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Adherence to US Preventative Services Task Force (USPSTF) cancer screening guidelines remains considerably lower than the recommendation of the Healthy People 2020 initiative. Patient populations recommended for screening are not screened at an appropriate rate, and populations not recommended for screening are inappropriately screened. Closer adherence to guidelines should improve outcomes and reduce costs, estimated to reach $158 billion/year by 2020. We evaluated whether a use of low-cost educational health maintenance (HM) card by medical residents at a university hospital could impact education and adherence to updated cancer screening guidelines. We also analyzed savings to the healthcare system. Adherence to cervical, breast, and colorectal cancer screening guidelines, defined as percentage that was screened (or not screened) in accordance with the USPSTF guidelines, in clinic visits from December 2012 (n = 336) was compared to those from December 2013 (n = 306) after a quality improvement intervention. Post-intervention, adherence to screening guidelines increased by 40.8% (p < 0.01) for cervical, 33.2% (p < 0.01) for breast, and 20.5% (p < 0.01) for colorectal cancer in average-risk patients. Inappropriate screening was reduced by 26.8% (p < 0.01) for cervical and 32.8% (p < 0.01) for breast cancer. A non-significant 1.1% decrease (p = 0.829) was observed for colorectal cancer. The annual potential savings from avoiding inappropriate screenings were $998,316 (95% CI; $644,484-$1,352,148). We showed a significant absolute increase in USPSTF knowledge of 28.3% irrespective of the house staff level that remained high at 2 years from the educational intervention. The low-cost HM card increased appropriate knowledgeable cancer screening adherence while reducing unnecessary testing and producing substantial savings to the healthcare system.
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Detección Precoz del Cáncer/normas , Adhesión a Directriz/normas , Costos de la Atención en Salud/normas , Implementación de Plan de Salud , Neoplasias/diagnóstico , Guías de Práctica Clínica como Asunto/normas , Mejoramiento de la Calidad/economía , Centros Médicos Académicos , Adulto , Anciano , Estudios Transversales , Detección Precoz del Cáncer/economía , Femenino , Adhesión a Directriz/economía , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/prevención & control , Neoplasias/psicología , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: Ongoing cancer cachexia trials evaluate sarcopenia by skeletal muscle index (SMI) at the L3 vertebrae level, commonly used as a standard. Routine chest CT institutional protocols widely differ in including L3. We investigated whether SMI at L1 assessment, rather than L3, would be reliable and more practicable for non-small cell lung cancer (NSCLC). METHODS: NSCLC patients with routine CT chest had SMI measurements performed at L1 using Slice-O-Matic software. Accuracy of including L1 level, imaging quality, and ability to detect sarcopenia was collected and correlation of L1 SMI with body mass index (BMI) was performed. RESULTS: Thirty-seven patients with NSCLC (73 CT assessments) were enlisted at three institutions. Characteristics: 47% female; medians: age 59, KPS 80%; BMI 25.49, weight 72.97 kg, SMI 59.24. Sarcopenia was detected in 14.7% of patients; 20% had sarcopenic obesity. Of the 73 CTs, 94.5% included L1 (95% CI 86.6-98.5%). Three images (4%) were difficult to evaluate. Inclusion of L1 was similar among the three participating institutions (90.4 to 96.7% inclusion). BMI correlation with SMI was weak (r = 0.329). CONCLUSIONS: SMI assessment at L1 is achievable in patients with NSCLC receiving routine chest CT, with 96% having acceptable quality evaluations. Similar to results previously reported at L3, BMI showed poor correlation and low sensitivity to detect muscle mass loss. The use of CT at L1 is reliable and presents the opportunity for easier patient evaluation of sarcopenia in patients with lung cancer without the need for additional testing or radiation exposure.
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Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Región Lumbosacra/fisiopatología , Neoplasias Pulmonares/complicaciones , Músculo Esquelético/patología , Sarcopenia/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Sarcopenia/diagnóstico por imagen , Sarcopenia/patologíaRESUMEN
Multipotent stromal cells (MSCs) derived from bone marrow, adipose tissue, cord blood, and other origins have recently received much attention as potential therapeutic agents with beneficial immunomodulatory and regenerative properties. In their native tissue environment, however, such cells also appear to have essential functions in building and supporting tumor microenvironments, providing metastatic niches, and maintaining cancer hallmarks. Here, we consider the varied roles of these tissue-resident stroma-associated cells, synthesize recent and emerging discoveries, and discuss the role, potential, and clinical applications of MSCs in cancer and regenerative medicine.-Ilmer, M., Vykoukal, J., Recio Boiles, A., Coleman, M., Alt, E. Two sides of the same coin: stem cells in cancer and regenerative medicine.
