Poorer survival in obese colorectal cancer patients possibly linked to lower chemotherapy doses

Lugano, Switzerland, 2 July 2021 – Obese patients with colorectal cancer get lower cumulative doses of adjuvant chemotherapy, relative to their body area (BSA), than non-obese patients, reveal arise from a big meta-analysis reported at the ESMO World Congress on Gastrointestinal Cancer 2021 (1). Further findings revealed that cumulative relative chemotherapy dosage was connected with survival so might discuss the poorer survival that has actually been seen in obese patients getting adjuvant chemotherapy for colorectal cancer. (2)

“Adjuvant chemotherapy is dosed according to a person’s body surface area, which is calculated from their height and weight. But in obese patients (with a high body mass index (BMI), and who are more likely to have high BSAs), doses are often capped, or based on an idealised weight, because of concern that large doses might increase side-effects. This means that obese patients may receive proportionately lower doses of chemotherapy” reported lead author Corinna Slawinski, from the Division of Cancer Sciences, University of Manchester, UK.

“Our study has demonstrated an association between increasing body mass index and modest reductions in the cumulative relative dose of adjuvant chemotherapy in patients with colorectal cancer. And we also saw an association between increased cumulative relative dose and improved survival,” she stated. “This supports the recently published ASCO guidance that full, weight-based chemotherapy doses should be used to treat obese adult patients” (3)

Commenting on the findings, Elizabeth Smyth, Addenbrooke’s Hospital in Cambridge, UK, member of the ESMO Faculty for Gastrointestinal tumours, stated: “Dose reductions for high BMI may be associated with lower cure rates in resected colon cancer treated with adjuvant chemotherapy.” She included: “Adjuvant chemotherapy has the potential to cure patients with residual micrometastatic disease following curative surgery, so it is important that we maximise the benefits for all patients.”

A variety of previous research studies have actually revealed that obese patients with colorectal cancer have even worse results than non-obese patients. But constraints with these research studies made it tough to draw conclusions as to whether having a greater body mass index was straight connected with survival or if the association was due to other aspects such as treatment (i.e. dosage administered).

“One important factor is how chemotherapy doses are calculated for individual patients. We carried out our study to better understand the relationship between BMI, chemotherapy dosing and survival in colorectal cancer,” described Slawinski.

The OCTOPUS research study evaluated information for 7269 patients getting adjuvant chemotherapy after alleviative surgical treatment for colon and/or rectal cancer in 4 big, randomised trials. The scientists analyzed the relationship in between BMI and chemotherapy dosing and the relationship in between chemotherapy dosing and survival.

“We looked at two ways of measuring how much chemotherapy had been received as a proportion of actual-to-expected standard doses: average cumulative relative dose (ACRD) and average relative dose intensity (ARDI).” ACRD is the percentage of the overall anticipated basic dosage (per system of body area) over the entire chemotherapy course that has really been gotten. ARDI nevertheless, likewise considers the period of treatment, and is the percentage of the predicted basic dosage strength (the overall dosage per system of BSA, divided by the variety of weeks of treatment) that has really been gotten. With both steps balanced over the variety of drugs in the routine, and revealed as a portion.

Results revealed that 5% increments in ACRD were substantially connected with enhancements in disease-free survival (risk ratio 0.953, 95% self-confidence interval 0926, 0.980, p=0.001). Overall survival was likewise connected with ACRD. However, there was no considerable association with ARDI. Slawinski recommended that the absence of association in between survival and ARDI might be since ARDI is a less delicate procedure of decreases in overall (cumulative) dosage of chemotherapy.

Further findings revealed that each BMI boost of 5kg/m2 was connected with a 2% decrease in the relative dosage of chemotherapy in the very first cycle of chemotherapy and 1% decreases in both ACRD and ARDI. This implies an obese client with a BMI of 37.5kg/m2 would have a 3% decrease of ACRD and ARDI compared to a non-obese client with a BMI of 22.5kg/m2.

“These results showed that elevated BMI is associated with a reduced relative dose of chemotherapy in the first treatment cycle and a modest reduction in ACRD. These indirect effects through sub-optimal treatment might explain poorer survival in obese patients, rather than direct effects of obesity resulting from, for example, tumour biology,” concluded Slawinski. “Our results so far support giving obese patients a full dose of chemotherapy based on their body weight. But we are still exploring toxicity data, examining the relationship between BMI, dose capping, toxicity and survival,” she warned. “Toxicity has the potential to reduce quality of life and can be life threatening. And there may also be other reasons for reducing chemotherapy doses, such as comorbidities, so it is important that dosing and treatment decisions are individualised to the patient.”

Smyth concurred: “The main message from this study is that we should consider whether dose reductions are necessary in patients with a high BMI when treating them with adjuvant chemotherapy.” But she included: “Dosing chemotherapy is complex and includes not only weight but fitness, co-morbidities including renal function and dihydropyrimidine dehydrogenase (DPD) testing results.”

Smyth thought about that more research studies are required prior to altering practice. “Prospective studies examining the impact of higher doses of chemotherapy may be needed, especially as there is an increase in the proportion of patients diagnosed with cancer and who are obese.” For now, she concluded: “We should take all aspects of the patient into account when making chemotherapy dosing decisions. Dose reductions do seem to be associated with less good survival in this study, but these may still be required for safety.”


