Long-term outcomes and toxicities of a large cohort of anal cancer patients treated with dose-painted IMRT per RTOG 0529.
Ontology highlight
ABSTRACT:
SUBMITTER: Mitra D
PROVIDER: S-EPMC5514246 | biostudies-other | 2017 Apr-Jun
REPOSITORIES: biostudies-other
Similar Datasets
Project description:BACKGROUND:Balancing the dose requirements between targets and normal tissue is a challenge in radiation of nasopharyngeal carcinoma (NPC). The purpose of this study is to evaluate the dosimetric parameters and clinical outcomes in NPC. METHODS:We presented a retrospective review of patients with T3-4 NPC treated by intensity-modulated radiation therapy (IMRT). Patient characteristics, dosimetric parameters, and the follow-up data for survival and late toxicities were analyzed. RESULTS:The 5-year overall survival, local relapse-free survival, and distant metastasis-free survival were 83.0%, 90.1%, and 82.4%, respectively. Multivariate analysis revealed that the volume of involved lymph node was an independent prognostic factor. The volume of primary tumor and the maximal dose were significant factors affecting temporal lobe injury. CONCLUSIONS:IMRT provided satisfactory local control for advanced T-stage NPC, with acceptable late toxicities. The dose constraint criteria of selected critical structures can be appropriately loosen.
| S-EPMC6973082 | biostudies-literature
Project description:Purpose/objectiveDefinitive radiotherapy (RT) is an alternative to radical cystectomy for select patients with muscle invasive bladder cancer (MIBC); however, there is limited data on dose-painted RT approaches. We report the clinical and dosimetric outcomes of a cohort of MIBC patients treated with dose-painted RT.Material/methodsThis was a single institution retrospective study of cT2-4N0M0 MIBC patients treated with external beam radiotherapy (EBRT) to the bladder, and sequential or concomitant boost to the tumor bed. The target delineation was guided by either intravesical injection of Lipiodol or through fusion of the pre-treatment imaging. The majority were treated with daily image-guidance. Kaplan-Meier was used to characterize overall survival (OS) and progression-free survival (PFS). Cumulative incidence function (CIF) was used to estimate local (intravesical) recurrence (LR), regional recurrence (RR) and distant metastasis (DM). Univariable and multivariable cause-specific hazard model was used to assess factors associated with LR and OS.Results117 patients were analyzed. The median age was 73 years (range 43, 95). The median EQD2 to the boost volume was 66 Gy (range 52.1, 70). Lipiodol injection was used in 64 patients (55%), all treated with IMRT/VMAT. 95 (81%) received concurrent chemotherapy, of whom, 44 (38%) received neoadjuvant chemotherapy. The median follow-up was 37 months (IQR 16.2, 83.3). At 5-year, OS and PFS were 79% (95% CI 70.5-89.2) and 46% (95% CI 36.5-57.5). Forty-five patients had bladder relapse, of which 30 patients (67%) were at site of the tumor bed. Nine patients underwent salvage-cystectomy. Late high-grade (G3-G4) genitourinary and gastrointestinal toxicity were 3% and 1%.ConclusionPartial boost RT in MIBC is associated with good local disease control and high rates of cystectomy free survival. We observed a pattern of predominantly LR in the tumor bed, supporting the use of a dose-painted approach/de-escalation strategy to the uninvolved bladder. Prospective trials are required to compare oncological and toxicity outcomes between dose-painted and homogeneous bladder RT techniques.
| S-EPMC10512471 | biostudies-literature
Project description:NRG Oncology RTOG 0529 assessed the feasibility of dose-painted intensity modulated radiation therapy (DP-IMRT) to reduce the acute morbidity of chemoradiation with 5-fluorouracil (5FU) and mitomycin-C (MMC) for T2-4N0-3M0 anal cancer. This secondary analysis was performed to identify patient and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs).NRG Oncology RTOG 0529 treatment plans were reviewed to extract dose-volume data for tightly contoured small bowel, loosely contoured anterior pelvic contents (APC), and uninvolved colon outside the target volume (UC). Univariate logistic regression was performed to evaluate association between volumes of each structure receiving doses ?5 to 60 Gy (V5-V60) in 5-Gy increments between patients with and without grade ?2 acute and late GI AEs, and grade ?3 acute GI AEs. Additional patient and treatment factors were evaluated in multivariate logistic regression (acute AEs) or Cox proportional hazards models (late AEs).Among 52 evaluable patients, grade ?2 acute, grade ?2 late, and grade ?3 acute GI AEs were observed in 35, 17, and 10 patients, respectively. Trends (P<.05) toward statistically significant associations were observed between grade ?2 acute GI AEs and small bowel dose (V20-V40), grade ?2 late GI AEs and APC dose (V60), grade ?3 acute GI AEs and APC dose (V5-V25), increasing age, tumor size >4 cm, and worse Zubrod performance status. Small bowel volumes of 186.0 cc, 155.0 cc, 41.0 cc, and 30.4 cc receiving doses greater than 25, 30, 35, and 40 Gy, respectively, correlated with increased risk of acute grade ?2 GI AEs.Acute and late GI AEs from 5FU/MMC chemoradiation using DP-IMRT correlate with radiation dose to the small bowel and APC. Such associations will be incorporated in the dose-volume normal tissue constraint design for future NRG oncology anal cancer studies.
