Publications Update # 29

Non-Medical Article of the Week
Unlearning Anxiety
On this Ezra Klein Show, neuroscientist Jud Brewer, author of "Unwinding Anxiety," describes anxiety as a learned habit. He breaks down the habit loop into three stages: trigger (like a stressful thought), behavior (such as worrying), and reward (relief from the behavior). This loop can become self-reinforcing, making anxiety a tough cycle to break. To disrupt it, Brewer suggests:
- Recognizing your triggers.
- Practicing mindfulness to observe thoughts and feelings.
- Questioning and reframing negative thoughts.
- Employing healthy coping methods like exercise or relaxation.
- Prioritizing self-compassion.
Brewer believes that understanding anxiety as a habit allows us to unlearn and combat it, leading to more fulfilling lives.
You can buy the book by searching for - Unwinding Anxiety by Judson Brewer
Ovarian Cancer
HIPEC in Ovarian Cancer
OVHIPEC study was published in 2018. Since then, the NCCN guidelines have added a footnote with the following text.
Hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin (100 mg/m2 ) can be considered at the time of IDS for stage III disease.
Two papers published this week further support the routine use of HIPEC in interval debulking surgery:

A 10-year final survival analysis of the original OVHIPEC study shows an overall survival benefit of 1 year (median OS 33·3 months vs. 44·9 months; p=0·011)
A second randomized controlled trial now shows the benefit of HIPEC in ovarian cancer patients undergoing interval debulking surgery.

In this study, 109 patients underwent HIPEC compared to 87 without HIPEC during interval debulking surgery. The median PFS was 23 months in the HIPEC group vs. 14 months (p = 0.05). Overall survival data are not mature completely (HIPEC median OS not reached vs. 53 months).
How does HIPEC improve OS in ovarian cancer?
Critiques have questioned why HIPEC yields a larger OS benefit despite only a modest improvement in PFS. The pattern of recurrence answers this question. In this study (Table 3) - patients with HIPEC had a much lower rate of intraperitoneal recurrence compared to those without HIPEC (32% vs. 64%) and much higher lymph node metastasis (46% vs. 25%). Intraperitoneal recurrences can easily become life-threatening if the bowel is compromised, while patients with visceral or lymphatic recurrences often keep tolerating therapies for recurrence.
How do we encourage people to consider using HIPEC?
Unfortunately, I can no longer find the tweet to give appropriate attribution but someone on twitter (sorry X) suggested - call it HIPECOMAB and the utilization will skyrocket. If you find this tweet, let me know, I will add it to this post :)
Immunotherapy in Ovarian Cancer
Two recent trials in ovarian cancer explored the role of atezolizumab in newly diagnosed ovarian cancer. The first trial - IMagyn050/GOG 3015/ENGOT-OV39, published in 2021. This trial showed no benefit of adding immune checkpoint inhibitors to the combination of chemotherapy (Carboplatin/Taxol) and Bevacizumab (median PFS 20.8 versus 18.5 months, p = n.s).

This week, the results from ATALANTE/ENGOT-ov29 trial were published. This trial used the same combination in recurrent platinum-sensitive ovarian cancer. The results were similar to the IMagyn050 trial. Adding immune checkpoint inhibitors does not improve survival in ovarian cancer.

Ongoing studies are being conducted to identify more effective ways of using immunotherapy for a subset of patients. However, traditional measures of success, such as PD-L1 receptor status and tumor mutational burden, have not been able to predict the response to immunotherapy in HGSOC patients.
Endometrial Cancer

Just read this paper for now; more on this topic next week !!
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