Chemotherapy Plus Atezolizumab Pre- and Post-Resection in Localized Esophageal or Gastroesophageal Junction Adenocarcinomas: A Phase I/II Single-Arm Study.

Efforts to improve the prognosis for patients with locally advanced esophageal or gastroesophageal junction (GEJ) adenocarcinoma have focused on neoadjuvant approaches to increase the pathological complete response (pathCR) rate, improve surgical resection, and prolong event-free and overall survival (OS). Building on the recent evidence that PD-1 inhibition plus chemotherapy improves the OS of patients with metastatic GEJ adenocarcinoma, we evaluated whether the application of this strategy in the neoadjuvant setting would improve the pathological response. This single-center phase I/II trial evaluated the safety, toxicity, and efficacy of neoadjuvant atezolizumab with oxaliplatin and 5-fluorouracil (modified FOLFOX) followed by esophagectomy followed by atezolizumab. The primary objective goal was to achieve 20% pathCR. From the twenty enrolled patients, eighteen underwent resection and two (10%, 95% CI: 1.24-31.7%) achieved pathCR. After a median follow-up duration of 40.7 months, 11 patients had disease recurrence and 10 had died. The median disease-free and OS were 28.8 (95% CI: 14.7, NA) and 38.6 months (95% CI: 30.5, NA), respectively. No treatment-related adverse events led to death. Although modified FOLFOX plus atezolizumab did not achieve the expected pathCR, an acceptable safety profile was observed. Our results support the continued development of a more refined strategy (neoadjuvant chemotherapy plus perioperative immunotherapy/targeted agents) with molecular/immune profiling in parallel.

A west African ancestry-associated SNP on 8q24 predicts a positive biopsy in African American men with suspected prostate cancer following PSA screening.

BACKGROUND: African American (AA) men have the highest incidence and mortality rates of prostate cancer (PCa) among all racial groups in the United States. While race is a social construct, for AA men, this overlaps with west African ancestry. Many of the PCa susceptibility variants exhibit distinct allele frequencies and risk estimates across different races and contribute substantially to the large disparities of PCa incidence among races. We previously reported that a single-nucleotide polymorphism (SNP) in 8q24, rs7824364, was strongly associated with west African ancestry and increased risks of PCa in both AA and Puerto Rican men. In this study, we determined whether this SNP can predict biopsy positivity and detection of clinically significant disease (Gleason score [GS] ≥ 7) in a cohort of AA men with suspected PCa. METHODS: SNP rs7824364 was genotyped in 199 AA men with elevated total prostate-specific antigen (PSA) (>2.5 ng/mL) or abnormal digital rectal exam (DRE) and the associations of different genotypes with biopsy positivity and clinically significant disease were analyzed. RESULTS: The variant allele carriers were significantly over-represented in the biopsy-positive group compared to the biopsy-negative group (44% vs. 25.7%, p = 0.011). In the multivariate logistic regression analyses, variant allele carriers were at a more than a twofold increased risk of a positive biopsy (odds ratio [OR] = 2.14, 95% confidence interval [CI] = 1.06-4.32). Moreover, the variant allele was a predictor (OR = 2.26, 95% CI = 1.06-4.84) of a positive biopsy in the subgroup of patients with PSA < 10 ng/mL and normal DRE. The variant allele carriers were also more prevalent in cases with GS ≥ 7 compared to cases with GS < 7 and benign biopsy. CONCLUSIONS: This study demonstrated that the west African ancestry-specific SNP rs7824364 on 8q24 independently predicted a positive prostate biopsy in AA men who were candidates for prostate biopsy subsequent to PCa screening.

Influence of lamina propria invasion extension on T1 high-grade non-muscle-invasive bladder cancer in patients undergoing BCG or radical cystectomy.

