Advanced recurrent ovarian cancer (ROC) is the leading cause of gynecologic cancer-related death in developed countries and new treatments are needed. Previous studies of immune checkpoint blockade ...showed low objective response rates (ORR) in ROC with no identified predictive biomarker.
This phase II study of pembrolizumab (NCT02674061) examined two patient cohorts with ROC: cohort A received one to three prior lines of treatment with a platinum-free interval (PFI) or treatment-free interval (TFI) between 3 and 12months and cohort B received four to six prior lines with a PFI/TFI of ≥3months. Pembrolizumab 200mg was administered intravenously every 3weeks until cancer progression, toxicity, or completion of 2years. Primary end points were ORR by Response Evaluation Criteria in Solid Tumors version 1.1 per blinded independent central review by cohort and by PD-L1 expression measured as combined positive score (CPS). Secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.
Cohort A enrolled 285 patients; the first 100 served as the training set for PD-L1 biomarker analysis. Cohort B enrolled 91 patients. ORR was 7.4% for cohort A and 9.9% for cohort B. Median DOR was 8.2months for cohort A and not reached for cohort B. DCR was 37.2% and 37.4%, respectively, in cohorts A and B. Based on the training set analysis, CPS 1 and 10 were selected for evaluation in the confirmation set. In the confirmation set, ORR was 4.1% for CPS<1, 5.7% CPS ≥1, and 10.0% for CPS ≥10. PFS was 2.1months for both cohorts. Median OS was not reached for cohort A and was 17.6months for cohort B. Toxicities were consistent with other single-agent pembrolizumab trials.
Single-agent pembrolizumab showed modest activity in patients with ROC. Higher PD-L1 expression was correlated with higher response.
Clinicaltrials.gov, NCT02674061
To develop and evaluate the performance of a radiomics and machine learning model applied to ultrasound (US) images in predicting the risk of malignancy of a uterine mesenchymal lesion.
Single-center ...retrospective evaluation of consecutive patients who underwent surgery for a malignant uterine mesenchymal lesion (sarcoma) and a control group of patients operated on for a benign uterine mesenchymal lesion (myoma). Radiomics was applied to US preoperative images according to the International Biomarker Standardization Initiative guidelines to create, validate and test a classification model for the differential diagnosis of myometrial tumors. The TRACE4 radiomic platform was used thus obtaining a full-automatic radiomic workflow. Definitive histology was considered as gold standard. Accuracy, sensitivity, specificity, AUC and standard deviation of the created classification model were defined.
A total of 70 women with uterine mesenchymal lesions were recruited (20 with histological diagnosis of sarcoma and 50 myomas). Three hundred and nineteen radiomics IBSI-compliant features were extracted and 308 radiomics features were found stable. Different machine learning classifiers were created and the best classification system showed Accuracy 0.85 ± 0.01, Sensitivity 0.80 ± 0.01, Specificity 0.87 ± 0.01, AUC 0.86 ± 0.03.
Radiomics applied to US images shows a great potential in differential diagnosis of mesenchymal tumors, thus representing an interesting decision support tool for the gynecologist oncologist in an area often characterized by uncertainty.
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•No imaging technique can effectively discriminate between sarcoma and myoma.•Inadequate surgery in case of occult sarcoma will worsen the patient's prognosis.•Radiomics allows to correlate radiological images to the tissue pathophysiology.•Radiomics applied to US images represents an effective diagnostic support tool.
To assess predictors of recurrence following laparoscopic radical hysterectomy (LRH) for apparent early stage cervical cancer (CC).
This is a retrospective multi-institutional study reviewing data of ...consecutive patients who underwent LRH for FIGO 2009 stage IA1 (with lymphovascular space invasion (LVSI)), IA2 and IB1(≤4 cm) CC, between January 2006 and December 2017. The following histotypes were included: squamous, adenosquamous, and adenocarcinoma. Multivariable models were used to estimate adjusted odds ratio (OR) and corresponding 95% CI. Factors influencing disease-free survival (DFS) and disease-specific survival (DSS) were also explored.
428 patients were included in the analysis. With a median follow-up of 56 months (1–162) 54 patients recurred (12.6%). At multivariable analysis, tumor size (OR:1.04, 95%CI:1.01–1.09, p = .02), and presence of cervical residual tumor at final pathology (OR: 5.29, 95%CI:1.34–20.76, p = .02) were found as predictors of recurrence; conversely preoperative conization reduced the risk (OR:0.32, 95%CI:0.11–0.90, p = .03). These predictors remained significant also in the IB1 subgroup: tumor size: OR:1.05, 95%CI:1.01–1.09, p = .01; residual tumor at final pathology: OR: 6.26, 95%CI:1.58–24.83, p = .01; preoperative conization: OR:0.33, 95%CI:0.12–0.95, p = .04. Preoperative conization (HR: 0.29, 95%CI: 0.13–0.91; p = .03) and the presence of residual tumor on the cervix at the time of surgery (HR: 8.89; 95%CI: 1.39–17.23; p = .01) independently correlated with DFS. No independent factors were associated with DSS.
In women with early stage CC the presence of high-volume disease at time of surgery represent an independent predictor of recurrence after LRH. Conversely, preoperative conization and the absence of residual disease at the time of surgery might play a protective role.
