (<em>n</em> = 4,941; 12 sites), followed by Canada (<em>n</em> = 1,700; 4 sites) and Europe (<em>n</em> = 561; sites = 5). The mean age was 61.7 (SD = 11.8). Most were English speakers (<em>n</em> = 6,794; 94.3%), used a smartphone (<em>n</em> = 5,480; 76.1%), and were, based on the module they were assigned, receiving systemic therapy (<em>n</em> = 6,468; 89.8%). The mean number of times a patient reported app satisfaction was 3.1 (SD = 1.6; range = 2-13). The mean of the patients’ first satisfaction score was 8.5 (SD = 2.5) and 5,704 (79.2%) rated the app ≥ 8. The satisfaction level was generally maintained across subsequent ratings. The regression model found that satisfaction levels for patients receiving radiation did not significantly differ (B = 0.205; <em>P</em> = 0.835) from those receiving systemic therapy after adjusting for the other 5 variables indicating that, over time, patients regardless of the treatment reported similar app satisfaction scores.</div></div><div><h3>Conclusion</h3><div>A single solution
{"title":"Comparing Radiation and Systemic Therapy Patients’ Longitudinal Satisfaction of a Cloud-Based Bidirectional App Used for Real-Time Communication of Patient-Reported Cancer Treatment Symptoms","authors":"","doi":"10.1016/j.ijrobp.2024.07.027","DOIUrl":"10.1016/j.ijrobp.2024.07.027","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>A cloud-based bidirectional app (ePRO) communicating real-time patient-reported cancer treatment symptom(s) and clinical care team (CCT) recommendation(s) can lessen treatment burden. However, symptoms manifest differently for radiation therapy (RT) and systemic therapies (ST) and CCTs require one solution to be effective for both groups across time. This study tests whether there is a longitudinal difference in app satisfaction scores, a proxy for overall app utility, between these two groups.</div></div><div><h3>Materials/Methods</h3><div>The study focuses on a subgroup of Noona users who have reported app satisfaction 2 or more times (<em>n</em> = 7,202). They, and all other patients, have access to three primary features. In the first, the CCT uses the software to administer CTCAE-derived items at a cadence based on the treatment regimen (e.g., weekly for radiation therapy). Patients can also complete it ad hoc. When patients report moderate or severe symptoms, they receive programmed recommendations and the software triages patient in order of urgency on a clinic-facing dashboard so that a team member can efficiently follow-up with additional questions or instructions. The app also includes a diary patients can use to record any personal information, as well as a secure communication feature which facilitates exchange of additional medical and non-medical information with the CCT. Data used for this study include passively collected, anonymized information and a patient satisfaction item that randomly asked those with active accounts > 30 days, “How likely are you to recommend (software name) to another patient” using an 11-point scale. Data are reported descriptively and analyzed using a linear mixed model with patient as a random effect and repeated measurements with an autoregressive covariance structure.</div></div><div><h3>Results</h3><div>Most patients were from the United States (<em>n</em> = 4,941; 12 sites), followed by Canada (<em>n</em> = 1,700; 4 sites) and Europe (<em>n</em> = 561; sites = 5). The mean age was 61.7 (SD = 11.8). Most were English speakers (<em>n</em> = 6,794; 94.3%), used a smartphone (<em>n</em> = 5,480; 76.1%), and were, based on the module they were assigned, receiving systemic therapy (<em>n</em> = 6,468; 89.8%). The mean number of times a patient reported app satisfaction was 3.1 (SD = 1.6; range = 2-13). The mean of the patients’ first satisfaction score was 8.5 (SD = 2.5) and 5,704 (79.2%) rated the app ≥ 8. The satisfaction level was generally maintained across subsequent ratings. The regression model found that satisfaction levels for patients receiving radiation did not significantly differ (B = 0.205; <em>P</em> = 0.835) from those receiving systemic therapy after adjusting for the other 5 variables indicating that, over time, patients regardless of the treatment reported similar app satisfaction scores.</div></div><div><h3>Conclusion</h3><div>A single solution","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":"142359416","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.2024.07.063
