In 'Cancer: The Emperor of all Maladies' PBS and Ken Burns probe disease's unique status

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Monday, March 23, 2015, 2:00 AM

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Ken Burns talking during a New York Daily News editorial board meeting Aug. 7, 2012.

IF WE can't always beat cancer, says Ken Burns, at least we need to strip away some of its psychological power.

“No other disease has the same impact as cancer,” says Burns, executive producer of “Cancer: The Emperor of All Maladies,” a three-part PBS series that will air March 30-April 1. It's directed by Barak Goodman and based on a book by Dr. Siddhartha Mukherjee.

“If you say you have heart disease, which is very serious and kills people every day, it doesn't have the same effect as saying you have cancer,” says Burns.

Part of the reason for this, he suggests, is that pretty much everyone either has had or knows someone who has had cancer.

“It's a shared experience,” Burns says. “It connects all of us in a very visceral way.”

And a deeply troubling way.

“No other disease,” says Mukherjee, “carries the same strong sense of betrayal. Your own body, for some reason you don't understand, is eating you alive.”

What we need to do, they all say, is look at cancer as a serious disease that in an increasing numbers of cases can be beaten.

They also say that contrary to some beliefs, the treatment is not worse than the disease.

“It's a mythology that most people with cancer die a terrible death,” says Burns. “We've made tremendous advances in pain management.”

That aspect of cancer treatment is particularly critical, says Mukherjee, “because it isn't death we fear. It's dying. We can take away the pain.”

Unfortunately, cancer probably won't be cured by a single magic vaccine.

“There are so many types of cancer,” says Burns. “At some point almost all of us may get some form. But we can see a day when most cancers will at worst be manageable conditions not death sentences.”

dhinckley@nydailynews.com

http://video.pbs.org/program/story-cancer-emperor-all-maladies/

http://www.nydailynews.com/entertainment/tv/pbs-air-cancer-emperor-maladies-article-1.2157242

The book weaves together Mukherjee's experiences as a hematology/oncology fellow at Massachusetts General Hospital as well as the history of cancer treatment and research.^[3][4] Mukherjee gives the history of cancer from its first identification 4,600 years ago by the Egyptian physician Imhotep. The Greeks had no understanding of cells, but they were familiar with hydraulics, so they used hydraulic metaphors, of humors, which were fluids whose proper balance, they believed, produced health and sickness. According to the book, cancer existed in silence in history until 440 BC, where the Greek historian Herodotus records the story of Atusa the queen of Persia and the daughter of Cyrus, who noticed a lump in her breast. The tumor was excised by her Greek slave named Demasitis, where the procedure is believed to be successful at least temporarily.

In the 19th century, surgical approaches were developed to deal with tumors. William Halsted developed an aggressive, disfiguring breast surgery as a strategy for removing not only existing cancer cells but also places to which they might have spread.

Leukemia, a cancer of blood cells, was first observed by Rudolph Virchow, and Franz Ernst Christian Neumann localized the pathology to the bone marrow. Leukemia cells are dependent on the enzyme dihydrofolate reductase. Sidney Farber used molecules developed by Yellapragada Subbarow to block the enzyme and destroy the leukemia cells, producing a temporary remission in the disease.

The book proceeds right on through to the latest research and therapies.

According to Mukherjee, the book was a response to the demand of a patient: "I’m willing to go on fighting, but I need to know what it is that I’m battling."^[5] Mukherjee states that two of his influences for the book were Randy Shilts' And the Band Played On and Richard Rhodes' The Making of the Atomic Bomb, but the defining moment for him was "when he conceived of his book as a biography".^[5]

It was described, by the magazine Time, as one of the 100 most influential books of the last 100 years, and by the New York Times magazine as among the 100 best works of non-fiction.

http://en.wikipedia.org/wiki/The_Emperor_of_All_Maladies

Doctors Are Now Inviting Patients To Help Design Their Own Medical Treatment

Posted: 03/23/2015 8:08 am EDT Updated: 2 hours ago

Anna Gorman, Kaiser Health News

SAN FRANCISCO -- Rose Gutierrez has a big decision to make.

Gutierrez, who was diagnosed with breast cancer last spring, had surgery and 10 weeks of chemotherapy. But the cancer is still there. Now Dr. Jasmine Wong, a surgeon at UC San Francisco, is explaining the choices – Gutierrez can either have another lumpectomy followed by radiation, or she can get a total mastectomy.