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Neoplasias/etiología , Neoplasias/terapia , Medicina Regenerativa/métodos , Células Madre/patología , Células Madre/fisiología , Humanos , Neoplasias/patologíaRESUMEN
The treatment of liver injuries or hepatocellular carcinoma (HCC) has been hindered by the lack of efficient drug delivery. Even with the help of nanoparticles or other synthetic delivering agents, a large portion of the dose is still sequestered in the reticuloendothelial system. As an alternative, adipose-derived mesenchymal cells (AD-MSCs), which have the capability of homing to the injured liver, can be used as a unique carrier for theranostic agents. Theranostic agents must have the capacity for being non-toxic to host cells during transportation, and for timely activation once they arrive at the injury sites. In this study, we loaded AD-MSCs with superparamagnetic iron oxide-coated gold nanoparticles (SPIO@AuNPs) and tested their effects against liver injury and HCC in cells and in mice. SPIO@AuNP is a non-toxic magnetic resonance (MR)-active contrast agent that can generate heat when irradiated with near-infrared laser. Our results showed that SPIO@AuNPs were successfully transfected into AD-MSCs without compromising either cell viability (P > 0.05) or cell differentiability. In vivo MR imaging and histologic analysis confirmed the active homing of AD-MSCs. Upon laser irradiation, the SPIO@AuNP-loaded AD-MSCs could thermally ablate surrounding HCC tumor cells. SPIO@AuNP-loaded AD-MSCs proved a promising theranostic approach for injured liver and HCC.
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Carcinoma Hepatocelular/tratamiento farmacológico , Oro/administración & dosificación , Hepatopatías/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Nanopartículas del Metal/administración & dosificación , Células Madre/metabolismo , Animales , Carcinoma Hepatocelular/metabolismo , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Células Hep G2 , Humanos , Hierro/metabolismo , Hepatopatías/metabolismo , Neoplasias Hepáticas/metabolismo , Ratones , Ratones Desnudos , Óxidos/metabolismoRESUMEN
INTRODUCTION: Among Hispanic-American (HA) men, prostatic cancer (PCa) accounts for nearly one-quarter of the total cancer burden. We sought to identify differences in PCa presentation and treatment status for HA subgroups based on country/region of origin. MATERIAL AND METHODS: Using the National Cancer Database, we identified patients with histologically confirmed prostate adenocarcinoma with reported race/ethnicity, clinical staging, Gleason score ≥ 6, and PSA level at diagnosis from 2010 to 2016. HAs were divided into 4 subgroups: Mexican, Puerto Ricans, Cubans, and Central/South Americans. Non-Hispanic White (NHW) men were used as a reference group. Statistical analysis was derived from the Kruskal-Wallis test for continuous variables and χ2 test for categorical variables. Models were constructed to evaluate the association of Hispanic country of origin with metastatic presentation and treatment status. RESULTS: A total of 428,829 patients were included, with 5625 (1.3%) classified as HA. Within the Hispanic group, 2880 (51.2%) were Mexican, 999 (17.8%) Puerto Rican, 477 (8.5%) Cuban, and 1269 (22.6%) South/Central American. Mexican men presented with higher median PSA, more Gleason 8 to 10 disease, and higher rates of metastatic presentation compared to NHW and other HA subgroups (all, p < .01). Metastatic rates over the study period for Mexican, Puerto Rican, Cuban, and South/Central Americans were 6.4 (±1.2), 5.3 (±3.0), 3.2 (±2.0), and 4.6% (±1.7), respectively (p = .01). Treatment rates were 89.1, 89.6, 92.4, and 89.3% for Mexican, Puerto Rican, Cuban, and South/Central Americans, respectively (p = .19). Mexican men had higher odds of initial metastatic presentation (OR: 1.32; 95%CI: 1.07-1.63, p = .01) but lower odds of receiving treatment (0.68; 0.55-0.85, p < .01). CONCLUSION: Men of Mexican origin presented with more advanced PCa when compared to NHW and other Hispanic subgroups. Our results warrant further investigation into potential biological factors affecting Hispanic patients as well as the identification of treatment barriers for this vulnerable population.
