Cancer-Preventing Vaccines Given To Less Than Half Of US Kids

Author: Carrie Feibel

U.S. regulators approved a vaccine to protect against the human papilloma virus (HPV) in 2006, but cancer experts say misconceptions and stigma continue to hamper acceptance by both doctors and parents.

Eighty percent of Americans are exposed to the human papilloma virus in their lifetimes. Some strains of HPV can cause genital warts, but most people experience no symptoms and clear the virus from their systems within a year or two. But for an unlucky minority, the virus causes damage that, years later, leads to cervical cancer, throat cancer, and other types.

Researchers at MD Anderson are frustrated that ten years after the first vaccine arrived on the market, only 42 percent of U.S. girls, and 28 percent of boys, are getting the three-shot series.

The series can be given to girls and boys between the ages of 9 and 26, but the immune response is strongest at younger ages, before sexual activity begins.

n 2007, then-Texas governor Rick Perry proposed making the HPV vaccine mandatory for all preteen girls.  At the time, the vaccine was only approved and marketed for girls.

Dr. Lois Ramondetta, a cervical cancer specialist at MD Anderson, remembers the outcry.

“A lot of people felt that was the right idea, but the wrong way to go about it. Nobody really likes being told what to do, especially in Texas,” Ramondetta said. “I think there was a lot of backlash.”

Eventually, the legislature rejected Perry’s plan, even though it included an opt-out provision. Ramondetta said too many politicians focused on the fact that HPV is sexually transmitted. That had the unfortunate effect of skewing the conversation away from health care and into debates about morality and sexuality. She said the best and most accurate way to discuss the vaccine is to describe it as something that can prevent illness and death.

“I try to remove the whole concept of sexuality,” Ramondetta said. “When you’re talking about an infection that infects 80 percent of people, you’re really talking about something that is part of the human condition. Kind of like, it’s important to wash your hands because staph and strep are on all of us.”

Today, only Virginia, Rhode Island and Washington, D.C. mandate HPV vaccines.

“Our vaccination rates are really terrible right now,” Ramondetta said.

In Texas, only 41 percent of girls get all three of the required shots, and only 24 percent of boys.


Kara Million of League City finds those numbers upsetting.  Million survived two rounds of treatment for cervical cancer.

“Even if you had a chance that your kid could have any kind of cancer, and you could have given them two shots or three shots for it? To me, it’s a no-brainer,” Million said.

Million always got regular Pap tests. But she missed one appointment during a busy time following the birth of her second child. When she went back, it had been only 15 months since her last Pap test. But the doctor found cervical cancer, and it had already progressed to stage 3.

“That was a huge surprise,” Million recalled.

Million had chemotherapy and radiation at MD Anderson. But a year later the cancer returned.

The next step was surgery, a radical procedure called a total pelvic exenteration.

Million and her husband looked it up online.

“When I was reading it, I was just, like, ‘this is so barbaric, there is no way they are still doing this in this day and age,’” Million said. “‘For certain, in 2010 we have better surgeries to do than this.’”

But there weren’t better surgeries. This was her only option.

“I had a total hysterectomy; they pulled all the reproductive system out,” she explained. “They take your bladder out, they take part of your rectum, they take part of your colon, they take your vagina, all of that in your pelvic area comes out.”

The surgery took 13 hours, and left her with a permanent colostomy bag and urostomy bag.

“At that point, with two kids at that age – I think they were one-and-a-half and three – there’s no option. I’m a mom, so I’m going to do whatever it takes so they can have their mom.”

Most women survive cervical cancer if it’s caught early enough. But Million’s cancer was diagnosed at a later stage, where only a third of women make it past five years. She has already made it past that five-year anniversary, and she’s not wasting any time.

She now volunteers as a peer counselor at MD Anderson to other cervical cancer patients, and she urges parents to vaccinate their kids.

“If most of cervical cancer is caused by HPV, and now we have something that can help prevent what I went through, and what my friends went through, and the friends that I lost?” Million says, “I don’t understand why people don’t line up at the door to get their kids vaccinated for it.”

But Dr. Ramondetta said parents can’t consent to the vaccination if pediatricians or family doctors don’t offer it. And they’re not offering it nearly enough, she said.

Some doctors don’t know how to broach the topic, fearing it will lead to a difficult conversation about sexual behavior. Some mistakenly think boys don’t need it, although they do – not only to protect their partners from HPV, but to protect themselves against oropharyngeal and anal cancers, which are also caused by HPV.  Ramondetta added that some doctors incorrectly assume that giving the vaccine will promote promiscuity.

Ramondetta says extensive research actually shows it doesn’t.

“There should be this understanding of an ethical responsibility. That this is part of cancer screening and prevention, just like recommending mammograms and colonoscopies.”

In Texas, only 41 percent of girls get all three of the required shots, and only 24 percent of boys.

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

September, 2016|Oral Cancer News|

Expert Asserts Pembrolizumab to Play Important Role in Head and Neck Cancer Treatment

Author: Laura Panjwani


The FDA approval of pembrolizumab (Keytruda) as a treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in August 2016 was extremely significant for this patient population, which previously had limited options following progression on a platinum-based chemotherapy.

The approval was based on the phase Ib KEYNOTE-012 study, which demonstrated that pembrolizumab had an overall response rate (ORR) of 18% and a stable disease rate of 17% in patients with recurrent/metastatic HNSCC.

Several other studies are further evaluating the immunotherapy agent in HNSCC.Preliminary results of the phase II KEYNOTE-055 study—which included 92 evaluable patients who received pembrolizumab after failing platinum and cetuximab therapies—were presented at the 2016 ASCO Annual Meeting.

In an interview with Targeted Oncology, lead study author Joshua M. Bauml, MD, an assistant professor of Medicine, Hospital of the University of Pennsylvania and the Veteran’s Administration Medical Center, discusses the impact of pembrolizumab’s success in HNSCC, the results of the KEYNOTE-055 study, and what he sees on the horizon for the PD-1 inhibitor in this field.

TARGETED ONCOLOGY: What role do you envision pembrolizumab having in this patient population?

Baumi: It is going to play a critical role in head and neck cancer. The other agents that are available have limited efficacy, and are associated with significant toxicities. This is a clear improvement for our patient population with limited options.

TARGETED ONCOLOGY: What were the key takeaways from KEYNOTE-055? Baumi: Patients with recurrent/metastatic head and neck cancer that is refractory to both platinum-based therapy and cetuximab (Erbitux) really have very few options. The historical reference population we usually use is patients treated with methotrexate, which has a response rate of 5% and an overall survival (OS) of only about 6 months. There is a really great need for this. For pembrolizumab, which is an anti–PD-L1 agent, there is biologic rationale to think that it would be active in this patient population. PD-L1 and PD-L2 are unregulated in head and neck cancer.

What KEYNOTE-055 did is really try and create a homogenous patient population. Rather than a large phase I study, here are patients all who have failed both platinum-based therapy and cetuximab. We have really identified the sickest patient population.

What we are able to show in this study was that the drug was well tolerated and it has a response rate of 17% to 18%, which compares favorably for the 5% seen with the prior data with methotrexate. The OS rate was 8 months, which again compares very favorably to the 6 months seen with methotrexate. This was true, even though 85% of patients had received at least 2 prior treatments for head and neck cancer.

TARGETED ONCOLOGY: What did this study tell us about the safety of pembrolizumab in head and neck cancer?

