1. Young, Robert C. MD

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Five years after the publication of the marvelous Pulitzer-Prize winning book by Siddhartha Mukherjee (see my review in OT's 2/10/11 issue), PBS has produced a three part, six-hour documentary series, CANCER: The Emperor of all Maladies." Shortly after the book was published, the Entertainment Industry Foundation obtained the television and film rights for its Stand Up to Cancer initiative. The result is this television special which is to air on PBS on March 30, March 31, and April 1.

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ROBERT C. YOUNG, MD.... - Click to enlarge in new windowROBERT C. YOUNG, MD. REVIEWED BY ROBERT C. YOUNG, MD Chairman,

In many ways, it is difficult and perhaps even unfair to compare the documentary with the book on which it is based. The book is a lyrical, masterwork that weaves the story of cancer in such an exceptional, multi-layered manner that it communicates beautifully with patients, families, practicing oncologists, and scientists as well as the public. The visually driven medium of film is forced to focus on a more abbreviated and less nuanced rendition of the complex cancer story.


Each version uses its strengths to best advantage. But each has its limitations. The documentary tells of Sir Percival Pott's chimney sweeps and William Halsted's radical mastectomy, all stories familiar to oncologists. Lost are the book's anecdotes about Pott's compulsive, reclusive nature and Halsted's addiction to cocaine. These facts may not be so familiar to oncologists. Much of the book's appeal for oncologists has been left on the cutting room floor. This is less a criticism of the documentary and more the recognition of the differences in the two types of media.


In contrast, the documentary succeeds in conveying the emotion and the epic personal struggles of patients and families in a manner that is difficult in a written "Biography of Cancer." It is often said that "statistics are just people with the tears washed away." The documentary is marvelous in capturing this very human aspect of the cancer story. No one could fail to be moved by the images of 14-month-old Olivia Blair with acute T-cell lymphoblastic leukemia, or by the agony experienced by Luca Assante's family when he developed acute leukemia from his treatment for rhabdomyosarcoma.


Here, real-time images trump the written word. The film sequence that depicts the torment of Olivia Blair's family struggling to decide on a randomized trial of an additional therapy or a placebo is a visual tour-de-force. It captures the gulf between the physician's analytical understanding of the rationale for such a trial and the overwhelming desire of the family to have their child get the "correct" treatment.


Episode 1

The first of the three episodes, titled "Magic Bullets," explores the early history of cancer and its treatment. The central focus, as in the book, is Sidney Farber and his study of methotrexate in childhood leukemia. The documentary is less Boston-centric than the book and does cover the early contributions of Tom Frei and Jay Freireich at the National Cancer Institute. But one still wonders why other early luminaries like David Karnofsky are not mentioned.


The format of this episode, like those that follow, couples elegant visual narrative with commentary by a veritable whose-who of cancer leaders. These experts provide excellent synopses of the take-home message of each segment.


This episode touches only superficially on radiation therapy, mostly with the visual portrayal of early skin toxicity. The message seems to be that systemic therapy is required for a systemic disease. From this viewer's perspective, it gives short shrift to the continued utility of radiation in the treatment of cancer.


The surgical spotlight, as in the book, is the Halsted radical mastectomy and its flawed scientific underpinning. While the criticism is certainly valid, the focus is narrow, and it seems to minimize the overall contributions of surgery to the present management of cancer patients.


Episode one ends with an arresting presentation of the power and influence of Mary Lasker on the ultimate passage of the National Cancer Act in 1971.


Episode 2

Episode two, "The Blind Man and the Elephant," begins with the story of Nixon's "War on Cancer" and the rapid expansion of both laboratory and clinical research and the widespread optimism it generated. While oncologists struggled to make incremental progress in the clinic, laboratory scientists begin to make substantial advances in our understanding of cancer causation.


Three theories emerge as possible causes-viruses, environmental carcinogens, and genetic flaws-and each proves to be partially responsible. This episode concentrates on the oncogene and the development of targeted therapies, especially Herceptin and Gleevec. One is left with the impression that targeted therapy will be transformative. In large part, this is where the book left off.


Episode 3

Episode Three is "Finding the Achilles Heel," and to its credit, dampens the optimism surrounding targeted therapy with the recognition of its utility in only limited populations of cancer patients and the frequent development of resistance. Cancer is presented as a bewildering array of complexity and a very plastic ability to develop resistance. Basic science advances with the Cancer Genome Atlas revealing new levels of complexity. Tumor-suppressor genes add to the challenge. Although spectacular responses with limited toxicity heighten enthusiasm for targeted therapies, resistance and relapse is common.


The episode highlights the staggering cost of many of the newer anti-cancer agents. Cost-effectiveness and incremental benefit for treatments of advanced disease lead into a powerful and quite effective segment on palliative and end-of-life care. Dr. Suzanne Cole, a young West Virginia medical oncologist, gives us a deft and brilliant demonstration of her communication skills. Cancer care would improve if all of us had the communication savvy of this young doctor.


This final episode ends on an optimistic note with a focus on cancer immunotherapy, which after living in the back-water of progress for over 50 years, now seems to be coming to the forefront. The groundbreaking work of Jim Allison at MD Anderson established that immunological blockade was central to the body's immunologic failure to irradiate cancer. This has led to the development of anti-PD-1 and CTLA-4 antibodies, which show great promise for a wide range of cancers.


That said, the focus of much of this segment is on the patient-specific immunotherapy approaches of Steve Rosenberg at the NCI and Carl June at the University of Pennsylvania. Both approaches are complex, resource intensive, and challenging to generalize to large patient populations. However, their complexity and intimate doctor-patient interactions make for better television.


With such a massive and complex subject as Cancer, it is dangerous to point out omissions. Something must always be left out. That said, it is difficult to see how one could cover the cure of childhood leukemia without highlighting the contributions of the group at St. Jude. While Don Pinkel has a cameo appearance, the advances he pioneered are not presented.


Likewise absent are the compelling adjuvant chemotherapy trials of Gianni Bonadonna and Umberto Veronesi in breast cancer, and the definitive large European clinical trials which resolved the controversy of bone marrow transplantation in breast cancer more convincingly than did the Boston studies of Bill Peters.


The documentary is a powerful depiction of the complexity of cancer science and the heartbreakingly slow progress towards a cure. It does not sugarcoat the challenges we face. It depicts the successes, failures, mistakes, and stumbles we have made as we struggle with The Emperor of All Maladies.


But the documentary, as with the book, leaves the viewer confident that those in search of the cure will never give up.




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