Measuring Outcomes: What the Newly Diagnosed Should Know

I open this post by offering key definitions that are helpful to anyone impacted by a cancer diagnosis, directly or indirectly, which speaks to nearly half of the population of the United States. Indeed, “Approximately 38.5 percent of men and women will be diagnosed with cancer of any site at some point during their lifetime” (reference). I explain the standard metrics for monitoring cancer response to treatment, and I discuss the role of these metrics in determining the standard of care protocol. I conclude with a discussion of the cancer experience that is not so easily quantified, or captured by the established metrics. My aim is that in this article, persons relatively new to the cancer experience may find tools to better equip their journey. The National Cancer Institute (NCI) offers a similar resource on understanding cancer prognosis (here).

 

Standards of care for treating cancer—that is, the established “protocols” for how, when, in what sequence, and guidelines for determining dosage, vary by cancer type, yet for at least 50 years, the general cancer treatment program is colorfully, if not cynically, called “slash and burn,” referring to the twin procedures of surgery and radiation therapy. Or, “slash, burn, and poison,” when cytotoxic (cell-killing) chemotherapy agents are ordered following surgery and radiation. The new era of “precision medicine,” which employs highly specialized treatments engineered to target the biological characteristics of a person’s cancer, promises to discard this primitive slash, burn, and poison program, but to date, hugely successful outcomes that result from targeted therapies in trial for quite specific cancers have failed to be borne out clinically in the general cancer patient population. In short, for all the hype of precision medicine, day-to-day treatment protocols across the country maintain the status quo.

 

The aim of any treatment protocol is to offer the therapy, singularly or in combination with others, that is most likely to produce the greatest degree of therapeutic efficacy, or “disease response.” Therapeutic efficacy, disease response, is measured with sophisticated diagnostic imaging tools such as MRI, CT, or PET scans. The overarching therapy effectiveness metric for cancer types is quantified by median overall survival (OS), meaning the time after diagnosis when half the measured population has died and the other half is still living. Median progression free survival (PFS) offers a similar metric quantifying the time following diagnosis that half the population has experienced disease growth or recurrence and the other half has not. Take my case, glioblastoma, with a median OS of roughly 15 months (reference). This indicates that 15 months following diagnosis, half of the diagnosed population is no longer living, and half of the population is continuing to live. My current time since diagnosis is today (August, 2017), 15 months out, meaning statistically, half of those who were diagnosed around the same time I was have since passed away. Some died very quickly after diagnosis, and others will live three, four, five, sometimes six or eight years longer. Of course I aim to be included in those outliers showing long-term survival of five or more years.

 

Protocols are tested against current standards of care, typically in randomized control trials, to measure OS and PFS against the current medians for the standard of care. Regulatory bodies, the Food and Drug Administration (FDA) for example, approve drugs, devices, and procedures, when those therapies increases either OS or PFS for the trial population above the current standard of care, without an intolerable side effect profile, or increased toxicity. Trial therapies that perform better than current standards, or when no current standard is established, have a likely chance to be approved. Sustained improvement in key metrics over time, reported in longevity studies, meaning spanning long time frames, or meta-analyses, meaning spanning large and diverse populations, may lead to a revision or new standard of care for a cancer type that is treated by the newly approved therapy.

 

In short, the standard of care is established for umbrella categories of cancer types based on measuring the same key metrics across large populations over a long period of time. Those therapies, or combination of therapies, that maximize OS and PFS, while mitigating toxicity are selected as the ongoing standard of care.

 

The politics of drug discovery and approval involve governmental regulatory agencies, multi-billion dollar pharmaceutical industries, and culturally embedded research paradigms. That is all too much to thoughtfully discuss in this article. I will say only this: reimbursement drives the systemic treatment of cancer. Standard of care therapies are typically covered by health insurers, but many experimental treatments or so-called “off-label drugs,” that is, drugs approved in the treatment of one disease that show promise for treating other diseases but are not yet proven in randomized control trials, often are not covered by insurance. Relatedly, the genomic sequencing that is required to determine the appropriate “precision medicine” to target a person’s specific cancer variant is currently not covered by the majority of health insurers.