<div><h3>Purpose/Objective(s)</h3><div>The standard of care for oncologic treatment is often established and refined through randomized phase III clinical trials. While the success of a trial is generally established through meeting statistical significance, there are few metrics to measure the robustness of a trial’s outcomes. Using the survival-inferred fragility index (SIFI), we performed an assessment of the fragility of oncology clinical trials.</div></div><div><h3>Materials/Methods</h3><div>We established a database of 332 phase III oncology trials from 2002-2020 for which Kaplan-Meier curves were digitally reconstructed to accurately reproduce survival time and censoring at the individual level. SIFI values were established by counting the number of patients that needed to be iteratively flipped between treatment arms to cause a positive trial to lose statistical significance or for a negative trial to gain statistical significance. This number was then normalized as a percentage of the total trial enrollment. We calculated SIFI using flipping of best (longest) survivor from the intervention arm (SIFI_B), worst (shortest) survivor from the control arm (SIFI_W), and median survivor in the control arm (SIFI_M). Trials were classified based on whether they were testing immune-checkpoint inhibitors (ICIs), targeted therapies, or others. The Mann-Whitney U test was used to perform pairwise comparisons and the Kruskal-Wallis test was used for comparisons of more than 2 groups. Statistical analyses were performed in R.</div></div><div><h3>Results</h3><div>Of the 332 trials assessed, 196 were positive and 136 were negative. There were 190 targeted therapy trials, 52 ICI trials, and 90 trials assessing other agents. The most common primary endpoint was progression-free survival (PFS) (154 trials), followed by overall survival (OS) (136 trials). For all trials, the median SIFI_B was 1.37%, SIFI_W was 1.71%, and SIFI_M was 2.74%. A practice changing ICI trial was the PACIFIC trial, which had SIFI_B of 1.96%, SIFI_W of 1.40%, and SIFI_M of 1.82%. Targeted therapy trials were significantly more robust than ICI trials with SIFI_W of 1.93% vs 1.28% (<em>P</em> = 0.037) and SIFI_M of 3.14% vs 1.98% (<em>P</em> = 0.012). Trials assessing OS as the primary endpoint were significantly more fragile than trials with PFS as the overall endpoint (SIFI_B 0.90% vs. 1.78%, <em>P</em> < 0.001; SIFI_W 1.33% vs. 2.96%, <em>P</em> < 0.001; SIFI_M 2.13% vs. 4.58%, <em>P</em> < 0.001). Lastly, trials with negative outcomes were significantly more fragile than trials with positive outcomes (SIFI_B 1.08% vs. 1.68%, <em>P</em> < 0.001; SIFI_W 1.36% vs. 2.32%, <em>P</em> < 0.001; SIFI_M 2.21% vs. 3.70%, <em>P</em> < 0.001).</div></div><div><h3>Conclusion</h3><div>We found that targeted therapy trials, trials with PFS as the primary endpoint, and positive trials tend to be the most robust. Further work will need to validate the use of SIFI in designing more
目的/目标：肿瘤治疗的标准通常是通过随机 III 期临床试验确立和完善的。虽然试验的成功一般是通过达到统计学意义来确定的，但很少有衡量试验结果稳健性的指标。材料/方法 我们建立了一个包含 2002-2020 年间 332 项 III 期肿瘤试验的数据库，对这些试验的 Kaplan-Meier 曲线进行了数字重建，以准确再现生存时间和个体水平的删减。SIFI值是通过计算需要在治疗臂之间反复翻转才能使阳性试验失去统计学意义或使阴性试验获得统计学意义的患者人数来确定的。然后将这一数字归一化为占试验总人数的百分比。我们通过翻转干预组的最佳（最长）存活者（SIFI_B）、对照组的最差（最短）存活者（SIFI_W）和对照组的中位存活者（SIFI_M）来计算 SIFI。试验的分类依据是它们是否在测试免疫检查点抑制剂（ICIs）、靶向疗法或其他疗法。成对比较采用 Mann-Whitney U 检验，两组以上比较采用 Kruskal-Wallis 检验。统计分析在 R 中进行。结果在评估的 332 项试验中，196 项为阳性，136 项为阴性。其中有 190 项靶向治疗试验、52 项 ICI 试验和 90 项评估其他药物的试验。最常见的主要终点是无进展生存期（PFS）（154 项试验），其次是总生存期（OS）（136 项试验）。在所有试验中，SIFI_B 的中位数为 1.37%，SIFI_W 为 1.71%，SIFI_M 为 2.74%。PACIFIC试验改变了ICI试验的做法，该试验的SIFI_B为1.96%，SIFI_W为1.40%，SIFI_M为1.82%。靶向治疗试验明显比 ICI 试验更稳健，SIFI_W 为 1.93% vs 1.28% (P = 0.037)，SIFI_M 为 3.14% vs 1.98% (P = 0.012)。以OS为主要终点的试验明显比以PFS为总终点的试验更脆弱（SIFI_B 0.90% vs. 1.78%, P < 0.001; SIFI_W 1.33% vs. 2.96%, P < 0.001; SIFI_M 2.13% vs. 4.58%, P < 0.001）。最后，阴性结果的试验明显比阳性结果的试验更脆弱（SIFI_B 1.08% vs. 1.68%，P < 0.001；SIFI_W 1.36% vs. 2.32%，P < 0.001；SIFI_M 2.21% vs. 3.70%，P < 0.001）。在设计更稳健的临床试验时，需要进一步验证 SIFI 的使用。
