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Intensity-Modulated Radiation Therapy Reduces Patient-Reported Chronic Toxicity Compared With Conventional Pelvic Radiation Therapy: Updated Results of a Phase III Trial.

ABSTRACT: Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The purpose of this update was to determine differences in patient-reported chronic toxicity and disease outcomes with intensity-modulated radiation therapy (IMRT) compared with conventional pelvic radiation. Patients with cervical and endometrial cancers who received postoperative pelvic radiation were randomly assigned to conventional radiation therapy (CRT) or IMRT. Toxicity and quality of life were assessed using Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domains, and Functional Assessment of Cancer Therapy-General. Between 2012 and 2015, 279 eligible patients were enrolled to the study with a median follow-up of 37.8 months. There were no differences in overall survival (P = .53), disease-free survival (P = .21), or locoregional failure (P = .81). One year after RT, patients in the CRT arm experienced more high-level diarrhea frequency (5.8% IMRT v 15.1% CRT, P = .042) and a greater number had to take antidiarrheal medication two or more times a day (1.2% IMRT v 8.6% CRT, P = .036). At 3 years, women in the CRT arm reported a decline in urinary function, whereas the IMRT arm continued to improve (mean change in EPIC urinary score = 0.5, standard deviation = 13.0, IMRT v -6.0, standard deviation = 14.3, CRT, P = .005). In conclusion, IMRT reduces patient-reported chronic GI and urinary toxicity with no difference in treatment efficacy at 3 years.

SUBMITTER: Yeung AR

PROVIDER: S-EPMC9851703 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Intensity-Modulated Radiation Therapy Reduces Patient-Reported Chronic Toxicity Compared With Conventional Pelvic Radiation Therapy: Updated Results of a Phase III Trial.

Yeung Anamaria R AR Deshmukh Snehal S Klopp Ann H AH Gil Karen M KM Wenzel Lari L Westin Shannon N SN Konski Andre A AA Gaffney David K DK Small William W Thompson J Spencer JS Doncals Desiree E DE Cantuaria Guilherme H C GHC D'Souza David P DP Chang Amy A Kundapur Vijayananda V Mohan Dasarahally S DS Haas Michael L ML Kim Yong Bae YB Ferguson Catherine L CL Pugh Stephanie L SL Kachnic Lisa A LA Bruner Deborah W DW

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20220812 27

<i>Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in</i> JCO <i>or elsewhere, for which the primary end point has already been reported.</i>The purpose of this update was to determine differences in patien ...[more]

PMID: 35960897

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Project description:BackgroundWhile chemo-radiotherapy improves local control in patients with locally advanced rectal cancer, it can also increase acute hematological toxicity (HT), which leads to poor outcomes. Patients receiving bone marrow radiation have been shown to develop acute HT. However, the safety and efficacy of bone marrow sparing is undetermined. The aim of our study was to explore the feasible dosimetric constraints for pelvic bone marrow (PBM) that can be widely used in rectal cancer patients undergoing chemo-radiotherapy.Methods112 rectal cancer patients were selected and divided into the PBM sparing IMRT group (60 cases) and the non-PBM sparing IMRT group (52 cases). All patients underwent pelvic radiotherapy with concurrent capecitabine-based chemotherapy. The PBM dosimetric constraints in the PBM sparing IMRT group were set to:V10 ≤ 85%, V20 ≤ 65% and V30 ≤ 45%. An independent sample t test was applied for the dose-volume parameters, and Chi-squared analysis was applied for clinical parameters and adverse events.ResultsThe radiation dose to PBM (V5~V45, Dmean, P<0.05), PBM sub-regions (V10~V35, Dmean, P<0.05) and both femoral heads (V5~V40, Dmean, P<0.05) decreased significantly in the PBM sparing IMRT group compared with that of the non-PBM sparing IMRT group (P<0.05). There was no significant difference in any dose-volume parameters of the bladder and small bowel in either groups, and none in the planning target volume (PTV) dose homogeneity and conformity (P>0.05). For acute HT observation, the incidence of grade 3 acute HT (χ2 = 7.094, P=0.008) was significantly reduced in patients treated with PBM sparing IMRT compared with patients treated with non-PBM sparing IMRT. There was no statistical difference in the incidence of vomiting, diarrhea, fatigue, anorexia, nausea, hand-foot syndrome, cystitis, perianal pain and perianal dermatitis in patients of both groups (P >0.05).ConclusionsApplying PBM dosimetric constraints (V10 ≤ 85%, V20 ≤ 65% and V30 ≤ 45%) can significantly reduce the radiation dose to PBM. The patients treated with PBM sparing IMRT had a lower incidence of acute HT compared with those treated with non-PBM sparing IMRT. Applying the PBM dosimetric constraints proposed by our study can benefits the patients with rectal cancer undergoing capecitabine-based chemo-radiotherapy.