Baumi: The rate of grade 3 through 5 treatment-related adverse events was 12% in our study. Nearly all of the side effects are what you would expect with pembrolizumab; those have been reported in multiple other studies. There was 1 treatment-related death due to pneumonitis, which is a rare side effect of this class of drugs.

Outside of that, it was a really well-tolerated agent. The fact that if you compared grade 3 through 5 toxicities of 12% with cytotoxic chemotherapy, this is a very well-tolerated agent.

TARGETED ONCOLOGY: How common is it for patients to fail both platinum-based therapy and cetuximab?

Baumi: Any patient who has recurrent or metastatic head and neck cancer is going to go through these agents if they survive long enough to get them. Basically, we know that these are the limited tools in our toolbox. We have platinum, we have cetuximab, and then we are really out of options. Many patients have received cetuximab in the locally advanced setting and so we have already lost one of our active treatments. This affects a lot of people.

TARGETED ONCOLOGY: What is next for pembrolizumab in head and neck cancer?

Baumi: There are currently phase III studies evaluating pembrolizumab in head and neck cancer both in combination with and versus traditional cytotoxic chemotherapy to see if we can move up the treatment earlier for patients. The key difference between pembrolizumab and cytotoxics is beyond the improved safety profile. However, we have durable responses; 75% of those patients who responded are still responding to this day. That is really not something that we see.

TARGETED ONCOLOGY: What are the biggest questions that remain regarding the treatment of patients with metastatic head and neck cancer?

Baumi: One of the key questions that relates to immunotherapy—and this covers all tumors—is trying to identify who the 20% of patients are that will respond. Eighty percent of our patients are not responding to our therapies.

Identifying a biomarker to enrich this patient population is very critical. Right now, I would not select patients for pembrolizumab by virtue of PD-L1 status because there were responses in the PD-L1–negative cohorts.

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

September, 2016|Oral Cancer News|

Expert says Nivolumab Poised to Change Standard of Care in SCCHN

Author: Laura Panjwani


Nivolumab (Opdivo) is a game-changing agent for the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN), according to Robert L. Ferris, MD, PhD.

“Recent findings have shown us that this agent is really the new standard-of-care option for all platinum-refractory patients with head and neck cancer,” says Ferris, vice chair for Clinical Operations, associate director for Translational Research, and co-leader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute. “This is regardless of whether patients are PD-L1–positive or negative or whether they are HPV-positive or negative.”

The PD-L1 inhibitor received a priority review designation by the FDA in July 2016 based on the CheckMate-141 study, which demonstrated a median overall survival (OS) with nivolumab of 7.5 months compared with 5.1 months with investigator’s choice of therapy (HR, 0.70; 95% CI, 0.51-0.96; P = .0101) in patients with recurrent or metastatic SCCHN.

The objective response rate (ORR) was 13.3% with nivolumab and 5.8% for investigator’s choice. The FDA is scheduled to make a decision on the application for the PD-1 inhibitor by November 11, 2016, as part of the Prescription Drug User Fee Act.

Ferris was the lead author on an analysis that further evaluated preliminary data from CheckMate-141, which was presented at the 2016 ASCO Annual Meeting. In an interview with OncLive, he discusses the findings of this study, potential biomarkers for nivolumab, and questions that remain regarding the use of the immunotherapy in SCCHN.

OncLive: What were the updated findings from CheckMate-141 presented at ASCO?

Ferris: The data that were presented at the 2016 ASCO Annual Meeting were further evaluations and follow-up on some preliminary data—originally presented at the 2016 AACR Annual Meeting—that listed the OS results.

At ASCO, we recapped the primary endpoint of OS as an important endpoint for immunotherapies because response rate and progression-free survival may not be as accurate. Ultimately, the FDA and people at large want OS. In this study, OS was 36% at 1 year in the nivolumab-treated arm and 16.6% in the comparator arm, which was investigator’s choice of single-agent chemotherapy, consisting of methotrexate, docetaxel, or cetuximab. In this phase III randomized trial, nivolumab was given in a 2:1 randomization: 240 patients received nivolumab and 120 received investigator’s choice.

Also at ASCO, we presented further evaluations consisting of what the regimens are in the comparator arm. There was about 20% each of docetaxel and methotrexate and 12% of cetuximab. Approximately 60% of the patients had prior cetuximab exposure and we stratified by cetuximab as a prior therapy. We also demonstrated the ORR, which was 13.3% in the nivolumab-treated arm versus 5.8% in the investigator’s choice arm.

Therefore, there was an improvement in overall response, but the difference seemed more modest than the OS benefit—which was a doubling—with 20% more patients alive at 1 year. This reinforces the concept that perhaps response rate may not be the best endpoint. Progression-free survival (PFS) was double at 6 months, with about 20% in the nivolumab arm versus about 9.9% in the investigator’s choice arm. The median PFS was not different, but the 6-month PFS was twice as high. The time to response was about 2 months in each arm at the first assessment.

Your analysis also looked at biomarkers. Can you discuss these findings and their significance?

The p16 or HPV-positive group had a better hazard ratio for OS than the overall study population. The hazard ratio was .73 for the overall population, using a preplanned interim analysis. With the HPV-positive group, we had a hazard ratio of .55 and the HPV-negative group had a hazard ratio of .99. It is still favoring the nivolumab-treated patients but, with the curves separated earlier in the HPV-positive group, one could see the improvement with nivolumab at about 1 to 2 months. It took 7 or 8 months with the HPV-negative group to show a separation of the curves in favor of nivolumab.

We looked at PD-L1 levels, and PD-L1—using a 1% or above level—had an improvement in the PD-L1–positive patients in favor of nivolumab in terms of OS and ORR. When we looked at 5% and 10% thresholds of PD-L1, the OS did not seem to improve. Therefore, in all levels above 1%, the OS was similarly beneficial over the PD-L1 less-than-1% group. However, essentially all levels of PD-L1–positivity and PD-L1–negativity still favored nivolumab, but the benefit was more when its levels were greater than 1%.

We could combine HPV status with PD-L1 status and look at subsets; however, essentially every subset benefited, whether it was PD-L1–negative or positive. This indicates that, in this group of patients, who progress within 6 months of platinum-based therapy, that no current systemic therapeutic options benefit patients as well as nivolumab.

With regard to these findings, what are you most excited about?

Head and neck cancer is a difficult disease. Until recently, we didn’t know the impact of this enrichment for HPV-positive virus-induced subsets and we didn’t know if this was an immune responsive cancer. Clearly, it is. We have all of the hallmarks that we have seen for a bright future—based on the melanoma data—and a series of other cancers indicating response rates in the 15% to 20% range, suggesting that we now have a platform of the PD-1 pathway to combine with other checkpoints and to integrate earlier in disease with radiation and chemotherapy.

We have a demonstration of head and neck cancer as an immune-responsive cancer. We are beginning to get an idea of the biomarkers and starting to be able to segment patients who will benefit. Now, we have a large comparative trial with an OS endpoint and tissue to look at biomarkers to try and understand what the best future combinations will be.

What are some questions that you still hope to answer regarding nivolumab in head and neck cancer?

We have to get down deeper into the nonresponders. We should acknowledge that the majority of patients neither had a response nor benefited. Understanding who is more likely to benefit is useful, but we also need to understand the levels of alternative checkpoint receptors or other biomarkers of resistance.

We have sequential lymphocyte specimens from the peripheral blood, tissues, and serum so those are intensively under evaluation. There are interferon gamma signatures that have risen from the melanoma checkpoint field that will certainty be applied, as well.

