Primary Central Nervous System Lymphoma: A Real-World Comparison of Therapy Access and Outcomes by Hospital Setting

Background This study analyzes sociodemographic barriers for primary CNS lymphoma (PCNSL) treatment and outcomes at a public safety-net hospital versus a private tertiary academic institution. We hypothesized that these barriers would lead to access disparities and poorer outcomes in the safety-net population. Methods We reviewed records of PCNSL patients from 2007-2020 (n = 95) at a public safety-net hospital (n = 33) and a private academic center (n = 62) staffed by the same university. Demographics, treatment patterns, and outcomes were analyzed. Results Patients at the safety-net hospital were significantly younger, more commonly Black or Hispanic, and had a higher prevalence of HIV/AIDS. They were significantly less likely to receive induction chemotherapy (67% vs 86%, p = 0.003) or consolidation autologous stem cell transplantation (0% vs. 44%, p = 0.001), but received more whole-brain radiation therapy (35% vs 15%, p = 0.001). Younger age and receiving any consolidation therapy were associated with improved progression-free (PFS, p = 0.001) and overall survival (OS, p = 0.001). Hospital location had no statistical impact on PFS (p = 0.725) or OS (p = 0.226) on an age-adjusted analysis. Conclusions Our study shows significant differences in treatment patterns for PCNSL between a public safety-net hospital and an academic cancer center. A significant survival difference was not demonstrated, which is likely multifactorial, but likely was positively impacted by the shared multidisciplinary care delivery between the institutions. As personalized therapies for PCNSL are being developed, equitable access including clinical trials should be advocated for resource-limited settings.

miRNA-331-3p Affects The Proliferation, Metastasis And Invasion of Osteosarcoma Through SOCS1/JAK2/STAT3

Background: MicroRNAs (miRNA) are regulatory small noncoding RNAs, which play a key role in many cancers. It has been found that miR-331-3p is involved in the development and progression of various cancers, but there are few reports in osteosarcoma. Methods: The public GEO database was used to analyze the survival difference of miR-331-3p in OS organizations. The level of cell proliferation assay was assessed by CCK-8 and colony formation. Tanswell and Wound-healing detect the transfer and invasion ability of miR-331-3p in OS. TargetScan, miRDBmiR, TarBase, and dual luciferase reporter gene assays were used to determine SOCS1 as a targeted regulator. Western blot and immunohistochemistry were used to detect the expression of protein levels. A mouse model of subcutaneously transplantable tumors is used to evaluate the proliferation of OS in vivo.Results: The low expression of miR-331-3p is negatively correlated with the overall survival of OS patients. Overexpression of miR-331-3p significantly inhibited cell proliferation, metastasis and invasion. miR-331-3p affects the occurrence and development of osteosarcoma by targeting the SOCS1/JAK2/STAT3 signaling pathway.Conclusion: miR-331-3p reduces the expression of SOCS1 by combining with its 3'UTR, thereby activating the JAK2/STAT3 signaling pathway to regulate the progression of OS.

Waiting Time for Second Kidney Transplantation and Mortality

Background and objectivesThe median kidney transplant half-life is 10–15 years. Because of the scarcity of donor organs and immunologic sensitization of candidates for retransplantation, there is a need for quantitative information on if and when a second transplantation is no longer associated with a lower risk of mortality compared with waitlisted patients treated by dialysis. Therefore, we investigated the association of time on waiting list with patient survival in patients who received a second transplantation versus remaining on the waiting list.Design, setting, participants, & measurementsIn this retrospective study using target trial emulation, we analyzed data of 2346 patients from the Austrian Dialysis and Transplant Registry and Eurotransplant with a failed first graft, aged over 18 years, and waitlisted for a second kidney transplantation in Austria during the years 1980–2019. The differences in restricted mean survival time and hazard ratios for all-cause mortality comparing the treatment strategies “retransplant” versus “remain waitlisted with maintenance dialysis” are reported for different waiting times after first graft loss.ResultsSecond kidney transplantation showed a longer restricted mean survival time at 10 years of follow-up compared with remaining on the waiting list (5.8 life months gained; 95% confidence interval, 0.9 to 11.1). This survival difference was diminished in patients with longer waiting time after loss of the first allograft; restricted mean survival time differences at 10 years were 8.0 (95% confidence interval, 1.9 to 14.0) and 0.1 life months gained (95% confidence interval, −14.3 to 15.2) for patients with waiting time for retransplantation of <1 and 8 years, respectively.ConclusionsSecond kidney transplant is associated with patient survival compared with remaining waitlisted and treatment by dialysis, but the survival difference diminishes with longer waiting time.