OBJECTIVE: To evaluate the prognostic value of T1 substaging in patients treated with bacillus Calmette-Guérin (BCG) or immediate radical cystectomy (iRC). MATERIALS AND METHODS: We performed an institutional review board-approved retrospective study analysing non-muscle-invasive bladder cancer (NMIBC) patients with pT1 disease treated with either BCG or iRC between 2000 and 2020. Lamina propria (LP) invasion characteristics were extracted from the pathology report. The Kaplan-Meier method was used to calculate overall survival (OS), cancer-specific survival (CSS) and metastasis-free survival (MFS). Multivariable Cox models were used to determine the association between progression-free survival (PFS) and characteristics in the BCG cohort. A logistic regression model explored the relationship between T1 substaging and upstaging to >pT2 at iRC. RESULTS: A total of 411 T1 high-grade patients were identified. LP invasion characteristics were as follows: not specified: 115 (28%); focal/superficial (F/S): 147 (35.8%); and extensive/multifocal (E/M): 149 (36.2%). Overall, 303 patients (73.7%) received BCG, and 108 patients (26.3%) underwent iRC. The median (interquartile range) follow-up was 53 (32-96) months. Patients with E/M LP invasion were significantly more likely to undergo iRC (34% vs. 19%; P = 0.003). Patients with E/M LP invasion showed poorer MFS and CSS compared to those with F/S LP invasion when treated with BCG but not when treated with iRC. Among BCG-treated patients, progression occurred in 41 patients and E/M LP invasion was independently associated with progression after BCG (hazard ratio 5.3, 95% confidence interval [CI] 2.2-13.1; P < 0.001). T1 substaging was not associated with upstaging at RC (odds ratio 3.15, 95% CI 0.82-12.12; P = 0.095). CONCLUSIONS: Extensive/multifocal LP invasion was associated with poor PFS, MFS and CSS in patients treated with BCG. T1 substaging provides valuable prognostic information and should be reported in pathology reports.

Robotic or open superficial inguinal lymph node dissection as staging procedures for clinically node negative high risk penile cancer.

OBJECTIVE: To evaluate perioperative and oncologic outcomes of a cohort of clinically node negative high-risk penile cancer patients undergoing robotic assisted inguinal lymph node dissection (RAIL) compared to patients undergoing open superficial inguinal lymph node dissection (OSILND). PATIENTS AND METHODS: We retrospectively reviewed the clinical characteristics and outcomes of clinically node negative high-risk penile cancer patients undergoing RAIL at MDACC from 2013-2019. We sought to compare this to a contemporary open cohort of clinically node negative patients treated from 1999 to 2019 at MDACC and Moffit Cancer Center (MCC) with an OSILND. Descriptive statistics were used to characterize the study cohorts. Comparison analysis between operative variables was performed using Fisher's exact test and Wilcoxon's rank-sum test. The Kaplan-Meier method was used to estimate survival endpoints. RESULTS: There were 24 patients in the RAIL cohort, and 35 in the OSILND cohort. Among the surgical variables, operative time (348.5 minutes vs. 239.0 minutes, P < 0.01) and the duration of operative drain (37 vs. 22 days P = 0.017) were both significantly longer in the RAIL cohort. Complication incidences were similar for both cohorts (34.3% for OSILND vs. 33.3% for RAIL), with wound complications making up 33% of all complications for RAIL and 31% of complications for OSILND. No inguinal recurrences were noted in either cohort. The median follow-up was 40 months for RAIL and 33 months for OSILND. CONCLUSIONS: We observed similar complication rates and surgical variable outcomes in our analysis apart from operative time and operative drain duration. Oncological outcomes were similar between the two cohorts. RAIL was a reliable staging and potentially therapeutic procedure among clinically node negative patients with penile squamous cell carcinoma with comparable outcomes to an OSILND cohort.

Polyploid speciation in Zea (Poaceae): cytogenetic insights.

MAIN CONCLUSION: The analysis of meiotic pairing affinities and genomic formulae in species and hybrids of Zea allowed us to speculate an evolutionary model to recreate the ancient polyploidization of maize and allied species. The meiotic pairing affinities and the genomic formulae analysis in Zea species and hybrids obtained in new and previous crosses, together with the molecular data known in the genus, allowed us to speculate an evolutionary model to attempt to recreate the ancient polyploidization process of Zea species. We propose that x = 5 semispecies are the ancestors of all modern species of the genus. The complex evolutionary process that originated the different taxa could be included hybridization between sympatric diploid ancestral semispecies (2n = 10) and recurrent duplication of the hybrid chromosome number, resulting in distinct auto- and allopolyploids. After the merger and doubling of independent genomes would have undergone cytological and genetical diploidization, implying revolutionary changes in genome organization and genic balance processes. Based on the meiotic behaviour of the 2n = 30 hybrids, that showed homoeology between the A subgenomes of all parental species, we propose that this subgenome A would be pivotal in all the species and would have conserved the rDNA sequences and the pairing regulator locus (PrZ). In the hypothetical model postulated here, the ancestral semispecies with the pivotal subgenome A would have had a wide geographic distribution, co-occurring and hybridizing with the semispecies harbouring B subgenomes, thus enabling sympatric speciation.

