High-dose Methotrexate and Rituximab Induction Regimen In Immunocompetent Patients With Primary CNS Lymphoma: A Retrospective Single-Center Study of Survival Predictors

Purpose:Primary Central Nervous System Lymphoma (PCNSL) is an aggressive tumor that is confined to the CNS. Although the provision of high-dose methotrexate (HD-MTX) has remarkably improved outcomes in PCNSL patients, the optimal treatment regimens and standard MTX dose have been largely controversial. Herein, we sought to explore the impact of adjuvant Rituximab and different dosages of HD-MTX on survival outcomes of immunocompetent patients with PCNSL.Methods:In this study, we examined patients with PCNSL treated at a single NCI-designated comprehensive cancer center to evaluate their survival outcomes. We conducted a retrospective analysis of 51 immunocompetent patients with PCNSL who received their induction chemotherapy at the University of Alabama at Birmingham (UAB) between 2001 and 2019. Only adult patients with a confirmed diagnosis of PCNSL who had either HD-MTX alone or in combination with Rituximab were included. Patients’ demographics, clinical characteristics, and survival data were collected and analyzed.Results:There is no significant difference in survival among patients who received MTX alone versus MTX plus Rituximab. Furthermore, lower doses of MTX were associated with worse survival outcomes; however, this difference in survival was not significant when adjusted to age.Conclusion:Our experience challenges the role of Rituximab in PCNSL during induction therapy. Our study also highlights the shorter survival in elderly patients with PCNSL which can be related, to some extent, to the relatively lower doses of HD-MTX. There is an unmet need to establish a consensus on the most effective upfront regimen in PCNSL through prospective studies.

Tumor-associated immune cell infiltrate density in penile squamous cell carcinomas

Penile squamous cell carcinomas are rare tumor entities throughout Europe. Early lymphonodal spread urges for aggressive therapeutic approaches in advanced tumor stages. Therefore, understanding tumor biology and its microenvironment and correlation with known survival data is of substantial interest in order to establish treatment strategies adapted to the individual patient. Fifty-five therapy naïve squamous cell carcinomas, age range between 41 and 85 years with known clinicopathological data, were investigated with the use of tissue microarrays (TMA) regarding the tumor-associated immune cell infiltrate density (ICID). Slides were stained with antibodies against CD3, CD8 and CD20. An image analysis software was applied for evaluation. Data were correlated with clinicopathological characteristics and overall survival. There was a significant increase of ICID in squamous cell carcinomas of the penis in relation to tumor adjacent physiological tissue. Higher CD3-positive ICID was significantly associated with lower tumor stage in our cohort. The ICID was not associated with overall survival. Our data sharpens the view on tumor-associated immune cell infiltrate in penile squamous cell carcinomas with an unbiased digital and automated cell count. Further investigations on the immune cell infiltrate and its prognostic and possible therapeutic impact are needed.

Valganciclovir as Add-on to Second Line Therapy in Patients with Recurrent Glioblastoma

IntroductionGlioblastoma invariably recurs despite aggressive and multimodal first line treatment and no standardized second line therapy exists. We previously reported that treatment with the antiviral drug valganciclovir as an add-on to standard therapy significantly prolonged overall survival in 102 patients with newly diagnosed glioblastoma. Here we present the results of retrospective survival analyses including patients with glioblastoma that initiated valganciclovir therapy after recurrence. MethodsBetween April 13, 2007 and March 31, 2021, 29 patients with recurrent glioblastoma received valganciclovir as an add-on to second line therapy. Contemporary controls were 111 patients with glioblastoma who received similar second line therapy at our institution. We retrospectively analyzed survival data of these patients. ResultsPatients with recurrent glioblastoma who received valganciclovir had longer median overall survival after recurrence than controls (12.1 vs 7.4 months, respectively, p=0.0017). The drug was well tolerated. Both patients who underwent re-operation and patients that were not re-operated after recurrence benefitted significantly from valganciclovir therapy. Valganciclovir prolonged survival after recurrence both in patients with an unmethylated or methylated MGMT promoter gene. ConclusionValganciclovir was safe to use and prolonged median survival after recurrence of patients with recurrent glioblastoma, re-operated or not after recurrence and with methylated or unmethylated MGMT promoter gene.