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

August, 2016|Oral Cancer News|

Knowledgeability, Attitude and Behavior of Primary Care Providers Towards Oral Cancer: a Pilot Study

Authors: Neel Shimpi, Aditi Bharatkumar, Monica Jethwani, Po-Huang Cyou, Ingrid Glurich, Jake Blamer, Amit Acharya


The objective of this study was to assess current knowledgeability, attitudes, and practice behaviors of primary care providers (PCPs) towards oral cancer screening. Applying a cross-sectional design, a 14-question survey was emailed to 307 PCPs practicing at a large, multi-specialty, rurally based healthcare system. Survey data were collected and managed using REDCap and analyzed applying descriptive statistics. A 20 % response rate (n = 61/307) was achieved for survey completion. Approximately 70 % of respondents were physicians, 16 % were nurse practitioners, and 13 % were physician assistants. Nearly 60 % of respondents were family medicine practitioners. Limited training surrounding oral cancer screening during medical training was reported by 64 %. Although 78 % of respondents reported never performing oral cancer screening on patients in their practice, >90 % answered knowledge-based questions correctly. Frequency rate for specialist referral for suspicious lesions by PCPs was 56 % “frequently”. Optimal periodicity for oral cancer screening on all patients selected by respondents was 61 % “annually”, 3 % “every 6 months”, 3 % “every visit”, 2 % “not at all”, and 31 % “unsure”. This study established a baseline surrounding current knowledgeability, practice patterns, and opinions of PCPs towards oral cancer screening at a single, large, regional healthcare system. In the absence of evidence-based support for population-based cancer screening, this study result suggests a need for better integration of oral cancer surveillance into the medical setting, supplemented by education and training with emphasis on assessment of high-risk patients to achieve early detection. Prospectively, larger studies are needed to validate these findings.

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

July, 2016|Oral Cancer News|

In an era of rapidly proliferating, precisely targeted treatments, every cancer case has to be played by ear.

Author: Sidhartha Mukherjee


15oncologist1-superJumbo-v5Illustration by Cristiana Couceiro. Photograph by Ansel Adams, via the National Archives, College Park, Md.


The bone-marrow biopsy took about 20 minutes. It was 10 o’clock on an unusually chilly morning in New York in April, and Donna M., a self-possessed 78-year-old woman, had flown in from Chicago to see me in my office at Columbia University Medical Center. She had treated herself to orchestra seats for “The Humans” the night before, and was now waiting in the room as no one should be asked to wait: pants down, spine curled, knees lifted to her chest — a grown woman curled like a fetus. I snapped on sterile gloves while the nurse pulled out a bar cart containing a steel needle the length of an index finger. The rim of Donna’s pelvic bone was numbed with a pulse of anesthetic, and I drove the needle, as gently as I could, into the outer furl of bone. A corkscrew of pain spiraled through her body as the marrow was pulled, and then a few milliliters of red, bone-flecked sludge filled the syringe. It was slightly viscous, halfway between liquid and gel, like the crushed pulp of an overripe strawberry.

I had been treating Donna in collaboration with my colleague Azra Raza for six years. Donna has a preleukemic syndrome called myelodysplastic syndrome, or MDS, which affects the bone marrow and blood. It is a mysterious disease with few known treatments. Human bone marrow is normally a site for the genesis of most of our blood cells — a white-walled nursery for young blood. In MDS, the bone-marrow cells acquire genetic mutations, which force them to grow uncontrollably — but the cells also fail to mature into blood, instead dying in droves. It is a dual curse. In most cancers, the main problem is cells that refuse to stop growing. In Donna’s marrow, this problem is compounded by cells that refuse to grow up.

Though there are commonalities among cancers, of course, every tumor behaves and moves — “thinks,” even — differently. Trying to find a drug that fits Donna’s cancer, Raza and I have administered a gamut of medicines. Throughout all this, Donna has been a formidable patient: perennially resourceful, optimistic and willing to try anything. (Every time I encounter her in the clinic, awaiting her biopsy with her characteristic fortitude, it is the doctor, not the patient, who feels curled and small.) She has moved nomadically from one trial to another, shuttling from city to city, and from one drug to the next, through a landscape more desolate and exhilarating than most of us can imagine; Donna calls it her “serial monogamy” with different medicines. Some of these drugs have worked for weeks, some for months — but the transient responses have given way to inevitable relapses. Donna is getting exhausted.

Her biopsy that morning was thus part routine and part experiment. Minutes after the marrow was drawn into the syringe, a technician rushed the specimen to the lab. There he extracted the cells from the mixture and pipetted them into tiny grain-size wells, 500 cells to a well. To each well — about 1,000 in total — he will add a tiny dab of an individual drug: prednisone, say, to one well, procarbazine to the next and so forth. The experiment will test about 300 medicines (many not even meant for cancer) at three different doses to assess the effects of the drugs on Donna’s cells.

Bathed in a nutrient-rich broth suffused with growth factors, the cells will double and redouble in an incubator over the course of the following two weeks, forming a lush outgrowth of malignant cells — cancer abstracted in a dish. A computer, taught to count and evaluate cells, will then determine whether any of the drugs killed the cancerous cells or forced them to mature into nearly normal blood. Far from relying on data from other trials, or patients, the experiment will test Donna’s own cancer for its reactivity against a panel of medicines. Cells, not bodies, entered this preclinical trial, and the results will guide her future treatment.

I explained all this to Donna. Still, she had a question: What would happen if the drug that appeared to be the most promising proved unsuccessful?

“Then we’ll try the next one,” I told her. “The experiment, hopefully, will yield more than one candidate, and we’ll go down the list.”

“Will the medicine be like chemotherapy?”

“It might, or it might not. The drug that we end up using might be borrowed from some other disease. It might be an anti-inflammatory pill, or an asthma drug. It might be aspirin, for all we know.”

My conversation with Donna reflected how much cancer treatment has changed in the last decade. I grew up as an oncologist in an era of standardized protocols. Cancers were lumped into categories based on their anatomical site of origin (breast cancer, lung cancer, lymphoma, leukemia), and chemotherapy treatment, often a combination of toxic drugs, was dictated by those anatomical classifications. The combinations — Adriamycin, bleomycin, vinblastine and dacarbazine, for instance, to treat Hodgkin’s disease — were rarely changed for individual patients. The prospect of personalizing therapy was frowned upon: The more you departed from the standard, the theory ran, the more likely the patient would end up being undertreated or improperly managed, risking recurrence. In hospitals and clinics, computerized systems were set up to monitor an oncologist’s compliance with standard therapy. If you chose to make an exception for a particular patient, you had to justify the choice with an adequate excuse. Big Chemo was watching you.

I memorized the abbreviated names of combination chemo — the first letter of each drug — for my board exams, and I spouted them back to my patients during my clinic hours. There was something magical and shamanic about the multiletter contractions. They were mantras imbued with promise and peril: A.B.V.D. for Hodgkin’s, C.M.F. for breast cancer, B.E.P. for testicular cancer. The lingo of chemotherapists was like a secret code or handshake; even the capacity to call such baleful poisons by name made me feel powerful. When my patients asked me for statistical data, I had numbers at my fingertips. I could summon the precise chance of survival, the probability of relapse, the chance that the chemo would make them infertile or cause them to lose their hair. I felt omniscient.

