But one in five will have cancer spread beyond their colon.

Better information about which patients will relapse could spare many from the risks of chemotherapy.

A new gene test announced at the 2011 Gastrointestinal Cancer Symposium in San Francisco helps provide answers to which patients are at highest risk and could help patients and their doctors make better decisions about follow-up chemotherapy after surgery.

ColoPrint, an 18 gene tumor tissue signature, found that three out of four patients with stage II colon cancer had only about a 5 percent risk of recurrence, very similar to stage I patients.  For the remaining high risk patients, one in five (20 percent) had cancer return.

In a series of 135 patients with stage II colon cancer, ColoPrint identified

• 73 percent at low risk of recurrence.  After  a median 97 months of followup, only 5 percent experienced a relapse.
• 27 percent at high risk.  During the 97 month follow-up, 20 percent had cancer return.

ColoPrint was developed by searching the whole genome for a fingerprint of genes that predicted recurrence from colon cancer.  The study reported at the GI Symposium is the second one to validate the test.  A third validation study of 600 patients is now underway at MD Anderson Cancer Center in Houston, with results expected later this year.

In a press briefing, surgeon Robert Rosenberg, MD, an assistant professor at the University Hospital of the Technical University in Munich, Germany said,

The ColoPrint gene expression test was the only significant factor that predicted the development of distant metastasis in our patient series, In this validation study, the performance of ColoPrint seemed to be independent of known clinical factors. ColoPrint was able to predict outcome in stage II patients, and this facilitates the identification of patients who may be safely managed without chemotherapy.

SOURCE: Rosenberg et al,, Independent validation of a prognostic genomic profile (ColoPrint) for stage II colon cancer (CC) patients, Abstract #358, 2011 Gastrointestinal Cancers Symposium.

Although about half of patients in the trial took a multivitamin supplement during their treatment, the vitamin didn’t improve their outcomes, nor did it reduce side effects.  At the same time, multivitamin use didn’t have a detrimental effect.

Researchers asked about 1,000 patients at the end of their chemotherapy and then about 6 months later about whether they took multivitamins during their chemo or afterwards.  Patients in the trial had randomly received one of two different chemos, and the trial showed no difference between the two treatments.

After about 7 years of follow-up there was no difference between patients who took multivitamins during chemotherapy and those who didn’t for cancer-free survival, recurrence, or overall survival.  There was also no difference for patients who said that they took multivitamins in the months after they finished chemo.

However, multivitamins taken during chemotherapy did appear to benefit patients who were 60 years old or younger.  who had about a 30 percent reduction in the risk of dying from cancer or having their colon cancer return.  This difference didn’t seem to be related to family history or microsatellite instability.  But taking multivitamins after chemotherapy was completed, didn’t improve outcomes for these younger patients.

Obese patients did derive benefit from multivitamin use, but those who were merely overweight actually did worse in terms of disease-free survival when they took them.  In normal weight people, vitamins didn’t make a difference.

Commenting on the study, Charles Fuchs, MD, director of gastrointestinal oncology at Dana-Farber Cancer Institute and the paper’s senior author, said.

This study adds to a growing body of research that questions the purported benefit of multivitamin use, and it underscores the need to investigate the use of individual vitamins, such as vitamin D, which may, in fact, provide real benefit.

Dr. Fuchs noted that most multivitamins contain a small dose of vitamin D.

Use of multivitamins during chemotherapy didn’t appear to affect side effects, with no significant differences between those who took them and those who didn’t for nausea, vomiting, diarrhea, or lowered white cell counts.  There was less severe fatigue in multivitamin users, with 10.8 percent of the nonusers experiencing grade 3 or 4 fatigue compared to 7.4 percent of those who took vitamins.

Lead author Kimmie Ng and her colleagues concluded,

Multivitamin use during and after adjuvant chemotherapy was not significantly associated with
improved outcomes in patients with stage III colon cancer.

SOURCE: Ng et al., Journal of Clinical Oncology, Early Release, August 30, 2010.

Stage II colon cancer patients have a tough time knowing how likely it is that their cancer will recur and making a decision about having chemotherapy after surgery.

