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BackgroundPrimary cytoreductive surgery followed by chemotherapy has been considered standard management for patients with advanced ovarian cancer over decades. An alternative approach of interval debulking surgery following neoadjuvant chemotherapy was subsequently reported by two randomized phase III trials (EORTC‐GCG, CHORUS), which were criticized owing to important limitations, especially regarding the rate of complete resection.Primary ObjectiveTo clarify the optimal timing of surgical therapy in advanced ovarian cancer.Study HypothesisPrimary cytoreductive surgery is superior to interval cytoreductive surgery following neoadjuvant chemotherapy for overall survival in patients with advanced ovarian cancer.Trial DesignTRUST is an international open, randomized, controlled multi-center trial investigating overall survival after primary cytoreductive surgery versus neoadjuvant chemotherapy and subsequent interval cytoreductive surgery in patients with FIGO stage IIIB–IVB ovarian, tubal, and peritoneal carcinoma. To guarantee adequate surgical quality, participating centers need to fulfill specific quality assurance criteria (eg, ≥50% complete resection rate in upfront surgery for FIGO IIIB–IVB patients, ≥36 debulking-surgeries/year) and agree to independent audits by TRUST quality committee delegates. Patients in the primary cytoreductive surgery arm undergo surgery followed by 6 cycles of platinum-based chemotherapy, whereas patients in the interval cytoreductive surgery arm undergo 3 cycles of neoadjuvant chemotherapy after histologic confirmation of the disease, followed by interval cytoreductive surgery and subsequently, 3 cycles of platinum-based chemotherapy. The intention of surgery for both groups is complete tumor resection according to guideline recommendations.Major Inclusion/Exclusion CriteriaMajor inclusion criteria are suspected or histologically confirmed, newly diagnosed invasive epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma FIGO stage IIIB–IVB (IV only if resectable metastasis). Major exclusion criteria are non-epithelial ovarian malignancies and borderline tumors; prior chemotherapy for ovarian cancer; or abdominal/pelvic radiotherapy.Primary EndpointOverall survival.Sample Size772 patients.Estimated Dates for Completing Accrual and Presenting ResultsAccrual completion approximately mid-2019, results are expected after 5 years' follow-up in 2024.Trial Registration NCT02828618.

Purpose Evidence supporting the use of neoadjuvant chemotherapy (NAC) in early breast cancer is based on studies mainly including women, whereas the utilization and effectiveness of NAC in men is less studied. The present study aimed to investigate the utilization and effectiveness of NAC in men and women with early breast cancer. Methods Eligible patients were identified through the Swedish National Breast Cancer Quality Register, that includes all newly diagnosed breast cancer cases in Sweden from 2008 and onwards. For the treatment utilization analysis, all patients with stage I–III between 2008 and 2020 were included (n = 82,888), whereas for the effectiveness analysis the cohort was restricted to patients receiving NAC (n = 6487). For both analyses, multivariate logistic regression models were applied to investigate potential sex disparities in NAC utilization and effectiveness, adjusted for patient- and tumor characteristics. Results In the NAC utilization analysis, 487 men and 82,401 women with stage I–III were included. No statistically significant difference between sexes in terms of NAC utilization was observed (adjusted Odds Ratio (adjOR): 1.135; 95% Confidence Interval (CI) 0.606–2.128) with an overall utilization rate of 4.9% in men compared to 7.8% in women. Among the 24 men and 6463 women who received NAC, the pathologic complete response (pCR) rates were 16.7% and 21.2%, respectively (adjOR: 1.141; 95% CI 0.141–9.238). Conclusion The present study did not find any sex disparities in NAC utilization or effectiveness in terms of pCR. This supports the current recommendations of treating men with breast cancer with the same indications for NAC as women.

Neoadjuvant chemotherapy (NAC) has shown promising results in patients with locally advanced penile cancer. However, no consensus exists on its applications for locally advanced penile cancer. Thus, it is unclear which kind of chemotherapy regimen is the best choice. Consequently, a systematic search of PubMed, Web of Science, and EMBASE was performed in March 2021 to assess the efficacy and safety of NAC for the treatment of patients with locally advanced penile cancer. The Newcastle-Ottawa Scale was used to assess the risk of bias in each study. This study synthesized 14 published studies. The study revealed that patients who achieved an objective response to NAC obtained a better survival outcome compared with those who did not achieve an objective response. In addition, the objective response rates (ORRs) and pathological complete response (pCR) rates were 0.57 and 0.11, respectively. The incidence of grade ≥3 toxicity was 0.36. Subgroup analysis found that the ORR and pCR of the taxane-platinum (TP) regimen group performed better than those of the nontaxane-platinum (NTP) regimen group (0.57 vs 0.54 and 0.14 vs 0.07, respectively). Moreover, the TP regimen group had more frequent toxicity than the NTP regimen group (0.41 vs 0.26). However, further studies were warranted to confirm the findings.

