Immunotherapy for Cancer

The latest approval of a cancer drug by the US Food and Drug Administration (FDA) changes the paradigm of cancer treatment — the new indication specifies a genetic defect without any mention of tumor types. It allows the drug to be used in any cancer that harbors the specified genetic defect, wherever the tumor appears in the body.

What: Historically, the US Food and Drug Administration (FDA) has approved cancer treatments based on where in the body the cancer started — for example, prostate or breast cancers. For the first time, the FDA approved a drug based on a tumor’s biomarker without regard to the tumor’s original location.

Details: The new approval is for the immunotherapy pembrolizumab (Keytruda, Merck & Co), which is already approved for use in several different tumor types, including melanoma and lung cancer. But this latest approval covers the use of pembrolizumab in tumors that have microsatellite instability-high (MSI-H) or are mismatch repair deficient (dMMR). These defects are found most commonly in colorectal, endometrial, and gastrointestinal cancers but also less commonly appear in cancers arising in the breast, prostate, bladder, thyroid gland, and other places, the agency notes.

Microsatellite instability & immunotherapy: It’s not just colorectal cancer: The results from that trial showed that patients with colorectal cancer with normal DNA repair (microsatellite stable) had zero response to pembrolizumab, whereas those with MSI and deficient DNA repair had a 50% response rate, she said. In addition, about 20% had stable disease. This is much higher than has been seen with immunotherapy in other tumor types, where fewer than 20% patients respond. But the trial also included patients with any solid tumor and MSI, and these patients also showed the 50% response rate and 20% stable disease results.

Downsides: Common side effects of pembrolizumab include fatigue, itchiness, diarrhea, decreased appetite, rash, fever, cough, dyspnea, musculoskeletal pain, constipation, and nausea. The drugs can also cause serious immune-mediated side effects, including lung, liver, kidney, or colon inflammation, endocrine problems.

Action point: All patients with advanced cancer who have had at least one standard therapy should be tested to see if their tumor harbors these genetic defects.

I’m Dr. Michael Hunter.

http://www.medscape.com/viewarticle/880537

Should doctors prescribe exercise?

“Although the data vary by different cancer types, there is a consistent trend suggesting that moderate daily exercise has a beneficial effect on preventing certain cancers. If you are a reasonably healthy adult, your should exercise regularly.” 

Let’s look at the relationship of exercise and selected cancers. The American Society of Clinical Oncology (ASCO) has done a nice job of summarizing:

Breast Cancer

While the amount of risk reduction varies among studies (20-80%), most suggest that 30 to 60 minutes of moderate to high-intensity exercise per day lowers breast cancer risk. Women who are physically active throughout their life appear to benefit the most, but those who increase physical activity after menopause also fare better than inactive women.1

Colon Cancer

Research suggests that people who increase their physical activity can lower the chance of developing colon cancer by 30 to 40% relative to sedentary adults.1,2 A decrease in colon cancer risk can be achieved regardless of body mass index (BMI) and people who are most active benefit the most. There is insufficient evidence of a protective effect of physical activity on the risk of rectal cancer (a protective effect was seen in some case-control studies, but not in cohort studies).3

Endometrial, Lung and Ovarian Cancer

A handful of studies have suggested that women who are physically active have a 20-40% reduced risk of endometrial cancer compared to those who don’t exercise.1 Higher levels of physical activity seem to also protect against lung cancer (up to 20% reduction in risk), particularly among men.1Although less consistent, research suggests that physical activity possibly reduces the risk of ovarian and prostate cancer.

What about Other Cancers?

While observational data on the benefits of exercise for prevention of the types of cancers listed above are fairly consistent, evidence of the effects of exercise on prevention of any other type of cancer either is either insufficient or inconsistent.2,4

Prostate Cancer

Prostate cancer is one disease in which the data are not consistent, however prostate cancer is a heterogeneous disease and risk factor associations for total non-aggressive disease are different from aggressive / lethal disease. Most population based studies show similar findings, with little effect of exercise on overall incidence of prostate cancer but lower risk of aggressive prostate cancers for those with the highest levels of VIGOROUS activity (rather than any type of activity). In the Health Professionals Follow-up Study men 65 years or older who engaged in vigorous physical activity, such as running, jogging, biking, swimming or tennis at least three hours per week  had a 67% lower risk of advanced prostate cancer and 74% lower risk of fatal prostate cancer.5

Conflicting data for other malignancies

For example, one recent study found no association between physical activity and risk of developing gastric, rectal, pancreatic, bladder, testicular, kidney and hematological cancers.4 In contrast, a pooled analysis of data from prospective trials with 1.4 million participants found that physical activity was linked to lower risk of 13 cancers: esophageal, lung, kidney, gastric, endometrial, myeloid leukemia, myeloma, colon, head and neck, rectal, bladder, and breast.6Interestingly, leisure-time physical activity was associated with a higher risk of melanoma (presumably due to time spent outdoors) and prostate cancer, although it is not clear from these data whether that association was with nonaggressive or aggressive prostate cancer.

