Older men with several kinds of cancer–including colon cancer–do as well or better in the Veterans’ Health Administration as men covered by Medicare, according to a new study published by the Journal of Clinical Oncology in an advanced online release.

The Veterans’ Administration is the nation’s largest integrated health system, providing care for 6 million veterans a year who are eligible because of either service-related disabilities or economic disadvantage. The VHA launched a major reorganization in the mid-1990s to improve its quality of care through electronic records, better care coordination and mistake detection, and improved screening.

In this large study, researchers examined survival rates in men over age 65 diagnosed with colon, rectal, lung, bone marrow cancer or lymphoma in men treated by the VHA compared to men covered by Medicare.

The VHA patients were more likely to be African American or lower income. But after adjusting for most population differences, the study found that men treated for colon cancer at the VHA survived an average of four years and one month, compared to three years and seven months among Medicare Fee-for-Service (FFS) patients—a significant finding in the five-year follow-up period. There were no differences in survival for rectal cancer.

The researchers suggested the improved colon cancer survival was due to earlier diagnoses resulting from comprehensive screening at the VHA. But despite sophisticated, powerful statistical analysis, they could not definitively prove reasons for better outcomes, such as better adherence to treatment guidelines.

In an accompanying editorial, Dr. Stephen Edge of the Roswell Park Cancer Institute noted,

This elegant study highlights the challenges that face those conducting and interpreting comparative effectiveness research when trying to define what specific actions improve outcomes.

Nonetheless, this study documents the real progress made by the VHA in improving the care and outcomes for American veter. In fact, the VHA may now be ahead of the private sector in quality improvement.

Mary Beth Landrum, PhD and her colleagues concluded,

The survival rate for older men with cancer in the VHA was better than or equivalent to the survival rate for similar FFS-Medicare beneficiaries. The VHA provision of high-quality care, particularly preventive care, can result in improved patient outcomes.

SOURCES: Landrum et al, Journal of Clinical Oncology, early online release March 5, 2012.

Edge, Journal of Clinical Oncology, early online release March 5, 2012.

Traditionally, people getting cancer treatments were told to rest and avoid exertion, to save their strength during treatment. But more experts now say that the best way to get through treatment, and possibly the best way to beat cancer, is to stay as physically active as possible.

The American College of Sports Medicine has revised its national recommendations, saying that cancer patients and survivors should strive for the same goal as everyone–about 150 minutes a week of moderate aerobic exercise, along with resistance training and stretching.

The panel does caution that workout plans must be adapted to each person’s condition and treatment. For example, some cancer treatments make bones more brittle, which will require exercise that place less stress on them. And immunosuppressed patients must avoid exercise in groups of people.

But the expert panel cited research showing that aerobic activity reduces fatigue, and loss of both muscle and bone mass. Exercise also can calm fear and restore a sense of control.

And the most important benefit, emerging evidence shows, may be a better chance of survival: Treatments can be more effective when the body can better withstand the effects of chemotherapy and radiation. Dr. Eleanor Walker, lead author of an ongoing study of exercise in cancer patients in Detroit, says her research is “potentially showing that even if you don’t start your exercise training until you’ve received your diagnosis, it can still be of some help. And if you’re in a healthier state before you get a [cancer] diagnosis, you’re going to do better because your body is in better shape and you have reserves…”

Source: HealthDay News

Should cancer care focused on quality of life wait until all treatment ends?  Or can it be integrated with medical treatment as soon as someone is diagnosed with a life-threatening illness?

In a study of 150 advanced lung cancer patients, starting palliative care along with standard life-prolonging treatment when patients were first diagnosed not only improved their mood and quality of life, it actually increased the time they lived.

Although patients who received early palliative care received less aggressive treatment at the end of life, they lived almost 3 months longer than patients who didn’t have such early support.

Study Plan

Newly diagnosed lung cancer patients at Massachusetts General Hospital were invited to participate in a randomized clinical trial where they either  received standard medical treatment for their cancer or had early palliative care along with that treatment.

Ten patients (14 percent) in the standard treatment arm who asked for it were able to receive care from the palliative team, but were not switched to the palliative arm of the trial.

Researchers measured quality of life, mood, and survival time in both groups.  They also looked at aggressive care at the end of life and whether patient’s preferences for resuscitation were recorded in the outpatient electronic medical record.

Palliative care was provided by a team of specialists who followed the guidelines of the National Consensus Project for Quality Palliative Care. Such teams are becoming more common in hospitals and some outpatient settings in the United States and are not limited to hospice programs.  More than 80 percent of large hospitals have them.