Oral Toxicities Associated with Immune Checkpoint Inhibitors: Meta-Analyses of Clinical Trials.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, their oral toxicity profile is not well elucidated. This review aimed to investigate the prevalence of oral toxicities including xerostomia, mucositis/stomatitis, dysgeusia, dysphagia, oral/oropharyngeal pain, oral infections, angular cheilitis, osteonecrosis, osteomyelitis, and oral mucosal reactions with ICIs. A review protocol was registered with PROSPERO (ID: CRD42023391674). A systematic search of ClinicalTrials.gov was conducted as of April 10, 2022. Studies were selected, assessed, and data extracted using PRISMA guidelines. Oral toxicity data were extracted from study arms using a single immunotherapy drug. Meta-analyses were conducted to summarize prevalence of oral toxicities using random-effects models. Of 750 screened records, 95 trials were included in the meta-analysis with published results. Time between study completion and first publication on ClinicalTrials.gov was 1 to 146 months (mean = 20.3, SD = 18.4). Weighted pooled prevalence was 5% (95% CI: 4-6%) for xerostomia, 3% (95% CI: 3-4%) for mucositis/stomatitis, 3% (95% CI: 2-3%) for dysgeusia, 2% (95% CI: 1-2%) for dysphagia, 3% (95% CI: 2-4%) for oropharyngeal/oral pain, 2% (95% CI: 1-3%) for oral candidiasis, and 2% (95% CI: 0-4%) for angular cheilitis. Subgroup differences based on ICI drugs were minimal. No trials reported lichenoid or pemphigoid mucosal reactions. Meta-analysis results revealed low prevalence of oral toxicities with ICIs; however, data reporting was limited and inconsistent. Limitations of study dataset reveal a significant need for systematic collection of oral morbidity data as well as improved consistency and compliance of reporting results on ClinicalTrials.gov.

Impact of age >70 years on oncological outcomes in patients with non-muscle-invasive bladder cancer treated with Bacillus Calmette-Guérin.

OBJECTIVE: To evaluate the impact of age on oncological outcomes in a large contemporary cohort of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adequate Bacillus Calmette-Guérin (BCG). PATIENTS AND METHODS: We performed an Institutional Review Board-approved retrospective study analysing patients with NMIBC treated with adequate BCG at our institution from 2000 to 2020. Adequate BCG was defined as per United States Food and Drug Administration (FDA) guidelines as being receipt of at least five of six induction BCG instillations with a minimum of two additional doses (of planned maintenance or of re-induction) of BCG instillations within a span of 6 months. The study's primary outcome was to determine if age >70 years was associated with progression to MIBC cancer or distant metastasis. The cumulative incidence method and the competing-risk regression analyses were used to investigate the association of advanced age (>70 years) with progression, high-grade (HG) recurrence and cancer-specific mortality (CSM). RESULTS: Overall, data from 632 patients were analysed: 355 patients (56.2%) were aged ≤70 years and 277 (43.8%) were >70 years. Age >70 years did not adversely affect either cumulative incidence of progression or HG recurrence (P = 0.067 and P = 0.644, respectively). On competing-risk regression analyses, age >70 years did not emerge as an independent predictor of progression or HG recurrence (sub-standardised hazard ratio [SHR] 1.57, 95% confidence interval [CI] 0.87-2.81, P = 0.134; and SHR 1.05, 95% CI 0.77-1.44, P = 0.749). Not unexpectedly, patients in the older group did have higher overall mortality (P < 0.001) but not CSM (P = 0.057). CONCLUSION: Age >70 years was not associated with adverse oncological outcomes in a large contemporary cohort of patients receiving adequate intravesical BCG for NMIBC. BCG should not be withheld from older patients seeking for bladder sparing options.

Development validation and evaluation of the knowledge test on cardiopulmonary resuscitation and correct use of the automated external defibrillator in Asunción 2023

Introduction: in out-of-hospital cardiac arrest, early and efficient intervention through cardiopulmonary resuscitation (CPR) maneuvers and the use of the automated external defibrillator (AED) are the cornerstone for survival. Instruments that improve education would increase the responsiveness of lay personnel. Objectives: to develop, validate and evaluate a knowledge test on cardiopulmonary resuscitation and correct use of the automated external defibrillator in Asunción during 2023. Methodology: observational cross-sectional study, non-probabilistic sample for convenience of lay personnel users of mass attendance centers in Asunción. An exclusive questionnaire was developed on knowledge in cardiopulmonary resuscitation and the use of the automated external defibrillator (KOR-AED) based on the chain of survival in out-of-hospital cardiac arrest. Content, construct, and internal consistency were validated using expert opinion, factor analysis and Cronbach's alpha. Results: a total of 200 lay people participated, mostly shopping mall customers, with a predominance of men (63.5 %) (127), between 25-29 years old 28.5% (57). 61.5 % (123) had a university education, 75.5 % (151) had not related to health, 52 % (104) had prior knowledge of CPR, but 81.5 % (163) did not. The test showed reliability and suitability for factor analysis (Cronbach's alpha 0.75, Kaiser-Meyers-Olkin; 0.78, Bartlett p<0.05). The questions covered the first three links in the chain of survival, with items of medium to high difficulty. Women performed significantly better (p=0.04). Conclusion: the KOR-AED test is a valid and reliable instrument to improve the education of the layperson in CPR and use of the AED based on the chain of survival.