| S-EPMC5639877 | biostudies-literature
Project description:Patterns of failure and long term outcomes were prospectively evaluated following tumor factors-stratified radiation dose for anal/perianal cancer.Between 2008-2013, patients with anal/perianal squamous cell carcinoma were accrued to an institutional REB-approved prospective study. All patients were treated with image-guided intensity-modulated radiation therapy (IG-IMRT). Radiation dose selection (27-36 Gy for elective target, and 45-63 Gy for gross target) was based on tumor clinico-pathologic features. Chemotherapy regimen was 5-fluorouracil/mitomycin-C (weeks 1&5). Local [LF], regional failure [RF], distant metastasis [DM], overall- [OS], disease-free [DFS], colostomy-free survival [CFS] and late toxicity were analyzed.Overall, 101 patients were evaluated; median follow-up: 56.5 months; 49.5% male; 34.7% T3/4-category, and 35.6% N+. Median radiation dose was 63 Gy. The most common acute grade ?3 toxicities were skin (41.6%) and hematological (30.7%). Five-year OS, DFS, CFS, LF, RF, DM rates were 83.4%, 75.7%, 74.7, 13.9%, 4.6% and 5% respectively. Five-year LF for patients with T1-2 and T3-4 disease were 0% and 39.2% respectively. All LF (n = 14, after 63 Gy, in tumors ?5 cm) were in the high dose volume except one marginal to the high dose volume. All RF (n = 4) were within elective dose volume except one within the high dose volume. On multivariable analysis, T3/4-category predicted for poor DFS, CFS and OS. The overall late grade ?3 toxicity was 36.2% (mainly anal [20%]).Individualized radiation dose selection using IG-IMRT resulted in good long term outcomes. However, central failures remain a problem for locally advanced tumors even with high dose radiation (63 Gy/7weeks).
| S-EPMC5945520 | biostudies-literature
Project description:PurposeOur primary aim was to prospectively validate retrospective dose-response models of chronic radiation-associated dysphagia (RAD) after intensity modulated radiotherapy (IMRT) for oropharyngeal cancer (OPC). The secondary aim was to validate a grade ≥2 cut-point of the published videofluoroscopic dysphagia severity (Dynamic Imaging Grade for Swallowing Toxicity, DIGEST) as radiation dose-dependent.Material and methodsNinety-seven patients enrolled on an IRB-approved prospective registry protocol with stage I-IV OPC underwent pre- and 3-6 month post-RT videofluoroscopy. Dose-volume histograms (DVH) for swallowing regions of interest (ROI) were calculated. Dysphagia severity was graded per DIGEST criteria (dichotomized with grade ≥2 as moderate/severe RAD). Recursive partitioning analysis (RPA) and Bayesian Information Criteria (BIC) were used to identify dose-volume effects associated with moderate/severe RAD.Results31% developed moderate/severe RAD (i.e. DIGEST grade ≥2) at 3-6 months after RT. RPA found DVH-derived dosimetric parameters of geniohyoid/mylohyoid (GHM), superior pharyngeal constrictor (SPC), and supraglottic region were associated with DIGEST grade ≥2 RAD. V61 ≥ 18.57% of GHM demonstrated optimal model performance for prediction of DIGEST grade ≥2.ConclusionThe findings from this prospective longitudinal registry validate prior observations that dose to submental musculature predicts for increased burden of dysphagia after oropharyngeal IMRT. Findings also support dichotomization of DIGEST grade ≥2 as a dose-dependent split for use as an endpoint in trials or predictive dose-response analysis of videofluoroscopy results.
