On Reducing Cancer Care Costs by Resetting Expectations, and Hope

Today we should move forward on the list published in the NEJM on Bending the Cost Curve in Cancer Care. We’re up to point 7 in our discussion, what’s 2nd in the authors’ proposed changes in attitudes and practice: “Both doctors and patients need to have more realistic expectations.”

This point follows closely from the previous, that doctors need to talk with patients earlier on end-of-life issues. But the central issue here is that most patients with cancer are unrealistic about their prognosis, and that oncologists do a terrible job in correcting their misperceptions:

…According to one recent study, most of the patients with lung cancer expected to live for more than 2 years even though the average length of survival is about 8 months.3

Resetting expectations will be difficult. Tools are available to help the oncologist provide truly informed consent by sharing anticipated response rates, chances of cure (always near zero for patients with metastatic solid tumors), and side effects…Many oncologists do not have these skills,43 so use of a decision aid may help…

What they’re describing amounts to Lake Wobegon effect, from the patient’s perspective, and that may be fair enough.

But I think these authors are letting oncologists off easy. Why it is that they lack “these skills,” i.e. what it takes to help patients face reality? It happens yesterday I was reading Dave deBronkart’s book, How to Laugh, Sing and Eat Like a Pig, on his experiences as a patient with metastatic kidney cancer, and he cites a terrific, pertinent excerpt in Dr. Jerome Groopman’s The Anatomy of Hope:

Hope, unlike optimism, is rooted in unalloyed reality. …Hope acknowledges the significant obstacles and deep pitfalls along the path. True hope has no room for delusion.

Clear-eyed, hope gives us the courage to confront our circumstances and the capacity to surmount them. For all my patients, hope, true hope, has proved as important as any medication.

Groopman’s point is that real hope rests in reality.

Going back to the NEJM piece –

I don’t think oncologists need (or better, should need) decision aids to help them reset patients’ unrealistic expectations. What they need is time, and thoughtfulness, and the capacity to be genuinely empathic.

If our health care system promoted trusting, and ideally longer, relationships of cancer patients with their physicians, patients would be less fearful of hearing the truth, and their doctors would be less afraid to speak honestly with them. This would reduce cancer care costs by lessening futile treatments, and would improve the quality of the patient-doctor relationships in oncology, besides the quality of care, in itself, and patients’ experiences as they near the end of life.

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Cathy Swims and Runs in Episode 6, Season 2 of the Big C

I almost liked the latest installment of the Big C. Cathy swims, for starters. I could relate.

She’s wearing goggles, no less. That’s universal “code” for seriousness about swimming, or acting. She swims well and pretty fast. Within seconds she befriends the competitive girl-swimmer in the next lane and, wouldn’t you know it, the girl’s team needs a new coach.

Cathy, who is undergoing treatment for Stage IV melanoma in a clinical trial about which the audience knows 0, steps in to coach the team. She meets some resistance from parents who worry about her condition and associated unreliability. She alludes, vaguely, to her rights as a cancer patient and firmly vows to lead the team.

“I can do it” is this episode’s message.

After some ups and downs, and after the viewer suffers from the director’s crude decision to mix the patient’s possibly having a pelvic rash as a side effect with her learning that she has crabs, aka pubic lice, Cathy goes running with the swim team members.

Cathy runs with the team in Showtime's 'The Big C'

How often can a metastatic cancer patient in the midst of serious systemic (meaning non-surgical, not focused radiation or minor) and non-hormonal cancer treatment run with athletes 25 years younger? Only on TV, or in very, very exceptional cases.

Some basics, please: How about feeling tired? Or a relevant rash?

A dose of reality might help this TV program that’s said to be about cancer, or life with cancer.

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Reducing Cancer Care Costs: Oncologists Need to Get a Grip on Reality, and Talk about Dying

We’ve reached the second half of our discussion on Bending the Cost Curve in Cancer Care. The authors of the NEJM paper, Drs. T. Smith and B. Hillner, go on to consider how doctors’ behavior influences costs in Changing Attitudes and Practice. Today’s point on the list: “Oncologists need to recognize that the costs of care are driven by what we do and what we do not do.”

In other words (theirs): “The first step is a frank acknowledgment that changes are needed.” A bit AA-ish, but fair enough –

The authors talk about needed, frank discussions between doctors and patients. They emphasize that oncologists/docs drive up costs and provide poorer care by failing to talk with patients about the possibility of death, end-of-life care, and transitions in the focus of care from curative intent to palliation.

They review published findings on the topic:

In a study at our institution of 75 hospitalized patients with cancer, the oncologist had initiated a discussion of advance directives with only 2 patients.31 In a prospective, multicenter study of 360 patients, only 37% of the patients and their families could recall having a discussion about impending death with the physician.32 Such a discussion is a prerequisite to good planning. Oncologists wait until symptoms appear or until they believe that nothing more can be done.33 In one study, at 2 months before their death, half the patients with metastatic lung cancer had not had a discussion with their doctors about hospice.34 This may explain why in a recent series the average length of stay in hospice for patients with lung cancer was 4 days.35

Although I have questions about the specific methods for some of these references, the bottom line is clear: Oncologists wait too long to talk with their patients about palliative or hospice care.