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Pueblos Caribeños , Etnicidad , Neoplasias de la Próstata , Humanos , Masculino , Hispánicos o Latinos , Antígeno Prostático Específico , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/epidemiología , Estados Unidos/epidemiología , BlancoRESUMEN
INTRODUCTION: Deciding on the optimal second-line (2L) treatment for metastatic clear-cell renal cell carcinoma (ccRCC) remains challenging due to the limited information comparing each of the available options and the influence of the newly expanding first-line (1L) agents. PATIENTS AND METHODS: We identified phase II/III randomized controlled trials (RCTs) evaluating 2L treatments in metastatic ccRCC. This Network Meta-analysis (NMA) evaluates the overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and severe adverse events (SAE). We used normal likelihood model to incorporate log hazard ratios (HRs), odds ratios (OR), and 95%-confidence-intervals (CI). Treatment p-scores were used for ranking. Data was analyzed in a fixed-effects model using the netmeta package in R v.1.5-0. RESULTS: All therapies demonstrated some benefits over placebo. Lenvatinibâ¯+â¯everolimus ranked first for OS (HRâ¯=â¯0.44; 95%CIâ¯=â¯0.24-0.82; p-scoreâ¯=â¯0.92), PFS (HRâ¯=â¯0.13; 95%CIâ¯=â¯0.07-0.24, p-scoreâ¯=â¯0.98), and ORR (ORâ¯=â¯35.95; 95%CIâ¯=â¯11.55-111.87; p-scoreâ¯=â¯0.93) compared to placebo, though with a higher SAE (ORâ¯=â¯5.27; p-scoreâ¯=â¯0.23). Cabozantinib ranked second for OS (HRâ¯=â¯0.57, p-scoreâ¯=â¯0.80), PFS (HRâ¯=â¯0.19; p-scoreâ¯=â¯0.86), and ORR (ORâ¯=â¯27.24, p-scoreâ¯=â¯0.84). Nivolumab was third for ORR (p-scoreâ¯=â¯0.79), fourth for OS (p-scoreâ¯=â¯0.69), fifth for PFS (p-scoreâ¯=â¯0.61), and last for SAE (p-scoreâ¯=â¯0.83). Lenvatinib monotherapy ranked worst SAE (ORâ¯=â¯5.89, p-scoreâ¯=â¯0.17) and third for OS and PFS. The latest drug, tivozanib, was sixth for PFS, OS, and ORR. The NMA matrix revealed no differential OS benefit between cabozantinib, lenvatinibâ¯+â¯everolimus, and nivolumab. Other regimens had no significant OS benefit when compared to placebo. CONCLUSION: Based on OS and PFS, the lenvtatinibâ¯+â¯everolimus combination yielded superior, followed by cabozantinib and Lenvatinib monotherapies; all were limited by a worse SAE profile. Nivolumab and pazopanib had the lowest odds of SAEs.
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Anilidas , Antineoplásicos , Carcinoma de Células Renales , Neoplasias Renales , Compuestos de Fenilurea , Piridinas , Quinolinas , Humanos , Carcinoma de Células Renales/patología , Antineoplásicos/uso terapéutico , Everolimus/uso terapéutico , Nivolumab/uso terapéutico , Neoplasias Renales/patología , Metaanálisis en RedRESUMEN
PURPOSE: Pembrolizumab is standard therapy for patients with metastatic urothelial cancer (mUC) who progress after first-line platinum-based chemotherapy; however, only approximately 21% of patients respond. Sacituzumab govitecan (SG) is a trophoblast cell surface antigen-2-directed antibody-drug conjugate with US Food and Drug Administration-accelerated approval to treat patients with locally advanced or mUC who previously received platinum-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report the primary analysis of TROPHY-U-01 cohort 3. METHODS: TROPHY-U-01 (ClinicalTrials.gov identifier: NCT03547973) is a multicohort, open-label phase II study. Patients were CPI-naïve and had mUC progression after platinum-based chemotherapy in the metastatic setting or ≤12 months in the (neo)adjuvant setting. Patients received 10 mg/kg of SG once on days 1 and 8 and 200 mg of pembrolizumab once on day 1 of 21-day cycles. The primary end point was objective response rate (ORR) per central review. Secondary end points included clinical benefit rate (CBR), duration of response (DOR) and progression-free survival (PFS) per central review, and safety. RESULTS: Cohort 3 included 41 patients (median age 67 years; 83% male; 78% visceral metastases [29% liver]). With a median follow-up of 14.8 months, the ORR was 41% (95% CI, 26.3 to 57.9; 20% complete response rate), CBR was 46% (95% CI, 30.7 to 62.6), median DOR was 11.1 months (95% CI, 4.8 to not estimable [NE]), and median PFS was 5.3 months (95% CI, 3.4 to 10.2). The median overall survival was 12.7 months (range, 10.7-NE). Grade ≥3 treatment-related adverse events occurred in 61% of patients; most common were neutropenia (37%), leukopenia (20%), and diarrhea (20%). CONCLUSION: SG plus pembrolizumab demonstrated a high response rate with an overall manageable toxicity profile in patients with mUC who progressed after platinum-based chemotherapy. No new safety signals were detected. These data support further evaluation of SG plus CPI in mUC.
