Stomach dose-volume predicts acute gastrointestinal toxicity in chemoradiotherapy for locally advanced pancreatic cancer
<h4>Aims</h4> <p>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 l...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2018
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| _version_ | 1797090603860754432 |
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| author | Holyoake, DLP Warren, DR Hurt, C Aznar, M Partridge, M Mukherjee, S Hawkins, MA |
| author_facet | Holyoake, DLP Warren, DR Hurt, C Aznar, M Partridge, M Mukherjee, S Hawkins, MA |
| author_sort | Holyoake, DLP |
| collection | OXFORD |
| description | <h4>Aims</h4> <p>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).</p> <h4>Materials and Methods</h4> <p>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.</p> <h4>Results</h4> <p>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, whereaswheras 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.</p> <h4>Conclusions</h4> <p>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.</p> |
| first_indexed | 2024-03-07T03:21:02Z |
| format | Journal article |
| id | oxford-uuid:b76cf8ec-dadf-4c0d-a540-5921e8e28471 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:21:02Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:b76cf8ec-dadf-4c0d-a540-5921e8e284712022-03-27T04:48:33ZStomach dose-volume predicts acute gastrointestinal toxicity in chemoradiotherapy for locally advanced pancreatic cancerJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b76cf8ec-dadf-4c0d-a540-5921e8e28471EnglishSymplectic Elements at OxfordElsevier2018Holyoake, DLPWarren, DRHurt, CAznar, MPartridge, MMukherjee, SHawkins, MA <h4>Aims</h4> <p>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).</p> <h4>Materials and Methods</h4> <p>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.</p> <h4>Results</h4> <p>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, whereaswheras 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.</p> <h4>Conclusions</h4> <p>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.</p> |
| spellingShingle | Holyoake, DLP Warren, DR Hurt, C Aznar, M Partridge, M Mukherjee, S Hawkins, MA Stomach dose-volume predicts acute gastrointestinal toxicity in chemoradiotherapy for locally advanced pancreatic cancer |
| title | Stomach dose-volume predicts acute gastrointestinal toxicity in chemoradiotherapy for locally advanced pancreatic cancer |
| title_full | Stomach dose-volume predicts acute gastrointestinal toxicity in chemoradiotherapy for locally advanced pancreatic cancer |
| title_fullStr | Stomach dose-volume predicts acute gastrointestinal toxicity in chemoradiotherapy for locally advanced pancreatic cancer |
| title_full_unstemmed | Stomach dose-volume predicts acute gastrointestinal toxicity in chemoradiotherapy for locally advanced pancreatic cancer |
| title_short | Stomach dose-volume predicts acute gastrointestinal toxicity in chemoradiotherapy for locally advanced pancreatic cancer |
| title_sort | stomach dose volume predicts acute gastrointestinal toxicity in chemoradiotherapy for locally advanced pancreatic cancer |
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