treatments

Can your own immune system kill cancer?

Source: www.cnn.com
Author: Jacqueline Howard

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There was another big win in the advancement of immunotherapy treatments for cancer this week.

The Food and Drug Administration approved an immunotherapy drug called Keytruda, which stimulates the body’s immune system, for the first-line treatment of patients with metastatic non-small-cell lung cancer.

In other words, the drug could be the very first treatment a patient receives for the disease, instead of chemotherapy. Keytruda is the only immunotherapy drug approved for first-line treatment for these patients.

So it seems, the future of cancer care may be in our own immune systems, but how exactly does it work, and what are its pros and cons?

“It’s certainly going to become an independent way of treating cancers,” said Dr. Philip Greenberg, head of immunology at the Fred Hutchinson Cancer Research Center in Seattle, during a Q&A session at the International Cancer Immunotherapy Conference in New York in September.

“We always talk about the three pillars of cancer therapy — radiation therapy, chemotherapy and surgery — and it’s become quite clear now that there’s going to be a fourth pillar, which is immunotherapy,” he said. “There are times where it will be used alone, and there will be times that it will be used in conjunction with the other therapies, but there’s very little to question that this is going to be a major part of the way cancers are treated from now on, going forward.”

Here’s a look at the past, present and future of cancer immunotherapy.

It began with Bessie

In the summer of 1890, 17-year-old Elizabeth Dashiell, affectionately called “Bessie,” caught her hand between two seats on a passenger train and later noticed a painful lump in the area that got caught, according to the Cancer Research Institute.

She met with a 28-year-old physician named Dr. William Coley in New York to address the injury. He performed a biopsy, expecting to find pus in the lump, probably from an infection. But what he found was more disturbing: a small gray mass on the bone. It was a malignant tumor from a type of cancer called sarcoma.

Dashiell had her arm amputated to treat the cancer, but the disease quickly spread to the rest of her body. She died in January 1891. A devastated Coley went on to devote his medical career to cancer research.

Coley is sometimes referred to as the “father of cancer immunotherapy,” according to the Memorial Sloan Kettering Cancer Center.

During his career, he noticed that infections in cancer patients were sometimes associated with the disease regressing. The surprising discovery prompted him to speculate that intentionally producing an infection in a patient could help treat cancer.

To test the idea, Coley created a mixture of bacteria and used that cocktail to create infections in cancer patients in 1893. The bacteria would sometimes spur a patient’s immune system to attack not only the infection but also anything else in the body that appeared “foreign,” including a tumor. In one case, when Coley injected streptococcal bacteria into a cancer patient to cause erysipelas, a bacterial infection in the skin, the patient’s tumor vanished — presumably because it was attacked by the immune system.

Coley’s idea was occasionally studied by various researchers in the 1900s but was not widely accepted as a cancer treatment approach until more recently.

“Immunotherapy has essentially undergone a sort of revolution in the last decade in the sense that something that was experimental — and there were still questions about what role it would have in the way cancer is treated — is completely turned around, and now it’s clear it’s effective,” Greenberg said.

German physician Dr. Paul Ehrlich, who won the Nobel Prize in physiology or medicine in 1908, proposed using the immune system to suppress tumor formation in the “immune surveillance” hypothesis — an idea that seems to follow Coley’s.

Yet it wasn’t until the early 2000s that the hypothesis became more widely accepted, according to the Cancer Research Institute. A landmark review published in the journal Nature Immunology in 2002 supported the validity of cancer immunosurveillance.

“Cancer immunotherapy really refers to treatments that use your own immune system to recognize, control and hopefully ultimately cure cancers,” said Jill O’Donnell-Tormey, CEO of the Cancer Research Institute, during the conference in New York last month.

“Many people for many years didn’t think the immune system was really going to have a role in any treatment for cancer,” she said, “but I think the entire medical community (and) oncologists now agree that immunotherapy’s here to stay.”

‘Turning oncology on its head’

One of the most famous cancer patients to have received a form of immunotherapy is former President Jimmy Carter, who had a deadly form of skin cancer called melanoma. Last year, he announced that he was cancer-free after undergoing a combination of surgery, radiation and immunotherapy.

