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The ongoing challenge of large anal cancers: prospective long term outcomes of intensity-modulated radiation therapy with concurrent chemotherapy.

ABSTRACT: 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).

SUBMITTER: Hosni A

PROVIDER: S-EPMC5945520 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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The ongoing challenge of large anal cancers: prospective long term outcomes of intensity-modulated radiation therapy with concurrent chemotherapy.

Hosni Ali A Han Kathy K Le Lisa W LW Ringash Jolie J Brierley James J Wong Rebecca R Dinniwell Robert R Brade Anthony A Dawson Laura A LA Cummings Bernard J BJ Krzyzanowska Monika K MK Chen Eric X EX Hedley David D Knox Jennifer J Easson Alexandra M AM Lindsay Patricia P Craig Tim T Kim John J

Oncotarget 20180417 29

<h4>Purpose</h4>Patterns of failure and long term outcomes were prospectively evaluated following tumor factors-stratified radiation dose for anal/perianal cancer.<h4>Methods</h4>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 b ...[more]

PMID: 29755663

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Project description:BackgroundDifferentiated thyroid cancer typically has an indolent clinical course but can cause significant morbidity by local progression. Oncologic surgical resection can be technically difficult due to the proximity to critical normal structures in the neck. Our objective was to review the safety, feasibility, and outcomes of definitive-intent intensity-modulated radiation therapy (IMRT) and to analyze whether patients receiving concurrent chemotherapy (CC-IMRT) had higher rates of disease control and survival over IMRT alone in patients with unresectable or gross residual disease (GRD).MethodsEighty-eight patients with GRD or unresectable nonanaplastic, nonmedullary thyroid cancer treated with definitive-intent IMRT between 2000 and 2015 were identified. Local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and overall survival (OS) were evaluated using the Kaplan-Meier method. Univariate and multivariate analyses using cox regression were used to determine the impact of clinical conditions and treatment on LPFS, DMFS, and OS.ResultsOf the 88 patients identified, 45 (51.1%) were treated CC-IMRT and 43 (48.9%) were treated with IMRT alone. All patients treated with CC-IMRT received weekly doxorubicin (10 mg/m2). The median follow-up among surviving patients was 40.3 months and 29.2 months for all patients. The LPFS at 4 years was 77.3%. Patients receiving CC-IMRT had higher LPFS compared with IMRT alone (CC-IMRT 85.8% vs. IMRT 68.8%, p = 0.036). The 4-year OS was 56.3% for all patients. Patients treated with CC-IMRT had higher OS compared to patients treated with IMRT alone (CC-IMRT 68.0% vs. IMRT 47.0%, p = 0.043). On multivariate analysis, receipt of concurrent chemotherapy was associated with a lower risk of death (HR 0.395, p = 0.019) and lower risk of local failure (HR 0.306, p = 0.042). Grade 3+ acute toxicities occurred in 23.9% of patients, the most frequent being dermatitis (18.2%) and mucositis (9.1%). 17.1% of patients required a percutaneous endoscopic gastrostomy (PEG) tube during or shortly after completion of RT, with 10.1% of patients needing a PEG more than 12 months after therapy. The rates of acute and late toxicities were not statistically higher in the CC-IMRT cohort, although trends towards higher toxicity in the CC-IMRT were present for dermatitis and PEG requirement.ConclusionsIMRT is a safe and effective means to achieve local control in patients with unresectable or incompletely resected nonanaplastic, nonmedullary thyroid cancer. Concurrent doxorubicin was not associated with worse toxicity and should be considered in these patients given its potential to improve local control and overall survival.

