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December 23, 2020
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6 years at the helm: A Decameron

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Since 2014, when we took the helm of HemOnc Today as joint Chief Medical Editors, the overall progress in oncology has been spectacular.

As has always been the case, oncological progress is mostly slow and steady, and there is no cause for breathless enthusiasm every 2 weeks (the cadence of our editorials); thus, we have sprinkled folklore, philosophy, obituaries and politics quite liberally into our musings about progress in our joint domains.

Derek Raghavan, MD, PhD, FACP, FRACP, FASCO
Derek Raghavan
John Sweetenham, MD, FRCP, FACP, FASCO
John Sweetenham

One way of considering the breadth and impact of this evolution in the past 6 years is to reconsider our editorial content, sampling more than 150 editorials that we wrote.

Our first submission was a joint editorial, published in July 2014 and titled, “From research funding to drug pricing: 12 questions to ask your political candidates.” This set the tone for our next 6.5 years of collaboration.

Game changers

It is probably an accurate representation that the biggest game changer in cancer treatment during our tenure has been the reemergence of immunotherapy — predicated on recognition of the benefits of checkpoint inhibition, targeted at PD-1/PD-L1 — in parallel with a host of other targeted therapies focused on other genes that stimulate cancer growth.

This has been enabled by the burgeoning field of precision medicine and the genuine equipoise in attempting to solve the conundrum of who should have paid for the research (especially before the techniques had been largely validated) — payers or patients who used the tests during their development or the companies that stood to benefit from the data generated by early studies and trials.

The challenges of setting a balance between speed to market and responsible scientific investigation are not new; while not wishing to repeat the fiasco of bone marrow transplantation for breast cancer, we also did not wish to see a delay in potentially life-saving therapies for the hematologic malignancies afforded by the use of chimeric antigen receptor T-cell therapy. The editorial “Who’s driving the CARs in the race?” covered this in detail, focused on the clearly high response rates in lymphoma and myeloma, but also on the importance of case selection bias in evaluating data (which also could be an issue in the assessment of the true utility and toxicity of the various COVID-19 vaccines).

We also raised concerns over the use and potential misuse of “real-world data” in this and other contexts. Of course, cost also will be a determining factor, and this initially slowed acceptance of CAR-T in many European nations, largely based on the disconnect between true cost of development of the therapy vs. the asking price.

Game-changing progress also has been made in genitourinary oncology. In addition to the impact of checkpoint inhibition in the management of locally advanced and metastatic cancers of the kidney, bladder and prostate, a series of novel second-line agents that interfere with the hypothalamic-pituitary-end organ axis have been shown to improve outcomes in metastatic prostate cancer dramatically; in fact, some of these agents appear to be finding a place in adjuvant therapy.

In parallel, a series of agents predicated on novel preclinical science, such as poly(ADP)-ribose polymerase, or PARP, inhibitors and antibody-drug conjugates (sacituzumab govitecan [Trodelvy, Immunomedics], enfortumab vedotin [Padcev; Astellas, Seagen]) are finding important roles in managing resistant prostate cancer, as discussed in “It’s a puzzlement.”

The changing treatment landscape of Hodgkin lymphoma required several editorials that emphasized the significant impact of novel therapies on outcome, but also noted that late effects remain very important, and that heart disease, infection and interstitial lung disease remain major causes of noncancer death.

Not to be forgotten is the importance of survivorship issues, including the troubling paucity of pretreatment conversations about the impact of treatment on fertility, which we described in “Engaging in conversations about fertility.”

Of course, there has been dramatic progress in so many domains, and it may be easier to identify areas where the progress has been less substantial — metastatic pancreatic cancer and advanced brain tumors seem to be at the top of that list.

COVID-19

Obviously, the COVID-19 pandemic and its impact on patients with cancer (and the clinicians who treat them) have occupied us both.

A long-lasting clinical impact of the pandemic has been the shift to virtual care, as summarized in “Learning to manage with less.” Of necessity, we have had to defer and deflect face-to-face (FTF) visits, but we have yet to learn whether the extent to which the absence of a physical exam and FTF history-taking will lead to missed or delayed diagnoses. The importance of medical diagnosticians has been eroded in recent years (“Having your prostate exam in the grocery store ... in the produce section”), and the move to virtual care is part of that continuum. Let us be clear — we are not at all opposed to this trend, but simply recognize that the hidden drawbacks have yet to be defined.

COVID-19 has certainly occupied the editorial pages of HemOnc Today because of its impact on clinical medicine, but perhaps not as stridently as the editorial “Trump lied about science,” published earlier this year in Science written by its editor-in-chief, H. Holden Thorp, PhD.

