Lugano (Switzerland), 2 July 2021 - Patients with colorectal carcinoma receive lower cumulative adjuvant chemotherapy doses relative to their body surface area (BSA) than patients who are not obese, according to a large meta-analysis presented at the ESMO World Congress on Gastrointestinal Cancer (2021). Additional findings revealed that the cumulative relative chemotherapy dose was associated to survival, which may explain why obese patients who receive adjuvant chemotherapy for colorectal carcinoma are less likely to survive. (2)Adjuvant chemotherapy doses are determined by a person's body area. This is calculated using their weight and height. Due to the possibility of side effects, doses for obese patients with a high body weight (or BMI) are often reduced or capped. According to Corinna, lead author of the Division of Cancer Sciences at University of Manchester, UK, this means that patients with obesity may receive lower doses of chemotherapy."Our study showed a link between an increase in body mass and a modest decrease in cumulative relative chemotherapy for patients with colorectal carcinoma. She also said that there was a correlation between higher cumulative relative doses and better survival rates. "This supports the ASCO guidance, which states that full-weight-based chemotherapy should be used for obese adults." (3)Elizabeth Smyth from Addenbrooke's Hospital, Cambridge, UK, a member of ESMO Faculty for Gastrointestinal Tumors, commented on the findings. She said that "dose reductions for high BMI might be associated with lower cure rates for resected colon carcinoma treated with adjuvant chemotherapy." She said that adjuvant chemotherapy could be used to treat patients with residual micrometastatic diseases after curative surgery. It is crucial that all patients reap the benefits of adjuvant chemotherapy.Numerous studies have previously shown that colorectal cancer patients who are obese have worse outcomes than those who are not obese. These studies were limited and it was difficult to determine if a higher body weight index was directly related to survival or whether the association was due other factors, such as treatment. Dosage."How individual patients are given chemotherapy doses is an important aspect. Slawinski explained that the study was done to understand the relationship between BMI and chemotherapy dosing, as well as survival in colorectal carcinoma.In four large randomised trials, the OCTOPUS study looked at data from 7269 patients who received adjuvant chemotherapy following curative surgery for colon or rectal cancer. Researchers examined the relationships between BMI, chemotherapy dosing, and survival.We looked at two methods of measuring the amount of chemotherapy received in relation to actual-to-expected standard doses. They were average cumulative relative dose (ACRD), and average relative dose intens (ARDI). ACRD refers to the expected standard dose per unit of body surface that was actually received. ARDI, however, takes into consideration the length of treatment and is the percentage of the expected standard dose intensity (the dose per unit of BSA divided by the number weeks of treatment). Both measures are averaged together and expressed as percentages.The results showed that ACRD increases of 5% were associated with improved disease-free survival rates (hazard ratio 0.953; 95% confidence interval 0926; 0.980, P=0.001). ACRD was also associated with overall survival. There was however no association with ARDI. Slawinski speculated that there was no association between survival and ARDI, possibly because ARDI is a sensitive measure of the reduction in total (cumulative), chemotherapy doses.Further research showed that a 5kg/m2 increase in BMI was associated with a 2% decrease in relative chemotherapy doses for the first cycle and 1% in ACRD and ARDI. A patient who is obese and has a BMI greater than 37.5kg/m2 will see a 3% decrease in ACRD or ARDI, compared to someone who is not obese with a 22.5kg/m2 BMI."These results revealed that an elevated BMI was associated with a lower relative dose of chemotherapy during the first cycle and a slight reduction in ACRD. Slawinski concluded that these indirect effects from sub-optimal treatment may explain poorer survival rates in obese patients rather than direct effects due to obesity, such as tumour biology. Our results support the recommendation to give obese patients chemotherapy according to their body weight. She cautioned that we are still investigating toxicity data and examining the relationship between BMI (body mass index), dose capping, toxicity, survival, and chemotherapy. Toxicity can have a negative impact on quality of life, and could even be life-threatening. There may be other reasons to reduce chemotherapy doses such as comorbidities. It is therefore important that each patient's treatment and dosing decisions are made individually.Smyth agreed, saying: "The main takeaway from this study was that dose reductions may be necessary for patients with high BMI when they are treated with adjuvant chemotherapy." She added, "Dosing chemotherapy involves more than weight. It also includes fitness and co-morbidities such as renal function and dihydropyrimidine (DPD) testing results.Smyth believes that further research is needed before changing practices. "Prospective studies that examine the effects of higher doses may be necessary, particularly as there has been an increase in patients with cancer and those who are obese. She concluded that we should consider all aspects of the patient when deciding on chemotherapy doses. Although dose reductions were associated with lower survival rates in this study, they may still be necessary for safety.