To compare the efficacy and safety of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC).

Background: Epithelial ovarian cancer (EOC) remains the leading cause of gynecologic cancer death worldwide due to the high recurrence rate. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an alternative modality for platinum-sensitive recurrent EOC. The latest studies demonstrate homologous recombination-related (HRR) mutation status increases the sensitivity to platinum-based chemotherapy drugs in EOC. However, the molecular analysis of recurrent EOC patient benefits from HIPEC is unknown. Thus, we aimed to evaluate the efficacy and safety of CRS combined with HIPEC for platinum-sensitive in recurrent EOC with HRR mutation. Methods: This is a phase III randomized controlled clinical trial in patients with platinum-sensitive recurrent EOC. Participants were divided into 2 groups based on the HRR mutation status and randomized to receive CRS + HIPEC. The patients then received periodic chemotherapy and follow-up. Results: The primary objective of this study was to evaluate the effect of CRS + HIPEC compared to CRS alone in patients with a platinum-sensitive recurrent EOC stratified for HRD status. We hypothesize that the addition of HIPEC to CRS improves the progression-free survival (PFS) of platinum-sensitive recurrent EOC patients with HRR mutation compared with patients without HRR mutation. Conclusion: Recurrent EOC has a poor prognosis due to implantation and metastasis in the abdominal cavity. Intraperitoneal chemotherapy reduced seeding by removing free tumor cells. HIPEC utilizes physical and biological properties to significantly increase the clearance rate of tumors. Van Driel WJ et al proposed that HIPEC using platinum-based chemotherapy improves the survival of patients with ovarian cancer. HRR mutation, as a common pathogenic mutation in ovarian cancer, has a predictive effect on the platinum sensitivity of ovarian cancer patients. Whether lobaplatin-based HIPEC will play a greater role in ovarian cancer patients with HRR mutations is currently unknown.

On July 26, 2021, the FDA granted approval to pembrolizumab in combination with chemotherapy for neoadjuvant treatment and then continued as a single agent for adjuvant treatment following surgery for patients with high-risk, early-stage triple-negative breast cancer. Approval was based on results from KEYNOTE-522, an ongoing randomized (2:1) trial evaluating pembrolizumab or placebo in combination with chemotherapy for neoadjuvant treatment and then as a single agent for adjuvant treatment. The co-primary endpoints were pathological complete response (pCR) rate and event-free survival (EFS). The trial demonstrated an improvement in pCR and EFS in the pembrolizumab arm compared with the control arm. The number of patients who experienced an EFS event was 123 (16%) and 93 (24%), respectively [HR: 0.63, 95% confidence interval (CI), 0.48-0.82, P = 0.00031]. Patients on the pembrolizumab arm experienced EFS benefit regardless of tumor PD-L1 status. The absolute pCR rate improvement with the addition of pembrolizumab was 7.5% (95% CI, 1.6-13.4). Among patients receiving pembrolizumab, 44% experienced an immune-related adverse reaction. This article summarizes FDA's review of pembrolizumab and the data supporting the favorable benefit-risk assessment.

Estrogen receptor (ER) expression is a prognostic parameter in breast cancer, and a prerequisite for the use of endocrine therapy. In ER+ early breast cancer, however, no receptor-associated biomarker exists that identifies patients with a particularly favorable outcome. We have investigated the value of ESR1 amplification in predicting the long-term clinical outcome in tamoxifen-treated postmenopausal women with endocrine-responsive breast cancer.

Treatment results for patients with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-mutated (FLT3mut+) acute myeloid leukemia (AML) ineligible for intensive chemotherapy are disappointing. This multicenter, open-label, phase 3 trial randomized (2:1) untreated adults with FLT3mut+ AML ineligible for intensive induction chemotherapy to receive gilteritinib (120 mg/d orally) and azacitidine (GIL + AZA) or azacitidine (AZA) alone. The primary end point was overall survival (OS). At the interim analysis (August 26, 2020), a total of 123 patients were randomized to treatment (GIL + AZA, n = 74; AZA, n = 49). Subsequent AML therapy, including FLT3 inhibitors, was received by 20.3% (GIL + AZA) and 44.9% (AZA) of patients. Median OS was 9.82 (GIL + AZA) and 8.87 (AZA) months (hazard ratio, 0.916; 95% CI, 0.529-1.585; P = .753). The study was closed based on the protocol-specified boundary for futility. Median event-free survival was 0.03 month in both arms. Event-free survival defined by using composite complete remission (CRc) was 4.53 months for GIL + AZA and 0.03 month for AZA (hazard ratio, 0.686; 95% CI, 0.433-1.087; P = .156). CRc rates were 58.1% (GIL + AZA) and 26.5% (AZA) (difference, 31.4%; 95% CI, 13.1-49.7; P < .001). Adverse event (AE) rates were similar for GIL + AZA (100%) and AZA (95.7%); grade ≥3 AEs were 95.9% and 89.4%, respectively. Common AEs with GIL + AZA included pyrexia (47.9%) and diarrhea (38.4%). Gilteritinib steady-state trough concentrations did not differ between GIL + AZA and gilteritinib. GIL + AZA resulted in significantly higher CRc rates, although similar OS compared with AZA. Results support the safety/tolerability and clinical activity of upfront therapy with GIL + AZA in older/unfit patients with FLT3mut+ AML. This trial was registered at www.clinicaltrials.gov as #NCT02752035.

