Monday, June 11, 2012

The rest of the appeal letter

In my first post, I published the cover letter of the winning appeal. Here is the rest of the letter.

Why My Condition Requires Proton Beam Therapy (PBT)


Proton radiotherapy is the preferred treatment modality for Ms. Call’s life-threatening malignant paraganglioma of the left carotid body. The targets will include the left neck to the base of the skull. Protons will minimize dose to the surrounding critical structures including the spinal cord and brainstem… Proton beam irradiation therapy will be particularly beneficial for Ms. Call given her young age of 28 years old and long life expectancy. (Dr. Adam Garden, M.D. Anderson Radiation Oncologist, Appeal letter to Anthem, May 11, 2012)


Within days of my diagnosis with this rare cancer, I met radiation oncologist Dr. Allen Chen at UC Davis Medical Center. As lead author of nine recent papers on head and neck cancers—two studies comparing different radiation treatment types, a study on radiation beam location and implications for tissue damage, and a study on IMRT outcomes for unknown cancers—he is among the top physicians in his field and uniquely qualified for work on rare tumors such as mine. Given the exceptional nature of this case, however, he quickly reached out to other colleagues in the radiation oncology community. It was under Dr. Chen’s encouragement that I sought a second opinion at M.D. Anderson.

There I met Dr. Adam Garden, who first introduced me to Proton Beam Therapy (PBR). Also specializing in head and neck radiation oncology, Dr. Garden has published eight articles on the detrimental side effects of radiation therapy. As I learned from Dr. Garden, PBR should minimize the risk of both acute and chronic side effects, including secondary cancers and damage to important structures in my neck, head, and jaw. With this information, the decision to pursue PBR was easy.

Anthem’s recommendation to the University of California to deny coverage for PBR is based on the claim that the medical reviewers have not seen any medical studies that show that PBT is as good as other treatments for my condition. Since immersing myself in the literature, I can only conclude that Anthem, acting on behalf of the University of California, simply has not looked. The evidence for PBR’s effectiveness for head and neck cancer—indeed its superiority—is overwhelming.  I believe that on a more thorough review of the literature, Anthem would overturn its previous recommendation to the University.

For example, Yoon, et al., (2010) compared IMRT and proton therapy for patients with head and neck tumors, prostate cancer, and brain tumors. They found that for head and neck treatment there was a lower relative secondary cancer rate for all organs, even for the thyroid gland, with PBT. Purdy (2008) explains that relative to IMRT, PBT reduces the radiation dose to healthy tissue and the risk of leakage and scattered radiation. In a study of conventional radiotherapy, IMRT, and PBT, Palm and Johansson (2007) find that “the data consistently show that proton beam therapy substantially decreases the OAR [organs at risk] average dose compared to the other two techniques.” Metz (2002) reaches a similar conclusion: “Side effects, both acute and long-term, typically seen with X-ray therapy can thus be markedly reduced with proton beams due to the sparing normal tissues that are situated around the tumor. These considerations are directly related to the physical characteristics of the proton beam, and require no demonstration or study. However, data are available from clinical series that support them.”

In addition to the physical benefits I expect from receiving PBT instead of IMRT, there is strong evidence that it will reduce my long-term healthcare costs as well. Lundkvist, et al., (2005) conduct a cost-benefit analysis and estimate that a patient of 65 years would spend over $5000 less in dental bills over her lifetime (in 2012 dollars) by choosing PBR over IMRT. This number would be substantial higher for me, since at 28 I have a longer life expectancy, and it does not include any valuation of quality of life or non-dental health-care costs. The long-term cost-savings and quality-of-life benefits of proton therapy are discussed by Pijls-Johannesma, et al., (2008), who write that “It is expected that in the long run, due to a decrease in the absorbed integral dose, fewer secondary cancers will be induced. Also, due to the expected decrease in side effects and increase in tumor control probability (TCP), it is expected that long-term costs will decrease as a result of less hospitalization, less palliative care and improved quality of life.”

Another head and neck cancer patient, Steve Harris, recently sought proton treatment at M.D. Anderson. Although his application for insurance coverage was initially denied, his appeal was upheld.  According to the radiation oncologist who treated Harris, “It's important to minimize any other side effects that can occur… With head and neck cancer, you’re close to the centers that affect taste and smell, the swallowing function, and day-to-day speech” (Work, 2012).

M.D. Anderson is not alone in supporting patients seeking PBR. In fact, “to most radiation oncologists and physicists, the benefit of proton therapy in many clinical cases is without question; protons allow sparing of normal tissue, which is unarguably beneficial to patients. Indeed, to a radiation oncologist experienced in delivery of proton therapy, the decision of whether or not to employ it in a given case is analogous to a surgeon’s decision regarding the choice of a particular scalpel or cautery device”’ (Hill-Kayser, et. al, 2011).