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Anticuerpos Monoclonales Humanizados , Camptotecina/análogos & derivados , Carcinoma de Células Transicionales , Inmunoconjugados , Humanos , Masculino , Anciano , Femenino , Platino (Metal)/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Inmunoconjugados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
OBJECTIVE: To evaluate trends and racial variations of pathologic complete response (CR) in patients with muscle-invasive bladder cancer undergoing cystectomy. MATERIALS AND METHODS: The National Cancer Database was queried for patients with non-metastatic muscle-invasive bladder cancer who underwent neoadjuvant chemotherapy and surgery. The primary endpoints, CR and mortality, were evaluated using the Cochran-Armitage test, multivariable regression, and Kaplan-Meier analyses. RESULTS: The cohort comprised 9955 patients. Non-Hispanic Black (NHB) patients were younger (Pâ¯<â¯.001), had a higher clinical tumor (Pâ¯<â¯.001), and had higher clinical node (Pâ¯=â¯.029) stages at presentation. CR for non-Hispanic White (NHW), NHB, and Hispanic patients were 12.6%, 10.1%, and 11.8%, respectively (Pâ¯=â¯.030). There was a significant increase in CR trends for NHW patients (Pâ¯<â¯.001) and increases in NHB (Pâ¯=â¯.311) and Hispanic patients (Pâ¯=â¯.236). On multivariable analysis, NHW females had lower odds of achieving CR (odds ratio: 0.83, 95% CI: 0.71-0.97); however, NHB males (hazard ratio: 1.21, 1.01-1.44) and NHB females (hazard ratio: 1.25, 1.03-1.53) had higher overall mortality in adjusted analysis. Survival differences were not observed in patients who achieved CR, regardless of racial background; however, for those with residual disease, the 2-year survival probabilities were 60.7%, 62.5%, and 51.1% for NHW, HW, and NHB patients, respectively (log-rank Pâ¯=â¯.010). CONCLUSION: Our findings revealed differences in chemotherapy response based on gender and race or ethnicity. The CR trends for all racial or ethnic groups increased over time. However, Black patients were found to have worse survival, particularly when residual disease was present. Clinical studies with more underrepresented minorities are needed to verify biological differences in response to neoadjuvant chemotherapy.
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Terapia Neoadyuvante , Neoplasias de la Vejiga Urinaria , Femenino , Humanos , Masculino , Negro o Afroamericano , Etnicidad , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/etnología , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugía , Población Blanca , Hispánicos o Latinos , Factores Sexuales , Resultado del Tratamiento , Inducción de RemisiónRESUMEN
BACKGROUND: There are few conflicting results regarding the treatment and outcomes of Hispanic patients with pancreatic cancer. This study comprehensively evaluated the differences in baseline characteristics, treatments, genomic testing, and outcomes among Hispanic (H) and Non-Hispanic (NH) patients with early-stage (ES) and late-stage (LS) pancreatic cancer (PC). METHODS: This is a retrospective analysis from 2013 to 2020 of 294 patients with pancreatic ductal adenocarcinoma; data collected included patient demographics, clinical characteristics, treatment regimens, response, germline and somatic genetic testing, and survival outcomes. Excluded those with insufficient data. Univariate comparisons used parametric and nonparametric tests as appropriate to evaluate for differences between H and NH groups. Fisher's exact tests were performed to evaluate the difference in frequency. Kaplan-Meier and Cox regression analysis assessed the survival. RESULTS: The analysis included 198 patients who had a late-stage disease and 96 patients with early-stage disease at the time of diagnosis. Among the early-stage patients, the median age at diagnosis was 60.7 years in the H versus 66.7 years in the NH (p = 0.03). No other differences were observed in baseline characteristics, treatments offered, and median overall survival (NH 25 vs. H 17.7 months, p = 0.28). Performance status, negative surgical margins, and adjuvant therapy were clinically significant and univariable with improved OS (p < 0.05), regardless of ethnicity. Hispanic patients with early pancreatic cancer were noted to be at a greater risk of death with a statistically significant hazard ratio of 3.1 (p = 0.005, 95% CI, 1.39-6.90). Among the late-stage patients, Hispanic patients with ≥ 3 predisposing risk factors for pancreatic cancer were 44% vs. 25% of NH (p = 0.006). No significant differences were noted in baseline characteristic treatments, progression-free, and median overall survivals (NH 10.0 vs. 9.2 months, p = 0.4577). In the late-stage genomic testing, germline testing performed in NH 69.4% vs. H 43.9% (p = 0.003) revealed no difference among groups. For the somatic testing, the pathogenic variants with actionable mutations were 2.5% of NH and 17.6% of H patients (p = 0.03). CONCLUSION: Hispanic patients with early-stage pancreatic adenocarcinoma present at a younger age and with more risk factors in the late stage. These patients have significantly lower overall survival compared to their non-Hispanic counterparts. Hispanic patients in our study were 2.9 less likely to receive germline screening and more like to have somatic genetic actionable pathogenic variants. Overall, only a minority of all patients were enrolled in a pancreatic cancer clinical trial or offered genomic testing, highlighting a critical need and missed opportunity in advancing progress and improving outcomes for this disease, mainly in the underrepresented Hispanic population.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Persona de Mediana Edad , Etnicidad , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Adenocarcinoma/genética , Adenocarcinoma/terapia , Estudios Retrospectivos , Neoplasias PancreáticasRESUMEN