Project description:BackgroundThe literature regarding pericardial effusion after definitive concurrent chemotherapy and intensity modulated radiotherapy (IMRT) for esophageal cancer was lacking. This study aimed to investigate the risk factors of pericardial effusion in esophageal cancer patients undergoing definitive concurrent chemotherapy and IMRT.MethodsA total of 126 consecutive esophageal cancer patients treated with definitive concurrent chemotherapy and IMRT between 2008 and 2018 were reviewed. The pericardial effusion was determined on computed tomography scan of the chest and graded by the Common Terminology Criteria for Adverse Events, version 4.0. The cumulative incidence of pericardial effusion was estimated by the Kaplan-Meier method and compared between groups by the log-rank test. The risk factors of pericardial effusion were determined with multivariate Cox proportional hazards regression analysis.ResultsThe median follow-up time was 14.0 months. Thirty-seven (29.4%) patients had pericardial effusion after a median interval of 6.6 months since the end of IMRT. The cumulative incidence of pericardial effusion of any grade was higher in patients with mean heart dose > 23.45 Gy (p = 0.00018), heart V30 > 33.55% (p = 0.00015), mean pericardium dose > 20.33 Gy (p = 0.00027), and pericardium V20 > 42.55% (p = 0.00018). Furthermore, eight (6.3%) patients had symptoms related to pericardial effusion and were considered as cases with pericardial effusion ≥ grade 3. The cumulative incidence of pericardial effusion ≥ grade 3 was higher in patients with pericardium V30 > 65.80% (p = 0.00028), V40 > 55.35% (p < 0.0001), and V60 > 24.70% (p = 0.0021). Multivariate analyses showed the above dose-volume parameters predicted the risk of pericardial effusion in esophageal cancer.ConclusionsDose-volume parameters predicting the risk of pericardial effusion were identified in esophageal cancer treated with definitive concurrent chemotherapy and IMRT. They could be applied as constraints of IMRT for esophageal cancer.

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Project description:ObjectiveTo report acute hematological toxicity (HT) in patients receiving post-operative bowel sparing intensity-modulated radiotherapy (IMRT) and cisplatin and its dosimetric predictors.MethodsClinical database of Phase III trial (NCT01279135), that randomized patients to post-operative conformal or intensity modulated radiation therapy, was searched to select patient strata that received bowel sparing IMRT (50 Gy/25#/5 wks) and concurrent cisplatin (40 mg m-2). Pelvic bone marrow (BM) was retrospectively delineated in two sets: whole bone (WB), and freehand (FH) inner cavity of bone. Dose volume histograms (DVH) of BM were obtained. Receiver operating characteristic (ROC) curve identified DVH thresholds that predicted for Grade≥ II HT with highest specificity. Univariate and multivariate analysis was performed.ResultsOverall 75 patients received concurrent cisplatin. Grades I-V HT was observed in 38.7%, 42.7%, 14.7%, 0%, and 0% patients, respectively. Grade ≥ II leukopenia, neutropenia, anemia, and thrombocytopenia were observed in 26%, 40%, 26.5%, and 1.4% respectively. None of the HT resulted in treatment break. On univariate analysis, whole pelvis+ lumbar FH V30 >55% & V40>35%, whole pelvis WB and FH V40 > 35%, and lower pelvis WB and FH V40 >20% correlated for Grade ≥ II leucopenia and neutropenia. None of the BM dose volume constraints predicted for overall HT or neutropenia on multivariate analysis.ConclusionThe IMRT arm of NCT01279135 (PARCER study) that employed strict bowel constraints had unintentional but desirable BM sparing. None of the BM subvolume DVH parameters could be validated on multivariate analysis.Advances in knowledgeThe prospective study reports feasibility of bone marrow sparing with bowel sparing post-operative pelvic IMRT and concurrent chemotherapy for cervical cancer. The present study reports low incidence of hematological and gastrointestinal toxicity during post-operative chemoradiation with IMRT. As both whole bone and freehand pelvis BM contours predicted for HT, hence an easier method of whole bone contouring should continue to be used till further validation of more specific BM subvolumes becomes available. The study results highlight the need for further research into dose volume constraints during post-operative IMRT.

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The ongoing challenge of large anal cancers: prospective long term outcomes of intensity-modulated radiation therapy with concurrent chemotherapy.

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The ongoing challenge of large anal cancers: prospective long term outcomes of intensity-modulated radiation therapy with concurrent chemotherapy.

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