{"title":"The Fragility of Phase III Trials in Oncology","authors":"","doi":"10.1016/j.ijrobp.2024.07.063","DOIUrl":"10.1016/j.ijrobp.2024.07.063","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>The standard of care for oncologic treatment is often established and refined through randomized phase III clinical trials. While the success of a trial is generally established through meeting statistical significance, there are few metrics to measure the robustness of a trial’s outcomes. Using the survival-inferred fragility index (SIFI), we performed an assessment of the fragility of oncology clinical trials.</div></div><div><h3>Materials/Methods</h3><div>We established a database of 332 phase III oncology trials from 2002-2020 for which Kaplan-Meier curves were digitally reconstructed to accurately reproduce survival time and censoring at the individual level. SIFI values were established by counting the number of patients that needed to be iteratively flipped between treatment arms to cause a positive trial to lose statistical significance or for a negative trial to gain statistical significance. This number was then normalized as a percentage of the total trial enrollment. We calculated SIFI using flipping of best (longest) survivor from the intervention arm (SIFI_B), worst (shortest) survivor from the control arm (SIFI_W), and median survivor in the control arm (SIFI_M). Trials were classified based on whether they were testing immune-checkpoint inhibitors (ICIs), targeted therapies, or others. The Mann-Whitney U test was used to perform pairwise comparisons and the Kruskal-Wallis test was used for comparisons of more than 2 groups. Statistical analyses were performed in R.</div></div><div><h3>Results</h3><div>Of the 332 trials assessed, 196 were positive and 136 were negative. There were 190 targeted therapy trials, 52 ICI trials, and 90 trials assessing other agents. The most common primary endpoint was progression-free survival (PFS) (154 trials), followed by overall survival (OS) (136 trials). For all trials, the median SIFI_B was 1.37%, SIFI_W was 1.71%, and SIFI_M was 2.74%. A practice changing ICI trial was the PACIFIC trial, which had SIFI_B of 1.96%, SIFI_W of 1.40%, and SIFI_M of 1.82%. Targeted therapy trials were significantly more robust than ICI trials with SIFI_W of 1.93% vs 1.28% (<em>P</em> = 0.037) and SIFI_M of 3.14% vs 1.98% (<em>P</em> = 0.012). Trials assessing OS as the primary endpoint were significantly more fragile than trials with PFS as the overall endpoint (SIFI_B 0.90% vs. 1.78%, <em>P</em> < 0.001; SIFI_W 1.33% vs. 2.96%, <em>P</em> < 0.001; SIFI_M 2.13% vs. 4.58%, <em>P</em> < 0.001). Lastly, trials with negative outcomes were significantly more fragile than trials with positive outcomes (SIFI_B 1.08% vs. 1.68%, <em>P</em> < 0.001; SIFI_W 1.36% vs. 2.32%, <em>P</em> < 0.001; SIFI_M 2.21% vs. 3.70%, <em>P</em> < 0.001).</div></div><div><h3>Conclusion</h3><div>We found that targeted therapy trials, trials with PFS as the primary endpoint, and positive trials tend to be the most robust. Further work will need to validate the use of SIFI in designing more ","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":"142359161","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.2024.07.056
Purpose/Objective(s)
Stereotactic body radiation therapy (SBRT) for spinal metastases improves symptomatic outcomes and local control compared to conventional radiotherapy (RT). Treatment failure most often occurs within the epidural space, where dose is constrained by the risk of radiation myelitis (RM). We conducted a retrospective cohort study of patients treated with 3-fraction spine SBRT to create modern risk assessments of RM.
Materials/Methods
Patients were treated at a single institution between 2014 and 2023 with 3-fraction spine SBRT to a level between C1-L2. Patients were excluded if they had received overlapping prior RT, had less than 1 month of magnetic resonance imaging (MRI) follow up, or had a maximal dose to a voxel of spinal cord (Dmax) of 0 Gy. RM was defined as radiographic evidence of cord injury in the treatment field and further classified into grade (G) 1-4 or G3+ by Common Terminology Criteria for Adverse Events version 5.0. We assessed multiple dosimetric parameters of the true spinal cord structure for association with risk of RM. Univariable, cause-specific hazards, competing risk regression models were fit for RM using the Cox proportional hazards model with robust standard errors to account for patient-level clustering, with the dosimetric variables as predictors. To generate a dose-response model of RM, predicted probabilities and 95% confidence interval (CI) limits were estimated at 2 years using the regression models for the dosimetric variables of the minimum dose to the 0.1 cm3 of spinal cord receiving the greatest dose (D0.1 cc) or Dmax.