Introducción: en la parada cardíaca extrahospitalaria la actuación precoz y eficiente mediante maniobras de reanimación cardiopulmonar (RCP) y uso del desfibrilador externo automático (DEA) constituyen la piedra angular para la supervivencia. Instrumentos que mejoren la educación aumentarían la respuesta del personal lego. Objetivos: desarrollar, validar y evaluar una prueba de conocimientos sobre reanimación cardiopulmonar y uso correcto del desfibrilador externo automático en Asunción durante el 2023. Metodología: estudio observacional corte transversal, muestro no probabilístico por conveniencia de personal lego usuarios de centros de concurrencia masiva de Asunción. Se desarrolló un cuestionario exclusivo sobre conocimientos en reanimación cardiopulmonar y uso del desfibrilador externo automático (COR-DEA) basado en la cadena de supervivencia en parada cardíaca extrahospitalaria. Se validó el contenido, el constructo y la consistencia interna mediante la opinión de experto, análisis de factores y el alfa de Cronbach. Resultados: participaron 200 legos mayormente clientes de shoppings, predominando hombres 63,5 % (127) entre 25-29 años 28,5 % (57). Con educación universitaria 61,5 % (123), no relacionados con la salud 75,5 % (151), con conocimientos previos en RCP 52 % (104), pero no en DEA 81,5 % (163). El test mostró fiabilidad y adecuación para análisis factorial (Alfa de Cronbach 0.75, Kaiser-Meyers-Olkin; 0.78, Bartlett p<0.05). Las preguntas abarcarón los tres primeros eslabones de la cadena de supervivencia, con ítems de dificultad media a alta. Las mujeres tuvieron significativamente mejor desempeñó (p=0.04). Conclusión: la prueba COR-DEA es un instrumento válido y fiable para mejorar la educación del lego en RCP y uso del DEA basado en la cadena de supervivencia.

Development validation and evaluation of the knowledge test on cardiopulmonary resuscitation and correct use of the automated external defibrillator in Asunción 2023 / Desarrollo validación y evaluación de la prueba de conocimientos sobre reanimación cardiopulmonar y uso correcto del desfibrilador externo automático en Asunción 2023

Introduction: in out-of-hospital cardiac arrest, early and efficient intervention through cardiopulmonary resuscitation (CPR) maneuvers and the use of the automated external defibrillator (AED) are the cornerstone for survival. Instruments that improve education would increase the responsiveness of lay personnel. Objectives: to develop, validate and evaluate a knowledge test on cardiopulmonary resuscitation and correct use of the automated external defibrillator in Asunción during 2023. Methodology: observational cross-sectional study, non-probabilistic sample for convenience of lay personnel users of mass attendance centers in Asunción. An exclusive questionnaire was developed on knowledge in cardiopulmonary resuscitation and the use of the automated external defibrillator (KOR-AED) based on the chain of survival in out-of-hospital cardiac arrest. Content, construct, and internal consistency were validated using expert opinion, factor analysis and Cronbach's alpha. Results: a total of 200 lay people participated, mostly shopping mall customers, with a predominance of men (63.5 %) (127), between 25-29 years old 28.5% (57). 61.5 % (123) had a university education, 75.5 % (151) had not related to health, 52 % (104) had prior knowledge of CPR, but 81.5 % (163) did not. The test showed reliability and suitability for factor analysis (Cronbach's alpha 0.75, Kaiser-Meyers-Olkin; 0.78, Bartlett p<0.05). The questions covered the first three links in the chain of survival, with items of medium to high difficulty. Women performed significantly better (p=0.04). Conclusion: the KOR-AED test is a valid and reliable instrument to improve the education of the layperson in CPR and use of the AED based on the chain of survival.