Multidisciplinary, they include professionals in the fields of medicine, nursing, social work, chaplaincy, counseling, nutrition, and rehabilitation.

The team paid special attention to:

• assessing physical and psychosocial symptoms
• establishing goals for care
• assisting with decision making regarding treatment
• coordinating care on the basis of the individual needs of the patient

Study Results

Quality of Life

• Compared to patients who received only standard cancer care, those who got early palliative care had scores for quality-of-life improve from the initial test to the one 12 weeks later.  Scores for the standard care group went down.
• The percentage of patients with depression was higher in the standard care group, although about 18 percent of patients in both groups got antidepressant medicines.
• Increased anxiety was about the same for both groups.

End-of-Life Care

When end-of-life care was analyzed, 105 (70 percent) of patients in the study had died.  For that group:

• 28 percent of standard care group had their wishes for resuscitation recorded in their charts, compared to 53 percent of those in early palliative care.
• Those in standard care spent a median of 4 days with hospice care, compared to 11 days for the early palliative care group.
• More than half (54 percent) of the standard group had some kind of aggressive care at the end of life, compared to a third (33 percent) of those who received care from the palliative team.

Aggressive care at the end of life was measured by any one of the following criteria:

• Chemotherapy within 14 days of death
• No hospice care
• Admission to hospice 3 days or less before death

Despite less aggressive care at the end of their lives, the early palliative care group lived a median of 11.6 months after their diagnosis, compared to 8.9 months for those who got standard lung cancer care.

Jennifer S. Temel, MD, and her team concluded,

Among patients with metastatic non–small-cell lung cancer, early palliative care led to significant improvements in both quality of life and mood. As compared with patients receiving standard care, patients receiving early palliative care had less aggressive care at the end of life but longer survival.

In an accompanying editorial, Amy S. Kelley, MD, MSHS., and Diane E. Meier, MD discuss the study in light of common beliefs that palliative care is only provided as an alternative to life-prolonging or curative care — “what we do when there is nothing more that we can do.”  They write,

This study is an example of research that shifts a long-held paradigm that has limited access to palliative care to patients who were predictably and clearly dying. The new approach recognizes that life threatening illness, whether it can be cured or controlled, carries with it significant burdens of suffering for patients and their families and that this suffering can be effectively addressed by modern palliative care teams.

The National Consensus Project for Quality Palliative Care Clinical Practice Guidelines define palliative care this way:

Palliative care is both a philosophy of care and an organized, highly structured system for delivering care. Palliative care expands traditional disease-model medical treatments to include the goals of enhancing quality of life for patient and family, optimizing function, helping with decision making, and providing opportunities for personal growth. As such, it can be delivered concurrently with life-prolonging care or as the main focus of care.

Far from being focused on dying, the Guidelines continue,

Palliative care affirms life by supporting the patient and family’s goals for the future, including their hopes for cure or life-prolongation, as well as their hopes for peace and dignity throughout the course of illness, the dying process, and death.

Healthcare reform legislation, the Affordable Care Act, will establish 15 pilot sites that offer palliative care integrated with treatment paid for by Medicare for people on Medicare. The new law also allows children who are enrolled in Medicaid or the Children’s Health Insurance Program (CHIP) to receive both hospice and curative care.

Some insurance programs will also cover hospice care and treatment at the same time, so ask your insurance plan about hospice coverage even if you want to continue therapy.

SOURCES: Temel et al., New England Journal of Medicine,Volume 363, Number 8, August 19, 2010.

Kelley and Meier, New England Journal of Medicine Editorial, Volume 363, Number 8, August 19,2010

What Does This Mean for Patients?

It is important to realize that this study was done with lung cancer patients, not those with colon or rectal cancer.  Only 150 patients at a single outpatient program were involved in the research.

It was completed in an outpatient program at a large Boston research hospital with access to a palliative care team.  Many outpatient settings might not have a similar team available.

While Medicare and insurance pay for palliative care in hospice programs, reimbursement is not as easily available when palliative care is integrated with chemotherapy or other treatment whose goal is to cure cancer or prolong life.

However, for this group of lung cancer patients aggressive care at the end of life did not help them to live longer which might help patients and families with other advanced cancers make decisions about moving to supportive care only near the end of life.

Young patients with stage II or III colon cancer get equal benefit from chemotherapy as older patients, and they have similar side effects.

Five years after treatment, 67 percent of patients under the age of fifty hadn’t had their cancer spread beyond the colon (recurrence-free interval), the same percentage that applied to patients who were fifty or over.