What they’re saying is that doctors need to get a grip on the problem (to overcome their denial and inability to talk about death), if they want to help patients come to terms with the inevitable. Doing so would save billions each year in the US, and would also spare patients from futile treatments and needless suffering.

I couldn’t agree more. It’s a potential win/win, if physicians think realistically about the situation and possible outcomes, and speak openly – and gently, no matter what, with their patients.

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Mammography Update!

This week I’ve come across a few articles and varied blog posts on screening mammography. The impetus for rehashing the topic is a new set of guidelines issued by the American College of Obstetricians and Gynecologists. That group of women’s health providers now advises that most women get annual mammograms starting at age 40.

Why every year? I have no idea. To the best of my knowledge, there are no data to support that annual mammograms are cost-effective or life-saving for women in any age bracket at normal risk for BC.

Pertinent also, is a recent paper* in the Annals of Internal Medicine supporting a personalized approach to BC screening and mammography for women over the age of 40, and an editorial* to go with it.

“Talk to your doctor,” is the point for patients. (Women’s breasts are not all the same.)

“Talk with your patient,” is the point for doctors: Consider your patient’s breast density, family health history and personal preferences. Great idea!

We need an Annals paper to tell us this?

My personal view, synthesizing all the medical literature of which I’m aware, and taking account all of my prior experiences as a practicing oncologist, and not forgetting I’m a woman, now 50, who had an early-stage breast cancer discovered by a radiologist – and this is not medical advice – is as follows:

For women of normal risk, such as without a strong family history or a prior cancer:

1. Start with a baseline, digital mammogram at age 40. The image should be digital first, because this kind of technology is better for visualizing dense breast tissue which is more common in pre-menopausal, younger women and second, because digital images can more easily be shared with another doctor, for a second or more expert opinion if necessary.

2. Get mammograms every other year, unless there’s a significant abnormality that requires follow-up sooner. Until what age? Hard to say. (A complex topic… hold that thought for another post.)

3. Supplement mammography every other year with monthly self-examination of the breast. This inexpensive method of feeling one’s own breasts, regularly and methodically, has not been shown to save lives in randomized clinical trials. But I am convinced that if it’s done right – when a gynecologist, PCP, internist or other caregiver takes the time to teach her patients how to do the breast self-exam properly  – as I used to instruct my patients in the clinic, women can help themselves to catch breast tumors early.

4. Mammograms should be done, exclusively, by appropriately-trained radiologists who spend the bulk of their time reading mammograms, performing sonograms of the breast and taking occasional biopsies, as appropriate. (Sorry, general radiologists, but that’s how it is. Would you want your mother’s breast image examined by a radiologist who also reads hip films and MRIs of the brain?) The rate of false positives is lower when mammograms are performed by specialized “breast” radiologists.

5. Take advantage of the fact that mammography centers have been regulated for nearly two decades by the FDA. Be sure that the place where you get your mammogram is MQSA-accredited.

All for now –

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*subscription required for full text

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Lowering Cancer Care Costs by Limiting Chemotherapy in Patients Who Aren’t Responding

This is the sixth post on Bending the Cost Curve in Cancer Care, based on the 10 suggestions put forth by Drs. Smith and Hillner in the May 26 NEJM.  We’re up to number 5 on the list for changing oncologists’ behavior: by limiting further chemotherapy to clinical trial drugs in patients who are not responding to three consecutive regimens.

They’re right.

Giving one drug or combination regimen, and then another, and another, and another, to cancer patients whose tumors resist multiple regimens is more likely to cause harm than good. Oncologists need be realistic with themselves and with their patients, in a kindly way, when treatments fail.

Options to consider, besides chemo, include palliation (which can be started at any time, including before and during chemotherapy), alternative approaches (such as hormonal or immune-based therapy, for some tumors), hospice care and participation in a clinical trial, as the authors suggest, based on the patient’s condition and preferences.

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The Big C: Cathy Goes For Treatment

In this week’s episode, Boo!, Cathy wakes up in the morning eager and ready to start treatment on a clinical trial. The day doesn’t go well – the local treatment center doesn’t have needed information about her insurance, which can’t be tracked down on time, her 15 year old son gets in trouble at school, and her husband loses his job.

That kind of day – when it seems like everything possible that can go wrong, goes wrong – will seem familiar to many if not all cancer patients. 

But the show continues to fail in providing any meaningful cancer information whatsoever. OK, I’m starting to accept the fact that ratings would suffer if the doctor gave even a 30 second mini-talk on BRAF mutations in melanoma. There will be no science on Showtime. But the scriptwriters could, at least, have included the discussion of the doctor and Cathy’s signing informed consent for the trial. There’s not a word about what treatment she’s getting, or what the shots she took in the last episode were for.

You’ve got to wonder if Laura Linney’s character, the “patient,” understands the purpose of the trial she’s on, the nature of the experimental treatment and risks.  The FDA approved Yervoy (ipilimumab) for patients with advanced melanoma months ago (considered here). Did her oncologist offer her that drug and, if so, why did she choose the clinical trial? Might the oncologist have a conflict of interest, in regard to the research? Is Cathy enrolled in a Phase I, II or III trial?

Please tell me something about her treatment! So far I see the Big C as a lost opportunity for teaching about cancer medicine – through humor and the potential talent of a terrific actress, or about meaningful and realistic patient-doctor relationships, or about informed consent.

