TALAPRO-3 clinical trial protocol: phase III study of talazoparib plus enzalutamide in metastatic castration-sensitive prostate cancer.

Poly(ADP-ribose) polymerase inhibitors in combination with androgen-receptor signaling inhibitors are a promising therapeutic option for patients with metastatic castration-sensitive prostate cancer (mCSPC) and homologous recombination repair (HRR) gene alterations. Here, we describe the design and rationale of the multinational, phase III, TALAPRO-3 study comparing talazoparib plus enzalutamide versus placebo plus enzalutamide in patients with mCSPC and HRR gene alterations. The primary end point is investigator-assessed radiographic progression-free survival (rPFS) per RECIST 1.1 in soft tissue, or per PCWG3 criteria in bone. The TALAPRO-3 study will demonstrate whether the addition of talazoparib can improve the efficacy of enzalutamide as assessed by rPFS in patients with mCSPC and HRR gene alterations undergoing androgen deprivation therapy. Clinical Trial Registration:NCT04821622 (ClinicalTrials.gov) Registry Name: Study of Talazoparib With Enzalutamide in Men With DDR Gene Mutated mCSPC. Date of Registration: 29 March 2021.

Localized Gastroesophageal Adenocarcinoma in the Elderly: Is Age a Factor Associated with Suboptimal Treatment?

INTRODUCTION: Gastroesophageal adenocarcinoma is relatively common in elderly patients as the incidence increases with age. However, the optimal treatment approach is not well established in this group of patients. The aim of this study is to review our experience for localized gastroesophageal adenocarcinoma in patients aged ≥80 years and to assess association between patient characteristics, clinical factors, and overall survival (OS) in order to optimize the therapeutic approaches for this population. METHODS: Patients ≥80 years old treated for localized gastroesophageal adenocarcinoma were retrospectively analyzed. Survival curves were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression models were applied to assess the association between patient characteristics and OS. Factors that were significant in the multivariate model were included in the final reduced model. RESULTS: 127 patients ≥80 years old, were included in this study with median age of 83 years. The median follow-up time was 3.2 years, and median OS was 2.5 years (95% CI: 2.0-3.1 years). Independent prognostic factors for OS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) (p = 0.003), baseline clinical stage (p = 0.01), and surgery (p = 0.001). ECOG PS, tumor location, baseline stage, tumor grade, and surgery were included in the final reduced model. CONCLUSION: Surgical treatment can improve survival in elderly patients. Therapeutic decisions should be based on the patients' general condition rather that age alone.

Talazoparib, a Poly(ADP-ribose) Polymerase Inhibitor, for Metastatic Castration-resistant Prostate Cancer and DNA Damage Response Alterations: TALAPRO-1 Safety Analyses.

BACKGROUND: The phase II TALAPRO-1 study (NCT03148795) demonstrated durable antitumor activity in men with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). Here, we detail the safety profile of talazoparib. PATIENTS AND METHODS: Men received talazoparib 1 mg/day (moderate renal impairment 0.75 mg/day) orally until radiographic progression, unacceptable toxicity, investigator decision, consent withdrawal, or death. Adverse events (AEs) were evaluated: incidence, severity, timing, duration, potential overlap of selected AEs, dose modifications/discontinuations due to AEs, and new clinically significant changes in laboratory values and vital signs. RESULTS: In the safety population (N = 127; median age 69.0 years), 95.3% (121/127) experienced all-cause treatment-emergent adverse events (TEAEs). Most common were anemia (48.8% [62/127]), nausea (33.1% [42/127]), decreased appetite (28.3% [36/127]), and asthenia (23.6% [30/127]). Nonhematologic TEAEs were generally grades 1 and 2. No grade 5 TEAEs or deaths were treatment-related. Hematologic TEAEs typically occurred during the first 4-5 months of treatment. The median duration of grade 3-4 anemia, neutropenia, and thrombocytopenia was limited to 7-12 days. No grade 4 events of anemia or neutropenia occurred. Neither BRCA status nor alteration origin significantly impacted the safety profile. The median (range) treatment duration was 6.1 (0.4-24.9) months; treatment duration did not impact the incidence of anemia. Only 3 of the 15 (11.8% [15/127]) permanent treatment discontinuations were due to hematologic TEAEs (thrombocytopenia 1.6% [2/127]; leukopenia 0.8% [1/127]). CONCLUSION: Common TEAEs associated with talazoparib could be managed through dose modifications/supportive care. Demonstrated efficacy and a manageable safety profile support continued evaluation of talazoparib in mCRPC. CLINICALTRIALS.GOV IDENTIFIER: NCT03148795.

