Overweight as a Favorable Clinical Biomarker for Checkpoint Inhibitor Therapy Response in Recurrent Gynecologic Cancer Patients

Despite increasing clinical interest in adapting checkpoint inhibitor (CPI) therapies for patients with gynecologic malignancies, no accurate clinical biomarkers to predict therapy response and prognosis are currently available. Therefore, we aimed to assess the predictive and prognostic value of pretherapeutic body mass index (BMI) for recurrent gynecologic cancer patients as previously validated for other solid tumors. We evaluated patients with programmed cell death ligand 1 (PD-L1) positive and, in endometrial cancer, also mismatch repair deficient (MMR) gynecologic malignancies, who received the PD-1 inhibitor pembrolizumab as monotherapy (200 mg fixed-dose q3 w) from 2017 to 2020 (n = 48). Thirty-six patients receiving at least four courses were included in the final analysis. Associations between a BMI increase per 5 kg/m2 and overall response rate (ORR; complete + partial response), disease control rate (DCR; ORR + stable disease), progression-free (PFS), and overall survival (OS) were assessed. An elevated BMI was univariately associated with ORR (OR 10.93 [CI 2.39–49.82], p = 0.002), DCR (OR 2.19 [CI 0.99–4.83], p = 0.048), prolonged PFS (HR 1.54 [CI 1.03–2.34], p = 0.038), and OS (HR 1.87 [CI 1.07–3.29], p = 0.028). All results could be confirmed in the multivariate analyses. Pretherapeutic BMI therefore appears to be a promising readily available biomarker to identify patients with PD-L1-positive and/or MMR-deficient gynecologic malignancies who could particularly benefit from CPI treatment

Strahlentherapie und Onkologie / The value of pretreatment serum butyrylcholinesterase level as a novel prognostic biomarker in patients with cervical cancer treated with primary (chemo-)radiation therapy

Hintergrund Für erniedrigte Butyrylcholinesterase(BChE)-Spiegel, die üblicherweise im Rahmen von Leberschäden, Entzündungsreaktionen oder Mangelernährung auftreten, wurden kürzlich auch Assoziationen mit schlechterem Überleben in verschiedenen onkologischen Erkrankungen beschrieben. Das Ziel dieser Studie war, die prognostische Bedeutung von prätherapeutischen BChE-Serumspiegeln für das Überleben von Zervixkarzinompatientinnen unter primärer (Chemotherapie- [Chemo-])Radiotherapie zu untersuchen. Methoden Prätherapeutische BChE-Werte im Serum aller Zervixkarzinompatientinnen, die im Zeitraum von 1998 bis 2015 mit einer primären (Chemo)Radiotherapie behandelt wurden, wurden retrospektiv erhoben und mit klinisch-pathologischen Parametern sowie dem Therapieansprechen korreliert. In uni- und multivariaten Überlebensanalysen wurde der Zusammenhang zwischen erniedrigten BChE-Spiegeln und progressionsfreiem (PFS), tumorspezifischem (CSS) und Gesamtüberleben (OS) untersucht. Ergebnisse Insgesamt konnten 356 Patientinnen mit einem medianen prätherapeutischen BChE-Spiegel (IQR) von 6180 IU/l (Spanne 49907710 IU/l) in die Analyse einbezogen werden. Die medianen BChE-Serumspiegel waren in Patientinnen mit niedrigerem Body-Mass-Index (p < 0,001), fortgeschrittenem Tumorstadium (p = 0,04), schlechtem Therapieansprechen (p = 0,002) und dem Auftreten eines Rezidivs signifikant erniedrigt (p = 0,003). In uni- und multivariaten Überlebensanalysen waren niedrigere BChE-Spiegel (<6180 IU/l) mit kürzerem PFS (HR 1,8 [1,22,6]; p = 0,002), CSS (HR 2,2 [1,43,5], p < 0,001) und OS (HR 2,0 [1,42,9]; p < 0,001) assoziiert. Schlussfolgerung Erniedrigte prätherapeutische BChE-Spiegel sind mit fortgeschrittenem Tumorstadium und schlechterem Therapieansprechen assoziiert und eignen sich als unabhängige Prognoseparameter für kürzeres PFS, CSS und OS bei Zervixkarzinompatientinnen unter primärer (Chemo-)Radiotherapie.Background Deficiency in butyrylcholinesterase (BChE), a condition commonly noticed in liver damage, inflammation, and malnutrition, has previously been associated with impaired prognosis in different malignancies. The aim of the present study was to investigate the value of pretreatment serum BChE levels as a prognostic biomarker in patients with cervical cancer treated with primary (chemotherapy-[chemo-])radiation therapy. Methods We retrospectively evaluated data of a consecutive series of patients with cervical cancer treated with primary (chemo-)radiation therapy between 1998 and 2015. Pretreatment serum BChE levels were correlated with clinico-pathological parameters and response to treatment. Uni- and multivariate survival analyses were performed to assess the association between decreased serum BChE levels and progression-free (PFS), cancer-specific (CSS), and overall survival (OS). Results A total of 356 patients were eligible for inclusion into the present study. The median (IQR) pretreatment serum BChE level was 6180 (49907710) IU/l. Lower serum BChE levels were associated with lower BMI (p < 0.001), advanced tumor stage (p = 0.04), poor treatment response (p = 0.002), the occurrence of disease recurrence (p = 0.003), and the risk of death (p < 0.001). In uni- and multivariate analyses, low pretreatment serum BChE levels were independently associated with shorter PFS (HR 1.8 [1.22.6]; p = 0.002), CSS (HR 2.2 [1.43.5], p < 0.001), and OS (HR 2.0 [1.42.9]; p < 0.001). Conclusions Low pretreatment serum BChE levels are associated with advanced tumor stage and poor response to treatment, and serve as an independent prognostic biomarker for shorter PFS, CSS, and OS in patients with cervical cancer treated with primary (chemo-)radiation therapy.(VLID)509263