If I hadn’t said I would follow the show and post on it this season, I’m not sure I’d bother watching it any further.

But I’m a compulsive sort of doctor-blogger-patient: I’ll keep watching it, at least for this year’s episodes, and I’ll keep you posted, in case you care about Cathy’s predicament, or if you want to share her thoughts on the show.

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Reducing Cancer Care Costs: Why Not Offer Neulasta in Smaller Vials?

This is the fifth in a series of posts on how we might reduce the costs of cancer care, based on 10 suggestions offered in a May, 2011 NEJM sounding board. We’re up to point 4:  oncologists should replace the routine use of white-cell-stimulating factors with a reduction in the chemotherapy dose in metastatic solid cancers.

In this section, the authors allude to what I think might be a cost-saving advance in oncology practice: why not make available lower doses of white blood cell (WBC) colony stimulating factors?

The issue is this: when people get high doses of chemotherapy, they’re compromised because the bone marrow doesn’t create new WBCs as it should. The risk of infection during chemo used to be so great that, in the 1980s and earlier, it was common for cancer patients to succumb to infection. With the advent of WBC stimulants in the early 1990s, the risks of infection during chemo dropped markedly.

These are complex and expensive drugs. And while I agree with the NEJM authors that chemotherapy is over-used, often, I don’t think it makes sense to cut down on potentially helpful doses or combinations of those drugs just because WBC stimulants are expensive.

Take Neulasta (pegfilgrastim), a long- acting stimulator of neutrophils manufactured by Amgen. This injectible drug costs over $ 2,000 for a single, 6 milligram vial. It’s supposed to be given every 2 weeks, although some oncologists might give it at a lesser frequency, depending on the chemo cycles. There’s only one size dose available for all patients; they’re all billed for the full 6 milligrams.

This is an ideal situation for Amgen, which takes in over $2000 for each 6 milligram vial. It’s far from perfect for patients who, even if there’s no toxicity, pay huge co-pays with each chemo cycle.

You can find some patients’ discussions of this issue at cancer support sites like these. There’s also a public correspondence between Medicare and the State of Wisconsin on the high costs of this drug.

Around 10 years ago, when I was practicing, I wondered why we couldn’t give some patients less than 6 milligrams of Neulasta. This would be useful in at least three situations: for patients who are physically small; for those who receive lower doses of chemo; and for people who are hyper-sensitive, for whom just a tiny bit is enough to raise the white count adequately. A frequent toxicity is bone pain; this is intense in some patients and, in theory, would be less problematic if a lower dose were available. Once, I almost got into administrative trouble for asking a pharmacist to draw up only half of the dose from a vial so that I might give a petite woman only 3 milligrams of this powerful drug.

Since then, nothing’s changed. I looked it up yesterday; there’s still only one dose of Neulasta: 6 milligrams.

So if Neulasta were sold in lower-dose vials, like 1, 2, 3 or 4 milligrams, patients could receive lesser doses, as is often appropriate. The costs of these drugs, when administered properly, might be halved, approximately, without compromising on recommended doses of chemotherapy.

Just my two cents, nothing more –

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Reducing Costs by Holding Back on Chemotherapy for Cancer Patients Who are Frail

This is the fourth in a series of posts on Bending the Cost Curve in Cancer Care, by Drs. Thomas J. Smith and Bruce E. Hillner, in a recent NEJM health policy piece. The authors’ third suggestion: to limit chemotherapy to patients with good performance status, with an exception for highly responsive disease, is surely one of the most controversial.

What they’re suggesting is a simple rule: “Patients must be well enough to walk unaided into the clinic to receive chemotherapy.” There are necessary exceptions, they point out, such as cancer patients disabled by another medical condition but who otherwise can carry out daily activities with relative normalcy. (I’ll offer an example: say a 50-year woman with multiple sclerosis who is wheel-chair bound but otherwise essentially well; she would be a candidate for treatment in this scenario.) But in general the authors would hold off on chemotherapy for cancer patients with a limited performance status  – a measure that oncologists use to assess how well, or disabled, a person is in their capacity to work, perform ordinary daily activities and care for him or herself.

I’m not sure I agree with the “walking” threshold, or ECOG performance status 3 or below, as the authors describe: “meaning that they are capable of only limited self-care and are confined to a bed or chair more than 50% of waking hours.” These criteria are subjective and problematic. But I do think the authors are onto a central, unavoidable issue in reducing health care costs. That is by limiting care, i.e. by rationing.

For elderly patients with cancer, especially for those who have significant other illnesses, it may not be appropriate for doctors to give chemotherapy and other, non-palliative cancer treatments. The authors don’t (dare) advise a particular age cut-off for therapy; they suggest using performance status criteria. They conclude this section of the paper on cutting cancer care costs with this statement:  “Implementation of such a simple threshold could dramatically decrease the use of chemotherapy at the end of life.”

The authors are right, that we (oncologists and other doctors) shouldn’t be in the business of routinely giving aggressive treatments to patients who are very old and frail, who are more likely to suffer harms of treatment than potential benefits. Not just because we can’t continue driving up U.S. health care costs indiscriminately, but because when very frail, elderly patients are given chemotherapy they’re less likely to recover after treatment. By not saying “no” to patients who are too fragile for a requested intervention, or by simply treating patients who are so feeble or demented, or both, that they’re unable to say “no” for themselves – such as sometimes happens in nursing homes and other chronic care facilities, doctors may cause more harm than good.