Yet as I spoke to Donna that morning, I realized how much that omniscience has begun to wane — unleashing a more experimental or even artisanal approach in oncology. Most cancer patients are still treated with those hoary standardized protocols, still governed by the anatomical lumping of cancer. But for patients like Donna, for whom the usual treatments fail to work, oncologists must use their knowledge, wit and imagination to devise individualized therapies. Increasingly, we are approaching each patient as a unique problem to solve. Toxic, indiscriminate, cell-killing drugs have given way to nimbler, finer-fingered molecules that can activate or deactivate complex pathways in cells, cut off growth factors, accelerate or decelerate the immune response or choke the supply of nutrients and oxygen. More and more, we must come up with ways to use drugs as precision tools to jam cogs and turn off selective switches in particular cancer cells. Trained to follow rules, oncologists are now being asked to reinvent them.

The thought that every individual cancer might require a specific individualized treatment can be profoundly unsettling. Michael Lerner, a writer who worked with cancer patients, once likened the experience of being diagnosed with cancer to being parachuted out of a plane without a map or compass; now it is the oncologist who feels parachuted onto a strange landscape, with no idea which way to go. There are often no previous probabilities, and even fewer certainties. The stakes feel higher, the successes more surprising and the failures more personal. Earlier, I could draw curtain upon curtain of blame around a patient. When she did not respond to chemotherapy, it was her fault: She failed. Now if I cannot find a tool in the growing kit of drugs to target a cancer’s vulnerabilities, the vector feels reversed: It is the doctor who has failed.

Yet the mapless moment that we are now in may also hold more promise for patients than any that has come before — even if we find the known world shifting under our feet. We no longer have to treat cancer only with the blunt response of standard protocols, in which the disease is imagined as a uniform, if faceless, opponent. Instead we are trying to assess the particular personality and temperament of an individual illness, so that we can tailor a response with extreme precision. It’s the idiosyncratic mind of each cancer that we are so desperately trying to capture.

Cancer — and its treatment — once seemed simpler. In December 1969, a group of cancer advocates led by the philanthropist Mary Lasker splashed their demand for a national war on cancer in a full-page ad in The New York Times: “Mr. Nixon: You Can Cure Cancer.” This epitomized the fantasy of a single solution to a single monumental illness. For a while, the centerpiece of that solution was thought to be surgery, radiation and chemotherapy, a strategy colloquially known as “slash and burn.” Using combination chemotherapy, men and women were dragged to the very brink of physiological tolerability but then pulled back just in time to send the cancer, but not its host, careering off the edge.

Throughout the 1980s and 1990s, tens of thousands of people took part in clinical trials, which compared subjects on standard chemo combinations with others administered slightly different combinations of those drugs. Some responded well, but for many others, relapses and recurrences were routine — and gains were small and incremental for most cancers. Few efforts were made to distinguish the patients; instead, when the promised cures for most advanced malignancies failed to appear, the doses were intensified and doubled. In the Margaret Edson play “Wit,” an English professor who had ovarian cancer recalled the bewildering language of those trials by making up nonsensical names for chemotherapy drugs that had been pumped into her body: “I have survived eight treatments of hexamethophosphacil and vinplatin at the full dose, ladies and gentlemen. I have broken the record.”

To be fair, important lessons were garnered from the trials. Using combinations of chemotherapy, we learned to treat particular cancers: aggressive lymphomas and some variants of breast, testicular and colon cancers. But for most men and women with cancer, the clinical achievements were abysmal disappointments. Records were not broken — but patients were.

A breakthrough came in the 2000s, soon after the Human Genome Project, when scientists learned to sequence the genomes of cancer cells. Cancer is, of course, a genetic disease at its core. In cancer cells, mutated genes corrupt the normal physiology of growth and ultimately set loose malignant proliferation. This characteristic sits at the heart of all forms of cancer: Unlike normal cells, cancer cells have forgotten how to stop dividing (or occasionally, have forgotten how to die). But once we could sequence tens of thousands of genes in individual cancer specimens, it became clear that uniqueness dominates. Say two identical-looking breast cancers arise at the same moment in identical twins; are the mutations themselves in the two cancers identical? It’s unlikely: By sequencing the mutations in one twin’s breast cancer, we might find, say, 74 mutated genes (of the roughly 22,000 total genes in humans). In her sister’s, we might find 42 mutations, and if we looked at a third, unrelated woman with breast cancer, we might find 18. Among the three cases, there might be a mere five genes that overlap. The rest are mutations particular to each woman’s cancer.

15oncologists4-master675-v2-1Dr. Azra Raza, left, speaking to Donna M., a patient who travels from Chicago for treatment for myelodysplastic syndromes, in a waiting room at NewYork-Presbyterian/Columbia. Credit Kirsten Luce for The New York Times


No other human disease is known to possess this degree of genetic heterogeneity. Adult-onset diabetes, for example, is a complex genetic disease, but it appears to be dominated by variations in only about a dozen genes. Cancer, by contrast, has potentially unlimited variations. Like faces, like fingerprints — like selves — every cancer is characterized by its distinctive marks: a set of individual scars stamped on an individual genome. The iconic illness of the 20th century seems to reflect our culture’s obsession with individuality.

If each individual cancer has an individual combination of gene mutations, perhaps this variability explains the extraordinary divergences in responses to treatment. Gene sequencing allows us to identify the genetic changes that are particular to a given cancer. We can use that information to guide cancer treatment — in effect, matching the treatment to an individual patient’s cancer.

Many of the remarkable successes of cancer treatments of the last decades are instances of drugs that were matched to the singular vulnerabilities of individual cancers. The drug Gleevec, for instance, can kill leukemia cells — but only if the patient’s cancer cells happen to carry a gene mutation called BCR-ABL. Tarceva, a targeted therapy for lung cancer, works powerfully if the patient’s cancer cells happen to possess a particular mutant form of a gene; for lung-cancer patients lacking that mutation, it may be no different from taking a placebo. Because the medicines target mutations or behaviors that are specific to cancer cells (but not normal cells), many of these drugs have surprisingly minimal toxicities — a far cry from combination chemotherapies of the past.

A few days after Donna’s visit to the clinic, I went to my weekly meeting with Raza on the ninth floor of the hospital. The patient that morning was K.C., a 79-year-old woman with blood cancer. Raza has been following her disease — and keeping her alive — for a decade.

“Her tumor is evolving into acute leukemia,” Raza said. This, too, is a distinctive behavior of some cancers that we can now witness using biopsies, CT scans and powerful new techniques like gene sequencing: We can see the cancers morphing from smoldering variants into more aggressive types before our eyes.

“Was the tumor sequenced?” I asked.

“Yes, there’s a sequence,” Raza said, as we leaned toward a screen to examine it. “P53, DNMT3a and Tet2,” she read from the list of mutant genes. “And a deletion in Chromosome 5.” In K.C.’s cancer, an entire segment of the genome had been lopped off and gone missing — one of the crudest mutations that a tumor can acquire.

“How about ATRA?” I asked. We had treated a few patients carrying some of K.C.’s mutations with this drug and noted a few striking responses.

“No. I’d rather try Revlimid, but at a higher dose. She’s responded to it in the past, and the mutations remain the same. I have a hunch that it might work.”


Cancer by Genes
Researchers have discovered that cancers they once assumed were quite different might be similar genetically, which means a treatment that used to work for only a small group of patients now might help a much larger group. Mutations in the gene E2F3, for example, are found in breast, lung, bladder and prostate cancers, among others. Knowing this, it’s possible to develop similar drugs that target the gene across different cancers.