Survival Based On The Pathologic Lymph Node Ratio For Local Advanced Gastric Cancer; Elderly Patients Versus Non Elderly Patients

Objective: The aim of this study was to clarify the prognostic value of the pathological lymph node ratio for elderly and non-elderly gastric cancer patients and to evaluate whether there is a difference in the survival of patients with the same LNR (Lymph Node Ratio).Materials and Methods: A total of 222 patients diagnosed with locally advanced gastric cancer and who underwent gastrectomy were included. The patients were divided into two groups according to age. Clinicopathological properties of the two groups were compared. Potential prognostic factors affecting survival were analyzed. Subsequently, the effect of lymphadenectomy and LNR on survival in both groups was evaluated. Results: Significant differences were detected in terms of the location of primary lesions, hemoglobin and albumin levels between elderly patients and non-elderly patients (p < .05). Overall survival (OS) was significantly worse in elderly patients (22 months vs. 67 months, p<0.001). The survival rates in elderly patients were significantly lower from those of non-elderly in the subgroup LNR Stage 2 (12.1% vs. 47.9 %, P = 0.004) and LNR Stage 3 classification (9.1% vs. 34.1%, P = 0.039). LNR was found to be significant for OS with a cut-off point of 0.18. Conclusion: A survival difference was found between the elderly and non-elderly patients with the same LNR. LNR was found to be an independent factor for survival especially in elderly patients. Survival was found to be further decreased in elderly patients compared to non-elderly patients with increasing LNR.

Combination of Immune Checkpoint Inhibitors and Liver-Specific Therapies in Liver-Metastatic Uveal Melanoma: Can We thus Overcome Its High Resistance?

Uveal Melanoma (UM) is a rare disease; however, it is the most common primary intraocular malignant tumor in adults. Hematogenous metastasis, occurring in up to 50% of cases, mainly to the liver (90%), is associated with poor clinical course and treatment failure. In contrast to dramatic benefits of immunotherapy in many tumor entities, as seen in cutaneous melanoma, immune checkpoint inhibitors (ICI) do not achieve comparable results in Metastatic UM (MUM). The aim of this study was to investigate whether the combination of ICI with liver-directed therapies provides a potential survival benefit for those affected. This retrospective, single-center study, including n = 45 patients with MUM, compared the effect of combining ICI with liver-directed therapy (“Cohort 1”) with respect to standard therapies (“Cohort 2”) on overall survival (OS). Our results revealed a significant survival difference between Cohort 1 (median OS 22.5 months) and Cohort 2 (median OS 11.4 months), indicating that this combination may enhance the efficacy of immunotherapy and thus provide a survival benefit. There is an urgent need for randomized, prospective trials addressing the combination of liver-directed therapies and various strategies of immunotherapy (such as ICI; IMCgp100; personalized vaccines) in order to establish regimens which finally improve the prognosis of patients with MUM.