Some readers of this blog may be wondering how I can reconcile this position with what I’ve said about access to Avastin for women with advanced BC. In my opinion, patients’ age and, broadly, their functionality – if they can think and communicate seems at least as relevant as whether they can walk – should be factored into the risk/potential benefits analysis of almost any medical treatment.

So if we’re going to consider restricting cancer drugs and interventions based on cost, indirectly or overtly, we should account for patients’ ages, the potential length and quality of life to be gained: If there’s a 50 year old patient who might benefit from a costly cancer treatment, it’s likely that person will benefit more from that drug than would a 70 year old patient, or a 90 year old patient. It’s also more likely, but not a sure thing, that a younger, otherwise healthier patient will tolerate a given treatment with fewer side effects.

Hard to know where and how to draw the lines.

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Reducing Cancer Costs by Giving One Drug at a Time, Sequentially

This is the third in a series of posts on Bending the Cost Curve in Cancer Care, based on the late-May NEJM health policy piece.

Today we’ll consider the second of the authors’ suggestions: to limit second and third-line treatments to sequential monotherapies for most solid tumors. This particular suggestion, one of the few proposed with which I disagree, falls under the rubric of how oncologists’ behavior might be modified. The authors write:

A Cochrane meta-analysis showed that combination therapy had a small advantage over single agents for first-line therapy but caused more toxicity, and the review left unresolved the question of whether sequential single agents were a better choice.

…patients will live just as long but will avoid toxic effects. Second, society will benefit from cost reductions associated with less chemotherapy, fewer supportive drugs, and fewer toxicity-associated hospitalizations.

This approach is tempting, cost-wise, but may be simplistic: The purpose of combination chemotherapy is to give agents that work additively or synergistically, typically each at a lower dose, to achieve more effective treatment. In cancer, the best-studied multidrug regimens are in lymphoma, leukemia and breast cancer. Similar principles apply to antibiotic regimens for some infectious diseases, such as the drug “cocktails” for HIV or tuberculosis.

It could be that the authors are right for certain agents and some tumor types. But, likely, some drugs, including new targeted treatments given to patients who’ve already had several treatments, may be most effective and, paradoxically, less toxic – because the dose of each drug can be lower. The likelihood of resistant clones emerging may be diminished, too.

The problem we’re left with, of course, is that testing the different combination regimens will be costly. But I wouldn’t assume it’s better or necessarily cost-effective to give cancer drugs one at a time.

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Patients’ Words, Unfiltered, Medical Journalism and Evidence

Yesterday’s post was not really about Avastin, but about medical journalism and how patients’ voices are handled by the media.

L. Husten, writing on a Forbes blog, cried that the press fawned, inappropriately, over patients’ words at the FDA hearing last week, and that led him to wonder why and if journalists should pay attention to what people with illness have to say, even if their words go against the prevailing medical wisdom.

There’s a fair amount of controversy on this. For sake of better discussion in the future, I think it best to break it up into 3 distinct but inter-related issues:

1. About health care journalism and patients’ voices:

A general problem I perceive (and part of why I started blogging) is how traditional medical journalists use patients’ stories to make a point. What some of my journalism professors tried to teach  me, and most editors I’ve dealt with clearly want, is for the reporter to find a person with an illness, as a lead,  and then tell about the relevant news, and provide some expert commentary – with at least one person speaking on each “side” of the issue, of course – and then end the story with some bit about the patient and the future.

I argue that this form of medical journalism reduces the patient to an object, used by the story-teller in order to capture the reader’s attention. So, with exceptions and always with the person’s consent, I prefer to offer my own story, from my perspective, so as not to use the patient as a vehicle or literary device.

So it appears that Husten is OK with using patients’ voices to tell a story (and sell papers/clicks?), but not with presenting their views unfiltered if they don’t mesh with the party line or a particular point an editor wants to make. This lies at the center of the journalism issue.

(As an aside, a few recent published studies have found value in analyses of patient-reported symptoms, unfiltered even by their doctors.)

2.  About Avastin:

My impression is that some beast cancer advocates, including a National Breast Cancer Coalition representative who spoke at the FDA hearing, have chosen to “take the hit” on this particular issue because they need and want to appear rational. The straightforward-seeming argument is that the data show Avastin doesn’t work and is often harmful, so it shouldn’t be FDA-approved for women with metastatic BC. From the perspective of a BC advocacy group, it may not be worth pushing for a drug that helps only around 5% of patients.

The problem is there’s no biomarker for Avastin responsiveness, because this drug doesn’t target a particular genetic marker. Rather it works by cutting the blood supply, which could vary even within a particular patient’s mets in different organs. The only way to test if Avastin works in a patient is to give the drug, with informed consent, and see how it goes. Unlike, say, a bone marrow transplant, which runs in the range of hundreds of thousands of dollars and, once done, is irreversible, you can give one dose of Avastin and stop it, or two and stop it, if it doesn’t work or it is not well-tolerated.

Based on my experience as an oncologist and patient who’s received some risky interventions, I don’t think Avastin is more toxic than many or even most cancer drugs. Rather, its side effects have been heavily pushed by the media and public health/epidemiology academics in the past two years, who perhaps wish to make a larger point about this costly drug and evidence based medicine (EBM).