Topical cidofovir and imiquimod can effectively treat approximately 55% of patients with vulval intraepithelial neoplasia (VIN), thus avoiding the need for surgery. Human papillomavirus (HPV) E⁢2 gene methylation predicts response to treatment but a methylation measurement is only obtainable in approximately 50% of patients.

VEGF inhibitors can enhance the efficacy of immunotherapy. However, despite high initial response rates, almost all patients eventually develop treatment resistance to EGFR tyrosine-kinase inhibitors. We aimed to evaluate the efficacy and safety of sintilimab with or without IBI305 plus pemetrexed and cisplatin, compared with pemetrexed and cisplatin alone, for the treatment of patients with locally advanced or metastatic EGFR-mutated non-small-cell lung cancer (NSCLC) who had disease progression after receiving EGFR tyrosine-kinase inhibitor therapy.

Germline genetic testing affords multiple opportunities for women with breast cancer, however, current UK NHS models for delivery of germline genetic testing are clinician-intensive and only a minority of breast cancer cases access testing.

Combination treatment with BRAF and MEK inhibitors has demonstrated benefits on progression-free survival (PFS) and overall survival (OS) and is a standard of care for the treatment of advanced BRAF V600-mutant melanoma. Here, we report the 5-year update from the COLUMBUS trial (ClinicalTrials.gov identifier: NCT01909453).

An endeavor central to precision medicine is predictive biomarker discovery; they define patient subpopulations which stand to benefit most, or least, from a given treatment. The identification of these biomarkers is often the byproduct of the related but fundamentally different task of treatment rule estimation. Using treatment rule estimation methods to identify predictive biomarkers in clinical trials where the number of covariates exceeds the number of participants often results in high false discovery rates. The higher than expected number of false positives translates to wasted resources when conducting follow-up experiments for drug target identification and diagnostic assay development. Patient outcomes are in turn negatively affected. We propose a variable importance parameter for directly assessing the importance of potentially predictive biomarkers and develop a flexible nonparametric inference procedure for this estimand. We prove that our estimator is double robust and asymptotically linear under loose conditions in the data-generating process, permitting valid inference about the importance metric. The statistical guarantees of the method are verified in a thorough simulation study representative of randomized control trials with moderate and high-dimensional covariate vectors. Our procedure is then used to discover predictive biomarkers from among the tumor gene expression data of metastatic renal cell carcinoma patients enrolled in recently completed clinical trials. We find that our approach more readily discerns predictive from nonpredictive biomarkers than procedures whose primary purpose is treatment rule estimation. An open-source software implementation of the methodology, the uniCATE R package, is briefly introduced.

In an interim analysis of this phase 3 trial, the addition of pembrolizumab to chemotherapy resulted in longer progression-free survival than chemotherapy alone among patients with advanced triple-negative breast cancer whose tumors expressed programmed death ligand 1 (PD-L1) with a combined positive score (CPS; the number of PD-L1-staining tumor cells, lymphocytes, and macrophages, divided by the total number of viable tumor cells, multiplied by 100) of 10 or more. The results of the final analysis of overall survival have not been reported.

To promote the identification of women carrying BRCA1/2 variants, the US Preventive Services Task Force recommends that primary care clinicians screen asymptomatic women for an increased risk of carrying a BRCA1/2 variant risk.

Approximately 50% of newly diagnosed glioblastomas (GBMs) harbor epidermal growth factor receptor gene amplification (EGFR-amp). Preclinical and early-phase clinical data suggested efficacy of depatuxizumab mafodotin (depatux-m), an antibody-drug conjugate comprised of a monoclonal antibody that binds activated EGFR (overexpressed wild-type and EGFRvIII-mutant) linked to a microtubule-inhibitor toxin in EGFR-amp GBMs.

The Complexity INdex in SARComas (CINSARC) is a transcriptional signature derived from the expression of 67 genes involved in mitosis control and chromosome integrity. This study aims to assess CINSARC value of in an independent series of high-risk patients with localized soft tissue sarcoma (STS) treated with preoperative chemotherapy within a prospective, randomized, phase III study (ISG-STS 1001).