The Term "Investigational" Has No Meaning When Applied to a Rare Cancer


Ms. Call should not be denied the options available for this treatment of her malignant paraganglioma of the left neck.  Proton therapy is the best and only treatment option and medically necessary for Ms. Call considering her age of 28 years and her prior surgical/treatment history. (Dr. Garden, Appeal letter to Anthem, May 11, 2012)


For my case, PBT is no more “investigational” a procedure than the IMRT therapy that Anthem is recommending the University of California offer. An investigational procedure, according to my Benefit Booklet, is one that is “not widely accepted as proven and effective within the organized medical community.” Anthem’s dismissal of my request for PBR on these grounds is problematic in several respects. First, as is detailed throughout this document, the organized radiation oncology community strongly supports the use of PBR for cancer treatment. Second, the rarity of my cancer and my young age relative to most radiation patients preclude the identification of a “proven and effective” treatment for my condition. Finally, advancement of the state of the art in radiation therapy has never relied solely on clinical trials. IMRT, for instance, was “widely adopted without comparative trials based on the same type of surrogate dose distribution modeling that supports the case for proton therapy” (Robert L. Foote, MD, Professor of Radiation Oncology, Mayo Clinic, as quoted in Morgan, 2009). Proton therapy for prostate has also been considered investigational (Suit, et al., 2008), but patient Paul A. Morgan was approved for treatment by Independence Blue Cross despite the lack of Randomized Phase III Clinical Trials comparing proton therapy to photon beam therapy.

Awaiting results on clinical trials in a case like mine raises ethical issues. In a particularly relevant recent article in the International Journal of Clinical Oncology, a leading journal for peer-reviewed papers on newer treatments, Ogino (2012) challenges the ethics of demanding clinical trials as criteria for coverage of care, especially for “rare malignancies … where the limited number of patients may not enable randomized clinical trials to be conducted. Therefore, a clinical decision regarding the optimal treatment should be taken even though the highest level of evidence may not be available.” As in the cases discussed by Ogino, my tumor’s life cycle is unknown and its rarity makes clinical trials infeasible. Anthem argues that “medical studies we have seen do not show that it is as good as other treatments for your condition.” Unfortunately for both me and Anthem, there are no studies of my condition. However, Chan (2006) studies another rare head and neck tumor and finds that it was more responsive to PBT than IMRT.

These ethical considerations are discussed in other top journals in the field as well. In the Journal of Clinical Oncology, Goiten and Cox (2008) make the following strong argument: “Although we can understand (though not necessarily agree with) the desire to rely on RCTs to establish the advantage of a superior therapy, we find it totally unacceptable to insist on what we judge to be unethical RCTs purely to establish the financial cost-effectiveness of an admittedly better technology—nor would patients, if fully informed, consent to participate in such studies.”

The most persuasive voice in my case, however, is that of my own radiation oncologist at M.D. Anderson. As he wrote in his appeal to Anthem, “proton therapy is FDA-approved and is neither investigational nor experimental.  It has the potential to expedite patient recovery after treatment and reduces the potential morbidities that may result from irradiating surrounding organs with more conventional techniques such as x-ray therapy.  This approach minimizes toxicity to the patient and results in a more rapid recovery resulting in less cost to her (as the patient) and to you (as her insurer).  Specifically, proton therapy will be an outpatient treatment, and will not require hospitalizations due to disease or treatment-related side effects.”

Reducing My Radiation-Related Side Effects Is Medically Necessary

PBT is medically necessary for the treatment of the rare malignant tumor in my left neck because this treatment would deliver less radiation dose to the surrounding healthy structures than any other treatment option.  The effects of radiation are detrimental—this is precisely why radiation will be used to target my tumor.  But if Anthem and the University of California refuse to approve the recommended PBT treatment, I will be forced to undergo IMRT, a less suitable form of radiation that will unnecessarily expose my submandibular (salivary) glands, oral cavity, spinal cord, and brain stem to radiation. 

As explained in greater detail below, leading experts in the field have determined that PBT is a less risky form of treatment for me, and is medically necessary for my treatment.  PBT likely will cause far fewer serious side effects than IMRT, resulting in significant improvement in quality of life, and it carries less than half the risk of secondary malignancy.  For all of these reasons, I request that Anthem and the University of California reverse the decision to override the recommendation of the experienced head and neck cancer specialists, and immediately authorize my treatment with PBT.

Leading experts in the field of head and neck oncology determined that PBT is medically necessary because it is the safest treatment option for the malignant paraganglioma in my neck, based on factors specific to my tumor.