3. About evidence-based medicine: I’m in favor of EBM, especially in principle. The problem is that published medical data is too-often flawed and also, that some patients are, really, outliers.

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No Room For Emotion or Exceptions to the Rule (on Avastin)

My cousin testified before the FDA oncology advisory board on Tuesday about her experience taking Avastin. This is a tragedy, to deny the only drug that is keeping a 51 year old woman alive.

image from p.3 of today’s NYTimes business section

You have to wonder, are the advisory panel members so rational in all their behavior and choices? Are they always so razor-like in their oncology decisions?

Unlikely.

These experts have an agenda, here: It’s to be perceived as scientists, even when their knowledge is imperfect and exceptions to the rule stand right in front of their eyes. But clinical medicine calls for flexibility, and tailoring of treatment to each case, and caring about each person, including those who fall at the tail, or in this case better end, of any Kaplan-Meier survival curve.

What would Larry Kramer do about this, I’ve been thinking: He’d scream, really loud, so loud he might break his eardrums. He’d wonder why others, affected and near, aren’t doing the same. And he’d understand why this picture is on page 3 of the business section, and not on the front cover; it’s because people don’t want to look or see or know or think about it too much, because it hurts.

That is the normal heart, and this is a normal response to what’s happening to women with metastatic breast cancer.

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Cathy Wants a New Doctor and a Second Opinion

Last night the Big C returned, not surprisingly with an opening dream sequence. Laura Linney, portraying Cathy Jamison in the Showtime series, is running. The scene turns out to be a nightmare, and she awakens with a headache and her husband by her side.

Laura Linney portrays Cathy, hugging her son in Showtime's "The Big C"

OK so far.

Within a few minutes, Cathy’s young oncologist informs her that the interleukin 2 hasn’t worked; after two rounds of “chemo” the melanoma hasn’t budged. Sitting at his desk in the consultation room, he suggests she roll some joints for relief of headaches. She says she wants another opinion. It’s about time.

The main problem Cathy faces in this episode is that she can’t get an appointment with her oncologist of choice, Dr. Atticus Sherman despite calling, calling and calling. So finally she thinks out of the box: “That would be a coffin,” intimates her deceased, elderly neighbor Marlene who visits, spiritually, from Season 1.

So Cathy dons a suit and heels, and pulls a small suitcase with wheels – in the style of a drug sales rep – to work her way into the famed oncologist’s office. This desperate strategy, reminiscent of that suggested by journalist Elizabeth Cohen in the Empowered Patient book, and tried at least once by Samantha in Sex in the City when she had breast cancer, seven years ago or so on HBO, nearly backfires. But in a stroke of changed fate, the same doctor’s office calls Cathy to let her know she’s got an appointment for next week.

Such drama, just to get an appointment didn’t move me. But perhaps I’m too removed from this sort of painfully real situation for the countless, frustrated patients who can’t get appointments with appropriate specialists.

I was disappointed with the episode for other reasons. It wasn’t rich with ideas. There was no meaningful discussion of Cathy’s cancer, and only a shallow exploration of her feelings.

Like other TV comedies, this show was about everyday junk and family life: her son’s farting habit, her friend’s active sex life and pregnancy, her brother’s insanity, her dog’s seeming to be dead and then turning out to be alive. This (non) focus is fair enough, I suppose; when a person has cancer, they’re indeed surrounded by people in their family and friends who have their own needs and issues.

A particular beef is this: Clearly Cathy needed a second opinion; that’s been the case all along. But the script-writers made it too easy by having the young oncologist be utterly clueless and behaving inappropriately. The value of a second opinion would be clarified if Cathy had chosen to seek another doctor’s input even if she were receiving seemingly expert care from a solid, more experienced physician.

And where is the Internet in all of this? Her friend Rebecca (Cynthia Nixon) might be looking some stuff up. Or her brother, for that matter, who’s now said to be manic depressive, could be maxing out on free and potentially useful information. His anger at his sister would be more credible if it were less extreme and if he were less bizarre; his is not a fair or typical depiction of his stated mental illness.

How will Cathy’s appointment with Dr. Sherman go next week? We’ll see.

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What’s Next on the Big C? (Hopefully a Second Opinion)

(Hopefully a second opinion)

When I last wrote on The Big C, a Showtime series in which the actress Laura Linney portrays a woman in her forties with advanced melanoma, I considered some of the options she might choose when the series resumes next Monday night.

Laura Linney, in Showtime's 'Big C'

At the end of Season 1, she elected to try a course of IL-2 as was recommended by her young oncologist. Meanwhile, the FDA has approved Ipilimumab (Yervoy), an antibody treatment that revs up the immune system. And she’s in line, according to the script, for possible entry into a clinical trial that likely involves a targeted therapy, like vemu­rafenib for patients whose malignant cells have a genetic mutation in B-RAF.

What I expect Cathy will do, before anything else happens and she receives any additional non-urgent treatment for her advanced melanoma, is get a second opinion. She’s a smart, sensible sort; in retrospect it’s hard to believe she didn’t do this earlier on and before starting the IL-2 therapy.

I wonder, also, if one of her family members or friends will do some research about melanoma on the Internet. That would help her find a doctor with appropriate expertise, and better know what questions she should ask of the oncologist during the consultation.

That’s all on Cathy’s decision, until next week.