Carter was taking Keytruda. It’s approved to treat melanoma, non-small-cell lung cancer, and head and neck cancer. However, it’s not the only approved immunotherapy option out there.

“The advances and the results we’ve seen with using the immune system to treat cancer in the last five years or so are turning the practice of oncology on its head,” said Dr. Crystal Mackall, a professor at the Stanford University School of Medicine and expert on cancer immunotherapy.

You don’t want to overstate it. As an immunotherapist, I see things from my vantage point, which is biased, but my clinical colleagues use words like ‘revolution,’ ” she said. “When I hear them say that, I think, ‘Wow, this really is a paradigm shifting for how we think about treating cancer.’ ”

Immunotherapy comes in many forms — treatment vaccines, antibody therapies and drugs — and can be received through an injection, a pill or capsule, a topical ointment or cream, or a catheter.

The FDA approved the first treatment vaccine for cancer, called sipuleucel-T or Provenge, in 2010. It stimulates an immune system response to prostate cancer cells and was found in clinical trials to increase the survival of men with a certain type of prostate cancer by about four months.

Another treatment vaccine, called T-VEC or Imlygic, was approved by the FDA in 2015 to treat some patients with metastatic melanoma.

Some antibody therapies have been approved, as well. Antibodies, a blood protein, play a key role in the immune system and can be produced in a lab to help the immune system attack cancer cells.

The FDA has approved several antibody-drug conjugates, including Kadcyla for the treatment of some breast cancers, Adcetris for Hodgkin lymphoma and a type of non-Hodgkin T-cell lymphoma, and Zevalin for a type of non-Hodgkin B-cell lymphoma.

The FDA also has approved some immunotherapy drugs known as immune checkpoint inhibitors. They block some of the harm that cancer cells can cause to weaken the immune system.

Keytruda, which Carter took, is a checkpoint inhibitor drug. Other such drugs include Opdivo to treat Hodgkin lymphoma, advanced melanoma, a form of kidney cancer and advanced lung cancer. Tecentriq is used to treat bladder cancer, and Yervoy is used for late-stage melanoma.

Additionally, there are many immunotherapy treatments in clinical trials, such as CAR T-cell therapy. The cutting-edge therapy involves removing T-cells from a patient’s immune system, engineering those cells in a lab to target specific cancer cells and then infusing the engineered cells back into the patient. The treatment is being tested to treat leukemia and lymphoma.

“The real excitement now in cellular therapy, in T-cell therapies, is it reflects the developments in an area that we call synthetic biology, which is that you can add genes to cells and you can change what they do, how they behave, how they function, what they recognize,” Greenberg said.

The high price of new immunotherapy drugs has also garnered attention in the field, according to the Fred Hutchinson Cancer Research Center. For instance, some estimates suggest that checkpoint inhibitor treatments could cost as much as $1 million per patient.

As approvals continue, many scientists caution that doctors and patients alike should prepare for potential severe side effects and downsides.

Boosting the immune system with such therapies may cause skin reactions, flu-like symptoms, heart palpitations, diarrhea and a risk of infection. New cancer immunotherapy drugs have even been linked to arthritis in some patients.

A clinical trial conducted by Juno Therapeutics to test the effectiveness of an experimental immunotherapy treatment for lymphoblastic leukemia was halted after three patients died. They suffered cerebral edema or brain swelling.

Greenberg is a scientific co-founder of Juno Therapeutics.

However, “one of the best attributes of immunotherapy and the future of medicine is that it’s very precise in the way that it kills tissue and spares normal tissue, so in some way, immunotherapy is less toxic (than other therapies). There are patients who are treated with checkpoint inhibitors who have essentially no side effects,” Mackall said. “That would never happen with chemotherapy. They would always have side effects.

“Still, you know, the fact remains that probably nothing is perfect, and there are likely to be some side effects, but as far as we know now, they are less likely to be as severe or prevalent.”

As immunotherapy continues to develop as an option for cancer treatment, experts plan to be realistic about forthcoming challenges.

The challenges of immunotherapy

Experts say they hope to better understand why some patients may have different responses to immunotherapy treatments than others — and why some treatments may result in remissions instead of relapses, or vice versa.

“There’s this whole problem of, you give people an immunotherapy, it looks like it’s working, and then it stops working. We get recurrences or progression after some period, and the question is, why did that happen? How can you change it?” Greenberg said.