“I think both options are reasonable,” Wong said. “It’s just a matter of how you feel personally about preserving your breast, how you feel about having radiation therapy.”

“I’m kind of scared about that,” said Gutierrez, 52, sitting on an exam table with her daughter on a chair beside her.
“Well if you made it through chemo, radiation is going to be a lot easier,” Wong told Gutierrez, who is from Merced, Calif.

In many hospitals and clinics around the country, oncologists and surgeons simply tell cancer patients what treatments they should have, or at least give them strong recommendations. But here, under a formal process called “shared decision making,” doctors and patients are working together to make choices about care.

It might seem like common sense: Each patient has different priorities and preferences; what’s right for one patient may be wrong for another. Of course patients should weigh in. But many aren’t accustomed to speaking up. Even the most engaged or educated patients may defer to their doctors because they are scared, they don’t want to be seen as difficult or they think the doctor knows best.

For their part, not all doctors want to cede control to patients who have far less medical knowledge or who may be relying on information they got from friends and the Internet. Also, many physicians don’t have the time for long discussions and the health care system isn’t set up to pay for them.

Even so, hospitals and clinics in several other states, including Massachusetts, Minnesota and Washington, have created collaborative programs to ensure that information and concerns flow back and forth between patient and doctor. UCSF’s approach, in particular, has been a model for other programs around the nation.

Putting Patients in the Driver’s Seat
The concept of shared decision making has been around for years, but it is gaining new traction with the nation’s health law, which specifically encourages its use.

“Patients and families need to be in the driver’s seat with their doctors, making decisions that are the right choice for them for their unique circumstances,” said UCSF associate professor Jeff Belkora, who runs the shared decision-making program also known as the Patient Support Corps.

That way, he said, patients avoid “a rocky, bumpy ride” of either too much or too little treatment.

At UC San Francisco, patients receive DVDs, pamphlets or links approved by the physicians that explain available options for treatment. During appointments, the doctors not only explain carefully the benefits and the risks of those options but also ask about patients’ priorities and goals.

Patients are paired with college students or recent graduates who help them make a list of questions for the doctor beforehand. These young people also record the visit and type notes for the patients, who then leave with a definitive account of what was said.

That’s important because patients are nervous and emotional after a cancer diagnosis and often freeze up, said premed student Edward Wang. Wang said his presence helps put them at ease. “You’re just making a question list and you’re just taking notes,” he said. “But these simple things really do matter to the patient and to the doctor as well.”

Shared decision making has been used for patients with breast and prostate cancer, heart disease, back pain and other conditions for which there are multiple treatment options that offer similar results.

“It’s a massive cultural change,” said Glyn Elwyn, who researches shared decision making at The Dartmouth Institute for Health Policy and Clinical Practice. “It’s going from ‘I’m the expert, take my recommendation’ to ‘I am going to inform you and respect your wishes.’”

Elwyn and other researchers have found that patients are more satisfied with their care when they have a say in it. Also, it may save money. Some research shows that patients who are involved in their treatment decisions are more likely to be conservative, opting against costly procedures or surgeries.

‘It’s All a Black Cloud’
That doesn’t mean the decisions are easy – even for knowledgeable patients.

Ilene Katz, a UCSF nurse who often works with cancer patients, was recently diagnosed with breast cancer and became a patient herself.

At first, she wanted a mastectomy. “My knee jerk reaction, which probably a lot of women have … is there is cancer in my body, cut it out, cut all of it out,” she said.

But on this February day, she came out of the exam room feeling different. A long conversation with the surgeon and the oncologist helped her decide that, for her, there was no real benefit to having a mastectomy over a lumpectomy.

Katz said she was relieved someone was there taking notes so she could go over it later. “I don't remember everything,” Katz said, her eyes red from crying. “It’s all a black cloud.”

Katz’s doctor, Laura Esserman, said some patients want her to make choices for them. But Esserman, head of the UCSF breast care center, sees herself more as a coach, often asking questions to make sure patients don’t act out of fear or lack of knowledge: What’s the most important thing to you? How do you feel about your body image? What complications are you worried about?