Urothelial carcinoma (UC) is the most common form of bladder cancer (BC) and is the variant with the most immunogenic response. This makes urothelial carcinoma an ideal candidate for immunotherapy with immune checkpoint inhibitors. Key immune checkpoint proteins PD-1 and CTLA-4 are frequently expressed on T-cells in urothelial carcinoma. The blockade of this immune checkpoint can lead to the reactivation of lymphocytes and augment the anti-tumor immune response. The only immune checkpoint inhibitors that are FDA-approved for metastatic urothelial carcinoma target the programmed death-1 receptor and its ligand (PD-1/PD-L1) axis. However, the overall response rate and progression-free survival rates of these agents are limited in this patient population. Therefore, there is a need to find further immune-bolstering treatment combinations that may positively impact survival for patients with advanced UC. In this review, the current immune checkpoint inhibition treatment landscape is explored with an emphasis on combination therapy in the form of PD-1/PD-L1 with CTLA-4 blockade. The investigation of the current literature on immune checkpoint inhibition found that preclinical data show a decrease in tumor volumes and size when PD-1/PD-L1 is blocked, and similar results were observed with CTLA-4 blockade. However, there are limited investigations evaluating the combination of CTLA-4 and PD-1/PD-L1 blockade. We anticipate this review to provide a foundation for a deeper experimental investigation into combination immune checkpoint inhibition therapy in metastatic urothelial carcinoma.
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INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy projected to be the 2nd leading cause of cancer related death in the USA by 2030. This manuscript discusses current and evolving treatment approaches in patients with pancreatic cancer. AREAS COVERED: PDAC is classified as: a) resectable, b) borderline resectable, c) unresectable (locally advanced and metastatic). The standard of care for patients who present with resectable pancreatic adenocarcinoma is six months of adjuvant modified (m) FOLFIRINOX, gemcitabine plus capecitabine, or single agent gemcitabine. For many reasons, there has been a paradigm shift to employing neoadjuvant chemotherapy. For resectable and borderline resectable patients, we generally start with systemic therapy and reevaluate resectability with subsequent scans specifically when the tumor is located in the head or body of the pancreas. Combined chemoradiation therapy can be employed in select patients. The standard of care for metastatic PDAC is FOLFIRINOX or gemcitabine and nab-paclitaxel. Germline and somatic genomic profiling should be obtained in all patients. Patients with a germline BRCA mutation can receive upfront gemcitabine and cisplatin. EXPERT OPINION: Thorough understanding of molecular pathogenesis in PDAC has opened various therapeutic avenues. We remain optimistic that future treatment modalities such as targeted therapies, cellular therapies and immunotherapy will further improve survival in PDAC.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias PancreáticasRESUMEN
BACKGROUND: There are no series evaluating penile squamous cell carcinoma (pSCC) based on human papillomavirus (HPV) infection. Herein, we present national registry data on clinical and survival outcomes for pSCC based on HPV status. METHODS: We performed a retrospective review of 1224 pSCC patients with known HPV staining from the National Cancer Database. Patients with cM1 disease, those who did not receive treatment, or had missing follow-up data were excluded. Logistic regression identified factors associated with locally aggressive disease. Univariable, multivariable, and inverse probability of treatment weighting (IPTW)-Cox proportional hazard modeling were used to assess hazard ratios (HR) associated with overall survival (OS). RESULTS: After exclusion criteria, we identified 825 cases of which 321 (38.9%) were HPV positive. The HPV-positivity rate did not significantly change by year. HPV-positive patients were younger, had lower Charlson-Deyo performance score, and resided in areas with both lower median household income and lower school education completion. HPV-positive tumors presented with lower American Joint Committee on Cancer clinical T-stage (cT), poorer differentiation, lower rates of lymphovascular invasion (LVI), but more node-positive disease (cN+). For those who underwent lymph node surgery, there were no differences in final pathologic stage, upstaging, or presence of extranodal extension. Only tumor differentiation, LVI, and performance score were independent predictors for locally aggressive disease. HPV status was not a predictor of OS (IPTW-HR:0.89, p = 0.13). CONCLUSIONS: In the largest series evaluating pSCC based on HPV status, HPV-positive tumors were associated with lower cT stages, less LVI, but more cN + disease. More studies on prognostic factors are needed, and time may still be immature to use HPV information for risk stratification.