 

Standard of care offers patients the protocol with the statistically demonstrated best shot at long-term survival. Standard of care is also the protocol commonly covered by insurance. On its face, this is a good thing that insurance covers the standard of care for a disease, but there is at least one downside. This schema ties patient treatment options to governmental budgeting priorities and big money lobbyists. In a purely hypothesized scenario, but not one divorced from reality, if a lawmaker hears from her lobbyist from big pharma that disease X is well controlled with approved treatment Y, then the prospect to increase funding to the National Institutes of Health (NIH) may appear less pressing to the lawmaker who sees little reason to pay the big price tag of experimental research, when the lobbyist is showing their company’s success rates. This introduces a feedback loop where the government fails to fund research, insurance companies have little reason to reimburse experimental therapies, and patients are offered fewer options to explore cutting edge therapies. It is for these reasons that I advocate for increased research funding for the NIH, its subsidiary arm, the NCI, and not-for-profits, like the National Brain Tumor Society (NBTS) who equip persons affected by brain tumors to raise their voices to lawmakers who may only be hearing one side of the experimental research budgeting issue.

 

Taking stock, so far I have roughly defined key metrics put in service to monitor the effectiveness of our treatment protocols, I have explained how these metrics are used to revise standards of care, and I have revealed one issue with our reimbursement-driven healthcare system, namely, that it serves as a barrier to funding trial research. Now, I turn my attention to the experience of illness—something not easily reported by standardized metrics. To resolve this issue, patients must learn to tell their stories! The fields of medicine and pharmaceuticals are becoming more interested in something called patient reported outcomes (PRO). These PRO metrics speak to the quality of life impact given a selected treatment protocol, but constructing a narrative, with the support of friends, family, and trusted clinical practitioners, is the best way for a patient to share their experience with lawmakers and medical teams to serve as a catalyst for change—whether the change is to ask congress for budgeting priorities or frame a conversation with a patient’s clinical specialist.

 

Harnessing the power of story telling can also be a powerful tool to communicate with loved ones who struggle to know how best to respond to the illness experience.

 

I disengaged my friend group at each of three milestones in my life: first, when I started grad school, I lost friends to my study commitments; I picked up an evening job in the service industry to help care for my kids during the day, attend class in the afternoon, and bartend for income at night. Second, when my wife and I grew our family by having kids, my friends were mostly grad students and bartenders, not the most family-friendly groups, and adjusting to family life created a rift in some of these relationships; third, when I was diagnosed with aggressive and incurable brain cancer.

 

I cancel on friends often: dinner plans, concerts, hanging out to catch the Cubbies play, I cancel these plans all the time. Sometimes because I am fatigued, sometimes because I know the environment will trigger a focal seizure, or at least bring on seizure-like symptoms: left-sided numbness, light-headedness, dizziness, and headache, or for what has been the case recently, I cancel because I just want to be home, with my wife and kids nearby. Brain cancer has dynamically changed my relationship with my wife. The emotional burden we carry cannot be overstated. The metrics, the open trials, morning email bulletins from medical news outlets all twist and turn their way through my mind each day. My wife works hard in a trauma hospital to support our family, to be the only driver in our home to get each of us in our family of five to where we need to be, to carry our family’s medical benefits, and she manages our monthly budget. She and I are both exhausted. She needs more sleep than she gets. I need support from friends who understand, but with a disease incidence rate of three in 100,000 and only 5% of the diagnosed population living five years, it is difficult to find a friend locally who shares my diagnosis, and among my non-cancer friends, it is tough to find one who not only listens, but who understands. I look for emotional support from my wife, which places yet more burden on my care partner to fulfill multiple roles in my life.