Introducción: en la parada cardíaca extrahospitalaria la actuación precoz y eficiente mediante maniobras de reanimación cardiopulmonar (RCP) y uso del desfibrilador externo automático (DEA) constituyen la piedra angular para la supervivencia. Instrumentos que mejoren la educación aumentarían la respuesta del personal lego. Objetivos: desarrollar, validar y evaluar una prueba de conocimientos sobre reanimación cardiopulmonar y uso correcto del desfibrilador externo automático en Asunción durante el 2023. Metodología: estudio observacional corte transversal, muestro no probabilístico por conveniencia de personal lego usuarios de centros de concurrencia masiva de Asunción. Se desarrolló un cuestionario exclusivo sobre conocimientos en reanimación cardiopulmonar y uso del desfibrilador externo automático (COR-DEA) basado en la cadena de supervivencia en parada cardíaca extrahospitalaria. Se validó el contenido, el constructo y la consistencia interna mediante la opinión de experto, análisis de factores y el alfa de Cronbach. Resultados: participaron 200 legos mayormente clientes de shoppings, predominando hombres 63,5 % (127) entre 25-29 años 28,5 % (57). Con educación universitaria 61,5 % (123), no relacionados con la salud 75,5 % (151), con conocimientos previos en RCP 52 % (104), pero no en DEA 81,5 % (163). El test mostró fiabilidad y adecuación para análisis factorial (Alfa de Cronbach 0.75, Kaiser-Meyers-Olkin; 0.78, Bartlett p<0.05). Las preguntas abarcarón los tres primeros eslabones de la cadena de supervivencia, con ítems de dificultad media a alta. Las mujeres tuvieron significativamente mejor desempeñó (p=0.04). Conclusión: la prueba COR-DEA es un instrumento válido y fiable para mejorar la educación del lego en RCP y uso del DEA basado en la cadena de supervivencia.

Diversity and conservation of mammals in indigenous territories of southern Mexico: proposal for an "Archipelago Reserve".

Southern Mexico's tropical forests are home to the country's highest richness of mammal species; La Chinantla region is situated within this area, its name from the indigenous group residing in the area and holding territorial ownership, namely the Chinantecos. In La Chinantla, there are no Protected Areas; instead, there are Areas Destined Voluntarily for Conservation (ADVC) and "Voluntary Conservation Areas" (VCA), that are managed by local inhabitants through social consensus. These ADVC may function as an archipelago reserve, which represents regional diversity, including the social context, through complementarity. To verify its biodiversity, we analyzed the richness, composition, distribution, and conservation of wild mammals in the region. Records were obtained from four sources-primary data collection, databases, scientific literature, and community monitoring-and were organized into four zones based on altitudinal and vegetation gradients. We compared the diversity between zones for three categories of mammals: small (<100 gr.), bats, and medium and large (>100 gr.). 134 species were identified comprising 11 orders, 26 families and 86 genera. The zone with highest elevation presented the greatest species richness for the assemblage of mammals and terrestrial mammals, while the zone with the lowest elevation had the highest richness of bats. For each mammal category, the zone with the most species also registered the highest number of exclusive species. For the assemblage of mammals and for medium and large mammals, the similarity index was highest between the two intermediate zones, while for small mammals and bats, the greatest similarity occurred between the areas of higher altitude. The study region was found to have the second highest richness of mammals in Mexico. Finally, we suggest that the conservation proposals by indigenous people could function as a set of "islands" that promote the conservation of biodiversity, possibly as an Archipelago Reserve.

Oncological Outcomes for Patients with European Association of Urology Very High-risk Non-muscle-Invasive Bladder Cancer Treated with Bacillus Calmette-Guérin or Early Radical Cystectomy.

BACKGROUND: European Urology Association (EAU) guidelines recommend immediate radical cystectomy (early RC) for patients with very high-risk (VHR) non-muscle invasive bladder cancer (NMIBC), with bacillus Calmette-Guérin (BCG) recommended only for those who refuse or are unfit for RC. OBJECTIVE: To describe oncological outcomes following BCG or early RC in a contemporary cohort of patients with VHR NMIBC (EAU criteria). DESIGN, SETTING, AND PARTICIPANTS: Patients diagnosed with VHR NMIBC between 2000 and 2020 were identified from our institutional NMIBC registry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcomes were overall survival (OS) and cancer-specific mortality (CSM). Secondary outcomes were the progression rate and high-grade recurrence (HGR) rate for patients receiving BCG. RESULTS AND LIMITATIONS: We identified 235 patients with VHR NMIBC, of whom 157 (67%) received BCG and 78 (33%) underwent early RC. The median follow-up was 52.8 mo. OS and CSM rates were 80.2% and 5.3% in the BCG group, and 88.1% and 4.9% in the early RC group, respectively with no significant difference in OS (p = 0.6) or CSM (p = 0.8) between the two groups. Among the patients treated with BCG, 5-yr HGR and progression rates were 41.9% and 17.4%, respectively; 39 patients (25%) underwent delayed RC after BCG. No significant difference in CSM emerged when comparing patients treated with delayed RC (after BCG) with those undergoing early RC (p = 0.86). CONCLUSIONS: Our findings suggest that intravesical BCG can be offered to patients as a resonable alternative to early RC for selected patients with VHR NMIBC. PATIENT SUMMARY: We evaluated outcomes for patients with very high-risk non-muscle-invasive bladder cancer (NMIBC) treated with BCG (bacillus Calmette-Guérin) versus early surgical removal of the bladder and found no differences in survival. We conclude that BCG could be offered to selected patients with this type of bladder cancer as a reasonable alternative to early bladder removal.

