Obesity and Its Impact on Outcomes in Patients With Stage III Colon Cancer Receiving Adjuvant Chemotherapy

Ding, Philip Q.; Batra, Atul; Xu, Yuan; McKinnon, Geoffrey P.; Cheung, Winson Y.

doi:10.1016/j.clcc.2020.02.010

Cited by 7 publications

(10 citation statements)

References 25 publications

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“…Further, the underlying condition and cancer-type appear to play a critical role as well. 53 The current study demonstrated that obese mice lost similar muscle mass and greater body weight with 5FU when compared to lean mice. Obese mice also had perturbed immune cell populations compared to their lean counterparts.…”

Section: Discussionsupporting

confidence: 51%

Obesity reduced survival with 5-fluorouracil and did not protect against chemotherapy-induced cachexia or immune cell cytotoxicity in mice

VanderVeen

Cardaci

McDonald

et al. 2022

Cancer Biology & Therapy

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Fluorouracil/5-flourouracil (5FU) is a first-line chemotherapy drug for many cancer types; however, its associated toxicities contribute to poor quality of life and reduced dose intensities negatively impacting patient prognosis. While obesity remains a critical risk factor for most cancers, our understanding regarding how obesity may impact chemotherapy’s toxicities is extremely limited. C56BL/6 mice were given high fat (Obese) or standard diets (Lean) for 4 months and then subjected to three cycles of 5FU (5d-40 mg/kg Lean Mass, 9d rest) or PBS vehicle control. Shockingly, only 60% of Obese survived 3 cycles compared to 100% of Lean, and Obese lost significantly more body weight. Dihydropyrimidine dehydrogenase (DPD), the enzyme responsible for 5FU catabolism, was reduced in obese livers. Total white blood cells, neutrophils, and lymphocytes were reduced in Obese 5FU compared to Lean 5FU and PBS controls. While adipocyte size was not affected by 5FU in Obese, skeletal muscle mass and myofibrillar cross section area were decreased following 5FU in Lean and Obese. Although adipose tissue inflammatory gene expression was not impacted by 5FU, distinct perturbations to skeletal muscle inflammatory gene expression and immune cell populations (CD45 + Immune cells, CD45 + CD11b + CD68 + macrophages and CD45 + CD11b + Ly6c lo/int macrophage/monocytes) were observed in Obese only. Our evidence suggests that obesity induced liver pathologies and reduced DPD exacerbated 5FU toxicities. While obesity has been suggested to protect against cancer/chemotherapy-induced cachexia and other toxicities, our results demonstrate that obese mice are not protected, but rather show evidence of increased susceptibility to 5FU-induced cytotoxicity even when dosed for relative lean mass.

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Section: Discussionsupporting

confidence: 51%

Obesity reduced survival with 5-fluorouracil and did not protect against chemotherapy-induced cachexia or immune cell cytotoxicity in mice

VanderVeen

Cardaci

McDonald

et al. 2022

Cancer Biology & Therapy

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“…The association between underweight BMI and poor survival is coherently observed in patients with CRC [ 4 , 7 , 8 , 10 , 18 , 21 , 22 ]. However, one study showed that underweight BMI showed no significant difference in OS compared to normal BMI in patients with stage III CRC (HR, 1.29; 95% CI, 0.77 to 2.19) [ 5 ], although the exact reason of this discordance was unclear. Some speculate that being underweight reflects a more advanced disease status and this may be translated into worse outcomes [ 8 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…Whether overweight is associated with better survival remains a debatable topic and studies regarding patients with CRC have offered conflicting insights: some report being overweight has a protective effect [ 7 , 10 , 12 ], some report a hazardous effect [ 21 ], and some failed to find an association at all [ 5 , 6 ]. In terms of obesity and survival, the better survival outcome in patients with overweight is known as the ‘obesity paradox.’ This relation is observed in many cancer types, including colorectal, renal, hematologic, and metastatic malignancies [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Proinflammatory factors, immune suppression, and changes in the metabolic functions of adipose tissue play an active role in establishing and promoting tumoral progression [ 1 , 4 ]. For this reason, many researchers have investigated the fundamental association of obesity with prognosis [ 5 – 13 ], however, the relationship is yet to be elucidated in patients with CRC. Although it is widely accepted that people with obesity are prone to cancer [ 14 ], many report that patients with cancer and overweight live longer [ 7 , 10 , 12 ], which is a phenomenon called the ‘obesity paradox’.…”