Disparities in esophageal cancer care based on race: a National Cancer Database analysis

Summary Esophageal cancer is one of the most common cancer killers in our country. The effects of racial disparities on care for esophageal cancer patients are incompletely understood. Using the National Cancer Database, we investigated racial disparities in treatment and outcome of esophageal cancer patients. The National Cancer Database was queried from 2004 to 2017. Logistic regression and survival analysis were used to determine racial differences in access, treatment and outcome. A total of 127,098 patients were included. All minority groups were more likely to be diagnosed at advanced stages versus Caucasians after adjusting for covariates (African American OR—1.64 [95% confidence interval 1.53—1.76], Hispanic OR—1.19 [1.08—1.32], Asian OR—1.78 [1.55—2.06]). After adjustment, all minorities were less likely at every stage to receive surgery. Despite these disparities, Hispanics and Asians had improved survival compared with Caucasians. African Americans had worse survival. Racial disparities for receiving surgery were present in both academic and community institutions, and at high-volume and low-volume institutions. Surgery partially mediated the survival difference between African Americans and Caucasians (HR—1.13 [1.10–1.16] and HR—1.04 [1.02–1.07], without and with adjustment of surgery).There are racial disparities in the treatment of esophageal cancer. Despite these disparities, Hispanics and Asians have improved overall survival versus Caucasians. African Americans have the worst overall survival. Racial disparities likely affect outcome in esophageal cancer. But other factors, such as epigenetics and tumor biology, may correlate more strongly with outcome for patients with esophageal cancer.

Clinical profile and initial treatment of non-small cell lung cancer: a retrospective cohort study at the Uganda Cancer Institute

Introduction: Lung cancer is a major global public health burden constituting 11.6% of all new cancer diagnoses and 18.4% of all cancer-related mortality. Purpose: To describe the clinical profile and initial treatment of non-small cell lung cancer in Uganda. Methods: We reviewed charts of a cohort of patients with a histologically confirmed diagnosis of non-small cell lung cancer, treated between January 2013 and November 2015 at the Uganda Cancer Institute. Results: A total of 74 patients met the inclusion criteria. The median age was 56 years (IQR 47-70), with 16.2% below the age 45 years, and 51% were female. Only 10 percent were active smokers and the most frequent histological subtype was adenocarcinoma (71%). The majority (91.9%) had stage IV disease at diagnosis and frequent metastases to contralateral lung, liver, and bones. Twenty-seven (27) patients received platinum-based chemotherapy, while 27 patients received erlotinib, and only 4 patients received palliative thoracic radiotherapy. The median survival time was 12.4 months, and the overall response rate was 32.7%. There was no survival difference by type of systemic treatment, and on multivariate analysis, poor performance status was predictive of adverse outcomes (p < 0.001). Conclusions: Patients with non-small cell lung cancer in Uganda frequently presented with late-stage disease at diagnosis. The majority of patients were female, never-smokers, and had predominantly adenocarcinoma subtype. Keywords: Non-small cell lung cancer; Uganda; erlotinib; lung cancer; Uganda Cancer Institute.

Morbidity, Prognostic Factors, and Competing Risk Nomogram for Combined Hepatocellular-Cholangiocarcinoma

Background. Combined hepatocellular-cholangiocarcinoma (CHC) is a rare and heterogeneous histological subtype of primary liver cancer, which is still poorly understood. This study aimed to describe the epidemiological and clinical features, investigate the prognostic indicators, and develop a competing risk nomogram for CHC. Methods. The study cohort was taken from the Surveillance, Epidemiology, and End Results database. The annual percent change (APC) in incidence was calculated using the joinpoint regression. The nomogram was developed based on multivariate competing risk survival analyses and validated by calibration curves. Akaike information criterion, Bayesian information criterion, Harrell’s C-index, and area under the receiver operating characteristic curves were obtained to compare prognostic performance. Decision curve analysis was introduced to examine the clinical value of the models. Results. The overall incidence of CHC was 0.062 per 100,000 individuals in 2004 and 0.081 per 100,000 individuals in 2018, with an APC of 1.0% ( P > 0.05 ). CHC displayed intermediate clinicopathological features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Race, tumor size, vascular invasion, extrahepatic invasion, distant metastasis, grade, surgery, and Metavir stage were confirmed as the independent predictors of cancer-specific survival. The constructed nomogram was well calibrated, which showed better discrimination power and higher net benefits than the current American Joint Committee on Cancer staging system. Patients with liver transplantation had better survival than those with hepatectomy, especially patients within the Milan Criteria ( P = 0.022 and P = 0.015 ). There was no survival difference between liver transplantation and hepatectomy in patients beyond the Milan Criteria ( P = 0.340 ). Conclusion. The morbidity of CHC remained stable between 2004 and 2018. The constructed nomogram could predict the prognosis with good performance, which was meaningful to individual treatment strategies optimization. CHC patients should also be considered as potential liver transplantation recipients, especially those within the Milan Criteria, but the finding still needs more evidence to be further confirmed.