Project description:ImportancePatients with oropharyngeal carcinoma (OPC) treated with radiotherapy often experience substantial toxic effects, even with modern techniques such as intensity-modulated radiation therapy (IMRT). Intensity-modulated proton therapy (IMPT) has a potential advantage over IMRT due to reduced dose to the surrounding organs at risk; however, data are scarce given the limited availability and use of IMPT.ObjectiveTo compare toxic effects and oncologic outcomes among patients with newly diagnosed nonmetastatic OPC treated with IMPT vs IMRT with or without chemotherapy.Design, setting, and participantsThis retrospective cohort study included patients aged 18 years or older with newly diagnosed nonmetastatic OPC who received curative-intent radiotherapy with IMPT or IMRT at a single-institution tertiary academic cancer center from January 1, 2018, to December 31, 2021, with follow-up through December 31, 2021.ExposuresIMPT or IMRT with or without chemotherapy.Main outcomes and measuresThe main outcomes were the incidence of acute and chronic (present after ≥6 months) treatment-related adverse events (AEs) and oncologic outcomes, including locoregional recurrence (LRR), progression-free survival (PFS), and overall survival (OS). Fisher exact tests and χ2 tests were used to evaluate associations between toxic effects and treatment modality (IMPT vs IMRT), and the Kaplan-Meier method was used to compare LRR, PFS, and OS between the 2 groups.ResultsThe study included 292 patients with OPC (272 [93%] with human papillomavirus [HPV]-p16-positive tumors); 254 (87%) were men, 38 (13%) were women, and the median age was 64 years (IQR, 58-71 years). Fifty-eight patients (20%) were treated with IMPT, and 234 (80%) were treated with IMRT. Median follow-up was 26 months (IQR, 17-36 months). Most patients (283 [97%]) received a dose to the primary tumor of 70 Gy. Fifty-seven of the patients treated with IMPT (98%) and 215 of those treated with IMRT (92%) had HPV-p16-positive disease. There were no significant differences in 3-year OS (97% IMPT vs 91% IMRT; P = .18), PFS (82% IMPT vs 85% IMRT; P = .62), or LRR (5% IMPT vs 4% IMRT; P = .59). The incidence of acute toxic effects was significantly higher for IMRT compared with IMPT for oral pain of grade 2 or greater (42 [72%] IMPT vs 217 [93%] IMRT; P < .001), xerostomia of grade 2 or greater (12 [21%] IMPT vs 68 [29%] IMRT; P < .001), dysgeusia of grade 2 or greater (16 [28%] IMPT vs 134 [57%] IMRT; P < .001), grade 3 dysphagia (4 [7%] IMPT vs 29 [12%] IMRT; P < .001), mucositis of grade 3 or greater (10 [53%] IMPT vs 13 [70%] IMRT; P = .003), nausea of grade 2 or greater (0 [0%] IMPT vs 18 [8%] IMRT; P = .04), and weight loss of grade 2 or greater (22 [37%] IMPT vs 138 [59%] IMRT; P < .001). There were no significant differences in chronic toxic effects of grade 3 or greater, although there was a significant difference for chronic xerostomia of grade 2 or greater (6 IMPT [11%] vs 22 IMRT [10%]; P < .001). Four patients receiving IMRT (2%) vs 0 receiving IMPT had a percutaneous endoscopic gastrostomy tube for longer than 6 months.Conclusions and relevanceIn this study, curative-intent radiotherapy with IMPT for nonmetastatic OPC was associated with a significantly reduced acute toxicity burden compared with IMRT, with few chronic toxic effects and favorable oncologic outcomes, including locoregional recurrence of only 5% at 2 years. Prospective randomized clinical trials comparing these 2 technologies and of patient-reported outcomes are warranted.