“This is where the science has come to play an important part: Is it because the immune response was working and somehow the tumor turned it off? And if that’s the case, then we have to look at ways in which we can reactivate the immune system,” he said. “Or is it not that, is it just that the immune system did what it’s supposed to do, but now a variant grew out, now a tumor grew out that’s no longer recognized by the immune response you are enforcing? If that’s the case, then we need ways to build subsequent immune responses to tackle that.”

Therefore, researchers have to better understand the behavior of not only the immune system but also cancerous tumors — and it’s no simple task.

“If there’s a perception that it’s easy, that’s a mistake. I think our lab has spent decades trying to figure out how to manipulate the immune response,” Greenberg said.

“Some patients are anticipating things to change overnight and be immediately available as a therapy. It takes quite a while,” he said, “but I’m quite certain immunotherapy is going to be enormously useful. It’s just, right now, we are limited in what can be done.”

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy

October, 2016|Oral Cancer News|

Cancer patients rarely request unnecessary testing

Source: www.cancernetwork.com
Author: Anna Azvolinsky, PhD

A new study suggests that cancer patients tend not to request unnecessary and sometimes costly tests or treatments. Of the 5,050 interactions between a clinician and patient analyzed, only 1% resulted in a patient request for a clinically unnecessary or inappropriate test or therapy. Clinicians complied with only 7 of 50 requests (14%).

The study goes against a common assumption that the high cost of healthcare in the United States is partly due to extra or unnecessary treatments and analyses done as a result of patients’ requests.

The results of the study were published in JAMA Oncology.

Researcher Ezekiel J. Emanuel, MD, PhD, of the department of medical ethics and health policy at the Perelman School of Medicine of the University of Pennsylvania, and colleagues analyzed a total of 5,050 outpatient interactions among 60 clinicians and 3,624 patients that occurred between October 2013 and June 2014 at three Philadelphia-area hospitals. The 60 clinicians—34 oncologists, 11 oncology fellows, and 15 nurse practitioners and physician assistants—were interviewed by trained research assistants on each patient-clinician encounter.

“We decided to look specifically at cancer patients’ demands because oncology is a setting where there are life-and-death stakes for patients and the drugs and tests can get very expensive,” said Emanuel in a statement. “However, we found, contrary to expectations, that patient demands are low and cannot be a key driver of increasing healthcare costs.”

Most of the patients in the study were women (58.7%), and of the 5,050 encounters, 57.5% were between a clinician and a female patient. More than 50% of patients were between 55 and 74 years of age; 69.4% were white. More than half of the patients had private insurance (56.3%), while 40.6% had Medicare. The most common cancer types diagnosed among the patients were hematologic malignancies (25.9%). The next most common cancer type was gastrointestinal cancer.

Of the 5,050 encounters, 8.7% (440) included a request for treatment, test, or imaging by the patient. Clinicians complied with 83% (365) of these requests. Of the 440 requests, clinicians considered 11.4% of them to be inappropriate or unnecessary.

“At least in oncology, ‘demanding patients’ seem infrequent and may not account for a significant proportion of costs,” concluded the authors.

Of the 440 demands, 49.1% were requests for imaging, 15.5% were for palliative treatments, and 13.6% were for laboratory testing. A lung or head and neck cancer diagnosis, a fair- or poor-quality patient-clinician relationship, and active treatment by the patient were all factors associated with patient requests (all P < .01).

The United States spent $3 trillion on healthcare in 2014; at least one prior analysis of physicians’ sentiments showed that they believe that the availability of information on the Internet and patient-directed marketing stimulate patients to request novel and expensive tests and therapies. Still, there is a dearth of data on whether these physician claims are substantiated—both the frequency of such requests and whether or how often clinicians catered to them.

“We observed very few patient demands for inappropriate treatments, and it was even rarer that a physician complied with the demand,” said study author Keerthi Gogineni, MD, MSHP, of Winship Cancer Institute of Emory University in Atlanta, in a statement. “In this age of unregulated consumer medical information on the Internet, it’s encouraging to see that this hasn’t translated to cancer patients requesting inappropriate—and often costly—tests and treatments.”

