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Stomach dose–volume predicts acute gastrointestinal toxicity in chemoradiotherapy for locally advanced pancreatic cancer

Stomach dose–volume predicts acute gastrointestinal toxicity in chemoradiotherapy for locally advanced pancreatic cancer
Stomach dose–volume predicts acute gastrointestinal toxicity in chemoradiotherapy for locally advanced pancreatic cancer
Aims: 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).

Materials and methods: 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.

Results: 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.

Conclusions: 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.
0936-6555
418-426
Holyoake, D.L.P.
02879e92-9097-4efe-9d19-23b53fa7ca1d
Warren, D.R.
fe0b6a13-c8f0-4712-ad15-a1c39ca2831c
Hurt, C.
bf8b37a0-8f08-4b47-b3f3-6fc65f7ab87f
Aznar, M.
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Partridge, M.
1f4b5cae-092f-4c89-983a-31d6f680c9a0
Mukherjee, S.
d9278fe6-ec80-45e0-b3ab-137e668787e8
Hawkins, M.A.
071fe07a-65d3-48e2-9822-707e6391fbb4
Holyoake, D.L.P.
02879e92-9097-4efe-9d19-23b53fa7ca1d
Warren, D.R.
fe0b6a13-c8f0-4712-ad15-a1c39ca2831c
Hurt, C.
bf8b37a0-8f08-4b47-b3f3-6fc65f7ab87f
Aznar, M.
2a5b24bc-9b85-43f9-9409-fb537214534c
Partridge, M.
1f4b5cae-092f-4c89-983a-31d6f680c9a0
Mukherjee, S.
d9278fe6-ec80-45e0-b3ab-137e668787e8
Hawkins, M.A.
071fe07a-65d3-48e2-9822-707e6391fbb4

Holyoake, D.L.P., Warren, D.R., Hurt, C., Aznar, M., Partridge, M., Mukherjee, S. and Hawkins, M.A. (2018) Stomach dose–volume predicts acute gastrointestinal toxicity in chemoradiotherapy for locally advanced pancreatic cancer. Clinical Oncology, 30 (7), 418-426. (doi:10.1016/j.clon.2018.02.067).

Record type: Article

Abstract

Aims: 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).

Materials and methods: 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.

Results: 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.

Conclusions: 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.

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Accepted/In Press date: 27 February 2018
e-pub ahead of print date: 28 March 2018
Published date: 4 June 2018

Identifiers

Local EPrints ID: 488219
URI: http://eprints.soton.ac.uk/id/eprint/488219
ISSN: 0936-6555
PURE UUID: 99d75297-c3da-46f6-9a8d-0fb3a415da6a
ORCID for C. Hurt: ORCID iD orcid.org/0000-0003-1206-8355

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Date deposited: 18 Mar 2024 17:56
Last modified: 18 Jun 2024 02:08

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Contributors

Author: D.L.P. Holyoake
Author: D.R. Warren
Author: C. Hurt ORCID iD
Author: M. Aznar
Author: M. Partridge
Author: S. Mukherjee
Author: M.A. Hawkins

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