Evaluation of children's cognitive load in processing and storage of their spatial working memory.

Working memory performance affects children's learning. This study examined objective (task performance), subjective (self-report), and physiological (pupil dilation) cognitive load (CL) while children completed a spatial working memory complex span task. Frist, 80 Taiwanese 11-year-olds (40 boys) who participated in Experiment 1 confirmed the suitability of the materials. Then, 72 Taiwanese 11-year-olds (35 boys) were assigned to high and low complexity groups to participate in Experiment 2 to test the study hypothesis. Children had to recall at the end of a dual-task list and answer two questions regarding the difficulty and mental effort involved in processing and storage. Their pupil diameters were recorded using an eye-tracker. Two-way mixed ANOVA found that the processing requirements and memory load reduced storage and aggravated the subjective CL of storage; the subjective CL of processing was higher under highly complex conditions. Stepwise regression analysis indicated that subjective CL of processing predicted memory performance in low CL conditions, and physiological CL of processing predicted it in high CL conditions.

Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): an open-label, phase 2 trial.

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors have antitumour activity against metastatic castration-resistant prostate cancers with DNA damage response (DDR) alterations in genes involved directly or indirectly in homologous recombination repair (HRR). In this study, we assessed the PARP inhibitor talazoparib in metastatic castration-resistant prostate cancers with DDR-HRR alterations. METHODS: In this open-label, phase 2 trial (TALAPRO-1), participants were recruited from 43 hospitals, cancer centres, and medical centres in Australia, Austria, Belgium, Brazil, France, Germany, Hungary, Italy, the Netherlands, Poland, Spain, South Korea, the UK, and the USA. Patients were eligible if they were men aged 18 years or older with progressive, metastatic, castration-resistant prostate cancers of adenocarcinoma histology, measurable soft-tissue disease (per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1]), an Eastern Cooperative Oncology Group performance status of 0-2, DDR-HRR gene alterations reported to sensitise to PARP inhibitors (ie, ATM, ATR, BRCA1, BRCA2, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C), had received one or two taxane-based chemotherapy regimens for metastatic disease, and progressed on enzalutamide or abiraterone, or both, for metastatic castration-resistant prostate cancers. Eligible patients were given oral talazoparib (1 mg per day; or 0·75 mg per day in patients with moderate renal impairment) until disease progression, unacceptable toxicity, investigator decision, withdrawal of consent, or death. The primary endpoint was confirmed objective response rate, defined as best overall soft-tissue response of complete or partial response per RECIST 1.1, by blinded independent central review. The primary endpoint was assessed in patients who received study drug, had measurable soft-tissue disease, and had a gene alteration in one of the predefined DDR-HRR genes. Safety was assessed in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, NCT03148795, and is ongoing. FINDINGS: Between Oct 18, 2017, and March 20, 2020, 128 patients were enrolled, of whom 127 received at least one dose of talazoparib (safety population) and 104 had measurable soft-tissue disease (antitumour activity population). Data cutoff for this analysis was Sept 4, 2020. After a median follow-up of 16·4 months (IQR 11·1-22·1), the objective response rate was 29·8% (31 of 104 patients; 95% CI 21·2-39·6). The most common grade 3-4 treatment-emergent adverse events were anaemia (39 [31%] of 127 patients), thrombocytopenia (11 [9%]), and neutropenia (ten [8%]). Serious treatment-emergent adverse events were reported in 43 (34%) patients. There were no treatment-related deaths. INTERPRETATION: Talazoparib showed durable antitumour activity in men with advanced metastatic castration-resistant prostate cancers with DDR-HRR gene alterations who had been heavily pretreated. The favourable benefit-risk profile supports the study of talazoparib in larger, randomised clinical trials, including in patients with non-BRCA alterations. FUNDING: Pfizer/Medivation.