 

I read, write, and research daily, fearing that I must approach my “work”—blogging, public speaking, working on a manuscript, with urgency because the course of my disease, or the effects of the treatments to control the disease, in time will negatively impact my higher level cognitive functioning. Here I am, a head full of medical knowledge, self-imposed restrictions on having pizza and beer, pretty disengaged from new music, sports news, and pop culture, and never much wanting to do anything other than do each day only those things that contribute to the big goals I set out for myself before I reach my dot on the overall survival normalization curve.

 

Practicing how we construct our stories to communicate these emotions, decisions, and reactions in a way to inform our friends and family and not alienate them is an acquired skill that will take each person impacted by a cancer diagnosis, directly or indirectly, some time to cultivate. It is my hope that equipped with the language in this article, and the glimpse into my personal experience, you may find your attention to these issues more focused.

7 thoughts on “Measuring Outcomes: What the Newly Diagnosed Should Know

  1. You are doing all the right things, making all the right choices. Your priorities are definitely in order. In addition you find the heart, courage and strength to articulate your journey and your experiences. Sending gentle long distance hugs to you and yours.

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  2. First of all, you made it thus far (!) and are helping those who read your words become more informed.
    I needed to retire from academia after my dx. in March 2014 having had only a biopsy, I read everything I could about gbm. because I didn’t think I would live very long and I wanted to know treatment options, trajectory, etc. I also made a will, started a scholarship at the school I worked at, made funeral arrangements, signed up for CaringBridge, etc. It really helped to have those “tasks” behind me and I then relaxed into my journey. While some friends fell away, new ones magically appeared.
    I now find myself grateful beyond words to wake up to another day.

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  3. Thanks again Adam for your guidance. After the last few weeks attending to the needs of Blake’s family due to Henry’s mesoblastic nephroma, I have a more personal understanding of all you have lived and all your family has lived over the 15 months of your diagnosis. I am so grateful for your response to this cancer. I know I have benefitted and I am sure many others are thanking God for your strength and insight into narrative medicine and faithful living. I look forward to seeing you and your family soon.

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  4. Adam, thank you so much for all that you do, and how you communicate it through this blog.

    My wife, Stefani, was diagnosed with a anaplastic astrocytoma in Dec2016, and, following a craniotomy after SoC RT and Chemo in April this year, a GBM. Needless to say, this lead us to your blog, and we’ve been along for the ride with you ever since. And we’re grateful for your approach and focus as neither of us are possessed of the skills nor focus you have. You’re helping us and others, so again, thank you.

    I am personally curious about the specifics you have learned as regards targeted therapies for GBM, specially, those in trail (as are most at this point if I understand correctly). Stef is in that stage where, following SoC and Gamma Knife, she’s “stable” with no progression in her bi-monthly MRIs. Hence, our neuro-oncologist, and other independent research indicates that she’s not currently a candidate for trials. Thus, it’s a bit difficult at this time to get details about “what’s next?”

    Yet, given your extensive research, I hope to glean some insight from what you’ve learned about what our next steps might be for Stef. What do you find most promising, if anything? And why?

    We send our love and support for you and yours all the time, Adam. We’re pulling on the oars with you, and always will.