Skin cancer incidence is increasing among Hispanics, who experience worse outcomes than non-Hispanic Whites. Precision prevention incorporating genetic testing for MC1R, a skin cancer susceptibility marker, may improve prevention behavior.

In RELAY, ramucirumab plus erlotinib (RAM + ERL) improved progression-free survival (PFS) in patients with untreated, metastatic, EGFR-mutated, non-small cell lung cancer (NSCLC). Here, we present the exposure-response relationship of RAM from RELAY.

The phase III POLO study demonstrated significant progression-free survival (PFS) benefit for active olaparib maintenance therapy versus placebo for patients with metastatic pancreatic adenocarcinoma and a germline BRCA mutation. Here, we report the final analysis of overall survival (OS) and other secondary end points.

Introduction and Aim: Obese women with polycystic ovarian syndrome (PCOS) have a reduced rate of spontaneous conception even when their cycles are ovulatory. Endometrial receptivity is an important factor for poor implantation and increased miscarriage rates. Mechanisms in which both pathologies modify the endometrium are not fully clarified. The aim of our study was to compare the endometrial transcriptomic profiles between infertile obese PCOS (O-PCOS) women and infertile normal weight subjects during the window of implantation in ovulatory menstrual cycles. Methods: We conducted a prospective transcriptomic analysis of the endometrium using RNA sequencing. In this way, potential endometrial mechanisms leading to the poor reproductive outcome in O-PCOS patients could be characterized. Endometrial samples during days 21-23 of the menstrual cycle were collected from infertile O-PCOS women (n = 11) and normal weight controls (n = 10). Subgroups were defined according to the ovulatory/anovulatory status in the natural cycles, and O-PCOS women were grouped into the O-PCOS ovulatory (O-PCOS-ovul) subgroup. RNA isolation, sequencing with library reparation, and subsequent RNAseq data analysis were performed. Results: Infertile O-PCOS patients had 610 differentially expressed genes (DEGs), after adjustment for multiple comparisons with normal weight infertile controls, related to obesity (MXRA5 and ECM1), PCOS (ADAMTS19 and SLC18A2), and metabolism (VNN1 and PC). In the ovulatory subgroup, no DEGs were found, but significant differences in canonical pathways and the upstream regulator were revealed. According to functional and upstream analyses of ovulatory subgroup comparisons, the most important biological processes were related to inflammation (TNFR1 signaling), insulin signaling (insulin receptor signaling and PI3/AKT), fatty acid metabolism (stearate biosynthesis I and palmitate biosynthesis I), and lipotoxicity (unfolded protein response pathway). Conclusions: We demonstrated that endometrial transcription in ovulatory O-PCOS patients is deranged in comparison with the control ovulatory endometrium. The most important pathways of differentiation include metabolism and inflammation. These processes could also represent potential mechanisms for poor embryo implantation, which prevent the development of a successful pregnancy. ClinicalTrials.gov ID: NCT03353948.

Direct-to-patient telegenetics, which uses video conferencing to connect health professionals directly to patients' devices, has been widely adopted during the pandemic. However, limited evidence currently supports its use in cancer genetic counselling.

This study aimed to investigate the effect of the mFOLFOX6 regimen combined with SHR-1210 on immune function and prognosis in patients with microsatellite instability CRC. For this purpose, 60 patients with microsatellite instability CRC in our hospital from January 2019 to October 2020 were randomly divided into control and observation groups. The control group was treated with the mFOLFOX6 regimen, and the observation group was treated with s SHR-1210. After continuous treatment for 3 months, the clinical effects of the two groups were compared; CD4+, CD8+, CD4+/CD8+; IgA, IgG, IgM; Incidence of adverse reactions and PFS. The results showed that compared with the control group (30.00%), the total clinical effective rate in the observation group (53.33%) was significantly higher (P < 0.05). After treatment, CD4+, CD4+/ CD8+ decreased significantly and CD8+ increased significantly, and the change range of the observation group was significantly less than the control group (P < 0.05. The levels of IgA, IgG and IgM in the two groups decreased significantly after treatment, and the decrease in the observation group was significantly less than the control group (P < 0.05). There was no significant difference in the incidence of abnormal liver function, bleeding, proteinuria, neurotoxicity, gastrointestinal reaction, leucopenia and hypertension between the two groups (P > 0.05). PFS in the observation group was significantly prolonged after treatment (P < 0.05). In general, the mFOLFOX6 regimen combined with SHR-1210 is effective in the treatment of microsatellite instability CRC. It can not only improve the immune function, but also not increase adverse reactions, prolong the survival time, and has a high clinical reference value.