| S-EPMC6595477 | biostudies-literature
Project description:ObjectivesFreedom from biochemical failure (FFBF) is a common primary outcome of randomized-controlled trials of prostate cancer (PCa). We aimed to determine how increasing the PCa biologically equivalent dose (BED) of external radiation therapy (RT) is correlated with FFBF and overall patient outcomes: overall survival (OS), distant metastasis (DM), and cancer-specific mortality (CSM); as well as genitourinary (GU), and gastrointestinal toxicities.Materials and methodsWe performed a meta-analysis of 6884 PCa patients from 12 randomized-controlled trials of external beam RT. Mixed effects regression models were used to estimate weighted linear relationships between BED and observed percentages of 5- and 10-year outcomes. For toxicities, a subset analysis of using 3-dimensional conformal RT (3D-CRT) versus intensity-modulated RT (IMRT) was performed.ResultsIncreasing BED correlated with improved FFBF: 10-year absolute improvement of 9.6% and 7.2% for low-risk and intermediate-risk patients, respectively (P<0.05); but not with improvement of OS, DM, or CSM at either time point. BED escalation was not correlated with increased acute toxicities; it was correlated with increased late gastrointestinal toxicities in patients treated with 3D-CRT (1.5% increase over BED range, P<0.01). IMRT patients had significantly fewer late toxicities, despite being treated at higher BED.ConclusionsRT BED escalation has resulted in significantly improved PCa FFBF at up to 10 years; but not with improvement in OS, DM, or CSM. Thus, FFBF is a poor surrogate of overall patient outcomes for trials of RT. Late toxicities were less frequent with IMRT than with 3D-CRT, even at higher BED.
| S-EPMC7592421 | biostudies-literature
Project description:ObjectivesTo evaluate the long-term survival outcomes and adverse effects of intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) and to summarise the experiences of IMRT in NPC in the past few decades in non-endemic northwest China.DesignA population-based retrospective study.SettingAn experience of using IMRT in non-endemic region of China.ParticipantsThe study included 792 newly diagnosed and non-metastatic NPC patients who received IMRT from January 2006 to September 2018 in Xijing Hospital.Outcome measuresThe survival outcomes, adverse effects and failure patterns were evaluated by univariate, multivariate and subgroup analyses.ResultsWith a median follow-up time of 46.2 months, the 5-year local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, disease-free survival (DFS) and overall survival (OS) rates were 90.8%, 97.0%, 82.8%, 69.6% and 78.0%, respectively. Multivariate analysis showed that age, N stage, clinical stage, pathological type and primary tumour volume of more than 23 cm3 were the independent prognosis factors for DFS (all p<0.05); age, N stage, pathological type, cervical lymph node necrosis, and anaemia were significantly associated with OS (all p<0.05). The most common acute toxicities of IMRT were dermatitis, mucositis and dysphagia. Xerostomia and hearing impairment were the top two late toxicities. The main failure patterns were distant metastasis and local and/or regional relapses.ConclusionsSimilar survival, toxicities and failure patterns have been observed in patients treated with IMRT in a non-endemic area of China when compared with that in endemic areas. Induction chemotherapy combined with concurrent chemoradiotherapy may benefit locally advanced NPC in non-endemic areas of China.
| S-EPMC8330594 | biostudies-literature
Project description:Intensity-modulated radiotherapy (IMRT) is the standard of care in chemoradiotherapy (CRT) for anal cancer. Until now, only a limited number of studies have analyzed the results with VMAT (volumetric modulated arc therapy). We conducted a retrospective study on patients treated at our institution. We included patients who received curative CRT for anal cancer. We compared VMAT-treated and 3DCRT (3D conformal radiotherapy)-treated patients. We analyzed toxicities (acute: CTCAE criteria; late: LENT/SOMA criteria), treatment compliance, overall survival, cancer-specific survival (CSS), distant control (DC), and locoregional control. A total of 149 patients (3DCRT: n = 87, VMAT: n = 62) were included. The median follow-up was longer in 3DCRT-treated patients (3DCRT: 61.3 months; VMAT: 39.1 months; p < 0.05). VMAT-treated patients had more G3 tumors (3DCRT: 12/87 (13.8%); VMAT: 18/62 (29.0%), p < 0.001). VMAT reduced acute toxicities ≥grade 3 (3DCRT: n = 48/87 (55.2%); VMAT: n = 11/62 (17.7%), p < 0.001). VMAT improved treatment compliance (less interruptions/delays) (3DCRT: 37/87, 42.5%; VMAT: 4/62, 6.5%; p < 0.001), provided a shorter median overall treatment time (3DCRT: 41 days; VMAT: 38 days; p = 0.02), and gave a higher median absolute 5-fluorouracil dose (3DCRT: 13,700 mg; VMAT: 14,400 mg; p = 0.001). Finally, we found improved CSS (p = 0.02; 3DCRT: 81.9% at 3 years; VMAT: 94.1% at 3 years) and DC (p = 0.01; 3DCRT: 89.4% at 3 years; VMAT: 100.0% at 3 years) with VMAT. Our study is the first to demonstrate improved treatment compliance and outcomes with VMAT for anal cancer. Previous studies have indicated that organs at risk sparing might be more improved with the use of VMAT vs. with conventional IMRT. Future studies should address whether these advantages lead to a further reduction in CRT-associated morbidity.