Results
There were 1,423 patients treated to 1,904 segments in the analysis. Median follow up was 13 months (interquartile range 7-26 months). We identified 30 cases of RM, 19 of which were G3+. At 2 years, the cumulative incidence of G1-4 RM was 1.8% (95% CI = 1.2%-2.5%), and the rate of G3+ RM was 1.1% (95% CI = 0.71%-1.7%). For patients who experienced RM, the median time to myelitis was 10 months (range = 3.7-29.7 months). Cord D0.1 cc was the most important dosimetric predictor of RM on univariable, cause-specific hazards regression (for G3+ RM, hazard ratio (HR) = 2.14, 95% CI = 1.68-2.72, P < 0.0001). Dmax was also an important predictor of RM (for G3+ RM, HR = 1.82, 95% CI = 1.48-2.24, P < 0.0001). According to our dose-response model, a true cord D0.1 cc of 19.1 Gy and Dmax of 20.8 Gy predict a 1% risk (95% CI = 0.3%-1.6% and 0.4%-1.6%, respectively) of G3+ RM 2 years from SBRT.
Conclusion
This is the largest series of RM cases after spine SBRT. A true cord D0.1 cc constraint of 19.1 Gy and a Dmax constraint of 20.8 Gy correspond with a 1% risk of G3+ RM at 2 years.
{"title":"Risk of Radiation Myelitis after Hypofractionated Spine Stereotactic Body Radiation Therapy","authors":"","doi":"10.1016/j.ijrobp.2024.07.056","DOIUrl":"10.1016/j.ijrobp.2024.07.056","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Stereotactic body radiation therapy (SBRT) for spinal metastases improves symptomatic outcomes and local control compared to conventional radiotherapy (RT). Treatment failure most often occurs within the epidural space, where dose is constrained by the risk of radiation myelitis (RM). We conducted a retrospective cohort study of patients treated with 3-fraction spine SBRT to create modern risk assessments of RM.</div></div><div><h3>Materials/Methods</h3><div>Patients were treated at a single institution between 2014 and 2023 with 3-fraction spine SBRT to a level between C1-L2. Patients were excluded if they had received overlapping prior RT, had less than 1 month of magnetic resonance imaging (MRI) follow up, or had a maximal dose to a voxel of spinal cord (Dmax) of 0 Gy. RM was defined as radiographic evidence of cord injury in the treatment field and further classified into grade (G) 1-4 or G3+ by Common Terminology Criteria for Adverse Events version 5.0. We assessed multiple dosimetric parameters of the true spinal cord structure for association with risk of RM. Univariable, cause-specific hazards, competing risk regression models were fit for RM using the Cox proportional hazards model with robust standard errors to account for patient-level clustering, with the dosimetric variables as predictors. To generate a dose-response model of RM, predicted probabilities and 95% confidence interval (CI) limits were estimated at 2 years using the regression models for the dosimetric variables of the minimum dose to the 0.1 cm<sup>3</sup> of spinal cord receiving the greatest dose (D0.1 cc) or Dmax.</div></div><div><h3>Results</h3><div>There were 1,423 patients treated to 1,904 segments in the analysis. Median follow up was 13 months (interquartile range 7-26 months). We identified 30 cases of RM, 19 of which were G3+. At 2 years, the cumulative incidence of G1-4 RM was 1.8% (95% CI = 1.2%-2.5%), and the rate of G3+ RM was 1.1% (95% CI = 0.71%-1.7%). For patients who experienced RM, the median time to myelitis was 10 months (range = 3.7-29.7 months). Cord D0.1 cc was the most important dosimetric predictor of RM on univariable, cause-specific hazards regression (for G3+ RM, hazard ratio (HR) = 2.14, 95% CI = 1.68-2.72, <em>P</em> < 0.0001). Dmax was also an important predictor of RM (for G3+ RM, HR = 1.82, 95% CI = 1.48-2.24, <em>P</em> < 0.0001). According to our dose-response model, a true cord D0.1 cc of 19.1 Gy and Dmax of 20.8 Gy predict a 1% risk (95% CI = 0.3%-1.6% and 0.4%-1.6%, respectively) of G3+ RM 2 years from SBRT.</div></div><div><h3>Conclusion</h3><div>This is the largest series of RM cases after spine SBRT. A true cord D0.1 cc constraint of 19.1 Gy and a Dmax constraint of 20.8 Gy correspond with a 1% risk of G3+ RM at 2 years.</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":"142359479","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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