Most patients with ovarian cancer will relapse after receiving frontline platinum-based chemotherapy and eventually develop platinum-resistant or platinum-refractory disease. We report results of ...avelumab alone or avelumab plus pegylated liposomal doxorubicin (PLD) compared with PLD alone in patients with platinum-resistant or platinum-refractory ovarian cancer.
JAVELIN Ovarian 200 was an open-label, parallel-group, three-arm, randomised, phase 3 trial, done at 149 hospitals and cancer treatment centres in 24 countries. Eligible patients were aged 18 years or older with epithelial ovarian, fallopian tube, or peritoneal cancer (maximum of three previous lines for platinum-sensitive disease, none for platinum-resistant disease) and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1:1) via interactive response technology to avelumab (10 mg/kg intravenously every 2 weeks), avelumab plus PLD (40 mg/m2 intravenously every 4 weeks), or PLD and stratified by disease platinum status, number of previous anticancer regimens, and bulky disease. Primary endpoints were progression-free survival by blinded independent central review and overall survival in all randomly assigned patients, with the objective to show whether avelumab alone or avelumab plus PLD is superior to PLD. Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02580058. The trial is no longer enrolling patients and this is the final analysis of both primary endpoints.
Between Jan 5, 2016, and May 16, 2017, 566 patients were enrolled and randomly assigned (combination n=188; PLD n=190, avelumab n=188). At data cutoff (Sept 19, 2018), median duration of follow-up for overall survival was 18·4 months (IQR 15·6–21·9) for the combination group, 17·4 months (15·2–21·3) for the PLD group, and 18·2 months (15·8–21·2) for the avelumab group. Median progression-free survival by blinded independent central review was 3·7 months (95% CI 3·3–5·1) in the combination group, 3·5 months (2·1–4·0) in the PLD group, and 1·9 months (1·8–1·9) in the avelumab group (combination vs PLD: stratified HR 0·78 repeated 93·1% CI 0·59–1·24, one-sided p=0·030; avelumab vs PLD: 1·68 1·32–2·60, one-sided p>0·99). Median overall survival was 15·7 months (95% CI 12·7–18·7) in the combination group, 13·1 months (11·8–15·5) in the PLD group, and 11·8 months (8·9–14·1) in the avelumab group (combination vs PLD: stratified HR 0·89 repeated 88·85% CI 0·74–1·24, one-sided p=0·21; avelumab vs PLD: 1·14 0·95–1·58, one-sided p=0·83). The most common grade 3 or worse treatment-related adverse events were palmar-plantar erythrodysesthesia syndrome (18 10% in the combination group vs nine 5% in the PLD group vs none in the avelumab group), rash (11 6% vs three 2% vs none), fatigue (ten 5% vs three 2% vs none), stomatitis (ten 5% vs five 3% vs none), anaemia (six 3% vs nine 5% vs three 2%), neutropenia (nine 5% vs nine 5% vs none), and neutrophil count decreased (eight 5% vs seven 4% vs none). Serious treatment-related adverse events occurred in 32 (18%) patients in the combination group, 19 (11%) in the PLD group, and 14 (7%) in the avelumab group. Treatment-related adverse events resulted in death in one patient each in the PLD group (sepsis) and avelumab group (intestinal obstruction).
Neither avelumab plus PLD nor avelumab alone significantly improved progression-free survival or overall survival versus PLD. These results provide insights for patient selection in future studies of immune checkpoint inhibitors in platinum-resistant or platinum-refractory ovarian cancer.
Pfizer and Merck KGaA, Darmstadt, Germany.
The AP (adaptor protein) complexes are heterotetrameric protein complexes that mediate intracellular membrane trafficking along endocytic and secretory transport pathways. There are five different AP ...complexes: AP-1, AP-2 and AP-3 are clathrin-associated complexes; whereas AP-4 and AP-5 are not. These five AP complexes localize to different intracellular compartments and mediate membrane trafficking in distinct pathways. They recognize and concentrate cargo proteins into vesicular carriers that mediate transport from a donor membrane to a target organellar membrane. AP complexes play important roles in maintaining the normal physiological function of eukaryotic cells. Dysfunction of AP complexes has been implicated in a variety of inherited disorders, including: MEDNIK (mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis and keratodermia) syndrome, Fried syndrome, HPS (Hermansky-Pudlak syndrome) and HSP (hereditary spastic paraplegia).
The survival of patients with ovarian cancer has improved because of surgery and chemotherapy. This study aimed to estimate the changes in survival rates among Korean women with ovarian cancer prior ...to the introduction of targeted therapy for ovarian cancer.
Data were obtained from the Korea Central Cancer Registry regarding patients who were diagnosed with epithelial ovarian cancer between 1995 and 2014. The relative survival rates were calculated for 5-year periods using the Ederer II method. Cox proportional hazard models were created to assess the associations of demographic and clinicopathological factors with ovarian cancer survival.