Effectiveness of Applying Evidence-based Guidelines for Nurses Training on Nasogastric Tube Care.

BACKGROUND: This study formulated clinical guidelines for assessing nasogastric tube placement and for health education guidance according to evidence-based recommendations. METHOD: This study used a single group, pre- and postintervention design. Purposive sampling was used to recruit participants from nursing institutions in Taiwan. RESULTS: Sixty-two individuals in charge of nursing institutions were recruited to participate in the in-service training program. Statistically significant differences were observed in the four major items in the self-directed learning readiness scale (t = 3.85, p < .00; t = 3.99, p < .00; t = 2.94, p < .01; t = 4.13, p < .00). With regard to program satisfaction, the mean score was 4.88 to 4.9 points. The mean score for teaching satisfaction was 4.94 to 4.9 points. Furthermore, the participants scored more than 80 points in the online course test and the nasogastric tube placement skill. CONCLUSION: The individuals in-charge are expected to be willing to apply and promote methods of literature collation and recommendation in their respective institutions. [J Contin Educ Nurs. 2021;52(7):326-334.].

Phase 1 study of combinatorial sorafenib, G-CSF, and plerixafor treatment in relapsed/refractory, FLT3-ITD-mutated acute myelogenous leukemia patients.

Stroma-leukemia interactions mediated by CXCR4, CD44, VLA4, and their respective ligands contribute to therapy resistance in FLT3-ITD-mutated acute myelogenous leukemia (AML). We conducted a phase 1 study with the combination of sorafenib (a FLT3-ITD inhibitor), plerixafor (a SDF-1/CXCR4 inhibitor), and G-CSF (that cleaves SDF-1, CD44, and VLA4). Twenty-eight patients with relapsed/refractory FLT3-ITD-mutated AML were enrolled from December 2010 to December 2013 at three dose levels of sorafenib (400, 600, and 800 mg twice daily) and G-CSF and plerixafor were administered every other day for seven doses starting on day one. Sorafenib 800 mg twice daily was selected for the expansion phase. While no dose-limiting toxicities (DLT) were encountered in the four-week DLT window, hand-foot syndrome and rash were seen beyond the DLT window, which required dose reductions in most patients. The response rate was 36% (complete response (CR) = 4, complete remission with incomplete platelet recovery (CRp) = 4, complete remission with incomplete hematologic recovery (CRi) = 1, and partial response (PR) = 1) for the intention to treat population. Treatment resulted in 58.4 and 47 mean fold mobilization of blasts and CD34 /38- stem/progenitor cells, respectively, to the circulation. Expression of the adhesion molecules CXCR4, CD44, and VLA4 on circulating leukemia cells correlated negatively with the mobilization of CD34+/38-, CD34+/38-/123+ "progenitor" cells (all P ≤ .002). Mass cytometry analysis of sequential samples from two patients demonstrated resistance emerging early on from sub-clones with persistent Akt and/or ERK signaling. In conclusion, the strategy of combined inhibition of FLT3 kinase and stromal adhesive interactions has promising activity in relapsed/refractory, FLT3-ITD-mutated AML, which warrants further evaluation in the front-line setting.

Taxane-based or platinum-based combination chemotherapy given concurrently with radiation followed by surgery resulting in high cure rates in esophageal cancer patients.

BACKGROUND: Preoperative chemoradiotherapy (CRT) is one standard option for localized esophageal or gastroesophageal junction (GEJ) cancer patients but an optimal concurrent chemotherapy combination is not established. METHODS: 412 patients with resectable (cT1N1M0 or cT2-4N0-3M0) esophageal or GEJ cancer treated at the MDACC between October 2002 and June 2016 were analyzed. Exposures: CRT with DF or FOX followed by surgery (trimodality; TMT). Main outcomes and measures: Primary endpoints were overall survival (OS) and disease-free survival (DFS). Univariate and multivariate Cox analyses were performed. RESULTS: Of the 412 patients analyzed, 264 (64%) received DF and 148 (36%) FOX. The median age was 60 years, and 95% had adenocarcinoma. The clinical complete response, positron-emission tomography response, and pathologic complete response rates were 73%, 73%, and 30%, respectively. Median follow-up was 60.4 months. Median OS for the entire cohort was 81.6 months (95% confidence interval [CI], 56.3-122.0); 81.6 months (95% CI, 55.9-not estimable) for the DF group and 67.7 months (95% CI, 41.6-not estimable) for the FOX group (P = .24). The median DFS was 45.6 months (95% CI, 33.1-61.7) for the entire cohort; 49.5 months (95% CI, 38.6-70.3) for DF and 33.0 months (95% CI, 18.1-70.4; P = .38) for FOX. Higher tumor location (unfavorable) and clinical complete response (favorable) were prognostic for both OS and DFS in the multivariate analysis. CONCLUSION: At our high-volume center, the outcome of 412 TMT esophageal cancer patients was excellent. Taxane-based chemotherapy produces nonsignificant favorable trend.