Overall survival and disease-free survival were somewhat better for young patients because they had fewer other reasons for dying.  Overall and disease-free survival reflect patients who are alive five years after beginning treatment.  Neither includes people who have died from any cause, including their cancer.

Researchers from the ACCENT Collaborative Group in cooperation with the LIVESTRONG Young Adult Alliance analyzed information from 33,574 individual colon cancer patients who took part in 24 different randomized Phase III clinical trials.

• 1,758 or 5.2 percent were under age 40
• 5,817 or 17.3 percent were under age 5o
• 299 or 0.9 percent were under age 30

Comparing outcomes at 5 years:

• Overall survival was 75 percent for those younger than 40, 76 percent for those under 50, and 71 percent for those 50 and over.
• Disease free survival was 68 percent for patients under 40, 68 percent for those under 50, and 61 percent for 50 and over.
• Five year recurrence-free intervals were experienced by 68 percent under 40, 67 percent under 50, and 67 percent 50 and older.

There were no clinically meaningful differences in serious side effects between younger and older patients.

Mayo Clinic biostatistican, Daniel J. Sargent, PhD, and his team concluded,

Among patients on chemotherapy, young (age 30-50) stage II and III CC patients had similar recurrence-free interval and adjuvant chemotherapy benefit as older patients, with no clinically meaningful differences in adverse events. Young patients have improved overall survival and disease-free survival, likely primarily due to fewer competing causes of death. Adjuvant chemotherapy is beneficial for colon cancer patients aged 30-50 meeting typical chemotherapy eligibility criteria.

SOURCE: Sargent et al., 2010 ASCO Annual Meeting Abstracts, Abstract #3523.

Briefly

• Hormone replacement therapy reduces risk of colon cancer.
• Smoking before age 30 increases chances that colon cancer will recur.
• Low CEA levels improve both survival and disease-free survival for stage II colon cancer.
• Most patients want videos of their colonoscopies and are willing to pay for them.

Use of hormone replacement therapy reduces colon cancer

Women in a study of California teachers who were taking hormone replacement therapy (HRT) after menopause had a 36 percent reduced risk of colon cancer over ten years than women who weren’t on HRT at the beginning of the study.  Risk reduction was even greater for women with a first-degree relative who had colon cancer.  Their risk fell 55 percent.

Over 57,000 women were part of the study, about 60 percent of them on HRT at the study start.  Over the next ten years, 444 got colon cancer.

Despite the reduction in colon cancer in the study, doctors caution women about using HRT because of raised risks for breast cancer, heart attack, stroke, and blood clots.  Advice is to use the lowest dose for the shortest time to offset severe menopausal symptoms.

Katherine DeLellis Henderson, PhD, reports the study results in the February 15, 2010 issue of the American Journal of Epidemiology.

Early smoking history reduces disease-free survival after colon cancer

Patients with stage III colon cancer who had a smoking history of 12 or more pack years before they were 30 had almost a 40 percent increased risk of having their cancer return within three years compared to patients who had never smoked.

Among the 1,045 study participants, 46 percent had never smoked, 44 percent were past smokers, and 10 percent were currently smoking.

Disease-free survival three years after treatment was about 18 percent greater for people who had never smoked than for past smokers.

The results, based on questionnaires filled out by patients in the CALGB 80893 adjuvant chemotherapy trial, were published by Nadine Jackson McCleary, MD, MPH,and her colleagues in Cancer, February 15, 2010. They wrote,

Total tobacco usage early in life may be an important, independent prognostic factor of cancer recurrences and mortality in patients with stage III colon cancer.

CEA levels before surgery important for stage II prognosis

Patients whose CEA (carcinoembryonic antigen) blood levels before surgery were low — below 5 ng/ml — had significantly better overall and disease free survival than those whose CEA’s were 5 or higher.  For those with low CEA, overall survival at five years was 81.7 percent compared to 69.9 percent for high CEA.  Disease-free survival was 82.4 percent for low CEA and 70.6 percent for CEA that was 5 ng/ml or higher.

However, CEA levels only made a difference in stage II patients.  There was no significance for stage I or III.

Writing in the Journal of Surgical Oncology, Korean surgeon Jung Wook Huh, MD and colleagues concluded,

Preoperative serum CEA is a reliable predictor of recurrence and survival after curative surgery in patients with colon cancer, particularly in those classified as having stage II disease.