Patients with ovarian high-grade serous carcinoma (OHGSC) gradually acquire resistance to standard chemotherapy following recurrence. In our previous study on OHGSC, histone deacetylase (HDAC) 6 upregulation led to a poor prognosis, and programmed death ligand-1 (PD-L1) expression was positively correlated with HDAC6 expression. We analyzed HDAC6 and PD-L1 expression before and after chemotherapy to investigate their association with chemotherapy resistance and patient survival. PD-L1 and HDAC6 expression were immunohistochemically analyzed using clinical samples from 54 patients with OHGSC before and after standard chemotherapy. High PD-L1 expression (≥ 5%) was detected in five and nine patients before and after chemotherapy, respectively. The mean PD-L1-positive rate after chemotherapy was 3.88%, which was significantly higher than the rate before chemotherapy (0.68%). The high HDAC6 expression frequency significantly increased from four patients before chemotherapy to 13 patients after. High PD-L1 expression after chemotherapy was significantly correlated with a chemotherapy response score of three, signifying a good chemo-response. High PD-L1 expression after chemotherapy was associated with poor progression-free survival and overall survival in patients who underwent complete surgical resection. In OHGSC, residual tumors after chemotherapy show enhanced HDAC6 and PD-L1 expression. Upregulated PD-L1 after neoadjuvant chemotherapy (NAC) has contradictory characteristics, indicating a good response to chemotherapy but unfavorable survival. It is a wolf in sheep’s clothing, and physicians should not make an optimistic prognosis even if the patient shows a good response to NAC. HDAC6 and PD-L1 may be therapeutic targets and prognostic factors for residual tumors after chemotherapy in OHGSC.

Triple-negative breast cancer (TNBC) remains the poorest-prognosis breast cancer (BC) subtype. Gene expression profiling has identified at least six different triple-negative subtypes with different biology and sensitivity to therapies. The heterogeneous nature of TN tumors may justify the difficulty in treating this BC subtype. Several targeted agents have been investigated in clinical trials without demonstrating a clear survival benefit. Therefore, systemic chemotherapy remains the cornerstone of current clinical practice. Improving the knowledge of tumor biology is mandatory for patient management. In stages II and III, neoadjuvant systemic treatment is an effective option of care. The achievement of a pathological complete response represents an optimal surrogate for survival outcome as well as a test for tumor drug sensitivity. In this review, we provide a brief description of the main predictive biomarkers for tumor response to systemic treatment. Moreover, we review the treatment strategies investigated for TNBCs in neoadjuvant settings focusing on experimental drugs such as immunotherapy and poly [ADP-ribose] polymerase inhibitors that hold promise in the treatment of this aggressive disease. Therefore, the management of TNBC represents an urgent, current, unmet need in daily clinical practice. A key recommendation is to design biology-driven clinical trials wherein TNBC patients may be treated on the basis of tumor molecular profile.

Neoadjuvant chemotherapy (NAC) is an effective therapeutic regimen for patients with breast cancer. However, some individuals cannot benefit from NAC because of drug resistance. To date, valid strategies about enhancing sensitivity of breast cancer to NAC are still scarce. miRNAs have been reported to proverbially be involved in the onset and development of malignancies including drug resistance. GSE73736 was downloaded from the GEO database. Student's -test was conducted to acquire differentially expressed-miRNAs (DE-miRNAs). Potential target genes of DE-miRNAs were predicted by miRTarBase. Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses for these target genes were performed by database for annotation, visualization, and integrated discovery. Protein-protein interaction network was constructed by STRING database and visualized through Cytoscape software. The hub target gene-miRNA network was also established by Cytoscape software. Next, the expression of potential functional miRNAs in breast cancer cell lines and tissues was determined. Finally, the roles of miR-3617-3p, miR-3136-3p, and miR-520b in modulating breast cancer chemoresistance were further examined. A total of 123 DE-miRNAs were identified, including 60 upregulated miRNAs and 63 downregulated miRNAs in the chemoresistant breast cancer group when compared with the chemosensitive group. Six hundred and seventeen and 1,146 potential target genes for the top 10 most upregulated and downregulated miRNAs were predicted, respectively. Enrichment analyses revealed that these target genes were enriched in some cancer-associated or chemo-resistance-associated pathways, such as MAPK signaling pathway, wnt signaling pathway, and p53 signaling pathway. and were identified as hub genes in the protein-protein interaction network. The top 25 hub genes were potentially regulated by 16 DE-miRNAs, among which miR-3617-3p and miR-3136-3p were commonly upregulated, whereas miR-520b was downregulated in two chemoresistant breast cancer cells compared with chemosensitive cell. By analyzing TCGA data, we found that expression of miR-3136-3p and miR-520b was increased and decreased in breast cancer tissues, respectively. Moreover, functional experiments demonstrated that miR-3136-3p and miR-3617-3p could reduce chemosensitivity of breast cancer, whereas miR-520b could reverse chemoresistance. The present study, based on bioinformatics analysis and experimental validation, brings to light novel mechanisms of breast cancer NAC resistance.

