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

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1700
Author(s):  
Thomas Bartl ◽  
Arina Onoprienko ◽  
Gerda Hofstetter ◽  
Leonhard Müllauer ◽  
Nina Poetsch ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Checkpoint Inhibitor ◽  
Gynecologic Cancer ◽  
Therapy Response ◽  
Final Analysis ◽  
Fixed Dose ◽  
Gynecologic Malignancies ◽  
Clinical Biomarkers ◽  
Predictive And Prognostic Value ◽  
Recurrent Gynecologic Cancer

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.

Use of nivolumab as salvage therapy in heavily pretreated patients with gynecologic malignancies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5593-5593
Author(s):  
Heather Williams ◽  
Jennifer Wang ◽  
Lynn Tran ◽  
Sara Mobley ◽  
Bunja Jane Rungruang ◽  
...  
Keyword(s):  
Treatment Response ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Gynecologic Cancer ◽  
Low Grade ◽  
Significant Activity ◽  
Gynecologic Malignancies ◽  
Heavily Pretreated ◽  
The Impact

5593 Background: There are limited effective treatments for gynecologic cancer patients who have been previously treated with multiple lines of chemotherapy. Immune checkpoint inhibitor (ICI) therapy has demonstrated significant activity in certain cancers but has been inconclusive in most gynecologic malignancies. The objective of this study was to determine the impact of salvage ICI therapy in heavily pretreated gynecologic oncology patients. Methods: An IRB approved retrospective study was performed of women with gynecologic cancer treated with nivolumab on a compassionate use program between October 2015 and January 2018. Patient demographics, disease characteristics, pathology and treatment history were collected. Survival probabilities were calculated. Results: Twenty-eight women were identified. Median age at start of treatment was 63 years with a median of 4 prior lines of chemotherapy. Median ECOG status was 2. Disease site was evenly distributed among uterus, ovary and cervix. 67.9% of patients completed 3 or more cycles of treatment. Median PFS of all patients was only 2.6 months however when comparing patients who received 2-3 cycles (n = 13) with those who received 4 or more (n = 9), median PFS was statistically significant 2.4 months vs 6.4 months (p = 0.0005). When looking at treatment response, 7 patients had partial response/stable disease after 3 cycles (25%). Median PFS of the 7 “responders” was 6.6 months vs 2.5 months of the non-responders (p < 0.001). Only 1 of 9 patients with uterine cancer had a disease response and that patient’s tumor was MSI high. Five patients had low grade serous ovarian cancer. Four of them had a treatment response with a median PFS of 6.1 months (range 3.8 – 25 months). Adverse events were experienced by 68% of patients; most commonly being fatigue (46.4%), arthralgia (25%), and anemia (21.4%). Only 1 patient experienced a grade 3-4 event (a diffuse maculopapular rash). Conclusions: In patients with heavily pretreated gynecologic malignancies with suboptimal performance status, immune checkpoint inhibitor therapy may prolong survival without significant toxicity. Also, there may be a role for ICI in patients with historically chemo resistant low grade serous ovarian cancers.

scholarly journals Usefulness of Vascular Clips in Surgery for Gynecologic Cancer

2021 ◽  
Author(s):  
Kazuho Nakanishi ◽  
Takashi Yamada ◽  
Shunji Suzuki
Keyword(s):  
Cervical Cancer ◽  
Endometrial Cancer ◽  
Pelvic Floor ◽  
Cancer Patients ◽  
Gynecologic Cancer ◽  
Pelvic Lymphadenectomy ◽  
Gynecological Surgery ◽  
Gynecologic Malignancies ◽  
Result Analysis ◽  
Titanium Clips

Abstract In gynecological surgery for cervical cancer and endometrial cancer with lymphadenectomy, many lymph vessels are ligated to prevent postoperative lymph leakage and lymphocele, and many blood vessels leading to the pelvic floor are ligated. Therefore, the labors required for ligation are very large. However, no studies have examined ligation methods in gynecologic cancer surgery. Therefore, we retrospectively examined gynecologic cancer patients who had been treated at our hospital by dividing them into a group using absorbent threads and a group using titanium clips. In addition, the surgical procedure was classified into three groups: a group with only pelvic lymphadenectomy, a group with pelvic and para-aortic lymphadenectomy, and a group with radical hysterectomy with pelvic lymphadenectomy. As a result, analysis of all cases clearly showed less complications and less time for surgery in the clip group. Furthermore, the analysis of RH + PLN group showed that surgery time was clearly shorter and less complications tended to occur in the clip group. In conclusion, by using this easily usable device, surgery for gynecologic malignancies will be more comfortable and safer.

Defining the impact of the use of granulocyte colony stimulating factors on the incidence of chemotherapy-induced neutropenia in patients with gynecologic malignancies

2016 ◽  
Vol 23 (2) ◽  
pp. 121-127 ◽  
Author(s):  
Justin M Julius ◽  
Aimee Hammerstrom ◽  
Caimiao Wei ◽  
Raeshmma Rajesh ◽  
Diane C Bodurka ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Gynecologic Cancer ◽  
Gynecologic Malignancies ◽  
Treatment Delays ◽  
Colony Stimulating Factors ◽  
Chemotherapy Induced Neutropenia ◽  
Number Of Treatment ◽  
Chemotherapy Agents ◽  
The Impact ◽  
Dose Reductions