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Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/virología , Infecciones por Papillomavirus/epidemiología , Neoplasias del Pene/mortalidad , Neoplasias del Pene/virología , Adulto , Carcinoma de Células Escamosas/patología , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias del Pene/patología , Sistema de Registros , Estudios Retrospectivos , Factores Sociodemográficos , Tasa de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: An accurate clinical and radiological staging is the pyramid of treatment decisions in locally advanced rectal cancer (LARC). Guidelines recommended neoadjuvant chemoradiation therapy (CRT) followed by surgical resection for fit patients with LARC. Determining the aggressiveness of intervention while avoiding needless morbidity according to patient risk remains an unmet pre-operative decision-making need. With newer magnetic resonance imaging (MRI) techniques and image acquisition available at our Cancer Center, we seek to retrospectively review the correlation between pre- and post-CRT MRI response to the surgical pathological stage in order to aide multidisciplinary team decision making. METHODS: Our Cancer Center Rectal Cancer Registry between 2011 and 2015 included 57 patients with LARC, 20 completed standard CRT with surgery, and of those 10 had repeated MRI after CRT. RESULTS: Our retrospective case series revealed that 90% of the patients had a downstage tumor response on surgical specimen compared to radiological evaluation after CRT, and furthermore, all patients who were re-staged with MRI prior to surgery correlated with the gold standard pathological stage (p = 0.02). CONCLUSIONS: Post-CRT MRI could potentially aide decision making to further avoid 20% of patients with a complete pathological response from a morbid surgery, whereas 10% of patients with an upstaged disease state may require a more aggressive neoadjuvant or planned surgical intervention. We concluded that future multidisciplinary oncology care treatment decision making would benefit from a repeat MRI after neoadjuvant CRT of LARC.
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Terapia Neoadyuvante/métodos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/tratamiento farmacológico , Adulto , Anciano , Toma de Decisiones , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Only 15-20% of pancreatic ductal adenocarcinoma (PDAC) patients are upfront surgical candidates at presentation, and for this cohort of patients, the 5-year survival is a mere 20% despite adjuvant therapy. Previous data indicate that in clinical practice most of these cases are "borderline-resectable," and there is currently no mature data on perioperative treatment. METHODS: We performed a retrospective electronic chart review of patients with "borderline-resectable"PDAC treated at an academic comprehensive cancer center, dividing them into groups based on surgery alone, surgery plus neoadjuvant, adjuvant, or neoadjuvant plus adjuvant perioperative treatment groups. The objectives were to determine the median overall survival (mOS), progression-free survival (PFS) and disease-free survival (DFS). Statistical analysis was performed to assess the association of demographic, tumor traits, and interventions with OS, PFS and DFS. RESULTS: Only surgery followed by adjuvant therapy showed an increase in mOS [hazard ratio (HR) 0.22; 95% CI, 0.09-0.51; P<0.001), after adjustment for radiation (yes vs. no), resection margins (R0 vs. R1 or R2), and tumor location (head vs. body or tail). Patients who received adjuvant therapy after surgery had 2.1 times greater odds to be alive at 24 months after diagnosis than those who had surgery alone (P=0.015). PFS and DFS were not statistically significantly different among treatment groups after adjustment. Those whose disease was located in the head of the pancreas had a significantly improved OS (HR =0.27; 95% CI, 0.11-0.64; P=0.003), PFS (HR =0.40; 95% CI, 0.17-0.94; P=0.035), and DFS (HR =0.30; 95% CI, 0.13-0.67; P=0.004). Negative margins led to a significant improvement in PFS (HR =0.30; 95% CI, 0.16-0.57; P<0.001) and DFS (HR =0.30; 95% CI, 0.16-0.57; P<0.001). Those who received radiation had a non-significantly improved OS, PFS, and DFS (P>0.05). CONCLUSIONS: Our study corroborated that patients treated with adjuvant therapy after surgical resection had an mOS benefit as reported on prior phase III clinical trials. Patients with "borderline-resectable" pancreatic cancer are encouraged to participate in a clinical trial or clinically be treated with adjuvant therapy until more mature results from the ongoing perioperative prospective study are available.