While we wait for confirmation and clarity on the role of exercise in preventing all the 200+ types of cancer – should doctors prescribe exercise? The answer is simple: yes, because evidence of the protective role of exercise is already strong for some of the most common cancers.

References

  1. Lee I, Oguma Y. Physical activity. In: Schottenfeld D, Fraumeni JF, editors. Cancer Epidemiology and Prevention. 3rd ed. New York: Oxford University Press, 2006.
  2. Slattery, ML. Physical activity and colorectal cancer. Sports Medicine 2004; 34(4): 239–252.
  3. Pham NM, et al. Physical activity and colorectal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 2012 Jan;42(1):2-13.
  4. Friedenreich CM, Neilson HK, Lynch BM. Eur J Cancer. State of the epidemiological evidence on physical activity and cancer prevention. 2010 Sep;46(14):2593-604.
  5. Giovannucci E, Liu Y, Leitzmann MF, et al. A prospective study of physical activity and incident and fatal prostate cancer. Arch Intern Med. 2005; 165(9):1005-1010.
  6. Moore SC, Lee IM, Weiderpass E, et al. Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults. JAMA Intern Med. 2016 Jun 1;176(6):816-25.
  7. http://www.asco.org/about-asco/press-center/asco-resources-media/cancer-perspectives/should-cancer-doctors-prescribe?et_cid=38723632&et_rid=463715101&linkid=Read+more

I’m Dr. Michael Hunter. Of course, the disclaimer: Do not begin an exercise program without input from an appropriate medical professional. Many can simply start with a brisk walk for 30 minutes daily, 5 days per week. Have a wonderful day!

Colorectal Cancer Disparities in USA: “We Should Be Embarrassed”

What You Need to Know: Lack of education, regardless of race or ethnicity, is the most important factor linked to disparities in mortality rates from colorectal cancer in the United States.

Background: It has long been known that there are disparities in mortality rates from colorectal cancer (CRC) between educated white and uneducated black populations in the United States. The study, led by Ahmedin Jemal, PhD, from the American Cancer Society in Atlanta, looked at the rate of death from CRC in people younger than 65 years (i.e., premature death) in each of the 50 states from 2008 to 2010. The researchers classified CRC patients 25 to 64 years of age by level of education (12 years or fewer, 13 to 15 years, and 16 years or more), race/ethnicity, and state.

Results:

They found there were significantly more premature CRC deaths in states with the lowest education levels than in those with higher levels. In fact, rates of premature death decreased with increased years of education, regardless of race or ethnicity.

  • In the white population, Delaware had the fewest premature CRC deaths, but even in that state, the rate was 15% higher in the least-educated than in the most-educated people (rate ratio [RR], 1.15; 95% confidence interval [CI], 0.66 – 2.01). New Mexico had the most premature CRC deaths; the rate was 3-fold higher in the least-educated than in the most educated people (RR, 3.18; 95% CI, 2.01 – 5.05).
  • In the black population, rate ratios ranged from 0.84 (95% CI, 0.54 – 1.30) in Mississippi to 2.41 (95% CI, 1.62 – 3.59) in Virginia. New York had the lowest death rate (12.9%) among those with the lowest level of education.
  • Blaise Polite, MD, MPP of the University of Chicago expressed this view in an editorial: “The major finding from this study…remains unaltered: If you are black or have low educational attainment, where you live in the United States determines how likely you are to die as a result of colorectal cancer. That is an experiment that has to end in the 21st-century United States.”

My Take: We should be embarrassed. Between 2008 and 2010, more than 23,000 deaths from colon cancer, 50% of the total, could have been prevented if all states had colon cancer equal to the five states with the lowest rates for the most educated whites. An equally important point is the variation among the states; 69% of deaths could have been prevented in Mississippi, compared with only 29% in Utah. While lifestyle factors no doubt contribute to disparities, access to colonoscopy is a key component to reducing your chance of dying from colorectal cancer.

