Comparing outcomes between neoadjuvant hormonal therapy followed by prostatectomy versus upfront prostatectomy in high-risk prostate cancer: The road ahead.
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ABSTRACT:
SUBMITTER: Bhargava P
PROVIDER: S-EPMC10249518 | biostudies-literature | 2023 Apr-Jun
REPOSITORIES: biostudies-literature
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Comparing outcomes between neoadjuvant hormonal therapy followed by prostatectomy versus upfront prostatectomy in high-risk prostate cancer: The road ahead.
Indian journal of urology : IJU : journal of the Urological Society of India 20230331 2
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Project description:BackgroundGlioblastoma multiforme (GBM) is an aggressive brain tumor with poor survival rates despite current treatments. The standard of care (SOC) includes surgery, followed by radiotherapy plus concurrent and adjuvant chemotherapy with temozolomide (TMZ). This phase II trial assessed the safety and efficacy of neoadjuvant TMZ (nTMZ) before and during chemoradiotherapy in newly diagnosed GBM patients.MethodsNewly diagnosed GBM patients who underwent maximal safe resection were randomized into 2 groups. One received nTMZ before standard chemoradiotherapy and adjuvant TMZ (intervention). The other received standard chemoradiotherapy followed by adjuvant TMZ (control). Primary endpoints were progression-free survival (PFS) at 6 and 12 months. Secondary endpoints included overall survival, radiological and clinical responses, and adverse events.ResultsOf 35 patients, 16 were in the intervention group and 19 in the control group. Median PFS was 9 months (95% CI: 3.93-14.06) versus 3 months (95% confidence interval [CI]: 1.98-4.01) in the control and intervention groups (P = .737), with a high progression rate (73.4%) during nTMZ treatment. The 6-month PFS rates were 58% versus 25% (P = .042), and 12-month PFS rates were 26% versus 25% (P = .390) in the control and intervention groups, respectively. Patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) and those with good performance status (PS) had significantly worse PFS with nTMZ. However, those who underwent larger extent of resection exhibited significantly better PFS with nTMZ. Adverse events were similar between groups.ConclusionsNeoadjuvant TMZ before SOC chemoradiotherapy did not improve outcomes for newly diagnosed GBM patients and is unsuitable for those with unmethylated MGMT and good PS. However, It may benefit patients with near or gross total resection. Further research is needed to refine GBM treatment strategies.
| S-EPMC11632829 | biostudies-literature
Project description:To compare cancer-specific survival (CSS) between patients who received neoadjuvant radiation followed by resection (NRR) and those who received upfront resection (UR) for locally advanced pancreatic cancer (LAPC).A total of 772 LAPC patients who underwent curative-intent surgical resection with or without neoadjuvant radiation from 2004 to 2013 were identified from the Surveillance, Epidemiology, and End Result (SEER) database. Propensity score matching (PSM) was conducted to eliminate possible bias. Kaplan-Meier method was used to analyze long-term outcome. Independent risk factors of CSS were predicted by Cox proportional hazards model. Subgroup analyses were done according to 5 variables.The propensity score model matched 196 patients from the whole cohort. Neoadjuvant radiation was an independent predictor of CSS no matter before or after PSM. After PSM, the 1-, 3-, 5-year CSS rates of NRR group were 82.7%, 39.2% and 17.1%, while 64.3%, 19.9% and 12.4% for UR group. The median CSS for NRR group was 25 months, while 17 months for UR group. In subgroup analyses, CSS rates or median CSS of NRR group were still superior to those of UR group in married, unmarried, pancreatic adenocarcinoma, G1+G2, G3+G4, N0 stage, N1 stage and M0 stage subgroups, but no differences were found in other histological types and M1 stage subgroups. Other predictors of CSS included histological type, tumor grade and marital status.Neoadjuvant radiation followed by resection has a significant survival benefit compared with upfront resection in LAPC patients. Therapeutic strategy for LAPC patients should be further explored.