As Raza and I returned to K.C.’s room to inform her of the plan, I couldn’t help thinking that this is what it had come down to: inklings, observations, instincts. Medicine based on premonitions. Chemo by hunch. The discussion might have sounded ad hoc to an outsider, but there was nothing cavalier about it. We parsed these possibilities with utmost seriousness. We studied sequences, considered past responses, a patient’s recent history — and then charged forward with our best guess. Our decisions were spurred by science, yes, but also a sense for the art of medicine.

Oncologists are also practicing this art in areas that rely less on genes and mutations. A week after Donna’s biopsy, I went to see Owen O’Connor, an oncologist who directs Columbia’s lymphoma center. O’Connor, in his 50s, reminds me of an amphibious all-terrain vehicle — capable of navigating across any ground. We sat in his office, with large, sunlit windows overlooking Rockefeller Plaza. For decades, he explained, oncologists had treated relapsed Hodgkin’s lymphoma in a standard manner. “There were limited options,” O’Connor said. “We gave some patients more chemotherapy, with higher doses and more toxic drugs, hoping for a response. For some, we tried to cure the disease using bone-marrow transplantation.” But the failure rate was high: About 30 percent of patients didn’t respond, and half of them died.

Then a year or two ago, he tried something new. He began to use immunological therapy to treat relapsed, refractory Hodgkin’s lymphoma. Immunological therapies come in various forms. There are antibodies: missile-like proteins, made by our own immune systems, that are designed to attack and destroy foreign microbes (antibodies can also be made artificially through genetic engineering, armed with toxins and used as “drugs” to kill cancer cells). And there are drugs that incite a patient’s own immune system to recognize and kill tumor cells, a mode of treatment that lay fallow for decades before being revived. O’Connor used both therapies and found that they worked in patients with Hodgkin’s disease. “We began to see spectacular responses,” he said.

Yet even though many men and women with relapsed Hodgkin’s lymphoma responded to immunological treatments, there were some who remained deeply resistant. “These patients were the hardest to treat,” O’Connor continued. “Their tumors seemed to be unique — a category of their own.”

15oncologists5-master675Dr. Siddhartha Mukherjee, left, speaking to K.C., who has acute myeloid leukemia, at NewYork-Presbyterian/Columbia. Credit Kirsten Luce for The New York Times


Lorenzo Falchi, a fellow training with O’Connor and me, was intrigued by these resistant patients. Falchi came to our hospital from Italy, where he specialized in treating leukemias and lymphomas; his particular skill, gleaned from his experience with thousands of patients, is to look for patterns behind seemingly random bits of data. Rooting about in Columbia’s medical databases, Falchi made an astonishing discovery: The men and women who responded most powerfully to the immune-boosting therapies had invariably been pretreated with another drug called azacitidine, rarely used in lymphoma patients. A 35-year-old woman from New York with relapsed lymphoma saw her bulky nodes melt away. She had received azacitidine as part of another trial before moving on to the immunotherapy. A man, with a similar stage of cancer, had not been pretreated. He had only a partial response, and his disease grew back shortly thereafter.

Falchi and O’Connor will use this small “training set” to begin a miniature trial of patients with relapsed Hodgkin’s disease. “We will try it on just two or three patients,” Falchi told me. “We’ll first use azacitidine — intentionally, this time — and then chase it with the immune activators. I suspect that we’ll reproduce the responses that we’ve seen in our retrospective studies.” In lung cancer too, doctors have noted that pretreating patients with azacitidine can make them more responsive to immunological therapy. Falchi and O’Connor are trying to figure out why patients respond if they are pretreated with a drug that seems, at face value, to have nothing to do with the immune system. Perhaps azacitidine makes the cancer cells more recognizably foreign, or perhaps it forces immune cells to become more aggressive hunters.

Falchi and O’Connor are mixing and matching unexpected combinations of medicines based on previous responses — departing from the known world of chemotherapy. Even with the new combination, Falchi suspects, there will be resistant patients, and so he will divide these into subsets, and root through their previous responses, to determine what might make these patients resistant — grinding the data into finer and finer grains until he’s down to individualized therapy for every variant of lymphoma.

Suppose every cancer is, indeed, unique, with its own permutation of genes and vulnerabilities — a sole, idiosyncratic “mind.” It’s obviously absurd to imagine that we’ll find an individual medicine to treat each one: There are 14 million new cases of cancer in the world every year, and several million of those patients will present with advanced disease, requiring more than local or surgical treatment. Trying to individualize treatment for those cases would shatter every ceiling of cost.

15oncologist2-superJumbo-v2Cancer Development
Cancer works the same way all life works, through the process of cell division and mutation. All living things grow and heal through cell division, and all living things evolve and change through the occasional mutations that occur as the cells divide. But some mutations can be deadly, leading to the unchecked growth that defines cancer. More than 14 million Americans have a history of cancer; it is expected to kill 600,000 Americans this year.


But while the medical costs of personalized therapy are being debated in national forums in Washington, the patients in my modest waiting room in New York are focused on its personal costs. Insurance will not pay for “off-label” uses of medicines: It isn’t easy to convince an insurance company that you intend to use Lipitor to treat a woman with pre-leukemia — not because she has high cholesterol but because the cancer cells depend on cholesterol metabolism for their growth (in one study of a leukemia subtype, the increasing cells were highly dependent on cholesterol, suggesting that high doses of Lipitor-like drugs might be an effective treatment).

In exceptional cases, doctors can requisition pharmaceutical companies to provide the medicines free — for “compassionate use,” to use the language of the pharma world — but this process is unpredictable and time-consuming. I used to fill out such requests once every few months. Now it seems I ask for such exceptions on a weekly basis. Some are approved. A majority, unfortunately, are denied.

So doctors like Falchi and O’Connor do what they can — using their wiles not just against cancer but against a system that can resist innovation. They create minuscule, original clinical trials involving just 10 or 20 patients, a far cry from the hundred-thousand-patient trials of the ’80s and ’90s. They study these patients with monastic concentration, drawing out a cosmos of precious data from just that small group. Occasionally, a patient may choose to pay for the drugs out of his or her own pockets — but it’s a rare patient who can afford the tens of thousands of dollars that the drugs cost.

But could there be some minimal number of treatments that could be deployed to treat a majority of these cancers effectively and less expensively? More than any other scientist, perhaps, Bert Vogelstein, a cancer geneticist at Johns Hopkins University, has tackled that conundrum. The combination of genetic mutations in any individual cancer is singular, Vogelstein acknowledges. But these genetic mutations can still act through common pathways. Targeting pathways, rather than individual genes, might reorganize the way we perceive and treat cancer.

15oncologists7-master675Deep freezers containing bone marrow, bone-marrow plasma and blood serum in Siddhartha Mukherjee’s research lab. Credit Kirsten Luce for The New York Times


Imagine, again, the cell as a complex machine, with thousands of wheels, levers and pulleys organized into systems. The machine malfunctions in the cancer: Some set of levers and pulleys gets jammed or broken, resulting in a cell that continues to divide without control. If we focus on the individual parts that are jammed and snapped, the permutations are seemingly infinite: Every instance of a broken machine seems to have a distinct fingerprint of broken cogs. But if we focus, instead, on systems that malfunction, then the seeming diversity begins to collapse into patterns of unity. Ten components function, say, in an interconnected loop to keep the machine from tipping over on its side. Snap any part of this loop, and the end result is the same: a tipped-over machine. Another 20 components control the machine’s internal thermostat. Break any of these 20 components, and the system overheats. The number of components — 10 and 20 — are deceptive in their complexity, and can have endless permutations. But viewed from afar, only two systems in this machine are affected: stability and temperature.