An author of the study adds: “Screening is recommended for people 50 to 75 years. In those with 12 years or less of education, only 40% get screened, compared with 70% of those with a college-level education,” he explained. Even worse, “in the uninsured population, it is only 19%. That is ridiculously low, and highlights the importance of access to care.”

I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minuteable now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

References: 

 

Do Apples and Berry Fruits Reduce Colon Cancer Risk?

Background: Colon cancer arises due to the conversion of precancerous polyps (benign) found in the inner lining of the colon.

  • Prevention is better than cure, and this is very true with respect to colon cancer.
  • Various epidemiologic studies have linked colorectal cancer with food intake.
  • Apple and berry juices are widely consumed among various ethnicities because of their nutritious values.

My Take: This thorough literature review suggests that various phenolic phytochemicals present in these fruit juices have the potential to inhibit colon cancer cell lines. We need more research on the use of diet to reduce cancer risk. In the meantime, eat those fruits and vegetables! I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: World Journal of Gastroenterology, 12/26/2014  Review Article

Colon Cancer: Why Pattern of Spread is Predictable

liver_metastases_extensive

What You Need to Know: The genes that favor staggered colon cancer metastasis have been discovered by researchers. Of the colon cancer patients that develop metastases, 40% develop metastasis first to the liver and later to the lung, always in this clinical order of appearance. The study reveals that the metastatic lesion in the liver is necessary for later metastasis to lung to occur, the former thus becoming a platform from which the cells prepare the subsequent lung metastatic niche to be colonized.

Without a previous lesion in the liver there is no lesion in the lung: Of colon cancer patients that develop metastases, 40% present metastasis first to the liver and later to the lung, always in this clinical order of appearance. Although this staggered behavioral pattern was known, it was not understood at the molecular level.

So What’s New? This study reveals that the metastatic lesion in the liver is necessary for later metastasis to lung to occur, the former thus becoming a platform from which the cells prepare the subsequent lung metastatic niche to be colonized. The researchers observed that established metastatic cells in the liver release a molecule called PTHLH. This molecule affects the cells of pulmonary blood vessels, which respond to PTHLH by triggering remodelling processes. When a tumor cells escapes from the liver to travel towards the lung, it releases more PTHLH, thus further stimulating the process. This causes the previously impermeable blood vessel walls to form gaps, which the metastatic cell exploits to cross into and colonize the lung.

“Without the signal from the liver, the tumour cells could hardly enter the lung. With PTHLH, the cells that have colonized the liver are armed with a system that facilitate their activity at a distant site and they are able to prepare a niche in which to generate a new lung lesion. The tumour cells gain capacity to form PTHLH when the levels of p38 MAPKinase are decreased,” explains Roger Gomis.

Of note, most patients that develop metastasis to the liver do not do so to the lung, thanks to maintenance — among other factors — of appropriate p38 MAPKinase levels. The experiments have been validated in 284 clinical samples from patients with stage II and III colon tumours. These are the most relevant cases clinically because they are patients that have not developed metastases but could have acquired this capacity. The results have also been confirmed in cell lines and mouse models.

I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

References: Jelena Urosevic, Xabier Garcia-Albéniz, Evarist Planet, Sebastián Real, María Virtudes Céspedes, Marc Guiu, Esther Fernandez, Anna Bellmunt, Sylwia Gawrzak, Milica Pavlovic, Ramon Mangues, Ignacio Dolado, Francisco M. Barriga, Cristina Nadal, Nancy Kemeny, Eduard Batlle, Angel R. Nebreda, Roger R. Gomis. Colon cancer cells colonize the lung from established liver metastases through p38 MAPK signalling and PTHLH. Nature Cell Biology, 2014; DOI: 10.1038/ncb2977; Institute for Research in Biomedicine-IRB. “Why colon cancer metastasis always follows the same invasive pattern.” ScienceDaily. ScienceDaily, 2 June 2014. <www.sciencedaily.com/releases/2014/06/140602101407.htm>.

 

 

 

Is a Home-Based Stool Test In Your Future?

colon rectum bowel GI gastrointestinal gut

The fecal immunochemical test (FIT), a simple at-home stool test that requires no change in diet to complete, can accurately detect 79% of colorectal cancers (CRCs). In addition, 2 of the most well-studied FIT brands are highly sensitive and specific, according to a meta-analysis of 19 studies.