That said, we addressed the topic ourselves, mirroring the angst of much of our readership. “The accidental ‘stupidpower’ — It is what it is” reflected the concerns about the foolishness of our political leaders and much of the population in challenging masking, social distancing and science in general. “How many errors to kill a population?” was sadly prescient, given its publication in April.

The other interesting sideline was summarized at the editorial level in a review of the Italian experience with androgen deprivation therapy for prostate cancer, which may have conferred a survival benefit to castrated men with respect to death of COVID-19 (“ADT and COVID-19 — A therapeutic discussion”).

Reading between the headlines

Some of our editorial titles over the past 6 years summarized our thoughts as one-liners: “Data-based medicine: When data and ‘opinion’ collide;” “Big data, big errors of interpretation;” “Difficult decisions: Slow changes for overuse of therapy at end of life;” “Right-to-try legislation: Primum non nocere just went out the window;” “Cure and the shopping CAR-T: Just pay millions at the cash register!;” “Schrödinger’s cat: PSA screening is alive and dead;” and “Obesity and cancer: Beware the festive season.”

We noted the untimely passing of several legends of the world of cancer medicine — Clara Derber Bloomfield, MD, Col. Charles A. Coltman Jr., MD, and Peter C. Nowell, MD — and reviewed their impact on science, medicine and oncology. In an editorial titled “When loss becomes personal,” we remarked upon the devastating loss of a relatively young breast cancer surgeon, Teresa Flippo Morton, MD, a victim of pancreatic cancer, who lost her battle in less than 2 months, and its impact on those who worked with her, and then treated her. In “A sad week,” we marked the passing of Jon Huntsman Sr., billionaire businessman and philanthropist who established the Huntsman Cancer Institute and did so much for patients with cancer throughout the U.S.

Looking to the future, “Oncology Care Model: Progress along the learning curve” epitomized some of the early wins, but also the pitfalls, of an experimental fiscal model for cancer care that will be around for some time.

Speaking of health finance, as equity and fiscal toxicity have been dominant themes for both of us at HemOnc Today, we are optimistic that there actually is slow and steady improvement in access for underserved populations to equal care and outcomes. “Access to cancer clinical trials may not entirely level the playing field” summarizes our view that the focus of government on access to trials — without adequate attention to infrastructure, reimbursement issues, access to care and navigation — will not resolve this crucial issue (“On killing innocents: Anzac Day revisited”). At the same time, financial pain is rapidly emerging as one of the major side effects of cancer care, and the medical establishment is finally attempting to address this in several ways (“The unspoken truth about financial toxicity”).

“‘Covfefe’ — the real meaning,” reflecting an early morning commentary from the “First Tweeter of the United States,” focused on strategies to bring down profligate health expense, such as linking anticipated survival vs. expense, more robust data regarding dosing and length of systemic treatment, the ASCO Choosing Wisely tenets and more use of pharmacokinetic data in prescribing. Unfortunately, not all future clinical (or societal) visions are rosy — “America’s new cancer: History repeats itself” reflects the continued inability of the U.S. government to address gun violence and gun control, and gun deaths, particularly among children and young people, continue to reflect the unique American affection for the right to own (and use) weapons that can kill many people at a time.

Influencers

After 6.5 years at the helm, we should (again) formally thank Harry S. Jacob, MD, FRCPath(Hon), and Joseph R. Bertino, MD, the founding medical editors of HemOnc Today, for launching the project that has absorbed us, and for setting initial standards. We hope that we have used their foundational work as a springboard and have further raised the standards of inclusion and reporting, and that we have been effective in focusing on high-quality data and rigor of assessment.

We owe a great debt to our professional publishing colleagues, including Peter Slack, John Carter, Mark Leiser and Sasha Todak, who have taught us, taken risks with our positions, and produced a very high-quality publication each time.

We also acknowledge the Editorial Board, whose wisdom, insights and perspectives have been key to the continued success of HemOnc Today — they have provided expert guidance and reminded us constantly that whatever benefits new technologies bring to medical publishing, the quality and relevance of the content are still the most valued asset.

Broadsheets like HemOnc Today are increasingly important, as they provide snapshots of the vast array of progress and set context for the busy clinicians who have to keep atop the increasingly complex preclinical and clinical science of the day. Our belief is that physicians must retain, as they have done for centuries, a key role as influencers in society and as commentators on ethical and moral dilemmas that affect our patients (and thus society at large).

We have observed the increasing pace of data generation, accompanied by the move from print media to electronic media, and anticipate that these roles will become even more important as information and progress proliferate at warp speed into the future.

Reference:

Thorp HH. Science. 2020;doi:10.1126/science.abe7391.

Join the Conversation:

Read past editorials by Derek Raghavan, MD, PhD, and John Sweetenham, MD, at healio.com/authors/draghavan and healio.com/authors/jsweetenham.