The Design of ZnO Nanorod Arrays Coated with MnOx for High Electrochemical Stability of a Pseudocapacitor Electrode.

Tremendous efforts have been made on the development of unique electrochemical capacitors or pseudocapacitors due to the overgrowing electrical energy demand. Here, the authors report a new and simple strategy for fabricating hybrid MnOx-coated ZnO nanorod arrays. First, the vertically aligned ZnO nanorods were prepared by chemical bath deposition (CBD) as a template providing a large surface area for active material deposition. The manganese oxide was subsequently coated onto the surface of the ZnO nanorods to form a hybrid MnOx-coated ZnO nanostructure by anodic deposition in a manganese acetate (MnA)-containing aqueous solution. The hybrid structure of MnOx-coated ZnO nanorod arrays exhibits a large surface area and high conductivity, essential for enhancing the faradaic processes across the interface and improving redox reactions at active MnOx sites. A certain concentration of the deposition solution was selected for the MnOx coating, which was studied as a function of deposition time. Cyclic voltammetry (CV) curves showed that the specific capacitance (SC) of the MnOx-coated ZnO nanostructure was 222 F/g for the deposition times at 10 s when the concentration of MnA solution was 0.25 M. The unique hybrid nanostructures also exhibit excellent cycling stability with >97.5% capacitance retention after 1200 CV cycles. The proposed simple and cost-effective method of fabricating hybrid nanostructures may pave the way for mass production of future intelligent and efficient electrochemical energy storage devices.

FADS Genetic Variants in Taiwanese Modify Association of DHA Intake and Its Proportions in Human Milk.

Our objective was to determine how docosahexaenoic acid (DHA) proportions in human milk are modulated by maternal FADS gene variants and dietary intake in Taiwanese women. Inclusion criteria included being healthy, 20-40 y old, having had a full-term baby that they intended to breast feed for at least 1 month, and willingness to participate in this study. Intake of DHA was assessed by food frequency questionnaire and fatty acids were analyzed in human milk samples collected 3-4 weeks postpartum. Based on multiple linear regression of data from 164 mothers that completed this study, there was 0.28% (FA%) reduction in milk DHA in high versus low genetic risk (stratified by whether minor allele numbers were ≥ 3 in rs1535 and rs174448) and 0.45% reduction in low versus high intake (stratified by whether DHA intake reached 200 mg/d). There was a significant gene-diet interaction; mothers with low genetic risk only had high milk DHA proportions with high DHA intake, whereas for mothers with high genetic risk, dietary effects were quite limited. Therefore, for FADS single nucleotide polymorphism in Taiwanese women, increasing DHA intake did not correct low milk DHA proportions in those with a high-risk genotype. Diet only conferred benefits to those with a low-risk genotype. Trial registration: This trial was retrospectively registered (Feb 12, 2019) in ClinicalTrials.gov (No. NCT03842891, https://clinicaltrials.gov/ct2/show/NCT03842891).

Linitis Plastica: a Distinct Type of Gastric Cancer.