Cancer, Vogelstein argues, is analogous. Most of the genes that are mutated in cancer also function in loops and circuits — pathways. Superficially, the permutations of genetic flaws might be boundless, but lumped into pathways, the complexity can be organized along the archetypal, core flaws. Perhaps these cancer pathways are like Hollywood movies; at first glance, there seems to be an infinite array of plot lines in an infinite array of settings — gold-rush California, the Upper West Side, a galaxy far, far away. But closer examination yields only a handful of archetypal narratives: boy meets girl, stranger comes to town, son searches for father.

How many such pathways, or systems, operate across a subtype of cancer? Looking at one cancer, pancreatic, and mapping the variations in mutated genes across hundreds of specimens, Vogelstein’s team proposed a staggeringly simple answer: 12. (One such “core pathway,” for instance, involves genes that enable cells to invade other tissues. These genes normally allow cells to migrate through parts of the body — but in cancer, migration becomes distorted into invasion.) If we could find medicines that could target these 12 core pathways, we might be able to attack most pancreatic cancers, despite their genetic diversity. But that means inventing 12 potential ways to block these core paths — an immense creative challenge for scientists, considering that they haven’t yet figured out how to target more than, at best, one or two.

Immunological therapies provide a second solution to the impasse of unlimited diversity. One advantage of deploying a patient’s own immune system against cancer is that immunological cells are generally agnostic to the mutations that cause a particular cancer’s growth. The immune system was designed to spot differences in the superficial features of a diseased or foreign cell, thereby identifying and killing it. It cares as little about genes as an intercontinental ballistic missile cares about the email addresses, or dietary preferences, of the population that it has been sent to destroy.

A few years ago, in writing a history of cancer, I interviewed Emil Freireich. Freireich, working with Emil Frei at the National Cancer Institute in the 1960s and ’70s, stumbled on the idea of deploying multiple toxic drugs simultaneously to treat cancer — combination chemotherapy. They devised one of the first standard protocols — vincristine, Adriamycin, methotrexate and prednisone, known as VAMP — to treat pediatric leukemias. Virtually nothing about the VAMP protocol was individualized (although doses could be reduced if needed). In fact, doctors were discouraged from trying alternatives to the formula.

Yet as Freireich recalled, long before they came up with the idea for a protocol, there were small, brave experiments; before trials, there was trial and error. VAMP was brought into existence through grit, instinct and inspired lunges into the unknown. Vincent T. DeVita Jr., who worked with Freireich in the 1960s, wrote a book, “The Death of Cancer,” with his daughter, Elizabeth DeVita-Raeburn. In it, he recalled a time when the leukemic children in Freireich’s trial were dying of bacterial meningitis during treatment. The deaths threatened the entire trial: If Freireich couldn’t keep the children alive during the therapy, there would be no possibility of remission. They had an antibiotic that could kill the microbe, but the medicine wouldn’t penetrate the blood-brain barrier. So Freireich decided to try something that pushed the bounds of standard practice. He ordered DeVita, his junior, to inject it directly into the spinal cords of his patients. It was an extreme example of off-label use of the drug: The medicine was not meant for use in the cord. DeVita writes:

“The first time Freireich told me to do it, I held up the vial and showed him the label, thinking that he’d possibly missed something. ‘It says right on there, “Do not use intrathecally,” ’ I said. Freireich glowered at me and pointed a long, bony finger in my face. ‘Do it!’ he barked. I did it, though I was terrified. But it worked every time.”

When I asked Freireich about that episode and about what he would change in the current landscape of cancer therapy, he pointed to its extreme cautiousness. “We would never have achieved anything in this atmosphere,” he said. The pioneer of protocols pined for a time before there were any protocols.

Medicine needs standards, of course, otherwise it can ramble into dangerous realms, compromising safety and reliability. But cancer medicine also needs a healthy dose of Freireich: the desire to read between the (guide)lines, to reimagine the outer boundaries, to perform the experiments that become the standards of the future. In January, President Obama introduced an enormous campaign for precision medicine. Cancer is its molten centerpiece: Using huge troves of data, including gene sequences of hundreds of thousands of specimens and experiments performed in laboratories nationwide, the project’s goal is to find individualized medicines for every patient’s cancer. But as we wait for that decades-long project to be completed, oncologists still have to treat patients now. To understand the minds of individual cancers, we are learning to mix and match these two kinds of learning — the standard and the idiosyncratic — in unusual and creative ways. It’s the kind of medicine that so many of us went to medical school to learn, the kind that we’d almost forgotten how to practice.

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

May, 2016|Oral Cancer News|

Cowboy raises awareness for oral cancer

Author: Annie Sabo
KRISTV cody interview

In an environment where smokeless and spit tobacco is prevalent, cowboy, Cody Kiser, says he feels like the luckiest guy in the world to represent the Oral Cancer Foundation.

He told us, “I just happened to be in a class with a classmate. Their sister works for the oral cancer foundation…one thing led to another and they said  we’ve been looking for a cowboy that doesn’t smoke or chew and we’d love to be able to work out some kind of deal where we help you out you help us out…now I’m here.”
Although Cody has not been personally affected by the cancer, he wears a special patch on his shirt to raise awareness for the deadly disease.

He said, “I’m very lucky that I haven’t had any family members or friends be affected by oral cancer. I’ve made friends with people that have been now and it’s a real eye opener.”

Since partnering with the oral cancer foundation, he works hard to promote this message: “Be smart don’t start…we want to get out to the kids and fans who haven’t smoking or chewing yet.”

Cody says the best part about working for the oral cancer foundation is serving as a role model for children. He told us, “You can be an elite athlete and an amazing cowboy without having to smoke or chew. That’s our goal is to get to those kids before they do that. I just want to be a good role model for these kids.”

Rodeo after Rodeo, Kiser hopes to make a difference.

10334178_GKiser wears this patch every time he competes.


View Cody Kiser’s full inter view here:

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

The burden of cancer isn’t just cancer

Author: Carolyn Y. Johnson

Money is low on the list of things most people want to think about after a doctor says the scary word “cancer.” And it’s not just patients — physicians also want to weigh the best treatment options to rout the cancer, unburdened by financial nitty gritty. But a growing body of evidence suggests that, far from crass, ignoring cost could be harmful to patients’ health.

In the age of $10,000-a-month cancer drugs and health plans that shift more of the cost of health care onto patients, research suggests we’ve been underestimating one of cancer’s real harms: “financial toxicity.”

The financial difficulties that stem from dealing with cancer can lead people to avoid or delay care or drugs, studies suggest, and also may cause stress that can lead to mental and physical health problems.

“When people are diagnosed, it behooves the provider to assess their financial risk at baseline — to find out if they’re at risk, and if they are, to be very aggressive with getting them to financial planning, to patient assistance programs to reduce their likelihood of having financial devastation,” said Scott Ramsey, a health economist and physician at the Fred Hutchinson Cancer Research Center in Seattle who showed in 2013 that people with cancer are 2.65 times more likely to file for bankruptcy than people without cancer. “We think unless you do, it’ll be hard to keep people from ending up in this situation.”

For years, the evidence has accrued that cancer patients experience greater financial challenges than other groups of sick people. A study in the Journal of Clinical Oncology found that 13 percent of non-elderly patients with cancer spend at least a fifth of their income on treatment. Among people on Medicare, cancer patients spent an average of $4,727 of their own money on health care, according to a 2013 Cancer study — about $1,000 more than people without cancer.