Typically, Esserman said, she tells patients, “I need to know more about your thought process … and how you are going to feel a year from now.”

Candace Walls, 41, appreciates having some control over her care. Diagnosed with cancer six years ago in Stockton, Walls said the doctor recommended a mastectomy and then did the surgery.

“I didn’t have lots to choose from,” Walls said. “It was just kind of like, ‘This is what I think you should do.'”

Since coming to UCSF a year ago, however, she has been very involved with her decisions about breast reconstruction, even asking the doctor to redo part of the surgery when she didn’t like how it turned out. At a February appointment, Dr. Wong answered her questions one by one. “It is a very good feeling to know you can say what you want to your doctor,” Walls said afterward.

Working as a Team
That same day, Gutierrez, the patient from Merced, sat nervously in Wong’s exam room as the doctor explained more about her surgery choices.

“With the partial mastectomy we just need to take a little bit more tissue out … and then we would have to do radiation,” Wong said, as a note taker sat typing quickly. “With the [total] mastectomy, you probably wouldn’t need radiation but obviously it’s a bigger operation.”

Gutierrez said that as a single woman in her 50s, she wasn’t too concerned about keeping her breast. But she was worried about how her body would react to radiation. Most important, she wanted to be sure doctors got rid of the cancer.

“I have 12 grandbabies,” she said. “I want to be here for them.”

Still, Gutierrez told the doctors she was leaning toward the lumpectomy, saying she felt nervous about the pain. “I’m a big sissy,” she said.

“No, you are doing great,” Wong said. She encouraged Gutierrez to take the time she needed to talk over the choices with her family and to call if she needed to talk more. “I don’t want you to feel like you are pressured to make a decision.”

A few days later, Gutierrez decided on a mastectomy, mostly to avoid the radiation and the worry about cancer’s return. She had surgery in early March.

Reached by telephone the next day, Gutierrez said she felt good about her decision – and how she made it with her doctors. “It makes us seem like we are a team,” she said.

Kaiser Health News (KHN) is a nonprofit national health policy news service.

http://www.huffingtonpost.com/2015/03/23/inviting-patients-to-decide_n_6890324.html

Cancer: The mysterious miracle cases inspiring doctors

 David Robson

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• Hospital
• Medicine

It's extremely unusual and shouldn't give false hope, but what makes the body beat cancer on its own? (Thinkstock)

A few patients have made rare and unexpected recoveries leaving doctors scratching their heads, says David Robson. Can these cases prIt was a case that baffled everyone involved. The 74-year-old woman had initially been troubled by a rash that wouldn’t go away. By the time she arrived at the hospital, her lower right leg was covered in waxy lumps, eruptions of angry red and livid purple. Tests confirmed the worst suspicions: it was carcinoma, a form of skin cancer.

Just one in 100,000 cancer patients shed the disease – but why? — The secrets could inform medicine

The future looked bleak. Given the spread of the tumours, radiotherapy would not have been effective; nor could the doctors dig the tumours from the skin. Amputation was perhaps the best option, says Alan Irvine, the patient’s doctor at St James’ Hospital, Dublin – but at her age, she was unlikely to adapt well to a prosthetic limb. After a long and frank discussion, they decided to wait as they weighed up the options. “We had a lot of agonising for what to do,” says Irvine.

Then the “miracle” started. Despite receiving no treatment at all, the tumours were shrinking and shrivelling before their eyes. “We watched for a period of a few months and the tumours just disappeared,” says Irvine. After 20 weeks, the patient was cancer-free. “There had been no doubt about her diagnosis,” he says. “But now there was nothing in the biopsies, or the scans.”

Somehow, she had healed herself of arguably our most feared disease. “Everyone was thrilled, and a bit puzzled,” Irvine says, with some understatement. “It shows that it is possible for the body to clear cancer – even if it is incredibly rare.”

The question is, how? Irvine’s patient believed it was the hand of God; she had kissed a religious relic just before the healing set in. But scientists are instead looking to the underlying biology of so-called “spontaneous regression” to hunt for clues that could make these rare cases of self-healing more common. “If you can train the body to do this on a broader scale, you could have something that’s very widely applicable,” says Irvine.

Knowing how to trigger an immune response may help beat cancer (SPL)

In theory, our immune system should hunt out and destroy mutated cells before they ever develop into cancer. Occasionally, however, these cells manage to sneak under the radar, reproducing until they grow into a full-blown tumour.