I was fortunate enough to be evaluated by leading experts in the field at M.D. Anderson, one of the nation’s foremost comprehensive cancer treatment centers. Dr. Garden is a graduate of Johns Hopkins Medical School and Board Certified Radiologist with 24 years of medical experience and practice in Radiation Oncology.  He specializes in the treatment of cancers affecting the head and neck and has published at least 30 peer-reviewed original research articles addressing the treatment of these cancers.  Based upon my specific case factors and the risks of radiation-related side effects, Dr. Garden determined that PBT is medically necessary for me:
 Proton beam radiation therapy has shown to deliver less radiation dose to other critical structures; in Ms. Call’s case this would include the surrounding organ/tissue  structures of the left neck, spinal cord and brainstem, where pared to x-ray treatment, including intensity modulated radiation therapy (IMRT).  We strongly feel that it is medically necessary that Ms. Call receive proton therapy for treatment of her life-threatening malignant paraganglioma of the left neck. (Appeal letter to Anthem, May 11, 2012)
The medical opinion of Dr. Garden should not be disregarded simply because of a lack of documentation in the medical literature on the treatment of my specific condition.   The medical evidence concerning the substantial risk of harm arising from treatment of the head and neck with IMRT are clear.  It is well-documented that PBT eliminates many of these risks.  For this reason alone, Anthem should follow the recommendation of the medical experts, and authorize my treatment with PBT.

PBT will cause fewer serious side effects than IMRT, resulting in significant improvement in my quality of life.


“Treatment-related toxic effects of radiation therapy for head and neck malignancies can be severe” (Slater, 2006).   The radiation exposure to the areas of my head and neck surrounding the tumor will likely cause both short- and long-term side effects. As a 28-year old soon-to-be cancer survivor, the detrimental side effects of IMRT could negatively impact my quality of life and my ability to be fully productive in my fieldwork for decades to come. 

The decreased exposure to radiation through treatment with PBT is significant in cases involving malignancies of the head and neck.  “With PBT, unnecessary dose to the adjacent normal head and neck structures can be limited, resulting in significant improvement in quality of life during and after treatment” (Slater, 2006).  PBT’s unique ability to target the tumor provides radiation oncologists with the means to deliver higher radiation doses to the target, improving chances of eliminating tumor cells, while significantly reducing radiation doses to the surrounding tissues, resulting in fewer radiation-related side effects.

IMRT causes more serious damage to critical organs than PBT.  In my case, submandibular (salivary) glands, oral cavity, spinal cord, and brain stem are located in the area surrounding the tumor bed, and would receive excessive radiation should Anthem limit my treatment options to IMRT.  A 2007 medical study compared dose distributions and impacts between PBT, conventional radiotherapy, and IMRT (Palm and Johannson).  This study found that proton therapy substantially decreases radiation to nearby organs compared to conventional radiotherapy and IMRT, while providing improved dose distribution in non-target tissues.  The reduced radiation can preserve organ function, significantly reducing the risk of normal tissue complications and secondary malignancies.

Two specific side effects arising from irradiation of the head and neck region are acute mucositis (painful inflammation and ulceration of the mucous membranes lining the digestive tract) and acute and chronic xerostomia.  Radiation treatment that is focused near the salivary glands may inflict temporary or permanent damage. Xerostomia occurs when the salivary glands do not make enough saliva, producing “serious negative effects on the patient’s quality of life, causing difficulties in tasting, chewing, swallowing, and speaking” and can lead to dental problems including causing mouth infections, sores, cavities, tooth loss, and gum disease (Lundkvist, et al., 2005).

The side effects of the course of treatment I am provided affect the efficacy of the treatment.  This is not solely a matter of eliminating my tumor.  The preservation of critical bodily functions also is important.

PBT carries less than half the risk of secondary malignancy caused by the radiation treatment.


The decreased exposure to radiation through treatment with PBT has a substantial effect on the risk of secondary malignancy.  A comparative analysis of secondary malignancy risk in 503 patients treated with proton therapy between 1974 and 2001 versus 1591 matched treated with conventional photon therapy, revealed a significantly lower risk of second malignancy after proton radiotherapy when compared with photon radiation therapy (Chung, et al, 2008).  Moreover, after adjustment for clinical and demographic variables, traditional photon radiation therapy was associated with almost a three-fold greater risk of second malignancy.

The reduction in secondary cancers has been specifically documented in the treatment of head and neck cancers (Yoon, et al., 2010).  In the medical literature, compared with IMRT, treatment with PBT for head and neck tumors carries a lower relative secondary cancer rate for all organs.