Whether the results can be generalized to inpatient interactions, other US geographies, and other practices outside of oncology is not clear. Most of the patients had private insurance; therefore, other studies should analyze whether the results are applicable to a larger Medicare and less affluent population.

In an accompanying editorial, Anthony L. Back, MD, of the Seattle Cancer Care Alliance and Fred Hutchinson Cancer Research Center at the University of Washington in Seattle, acknowledged what he called the “myth of the demanding patient.”

“The real point of the study, however, is this: we have to stop blaming patients for being demanding. In reality, it is hardly happening. The myth of the demanding patient is more about our own responses and how lackluster communication skills can contribute to difficult situations that stick in our throats and our memories. And when we have calmed down enough to look up, we see that what is really happening between patients and physicians these days is something quite different,” wrote Back. “It is possible that what the study by Gogineni et al documents is a point in the evolution of the patient-physician relationship when both sides recognize that the complexity of cancer care belies a simple fix. Perhaps this ‘negative’ study is pointing to an important truth: that we need to redirect our attention from the myths that are distracting us.”

February, 2015|Oral Cancer News|

Researchers discover genetic fingerprint of HPV virus in some head and neck cancers

Author: Staff
Source: cancerreasearchuk.org

A large US study(link is external) has pinpointed genetic errors that mark out head and neck cancers caused by the human papillomavirus (HPV).

If confirmed in further studies this could be used to develop potential new treatments.

Head and neck cancers include tumours of the throat, mouth, nasal cavity, larynx, salivary gland among other tissues and organs.

Some are linked to tobacco or alcohol use, while others are caused by infection with HPV, more commonly associated with no deposit casino bonuses cervical cancers.

Rates of HPV-linked head and neck cancers are on the increase.

The US study, published in the journal Nature, was carried out as part of The Cancer Genome Atla (TCGA) project.

Using cutting-edge DNA analysis, the team found several similarities between the DNA from head and neck tumour cells and other cancer types – as well as new subtypes of smoking-related head and neck cancer.

The US team studied samples from 279 head and neck squamous cell carcinomas (HNSCC) from untreated patients, around eight in 10 of whom were smokers. Most of the samples were oral cavity cancers and larynx cancers (61 per cent and 26 per cent respectively).

The researchers found that specific alterations in genes called FGFR3 and PIK3CA – which produce important protein molecules that help cells grow – were common in many patients with HPV-related cancers.

These genes are also present in a wider set of faults found in smoking-related tumours.

But faults in the epidermal growth factor receptor (EGFR) gene, which produces another important growth molecule, were rare among HPV-positive cancers, despite being frequently altered in HPV-negative tumours.

Similarities between the DNA of head and neck tumours cells and other cancers – including squamous cell lung cancer, and cervical cancer – were also found, suggesting there may be common paths of cancer development – and potentially treatment.

Calling the study “important”, Professor Nick Coleman – a Cancer Research UK expert in HPV and cancer – went on to say: “It greatly improves our understanding of the biology of head and neck cancer, pinpointing crucial genetic differences between those tumours caused by HPV infection, and others linked with risk factors like smoking.

“HPV-linked head and neck cancers are becoming more common, and this study suggests that the virus may trigger a small number of genetic faults that are causing the disease. This opens up important new avenues of research, with the possibility of developing treatments targeted to these faults to help tackle head and neck cancer in the future.”

Director of the National Human Genome Research Institute in the US, Dr Eric Green, said that the new findings “help establish a genomic map of various head and neck cancers, provide new insights into other similar cancers and may further our understanding of how viruses can impact disease.”

For more information: http://www.nih.gov/news/health/jan2015/nhgri-28.htm

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
January, 2015|Oral Cancer News|

HPV and on HPV oral cancers need to be treated differently to reduce toxicity and improve out comes in each type

The National Cancer Institute

In a large randomized European clinical trial, accelerated radiation therapy for locally advanced, inoperable head and neck cancer—given either with or without chemotherapy—did not prolong the time to disease progression compared with standard radiation therapy plus concurrent chemotherapy, which has been the standard of care in Europe and the United States. Results from the study were published online January 18 in Lancet Oncology.