| S-EPMC8196749 | biostudies-literature
Project description:Clinical trials that led to ibrutinib's approval for the treatment of chronic lymphocytic leukemia showed that its side effects differ from those of traditional chemotherapy. Reasons for discontinuation in clinical practice have not been adequately studied. We conducted a retrospective analysis of chronic lymphocytic leukemia patients treated with ibrutinib either commercially or on clinical trials. We aimed to compare the type and frequency of toxicities reported in either setting, assess discontinuation rates, and evaluate outcomes. This multicenter, retrospective analysis included ibrutinib-treated chronic lymphocytic leukemia patients at nine United States cancer centers or from the Connect® Chronic Lymphocytic Leukemia Registry. We examined demographics, dosing, discontinuation rates and reasons, toxicities, and outcomes. The primary endpoint was progression-free survival. Six hundred sixteen ibrutinib-treated patients were identified. A total of 546 (88%) patients were treated with the commercial drug. Clinical trial patients were younger (mean age 58 versus 61 years, P=0.01) and had a similar time from diagnosis to treatment with ibrutinib (mean 85 versus 87 months, P=0.8). With a median follow-up of 17 months, an estimated 41% of patients discontinued ibrutinib (median time to ibrutinib discontinuation was 7 months). Notably, ibrutinib toxicity was the most common reason for discontinuation in all settings. The median progression-free survival and overall survival for the entire cohort were 35 months and not reached (median follow-up 17 months), respectively. In the largest reported series on ibrutinib- treated chronic lymphocytic leukemia patients, we show that 41% of patients discontinued ibrutinib. Intolerance as opposed to chronic lymphocytic leukemia progression was the most common reason for discontinuation. Outcomes remain excellent and were not affected by line of therapy or whether patients were treated on clinical studies or commercially. These data strongly argue in favor of finding strategies to minimize ibrutinib intolerance so that efficacy can be further maximized. Future clinical trials should consider time-limited therapy approaches, particularly in patients achieving a complete response, in order to minimize ibrutinib exposure.
| S-EPMC5927982 | biostudies-literature
Project description:A new 2D array Seven 29T model (PTW, Freiburg), equipped with 729 vented plane-parallel ion chambers, projected for pretreatment verification of radiotherapy plans, was used as a detector for the transmitted or portal dose measurements below a Rando phantom. The dosimetric qualities of the 2D array make it attractive for measuring transmitted dose maps from step-and-shoot intensity-modulated radiotherapy (IMRT). It is well known that for step-and-shoot IMRT beams that use a small number of monitor units (MUs) per sequence, the early and recent electronic portal imaging devices (EPIDs) present a different response at X-ray start-up that affects the accuracy of the measured transmitted dose. The comparison of portal doses measured to those calculated by a commercial treatment-planning system (TPS) can verify correct dose delivery during treatment. This direct validation was tested by irradiating a simulated head tumor in a Rando anthropomorphic phantom by step-and-shoot IMRT beams. The absolute transmitted doses on a plane orthogonal to the beam central axis below the phantom were measured by the 2D array calibrated in terms of dose to water and compared with the computed portal dose extracted by custom software. In a previous paper, the comparison between the IMRT portal doses, computed by a commercial TPS and measured by a linear array that supplied a 1 mm spatial dose resolution, was carried out. The gamma-index analysis supplied an agreement of more than 95% of the dose point with acceptance criteria, in terms of dose difference, DeltaDmax, and distance agreement, deltadmax, equal to 4% and 4 mm, respectively. In this paper, we verify the possible use of the PTW 2D array for measurements of the transmitted doses during several fractions of head and neck tumor radiotherapy. There are two advantages in the use of this 2D array as a portal dose device for the IMRT quality assurance program: first is the ability to perform absolute dose comparisons for hundreds of measurement positions to verify the correct dose delivery in several fractions of the therapy; second is the efficiency in time to detect these kinds of dose distributions within the field of view area of the CT scanner.
| S-EPMC5722422 | biostudies-literature