What has been far less clear is whether the distress is simply a financial problem or also a health issue. No one would say financial stress is desirable, but does it affect how long or well cancer patients lived? Were people skipping doctor’s visits, drugs or other treatments?

There’s some evidence that higher co-pays deter patients from filling their prescriptions — one study found that a copay of about $50 a month or more was enough to keep nearly a fifth of patients from continuing to fill prescriptions for a remarkably effective rare leukemia treatment.

But cancer’s burden isn’t just high drug costs. Last month, Ramsey and colleagues reported that not only are cancer patients more likely to declare bankruptcy than those without; those who declared bankruptcy were 1.8 times as likely to die of any cause than cancer patients with the same diagnoses and initial treatments who did not.

Another study published in the journal Cancer last month examined Medicare data and found that among nearly 20 million cancer survivors, 29 percent reported financial burden of some kind, ranging from bankruptcy to borrowing money to not being able to pay for medical visits. Among those reporting financial burdens, 86 percent had health insurance during their cancer treatment.

“Another thing that concerns me with the way most insurance policies are set up is it seems they do a good job of protecting you at sort of middle-range expenses, but if you get to really high expenses, people incur a lot of out-of-pocket costs. The thing you want insurance to insure you against is financial catastrophe, but the way these policies are set up, for a lot of people, they don’t,” said Norman Carroll, a professor of pharmacoeconomics and health outcomes at the Virginia Commonwealth University School of Pharmacy who led the Cancer study.

How financial toxicity hurts

The big question underlying this research is how financial distress hurts and what should be done about it. Are patients skipping appointments and not taking drugs that could extend their lives because they’re going broke? Or are they losing their jobs or earning less after cancer and is worry about going broke having a snowball effect, bringing on other ill health effects?

There aren’t definitive answers, but worrisome hints.

A 2013 study published in The Oncologist found that nearly half of cancer patients with insurance surveyed cut back on their spending on food and clothing or dipped into savings to pay for their treatment. The majority cut back on leisure activities. Three-quarters of them received financial assistance with their drug copayments.

A study of Medicare beneficiaries in the Journal of Managed Care Pharmacy found that for expensive cancer drugs that are given as pills, patients were more likely to stop or delay drug therapy as the portion they paid increased. For every $10 increase in out of patient costs per month, the likelihood of stopping or delaying use of the drug increased — 12.7 percent for a leukemia drug called imatinib.

Add to that Carroll’s recent study, which found cancer patients who reported three or more financial problems had clinically meaningful differences in physical health. The study also tracked depression, and people with any kind of financial burden had meaningful differences in mental health — and as the number of financial problems increased, so did the mental health burden.

“Physicians probably should focus more on shared decision-making with patients to the extent that’s possible, and spend more time than I think has been spent in the past to see if you can find equally effective, lower cost treatment,” Carroll said.

But researchers still don’t know enough about the problem — or what the best therapy is. Ramsey said he is now working on a pilot where financial information will be collected at oncology clinics when people are seen, to see how treatments affect patients’ financial health in real time.

“It’s easy for me to say that, but it’s hard to really do, because doctors don’t really want to deal with it, patients don’t want to,” Ramsey said

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

April, 2016|Oral Cancer News|

Why a Cure For Cancer Is Possible

Author: Robert Mulroy

BERLIN, GERMANY - SEPTEMBER 05:  A doctor holds a stethoscope on September 5, 2012 in Berlin, Germany. Doctors in the country are demanding higher payments from health insurance companies (Krankenkassen). Over 20 doctors' associations are expected to hold a vote this week over possible strikes and temporary closings of their practices if assurances that a requested additional annual increase of 3.5 billion euros (4,390,475,550 USD) in payments are not provided. The Kassenaerztlichen Bundesvereinigung (KBV), the National Association of Statutory Health Insurance Physicians, unexpectedly broke off talks with the health insurance companies on Monday.  (Photo by Adam Berry/Getty Images)

Cutting drug prices is not out of the question.

A crapshoot is defined as a risky or uncertain matter; something that could produce a good or bad result. President Obama’s moonshot on cancer is different in terms of its greater complexity and higher moral purpose — but unfortunately, not in its probability of success.

The Audacity of Scope

President Obama has asked Congress for $755 million to “focus” on immunotherapy, combination therapy, vaccines that prevent cancer causing viruses, and early detection techniques. According to Vice President Joe Biden, who will coordinate 13 government institutions in this research, “Our job is to clear out the bureaucratic hurdles, and let science happen.”

It is hard not to welcome such an initiative. Cancer has deposed heart disease as the number one killer in 22 American states. Experts project the number of global cancer cases will double in the next 15 years. But we are better at projecting the demand for innovation than we are at producing it; and we are even better at making promises we can’t keep and polices that don’t work.

President Roosevelt created the National Cancer Institute in 1937. Nixon declared a “war on cancer” with the National Cancer Act in 1971. The Bush administration spoke in 2003 of spending $600 million per year to rid the world of cancer by 2015. Obama and Biden made campaign promises to fight cancer in 2008, and should be lauded for trying to keep them, but their approach needs a lot of work.

The underlying assumption is that we should spend as much money, and use as many public and private constituencies to do as much as we can on as many paths as possible. There are three things wrong with this: first, $755 million is a measly sum under the current paradigm drug development. It can cost a company up to $5 billion and a full decade to bring one cancer-fighting drug to market. Second, we have tried this strategy before. Doing the same thing again, only harder, will lead to numerous failures whose cost will be passed on to the insurance companies and their customers in the form of high drug prices. Third, the answer is right in front of us.

We use the term moonshot to reference JFK’s successful space program, but don’t apply its deepest insights. We in the cancer fighting community lack that program’s predictive models, which were the key to its success. Despite severe technological limitations, NASA believed in predictive models based in math, engineering and physics. They modeled, for example, gravity’s influence on earth launches, moon landings, and human tissue. The models told them exactly what tools were needed to do the job. Only then did they build spacecraft to accomplish our goals.

Meanwhile, back on earth, we build tools before we understand the problem of cancer. Two-thirds of published research cannot be reproduced. In the post-genomic era, the FDA approves only 7% of drugs that enter cancer clinical research. Over the past five years, twice as many trials have resulted in only a 10% increase in approvals. Industry investment in R&D has gone backwards, and with it comes a soaring cost of innovation that drives drug prices. Imagine the public tumult, the demand for our leaders to resign, if only one in 14 of rockets carried our astronauts safely!

Great Strategy is Reconciling what Others Believe are Opposites

The discussion we should be having is how to cure cancer and lower drug prices at the same time. Cancer is a multidimensional, ever-changing disease of the entire cell system. The standard focus on individual targets — while supporting publications to drive academic careers and intellectual property that supports high-risk industry investment — has failed. The secrets of biology lay in the interactions between molecules: the dynamics. We need to hack into a human cell as if it were a computer and decode the operating system: switch these proteins off to cure pancreatic cancer, turn others on to end heart disease, and deliver smart growth factors to regenerate neural tissue.

If predictive engineering was the impetus behind space travel, then systems biology can spur innovation and foster initiatives of “cell exploration.” Systems biology is the method of building models of complex biological environments so we can design the right drug from the start. These drugs would have fewer off-target effects and last longer at the disease site. They would also cost less because the cost of failure of the present “scattershot” system of drug discovery would not be passed along to the consumer.

The NIH is a national treasure that houses the tiny National Centers for Systems Biology, a network of our top academic institutions and thought leaders who are already on the path to uncovering cellular secrets. But last year, of the $25 billion in grants supported by the NIH, those aimed at the truly transformational opportunity of systems biology totaled a mere $8 million, or .032% of the total.