By the time the cancer has reached the attention of doctors, unaided recovery is highly unlikely: overall, just one in 100,000 cancer patients are thought to shed the disease without treatment.

Disappearing act

Within those scant reports, though, there are some truly incredible stories. A hospital in the UK, for instance, recently reported the case of a woman who had experienced long-lasting fertility problems. She then discovered that she had a tumour between her rectum and her uterus, but before doctors could operate, she finally conceived. All went well and a healthy baby was delivered – only for the doctors to find that the cancer had mysteriously vanished during the pregnancy. Nine years later, she shows no sign of relapse.

What was it about the body of one pregnant woman that beat cancer? (Thinkstock)

Similarly spectacular recoveries have now been recorded in many different kinds of cancer, including extremely aggressive forms like acute myeloid leukaemia, which involves the abnormal growth of white blood cells. “If you leave the patient untreated, they usually die within weeks, if not days,” says Armin Rashidi at Washington University in St Louis. Yet he has found 46 cases in which acute myeloid leukaemia regressed of its own accord, although only eight avoided a relapse in the long term. “If you find a random oncologist and ask if this can this happen, 99% would say no – it makes no sense,” says Rashidi, who worked with colleague Stephen Fisher on the paper.

Agonising wait
In contrast, dramatic recoveries from a childhood cancer called neuroblastoma are surprisingly frequent – offering some of the best clues about what might trigger spontaneous remission. This cancer arises from tumours in the nervous system and hormonal glands. If it then spreads, or metastasises, it can lead to nodules on the skin and growths in the liver, with swelling in the abdomen that makes it difficult for the infant to breathe.

(Thinkstock)

Neuroblastoma is very distressing, yet it can sometimes disappear as quickly as it came, even without medical intervention. In fact, for infants less than one year old, regression is so common that doctors tend to avoid starting chemotherapy immediately, in the hope that the tumour will shrink by itself. “I can remember three cases with rather impressive skin metastases and an enlarged liver, but we literally just observed them – and they did well,” says Garrett Brodeur at the Children’s Hospital of Philadelphia.

The decision to sit and observe can be difficult, though: although the chance to avoid harrowing treatment comes as a relief to some parents, others find inaction and helplessness difficult to stomach. The agony of that period is one of the reasons that Brodeur wants to understand the mechanisms behind the cancer’s vanishing act. “We want to develop very specific agents that might initiate regression – so we don’t need to wait for nature to run its course or for ‘god’ to decide,” he says. 

Vital clues

So far, Brodeur has some strong leads. For instance, unlike other nerve cells, the cells in neuroblastoma tumours seem to have developed the ability to survive without “nerve growth factor” (NGF) – allowing them to flourish in the wrong parts of the body where NGF is absent. Spontaneous remission may be triggered by a natural change in the neuroblastoma tumour cells, perhaps involving the cell receptors that NGF binds to. Whatever the change is, it might mean that the cells can no longer survive without the essential nutrient. 

(Thinkstock)

If so, a drug that targets those receptors could kick-start recovery in other patients. Brodeur says that two drug companies already have some candidates, and he hopes trials will begin soon. “It would selectively kill tumour cells that are sensitive to this pathway, so it could spare patients from chemotherapy, radiotherapy or surgery,” he says. “It wouldn’t make them sick or their hair fall out, or cause their blood cell count to fall.”

Friendly fire

Unfortunately, unexpected recoveries from other kinds of cancer have been less well studied, perhaps because of their rarity. But there are some clues, and they could come from the pioneering work of a little-known American doctor more than 100 years ago.

It was the late 19th Century, and William Bradley Coley was struggling to save a patient with a large tumour in his neck. Five operations had failed to eradicate the cancer. Then the patient caught a nasty skin infection with a scorching fever. By the time he’d recovered, the tumour was gone. Testing the principle on a small number of other patients, Coley found that deliberately infecting them with bacteria, or treating them with toxins harvested from microbes, destroyed otherwise inoperable tumours.