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Lowering Cancer Care Costs by Reducing Tests After Treatment

This is the second in a series of posts on Bending the Cost Curve in Cancer Care. We should consider the proposal, published in the NEJM, gradually over the course of this summer, starting with “suggested changes in oncologists’ behavior,” #1:

1. Target surveillance testing or imaging to situations in which a benefit has been shown. This point concerns the costs of doctors’ routinely ordering CTs, MRIs and other imaging exams, besides blood tests, for patients who’ve completed a course of cancer treatment and are thought to be in remission.

The NEJM authors consider that after a cancer diagnosis many patients, understandably, seek reassurance that any recurrence will be detected early, if it happens. Doctors, for their part, may not fully appreciate the lack of benefit of detecting a liver met when it’s 2 cm rather than, say, just 1 cm in size. What’s more, physicians may have a conflict of interest, if they earn ancillary income by ordering lab and imaging tests.

My take:

It’s clear that some and possibly most cancer patients get too many and too frequent post-treatment surveillance tests. Believe it or not, yours truly, whose life was saved by a screening digital mammogram, maintains a healthy fear of excess radiation exposure. I agree to x-rays, CT scans, myelograms and whatever else my doctors suggest only when I’m reasonably confident that the test result would influence a treatment decision.

My impression is that, in general, oncologists’ habits of ordering routine, interval-based imaging for patients in remission after cancer treatment (such as a scan every 3 or 4 or 6 or 12 months) are arbitrary and unsupportable by any published data. These sorts of practices, which vary among communities, arise like this: A senior, smart and well-intentioned oncologist at a major teaching hospital, circa 1990, orders newfangled CT scans of the chest, abdomen and pelvis on his lymphoma patients every 4 months for two years, and then every 6 months for two years, and then every 12 months, for no reason other that he thinks it’s a good idea. The patients like it; they’re reassured, and he (the oncologist) feels good about having prescribed the drugs that caused their sustained remission.

Talk about a positive feedback loop! (We needn’t even invoke financial incentives as a motivating force.) And then that’s just how it’s done by all the fellows he’s taught over the years, who then branch out into other communities and even other countries, and teach…

Why not?

Now things may be changing a bit, as patients like me are starting to fear radiation exposure, and also are starting to question doctors’ recommendations more than they did even a few years ago. Younger doctors, too, have more requirements to continue their medical education in order to keep practicing at most hospitals and maintain their board certificates, and so they, too, may be more questioning of these archaic practices.

About post-treatment screening with scheduled blood work, I see this issue somewhat differently than do the NEJM authors, mainly in that I’m optimistic about simple blood tests, in the future, that may provide affordable and clinically relevant information to patients who’ve undergone treatment with tumors at high risk of recurrence.

As the authors point out, there are some old tests, such as CEA screening, that can be helpful in monitoring for recurrence in patients with a history of colon cancer. In general, blood tests are less dangerous and less expensive than imaging studies. Besides, in patients with aggressive tumors that might respond to new targeted drugs, tests that measure circulating tumor cells (CTCs) in small blood samples, and could assess cells for new mutations, at low costs in the future (not now), might render some blood tests useful and even cost-effective, in the future.

Finally, I’d like to throw in a concern I have about some clinical trials, in case any study designers or persuasive cancer IRB members happen to be reading this post:

Some of the clinical trials for new cancer drugs may require too many follow-up MRIs, CTs and other scans. Even if Pfizer or any other company foots the bill, by participating in the trials patients shouldn’t be subjected to excessive radiation or even just the unpleasantness and hassle of a said-to-be-safe test like an MRI. This pet peeve is especially concerning in some trials requiring multiple post-treatment PET scans, the most rad-intense of common imaging methods.

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FDA Approves New Assay for Her2 in Breast Cancer

This week the FDA approved a new assay for Her2 expression in breast cancer biopsies. The technology, Inform Dual ISH, is manufactured by Ventana Medical Systems, a Roche subsidiary.

From Ventana Medical: the HER2 and Chromosome 17 probes are detected using two color chromogenic in situ hybridization (ISH)

Inform Dual ISH works like this: technicians, typically working under the supervision of a pathologist, expose a tiny bit of a breast biopsy specimen, fixed on a microscope slide, to probes for Her2. This gene, normally found on human chromosome 17, is amplified in some breast cancer cells. The assay exploits an enzyme, linked to the genetic probe, which creates a color (in this case, red) upon exposure to a chemical. The system allows a pathologist, using a microscope, to “see” and measure the gene’s presence on chromosomes in cells of an ordinary biopsy sample.

What’s interesting about this in situ hybridization (ISH) kit is that it doesn’t require a fluorescent microscope for imaging. The Ventana probe generates a simpler, ordinary color signal that can be detected by a light microscope. Most commercial assays for Her2 use a method called immunohistochemistry (IHC); that technique relies on antibodies that bind Her2, a cell surface receptor that’s implicated in cancer cell signaling and growth. This and other ISH assays measure genes directly on the chromosomes; by contrast, IHC usually tests for protein.

Her2 is the molecular target for Herceptin, and there’s been considered discussion about how and where it might be accurately assessed. So the “readout” from this diagnostic test might inform a woman and her doctor in deciding whether or not she should receive treatment with Herceptin.