Many of us now know that a “war on cancer,” campaign promises massive infusions of capital, top-down political coordination and even the genomic revolution do not come close to the value created by a greater understanding of systems biology. If we call it a moonshot, but don’t comprehend the real key to putting a man on the moon, how is that different than a crapshoot?

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

March, 2016|Oral Cancer News|

Here’s why the drug that helped Jimmy Carter get ‘cancer-free’ is such a big deal

Author: Lydia Ramsey


Former US President Jimmy Carter announced on Sunday that his latest brain scan showed no sign of cancer, a few months after revealing that he had been diagnosed with melanoma that had spread from his liver to his brain.

Carter was being treated with a cancer drug called Keytruda that uses the immune system to fight off cancerous cells.

Keytruda, made by pharmaceutical company Merck, was originally approved by the FDA in September 2014 to treat melanoma, a deadly form of skin cancer that can also show up in other organs of the body, as it did in Carter’s case.

In someone with melanoma, certain proteins called PD-1 stop the immune system from doing its job and fighting the cancerous cells. Keytruda works by getting in the way of those proteins, allowing the immune system to access the cancer cells. Then, with the help of radiation therapy, which works to shrink tumors by killing cancer cells, it can knock the cancer out.

The drug is delivered intravenously every three weeks, costing about $12,500 a month.

And the drug isn’t just being used in cases like Carter’s. Keytruda, which got approved to treat a form of lung cancer in October, is also being explored to treat a number of other cancers, including head and neck, breast, and bladder cancers and Hodgkin lymphoma.

It’s also not the first cancer immunotherapy drug. Scientists have been seriously exploring using the immune system to battle cancerous cells for decades as an alternative to chemotherapy, radiation therapy, and surgery. But it’s taken a long time for the treatments to be effective in humans.

On Monday, Merck also announced that it has initiated two final phase trials using Keytruda in patients with multiple myeloma, a type of blood cancer that affects a type of white blood cell called plasma cells.

In November, the FDA approved three multiple myeloma drugs, including another cancer-immunotherapy drug called Empliciti.


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

December, 2015|Oral Cancer News|

A cancer on the rise, and the vaccine too late for Gen X

Author: Martha Shade

(CNN)The vaccine given to prevent cervical cancer in women could end up saving men’s lives, too.

Evidence is mounting that the HPV vaccine is also effective in preventing other HPV-related cancers, including those of the head and neck. Although most people who get HPV do not develop cancer, rates of HPV-related head and neck cancers are dramatically rising for men aged 40 to 50, according to Dr. Maura L. Gillison, the Jeg Coughlin Chair of Cancer Research at the Ohio State University Comprehensive Cancer Center.

When Gillison recently gave a presentation showing the increasing rate of HPV-related head and neck cancer among men, her audience was shocked. “I’ve never shown a slide where the audience gasps,” she said.

Related: Yes, oral sex can lead to cancer

“The risk of getting this cancer is strongly related to when you were born. If you are currently a 40- to 45-year-old man, your risk of getting this cancer is dramatically higher than a 40- to 45-year-old man three or four decades ago,” Gillison said.

Today’s 40- to 50-year-old men have had more sexual partners and have engaged in more oral sex than previous generations, according to experts, significantly raising their risk of an HPV-related head and neck cancer.

Actor Michael Douglas made headlines in 2013 when he announced he was battling an HPV-related cancer and that he got it from performing oral sex. Douglas was 68 when he was diagnosed, but many of the men being diagnosed with these HPV-related cancers are much younger.

What’s a Gen X’er to do?

HPV is usually acquired when young. It can lay dormant, and most oropharyngeal cancer (a type of head and neck cancer) is diagnosed decades later, beginning around age 40 to 50. And the more partners you have, the greater your risk.

HPV vaccines weren’t recommended and approved in the United States until 2006. And the vaccine was not even recommended for boys until 2011.

So what’s an aging Gen X’er to do?

“You’re starting to get colonoscopies; you’re starting to get checked for prostate cancer. This is one more thing to add to that list that you really have to watch for,” said Brian Hill, founder of the Oral Cancer Foundation.

Warning signs of HPV-related head and neck cancer

• Persistent lump on neck

• Persistent earache on one side

• Swelling or lump in the mouth

• Chronic sore throat

• Difficult or painful swallowing

• Change in voice

Source: Oral Cancer Foundation, Dr. Carole Fakhry

Symptoms of HPV-related head and neck cancer include a change in voice, a sore throat that doesn’t go away, an earache on one side and difficult or painful swallowing.

Hill’s story is typical: His doctors initially assumed he had an enlarged lymph node due to an infection. Two doctors gave him antibiotics before he was diagnosed with late-stage oropharyngeal cancer. His experience led him to form the Oral Cancer Foundation.

Finding the disease at an early stage is lifesaving. When it’s diagnosed early, these HPV-related cancers are survivable, according to Dr. Carole Fakhry of the Johns Hopkins Head & Neck Cancer Center. “If you have a lump in your neck, make sure to get checked.

“A very common story is: ‘I was shaving and I noticed this lump in my neck,” she said. “And he goes through two or three rounds of antibiotics and then someone finally thinks about cancer.”

‘Dental hygienists are becoming the best screeners’

Traditionally, cancers of the head and neck were often linked to alcohol or smoking, and these non-HPV cancers tend to be located at the front of the mouth and the voice box. Incidence of these cancers are dropping.

“The truth of the matter is that smoking-related cancers are declining,” Fakhry said. “On the other hand, cancers related to HPV are increasing.”

HPV-related cancers usually originate in the back of the mouth. “Most of these cancers are tonsils and back-of-tongue cancers,” she said. “Tonsils are basically these crypts, and tumors grow deep within these crypts, so these tumors can be hard to find.”

Since tumors are often hidden, dentists and dental hygienists are becoming the first line of attack. Men may also be more likely to visit a dentist regularly than a doctor, according to Hill.

“Dental hygienists are becoming the best screeners for this. They’re becoming the point at the end of the spear when it comes to screening and finding abnormalities,” he said.

Dentists and hygienists are encouraged to look for telltale signs of HPV-related cancer: asymmetrical or swollen tonsils, or a lesion in the back of the throat. But these cancers are notoriously tough to spot and tend to be diagnosed after patients develop a lump in the neck.

So what can you do?

“Make sure you get your kids vaccinated (for HPV),” Fakhry said.

Dr. Dan Beachler, lead author of a new study that found further evidence the HPV vaccine protects against multiple types of HPV-related cancers, agrees: “We still don’t know that much about oral HPV. Primary prevention through vaccination might have the most potential.”

Besides the cervix and the head and neck, some strains of HPV can also lead to cancer of the anus, penis and vulva.

A preventive HPV vaccine is most effective when given to children before they become exposed to HPV. The three dose series is recommended at age 11 or 12.

Initially recommended just for girls, the Centers for Disease Control and Prevention now recommends that boys be vaccinated, too. In addition, vaccination is recommended through the age of 26 in women and through age 21 in men who were not vaccinated previously.

“Young people do not avoid oral sex. That being a given, the best thing we can do is increase the vaccination rate. The second thing we can do is be highly aware of signs and symptoms,” Hill said.

And don’t panic. Although HPV-related cancers are on the rise, they’re still uncommon.

“Even though the rates are dramatically increasing, it’s still a relatively rare cancer. We don’t want to create a panic. We just want to raise awareness,” Gillison said.