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Patterns and Predictors of Relapse Following Radical Chemoradiation Therapy Delivered Using Intensity Modulated Radiation Therapy With a Simultaneous Integrated Boost in Anal Squamous Cell Carcinoma.

ABSTRACT: PURPOSE:Our purpose was to describe the patterns and predictors of treatment failure in patients receiving definitive chemoradiation therapy (CRT) for anal squamous cell carcinoma (ASCC), delivered using intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS:Our study was a retrospective cohort analysis of consecutive patients treated with curative intent for ASCC using CRT delivered with a standardized IMRT technique in 5 UK cancer centers. Patients were included from the start of UK IMRT guidance from February 2013 to October 31, 2017. Collected data included baseline demographics, treatment details, tumor control, sites of relapse, and overall survival. Statistical analysis to calculate outcomes and predictive factors for outcome measures were performed using SPSS and R. RESULTS:The medical records of 385 consecutive patients were analyzed. Median follow-up was 24.0 months. Within 6 months of completing CRT, 86.7% of patients achieved a complete response. Three-year disease-free survival and overall survival were 75.6% and 85.6%, respectively. Of all relapses, 83.4% occurred at the site of primary disease. There were 2 isolated relapses in regional nodes not involved at outset. Predictive factors for cancer recurrence included male sex, high N-stage, and failure to complete radiation therapy as planned. CONCLUSIONS:The treatment results compare favorably to published outcomes from similar cohorts using 3-dimensional conformal CRT. The observed patterns of failure support the current UK IMRT voluming guidelines and dose levels, highlighting our prophylactic nodal dose as sufficient to prevent isolated regional relapse in uninvolved nodes. Further investigation of strategies to optimize CR should remain a priority in ASCC because the site of primary disease remains the overwhelming site of relapse.

SUBMITTER: Shakir R

PROVIDER: S-EPMC6961207 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Patterns and Predictors of Relapse Following Radical Chemoradiation Therapy Delivered Using Intensity Modulated Radiation Therapy With a Simultaneous Integrated Boost in Anal Squamous Cell Carcinoma.

Shakir Rebecca R Adams Richard R Cooper Rachel R Downing Amy A Geh Ian I Gilbert Duncan D Jacobs Clare C Jones Christopher C Lorimer Cressida C Namelo Wanangwa C WC Sebag-Montefiore David D Shaw Paul P Muirhead Rebecca R

International journal of radiation oncology, biology, physics 20191017 2

<h4>Purpose</h4>Our purpose was to describe the patterns and predictors of treatment failure in patients receiving definitive chemoradiation therapy (CRT) for anal squamous cell carcinoma (ASCC), delivered using intensity modulated radiation therapy (IMRT).<h4>Methods and materials</h4>Our study was a retrospective cohort analysis of consecutive patients treated with curative intent for ASCC using CRT delivered with a standardized IMRT technique in 5 UK cancer centers. Patients were included fro ...[more]

PMID: 31629837

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Project description:PurposeWhile intensity modulated proton therapy can deliver simultaneous integrated boost (SIB) to the dominant intraprostatic lesion (DIL) with high precision, it is sensitive to anatomic changes. We investigated the dosimetric effects from these changes based on pretreatment cone-beam computed tomographic (CBCT) images and identified the most important factors using a multilayer perceptron neural network (MLPNN).Methods and materialsDILs were contoured based on coregistered multiparametric magnetic resonance images for 25 previously treated prostate cancer patients. SIB plans were created with (1) prostate clinical target volume - V70 Gy = 98%; (2) DIL - V98 Gy > 95%; and (3) all organs at risk (OARs)"?> within clinical constraints. SIB plans were applied to daily CBCT-based deformed planning computed tomography (CT)"?>. DIL - V98 Gy, bladder/rectum maximum dose (Dmax) and volume changes, femur shifts, and the distance from DIL to organs at riskOARs"?> in both planning computed tomogramsCT"?> and CBCT were calculated. Wilcoxon signed-ranks tests were used to compare the changes. MLPNNs were used to model the change in ΔDIL - V98 Gy > 10% and bladder/rectum Dmax > 80 Gy, and the relative importance factors for the model were provided. The performances of the models were evaluated with receiver operating characteristic curves.ResultsComparing initial plan to the average from evaluation plans, respectively, DIL - V98 Gy was 89.3% ± 19.9% versus 86.2% ± 21.3% (P = .151); bladder Dmax 71.9 ± 0.6 Gy versus 74.5 ± 2.9 Gy (P < .001); and rectum Dmax 70.1 ± 2.4 Gy versus 74.9 ± 9.1Gy (P = .007). Bladder and rectal volumes were 99.6% ± 39.5% and 112.8% ± 27.2%, respectively, of their initial volume. The femur shift was 3.16 ± 2.52 mm. In the modeling of ΔDIL V98 Gy > 10%, DIL to rectum distance changes, DIL to bladder distance changes, and rectum volume changes ratio are the 3 most important factors. The areas under the receiver operating characteristic curves were 0.89, 1.00, and 0.99 for the modeling of ΔDIL - V98 Gy > 10%, and bladder and rectum Dmax > 80 Gy, respectively.ConclusionsDosimetric changes in DIL SIB with intensity modulated proton therapy can be modeled and classified based on anatomic changes on pretreatment images by an MLPNN.