Bladder-sparing Treatment in Patients with Bacillus Calmette-Guerin-unresponsive Non-muscle-invasive Bladder Cancer: An Analysis of Long-term Survival Outcomes.

Background: Data for bladder-sparing treatment (BST) in bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients report short-term outcomes limited to 1-2 yr. Objective: To assess long-term survival outcomes of BCG-unresponsive NMIBC patients treated with BST. Design setting and participants: BCG-unresponsive NMIBC patients diagnosed between January 2000 and September 2021 from an institutional NMIBC registry were evaluated. Intervention: Long-term survival outcomes for patients receiving BST, early radical cystectomy (RC), and delayed RC were compared. Outcome measurements and statistical analysis: The primary endpoints were overall survival (OS) and cancer-specific survival (CSS). Results and limitations: In total, 114 patients with a median follow-up of 71.2 mo (interquartile range: 32.6-132.2) were analyzed. There were no significant differences in OS (hazard ratio [HR]: 1.40, 95% confidence interval [CI]: 0.68-2.89, p = 0.4) or CSS (HR: 0.88, 95% CI: 0.22-3.55, p = 0.9) between patients undergoing early RC (n = 38) and BST (n = 76). At 60 mo, BST patients had a high-grade recurrence-free rate, muscle-invasive disease/metastasis progression-free rate, and avoidance of RC rate of 37%, 83%, and 58%, respectively. Current smoker status (HR: 4.44, 95% CI: 1.41-13.97, p = 0.011) was the only variable predictive of high-grade recurrence following a multivariable analysis. The median time to RC from BCG-unresponsive date was 2.1 and 11.7 mo for those undergoing early RC and delayed RC (after BST), respectively. Patients treated with early RC had a higher incidence of cT1 disease (53% vs 36%, p = 0.049) and lymphovascular invasion (LVI; 11% vs 0%, p = 0.011) compared to patients treated with BST. Survival outcomes were similar between groups: 10-yr OS-58% versus 50% (HR: 1.40, 95% CI: 0.68-2.89, p = 0.4), and 10-yr CSS-81% versus 85% (HR: 0.88, 95% CI: 0.22-3.55, p = 0.9). Conclusions: An analysis of long-term survival of BCG-unresponsive NMIBC patients receiving BST suggests that it may be safe in patients without LVI and/or variant histology and nonsmokers. Survival outcomes for patients treated with BST may not be inferior to those receiving early RC. Patient summary: Bladder-sparing treatment can be offered to appropriately selected patients who have bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer. Long-term outcomes may not be inferior to those for patients who opt for early radical cystectomy.

Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer.

IMA101 is an actively personalized, multi-targeted adoptive cell therapy (ACT), whereby autologous T cells are directed against multiple novel defined peptide-HLA (pHLA) cancer targets. HLA-A*02:01-positive patients with relapsed/refractory solid tumors expressing ≥1 of 8 predefined targets underwent leukapheresis. Endogenous T cells specific for up to 4 targets were primed and expanded in vitro. Patients received lymphodepletion (fludarabine, cyclophosphamide), followed by T-cell infusion and low-dose IL2 (Cohort 1). Patients in Cohort 2 received atezolizumab for up to 1 year (NCT02876510). Overall, 214 patients were screened, 15 received lymphodepletion (13 women, 2 men; median age, 44 years), and 14 were treated with T-cell products. IMA101 treatment was feasible and well tolerated. The most common adverse events were cytokine release syndrome (Grade 1, n = 6; Grade 2, n = 4) and expected cytopenias. No patient died during the first 100 days after T-cell therapy. No neurotoxicity was observed. No objective responses were noted. Prolonged disease stabilization was noted in three patients lasting for 13.7, 12.9, and 7.3 months. High frequencies of target-specific T cells (up to 78.7% of CD8+ cells) were detected in the blood of treated patients, persisted for >1 year, and were detectable in posttreatment tumor tissue. Individual T-cell receptors (TCR) contained in T-cell products exhibited broad variation in TCR avidity, with the majority being low avidity. High-avidity TCRs were identified in some patients' products. This study demonstrates the feasibility and tolerability of an actively personalized ACT directed to multiple defined pHLA cancer targets. Results warrant further evaluation of multi-target ACT approaches using potent high-avidity TCRs. See related Spotlight by Uslu and June, p. 865.

Impact of type of induction therapy on outcomes in older adults with AML after allogeneic stem cell transplantation.