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Introduction: PDAC is a lethal malignancy with a clear unmet need; almost all patients fail 1st, 2nd, and 3rd line multi-agent cytotoxic chemotherapy. The mammalian target of rapamycin (mTOR) has been identified as a key signaling node enhancing tumor survival and drug resistance in PDAC; hence, it is considered a promising therapeutic target. Areas covered: We comprehensively reviewed the evidence from preclinical and phase I and II clinical trials, based on the authors'clinical experience and a PubMed, Cochrane library, Embase, and Google Scholar search everolimus + pancreatic cancer. Expert opinion: Everolimus has not demonstrated efficacy in PDAC; however, an mTOR inhibitor in combination with stroma-targeted therapies may be a promising area to explore in clinical trials.
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Carcinoma Ductal Pancreático/tratamiento farmacológico , Everolimus/administración & dosificación , Neoplasias Pancreáticas/tratamiento farmacológico , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Carcinoma Ductal Pancreático/patología , Resistencia a Antineoplásicos , Everolimus/farmacología , Humanos , Terapia Molecular Dirigida , Neoplasias Pancreáticas/patología , Sobrevida , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: Post-surgical pathology (SP) staging correlates with long-term survival. Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have been shown to predict prognosis and extent of tumor in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). This study aimed to correlate NLR and PLR to radiological clinical staging (CS), carbohydrate antigen (CA) 19-9 tumor marker and SP staging in patients with resectable-PDAC (R-PDAC); and to investigate NLR and PLR as potential markers to guide neoadjuvant therapy. METHODS: Data were collected retrospectively from R-PDAC patients who received upfront surgery from November 2011 to December 2016. NLR and PLR values on the day of diagnosis and surgery were collected. SP, tumor size, location, resected margins (RM), lymphovascular/perineural invasion (LVI/PNI), lymph node involvement, and AJCC/TNM 8th Edition staging were obtained. Associations were assessed using linear, ordinal logistic, and poison regressions or Kruskal Willis Rank Sum Test per the nature of outcome variables, with statistical significance at p-value <0.05. RESULTS: Fifty-five patients were identified with resectable stage I (61%) and II (38%). They had a mean age of 66 years (48-87 years) and were 47.2% male, 83.6% white, 90.9% non-Hispanic and 89% with ECOG 0-1. NLR/PLR at diagnosis for R0, R1 and R2 were 6.7/241, 4.8/224, and 2.9/147 (P=0.01/0.002), respectively. NLR/PLR for N0 and N1 were 5.1/212 and 2.7/138.3 (P=0.03/0.009) at diagnosis. No other significant association was detected. CONCLUSIONS: These findings suggest that NLR/PLR inversely correlates with RM and lymph node status in patients with R-PDAC, but require prospective evaluation in clinically defined scenarios.
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BACKGROUND: Gastrointestinal cancer (GICA) is associated with a higher incidence of venous thromboembolism (VTE) compared to other solid tumors, moreover, recurrent VTE and major bleeding (MB) complications during anticoagulation treatment have an associated increase rate. GICA-VTE remains a challenging clinical scenario with MB concerns for utilization of direct oral anticoagulants (DOAC), especially with active cancer therapies. AIM: To evaluate patient risk factors, effectiveness (VTE) and safety (MB) of DOACs and low molecular weight heparin (LMWH) in patients with active GICA-VTE. METHODS: A retrospective chart review of patients receiving DOACs and LMWH with GICA and symptomatic or incidental VTE treated at comprehensive cancer center from November 2013 to February 2017 was performed. Inclusion criteria included active GI cancer diagnosed at any stage or treatment +/- 6 mo of VTE diagnosis, whom were prescribed 6 mo or more of DOACs or LMWH. The Chi-squared test was used for overall and the Fisher exact test for pairwise comparisons of the proportions of patients experiencing recurrent VTE and MB events. Odds ratios were used to compare the relative odds of the occurrence of the outcome given exposure to the risk factor. RESULTS: A total of 144 patients were prescribed anticoagulation, in which 106 fulfilled inclusion criteria apixaban (27.3%), rivaroxaban (34.9%) and enoxaparin (37.7%), and 38 were excluded. Patients median age was 66.5 years at GICA diagnosis and 67 years at CAVTE event, with 62% males, 80% Caucasian, 70% stage IV, pancreatic