Clinical utility of targeted next generation sequencing assay in IDH-wildtype glioblastoma for therapy decision-making

BACKGROUND Targeted gene NGS testing is available through many academic institutions and commercial entities and is increasingly incorporated in practice guidelines for glioblastoma (GBM). This single-center retrospective study aimed to evaluate the clinical utility of incorporating NGS results in the management of GBM patients at a clinical trials-focused academic center. METHODS We identified 1,011 consecutive adult patients with pathologically confirmed GBM (IDHwt or IDHmut) who had somatic tumor sequencing (Oncopanel, ~500 cancer gene panel) at DFCI from 2013-2019. Clinical records of all IDHwt GBM patients were reviewed to capture clinical trial enrollment and off-label targeted therapy use based on NGS results. RESULTS Of the 557 IDHwt GBM patients with sequencing, 182 entered clinical trials at diagnosis (32.7%) and 213 (38.2%) entered after recurrence. Sequencing results for 130 patients (23.3%) were utilized for clinical trial enrollment for either targeted therapy indications (6.9 % upfront and 27.7% at recurrent clinical trials and 3.1% for off-label targeted therapy) or exploratory studies (55.4% upfront and 6.9% recurrent clinical trials). Median overall survival was 20.1 months with no survival difference seen between patients enrolled in clinical trials compared to those who were not, in a post hoc analysis. CONCLUSIONS While NGS testing has become essential for improved molecular diagnostics, our study illustrates that targeted gene panels remain underutilized for selecting therapy in GBM-IDHwt. Targeted therapy and clinical trial design remain to be improved to help leverage the potential of NGS in clinical care.

Exploration of Various Roles of Hypoxia Genes in Osteosarcoma

Background: Osteosarcoma is a primary malignant tumor that often metastasizes in orthopedic diseases. Although multi-drug chemotherapy and surgical treatment have significantly improved the survival and prognosis of patients with osteosarcoma, the survival rate is still very low due to frequent metastases in patients with osteosarcoma. In-depth exploration of the relationship between various influencing factors of osteosarcoma is very important for screening promising therapeutic targets. Methods: This study used multivariate COX regression analysis to select the hypoxia genes SLC2A1 and FBP1 in patients with osteosarcoma, and used the expression of these two genes to divide the patients with osteosarcoma into high-risk and low-risk groups. Then, we first constructed a prognostic model based on the patient's risk value, and compared the survival difference between the high expression group and the low expression group. Second, in the high expression group and the low expression group, compare the differences in tumor invasion and inflammatory gene expression between the two groups of immune cells. Finally, the ferroptosis-related genes with differences between the high expression group and the low expression group were screened, and the correlation between these genes was analyzed. Results: In the high-risk group, immune cells with higher tumor invasiveness, macrophages M0 and immune cells with lower invasiveness included: mast cell resting, regulatory T cells (Tregs) and monocytes. Finally, among genes related to ferroptosis, we found AKR1C2, AKR1C1 and ALOX15 that may be related to hypoxia. These ferroptosis-related genes were discovered for the first time in osteosarcoma. Among them, the hypoxia gene FBP1 is positively correlated with the ferroptosis genes AKR1C1 and ALOX15, and the hypoxia gene SLC2A1 is negatively correlated with the ferroptosis genes AKR1C2, AKR1C1 and ALOX15. Conclusion: This study constructed a prognostic model based on hypoxia-related genes SLC2A1 and FBP1 in patients with osteosarcoma, and explored their correlation with immune cells, inflammatory markers and ferroptosis-related genes. This indicates that SLC2A1 and FBP1 are promising targets for osteosarcoma research.