Background Investigate the impact of interval cytoreductive surgery (ICS) on progression in an orthotopic mouse model of ovarian cancer and the impact of chemotherapy delivered at various timelines following surgery. Methods Luciferase-expressing ID8 murine ovarian cancer cells were implanted intra-bursally and IP to C57BL/7 mice. Once disease was established by bioluminescence, 2 cycles of neoadjuvant cisplatin were administered, and animals received either ICS (removal of the injected bursa/primary tumor) or anesthesia alone. Postsurgical chemotherapy was administered on the same day as the intervention (ICS/anesthesia), or on day 7 or day 28 following the intervention. Progression was quantified serially with in vivo bioluminescence imaging. Volume of ascitic fluid volume collected at necropsy was measured. Results Animals were matched for tumor burden at stratification. There was no accelerated growth of residual tumor after interval cytoreduction compared to controls. Animals who received chemotherapy on postoperative day (POD) 7 had better disease control compared to standard-of-care POD 28. Animals who underwent surgery had less ascites at necropsy compared to those who had anesthesia alone. Conclusions In this animal model, surgical wounding with suboptimal cytoreduction after neoadjuvant chemotherapy did not cause accelerated expansion of residual disease. Surgical wounding appears to impair cisplatin activity when given at time of surgery.

Effects of changes in body composition during neoadjuvant chemotherapy (NAC) on perioperative complications and prognosis are unknown in patients with esophageal squamous cell carcinoma (ESCC). A total of 175 patients who underwent surgery for ESCC in our hospital between 2016 and 2019 were examined. The psoas muscle index (PMI) was calculated from the total psoas muscle area, and the visceral fat mass (VFM) at the umbilical level was measured. We defined body composition change (BCC) group as those with increased VFM of ≥ 3% and decreased PMI of ≥ 3% during NAC. Sarcopenia (S) was defined as PMI < 5.89 (male) and <4.06 (female). Nutritional assessment using the Subjective Global Assessment tool was performed upon admission. The percentages of BCC group, pre-NAC S, and post-NAC S was 32.5%, 79.4%, and 80.0%, respectively. BCC group had significantly more postoperative complications (p < 0.01) and longer hospital stays (p = 0.03) than groups pre-NAC S and post-NAC S. Overall survival (OS) analysis using the Cox hazard model showed that stage III (p < 0.01) and post-NAC S (p = 0.03) were poor prognostic factors. Changes in body composition during NAC affected perioperative complications and prognosis of patients with ESCC.

Immunotherapy has become a pillar of advanced solid tumors treatment. Patients are more likely to benefit from neoadjuvant immunotherapy compared with traditional neoadjuvant therapy. However, the safety and efficacy of neoadjuvant immunotherapy for the treatment of locally advanced, surgically resectable Esophageal squamous cell carcinoma (ESCC) remain unknown. ESCC patients who received neoadjuvant treatment following minimally invasive esophagogastrostomy were enrolled from June 2020 to September 2021. The characteristics of neoadjuvant treatment and surgery were investigated to determine the safety and efficacy of the neoadjuvant combination of chemotherapy and immunotherapy (NCI). A total of 149 patients were included in the study. Patient ratio was 40:109 between NCI and neoadjuvant chemotherapy plus radiotherapy (NCR) groups. No significant difference was found in terms of pathological characteristics, including ypN stage, ypTNM stage, differentiation, lymphovascular invasion, perineural invasion, pathological complete regression and tumor regression score, and these parameters were not correlated with NCI or NCR (all >0.05). Regarding to the operation, the NCI group had less blood loss (49.25 ± 13.47 . 57.02 ± 47.26, p<0.001), and shorter operation time (247.75 ± 28.28 . 285.83 ± 52.43, p<0.001) than the NCR group. Additionally, the NCI group demonstrated a lower rate of overall perioperative complications (p=0.003) and grade >2 perioperative complications ( =0.042) than the NCR group. Overall, the findings reported here indicate NCI could result in better outcome and less complications to locally advanced ESCC patients compared with NCR therapy. As a novel therapeutic option, the efficacy and safety of NCI appears to be feasible and safe, while long-term survival data is still needed.