Project description:ImportancePatients with nonmetastatic nasopharyngeal carcinoma (NPC) are primarily treated by radiotherapy with curative intent with or without chemotherapy and often experience substantial treatment-related toxic effects even with modern radiation techniques, such as intensity-modulated radiation therapy (IMRT). Intensity-modulated proton therapy (IMPT) may improve the toxicity profile; however, there is a paucity of data given the limited availability of IMPT in regions with endemic NPC.ObjectiveTo compare toxic effects and oncologic outcomes among patients with newly diagnosed nonmetastatic NPC when treated with IMPT vs IMRT with or without chemotherapy.Design, setting, and participantsThis retrospective cohort study included 77 patients with newly diagnosed nonmetastatic NPC who received curative-intent radiotherapy with IMPT or IMRT at a tertiary academic cancer center from January 1, 2016, to December 31, 2019. Forty-eight patients with Epstein-Barr virus (EBV)-positive tumors were included in a 1:1 propensity score-matched analysis for survival outcomes. The end of the follow-up period was March 31, 2021.ExposuresIMPT vs IMRT with or without chemotherapy.Main outcomes and measuresThe main outcomes were the incidence of acute and chronic treatment-related adverse events (AEs) and oncologic outcomes, including locoregional failure-free survival (LRFS), progression-free survival (PFS), and overall survival (OS).ResultsWe identified 77 patients (25 [32.5%] women; 52 [67.5%] men; median [interquartile range] age, 48.7 [42.2-60.3] years), among whom 28 (36.4%) were treated with IMPT and 49 (63.6%) were treated with IMRT. Median (interquartile range) follow-up was 30.3 (17.9-41.5) months. On multivariable logistic regression analyses, IMPT was associated with lower likelihood of developing grade 2 or higher acute AEs compared with IMRT (odds ratio [OR], 0.15; 95% CI, 0.03-0.60; P = .01). Only 1 case (3.8%) of a chronic grade 3 or higher AE occurred in the IMPT group compared with 8 cases (16.3%) in the IMRT group (OR, 0.21; 95% CI, 0.01-1.21; P = .15). Propensity score matching generated a balanced cohort of 48 patients (24 IMPT vs 24 IMRT) and found similar PFS in the IMPT and IMRT groups (2-year PFS, 95.7% [95% CI, 87.7%-100%] vs 76.7% [95% CI, 60.7%-97.0%]; hazard ratio [HR], 0.31; 95% CI, 0.07-1.47; P = .14). No locoregional recurrence or death was observed in the IMPT group from the matched cohort. Two-year LRFS was 100% (95% CI, 100%-100%) in the IMPT group and 86.2% (95% CI, 72.8%-100%) in the IMRT group (P = .08). Three-year OS was 100% (95% CI, 100%-100%) in the IMPT group and 94.1% (95% CI, 83.6%-100%) in the IMRT group (P = .42). Smoking history was the only clinical factor significantly associated with both poor LRFS (HR, 63.37; 95% CI, 3.25-1236.13; P = .006) and poor PFS (HR, 6.33; 95% CI, 1.16-34.57; P = .03) on multivariable analyses.Conclusions and relevanceIn this study, curative-intent radiotherapy with IMPT for nonmetastatic NPC was associated with significantly reduced acute toxicity burden in comparison with IMRT, with rare late complications and excellent oncologic outcomes, including 100% locoregional control at 2 years. Prospective trials are warranted to direct the optimal patient selection for IMPT as the primary radiotherapy modality for nonmetastatic NPC.