How pathologists evaluate breast biopsy specimens matters a lot, especially when you’re on the receiving end of a diagnosis and you’re choosing among treatments. In 2007, ASCO and the College of American Pathologists published guidelines on Her2 testing in the Journal of Clinical Oncology. These groups recently updated the recommendations. How this new assay will be received by these societies, I’m not sure.

A key question, in this author’s mind, is where the Her2 measurements take place, and whether women should rely on local labs’ assays – by whatever method – to determine the Her2-ness of their breast tumors.

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Running 2 Lists That Might Lessen the Costs of Oncology Care

Recently the NEJM ran a Sounding Board piece on Bending the Cost Curve in Cancer Care. The authors take on this problem:

Annual direct costs for cancer care are projected to rise — from $104 billion in 20061 to over $173 billion in 2020 and beyond.2…Medical oncologists directly or indirectly control or influence the majority of cancer care costs, including the use and choice of drugs, the types of supportive care, the frequency of imaging, and the number and extent of hospitalizations…

The article responds, in part, to Dr. Howard Brody’s 2010 proposal that each medical specialty society find five ways to reduce waste in health care. The authors, from the Divisions of Hematology-Oncology and Palliative Care at Virginia Commonwealth University in Richmond VA, offer two lists:

Suggested Changes in Oncologists’ Behavior (from the paper, verbatim – Table 1):

1. Target surveillance testing or imaging to situations in which a benefit has been shown.

2. Limit second-line and third-line treatment for metastatic cancer to sequential monotherapies for most solid tumors.

3. Limit chemotherapy to patients with good performance status, with an exception for highly responsive disease.

4. Replace the routine use of white-cell-stimulating factors with a reduction in the chemotherapy dose in metastatic solid cancer.

5. For patients who are not responding to three consecutive regimens, limit further chemotherapy to clinical trials.

Suggested Changes in Attitudes and Practice (same, Table 2):

1. Oncologists need to recognize that the costs of cancer care are driven by what we do and what we do not do.

2. Both doctors and patients need to have more realistic expectations.

3. Realign compensation to value cognitive services, rather than chemotherapy, more highly.

4. Better integrate palliative care into usual oncology care (concurrent care).

5. The need for cost-effectiveness analysis and for some limits on care must be accepted.

—-

For today, I’ll leave this provocative list without comment except to say that it should engender some long and meaningful, even helpful discussion.

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Quotes on Oncology, Via Forbes, and a Spiraling Helix

Forbes kept a close eye on the annual ASCO meeting in Chicago. On THE MEDICINE SHOW, Forbes’ Matthew Herper provides a précis of a speech by outgoing ASCO President Dr. George Sledge.

Here are my two favorite parts:

“So what happens when, a few years from now, a patient walks into a doctor’s office and hands a physician a memory stick loaded with gigabytes of personal genomic data?” Sledge asks. His answer: the flood of data will help doctors and patients, but things will get “very, very complicated.”

and

…Doctors will need real-time access to clinical data from all practice settings. This in turn will require interoperable databases using common terminology. Health information technology should offer on-the-spot decision support to oncologists and patients facing the increasingly complex tapestry revealed by modern genomics. It should provide individualized, ready access to a clinical trials systems. It should support appropriate coverage and reimbursement for services. And it should aggregate data so that we can learn from every patient’s experience.

DNA orbit animated smallWhat he’s saying, in a nutshell, is that oncologists will need to know science and have access to effective HIT to interpret and act upon the ever-growing pile of info on cancer genetics as it applies to people in general and individual patients. I recommend the full read.

An added perk in the MEDICINE SHOW piece is a terrific, gyrating DNA model courtesy of Wikipedia (@Forbes!).

For an additional twist (PM, 6/7), turns out Wikipedia offers a mutable Medicine Show of its own.

What goes around…?

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Considering Aromasin for Healthy Women, and the New Breast Cancer Prevention Study

I’m minding the annual meeting of the American Society of Clinical Oncology from a distance this year.

So far, the big breast cancer story syncs with a NEJM paper published yesterday on-line, on the use of exemestane (brand name: Aromasin, manufactured by Pfizer) to prevent invasive breast cancer. These patent-protected pills block the body’s normal production of estrogen.

The main finding was that for women deemed “at risk” for developing BC – as defined by the investigators – the incidence of cancer was significantly reduced when they took Aromasin as compared to a placebo. At a median observation point of 35 months, there was no observed effect on the women’s survival.

What’s right about the study: it’s prospective, randomized and large, including over 4560 women. The results are clear in terms of percents and relative risks: There was a 65% relative reduction in the annual incidence of invasive breast cancer (0.19% vs. 0.55%) and a hazard ratio of 0.35 (with confidence interval 0.18 to 0.70; P=0.002). So they’ve got strong stats.

Estrogen, typically depleted but not absent in post-menopausal women, can promote growth of breast cancer cells. From the paper’s first section: “Aromatase inhibitors profoundly suppress estrogen levels in postmenopausal women and inhibit the development of breast cancer in laboratory models.” So the findings are plausible, which helps, too.

The first problem (or non-problem, really) is there were only 43 cases of invasive BC in total; there wasn’t much cancer, or its reduction, in either arm of the study in terms of absolute numbers. This makes the divergent percents reported seem far less impressive. Second, and more importantly – the long-term consequences of taking this relatively new estrogen-inhibiting drug, in terms of women having thinner bones, possibly more cardiovascular disease, diminished libido and other side effects, are unknown.