Notes to Editors

Please ensure to utilize the main name of the conference in your reports: ESMO World Congress on Gastrointestinal Cancer 2021

Official Congress Hashtag: #WorldGI2021


This news release includes details supplied by the author of the highlighted abstract and shows the material of this abstract. It does not always show the views or viewpoints of the ESMO WGI Organisers who cannot be delegated the precision of the information. Commentators estimated in journalism release are needed to abide by the ESMO Declaration of Interests policy and the ESMO Code of Conduct.


1 Abstract O-4 ‘Average cumulative relative dosage (ACRD) of adjuvant chemotherapy is more crucial than typical relative dosage strength (ARDI) for colorectal cancer survival, with ramifications for dealing with obese patients: the OCTOPUS consortium’ will exist by Corinna Slawinski throughout Session VII: Presentation of Selected Colorectal Cancer Abstracts on Friday, 2 July, 08:00-12:00 CEST. Annals of Oncology, Volume 32, Supplement 3, July 2021 – https://www.worldgicancer.com

2 Parkin et al. Excess adiposity and survival in patients with colorectal cancer: an organized evaluation (2014). 15(5): 434-451.

3 Griggs JJ, Bohlke K, Balaban EP et al. Appropriate systemic treatment dosing for obese adult patients with cancer: ASCO Guideline Update. J Clin Oncol 2021 DOI https://doi.org/10.1200/JCO.21.00471

About the European Society for Medical Oncology (ESMO)

ESMO is the leading expert organisation for medical oncology. With more than 25,000 members representing oncology specialists from over 160 nations worldwide, ESMO is the society of referral for oncology education and details. Driven by a shared decision to protect the very best possible results for patients, ESMO is devoted to standing by those who appreciate cancer through resolving the varied requirements of #ONEoncologycommunity, providing #educationforLIFE, and promoting for #accessiblecancerCARE. Visit http://www.esmo.org

About the ESMO World Congress on Gastrointestinal Cancer

The ESMO World Congress on Gastrointestinal Cancer represents the year’s premier event of worldwide oncology specialists, going over the current emerging information and brand-new research study in this quickly advancing clinical field and devoted to enhancing the lives of patients affected by illness of the GI system.

O-4 – Average cumulative relative dosage (ACRD) of adjuvant chemotherapy is more crucial than typical relative dosage strength (ARDI) for colorectal cancer survival, with ramifications for dealing with obese patients: the OCTOPUS consortium

C. Slawinski1, L. Malcomson1, J. Barriuso2, H. Guo1, A. Harkin3, T. Iveson4, R. Glynne-Jones5, C. Van de Velde6, A. Renehan2

1University of Manchester, Manchester, United Kingdom, 2University of Manchester / The Christie NHS Foundation Trust, Manchester, United Kingdom, 3Cancer Research UK Glasgow Clinical Trials Unit, Glasgow, United Kingdom, 4University of Southampton, Southampton, United Kingdom, 5Mount Vernon Cancer Centre, Northwood, United Kingdom, 6Leiden University Medical Center, Leiden, Switzerland

Background: After alleviative surgical treatment for colorectal cancer (CRC), some research studies show poorer survival in obese patients. Adjuvant chemotherapy (ACT) for CRC is frequently topped at a body area (BSA) 2.2m2, possibly lowering chemotherapy typical cumulative relative dosage (ACRD) and typical relative dosage strength (ARDI) in obese patients.

Methods: Individual participant-level information from MOSAIC, SCOT, PROCTORSCRIPT and CHRONICLE (CRC-ACT) randomised-trials, with derivable BMI, BSA and chemotherapy doses, were consisted of from the OCTOPUS consortium. ARDI and ACRD were computed as portions of real to anticipated (complete BSA-based) dosage strength (cumulative dose/treatment period in weeks) or cumulative dosage respectively, balanced throughout the drugs in the routine. A two-stage random-effects meta-analyses of direct or Cox proportional threats regression designs were carried out to check out BMI-ARDI/-ACRD and ARDI-/ACRD-survival relationships respectively. The main result was disease-free survival (DFS), and secondary results were general (OS) and cancer-particular (CSS) survival, in addition to ARDI and ACRD. All designs where changed for age, sex, efficiency status, t-stage and n-stage (in addition to BMI in the survival designs).

Results: 7269 patients were qualified. BMI 5kg/m2 increments were connected with a 2.04% decrease in cycle 1 dosage (95% CI:-2.45,-1.64; p

ACRD 5% increments were connected with enhanced DFS (HR 0.953 (0.926, 0.980); p=0.001), OS (HR 0.931(0.908, 0.955); p

Conclusion: ACRD is more crucial than ARDI in figuring out survival. Elevated BMI is connected with a lowered cycle 1 dosage and a modest ACRD decrease. These indirect impacts through under-treatment may discuss poorer survival in obese patients, instead of direct impacts of weight problems arising from, for instance, tumour biology.

Legal Entity Responsible for this Study: The authors.

Funding: This work was supported by Cancer Research UK through the financing to Cancer Research UK Manchester Centre: [C147/A18083] and [C147/A25254]. A.G. Renehan is supported by the Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007).

Disclosure: All authors have actually stated no disputes of interest

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