Although venetoclax-based lower-intensity regimens have greatly improved outcomes for older adults with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy, the optimal induction for older patients with newly diagnosed AML who are suitable candidates for hematopoietic stem cell transplant (HSCT) is controversial. We retrospectively analyzed the post HSCT outcomes of 127 patients ≥60 years of age who received induction therapy at our institution with intensive chemotherapy (IC; n = 44), lower-intensity therapy (LIT) without venetoclax (n = 29), or LIT with venetoclax (n = 54) and who underwent allogeneic HSCT in the first remission. The 2-year relapse-free survival (RFS) was 60% with LIT with venetoclax vs 54% with IC, and 41% with LIT without venetoclax; the 2-year overall survival (OS) was 72% LIT with venetoclax vs 58% with IC, and 41% with LIT without venetoclax. The benefit of LIT with venetoclax induction was greatest in patients with adverse-risk AML (2-year OS: 74%, 46%, and 29%, respectively). Induction with LIT, with or without venetoclax, was associated with the lowest rate of nonrelapse mortality (NRM) (2-year NRM: 17% vs 27% with IC; P = .04). Using multivariate analysis, the type of induction therapy did not significantly affect any of the post HSCT outcomes evaluated; hematopoietic cell transplantation-specific comorbidity index was the only factor that independently predicted RFS and OS. LIT plus venetoclax followed by HSCT is a feasible treatment strategy in older, fit, HSCT-eligible patients with newly diagnosed AML and may be particularly beneficial for those with adverse-risk disease.

Utility of Established Prognostic Scoring Systems for Patients with Advanced Pancreatic Adenocarcinoma Enrolled in Immunotherapy-Based Early-Phase Clinical Trials.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy for which multiagent chemotherapy is the mainstay of treatment resulting in limited survival and symptomatic benefit. Treatment with immune checkpoint inhibitors (ICI) has proven effective in a growing number of solid tumors but has yet to show clinical benefit in patients with PDAC. Given the growing number of ICI-based clinical trials in development for patients with PDAC and lack of clinical benefit thus far with ICI-based therapies in these patients, we sought to (1) determine the outcomes of patients with PDAC treated with ICI-based therapies as part of an early phase clinical trial, (2) validate the utility of established prognostic scoring systems, and (3) identify novel prognostic factors in an attempt to better identify patients that would benefit from enrollment onto an ICI-based early phase clinical trial. METHODS: We conducted a single-center retrospective analysis of patients with advanced PDAC who were treated with ICI-based therapy as part of an early-phase clinical trial. RESULTS: Patients were only able to stay on study for a limited time due to disease progression and/or a change in performance status and had a poor overall survival. Established prognostic scoring systems were not effective in predicting outcomes in this patient population, but factors such as pre-treatment albumin neutrophil to lymphocyte ratio (NLC) may be helpful in patient selection. CONCLUSIONS: This study underscores the need for larger studies to help identify patient and tumor intrinsic factors that predict response to ICI-based therapies in patients with PDAC.

Patient-reported Bowel Function and Bowel-related Quality of Life After Pelvic Radiation for Rectal Adenocarcinoma: The Impact of Radiation Fractionation and Surgical Resection.

INTRODUCTION: Multimodality treatment for locally advanced rectal cancer (LARC) can include long-course radiotherapy (LCRT) or short course radiotherapy (SCRT). Nonoperative management is increasingly pursued for those achieving a complete clinical response. Data regarding long-term function and quality-of-life (QOL) are limited. METHODS: Patients with LARC treated with radiotherapy from 2016 to 2020 completed the Functional Assessment of Cancer Therapy- General (FACT-G7), the Low Anterior Resection Syndrome Score (LARS) and the Fecal Incontinence QOL Scale (FIQOL). Univariate and multivariable linear regression analyses identified associations between clinical variables including radiation fractionation and the use of surgery versus non-operative management. RESULTS: Of 204 patients surveyed, 124 (60.8%) responded. Median (interquartile range) time from radiation to survey completion was 30.1 (18.3-43) months. Seventy-nine (63.7%) respondents received LCRT, and 45 (36.3%) received SCRT; 101 (81.5%) respondents underwent surgery, and 23 (18.5%) pursued nonoperative management. There were no differences in LARS, FIQoL or FACT-G7 between patients receiving LCRT versus SCRT. On multivariable analysis, only nonoperative management was associated with lower LARS score signifying less bowel dysfunction. Nonoperative management and female sex were associated with a higher FIQoL score signifying less disruption and distress from fecal incontinence issues. Finally, lower BMI at the time of radiation, female sex, and higher FIQoL score were associated with higher FACT-G7 scores signifying better overall QOL. CONCLUSIONS: These results suggest long-term patient-reported bowel function and QOL may be similar for individuals receiving SCRT and LCRT for the treatment of LARC, but nonoperative management may lead to improved bowel function and QOL.

