The Language of Science Is No Longer Just for Clinicians

In a provocative commentary entitled “Scientists: When Talking to the Public, Please Speak Plainly” that was published in Scientific American, Naomi Oreskes, PhD, chastises the scientific community for frequently “speaking in code.”¹ Language used by individuals working in a specific area may be understood but that may not be the case for the broader scientific community and certainly not the general public. This is potentially problematic as the public becomes increasingly exposed to scientific discourse and publications.

Oreskes, the Henry Charles Lea Professor of the History of Science at Harvard University in Boston, Massachusetts, gives several examples of how terminology may be confusing and lead to incorrect and even dangerous interpretations by nonexperts. She notes, “Studies show that alien terms are, in fact, alienating; they confuse [individuals] and make them feel excluded. One study showed that even when participants were given definitions for the terms being used, jargon-laden materials make them less likely to identify with the scientific community and decreased their overall interest in the subject. In plain words: jargon turns people off…. If scientists could speak plainly, it would help us understand their claims and better appreciate their work.”¹

What Does It Mean?

An unfortunate real-world example of this concern is the FDA regulatory jargon related to the approval process and labeling of COVID-19 vaccines. Despite the unquestionably clearly documented safety and efficacy of several commercially available COVID-19 vaccine products, the FDA just recently granted “full approval” to the agents.² Unfortunately, it must be asked: What does the use of the term full approval signify to the vaccine-hesitant or vaccine-resistant populations? They may raise questions such as: Was the vaccine—administered these many months to billions of individuals—just part of a worldwide experiment prior to this now-stated stamp of approval?

Why not use terminology that provides reassurance to the public rather than information that leads to the questioning of government and public health officials who have been struggling to encourage vaccination?

In the oncology arena, terms frequently used by investigators in clinical trials—and subsequently in clinical practice—to describe the goals of therapy can lead to questions from patients and their families. At times it may even be asked if the treating physician will be able to provide a satisfactory explanation.

Consider, for example, the increasingly used term maintenance therapy. What is the basic meaning of this therapeutic strategy? Does the meaning apply to all settings where the oncology community states a maintenance strategy is being employed?

It is important to understand the history of anticancer drug therapy and specifically the administration of cytotoxic drugs. Until relatively recently, the duration of drug therapy delivery in the management of advanced or metastatic cancers was quite limited. This was because the known serious toxicity profiles of available clinically useful agents prevented extended use. Such adverse effects (AEs) included the risk of intense emesis (nausea, vomiting, or both), peripheral neuropathy (short term and persistent), life-threatening cardiotoxicity, and debilitating fatigue. Furthermore, the risks of such events in most circumstances worsened as therapy was prolonged.

In general, it was unlikely that most patients would be able to tolerate more than approximately 6 to 9 cycles of these agents delivered every 3 or 4 weeks. These limitations of treatment duration were particularly relevant for platinum agents (cisplatin, carboplatin, oxaliplatin), doxorubicin, and the taxanes (paclitaxel, docetaxel), which historically are among the most effective cytotoxic agents in many solid tumor types.

Therefore, investigators advanced the idea that following the delivery of a limited number of courses of an alternative, less-toxic approach might be substituted to maintain an observed response. It is not difficult to explain this laudable but understandably narrow aim. However, what else does the term maintenance imply?

Let’s consider that a clinical goal is to administer treatment to cure a patient’s illness, improve overall survival, or, more modestly, improve time to subsequent symptomatic disease progression without meaningfully affecting overall survival. Assuming there is an acceptable profile for AEs, is the intent to continue maintenance indefinitely, perhaps for the remainder of the patient’s life? Or is it to deliver therapy for a defined period and then discontinue treatment until evidence of disease progression?

It is relevant to note the potential heterogeneity of possible responses to these questions in contrast with a somewhat related older term, consolidation, which is used in hematologic malignancies. When employing a consolidation approach, once initial therapy is discontinued, patients receive 1 or 2 cycles of intensive therapy delivered with the very specific goal of consolidating the response and curing the malignancy. The AEs observed from the consolidative regimen may be even greater than the initial regimen, but the duration of such therapy will be limited and has the clear goal of increasing the opportunity for cure.

The unambiguous aim of this therapy will almost certainly not be conveyed through the term maintenance. Consider 2 examples that using “maintenance therapy” implies for anticipated outcomes, specifically, the observed outcomes from using one of several PARP inhibitors in the firstline treatment of patients with BRCA mutation–positive advanced epithelial ovarian cancer^3,4 vs those with BRCA mutation–positive metastatic pancreatic cancer.⁵ In pancreatic cancer, unfortunately, the likely duration of maintenance treatment will be limited. As a result, the use of traditional cytotoxic regimens and continuing therapy until disease progression or unacceptable AEs will generally apply to this patient population. However, investigators have observed that maintenance therapy used in the first line for patients with BRCA mutation–positive advanced epithelial ovarian cancer remarkably extended progression-free survival.

Further, the potential benefits of maintenance therapy in ovarian cancer vary based on the prior status of the malignancy (primary, first recurrence, second recurrence, etc) and, in the case of PARP inhibitors, the presence or absence of BRCA mutations or molecular evidence of homologous recombination deficiency or proficiency.

As a result, in the case of ovarian cancer where extended progression-free survival has been observed, it is necessary to ask the questions previously posed in this commentary. Should treatment be continued indefinitely for years if AEs are minimal or tolerable? Is continued treatment simply suppressing cancer for as long as it is delivered, or can extended delivery actually cure the condition? Answers to these questions are eagerly awaited.

Investigators should look at these 2 uses of maintenance therapy and determine if the definition of the term is applicable for similar treatments with different goals among both populations.

References

1. Oreskes N. Scientists: when talking to the public, please speak plainly. Scientific American. October 1, 2021. Accessed February 18, 2022. bit.ly/3v0W7kK
2. Coronavirus (COVID-19) update: FDA takes key action by approving second COVID-19 vaccine. News release. FDA. January 31, 2022. Accessed February 18, 2022. bit.ly/3LMuK3N
3. Pothuri B, O’Cearbhaill R, Eskander R, Armstrong D. Frontline PARP inhibitor maintenance therapy in ovarian cancer: a Society of Gynecologic Oncology practice statement. Gynecol Oncol. 2020;159(1):8-12. doi:10.1016/j.ygyno.2020.07.097
4. Tew WP, Lacchetti C, Ellis A, et al. PARP inhibitors in the management of ovarian cancer: ASCO guideline. J Clin Oncol. 2020;38(30):3468-3493. doi:10.1200/JCO.20.01924
5. Golan T, Hammel P. Management of BRCA mutation carriers with pancreatic adenocarcinoma. J Natl Compr Canc Netw. 2021;19(4):469-473. doi:10.6004/jnccn.2021.7031