Background: CRC is the second leading cause of cancer-related deaths in the United States, after lung cancer, according to the Centers for Disease Control and Prevention (CDC). Although screening is helpful in preventing cancer, the other at-home test, the fecal occult blood test, only detects 13% to 50% of cancers with a single round of screening, according to Dr. Lee and coauthors. Colonoscopy resources also are limited in some locations, the researchers note. The CDC reports that 1 in 3 adults aged 50 to 75 years (or more than 20 million people) have not been tested for colorectal cancer as recommended by the US Preventive Services Task Force (USPSTF). A growing number of medical professional societies are advocating for the use of FIT, but precise estimates of the sensitivity of the testing are lacking.

The Study: The authors reviewed the evidence to gauge how accurate FIT is in diagnosing CRC. They conducted a full-text review of 53 studies, including 9 studies examined by the USPSTF in 2008. Of those, they included 19 articles in their analysis. The studies had sample sizes ranging from 80 to 27,860 and examined 8 different FIT brands. Twelve of the studies used colonoscopy regardless of FIT results, and 7 studies used colonoscopy only in patients with positive FIT results.

Results: FIT “detects 4 in 5 cancers with just a single testing and points to 94% of people who don’t have cancer,” Elizabeth G. Liles, MD, MCR, a researcher at Kaiser Permanente’s Center for Health Research in Portland, Oregon, told Medscape Medical News. FIT remains “a viable option for screening. It has great potential for being accurate. We already know it’s a really convenient way to screen and could be accessible to a lot of people.”

It remains unclear whether FIT should be the CRC screening test of first resort, with colonoscopy reserved for patients with positive FIT results. “You would need to directly compare those 2 tests. The studies we looked at didn’t ask that question,” Dr. Liles said. Two ongoing randomized controlled trials (one [Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM)] being conducted in the United States and the other in Spain) should answer that question within 3 to 5 years, she says. Both trials compare colonoscopy with FIT effectiveness for screening; each is enrolling about 50,000 participants.

Two of the brands included in the current meta-analysis, OC-Micro/Sensor (Eiken Chemical) and OC-Light (Polymedco), had several studies that could be pooled and that demonstrated similar sensitivity and specificity (93% and 91% for OC-Light and 86% and 91% for OC-Micro/Sensor, respectively).

Although patients are more likely to complete FIT because of ease of use, it is unlikely to pare healthcare spending. Kaiser, for instance, uses automatic reminder calls with FIT tests, sends letters (which results in postage and additional costs), and engages support staff to contact patients directly, Dr. Liles said.

I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad:  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: Lee JK, et al. Annals of Internal Medicine 2014; 160 (3).

Rectal Cancer: Is Local Excision Inferior?

rectum

The gold standard of care for most Stage I rectal cancers is known as a total mesorectal excision. Local excision is considered an alternative management approach only for highly selected patients (stage T1, N0, M0 tumors that are less than 3cm in size, are not high grade/poorly-differentiated/G3, and have no lymphvascular or perineural invasion).

Local Excision On the Rise: “The use of local excision alone for higher-risk stage I rectal cancers is an inferior cancer management approach, but despite this, we are seeing a rise in the use of local excision,” reports karyn B. Stitzenberg, MD, MPH of the University of North Carolina (USA). A US National Cancer Data Base (NCDB) study found a steady increase in the use of local excision from 1989 to 2003 (Ann Surg 2007;245:726-733). This trend continues as evidenced by a recent study by Dr. Stitzenberg published in Journal of Clinical Oncology on 01 December 2013. These data show that guideline-based adoption of local excision for appropriate patients with Stage I rectal cancer is increasing. However, the use of local excision (as opposed to more extensive surgery) is increasing for higher risk cancers that do not meet guideline criteria for its use.

My Take: Local excision is appropriate only if you meet strict criteria for it. Otherwise a more extensive mesorectal excision by a qualified surgeon offers the best results for the vast majority of patients. Local excision reduces the risk of complications, stomas, and can be associated with a better quality of life (as compared to more radical surgery), but should not be used inappropriately: Salvage surgery after local relapse is suboptimal, and recurrences are often more advanced than the original presentation. Local recurrences following local only excisions are on the order of over 25% for T1 lesions, and roughly 25-46% for T2 tumors. I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad:  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: J Clin Oncol 2013;31P4273-4275.