BACKGROUND: The prognosis of patients with linitis plastica (LP) gastric cancer is reported to be poor. The purpose of our retrospective study was to characterize the clinicopathologic features and survival outcomes of patients with LP, using a univocal definition. METHODS: We defined LP as gastric cancer that involves more than 1/3 of the gastric wall macroscopically. We reviewed a prospectively maintained institutional database of gastric cancer patients and summarized and compared clinicopathologic factors of patients with and without LP who had undergone gastrectomy. Patients were matched 1:1 using propensity score matching, and their overall survival (OS) rates and durations were compared. Multivariable Cox regression analyses were conducted, using gastrectomy as a time-varying covariate. RESULTS: We identified 740 patients with radiographically non-metastatic gastric cancer, 157 (21.2%) of whom had LP. Most patients with LP had advanced-stage disease (75.8% had stage IV disease, mainly due to peritoneal involvement). Patients with LP had significantly shorter OS durations than did those without LP in the entire cohort (median OS, 14.0 vs. 33.5 months; p value < 0.001) and in the surgical cohort (median OS after gastrectomy, 21.8 vs. 91.0 months; p < 0.001), as well as in the propensity-matched surgical cohort. In the LP cohort, chemotherapy (hazard ratio [HR] = 0.594; p = 0.076), chemoradiation therapy (HR = 0.346; p = 0.001), and gastrectomy (HR = 0.425; p = 0.003) were associated with a longer OS. CONCLUSIONS: LP is a phenotype of gastric cancer that often presents at an advanced stage, with a high rate of peritoneal involvement. The survival durations of patients with LP were poor in our study, even in the surgical cohort. The use of preoperative chemotherapy, chemoradiation therapy, and gastrectomy appeared to be important in carefully selected patients with localized LP.

Association of gene mutations with time-to-first treatment in 384 treatment-naive chronic lymphocytic leukaemia patients.

This study correlated somatic mutation results and known prognostic factors with time-to-first treatment (TTFT) in 384 treatment-naïve (TN) chronic lymphocytic leukaemia (CLL) patients to help determine disease-specific drivers of early untreated CLL. CLL DNA from either peripheral blood or bone marrow underwent next generation targeted sequencing with a 29-gene panel. Gene mutation data and concurrent clinical characteristics, such as Rai/Binet stage, fluorescence in situ hybridisation (FISH), ZAP70/CD38, karyotype and IGHV mutation, status were analysed in univariable and multivariable analyses to identify associations with TTFT. TTFT was defined as time from diagnosis to initial treatment. In univariable analyses, mutated ATM (P < 0·001), NOTCH1 (P < 0·001) and SF3B1 (P = 0·002) as well as unmutated IGHV (P < 0·001), del(11q) (P < 0·001) and trisomy 12 (P < 0·001) by hierarchal FISH and advanced Rai (P = 0·05) and Binet (P < 0·001) stages were associated with shorter TTFT. Importantly, del(17p), mutated TP53 and complex karyotype were not associated with shorter TTFT. In a reduced multivariable analysis, mutated ATM (P < 0·001) and unmutated IGHV status (P < 0·001) remained significant, showing their importance in early leukaemogenesis. High-risk prognostic markers such as del(17p), mutated TP53 and complex karyotype, were not correlated with TTFT, suggesting that these abnormalities have limited roles in early disease progression but are more important in relapsed CLL.

Routine sequencing in CLL has prognostic implications and provides new insight into pathogenesis and targeted treatments.

Chronic lymphocytic leukaemia (CLL) is a genetically heterogeneous disease characterised by genomic alterations and gene mutations that may portend worse survival or resistance to treatments. A total of 680 blood or bone marrow samples underwent targeted sequencing of 29 genes previously identified as being mutated in CLL, which were correlated to known prognostic clinical characteristics. Overall, 400 (59%) patients were treatment-naïve (TN) and 280 (41%) were relapsed/refractory (R/R). Most patients (70%) had ≥1 mutation, with TP53 (22%), SF3B1 (18%), NOTCH1 (13%) and ATM (13%) being the most commonly mutated genes. A higher proportion of R/R patients had mutations in SF3B1 (P = 0·01) and TP53 (P < 0·001). Patients with mutated IGHV CLL more often had mutations in KLHL6 (P = 0·001) and MYD88 (P < 0·001). Pairwise associations showed mutational co-occurrences in the TN group including SF3B1/ATM [false discovery rate (FDR) < 0·05] and NOTCH1/POT1 (FDR < 0·01). Recurrent mutations resulting in premature truncation prior to the ubiquitination domains of NOTCH1 in its PEST domain and BIRC3 in its RING domain can produce proteins that constitutively activate CLL. Frequent missense mutations, such as K700E in SF3B1 and E571K in XPO1, have unknown function but are most likely to be activating mutations. Future directions include using these mutations to identify pathways for therapeutic targeting and rational drug design.