During the study period, 22,880 women were diagnosed with epithelial ovarian cancer. The 5-year relative survival rate improved from 57.2% during 1995-1999 to 63.8% during 2010-2014 (P < 0.001). Survival outcomes improved between 1995 and 1999 and 2010-2014 for the serous and endometrioid carcinoma subtypes (P < 0.001). However, no improvements were observed for the mucinous and clear cell carcinoma subtypes (P = 0.189 and P = 0.293, respectively). Multivariate analysis revealed that younger age, early stage, recent diagnosis, primary surgical treatment, and non-serous histological subtype were favorable prognostic factors.
Survival outcomes have improved for serous and endometrioid epithelial ovarian cancer in the last 20 years. However, no improvement was observed for patients with mucinous and clear cell carcinoma subtypes.
An NCI-sponsored, randomized clinical trial tested whether patients with relapsed ovarian cancer might benefit from surgical debulking of tumors followed by chemotherapy, as compared with ...chemotherapy alone. No significant outcome differences were noted between the patients who underwent surgery and those treated with chemotherapy alone.
We aimed to evaluate the prognosis in patients with synchronous endometrial and ovarian cancer (SEOC) by comparing the differences between double primary cancer (DPC) and metastatic cancer (MC).
The ...medical records of 47 patients diagnosed synchronously with endometrial and ovarian cancer between January 2006 and December 2018 were retrospectively reviewed. Twenty-eight and 19 patients were diagnosed with DPC and MC, respectively. Demographics, recurrence-free survival (RFS), and 5-year overall survival (OS) were compared. The clinical factors affecting survival were evaluated using univariate and multivariate analyses.
The demographics were not different between both groups. Endometrioid histology and the International Federation of Gynecology and Obstetrics grade were higher in the MC group than in the DPC group (42.1% vs. 10.7%; P = 0.018, P = 0.002, respectively). The ratio of post-operative adjuvant therapy was not different in both groups. Recurrence occurred in five patients with DPC and seven with MC. The difference in RFS was not significantly different (P = 0.131) but the OS was different between both groups (P = 0.020). Histology and para-aortic lymph node metastasis were associated wtih RFS in univariate analysis, but no difference was found in multivariate analysis.
Although DPC patients had longer OS, multivariate analysis did not identify any influential factors. Focus should be placed on defining the appropriate adjuvant treatment for high-risk patients, which will improve prognosis, rather than on discriminating between DPC and MC.
Considering the high morbidity and mortality of Coronavirus disease 2019 (COVID-19) in patients with malignancy, they are regarded as a priority for COVID-19 vaccination. However, general vaccine ...uptake rates among cancer patients are known to be lower than in their healthy counterparts. Thus, we aimed to investigate the attitude and acceptance rates for the COVID-19 vaccine in cancer patients and identify predictive factors for vaccination that could be modified to increase vaccine uptake rates, via a paper-based survey (58 items over six domains). A total of 1001 cancer patients participated in this nationwide, multicenter survey between February and April 2021. We observed that 61.8% of respondents were willing to receive the COVID-19 vaccine. Positive predictive factors found to be independently associated with vaccination were male gender, older age, obesity, previous influenza vaccination history, absence of cancer recurrence, time since cancer diagnosis over 5 years, and higher EuroQol Visual Analogue Scale scores. Along with the well-known factors that are positively correlated with vaccination, here, we report that patients’ disease status and current health status were also associated with their acceptance of the COVID-19 vaccination. Moreover, 91.2% of cancer patients were willing to be vaccinated if their attending physicians recommend it, indicating that almost 30% could change their decision upon physicians’ recommendation. Unlike other factors, which are unmodifiable, physicians’ recommendation is the single modifiable factor that could change patients’ behavior. In conclusion, we firstly report that Korean cancer patients’ acceptance rate of the COVID-19 vaccination was 61.8% and associated with disease status and current health status. Physicians should play a major role in aiding cancer patients’ decision-making concerning COVID-19 vaccines.