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Project description:BackgroundIn contrast to pancreatic ductal adenocarcinoma (PDAC), neoadjuvant therapy (NAT) for periampullary adenocarcinomas is not well studied, with data limited to single-institution retrospective reviews with small cohorts. We sought to compare outcomes of NAT versus upfront resection (UR) for non-PDAC periampullary adenocarcinomas.Patients and methodsUsing the National Cancer Database (NCDB), we identified patients who underwent surgery for extrahepatic cholangiocarcinoma, ampullary adenocarcinoma, or duodenal adenocarcinoma from 2006 to 2016. We compared outcomes between NAT versus UR groups for each tumor subtype with 1:3 propensity score matching. Cox regression was used to identify predictors of survival.ResultsAmong 7656 patients who underwent resection for non-PDAC periampullary adenocarcinoma, the proportion of patients who received NAT increased from 6 to 11% for cholangiocarcinoma (p < 0.01), 1 to 4% for ampullary adenocarcinoma (p = 0.01), and 5 to 8% for duodenal adenocarcinoma (p = 0.08). Length of stay, readmission, and 30-day mortality were comparable between NAT and UR. All tumor subtypes were downstaged following NAT (p < 0.01). The R0 resection rate was significantly higher in patients with extrahepatic cholangiocarcinoma who received NAT, and these patients had improved median overall survival (38 vs 26 months, p < 0.001). After adjustment for clinicopathologic factors and adjuvant chemotherapy, use of NAT was associated with improved survival in patients with cholangiocarcinoma [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.54-0.89, p = 0.004] but not duodenal or ampullary adenocarcinoma. The survival advantage for cholangiocarcinoma persisted after propensity matching.ConclusionThis national cohort analysis suggests, for the first time, that neoadjuvant therapy is associated with improved survival in patients with extrahepatic cholangiocarcinoma.
| S-EPMC11186695 | biostudies-literature
Project description:BackgroundRoutine use of neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP) is not recommended, but it is sometimes performed to reduce the prostate size and tumor volume or to prevent tumor progression during the wait times for surgery in clinical practice. On the other hand, the impact of NHT on the pattern of biochemical recurrence (BCR) is unknown.MethodsWe retrospectively examined 1749 consecutive patients who underwent RP between 1996 and 2017. Among the patients who met the inclusion criteria, BCR developed in 240 of non-NHT patients and in 120 of NHT patients during the mean follow-up period of 6.9 years. We examined the impact of NHT on the PSA-doubling time (DT) following BCR at different times after RP.ResultsThe median PSA-DTs in non-NHT patients who experienced BCR in the first year after surgery, between 1 and 2 years, between 2 and 3 years, between 3 and 4 years, between 4 and 5 years, and at > 5 years were 5.5, 8.8, 11.3, 17.7, 18.2, and 18.4 months, respectively. On the other hand, those in NHT patients were 1.4, 4.1, 9.1, 13.4, 27.2, and 19.3 months, respectively. The differences of PSA-DTs in the first year after surgery (p < 0.001) and between 1 and 2 years (p = 0.005) were significant between non-NHT and NHT patients.ConclusionPatients who received NHT had a higher risk of a rapid PSA increase when they experienced BCR, especially within 2 years after RP. In order to not miss the optimal timing of salvage treatment for BCR, intensive PSA follow-up is necessary.
| S-EPMC8175233 | biostudies-literature
Project description:BackgroundProstate cancer (PC) is the most commonly diagnosed noncutaneous malignancy in American men. PC, which exhibits a slow growth rate and multiple potential target epitopes, is an ideal candidate for immunotherapy. GVAX for prostate cancer is a cellular immunotherapy, composed of PC-3 cells (CG1940) and LNCaP cells (CG8711). Each of the components is a prostate adenocarcinoma cell line that has been genetically modified to secrete granulocyte-macrophage colony-stimulating factor. Hypothesizing that GVAX for prostate cancer could be effective in a neoadjuvant setting in patients with locally advanced disease, we initiated a phase II trial of neoadjuvant docetaxel and GVAX. For the trial, the clinical effects of GVAX were assessed in patients undergoing radical prostatectomy (RP).MethodsPatients received docetaxel administered at a dose of 75 mg/m(2) every 3 weeks for 4 cycles. GVAX was administered 2-3 days after chemotherapy preoperatively for four courses of immunotherapy. The first dose of GVAX was a prime immunotherapy of 5×10(8) cells. The subsequent boost immunotherapies consisted of 3×10(8) cells. After RP, patients received an additional six courses of immunotherapy. Pathologic complete response, toxicity, and clinical response were assessed. The primary endpoint of the trial was a pathologic state of pT0, which is defined as no evidence of cancer in the prostate.ResultsSix patients completed neoadjuvant docetaxel and GVAX therapy. No serious drug-related adverse events were observed. Median change in prostate-specific antigen (PSA) following neoadjuvant therapy was 1.47 ng/ml. One patient did not undergo RP due to the discovery of positive lymph nodes during exploration. Of the five patients completing RP, four had a downstaging of their Gleason score. Undetectable PSA was achieved in three patients at 2 months after RP and in two patients at 3 years after RP.ConclusionsNeoadjuvant docetaxel/GVAX is safe and well tolerated in patients with high-risk locally advanced PC. No evidence of increased intraoperative hemorrhage or increased length of hospital stay postoperatively was noted. These results justify further study of neoadjuvant immunotherapy.