Patients want videos of their colonoscopies

Eight out of ten patients having colonoscopies said that they would like to have a video recording of their colonoscopy, and more than 6 of 10 (63 percent) were willing to pay for it.  After reading a brief paragraph explaining missed lesions during colonoscopy, over half (54 percent) were more interested in a video and none were less interested.

Meghana Raghavendra surveyed 248 outpatients at the Indiana University School of Medicine and reported the results in the World Journal of Gastroenterology, in an early online article January 28, 2010.

Patients with stage IV colorectal cancer live longer when tumors in their liver can be removed surgically, but not all patients have cancer that can be operated on.

Separating patients with liver tumors from colorectal cancer into three groups according to possible liver resectability, British doctors found a wide variation in both overall survival and progression-free survival three years later.

A team of surgeons, medical oncologists, and radiologists at the Royal Marsden Hospital in London divided patients in a clinical trial studying CAPOX chemotherapy into three groups:

• A — those whose treatment was considered to be palliative and not treatable with surgery.
• B — those where chemotherapy might convert initially unresectable metastases and make surgery possible.
• C — patients with resectable liver mets receiving neoadjuvant chemotherapy before surgery.

Among 128 patients who were part of the study, 74 were in the palliative group, 22 in the conversion, and 32 in the neoadjuvant groups.

Patients had scans every four  chemotherapy cycles, and when it was possible liver surgery was attempted after four or eight cycles.

• Ten patients (45 percent) of the conversion group and 19 (59 percent) of the neoadjuvant group eventually had surgery.
• Three years later, 10 percent of the conversion and 37 percent of the neoadjuvant group were alive and their cancer had not gotten worse (progression-free survival).

Median overall survival for all three groups:

• Palliative treatment — 14.6 months
• Conversion chemotherapy — 24.5 months
• Neoadjuvant chemo — 52.9 months

Patients in the study received CAPOX chemotherapy in three week cycles.  The CAPOX regimen was oral Xeloda® (capecitabine) daily for 14 days after an initial infusion of oxaliplatin on day one.

The team concluded,

This prospective study shows the wide variation in outcome according to baseline resectability status and highlights the potential clinical value of a modified staging system to distinguish between these patient subgroups.

SOURCE: Watkins et al., British Journal of Cancer, Volume 102, pp. 255-261, published online January 19, 2010.

More evidence is emerging that right-sided colon cancers are different in significant ways from those on the left side.

Information from 17,641 colon cancer patients in the German Colon/Rectum Cancer Study Group found that people with cancers on the right side of the colon were older, had more chronic illness, and were more likely to be women.  There were significantly more deaths in this group.

While the rate of metastastic cancer spread was similar for both right and left sided tumors, spread to the liver or lungs was more common in the left-sided cancers and peritoneal carcinomatosis from tumors on the right.

Right-sided tumors were more often poorly differentiated and found in nearby lymph nodes (stage III.)

Even after adjusting for risk factors, survival was worse for cancers on the right side.

Right-sided tumors (proximal) included those in the the ascending and transverse colon, while the left side includes the descending and sigmoid colon nearest to the rectum (distal).

Frank Benedix, MD and the team from the Colon/Rectum Carcinomas Study Group concluded,

We found that right- and left-sided colon cancers are significantly different regarding epidemiological, clinical, and histological parameters. Patients with right-sided colon cancers have a worse prognosis. These discrepancies may be caused by genetic differences that account for distinct carcinogenesis and biological behavior. The impact of these findings on screening and therapy remains to be defined.

SOURCE: Benedix et al., Diseases of the Colon and Rectum, Volume 53, Issue 1, pp 57-64, January 2009.

Image courtesy of the National Cancer Institute Visuals Online.

For stage II and III colon cancer, a tumor mutation in the KRAS gene does not impact either relapse-free survival or overall survival.

BRAF mutations, which are less common, don’t help with prognosis for relapse-free survival, but do provide information about overall survival in some tumors.   Patients with BRAF mutations and microsatellite-low or stable tumors had poorer overall survival than those without mutations.

As colon cancer develops, changes in genes accumulate that affect cell division and cell death.  When cells no longer divide or die normally, tumors get larger and some cells may break off and move to new and dangerous sites.

In earlier studies, changes in the KRAS and BRAF genes have been able to predict whether or not advanced colorectal cancer would respond to drugs that target epidermal growth factor receptors (EGFR).  Patients with tumors that have mutated KRAS or BRAF don’t benefit from either Erbitux® (cetuximab) or Vectibix™ (panitumumab).

But it has been unclear whether mutations in these two genes can provide information about whether early stage II or III colon cancer would recur or what the mutations meant for eventual survival.