Project description:BackgroundNeoadjuvant radio(chemo)therapy of non-metastasized, borderline resectable or unresectable locally advanced pancreatic cancer is complex and prone to cause side-effects, e.g., in gastrointestinal organs. Intensity-modulated proton therapy (IMPT) enables a high conformity to the targets while simultaneously sparing the normal tissue such that dose-escalation strategies come within reach. In this in silico feasibility study, we compared four IMPT planning strategies including robust multi-field optimization (rMFO) and a simultaneous integrated boost (SIB) for dose-escalation in pancreatic cancer patients.MethodsFor six pancreatic cancer patients referred for adjuvant or primary radiochemotherapy, four rMFO-IMPT-SIB treatment plans each, consisting of two or three (non-)coplanar beam arrangements, were optimized. Dose values for both targets, i.e., the elective clinical target volume [CTV, prescribed dose Dpres =?51Gy(RBE)] and the boost target [Dpres =?66Gy(RBE)], for the organs at risk as well as target conformity and homogeneity indexes, derived from the dose volume histograms, were statistically compared.ResultsAll treatment plans of each strategy fulfilled the prescribed doses to the targets (Dpres(GTV,CTV) =?100%, D95%,(GTV,CTV) ??95%, D2%,(GTV,CTV) ??107%). No significant differences for the conformity index were found (p >?0.05), however, treatment plans with a three non-coplanar beam strategy were most homogenous to both targets (p <?0.045). The median value of all dosimetric results of the large and small bowel as well as for the liver and the spinal cord met the dose constraints with all beam arrangements. Irrespective of the planning strategies, the dose constraint for the duodenum and stomach were not met. Using the three-beam arrangements, the dose to the left kidney could be significant decreased when compared to a two-beam strategy (p <?0.045).ConclusionBased on our findings we recommend a three-beam configuration with at least one non-coplanar beam for dose-escalated SIB with rMFO-IMPT in advanced pancreatic cancer patients achieving a homogeneous dose distribution in the target while simultaneously minimizing the dose to the organs at risk. Further treatment planning studies on aspects of breathing and organ motion need to be performed.

Project description:Purpose:To evaluate 2 published normal tissue complication probability models for radiation-induced hypothyroidism (RHT) on a large cohort of oropharyngeal carcinoma (OPC) patients who were treated with intensity-modulated radiation therapy (IMRT). Methods and Materials:OPC patients treated with retrievable IMRT Digital Imaging and Communications in Medicine (DICOMs) data and available baseline and follow-up thyroid function tests were included. Mean dose (Dmean) to the thyroid gland (TG) and its volume were calculated. The study outcome was clinical HT at least 6 months after radiation therapy, which was defined as grade ?2 HT per Common Terminology Criteria for Adverse Events grading system (symptomatic hypothyroidism that required thyroid replacement therapy). Regression analyses and Wilcoxon rank-sum test were used. Receiver operating characteristic curves and area under the curve for the fitted model were calculated. Results:In the study, 360 OPC patients were included. The median age was 58 years. Most tumors (51%) originated from the base of tongue. IMRT-split field was used in 95%, and median radiation therapy dose was 69.96 Gy. In the study, 233 patients (65%) developed clinical RHT that required thyroid replacement therapy. On multivariate analysis higher Dmean and smaller TG volume maintained the statistically significant association with the risk of clinical RHT (P < .0001). Dmean was significantly higher in patients with clinical RHT versus those without (50 vs 42 Gy, P < .0001). Patients with RHT had smaller TG volume compared with those without (11.8 compared with 12.8 mL, P < .0001). AUC of 0.72 and 0.66 were identified for fitted model versus for the applied Boomsma et al and Cella et al models, respectively. Conclusions:Volume and Dmean of the TG are important predictors of clinical RHT and shall be integrated into normal tissue complication probability models for RHT. Dmean and thyroid volume should be considered during the IMRT plan optimization in OPC patients.

Dataset Information

Patterns and Predictors of Relapse Following Radical Chemoradiation Therapy Delivered Using Intensity Modulated Radiation Therapy With a Simultaneous Integrated Boost in Anal Squamous Cell Carcinoma.

Publications

Patterns and Predictors of Relapse Following Radical Chemoradiation Therapy Delivered Using Intensity Modulated Radiation Therapy With a Simultaneous Integrated Boost in Anal Squamous Cell Carcinoma.

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