Chemotherapy Versus Chemoradiation as Preoperative Therapy for Resectable Pancreatic Ductal Adenocarcinoma: A Propensity Score Adjusted Analysis.

OBJECTIVES: Although the use of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma is increasing, the optimal preoperative treatment regimen remains poorly defined. METHODS: All patients with resectable pancreatic ductal adenocarcinoma who received preoperative chemotherapy alone (12%) or chemoradiation therapy (CRT) alone (88%) before pancreatectomy between 1999 and 2014 were included. Propensity score matching with inverse probability weighting was conducted based on age, baseline carbohydrate antigen 19-9, and procedure type. RESULTS: Patients who received preoperative CRT were more likely to undergo a margin negative (91% vs 79%, P < 0.01) and node negative (53% vs 23%, P < 0.01) resection and experience less locoregional recurrence (LR; 16% vs 33%, P < 0.01) but similar median overall survival (OS; 33.6 vs 26.4 months, P = 0.09). On multivariate analysis, carbohydrate antigen 19-9 (hazard ratio, 1.2; 95% confidence interval [CI], 1.1-1.3) and positive lymph nodes (hazard ratio, 1.5; 95% CI, 1.0-2.2) were associated with OS, whereas tumor size (odds ratio [OR], 1.5; 95% CI, 1.3-1.8), positive lymph nodes (OR, 3.1; 95% CI, 1.8-5.6), and preoperative chemotherapy (OR, 1.8; 95% CI, 1.1-2.9) were associated with LR. CONCLUSIONS: Preoperative CRT is associated with less margin and lymph node positivity, reduced LR, and similar OS compared with preoperative chemotherapy.

Biliary Decompression in Perihilar Cholangiocarcinoma Improves Survival: A Single-Center Retrospective Analysis.

BACKGROUND AND AIMS: The complex biliary strictures of perihilar cholangiocarcinoma present significant challenges for providing adequate and long-lasting biliary drainage. The best approach to relieve obstruction remains controversial. The purpose of this study was to assess stenting outcomes in perihilar cholangiocarcinoma. METHODS: This study was approved by the center's institutional review board. Subjects with a diagnosis of perihilar cholangiocarcinoma who underwent endoscopic retrograde cholangiopancreatography (ERCP) were identified from endoscopic and pathologic databases from 1997 to 2014. Patient characteristics, endoscopic data, and follow-up evaluation data were retrospectively collected via review of available medical records. RESULTS: A total of 199 patients with perihilar cholangiocarcinoma who underwent a total of 504 ERCPs were included in the study. Nine of 504 (1.8%) procedures were technical failures. Among the 495 technically successful procedures, 347 (70.1%) procedures were clinical successes. Clinical success was significantly associated with longer overall survival (HR 0.57; p = 0.002). A higher proportion of patients with bilateral drainage had clinical success, compared with those with unilateral drainage. Cholangitis was not more common in the bilateral group compared to the unilateral group except in the group where a segment was not drained (1.9% vs 1.6% vs 7.1%, respectively). Patients with metal stents were 3.8 times more likely to have clinical success than those with plastic stents. CONCLUSIONS: In conclusion, adequate biliary drainage improves overall survival. Bilateral stenting if anatomy permits with self-expanding metal stents rather than plastic stents appears to provide the optimal chance of clinical success.

Safety of endoscopy in cancer patients with thrombocytopenia and neutropenia.