    Ced and Stef

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    1. Ced and Stef (I thought first to respond to Cedric and Stefanie, but “Ced and Stef is perfect, and people refer to my wife, Whitney, and I as “A&W,” so Ced and Stef it is! 🙂 Thanks for reading along, and I appreciate your kind and generous words. I know exactly what you mean, wondering “what’s next? what now?” Though I haven’t (yet) dedicated a post to this, Whitney and I decided recently to discontinue Temodar, after 11 monthly “5/23” cycles. I suspect you both know, but if not, and to others who may be reading the comments, I’ll start with a little explanation: the standard protocol for glioblastoma calls for surgery, then 60 days of daily chemotherapy, temozolomide (Temodar), with radiation therapy, followed by six cycles of temozolomide. Each cycle includes five days of high-dose (usually 2-3x the daily dose that is administered during radiation therapy) followed by 23 days “off” to recover. Voila! Five-twenty-three, or “5/23,” TMZ (temozolomide). My oncologist said he would stop after twelve cycles, and he spoke to us plainly that there is no decisive evidence to support that 10 or 11 cycles is any better than 12, and anyway, the standard protocol is six. OK! Enough preliminaries! My MRI scans have all been stable, not counting the “post-surgical” changes (reduced swelling, fluid collection and depletion, etc). I have not had recurrence, or stated more cynically, standard of care has not yet failed. Like Stefanie, I am not currently eligible for trials, which is a double-edged sword because I’m ineligible for trials having had a near total resection (removal) of the tumor and no recurrence. Reason to celebrate! The flip, of course, is that I am not on any active treatment, and there is this terrible anxiety that we are just waiting around for the tumor to come back. I’d guess that is how many of in the brain tumor community feel. You asked about my personal research into the most promising experimental therapies, and my response is sort of a let-down, but I do not mean for it to be. My response is that I really just do not know. Most importantly I want to emphasize that I have zero medical training, right, and that does not mean I cannot be a resource, of course, I actively work on this blog so I *can* be a resource! But I think there is a step between posting informational and autobiographical content and the jump to endorsing specific therapies. Another, less “legally” reason is that the genetic profile of Stefanie’s cancer may advise for or against certain treatments. Mutations on some genes increase the disease response rate to chemo, other mutations increase the resistance to chemo, and so on. I do want to say more than nothing, though, so I’ll say this: immunotherapy continues to carry the day in all of the medical journalism that I’m reading a regular basis, so I focus some of my time tracking those trials. My best advice is to become familiar with trials and their eligibility criteria. National Brain Tumor Society has a good trial finder (http://trials.braintumor.org). Eligibility criteria varies from age, other drugs a patient is on, other past therapies, genetic profile, and so on… Once you identify a few trials for which Stefanie may be eligible, you can track their status. That way if and when the tumor recurs, you can feel like you’ve already “done your homework.” Psychologically that may help you feel more at ease. And seriously, drop me an email and keep me updated! We are definitely all in this together! Talk soon… Cheers, A.

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      1. Hello Adam,
        I follow your blog almost daily and appreciate your comments very much. Today is the 1st anniversary of my diagnosis (my daughter called “911” when she noticed graphic changes in my mental status). After ceaseless seizures, on life support for a while, craniotomy and debulking of much of the tumor, I did the TMZ/radiation route for 42 sessions, then the intense (7/35) TMZ for months afterwards. I couldn’t get in one of the clinical trials for nanoparticle therapy until after a certain period without TMZ, so I opted for Avastin IV (not considered chemo) each 2-3 weeks and MRIs, like yours, have shown no “progression”. I was surprised that the Avastin, which prevents new tumor growth by preventing capillary growth in said new growth and is the same med used to inject into the eyeballs of Wet Macular Degeneration in some of my peers (I’m 71). As you shared, age may be an obstacle to some therapies as genetic differences in the tumor or patient himself. My oncologist is the director of clinical trials and research at the University of New Mexico Cancer Center and had shared some of the available treatments for this invader and I understood that Avastin, like any other intervention, comes with a number of risks along with the benefits it offers and it is one therapy that doesn’t preclude entering a clinical trial with another agent. Like you, Adam, I am not a professional trained in oncology, but don’t mind sharing my own experience and resources. For anyone reading your blogs, I also have gained much information from the National Brain Tumor Society.

        Looking forward to future blogs by you, Adam. Your integrity, honesty, compassion and presentation are priceless. My best wishes and prayers for all of us GBMers. Thanks, again!

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  5. Very courageous. Great attitude. Stay positive. Get through today, tomorrow will take care of itself. I’m all about support now for fellow GBM patients and advocacy, Race for Hope Philly and Head to the Hill every May. I attend my Brain Tumor Support Group at HUP every month. I’m there for the newly diagnosed with the deer in the headlights look in their eyes and tell them with all the conviction I can muster, “If it can happen to me, I see no reason why you can’t have the same outcome.” A little bit of hope goes a long way.

    So far? So good.

    Be well Adam. Hang in there…
    Lindsay
    Gr IV GBM – Dx 2007 – 10 yr survivor

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