A plea to oncologists to confront the treatment of rare diseases

A plea to oncologists to confront the treatment of rare diseasesI only met her once; she was young—in her mid-thirties—and she had been diagnosed with ovarian cancer during her pregnancy. Following chemotherapy and the delivery of a healthy baby, she underwent a hysterectomy and staging. She was ultimately diagnosed with a rare ovarian cancer: small cell carcinoma. She underwent postoperative chemotherapy and had gone into remission.

Unfortunately, it was short lived, and she had been referred to me following her recurrence. I still remember that meeting—she looked scared but remarkably well; the only sign of cancer was the lack of hair on her head. She was nervous, searching for answers, desperately trying to remain hopeful, in control.

We discussed statistics, prognosis, treatments. I struggled to answer her questions; she had wanted specific information about small cell carcinomas of the ovary: what did it mean that she had recurred? What should be done to treat this type of cancer? I had told her it was not curable and that one day (hopefully not soon) she would likely succumb to her disease. But, she was a new mother—she wanted to fight, to explore every option.

We talked about standard treatments and clinical trials. Her tumor was rare—any experience in treating women with this cancer (including mine) was anecdotal. A path to remission, a direction towards the most promising treatment for her cancer was unknown.

At the end of the day, I am not sure I helped very much. I recommended a standard treatment approach; one that worked for ovarian cancer in general. She was eligible for several clinical trials, though none of them were specifically for small cell carcinoma. I gave her informed consents for a couple of studies and asked her to consider them. I told her I would keep my eye out for anything promising, or else she could see me again if there was a need to switch her current treatment.

As she walked out of my office, I was overcome by the unfairness of her situation, of life itself. Why would she be dealt this particular card? She who had just become a mother? Despite our work on genetic susceptibility and risk factors, we cannot predict who specifically will go on to be diagnosed with cancer, let alone what type of cancer they will develop. There are limitations to what the evidence tells us in oncology, particularly when it comes to rare tumor histologies like hers.

I was reminded of this patient and this encounter when I read an article entitled, “Lack of Data” by Dr. Julie Maher. Dr. Maher was a physician and, like my patient, a new mother. Like my patient, she was also diagnosed with small cell carcinoma, although in her case, it began in the cervix. She discusses her diagnosis and then her recurrence, treatments, and searching for ways to treat her cancer. She lamented the lack of evidence-based data to help guide the treatment of rare tumors.

There is a plea in Dr. Maher’s piece for the oncology community to confront the treatment of rare diseases. How to do this is challenging because randomized clinical trials (the evidence-based gold standard) will take time—a lot of time. Still, there is a concerted effort underway to address rare tumors. As an example, the Gynecologic Oncology Group (GOG) has assembled the Rare Tumor Working Group to conduct these trials.

But what Dr. Maher is asking for is a much more immediate solution than even what the GOG has implemented, because she (and my own patient) did not have the luxury of time. Indeed, both Dr. Maher and my patient ultimately succumbed to their cancer. I must admit, even to this day, I lament not being more helpful in guiding my own patient in an “evidence-based” direction (because the evidence does not exist).

I encourage all to read Dr. Maher’s piece, as the words come from one of “us,” taken all too soon. As an oncologist who has devoted himself to the treatment of women’s cancers, I am interested in how to respond to her call for action. Indeed, it is a discussion I am ready to be a part of.

Don S. Dizon is an oncologist who blogs at ASCO Connection, where this post originally appeared.

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  • Suzi Q 38

    So sad.
    My sister was diagnosed with colon-rectal cancer this past year.
    Two years ago, I had a hysterectomy due to endometriosis, pre uterine cancer, and a low malignant potential borderline proliferating tumor in my ovary. The geneticist suspected Lynch’s syndrome, which means that my sister and I have the odd capability of getting each other’s cancers.
    Time will tell. At least with the research, I can get my colonoscopies a bit more often than normally expected, and she can watch for excessive bleeding and get regular paps.
    My sister has had her surgery, chemo, and radiation.
    I just had my surgery.
    Cancer is always in the back of my mind, behind a heart attack or stroke.
    Keep fighting.
    Thank you.