A test is now on the market that can help with that decision.  OncoType DX® Colon Assay analyzes 12 key genes from a tumor sample to produce a recurrence score that indicates how likely stage II colon cancer will return.

While OncoType DX Colon can’t predict whether chemotherapy will reduce the chance that cancer will come back, it can help patients and their doctors decide on chemotherapy in combination with other factors.

Based on many years of studying tumor samples saved in paraffin during clinical trials, OncoType DX analyzes expression of 12 genes in colon tumors.  The resulting recurrence score determines the likelihood that cancer will recur in the following three years.

At ASCO in 2009, development and validation of the 12 gene test was announced, and Genomic Health predicted a commercial launch of the test in early 2010.

Range of recurrence scores:

• Low — About 44 percent of patients will have about a 12 percent risk of recurrence.
• Intermediate — About 31 percent will have an 18 percent risk of recurrence.
• High — 26 percent will have a 22 percent risk

Genomic Health scientists recommend that the actual recurrence core itself be considered, rather than a general low, intermediate, or high.

Two other factors that are important in deciding whether or not to use chemotherapy are

• Mismatch repair status: In about 15 percent of stage II colon cancer, genes that help repair damaged DNA are mutated.  Mismatch repair is deficient (dMMR).  Patients with these tumors have good survival prospects and are much less likely to experience recurrence.  Studies show that chemotherapy doesn’t reduce recurrence or improve survival, and some studies show reduced benefit with chemo, although this remains controversial.  Most tumors, however, are have not lost the ability to repair DNA and are labeled MMR proficient (pMMR).
• T-stage: Stage II colon cancer is either T3 or T4. In T3 colon cancer, the tumor has grown outer muscular layer of the colon and into the outermost layers not through them. It has not reached any nearby organs or tissues. A cancer that has broken through the wall of the colon and may be in nearby tissues is classified as T4.  T4 cancers have almost double the risk of recurrence.

Most oncologists would agree that risk is high for T4 tumors with proficient mismatch repair and chemotherapy is probably warranted after surgery.  For T3 tumors that have deficient mismatch repair, chemotherapy probably has no benefit and may even be detrimental.

But three out of four stage II colon cancers fall into an intermediate risk category of T3 stage and proficient mismatch repair.  For patients with these tumors, the OncoType DX recurrence score can be valuable in helping make a decision about further treatment.

Disclosure: C3 has accepted funding for projects and educational programs from Genomic Health in the form of unrestricted educational grants. C3 has ultimate authority over website content.

Pam’s experience with colorectal cancer research advocacy goes back more than a decade.  She has been a patient advocate with several cancer cooperative groups and now chairs the Radiation Therapy Oncology Group (RTOG) Patient Advocacy Committee.

While most patients with stage II colon cancer are at low risk of recurrence, there are patients in this group who are at increased risk and who may need chemotherapy to reduce their risk.

The average stage II patient has an absolute benefit of only 1 or 2 percent from chemotherapy. In other words, the average Stage II patient will decrease risk of recurrence by only 1 or 2 percent it they have chemotherapy. And since chemotherapy has its own risks, it is important to identify those at increased risk whose potential benefit would be greater than average.

Currently a variety of factors are used to try to identify which stage II patients are at increased risk of recurrence.

• One  is the number of lymph nodes examined. Not only is examination of at least 8 to 12 nodes essential to accurate staging but the number of nodes removed is a strong prognostic indicator. In other words, people with more nodes removed do better than people with fewer.  At the 2010 Gastrointestinal Cancer Symposium it was again confirmed that patients with 12 or more lymph nodes examined had a recurrence risk at 3 years about 5% lower than those with examined fewer nodes. It was further noted that the prognostic value of lymph node number was independent of the 12 gene recurrence score.
• The 12 gene recurrence score (Oncotype DX Colon recently released by Genomic Health) reports patients as at high, medium or low risk of recurrence at 3 years. The recurrence scores range from an average risk of 12 % for low risk, 18% for medium risk to 22% for high risk.
• Also frequently used to evaluate stage II tumors is lymphovascular invasion (the visualization of cancer cells in small vessels within the tumor), T stage (T3 versus T4), and the markers 18qLOH and MSI (microsatellite instability).
• Microsatellite status has been shown to be a prognostic indicator in stage II colon cancer. Patients with pMMR (proficient mismatched repair) have worse outcomes than those who are deficient in mismatch repair (dMMR or MSI-H). The 5 year survival for patients who have pMMR is less than 75% in comparison with those who have dMMR (MSI-H) whose 5 year survival is greater than 90%. About 15% of patients have deficient mismatch repair (are MSI) and are a reduced risk of recurrence. A presentation at the ASCO Gastrointestinal Symposium indicated a need for physician education on the value of mismatch repair testing and use in treatment planning.
• Those who have loss of heterozygosity at 18q, a place on a chromosome, (18qLOH) are at increased risk of recurrence.

