Obesity Increases Risk for Metastases in Pancreatic Cancer

Zosia Chustecka

March 19, 2009

March 19, 2009 — Obesity greatly increased the risk for metastasis, as well as for recurrence and death, according to a study of pancreatic cancer patients reported in the March issue of the Archives of Surgery.

In a series of 285 patients who underwent potentially curative surgery, a small group of obese patients with a body mass index (BMI) of more than 35 kg/m2 was found to have a 12-fold higher risk for lymph node metastases and an almost doubled risk for cancer recurrence and death, compared with all the other patients.

The surgery was similar in all of the patients, which suggests that "obesity is a host factor affecting tumor biology, independent of the difficulties involved in delivering oncologic care in obese patients," the researchers comment.

The implication from this study, and from other emerging evidence, is that solid tumors behave differently in patients who are obese and in those who are not obese, lead author Jason Fleming, MD, from the University of Texas MD Anderson Cancer Center, in Houston, told Medscape Oncology. He noted that obesity has also been linked to increased recurrence and poor survival in breast cancer, and that a positive influence on lymph node metastasis has been suggested.

However, when asked whether there are any practical implications from these findings, Dr. Fleming said: "It is still unclear whether some weight-loss or dietary-modification strategy would help patients after they have been diagnosed with cancer. Attempts to lose weight during therapy or before or after surgery could be unsafe."

"We are currently developing a 'prehabilitation program,' in which patients embark on supervised dietary modification, physical therapy, and counseling prior to surgery," he said. "We hope that this will result in tangible improvements in cancer-therapy delivery and, ultimately, patient survival."

Differences Did Not Stem From Surgery

All of the patients had pancreatic adenocarcinoma. Most of the patients underwent a pancreaticoduodenectomy (262 patients; 89%), but some underwent subtotal distal pancreatectomy (31 patients; 10%), and 3 patients (1%) underwent a total pancreatectomy.

The median time to last follow-up or death for the entire group of 285 patients was 16 months, with surviving patients followed for a median of 19.8 months. At last follow-up, 133 patients were alive, 90 (32%) of whom had no evidence of disease and 43 (15%) of whom were living with disease.

Patients were divided into 5 different cohorts according to BMI, but there were no significant differences in outcomes among the cohorts, with the exception of the highest. The small subgroup of 20 patients with a BMI higher than 35 kg/m2 was "unique from the others," the researchers comment.

Compared with the other patients, this subgroup of patients with a BMI higher than 35 kg/m2 had a significantly increased risk of having positive lymph nodes (P =.02). Nearly all these patients (95%) had positive lymph nodes, compared with 56% in all study patients.

In addition, this subgroup of obese patients was at approximately a 2-fold higher risk for recurrence (P = .005) and a 1.95-fold higher risk for death (P = .02) than the other patients.

These differences did not stem from differences in the surgery performed, the authors comment. Although obesity can complicate surgery, there were no differences among the various BMI cohorts in this study in the number of lymph nodes that were examined or in the negative resection margin — both of which are important in defining the oncologic completeness of pancreatectomy, they note.

"These data suggest that increasing BMI did not impair our ability to perform safe and oncologically sound pancreas resection in patients with adenocarcinoma," they comment.

There was a difference in preoperative radiotherapy, with obese patients being less likely to receive this treatment. "We are uncertain of the reason for this observed difference," the researchers say, but they add that even when they controlled for this difference, the influence of BMI on lymph node metastasis "remained strong."

"To our knowledge, the relationship between obesity and lymph node metastases observed in this study is the strongest reported in the literature to date, and it is supported by clinical and laboratory studies showing a relationship between obesity and cancer progression," the researchers note.

Why Does Obesity Increase Risk?

Several explanations for why obesity can increase risk in cancer patients have been proposed. One of these centers on insulin, which is increased in obese individuals. "Insulin and insulin-like growth factors are known to be positive stimulators of cancer cell growth," Dr. Fleming explained, and "it has been postulated that these factors could stimulate cancer cell growth in obese patients."

Another explanation that has been proposed recently, from an experimental study, is that excess lipids may alter cancer-cell membranes, which enhances their ability to separate and spread, as reported by Medscape Oncology.

Intriguingly, in this study of pancreatic cancer patients, the strong association with an increased risk was seen only in patients with a BMI of more than 35 kg/m2, and but not in patients with a BMI from 30 to 35 kg/m2. This finding is "a puzzle to us," Dr. Fleming said. The BMI groupings are somewhat artificial because BMI is really a continuous variable, he said, but the data could be interpreted as suggesting a "dose-dependent" negative effect, with the highest BMI having the most profound negative effect.

However, Dr. Fleming also noted that "pancreatic cancer has a poor outcome for most patients, regardless of their BMI, so identifying any 1 factor that contributes to that is difficult."

The study was supported by a grant from the National Institute of Health and by the Various Donor Found for Pancreatic Cancer Research. The researchers have disclosed no relevant financial relationships.

Arch Surg. 2009;144;216-221. Abstract

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