    • drdondizon

      Dear Suzi, Thanks for your post, and I am wishing you and your family a healthy New Year. Best wishes, always! D

  • Neil Pfister

    Research being conducted for the more ‘common’ tumor types directly and significantly aids in the future treatment (10, 20, or 30 years depending on government support of such research) of rare cancers like small cell carcinoma of the ovary/cervix. These rare tumors, like the common ones, are caused by specific genetic mutations that are unique to each person’s tumor, and luckily there are many common mutations in genes such as p53, PTEN, H/K Ras, Rb, EGFR, and so on. While studying the common tumors, we are understanding how specific combinations of mutations drive tumor growth and choice / response to treatment.

    For patients with rare tumors, we will rely on ‘omics’ type data for the patient. We will define hundreds to thousands of specific normal / mutant genes for the patient’s tumor, and we will hopefully integrate this into how this affects the transcriptome for a particular patient, such that they may be over-expressing a particular receptor tyrosine kinase (nearly all of which can be targeted by current drugs). This will be cost-effective and quite routine in the near future. If there is a more concerted effort into understanding all cancers and implementing these large-scale molecular tests, we will soon have personalized tumor therapy, where by I receive these 1-5 drugs +/- radiation and surgery, and you receive those 1-5 different drugs +/- radiation and surgery, and they will work.

    Sadly, some super-aggressive cancers (like small cell) may never be cured with drugs once they are at a certain stage. Earlier diagnosis quite certainly may have saved this ladies’ life. Could this cancer not have been seen on routine ultrasound and not misdiagnosed as an ovarian cyst or other entity and not given a second thought at the time, for the grim alternative was so rare? Do we need to be investing more into diagnostic research (such as blood tests such as the PSA for prostate cancer), giving a panel test to certain aged folks every 5-10 years for cancer-related proteins? (We are not yet here clinically except for a handful of cancers).

    • drdondizon

      Dear Neil,
      Thank you for your great response. I share your hope for the era of genomics in oncology. Targeted treatment, although relevant to a subpopulation, will hopefully usher in a better way to approach cancer. Earlier detection is the key to cancer control, though some cancers are notoriously agressive even when diagnosed at an earlier stage (uterine carcinosarcoma, small cell cancer).
      In Dr. Maher’s case, she was diagnosed at an early stage- when adjuvant treatment was not indicated (based on known prognostic factors for cervical cancer in general). Unfortunately, she still experienced metastatic disease and ultimately succumbed to it.
      Obviously, there remains much to learn about cancers in general while we await a better way to treat them.
      Happy New Year Neil. DSD

  • http://twitter.com/Katiissick Kati Debelic

    i would rather have a rare cancer than what I got now, myalgic encephalomyelitis, aka chronic fatigue syndrome, be ause at least with the rare cancer, there would already be clinical trials happening and dozes of colleagues offering suggestions. with Me/CFS you get the boot with “no need to come back there is nothing I can do for you”.

    -previously healthy, endorphin addict, long distance cyclist, got sick with primary EBV infection, after 4years, almost bedridden.
    Health care is 2000 miles away.

    • michelle

      Sorry, don’t think you’re going to die in the next 1 to 5 years. I’m sure they’d all trade with you. I’ve witnessed moms of sweet little babies dying of funky cancers, hoping for a cure. Watching their babies grow up never having known mom is the worst.

      • drdondizon

        Hi Michelle- seeing young women die of their cancer leaving behind their kids is perhaps one of the worst things I have seen as an oncologist. Although not as painful, seeing patients suffer while living with cancer and its treatment-related side effects is also quite difficult.
        As oncologists, we have a duty to provide treatment and maintain quality of life. Let’s strive for both, not “either-or”.
        Happy new year, DSD

    • penguin50

      I don’t think you understand the nature of having a rare cancer. The
      point is that there are ZERO clinical trials or known successful
      treatments for very rare diseases. NONE. I have an extremely rare cancer
      from which I am expected to die soon, and there are so few of us that
      it is impossible to scrape together enough people to set up a trial, if
      any pharmaceutical company were crazy enough to think they could make
      money by selling a treatment meant for only the couple of hundred people
      with my illness. But I’m very sorry to hear of your CFS. It’s terrible
      to have a disease that is so misunderstood and discounted and leaves you
      feeling absolutely drained much of the time. I wish you all the best.