BACKGROUND AND AIMS: Cancer patients are prone to thrombocytopenia and neutropenia, which increase the risk of bleeding and infection. We assessed the safety of endoscopic procedures in cancer patients with thrombocytopenia and/or neutropenia. METHODS: We studied consecutive cancer patients with thrombocytopenia and/or neutropenia who underwent endoscopic procedures from 2010 through 2015. Neutropenia was defined as an absolute neutrophil count (ANC) <1000 cells/µL, and thrombocytopenia as a platelet count <100 × 103/µL. Univariate and multivariate generalized estimating equation models were used to assess factors associated with risk of adverse events (AEs) or death. RESULTS: We identified 588 patients who underwent 783 procedures; 608 procedures were performed in the setting of thrombocytopenia and 675 procedures in the setting of neutropenia. Concurrent neutropenia and thrombocytopenia were recorded in 500 endoscopies. Twenty-four patients (4.1%) experienced infectious AEs, whereas 29 (4.9%) experienced bleeding AEs within 1 week of the procedure. On multivariate analysis, platelet count ≤50 × 103/µL was associated with risk of bleeding AEs. In contrast, poor performance status was associated with increased risk of infection AEs (P < .01). No association was observed between low ANC and infectious AEs. Poor performance status (P < .01) and platelet count ≤100 × 103/µL (P < .05) were associated with increased risk of 30-day mortality. A persistent platelet count <20 × 103/µL after the procedure, with a baseline platelet count of ≤20 × 103/µL before the procedure, was associated with significant risk of bleeding AEs compared with a platelet count >20 × 103/µL after the procedure (P < .01); furthermore, if the platelet count increased to >50 × 103/µL after the procedure, the bleeding risk after the procedure was greatly reduced (P < .01). CONCLUSIONS: Endoscopic procedures are relatively safe in cancer patients with platelet count >50 × 103/µL. Nevertheless, a platelet count of ≥20 × 103/µL could be an appropriate threshold for platelet transfusion if 50 × 103/µL is difficult to achieve. The functional status of the patient, in the absence of the need for urgent or necessary endoscopic interventions, should be considered when deciding whether to perform endoscopy. The risk of procedure and the ANC did not seem to affect the outcomes.

Minimally invasive management of the entire treatment sequence in patients with stage IV colorectal cancer: a propensity-score weighting analysis.

BACKGROUND: In patients with stage IV colorectal cancer (CRC), minimally invasive surgery (MIS) may offer optimal oncologic outcome with low morbidity. However, the relative benefit of MIS compared to open surgery in patients requiring multistage resections has not been evaluated. METHODS: Patients who underwent totally minimally invasive (TMI) or totally open (TO) resections of CRC primary and liver metastases (CLM) in 2009-2016 were analyzed. Inverse probability of weighted adjustment by propensity score was performed before analyzing risk factors for complications and survival. RESULTS: The study included 43 TMI and 121 TO patients. Before and after adjustment, TMI patients had significantly less cumulated postoperative complications (41% vs. 59%, p = 0.001), blood loss (median 100 vs. 200 ml, p = 0.001) and shorter length of hospital stay (median 4.5 vs. 6.0 days, p < 0.001). Multivariate analysis identified TO approach vs. MIS (OR = 2.4, p < 0.001), major liver resection (OR = 4.4, p < 0.001), and multiple CLM (OR = 2.3, p = 0.001) as independent risk factors for complications. 5-year overall survival was comparable (81% vs 68%, p = 0.59). CONCLUSION: In patients with CRC undergoing multistage surgical treatment, MIS resection contributes to optimal perioperative outcomes without compromise in oncologic outcomes.

Preoperative chemoradiation therapy induces primary-tumor complete response more frequently than chemotherapy alone in gastric cancer: analyses of the National Cancer Database 2006-2014 using propensity score matching.

BACKGROUND: The benefit of preoperative chemoradiation (CXRT) over preoperative chemotherapy alone ("chemotherapy" hereafter) is unknown. By analyzing the National Cancer Database (NCDB), we investigated whether preoperative CXRT improves the incidence of primary tumor pathologic complete response (ypT0) and overall survival (OS) compared with preoperative chemotherapy in patients with gastric cancer. METHODS: Patients with non-metastatic gastric adenocarcinoma who underwent CXRT or chemotherapy followed by gastrectomy were included. Propensity score matching with a ratio of 1:1 was implemented to reduce selection bias. A conditional logistic regression model was used to compare incidences of ypT0 between groups, and Cox proportional hazards model was used to compare OS. RESULTS: We identified 8464 patients. Median patient age was 63 years; 76% were male and 79% were white. ypT0 was observed in 16.1% of patients in the CXRT group and 6.6% in the chemotherapy group (p < 0.001). After propensity score matching, a total of 2408 patients were matched. CXRT was associated with a higher incidence of ypT0 (OR 2.28, 95% CI 1.76-2.95; p < 0.0001) and higher frequency of R0 resection (92 vs. 86%; p < 0.001). However, CXRT was not associated with longer OS (HR 1.03, 95% CI 0.92-1.15; p = 0.63). Safety profiles (30-day mortality, 30-day readmission, and length of hospital stay) were equivalent between groups. CONCLUSIONS: In this study of gastric cancer patients from the NCDB, CXRT was associated with a higher incidence of ypT0 and R0 resection compared with chemotherapy, although it was not associated with a longer OS.