Already there are two drugs marketed to prevent breast cancer in some women: tamoxifen and raloxifene. These drugs, also anti-estrogens, have significant side effects including blood clots, and few women choose to take them as prophylaxis for breast cancer. The new study suggests Aromasin is better because it’s got fewer side effects; Pfizer’s idea is that it’s a safer option for women who want to reduce their risk of developing BC.

But what caught my attention is who qualified for this trial: Most healthy women over the age of 60 – that’s a whopping, growing population of potential Aromasin-takers, besides the relatively small number of women with known pathology such as precancerous or stage 0 breast cancer (conditions like LCIS and DCIS, for which a preventive drug seems justifiable) or high risk-conferring BRCA-1 or -2 mutations.

Reading over the trial’s eligibility, I had to wonder, how could anyone think it reasonable to treat all women over the age of 60 with an estrogen inhibitor? And who populated the IRBs that approved this protocol? (Imagine if oncologists were to propose testing the effects of chemical castration in thousands of men over the age of 60; few would support such a trial, although in all likelihood androgen ablation would reduce the incidence of prostate cancer in men.)

The NEJM article lists support for the work from the Canadian Cancer Society Research Institute, the Canadian Institutes for Health Research, Pfizer, and the Avon Foundation. Among my many questions, I’d like to know what exactly what fraction of the study’s support came from Pfizer. The Journal (and every) should break this down for a published non-advertisement: If Pfizer provided 5% or 50% or 95% of funding for the trial, readers should be informed, as should women who might choose to take this drug and their doctors who might prescribe it.

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First Look at the Burns Collection of Early Medical Photographs

CBS News has posted a gripping set of images, mostly of cancer patients, dating to the 1880s. The photos from the Burns Archive are graphic, as much as they’re telling, instructive and rare.

 

This photograph, taken in New York City in 1886, is one of the earliest ever taken of breast surgery. Surgeons had begun to adopt infection-control measures in the operating room, but at this point they hadn’t yet adopted the use of surgical masks and hats and their surgical gowns were simply put on over their street clothes. The anesthesiologist whose hands are visible holding the patient’s arm on the left side of the frame is wearing street clothes. Anesthesiologists were the last doctors to don surgical clothing in the operating room.

Credit: Dr. Stanley B. Burns, via CBS News

According to its website, the Burns Archive houses the nation’s largest and most comprehensive collection of early medical photography (1840-1920). It turns out the collection is based on East 38th Street. It’s nearby, and I should explore it for real.

Meanwhile, I recommend that my non-squeamish readers take a look at the CBS-published images. If nothing else, these digitized relics display how far improved are surgical methods – and cancer treatments – since the late 19th Century.

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Defining a Cluster of Differentiation, or CD

One of the goals of this blog is to introduce readers to some of the language of medicine. As much as jargon is sometimes unnecessary, sometimes the specificity and detail in medical terms aids precision.

So what is a cluster of differentiation, or CD?

In medical practice, the two-letter acronym specifies a molecule, or antigen, usually on a cell’s surface. In 1982, an international group of immunologists got together for the First International Workshop on Human Leukocyte Differentiation Antigens. The initial focus was on leukocyte (white blood cell) molecules. The goal was to agree on definitions of receptors and other complex proteins to which monoclonal antibodies bind, so that scientists could communicate more effectively.

A few examples of CDs about which you might be curious:

CD1 – the first-named CD; this complex glycoprotein is expressed in immature T cells, some B cells and other, specialized immune cells in the skin; there are several variants (CD1a, -b, -c…) encoded by genes on human chromosome 1.

CD4 – a molecule on a mature “helper” T cell surface; T lymphocytes with CD4 diminish in people with untreated HIV disease.

CD20 – a molecule at the surface of immature B lymphocytes that binds Rituxan, an antibody used to treat some forms of lymphoma, leukemia and immune disorders.

 

In this schematic, an antibody recognizes a specific molecule, or cluster of differentiation, at a cell surface.

The CDs were named (i.e. numbered) not necessarily by the order of discovery, but by the order of their being deemed as bona fide CDs by HLA Workshop participants. There’s a pretty good, albeit technical, definition in FEBS Letters, from 2009:

Cluster of differentiation (CD) antigens are defined when a surface molecule found on some members of a standard panel of human cells reacts with at least one novel antibody, and there is good accompanying molecular data.

Perhaps the best way to think about CDs is that they’re unique structures, usually at a cell’s surface, to which specific antibodies bind. By knowing the CDs, and by examining which antibodies bind to cells in a patient’s tumor specimen, pathologists can distinguish among cancer types. Another use is in the clinic, when oncologists give an antibody, like Campath – which binds CD52, the responsiveness might depend on whether the malignant cells bear the CD target.

Still, I haven’t come across an official (such as NIH), open-source and complete database for all the CDs. Most can be found at the Human Cell Differentiation Molecules website, and information gleaned through PubMed using the MeSH browser or a straight literature search.

Wikipedia is disappointing on this topic; the list thins out as the CD numbers go higher, and the external references are few. To my astonishment, I found a related page on Facebook. Neither makes the grade.

Where should patients get information about these kinds of things? Or doctors, for that matter?

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