Project description:PurposeDose-volume histogram (DVH) toxicity relationships are poorly defined in men who receive radiation after radical prostatectomy (RP). We evaluated Radiation Therapy Oncology Group (RTOG) study 0534 and institutional intact normal-tissue sparing guidelines, as well as dose to bladder trigone, for ability to minimize late toxicity.Methods and materials164 men received intensity modulated radiation therapy (RT) to a median prostate bed dose of 66.6 Gy at a median of 22 months after RP. 46% of men were prescribed androgen deprivation therapy and pelvic lymph node irradiation to a median dose of 50.4 Gy. DVH relationships for the rectum, bladder, trigone, and bladder excluding the clinical target volume (bladder-CTV) were analyzed against the Common Terminology Criteria for Adverse Events late grade 2 + (G2+) gastrointestinal (GI) and genitourinary (GU) toxicity by log-rank test. RTOG 0534 (rectum V65, 40 Gy ≤35, 55%, and bladder-CTV V65, 40 ≤50, 70%) and intact prostate RT institutional guidelines (rectum V70, 65, 40 ≤20, 40, 80% and bladder V70, 65, 40 ≤30, 60, 80%, respectively) guidelines were evaluated.ResultsWith a median follow-up time of of 33 months, the 4-year freedom from G2 + GI and GU toxicity were both 91%. G2 + GI (n = 12) and GU (n = 15) toxicity included 4% diarrhea (n = 6), 4% hemorrhage (n = 6), 1% proctitis (n = 1), and 4% urinary frequency (n = 7), 1% obstructive (n = 2), 2% cystitis (n = 3), and 3% incontinence (n = 5), respectively. RTOG 0534 rectum and bladder goals were not achieved in 65% and 41% of cases, while the institutional intact prostate goals were not achieved in 21% and 25% of cases, respectively. Neither dose to the bladder trigone nor any of the proposed normal tissue goals were associated with late toxicity (P > .1). In the univariate analysis, age, pelvic RT, RT dose, anticoagulation use, androgen deprivation therapy, time from RP to RT, and tobacco history were not associated with toxicity.ConclusionsMore than 90% of men were free from late G2 + toxicity 4 years after post-RP intensity modulated RT. No tested parameters were associated with late toxicity. In the absence of established normal-tissue DVH guidelines in the postoperative setting, the use of intact guidelines is reasonable.

Project description:PurposeIntensity-modulated radiation therapy (IMRT) has allowed optimization of three-dimensional spatial radiation dose distributions permitting target coverage while reducing normal tissue toxicity. However, radiation-induced normal tissue toxicity is a major contributor to patients' quality of life and often a dose-limiting factor in the definitive treatment of cancer with radiation therapy. We propose the next logical step in the evolution of IMRT using canonical radiobiological principles, optimizing the temporal dimension through which radiation therapy is delivered to further reduce radiation-induced toxicity by increased time for normal tissue recovery. We term this novel treatment planning strategy "temporally feathered radiation therapy" (TFRT).MethodsTemporally feathered radiotherapy plans were generated as a composite of five simulated treatment plans each with altered constraints on particular hypothetical organs at risk (OARs) to be delivered sequentially. For each of these TFRT plans, OARs chosen for feathering receive higher doses while the remaining OARs receive lower doses than the standard fractional dose delivered in a conventional fractionated IMRT plan. Each TFRT plan is delivered a specific weekday, which in effect leads to a higher dose once weekly followed by four lower fractional doses to each temporally feathered OAR. We compared normal tissue toxicity between TFRT and conventional fractionated IMRT plans by using a dynamical mathematical model to describe radiation-induced tissue damage and repair over time.ResultsModel-based simulations of TFRT demonstrated potential for reduced normal tissue toxicity compared to conventionally planned IMRT. The sequencing of high and low fractional doses delivered to OARs by TFRT plans suggested increased normal tissue recovery, and hence less overall radiation-induced toxicity, despite higher total doses delivered to OARs compared to conventional fractionated IMRT plans. The magnitude of toxicity reduction by TFRT planning was found to depend on the corresponding standard fractional dose of IMRT and organ-specific recovery rate of sublethal radiation-induced damage.ConclusionsTFRT is a novel technique for treatment planning and optimization of therapeutic radiotherapy that considers the nonlinear aspects of normal tissue repair to optimize toxicity profiles. Model-based simulations of TFRT to carefully conceptualized clinical cases have demonstrated potential for radiation-induced toxicity reduction in a previously described dynamical model of normal tissue complication probability (NTCP).

Dataset Information

Intensity-Modulated Radiation Therapy Reduces Patient-Reported Chronic Toxicity Compared With Conventional Pelvic Radiation Therapy: Updated Results of a Phase III Trial.

Publications

Intensity-Modulated Radiation Therapy Reduces Patient-Reported Chronic Toxicity Compared With Conventional Pelvic Radiation Therapy: Updated Results of a Phase III Trial.

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