Central Lymph Node Metastasis in Gastric Cancer Is Predictive of Survival After Preoperative Therapy.

BACKGROUND: It is unclear how preoperative therapy for gastric cancer affects the metastasis rate of lymph nodes (LNs) and whether the location of positive LNs affects survival after preoperative therapy. Therefore, we determined the association between positive central lymph nodes (CnLNs) and disease stage and overall survival (OS). METHODS: We reviewed a prospectively maintained database to identify patients who had undergone resection of gastric adenocarcinoma at our institution from 2005 to 2015. CnLNs were defined as common hepatic, celiac, and proximal splenic artery LNs (stations no. 8, 9, and 11p). The frequency of CnLN metastases and risk factors affecting OS were examined. RESULTS: We identified 356 patients. Preoperative therapy was administered to 66% of patients. D2 LN dissection was performed in 80% of patients, and the median number of LNs examined was 25 (IQR, 18-34). In 243 patients (68%), CnLNs had undergone separate pathologic examination; the CnLN-positive rate was 9.1% (22 of 243; station no. 8, 4.5%; no. 9, 2.1%; and no. 11p, 4.8%). CnLN metastasis was associated with shorter 3-year OS in patients with pN2/3 disease (33 vs. 62%; p = 0.004). Among patients who had undergone preoperative therapy, ypT3-4 stage (HR 2.44; p = 0.01) and positive CnLNs (HR 5.44; p < 0.001) were negatively associated with OS by multivariate analysis. CONCLUSIONS: CnLN metastases are uncommon in gastric cancer and have an adverse effect on OS in patients who have undergone preoperative therapy. Larger multi-institutional studies are needed to determine whether CnLN positivity requires a separate staging category after preoperative therapy.

Quality of life after brachytherapy or bilateral nerve-sparing robot-assisted radical prostatectomy for prostate cancer: a prospective cohort.

OBJECTIVE: To provide comparative data on quality of life (QoL) after prostate cancer treatment to help patients make an informed decision regarding their choice of treatment. METHODS: Patients with pathologically proven, non-metastatic, T1-T3bN0 prostate cancer were included in this prospective non-randomized study if they were to receive treatment with curative intent. Sample size was at least 181 patients per cohort/treatment type. QoL was recorded at baseline and at each follow-up using the Expanded Prostate Cancer Index Composite (EPIC) instrument. The minimal clinically important difference was defined as half of the standard deviation of the baseline score for each domain. A mixed effects model was used to compare the different treatments. Data are presented on the brachytherapy and the bilateral nerve-sparing robot-assisted radical prostatectomy (RARP) cohorts. Hormonotherapy was not allowed. RESULTS: Between November 2007 and January 2013, 181 patients who received brachytherapy and 210 patients who underwent RARP were included. Of the patients who underwent RARP, 178 had bilateral nerve-sparing and were included in the present analysis. Response rate to EPIC questionnaires were higher in the brachytherapy than in the RARP arm: 82% vs 57% at 2 years after treatment and 55% vs 45% at 4 years after treatment. In the mixed effects model, patients in the RARP arm had better QoL with regard to urinary irritation/obstruction or bother and bowel function, and lower QoL regarding sexual function and urinary incontinence. Results were confirmed in a propensity score-matched model. Patient satisfaction was significantly higher in the brachytherapy group at 1, 2 and 3 years after treatment. CONCLUSION: This prospective non-randomized study shows long-term differences in QoL domains after bilateral nerve-sparing RARP and brachytherapy. Differences in patient satisfaction should be further explored. These results could be used to counsel patients in the decision-making process.