Purpose The objectives of this study were to characterize the incidence of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) with specific chemotherapy agents commonly used in the treatment of gynecologic malignancies, as well as defining the impact of granulocyte colony stimulating factors (G-CSF) on the prevention of CIN and FN in this patient population. Methods This retrospective analysis was conducted from a database of 635 gynecologic cancer patients who received chemotherapy between 1 September 2007 and 31 August 2008. A logistic regression analysis was conducted to determine the impact of potential covariates on the overall incidence of CIN. Results Overall, 28.3% of patients experienced CIN with one or more cycles chemotherapy, and 13.1% had treatment delays or dose reduction associated with CIN. The use of G-CSF prior to administration of chemotherapy resulted in a decrease in the incidence of CIN from 29.8% to 19.6% compared to no G-CSF use. No difference was observed in number of treatment delays or dose reductions in the 46 (7.2%) of gynecologic cancer patients that received G-CSF prophylaxis. Multivariate analysis found that both age and the number of current cycles jointly may predict risk of CIN. Conclusions Patients with gynecologic malignancies appear to be at a higher risk of development of neutropenia when treated with chemotherapy. The proactive use of G-CSF did decrease the risk of CIN by over 30%. Prospective study is warranted to determine the impact of G-CSF to reduce CIN in patients with gynecologic malignancies receiving chemotherapy.

Evaluating the effect of a group pre-treatment chemotherapy psycho-education session for chemotherapy-naive gynecologic cancer patients and their caregivers

2021 ◽  
Vol 160 (1) ◽  
pp. 234-243
Author(s):  
Diana Samoil ◽  
Nazek Abdelmutti ◽  
Lisa Ould Gallagher ◽  
Nazlin Jivraj ◽  
Naa Kwarley Quartey ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Gynecologic Cancer ◽  
Education Session ◽  
Pre Treatment

scholarly journals Survival in endometrial cancer in relation to minimally invasive surgery or open surgery – a Swedish Gynecologic Cancer Group (SweGCG) study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Christer Borgfeldt ◽  
Erik Holmberg ◽  
Janusz Marcickiewicz ◽  
Karin Stålberg ◽  
Bengt Tholander ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Endometrial Cancer ◽  
Minimally Invasive ◽  
Cancer Patients ◽  
Surgical Approach ◽  
Open Surgery ◽  
Gynecologic Cancer ◽  
Multivariable Analysis ◽  
Figo Stage

Abstract Background The aim of this study was to analyze overall survival in endometrial cancer patients’ FIGO stages I-III in relation to surgical approach; minimally invasive (MIS) or open surgery (laparotomy). Methods A population-based retrospective study of 7275 endometrial cancer patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed from 2010 to 2018. Cox proportional hazard models were used in univariable and multivariable survival analyses. Results In univariable analysis open surgery was associated with worse overall survival compared with MIS hazard ratio, HR, 1.39 (95% CI 1.18–1.63) while in the multivariable analysis, surgical approach (MIS vs open surgery) was not associated with overall survival after adjustment for known risk factors (HR 1.12, 95% CI 0.95–1.32). Higher FIGO stage, non-endometrioid histology, non-diploid tumors, lymphovascular space invasion and increasing age were independent risk factors for overall survival. Conclusion The minimal invasive or open surgical approach did not show any impact on survival for patients with endometrial cancer stages I-III when known prognostic risk factors were included in the multivariable analyses.

scholarly journals Identification of NOTCH4 mutation as a response biomarker for immune checkpoint inhibitor therapy

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Junyu Long ◽  
Dongxu Wang ◽  
Xu Yang ◽  
Anqiang Wang ◽  
Yu Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bladder Cancer ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Esophagogastric Cancer ◽  
Clinical Benefits

Abstract Background Immune checkpoint inhibitor (ICI) therapy elicits durable antitumor responses in patients with many types of cancer. Genomic mutations may be used to predict the clinical benefits of ICI therapy. NOTCH homolog-4 (NOTCH4) is frequently mutated in several cancer types, but its role in immunotherapy is still unclear. Our study is the first to study the association between NOTCH4 mutation and the response to ICI therapy. Methods We tested the predictive value of NOTCH4 mutation in the discovery cohort, which included non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, esophagogastric cancer, and bladder cancer patients, and validated it in the validation cohort, which included non-small cell lung cancer, melanoma, renal cell carcinoma, colorectal cancer, esophagogastric cancer, glioma, bladder cancer, head and neck cancer, cancer of unknown primary, and breast cancer patients. Then, the relationships between NOTCH4 mutation and intrinsic and extrinsic immune response mechanisms were studied with multiomics data. Results We collected an ICI-treated cohort (n = 662) and found that patients with NOTCH4 mutation had better clinical benefits in terms of objective response rate (ORR: 42.9% vs 25.9%, P = 0.007), durable clinical benefit (DCB: 54.0% vs 38.1%, P = 0.021), progression-free survival (PFS, hazard ratio [HR] = 0.558, P < 0.001), and overall survival (OS, HR = 0.568, P = 0.006). In addition, we validated the prognostic value of NOTCH4 mutation in an independent ICI-treated cohort (n = 1423). Based on multiomics data, we found that NOTCH4 mutation is significantly associated with enhanced immunogenicity, including a high tumor mutational burden, the expression of costimulatory molecules, and activation of the antigen-processing machinery, and NOTCH4 mutation positively correlates activated antitumor immunity, including infiltration of diverse immune cells and various immune marker sets. Conclusions Our findings indicated that NOTCH4 mutation serves as a novel biomarker correlated with a better response to ICI therapy.

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