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How I discuss treatment of desmoid tumors
A patient-centered approach
Obligatory—this is not medical advice
I strongly believe in the importance of being completely transparent when providing medical advice and presenting the evidence behind it. It is not sufficient to simply give firm recommendations without providing the necessary context. During my appointments, I devote a significant amount of time to discussing the advantages and disadvantages of various treatment options with each individual patient.
In certain cases, there are established practices for additional treatment, such as prescribing adjuvant imatinib for patients with KIT mutated high risk gastrointestinal stromal tumors (GISTs). However, the decision to pursue treatment and weigh the benefits of improved survival or event-free survival against the potential side effects of a medication is highly subjective and varies depending on the person involved.
Before I meet a patient for the first time, I make it a point to review their medical records thoroughly. I want to have a clear understanding of their treatment history, including the timing and types of therapies they have received, as well as the duration of their diagnosis and the progression of their disease. Although past events may not always predict the future accurately, studying a patient's medical journey can provide valuable insights into their condition. I discuss and confirm the information I have gathered with the patient, creating a collaborative environment for our discussion. We review what they know about the diagnosis, much of which is covered here. Only after we have established a shared understanding of their medical history do we proceed to the next steps.
Over the past decade, there have been significant changes in the guidelines for managing desmoid tumors. The focus has shifted from primarily relying on surgical interventions to adopting a more cautious approach, which includes watchful waiting or medical therapy. This change in approach has been driven by a growing recognition of the high recurrence rate after surgery and a considerable rate of spontaneous regression. You can refer to a figure from a study by Gounder et al. published in the New England Journal of Medicine in 2018, which illustrates this shift in emphasis. It is noteworthy that approximately 20% of patients experience regression without any treatment, even though they had shown at least a 10% increase in tumor size in the six months prior to enrollment. A similar trend was observed in the Defi trial.
I make it a point to highlight the potential toxicity associated with treatments. Currently, there are several options available for medical management, which I focus on during our discussions. These options include sorafenib, pazopanib, imatinib, liposomal doxorubicin, and methotrexate/(vinblastine or vinorelbine).It is worth noting that most of these options have not been compared directly in prospective studies, although there is interest in conducting such comparisons in the future.
In the absence of head-to-head comparisons, we place emphasis on the available evidence and the clarity of the results. For example, it is easier to discuss the relative response rates of sorafenib or nirogacestat compared to placebo, as these have been studied prospectively in randomized trials. In a phase 2 study, pazopanib was shown to be superior to methotrexate-vinblastine in terms of disease control. However, questions remain about the sequencing of treatments and whether pursuing multiple therapies with similar mechanisms, such as pazopanib and sorafenib, will still yield successful outcomes.
The results of multiple trials have been discussed in this blog before and can be reviewed at this link.
Given the demographics of patients with desmoid tumors, we must consider the impact of certain life events and the potential long-term consequences of therapy. Desmoid tumors can change over time. A notable abstract presented at ASCO 2023 by Fiore et al. (#11513) provided a retrospective analysis of patients of child-bearing age with desmoid tumors. The analysis demonstrated the following findings:
There was a 5% risk of tumor progression during pregnancy.
The risk of progression in the postpartum period was 9%.
Treatment was necessary for only 6% of patients.
These findings highlight the importance of considering individual circumstances when making decisions about treatment for desmoid tumors.
It is crucial to thoroughly review the administration, monitoring, and outcomes associated with each treatment option. While we may need to prioritize and focus on the most critical information, it is important to explore the reasons why a patient might choose each option.
One aspect of the Defi trial that provides valuable insight is its impact on ovarian function. It is worth emphasizing that this aspect of therapy had not been prospectively measured before for patients with desmoid tumors, and it is essential to discuss the implications of treatment. Outcomes related to ovarian function were assessable for 25 out of 27 patients, and they appeared to be directly linked to drug exposure, resolving after stopping nirogacestat. 2 patients, unfortunately, were not asessable on study, and so their outcomes are unknown. 5 patients elected to continue treatment with nirogacestat despite this side effect.
There is a great deal of nuance involved in the evaluation of therapy for patients with desmoid tumors. The right answer can only be found through comprehensive discussions. We must empower our patients with knowledge and understanding so that we can work together to make the best treatment decisions. The landscape of therapy for desmoid tumors has undergone significant changes and will continue to evolve in the future. With an increasing number of options available, it is crucial for us to be candid and transparent about what we know and what we still need to learn.