cancer (40.5%), 30% Khorana Score (≥ 3 points), and 43.5% on active chemotherapy. Sixty-four percent of patients completed anticoagulation therapy (range 1 to 43 mo). Recurrent VTE at 6 mo was noted in 7.5% (n = 3), 6.8% (n = 2) and 2.7% (n = 1) of patients on enoxaparin, apixaban and rivaroxaban, respectively (all P = NS). MB at 6 mo were 5% (n = 2) for enoxaparin, 6.8% (n = 2) for apixaban and 21.6% (n = 8) for rivaroxaban (overall P = 0.048; vs LMWH P = 0.0423; all other P = NS). Significant predictors of a primary or secondary outcome for all anticoagulation therapies included: Active systemic treatment (OR = 5.1, 95%CI: 1.3-19.3), high Khorana Score [≥ 3 points] (OR = 5.5, 95%CI: 1.7-17.1), active smoker (OR = 6.7, 95%CI: 2.1-21.0), pancreatic cancer (OR = 6.8, 95%CI: 1.9-23.2), and stage IV disease (OR = 9.9, 95%CI: 1.2-79.1). CONCLUSION: Rivaroxaban compared to apixaban and enoxaparin had a significantly higher risk of MB on GICA-VTE patients with equivocal efficacy.
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Introduction: Early phase clinical trials are the first clinical research step to bringing new cancer therapeutics to patients. At this stage, a new drug's safety, dosing, and scheduling profiles are established as the main endpoints. However, excellent responses due to biomarker-guided and immune checkpoint trials in early phase have resulted in direct approvals of new anti-cancer drugs. Despite doubling of the success rate of new drug approvals, many barriers exist to expeditiously bring active new drugs to the clinic. Areas covered: This review covers roles of members of the early phase program and the challenges they face in enrolling advanced cancer patients to trials. Practical solutions are provided from the perspective of the investigators, regulatory, investigational pharmacy, research nurses, clinical research coordinators, budgets, contracts, and data management. Expert opinion: We are witnessing a burgeoning era in drug development with rapid approval of efficacious drugs. This is achieved by a strong collaboration between investigators, academic institutions, pharmaceutical sponsors, scientists, Food and Drug Administration (FDA), and community practices. Herein, we discuss some of the challenges faced by early phase clinical trials programs and discuss methods of improvement.
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Antineoplásicos/administración & dosificación , Ensayos Clínicos como Asunto/métodos , Neoplasias/tratamiento farmacológico , Antineoplásicos/efectos adversos , Biomarcadores de Tumor/metabolismo , Conducta Cooperativa , Aprobación de Drogas , Desarrollo de Medicamentos/métodos , Humanos , Selección de Paciente , Estados Unidos , United States Food and Drug AdministrationAsunto(s)
Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Colangiocarcinoma/genética , Colangiocarcinoma/secundario , Perfilación de la Expresión Génica , Neoplasias Primarias Desconocidas/genética , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Successful treatment of solid cancers mandates targeting cancer stem cells (CSC) without impact on the physiology of normal tissue resident stem cells. C-Jun N-terminal kinase (JNK) signaling has been shown to be of importance in cancer. We test whether JNK inhibition would sensitize pancreatic CSCs to induction of apoptosis via low-dose TNFα-related apoptosis-inducing ligand (TRAIL). DESIGN: Effects of JNK inhibition (JNKi) were evaluated in vitro in functional assays, through mRNA and protein expression analysis, and in in vivo mouse studies. CSCs were enriched in anoikis-resistant spheroid culture and analyzed accordingly. RESULTS: We confirmed that the JNK pathway is an important regulatory pathway in pancreatic cancer stem cells and further found that JNK inhibition downregulates the decoy receptor DcR1 through IL-8 signaling while upregulating pro-apoptotic death receptors DR4/5, thereby sensitizing cells - even with acquired TRAIL-resistance - to apoptosis induction. Treatment of orthotopic pancreatic cancer xenografts with either gemcitabine, JNKi or TRAIL alone for 4 weeks showed only modest effects compared to control, while the combination of JNKi and TRAIL resulted in significantly lower tumor burden (69%; p < 0.04), reduced numbers of circulating tumor cells, and less distant metastatic events, without affecting the general health of the animals. CONCLUSIONS: The combination of JNKi and TRAIL significantly impacts on CSCs, but leaves regular tissue-resident stem cells unaffected - even under hypoxic stress conditions. This concept of selective treatment of pancreatic CSCs warrants further evaluation.