Examination of these factors and others can assist patients and their physicians to decide whether or not to have chemotherapy. At this point, no single factor is adequate to guide treatment decisions. When many factors available are used together, though, sufficient information is available to assist physicians and their patients decide whether or not chemotherapy is warranted.

Since patients vary widely in the amount of decreased risk is necessary to justify the toxicity and expense of chemotherapy, the decision must be made on an individual basis. This will require better education of physicians so they can better inform their patients.

Colon cancer patients over 70 actually had a greater reduction in disease-free survival than did younger ones with a new regimen of Xeloda® and oxaliplatin compared to older IV 5-FU treatments according to a new analysis reported at the GI Cancers Symposium in Orlando.

With the bolus IV 5-FU and leucovorin regimens, stage III colon cancer patients over 70 had about a 60 percent chance of being alive and free from cancer three years after surgery. With a combination of Xeloda (capecitabine) and oxaliplatin in a treatment called XELOX, their three-year disease-free survival was 66 percent.

Younger patients had about a 3 percent absolute improvement between the two treatments from 69 percent to 72 percent.

The Xeloxa clinical trial compared the oral drug Xeloda plus intravenous oxaliplatin to then standard IV 5-FU and leucovorin regimens after surgery for stage III colon cancer. The trial (NO16968) enrolled nearly 1,900 patients, including more than 400 who were age 70 and over.

After three years, there was a six percentage point increase in disease-free survival in the older patients. The spread remained true when the cut-off age was dropped to 65. Patients 65 and older had a 62 percent chance of disease-free survival at three years on the older 5-FU treatments compared to 68 percent on the XELOX regimen.

Speaking during a GI Symposium press briefing, Daniel G Haller, MD, of the University of Pennsylvania, said,

XELOX is a new standard of care for patients with early colon cancer, regardless of age. Patients receiving XELOX immediately after surgery live disease-free for longer, and there is a trend towards superior overall survival with XELOX.

SOURCE: Haller et al., Efficacy findings from a randomized phase III trial of capecitabine plus oxaliplatin versus bolus 5-FU/LV for stage III colon cancer (NO16968): No impact of age on disease-free survival (DFS), Abstract #284, 2010 GI Cancers Symposium.

Disclosure: C3 has accepted funding for projects and educational programs from Roche and sanofi-aventis in the form of unrestricted educational grants. C3 has ultimate authority over website content.

These data have been discussed by Kate Murphy. However I wanted to follow up with the significance of the data. To increase the risk of recurrence from 12% to 22% is not in any way or form helpful in the clinic, particularly because this outcome is independent of treatment effect.

In other words the technology used by Genomic Health did not result in any clinically meaningful markers which are helpful to decide whether chemotherapy should be given or not.

I was surprised that the data was presented like these are positive data because they have no impact on daily practices. These data need to be improved to make a difference so that they can be used to identify the patients who are at significantly higher risk.

Patients with stage II colon cancer have on average a 15 percent chance of cancer recurring. This is a big challenge! Should we treat everyone and treat many patients with no benefit to make sure we treat everyone who really is at higher risk.?

If we had a genetic marker set which could isolate these patients who are at higher risk, we could spare the ones with very low risk  from chemotherapy for 6 months.

The Genomic Health approach was not successful partly because they did not take advantage of the whole genetic make up. The technology is able to measure 40-50 thousand genes in one test and to figure out what signature would predict recurrence would be the solution.

In breast cancer they have developed a signature to predict recurrence risk and whether chemotherapy should be given.