(SPL)

Could infection be the key to stimulating spontaneous remission more generally? Analyses of the recent evidence certainly make a compelling case for exploring the idea. Rashidi and Fisher’s study found that 90% of the patients recovering from leukaemia had suffered another illness such as pneumonia shortly before the cancer disappeared. Other papers have noted tumours vanishing after diphtheria, gonorrhoea, hepatitis, influenza, malaria, measles, smallpox and syphilis. What doesn’t kill you really can make you stronger in these strange circumstances.

It’s not the microbes, per se, that bring about the healing; rather, the infection is thought to trigger an immune response that is inhospitable to the tumour. The heat of the fever, for instance, may itself render the tumour cells more vulnerable, and trigger cell suicide. Or perhaps it’s significant that when we are fighting bacteria or viruses, our blood is awash with inflammatory molecules that are a call to arms for the body’s macrophages, turning these immune cells into warriors that kill and engulf microbes – and potentially the cancer too. “I think the infection changes the innate immune cells from helping the tumours to killing them,” says Henrik Schmidt at Aarhus University Hospital in Denmark. That, in turn, may also stimulate other parts of the immune system – such as our dendritic cells and T-cells – to learn to recognise the tumorous cells, so that they can attack the cancer again should it return.

(SPL)

Schmidt thinks that understanding the process of spontaneous remission is vital, since it could help refine the emerging class of “immunotherapies” that hijack our natural defences to combat cancer. In one treatment, for instance, doctors inject some cancer patients with inflammatory “cytokines” in order to kick the immune system into action. The side effects – such as high fever and flu-like symptoms – are typically treated with drugs like paracetamol, to improve the patient’s comfort.

But given that the fever itself may trigger remission, Schmidt suspected that the paracetamol might sap the treatment’s potency. Sure enough, he has found that more than twice as many patients – 25% versus 10% – survive past the two-year follow-up, if they were instead left to weather the fever.

There could be many other simple but powerful steps to improve cancer treatment inspired by these insights. One man experienced spontaneous remission after a tetanus and diphtheria vaccination, for instance – perhaps because vaccines also act as a call to arms for the immune system. Along these lines, Rashidi points out that a receiving standard vaccine booster – such as the BCG jab against tuberculosis – seems to reduce the chance of melanoma relapse after chemotherapy.

Catching a cure
Others are considering a far more radical line of attack. For instance, one approach aims to deliberately infect cancer patients with a tropical disease.

Should we infect cancer patients with tropical diseases? (SPL)

The technique, developed by American start-up PrimeVax, involves a two-pronged approach. It would begin by taking a sample of the tumour, and collecting dendritic cells from the patient’s blood. These cells help coordinate the immune system’s response to a threat, and by exposing them to the tumour in the lab, it is possible to programme them to recognise the cancerous cells. Meanwhile, the patient is given a dose of dengue fever, a disease normally carried by mosquitoes, before they are injected with the newly trained dendritic cells.

Under the supervision of doctors in a hospital, the patient would begin to develop a 40.5C fever, combined with the widespread release of inflammatory molecules – putting the rest of the immune system on red alert. Where the tumour was once able to lurk under the radar, it should now become a prime target for an intense attack from the immune cells, led by the programmed dendritic cells. “Dengue fever crashes and regroups the immune system, so that it is reset to kill tumour cells,” says Bruce Lyday at PrimeVax.

(Thinkstock)

Infecting vulnerable patients with a tropical illness may sound foolhardy, but dengue fever is less likely to kill the average adult than the common cold – making it the safest choice of infection. Importantly, once the fever has subsided, the programmed immune cells will remain on the lookout for the tumour, should it reappear. “Cancer is a moving target. Most therapies attack from just one side – but we’re trying to put it in a lose-lose situation, now and in the future,” says Lyday.

No one could fault the ambition behind this kind of therapy. “Our mission is to replicate spontaneous remission in as standardised way as possible,” says Lyday’s colleague Tony Chen. Even so, they are keen to emphasise that their idea is still at a very early stage of development – and they cannot know how it will play out until they begin a clinical trial. The first tests, they hope, will begin with advanced melanoma patients, perhaps by the end of the year.

Clearly, caution is necessary. As Irvine points out: “Spontaneous remission is a little clue in a big complicated jigsaw.” But if – and that is a massive if – they succeed, the implications would be staggering. A rapid, relatively painless recovery from cancer is now considered a miracle. The dream is that it might just become the norm.