| S-EPMC4063395 | biostudies-literature
Project description:Current efforts in precision oncology largely focus on the benefit of genomics-guided therapy. Yet, advances in sequencing techniques provide an unprecedented view of the complex genetic and nongenetic heterogeneity within individual tumors. Herein, we outline the benefits of integrating genomic and transcriptomic analyses for advanced precision oncology. We summarize relevant computational approaches to detect novel drivers and genetic vulnerabilities, suitable for therapeutic exploration. Clinically relevant platforms to functionally test predicted drugs/drug combinations for individual patients are reviewed. Finally, we highlight the technological advances in single cell analysis of tumor specimens. These may ultimately lead to the development of next-generation cancer drugs, capable of tackling the hurdles imposed by genetic and phenotypic heterogeneity on current anticancer therapies.
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| S-EPMC9466315 | biostudies-literature
Project description:A great deal of excitement and hope has followed the successful trials and US Food and Drug Administration approval of the drug ivacaftor (Kalydeco), the first therapy available that targets the underlying defect that causes cystic fibrosis (CF). Although this drug has currently demonstrated a clinical benefit for a small minority of the CF population, the developmental pathway established by ivacaftor paves the way for other CF transmembrane conductance regulator (CFTR) modulators that may benefit many more patients. In addition to investigating CFTR modulators, researchers are actively developing numerous other innovative CF therapies. In this review, we use the catalog of treatments currently under evaluation with the support of the Cystic Fibrosis Foundation, known as the Cystic Fibrosis Foundation Therapeutics Pipeline, as a platform to discuss the variety of candidate treatments for CF lung disease that promise to improve CF care. Many of these approaches target the individual components of the relentless cycle of airway obstruction, inflammation, and infection characteristic of lung disease in CF, whereas others are aimed directly at the gene defect, or the resulting dysfunctional protein, that instigates this cycle. We discuss how new findings from the laboratory have informed not only the development of novel therapeutics, but also the rationales for their use and the outcomes used to measure their effects. By reviewing the breadth of candidate treatments currently in development, as well as the recent progress in CF therapies reflected by the evolution of the therapeutics pipeline over the past few years, we hope to build upon the optimism and anticipation generated by the recent success of Kalydeco.
| S-EPMC3610617 | biostudies-other
Project description:BackgroundThe favorable effect of postoperative chemotherapy on long-term survival has been well acknowledged in non-small cell lung cancer (NSCLC), while the role of neoadjuvant chemotherapy (NAC) remains obscure. This meta-analysis enrolling high-quality randomized controlled trials (RCTs) aimed at comparing NAC followed by surgery with upfront surgery (US) in efficacy and safety among non-metastatic NSCLC patients.Materials and methodsRelevant literatures were searched systematically from MEDLINE, EMBASE, and the Cochrane Library. We also screened references of relevant publications and conference proceedings. Primary outcomes were overall survival (OS), disease free survival (DFS), 3-year and 5-year survival rates, mortality, and recurrence. Secondary outcomes included tumor-free (R0) resection rates, response rate, and postoperative complications. Subgroup analysis according to ethnicity was further conducted.ResultsA total of 11 eligible RCTs comparing NAC (n = 1624) with US (n = 1639) and published from 1998 to 2013 were included. Compared to US, NAC contributed to longer OS and DFS, higher 3-year and 5-year DFS rates, and lower incidences of total mortality, overall recurrence and metastasis, and tended to cause higher 5-year OS rates. NAC was associated with reduced risks in recurrence compared to US. Patients receiving NAC had lower surgery and resection rates, but higher R0 resection incidence among resected cases. NAC especially benefited occident patients. The overall NAC response rate was 52.1%, and NAC-related toxicity rate was 58.3%.ConclusionNAC may provide better survival, reduced recurrence, and improved R0 resection rates among NSCLC patients who had surgery, especially in occident patients. Further studies are needed to clarify the ethnic differences.
| S-EPMC5685753 | biostudies-literature