Objective This study investigated site-specific differences in clinical factors for recurrence in patients who were newly diagnosed and treated for endometrial cancer. A model for predicting ...recurrence sites was generated. Methods Electronic medical records' data were retrieved from January 2006 to December 2018 for patients who were diagnosed with endometrial cancer at the National cancer center in Korea. Recurrence sites were classified as local, regional, or distant. We used multinomial logistic regression models that modeled the log-odds for the three recurrence sites relative to non-recurrence as a linear combination of possible risk factors for the recurrence of endometrial cancer. Results The data of 611 patients were selected for analysis; there were 20, 12, and 25 cases of local, regional, and distant recurrence, respectively, and 554 patients had no recurrence. High-grade disease was associated with local recurrence; non-endometrioid histology and parametrial invasion were risk factors for regional recurrence; additionally, parametrial invasion and no lymphadenectomy were associated with distant metastasis. Conclusion We identified different risk factors specific for each type of recurrence site. Using these risk factors, we suggest that individually tailored adjuvant treatments be introduced for patients. Keywords: Endometrial cancer, Lymph node, Lymph node dissection, Survival rate
Background Ureteral reconstruction is required after surgical resection of the tumor invading the urinary tract in ovarian cancer with low incidence. There are no currently reported surgical outcomes ...of ureteral reconstruction during cytoreductive surgery. The aim of the study is to investigate the clinical features and surgical outcomes of ureteral reconstruction during primary, interval and secondary cytoreductive surgery for ovarian cancer. Methods A total of 3226 patients who underwent primary, interval or secondary cytoreductive surgery for ovarian cancer between January 2000 and May 2021 were reviewed. Fifty-six patients who underwent ureteral reconstruction during cytoreductive surgery were included in the analysis. Results Ureteral reconstruction was required in 1.7% (56/3226) of ovarian cancer patients. Of the 56 patients who underwent ureteral reconstruction during cytoreductive surgery, 35 (62.5%) had primary ovarian cancer, and 21 (37.5%) had recurrent ovarian cancer. The median tumor size invading the lower urinary tract was 2.0 cm (range, 0.4-9.5 cm). Ureteroneocystostomy with direct implantation (51.8%) and psoas hitch (8.9%), transureteroureterostomy (7.1%), and ureteroureterostomy (32.1%) were required as part of cytoreductive surgery. Complete cytoreduction with ureteral reconstruction was achieved in 83.9% (47/56) and the rest of the patient population (16.1%) achieved a gross residual tumor size of less than 1 cm. All complications, including hydronephrosis (33.9%), were managed, none resulting in long-term sequelae. In primary ovarian cancer, the 5-year disease-free survival and overall survival were 50.0% and 89.5%, respectively. In patients with recurrent ovarian cancer, the 5-year disease-free survival and overall survival were 23.6% and 64.0%, respectively. Conclusions Ureteral reconstruction as a part of cytoreductive surgery for ovarian cancer could be performed with acceptable morbidities. Complete cytoreduction by a multidisciplinary surgical team, including urologic oncologists, should be pursued for the surgical management of ovarian cancer. Trial registration Retrospectively registered. Keywords: Ovarian cancer, Cytoreductive surgery, Ureteral reconstruction
Despite the great potential of polymer microfibers in human-friendly wearable electronics, most previous polymeric electronics have been limited to thin-film-based devices due to practical ...difficulties in fabricating microfibrillar devices, as well as defining the active channel dimensions in a reproducible manner. Herein, we report on conducting polymer microfiber-based organic electrochemical transistors (OECTs) and their application in single-strand fiber-type wearable ion concentration sensors. We developed a simple wet-spinning process to form very conductive poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) microfibers using aqueous sulfuric acid solutions and carefully examined their electrical/electrochemical properties. In conjunction with fabricating substrate-free PEDOT:PSS microfiber-based OECT devices, the proposed novel characterization method demonstrated that the current variation ratio can be a reliable method for evaluating the device performance for sensing ion concentrations, regardless of the actual channel dimensions. Finally, we developed single-strand fiber-type skin-mountable OECTs by introducing a source-gate hybrid electrode and demonstrated that the resultant microfiber sensors can perform real-time repetitive measurements of the ion concentration in human sweat.
To investigate the outcomes of children, adolescents, and young adults (AYAs) with malignant ovarian germ cell tumors (MOGCTs), we analyzed the data of 61 patients aged ≤39 years diagnosed with MOGCT ...between 2006 and 2022. Among 59 patients who received chemotherapy after initial diagnosis, 57 received BEP (standard dose of bleomycin with 30 units per week, n = 13) or bEP (reduced dose of bleomycin with 15 units/m2 on day 1, n = 44). The 5-year overall survival (OS) and event-free survival (EFS) rates were 98.3% and 84.9%, respectively. Reduced bleomycin dose did not adversely affect survival. Normalization of tumor markers within 3 months after surgery was significantly associated with better EFS (p < 0.01). Of the 59 surviving patients, 8 experienced surgery-related menopause, while 49 demonstrated menstrual recovery. After completion of chemotherapy, there was no significant difference in pulmonary function regarding bleomycin dose, and no overt nephrotoxicity. Approximately 60% and 25% of survivors experienced peripheral neuropathy at the end of chemotherapy and after 1 year, respectively (p < 0.01). Children and AYAs with MOGCT have favorable survival rates with minimal long-term toxicity, which are not influenced by a reduced bleomycin dose. Rapid normalization of tumor markers is associated with improved outcomes.
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