•High-volume disease at time of surgery was an independent predictor of recurrence after laparoscopic radical hysterectomy.•Absence of residual tumor at final pathology had a protective role following laparoscopic surgery for early-stage disease.•Preoperative conization positively influenced disease-free survival in IA1(positive LVSI) – IB1cervical cancer.
Abstract Objective The international acceptance of a universal classification system for radical hysterectomy is one of the important challenges in gynecologic oncology. The recently published ...classification system by Querleu and Morrow is a relevant proposal that has been well received by the professional community. However, it does not include a description of parametrial resection in three dimensions, which mostly determines post-operative morbidity. Methods The intention of this follow-up paper was to further develop the classification system based on the four proposed types of radical hysterectomy (A–D) into a three-dimensional model using standard anatomical landmarks for definition of resection margins in longitudinal and transverse dimensions and demonstrate it on pictures. Results Resection margins were defined in longitudinal and transverse dimensions for each suggested type of radical hysterectomy on all three parts of the parametria. Besides precise description using stable anatomical landmarks, all resection lines have been shown on intra-operative photographs. Conclusion Four types of radical hysteretomy can be precisely defined on a three-dimensional anatomical template, including nerve sparing procedure. Our paper should contribute to better standardization (including nomenclature) of the radical hysterectomy, enhancing harmonization of clinical practice in gynecological oncology.
Immunotherapy has transformed the endometrial cancer treatment landscape, particularly for those exhibiting mismatch repair deficiency MMRd/microsatellite instability-hypermutated (MSI-H). A growing ...body of evidence supports the integration of immunotherapy with chemotherapy as a first-line treatment strategy. Recently, findings from ongoing trials such as RUBY (NCT03981796), NRG-GY018 (NCT03914612), AtTEnd (NCT03603184), and DUO-E (NCT04269200) have been disclosed.
This paper constitutes a review and meta-analysis of phase III trials investigating the role of immunotherapy in the first-line setting for advanced or recurrent endometrial cancer.
The pooled data from 2320 patients across these trials substantiate the adoption of chemotherapy alongside immunotherapy, revealing a significant improvement in progression-free survival compared to chemotherapy alone hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.62-0.79 across all patient groups. Progression-free survival benefits are more pronounced in MMRd/MSI-H tumors (n = 563; HR 0.33, 95% CI 0.23-0.43). This benefit, albeit less robust, persists in the MMR-proficient/microsatellite stable group (n = 1757; HR 0.74, 95% CI 0.60-0.91). Pooled data further indicate that chemotherapy plus immunotherapy enhances overall survival compared to chemotherapy alone in all patients (HR 0.75, 95% CI 0.63-0.89). However, overall survival data maturity remains low.
The incorporation of immunotherapy into the initial treatment for advanced and metastatic endometrial cancer brings about a substantial improvement in oncologic outcomes, especially within the MMRd/MSI-H subset. This specific subgroup is currently a focal point of investigation for evaluating the potential of chemotherapy-free regimens. Ongoing exploratory analyses aim to identify non-responding patients eligible for inclusion in clinical trials.
•Immunotherapy added to chemotherapy improves disease-free and overall survival in advanced and metastatic endometrial cancer.•Endometrial cancer is the malignancy with the highest prevalence of MMRd/MSI-H.•MMRd/MSI-H is an agnostic biomarker suggesting the efficacy of immunotherapy.•Immunotherapy plus chemotherapy improves progression-free survival even in the MMR-proficient population.
The management of cervical cancer patients with intraoperative detection of lymph node involvement remains controversial. Since all these patients are referred for (chemo)radiation after the surgery, ...the key decision is whether radical hysterectomy should be completed as originally planned, taking into account an additional morbidity associated with extensive surgical dissection prior to adjuvant treatment. The ABRAX study investigated whether completing a radical uterine procedure is associated with an improved oncological outcome of such patients.
We performed retrospective analyses of 515 cervical cancer patients (51 institutions, 19 countries) who were referred for primary curative surgery between 2005 and 2015 (stage IA–IIB, common tumour types) in whom lymph node involvement was detected intraoperatively. Patients were stratified according to whether the planned uterine surgery was completed (COMPL group, N = 361) or abandoned (ABAND group, N = 154) to compare progression-free survival. Definitive chemoradiation was given to 92.9% patients in the ABAND group and adjuvant (chemo)radiation or chemotherapy to 91.4% of patients in the COMPL group.
The risks of recurrence (hazard ratio HR 1.154, 95% confidence intervals CI 0.799–1.666, P = 0.45), pelvic recurrence (HR 0.836, 95% CI 0.458–1.523, P = 0.56), or death (HR 1.064, 95% CI 0.690–1.641, P = 0.78) were not significantly different between the two groups. No subgroup showed a survival benefit from completing radical hysterectomy. Disease-free survival reached 74% (381/515), with a median follow-up of 58 months. Prognostic factors were balanced between the two groups. FIGO stage and number of pelvic lymph nodes involved were significant prognostic factors in the whole study cohort.
We showed that the completion of radical hysterectomy does not improve survival in patients with intraoperatively detected lymph node involvement, regardless of tumour size or histological type. If lymph node involvement is confirmed intraoperatively, abandoning uterine radical procedure should be considered, and the patient should be referred for definitive chemoradiation.
NCT04037124.
•Radical hysterectomy does not improve outcome of N1 cervical cancer patients.•Surgery completion brings no survival benefit irrespective of tumour size or type.•If N1 is diagnosed intraoperatively, further radical procedure should be abandoned.
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