Undetectable measurable residual disease is associated with improved outcomes in AML irrespective of treatment intensity.

Acute myeloid leukemia (AML) can be treated with either high- or low-intensity regimens. Highly sensitive assays for measurable residual disease (MRD) now allow for a more precise assessment of response quality. We hypothesized that treatment (Rx) intensity may not be a key predictor of outcomes, assuming that an optimal response to therapy is achieved. We performed a single-center retrospective study including 635 patients with newly diagnosed AML responding to either intensive cytarabine/anthracycline-based chemotherapy (IA; n = 385) or low-intensity venetoclax-based regimens (LOW + VEN; n = 250) and who had adequate flow cytometry-based MRD testing performed at the time of best response. The median overall survival (OS) was 50.2, 18.2, 13.6, and 8.1 months for the IA MRD-, LOW + VEN MRD-, IA MRD+, and LOW + VEN MRD+ cohorts, respectively. The 2-year cumulative incidence of relapse (CIR) was 41.1%, 33.5%, 64.2%, and 59.9% for the IA MRD-, LOW + VEN MRD-, IA MRD+, and LOW + VEN MRD+ cohorts, respectively. The CIR was similar between patients within MRD categories irrespective of the treatment regimen received. The IA cohort was enriched for younger patients and favorable AML cytogenetic/molecular categories. Using multivariate analysis, age, best response (complete remission [CR]/CR with incomplete hematologic recovery/morphologic leukemia-free state), MRD status, and European LeukemiaNet (ELN) 2017 risk remained significantly associated with OS, whereas best response, MRD status, and ELN 2017 risk were significantly associated with CIR. Treatment intensity was not significantly associated with either OS or CIR. Achievement of MRD- CR should be the key objective of AML therapy in both high- and low-intensity treatment regimens.

Hybrid Systems of Nanofibers and Polymeric Nanoparticles for Biological Application and Delivery Systems.

Nanomedicine is a new discipline resulting from the combination of nanotechnology and biomedicine. Nanomedicine has contributed to the development of new and improved treatments, diagnoses, and therapies. In this field, nanoparticles have notable importance due to their unique properties and characteristics, which are useful in different applications, including tissue engineering, biomarkers, and drug delivery systems. Electrospinning is a versatile technique used to produce fibrous mats. The high surface area of the electrospun mats makes them suitable for applications in fields using nanoparticles. Electrospun mats are used for tissue engineering, wound dressing, water-treatment filters, biosensors, nanocomposites, medical implants, protective clothing materials, cosmetics, and drug delivery systems. The combination of nanoparticles with nanofibers creates hybrid systems that acquire properties that differ from their components' characteristics. By utilizing nanoparticles and nanofibers composed of dissimilar polymers, the two synergize to improve the overall performance of electrospinning mats and nanoparticles. This review summarizes the hybrid systems of polymeric nanoparticles and polymeric nanofibers, critically analyzing how the combination improves the properties of the materials and contributes to the reduction of some disadvantages found in nanometric devices and systems.

A decade's experience of managing suspected pancreatic adenocarcinoma at a tertiary cancer center.

Background: We present our experience and established management strategy for endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) in diagnosing suspected pancreatic neoplasms at a tertiary referral cancer hospital. Method: Relevant data were extracted from our database for patients who underwent EUS-FNA for suspected pancreatic neoplasms at our institution between 2007 and 2016. Results: Among the 309 patients, the median age was 67 years and 56% were men. The most common presenting symptoms were abdominal pain (37%) and jaundice (29%). Concordance between radiographic diagnosis and final pathology was 89%. The mean lesion size was 34.9 mm on computed tomography and 31.5 mm on EUS. There were 197 patients (64%) with localized disease, of whom 115 (58%) had resectable lesions, 61 (31%) had borderline resectable, and 21 (11%) had unresectable lesions (mean CA 19-9 levels 1705 U/mL, 2490 U/mL, and 479 U/mL, respectively). A median of 3 FNA passes were performed to establish a pathologic diagnosis. Two patients (1%) had postprocedural adverse events. Median overall survival was 47 months in those who underwent surgery after EUS and 12 months in those who did not (P<0.001). Conclusions: A multidisciplinary approach is employed for management of suspected pancreatic neoplasm at our tertiary cancer center. A combination of cross-sectional imaging and EUS-FNA serves as a highly effective duo in establishing a tissue diagnosis and staging with a low adverse event rate. Counterintuitively, CA 19-9 is not necessarily higher with resectable lesions than with unresectable lesions, indicating the limitation of CA 19-9 as a pancreatic tumor marker.