It is unethical to disregard the documented tissue-sparing effect of PBT—resulting from the inherent characteristics of the proton beam—simply because there is a lack of medical literature documenting its application to rare malignant carotid body tumors such as mine.


PBT’s sparing of normal tissue is well documented in the medical literature, including in the treatment of head and neck cancers.  For rare malignancies like mine, where the limited number of patients does not enable randomized clinical trials to be conducted, it is unethical to deny treatment as investigative simply because the highest level of evidence is not be available.  The well-documented tissue-sparing effects of PBT result directly from the physical characteristics of the proton beam (Metz, 2002).  Anthem and the University of California should not require proof of the impossible: that the documented tissue-sparing effect applies equally to malignant carotid body tumors.  The tissue-sparing effect is unambiguous.  PBT would spare the tissues surrounding the tumor in my neck from unnecessary damaging radiation.  The recommendation of the head and neck specialists who evaluated my tumor have cited this tissue-sparing effect as supporting their determination that PBT is the optimal treatment for my condition.  This recommendation should not be disregarded.  It is unethical for Anthem to authorize only a treatment that carries a documented significantly greater risk of harm to my submandibular glands, spinal cord, and brainstem when the less risky treatment option of PBT could be made available to me.

Anthem has justified authorizing PBT for other cancers based on these factors. The same authorization is justified here. 


Anthem’s own policy, justifying the use of PBT:
Anthem considers Proton beam radiation therapy “medically necessary” for the initial monotherapy radiation treatment of localized prostate cancer. … This is based on evidence that demonstrates that PBT is able to deliver higher doses of radiation to a targeted area while decreasing exposure to adjacent healthy tissue. (Policy #: RAD.00015)
Anthem’s policy justifying PBT coverage for prostate cancer uses the same reasoning that should be used in my case. It appears that the only reason that prostate cancer would be covered when my cancer is not has to do with my cancer’s rarity.  Indeed, PBT is also offered for CNS lesions whose pathologies similar to mine: a) close to delicate, nonhealing and crucially functioning parts of the anatomy and b) not a whole body metastasis which would make such an expensive and focused treatment futile.

In sum, the increased radiation-related side effects resulting from treatment with IMRT are clearly established.  These consequences are not insignificant, but have the potential to affect the quality of my life for the next seventy-plus years.  Because PBT will leave me with fewer serious side effects than IMRT, PBT is medically necessary for me.

Anthem and the University Have Caused Dangerous Delay

When first considering proton therapy in late April, I called Anthem customer service to verify that it would be covered. The representative told me that it would be, so long as the procedure was FDA-approved.  M.D. Anderson’s proton therapy facility has been operating with FDA-approval since May 2008 (Matsuda, et al., 2009). I reached out to friends to set up lodging for me in Houston and prepared to leave home for the six to eight weeks of treatment. Since then, I have been waiting for confirmation daily.

Receiving Anthem’s denial was unexpected, and navigating the appeals process under this time pressure has been extremely confusing and anxiety producing. My Benefit Booklet specifies that “Only the Peer Clinical Reviewer may determine that the proposed services are not medically necessary and appropriate.” He or she must be “licensed in California with the same license category as the requesting provider.”  If my request for treatment is denied, the denial letter should include the name and telephone number of the Peer Clinical Reviewer who made the decision. It did not. The letter includes the name of the medical reviewer who made the determination not to approve PBT (Steven Rosenblum) as well as the Medical Director (Gil Solomon), but neither are board certified in radiation oncology or experienced with diseases of the head and neck.

Dr. Garden appealed Anthem’s denial on May 11. Both he and Dr. Chen recommended that my therapy start four to eight weeks after surgery, i.e. no later than May 16. I was not able to obtain documentation of Anthem’s decision to deny Dr. Garden’s appeal until May 23. Again, the outside doctor is unnamed. I called Anthem to request his or her name and written opinion, but was told I would have to wait up to thirty days.  If I had to wait thirty more days, I would receive the relevant information on June 22, more than five weeks after the 8-week maximum post-surgical wait prescribed by the experts who treated me.  Anthem and the University of California are asking me to choose between submitting to more harmful and less effective treatment without making available their reasoning for doing so, and putting my life in danger by further delaying treatment.

Whereas the doctors recommending PBT for my treatment are highly qualified practicing radiation oncologists, those denying my right to the treatment have unclear qualifications. Furthermore, by restricting access to information about the outside reviewers, Anthem has violated its own policies. Meanwhile, each additional day of delay in approving my treatment reduces my chances of beating this cancer. I urge Anthem and UC officials to immediately overturn the denial and grant me the care I need to survive.

References

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