Another trial published in 2010, by the U.S. Radiation Therapy Oncology Group (RTOG), showed similar results, but the two research teams have drawn different conclusions, which will affect ongoing clinical trials and, potentially, future research collaborations.

The researchers, from the European Groupe d’Oncologie Radiothérapie Tête et Cou (GORTEC), compared two experimental regimens with standard chemoradiotherapy in the trial, called GORTEC 99-02. All participating patients had stage III or stage IV head and neck squamous-cell carcinoma that had not metastasized but that could not be removed surgically.

The 244 patients in the conventional chemoradiotherapy arm received three cycles of chemotherapy with the drugs carboplatin and fluorouracil plus 70 Gy of radiation given over the standard 7 weeks.

In one experimental arm, 245 patients received “accelerated chemoradiotherapy,” which consisted of two cycles of the same chemotherapy drugs plus radiation therapy accelerated by 1 week. In the second experimental arm, 242 patients received only “very accelerated” radiation therapy, which consisted of a total dose of 64.8 Gy given over 3.5 weeks.

The GORTEC trial results are somewhat difficult to interpret because the trial “didn’t change just one variable, it changed two—in addition to the radiation regimen, it also changed the chemotherapy,” explained Dr. Bhadrasain Vikram, chief of the Clinical Radiation Oncology Branch of the Radiation Research Program in NCI’s Division of Cancer Treatment and Diagnosis.

Same Results, Divergent Conclusions

Because patients in the accelerated chemoradiotherapy group received two, rather than three, cycles of chemotherapy (although those two cycles were longer in duration), they received 17 percent less chemotherapy overall than patients in the conventional chemoradiotherapy group.

The RTOG trial that showed similar results (RTOG-0129) also reduced the amount of chemotherapy given, and not just because of fears of toxicity, explained Dr. Maura Gillison, RTOG investigator and professor of medicine at the James Comprehensive Cancer Center at Ohio State University.

All of the studies have shown that it’s critical to give the chemotherapy with the radiation – Dr. Gillison

“All of the studies have shown that it’s critical to give the chemotherapy with the radiation,” she stressed. Chemotherapy given alone does not have as potent an antitumor effect in head and neck cancer, and in the accelerated chemoradiotherapy arms of the two trials, shortening the duration of radiation therapy did not leave enough time for a third cycle of chemotherapy.

Because only about 60 percent of patients with advanced head and neck cancer are healthy enough to complete the third cycle of chemotherapy with conventional chemoradiotherapy, and because the patients in RTOG-0129 who received conventional and accelerated chemoradiotherapy survived for a similar length of time, “we thought that to some extent our results are an advance,” Dr. Gillison said. “You can shorten the treatment to 6 weeks instead of 7, and shortening the treatment means you don’t have to give that third cycle of chemotherapy, with all its associated toxicities.”

While the GORTEC investigators did not see a benefit from accelerated chemoradiotherapy, the RTOG investigators have chosen to use an accelerated chemoradiotherapy regimen as the standard of care in their trials of advanced head and neck cancer.

This decision for trials in the United States was also influenced by changes in modern radiation therapy technology, explained Dr. K. Kian Ang, professor of radiation oncology at the University of Texas M. D. Anderson Cancer Center and former chair of RTOG’s Head and Neck Committee. The more widespread availability of intensity modulated radiation therapy (IMRT) has allowed radiation oncologists to reduce the number of visits required for irradiation even further than in the RTOG-0129 trial, which makes it more practical for patients to complete therapy, added Dr. Ang.

HPV Status Makes a Difference

The recent understanding of the importance of human papilloma virus (HPV) as a cause of oropharyngeal cancer also limits the application of the GORTEC results to current practice, added Dr. Vikram. That trial began “before the huge importance of HPV status [in head and neck cancer] was recognized. One would expect about 40 to 50 percent of the tumors in this trial to have been HPV-positive, but the paper unfortunately has no information on that, so we have no idea from this trial if one of the regimens tested might work better for subsets of patients with HPV-positive or HPV-negative tumors,” he explained.

The recent understanding of the importance of HPV as a cause of oropharyngeal cancer also limits the application of the GORTEC results to current practice.