      • drdondizon

        Dear Penguin,
        My hope is that the era of cancer genomics will usher in better drugs, although they will be only helpful to a small subset of patients. We are seeing this come to fruition for patients with lung cancer and melanoma.
        We all wish it was happening at a much quicker pace; Dr. Maher’s plea is for speedier research, although she unfortunately will not be a beneficiary.
        As we wait, a partnership between patients and providers searching for options (reflecting thinking in and out of the proverbial box), and a call to publish reports of success, is required.
        Specialized centers in the NCI designated comprehensive cancer centers across the country should be able to assist as a repository of such information. Perhaps as a community we can urge the creation of such a national database. Many who were touched by Dr. Maher’s JAMA article appear willing to help, including me.
        In the meantime- I wish you the best and will keep you in my thoughts for the coming year.
        DSD

        • Suzi Q 38

          I understand the researchers and the pharmaceutical companies. Like it or not, they need to treat the masses or not make enough money. It is sad that it has to be about the money, when you can look at the face of a beautiful person (Dr. Maher) that had to leave it all (her life) so soon.

          I read her letter, to the JAMA through your link. I wanted to read more, but I was not a subscriber. Reading it will just have to wait until I get to a teaching hospital computer.

          I think she wanted any information about the treatment of small cell. Maybe there were cases out there in the U.S., if not the world that had experienced some success with prolonging life.

          She is so right on.
          If the doctors do not have time to publish such experiences with certain patients, then maybe we as patients can publish our own anecdotal experiences with certain rare illnesses or cancers.

          If it helps one or more people with said illness, it would be worth it.

          • drdondizon

            Dear Suzi:
            There are so many variables out there that play a piece in medical research. I still hold out hope that the primary objective of all the players is to help people. Having many friends from medicine who joined the pharmaceutical field has convinced me that their primary motivation was the desire to make more of a difference from the R&D side than the financial aspects of that career. Still, I think we are living in an era of shared partnership and a larger venue for information exchange that will see more opportunities for patients to share and learn from each other- I just hope it is in concert with their doctors, who must also embrace that medical knowledge may come from more and more unconventional sources. Its both an unexciting and unchartered time in medicine; tread carefully…
            DSD

          • Suzi Q 38

            Yes, doctor. Thank you for making the point that we need to always include our doctors in our ideas and subsequent plans.
            Most of the time, people follow the protocols and do what the oncologist says.

            On the other hand, when you have a desperate situation, without any approved methods or ideas for treatment,
            the patient says, “What the heck, why not try?”

            This is why some of the patients end up in Mexico or other countries, like India.

            Maybe the FDA rules are not so strict, and after all hope is almost gone, they figure out the plane ticket to another country may be worth a look.

            I have had friends that took the last ditch trip to Mexico.
            They were terminal, and getting weak.

            Sad, but they died out of the country and obviously we missed precious time with them. On the other hand, they died trying wil hope that it would work, and they might get better.

            This effort would not be for me, but I can understand the desperation of others.

          • drdondizon

            Dear Suzi,
            I appreciate the thoughtfulness in your post. I think communication is key, especially in scenarios where there is little hope- whether it be to disease progression, lack of resources, or lack of options.

            As physicians we can only offer honest opinions, and the support for our patients in every decision they face. Sometimes it will be against our recommendation, but in the end, it is up to that person to decide.

            DSD

    • drdondizon

      Dear Kati, Having friends with chronic fatigue, I understand your difficulties with finding a physician who can compassionately treat your condition. I would like to thing there is a growing realization in medicine it is truly a real condition, particularly for a previously healthy female.

      Still, as the responses below to yours shows, here is a tendency in medical “politics” to see diseases as “competing for attention” which is so unfortunate. Every disease warrants research and every voice should be heard.

      I think my blog is somewhat applicable to your own journey in medicine as well- a search for answers, direction, and treatment. Aterall, living and living well is what everyone hopes for. Certainly, it is what patients with rare cancers share with you.

      Happy New year, DSD

  • visitor

    the idea that every treatment decision must be evidence-based breaks down in these scenarios. additional tools and protocols are needed for dealing with rare pathologies, and also for dealing with those that haven’t attracted a lot of research interest/funding. seriously, in our everyday lives, most decisions are made based on hypotheses being tested on very small datasets. likely most evidence that saved our ancestors from accidental poisoning was even anecdotal. solid decisionmaking is essential; we just need to apply rigorously all of our ways of knowing.