Section: Introductionmentioning

confidence: 99%

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Association of Body Mass Index with Survival in Asian Patients with Colorectal Cancer

Lee

et al. 2022

Cancer Res Treat

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The clinical significance of body mass index (BMI) on long-term outcomes has not been extensively investigated in Asian patients with colorectal cancer (CRC). This study aims to describe the association between BMI and survival, plus providing BMI cut-off value for predicting prognosis in CRC patients. Materials and MethodsA total of 1,182 patients who had undergone surgery for stage I-III CRC from June 2004 to February 2014 were included. BMI was categorized into four groups based on the recommendation for Asian ethnicity. The optimal BMI cut-off value was determined to maximize overall survival (OS) difference. ResultsIn multivariable analysis, underweight BMI was significantly associated with poor OS (hazard ratio [HR] = 2.38, 95% confidence interval [CI] = 1.55-3.71, p<0.001) and obese BMI was associated with better OS (HR = 0.72, 95% CI = 0.53-0.97, p=0.036) compared with the normal BMI. Overweight and obese BMI were associated with better recurrence-free survival (RFS) (HR = 0.64, 95% CI = 0.42-0.99, p=0.046; HR = 0.58, 95% CI = 0.38-0.89, p=0.014, respectively) compared with the normal BMI group. BMI cut-off value was 20.44 kg/m 2 .Adding the BMI cut-off value to cancer staging could increase discriminatory performance in terms of integrated area under the curve and Harrell's concordance index. ConclusionCompared to normal BMI, underweight BMI was associated with poor survival whereas obese BMI was associated with better survival. BMI cut-off value of 20.44 kg/m 2 is a useful discriminator in Asian patients with CRC.

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Post‐diagnosis adiposity and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta‐analysis

Becerra‐Tomás,

Markozannes,

Cariolou

et al. 2024

Intl Journal of Cancer

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The adiposity influence on colorectal cancer prognosis remains poorly characterised. We performed a systematic review and meta‐analysis on post‐diagnosis adiposity measures (body mass index [BMI], waist circumference, waist‐to‐hip ratio, weight) or their changes and colorectal cancer outcomes. PubMed and Embase were searched through 28 February 2022. Random‐effects meta‐analyses were conducted when at least three studies had sufficient information. The quality of evidence was interpreted and graded by the Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel. We reviewed 124 observational studies (85 publications). Meta‐analyses were possible for BMI and all‐cause mortality, colorectal cancer‐specific mortality, and cancer recurrence/disease‐free survival. Non‐linear meta‐analysis indicated a reverse J‐shaped association between BMI and colorectal cancer outcomes (nadir at BMI 28 kg/m2). The highest risk, relative to the nadir, was observed at both ends of the BMI distribution (18 and 38 kg/m2), namely 60% and 23% higher risk for all‐cause mortality; 95% and 26% for colorectal cancer‐specific mortality; and 37% and 24% for cancer recurrence/disease‐free survival, respectively. The higher risk with low BMI was attenuated in secondary analyses of RCTs (compared to cohort studies), among studies with longer follow‐up, and in women suggesting potential methodological limitations and/or altered physiological state. Descriptively synthesised studies on other adiposity‐outcome associations of interest were limited in number and methodological quality. All the associations were graded as limited (likelihood of causality: no conclusion) due to potential methodological limitations (reverse causation, confounding, selection bias). Additional well‐designed observational studies and interventional trials are needed to provide further clarification.

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Obesity and Its Impact on Outcomes in Patients With Stage III Colon Cancer Receiving Adjuvant Chemotherapy

Cited by 7 publications

References 25 publications

Obesity reduced survival with 5-fluorouracil and did not protect against chemotherapy-induced cachexia or immune cell cytotoxicity in mice

Obesity reduced survival with 5-fluorouracil and did not protect against chemotherapy-induced cachexia or immune cell cytotoxicity in mice

Association of Body Mass Index with Survival in Asian Patients with Colorectal Cancer

Post‐diagnosis adiposity and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta‐analysis

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