Dividing patients into those whose tumors are HPV-positive versus HPV-negative will be increasingly important in future trials for head and neck cancer, as the rate of oral HPV infection continues to rise. In the RTOG-0129 trial, people whose oropharyngeal tumors contain the HPV virus were found to respond much better to treatment than patients with HPV-negative tumors.

“After so many years, we’ve really started to understand that, although [HPV-positive and HPV-negative tumors] are located in the same small anatomical region, we are dealing with different types of cancers,” said Dr. Ang. “Because HPV-positive patients do relatively well on current treatments, one of our main goals now is to reduce toxicity. And for HPV-negative patients, because they do so badly with what we have now, we want to know how we can intensify treatment in order to improve outcomes.

“With these completely different objectives, we don’t think we can put [these two groups] in the same protocol—we need to do separate trials,” he continued. RTOG recently launched its first trial for HPV-positive patients only (RTOG-1016), to see if using the targeted drug cetuximab instead of cisplatin can reduce the side effects of treatment while controlling tumors.

A big challenge, added Dr. Ang, is that “head and neck cancer is relatively rare, and now we’re dividing it into smaller and smaller subsets. International trials will be a necessity to enroll enough patients.”

And along with the normal challenges of cross-border funding, quality control, and tumor sample transportation, what should actually be tested will also have to be agreed upon. “Investigators will need to agree on what are the best scientific questions to ask,” concluded Dr. Ang.

This article was sourced by the Oral Cancer Foundation, and vetted for accuracy and appropriateness

February, 2012|Oral Cancer News|

George Karl takes cancer message to fundraiser in Spokane

Source: www.nba.com
Author: Aaron J. Lopez, Nuggets.com

Nuggets coach George Karl will be the first person to admit that his fashion sense is more faux pas than je ne sais quoi.

He prefers shorts and golf shirts over dress shoes and designer ties, and he often jokes that his clothing choice for the day is determined by what’s on top of the hamper.

When it comes to assisting in the fight against cancer, Karl will meet even the strictest of dress codes.

Karl, who has survived head and neck cancer and prostate cancer in the past six years, will don a tuxedo this weekend when he serves as the guest speaker at a Coaches vs. Cancer fundraiser in Spokane, Wash. It is the 10th year of the event founded by Gonzaga men’s basketball coach Mark Few and his wife Marcy.

“I enjoy speaking about cancer,” Karl said. “It’s become my hobby/ambassadorship, whatever word you want to use. I play amateur sociologist and try to help people become more aware about what is going on.”

Karl, 60, has become extremely educated about cancer treatments, research and funding options since recovering from his latest battle over the past 20 months. He is a spokesman for the Cancer Care Initiative at Swedish Medical Center in Englewood and St. Jude Research Hospital in Memphis, Tenn. He also is active with the Cancer League of Colorado and the American Cancer Society.

“With all the information and knowledge we have our hands on now, it seems like we spend it in frivolous areas more than real areas,” Karl said. “I’m sure people find good information but sometimes we need a navigator for our information.”

Since its inception in 2002, the Fews have helped raise more than $4.7 million for the American Cancer Society and Washington-area cancer organizations. Their event is the largest Coaches vs. Cancer fundraiser in the country. More than $675,000 has been donated to Camp Goodtimes, a camp held annually for children with cancer.

“It is a huge honor to have coach Karl attend and speak at our event in Spokane,” Mark Few said. “I have always admired him as a coach. He is tenacious, passionate and obviously a tremendous teacher of the game.

“When he spoke out about his fight against cancer, I admired him that much more. What a great example to my wife and I to continue what we are doing and be a voice for those who need our help to raise money to defeat this disease. For coach Karl to take time out of his busy schedule to help us out is huge. It makes our 10th annual event that much more special.”

Karl will participate in a charity golf tournament Saturday and then deliver the keynote speech at a gala later that night. University of Colorado men’s basketball coach Tad Boyle is one of several college coaches scheduled to attend.

“I always enjoy the adventure of being with a lot of college coaches,” Karl said. “It will be an arena of basketball, but it won’t be my arena. We get into heated discussions on the game. I believe we coach different games.”

Karl and Boyle talked hoops recently during a round of golf at Boulder Country Club. Karl and his coaching staff are planning a clinic with Colorado and Wyoming college coaches sometime next month.

August, 2011|Oral Cancer News|