###Notes for EditorsPlease use the official name of this meeting in your reports: ESMO World Congress on Gastrointestinal Cancer 2020Official Congress Hashtag #WorldGI2021DisclaimerThis press release includes information provided by the author for the highlighted abstract. It also reflects the content in the abstract. This press release does not necessarily reflect or represent the views of the ESMO WGI Organisations. They cannot be held responsible if the data is incorrect. The press release requires commentators to adhere to the ESMO Declaration of Interests policy as well as the ESMO Code of conduct.Refer to1 Abstract O-4 "Average cumulative relative dosage (ACRD), of adjuvant chemotherapy for colorectal carcinoma survival is more important than average relative dose intensity (ARDI), with implications for treating obese patients: The OCTOPUS consortium" will be presented on Friday, July 2, 08:00-12:00 CEST by Corinna Swinski. Annals of Oncology Volume 32, Supplement 3 July 2021 - http:////www. worldgicancer. com2 Parkin et.al. A systematic review (2014) of excess adiposity in colorectal cancer patients: survival and the relationship between it and its complications. 15(5): 434-451.3 Griggs JJ. Bohlke K. Balaban EP. ASCO Guideline Update: Appropriate systemic treatment dosing for obese adults with cancer J Clin Oncol 2021 DOI https:/// / doi. http://www.jclinoncol.org/ 10. 1200/ JCO. 21. 21.About the European Society for Medical Oncology.ESMO is the most prominent professional organization for medical oncology. ESMO has more than 25,000 members who represent oncology professionals in over 160 countries. It is the leading society for oncology information and education. ESMO was founded by a common determination to ensure the best possible outcome for patients. It is dedicated to supporting those who care for cancer by addressing the many needs of #ONEoncologycommunity and offering #educationforLIFE. Visit http://www. Visit http://www. orgInformation about the ESMO World Congress on Gastrointestinal CancerThe ESMO World Congress on Gastrointestinal Cancer is the premier international gathering of oncology professionals. It discusses the most recent research and data in this rapidly evolving scientific field.O-4 - The average cumulative relative dose (ACRD), of adjuvant chemotherapy, is more important than the average relative dose intens (ARDI) in colorectal cancer survival. This has implications for treating obese patients.C. Slawinski1, L. Malcomson1, J. Barriuso2, H. Guo1, A. Harkin3, T. Iveson4, R. Glynne Jones5, C. Van de Velde6, A. Renehan21University 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 Medicine Center Leiden, SwitzerlandBackground: Some studies show that obese patients are less likely to survive after curative surgery for colorectal carcinoma (CRC). CRC adjuvant chemotherapy (ACT), is often capped at a BSA of 2.2m2. This could reduce the average cumulative relative dose (ACRD), and the average relative dose intensity(ARDI) in obese patients.Methods: Participants-level data from MOSAIC and SCOT, PROCTORSCRIPT, and CHRONICLE (CRC ACT) randomised trials, with derivable BMI and BSA, were included from OCTOPUS. ACRD and ARDI were calculated as percentages (full BSA-based), of the actual to expected dose intensity (cumulative dosage/treatment duration in week) or cumulative dose, respectively, across all drugs in the regimen. To explore the BMI-ARDI/ACRD relationship and ARDI/ACRD-survival relationships, a random-effects meta analysis of linear or Cox proportional hazards regression model was performed. Primary outcome was disease-free survival (DFS), while secondary outcomes were overall survival (OS) as well as survival from cancer-specific (CSS), in addition to ARDI/ACRD. All models were adjusted for age, gender, performance status, and BMI (in addition to the survival models).Results: 7269 eligible patients. A reduction of 2.04% in the cycle 1 dose was associated with BMI 5kg/m2 increments (95% CI:-2.45;-1.64; P=0.001) and small reductions in ACRD (0.84, 0.26; p=0.009), and ARDI (0.022, -0.62); both p0.001. Study effect modification was shown for ARDI (female and male: 1.55% (0.97?2.13); P0.001) but not ACRD. (female and male: 0.88% (0.14, 1.89); P=0.092).ACRD 5% increases were associated with better DFS (HR 995 (0.926, 0.9980); p=0.001) OS (HR 993(0.908), 0.955; p0.001) and CSS(HR 0.941(0.924), 0.959; p0.001) survival. However, there was no relationship for ARDI (DFSHR 1.015 (0.967), 1.065); p=0.552; OSHR 1.035 (0.990; 1.081); p 0.134, CSS HR 1.022 (1.092, 1.064); p=0.282; p = 0.282; sex-interactions between ACRD and ARDI; p = 0.282.Conclusion: ACRD is more crucial than ARDI when it comes to determining survival. An elevated BMI is associated to a lower cycle 1 dose and a slight reduction in ACRD. Indirect effects from undertreatment may explain lower survival rates in obese patients than direct effects such as tumour biology or obesity.This Study is being done by the Legal Entity: The Authors.Funding: The funding to Cancer Research UK Manchester Centre [C147/A18083] & [C147/A25254] was used to support this work. A.G. Renehan receives support from the Manchester NIHR Biomedical Research Centre, (IS-BRC-1215–20007).Disclosure: None of the authors have disclosed conflicts of interest
