Loading…

Stomach Dose–Volume Predicts Acute Gastrointestinal Toxicity in Chemoradiotherapy for Locally Advanced Pancreatic Cancer

Gastrointestinal toxicity impedes dose escalation in chemoradiotherapy for hepatobiliary malignancies. Toxicity risk depends on clinical and radiotherapy metrics. We aimed to identify predictive factors using data from two prospective phase II clinical trials of locally advanced pancreatic cancer (L...

Full description

Saved in:
Bibliographic Details
Published in:Clinical oncology (Royal College of Radiologists (Great Britain)) 2018-07, Vol.30 (7), p.418-426
Main Authors: Holyoake, D.L.P., Warren, D.R., Hurt, C., Aznar, M., Partridge, M., Mukherjee, S., Hawkins, M.A.
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Gastrointestinal toxicity impedes dose escalation in chemoradiotherapy for hepatobiliary malignancies. Toxicity risk depends on clinical and radiotherapy metrics. We aimed to identify predictive factors using data from two prospective phase II clinical trials of locally advanced pancreatic cancer (LAPC). Ninety-one patients with available data from the ARCII (59.4 Gy in 33 fractions with gemcitabine, cisplatin and nelfinavir, n = 23) and SCALOP (50.4 Gy in 28 fractions with capecitabine or gemcitabine, n = 74) trials were studied. The independent variables analysed comprised age, sex, performance status, baseline symptoms, tumour size, weight loss, chemotherapy regimen and dose–volume histogram of stomach and duodenum in 5 Gy bins. The outcome measures used were Common Terminology Criteria of Adverse Events (CTCAE) grade and risk of CTCAE grade ≥2 acute upper gastrointestinal toxicity (anorexia, pain, nausea and/or vomiting). The risk of CTCAE grade ≥2 events was modelled using multivariable logistic regression and prediction of severity grade using ordinal regression. CTCAE grade ≥2 symptoms occurred in 38 patients (42%). On univariate analysis, stomach V35–45Gy was predictive of risk (odds ratio 1.035, 95% confidence interval 1.007–1.063) and grade (1.023, 1.003–1.044) of toxicity. The area under the curve was 0.632 (0.516–0.747) with toxicity risk 33/66 (50%) above and 5/25 (20%) below the optimal discriminatory threshold (7.1 cm3). Using a threshold of 30 cm3, risk was 13/20 (65%) versus 25/71 (35%). The optimal multivariable logistic regression model incorporated patient sex, chemotherapy regimen and stomach V35–45Gy. Receiving gemcitabine rather than capecitabine (odds ratio 3.965, 95% confidence interval 1.274–12.342) and weight loss during induction chemotherapy (1.216, 1.043–1.419) were significant predictors for the SCALOP cohort, whereas age predicted toxicity risk in ARCII only (1.344, 1.015–1.780). Duodenum dose–volume did not predict toxicity risk or severity in any cohort. In chemoradiotherapy for LAPC the volume of stomach irradiated to a moderately high dose (35–45 Gy) predicts the incidence and severity of acute toxicity. Other predictive factors can include age, sex, recent weight loss and concomitant chemotherapy agents. •Acute gastrointestinal toxicity was analysed for chemoradiotherapy of locally advanced pancreatic cancer in two prospective phase II trials.•Stomach dose–volume (in the ‘moderate’ dose region of 35–45 Gy) and patient c
ISSN:0936-6555
1433-2981
DOI:10.1016/j.clon.2018.02.067