Using over 1,400 tumor specimens collected during a large, randomized trial of chemotherapy for stage II and III colon cancer, researchers were able to analyze KRAS and BRAF mutations and their impact on both relapse-free and overall survival.  The scientists also looked at microsatellite instability (MSI) and coordinated it with the KRAS and BRAF results.  They had good long-term information about patient relapse and survival.

About 1 in 3 tumors (37 percent) had a KRAS mutation, similar to the percentages found in other studies in metastatic colorectal cancer.  7.9 percent had a BRAF mutation, and the two mutations were mutually exclusive.  Neither KRAS nor BRAF mutations differed between stages II or III.

KRAS mutations

• Were significantly more frequent in l0w-grade tumors and right-sided tumors.
• Were borderline more common in microsatellite-low and microsatellite-stable tumors.
• Did not predict relapse-free survival or overall survival.

BRAF mutations

• Were more frequent in right-sided tumors, high-grade tumors, and tumors that were MSI-high.
• Were more frequent in patients over 60 and in women.
• Did not predict relapse-free survival.
• Did predict poorer overall survival, particularly in patients with MSI-low or MSI-stable tumors.

Arnaud D. Roth, MD and his colleagues concluded,

In stage II-III colon cancer, the KRAS mutation status does not have major prognostic value. BRAF is prognostic for OS in MS-L/S tumors.

SOURCE:  Roth et al., Journal of Clinical Oncology, Early Release, December 14, 2009.

Using non-steroidal anti-inflammatory medicines (NSAIDS) before being diagnosed with colorectal cancer reduced women’s deaths both from any cause and from colorectal cancer five years later.

Women followed as part of the California Teachers Study who used NSAIDS regularly had more than 40 percent reduction in colorectal cancer deaths and a 30 percent  reduced chance of dying overall.

Among women in the study, there were 621 women wh developed colorectal cancer.  In that group

• 64 percent had no pre-diagnosis use of NSAIDS including aspirin and ibuprofen.
• 17 percent used them 1-6 days a week.
• 20 percent used them daily.
• 17 percent reported less than 5 years of NSAID use.
• 18 percent reported use for more than 5 years.

After adjusting for other colorectal cancer risk factors, regular use (1-3 days a week, 4-6 days a week, and daily) resulted in a 29 percent overall survival (HR 0.71) and 42 percent colorectal cancer survival (HR 0.58) improvement compared to those women who didn’t use NSAIDS at all.

Women who used NSAIDs for five years or more had 35 percent reduced risk  of dying from any disease and a 60 percent increase in colorectal cancer specific survival.

Writing in Cancer, Jason A. Zell, DO, MPH, and his colleagues concluded,

When used regularly or over a prolonged duration before CRC diagnosis, NSAIDs are associated with decreased mortality among female CRC patients.

SOURCE: Zell et al., Cancer, published early online October 13, 2009.

Two gene changes that occur in some colorectal cancers can forecast chances for good or poor survival.

Patients whose cancers had high microsatellite instability (MSI) had significantly better outcomes at every stage, but mutations in the KRAS gene predicted poorer survival.

Scientists in New York cancer centers assessed MSI and KRAS genetic mutations in 532 primary colorectal cancers removed during surgery.  Twelve percent of cancer had high levels of microsatellite instability (MSI), while 36 percent had mutations in the KRAS gene.

MSI was more common in early stages with very little MSI in cancers diagnosed at stage IV where cancer had spread beyond the colon:

• stage I– 15 percent
• stage II — 21 percent
• stage III — 10 percent
• stage IV — 2 percent

KRAS mutations were more evenly distributed across stages:

• stage I– 36 percent
• stage II — 34 percent
• stage III — 35 percent
• stage IV — 40 percent

Patients with MSI were much less likely to die of cancer within five years of their diagnosis.  More than 9 out of ten (92 percent) were alive five years later compared to 6 of 10 (59 percent) of those who didn’t show MSI.

KRAS was the opposite story.  Mutations in KRAS led to poorer five year survival with 55 percent alive compared to 68 percent of patients with normal KRAS (wild-type).

The researchers noted that there was a group of stage I and II patients who had a particularly poor chance of living 5 years.  Those patients didn’t have MSI but did have KRAS mutations.

Garrett M. Nash from the Department of Surgery at Memorial Sloan Kettering and his colleagues concluded,

MSI and KRAS mutation provide fundamental genetic signatures influencing tumor behavior across patient subsets and stages of tumor development.

SOURCE: Nash et al., Annals of Surgical Oncology, published online October 8, 2009.