Role of a Pyroptosis-Related lncRNA Signature in Risk Stratification and Immunotherapy of Ovarian Cancer

Background: Pyroptosis is a newly recognized form of cell death. Emerging evidence has suggested the crucial role of long non-coding RNAs (lncRNAs) in the tumorigenesis and progression of ovarian cancer (OC). However, there is still poor understanding of pyroptosis-related lncRNAs in OC.Methods: The TCGA database was accessed for gene expression and clinical data of 377 patients with OC. Two cohorts for training and validation were established by random allocation. Correlation analysis and Cox regression analysis were performed to identify pyroptosis-related lncRNAs and construct a risk model.Results: Six pyroptosis-related lncRNAs were included in the final signature with unfavorable survival data. Subsequent ROC curves showed promising predictive value of patient prognosis. Further multivariate regression analyses confirmed the signature as an independent risk factor in the training (HR: 2.242, 95% CI: 1.598–3.145) and validation (HR: 1.884, 95% CI: 1.204–2.95) cohorts. A signature-based nomogram was also established with a C-index of.684 (95% CI: 0.662–0.705). Involvement of the identified signature in multiple immune-related pathways was revealed by functional analysis. Moreover, the signature was also associated with higher expression of three immune checkpoints (PD-1, B7-H3, and VSIR), suggesting the potential of the signature as an indicator for OC immunotherapies.Conclusion: This study suggests that the identified pyroptosis-related lncRNA signature and signature-based nomogram may serve as methods for risk stratification of OC. The signature is also associated with the tumor immune microenvironment, potentially providing an indicator for patient selection of immunotherapy in OC.

Elevated SOX11 expression distinguishes basal-like human breast cancer.

Patients diagnosed with basal-like breast cancer face a more aggressive disease course and more dismal prognosis than patients diagnosed with luminal A and luminal B breast cancer molecular subtypes (1-4). We mined published microarray data (5, 6) to understand in an unbiased fashion the most distinguishing transcriptional features of tumors from patients with basal or basal-like subtype breast cancer. We observed transcriptome-wide differential expression of SRY-box 11, SOX11, when comparing tumors of patients with basal-like breast cancer with that of other PAM50 molecular subtypes. SOX11 mRNA was present at significantly higher quantities in the tumors of patients with basal-like breast cancer. Analysis of patient survival data revealed that SOX11 primary tumor expression was correlated with overall survival, with higher SOX11 associated with inferior outcomes - in basal-like patients but not in luminal A, luminal B, HER2+, or normal-like patients. Elevated SOX11 expression appears to distinguish basal-like human breast cancer from the other molecular subtypes.

Population-based survival for cancer patients in Saudi Arabia for the years 2005–2009

The Saudi Cancer Registry reported in 2007 the 5-year observed survival for the most common cancer sites for the years 1994–2004. In this report we looked at the cancer survival in the period 2005–2009 and evaluated the trend over the 15 years period from 1994 to 2009. Cases of the top 14 cancer sites reported by the population based Saudi Cancer Registry from 1 January 2005 to December 31, 2009, were submitted for survival analysis. The vital status of those patients was collected. Analysis of survival for the above period was compared with the prior reported 2 periods (1994–1999, 2000–2004). In addition, analysis was done according to age, sex, disease stage and the province. Data of 25,969 patients of the commonest cancer sites were submitted. Of those 14,146 patients (54%) had complete demographic data available and vital status was reported. Thyroid cancer had the highest 5- year observed survival of 94% (95% confidence interval (CI) 93–95%)), followed by Breast (72%, 95% CI 71–74%). In hematological malignancies, Hodgkin’s Lymphoma had the highest 5-year survival of 86% (95% CI 84–88%). Survival rates has improved in most of the cancers sites for the studied periods except for lung, uterine and Hodgkin’s lymphoma which plateaued. Our study confirms a steady improvement in the 5-year observed survival over time for the majority of cancers. Our survival data were comparable to western countries. This data should be used by policy makers to improve on cancer care in the kingdom.

A Novel Autophagy-Related Prognostic Risk Model and a Nomogram for Survival Prediction of Oral Cancer Patients

Background. This study is aimed at constructing a risk signature to predict survival outcomes of ORCA patients. Methods. We identified differentially expressed autophagy-related genes (DEARGs) based on the RNA sequencing data in the TCGA database; then, four independent survival-related ARGs were identified to construct an autophagy-associated signature for survival prediction of ORCA patients. The validity and robustness of the prognostic model were validated by clinicopathological data and survival data. Subsequently, four independent prognostic DEARGs that composed the model were evaluated individually. Results. The expressions of 232 autophagy-related genes (ARGs) in 127 ORCA and 13 control tissues were compared, and 36 DEARGs were filtered out. We performed functional enrichment analysis and constructed protein–protein interaction network for 36 DEARGs. Univariate and multivariate Cox regression analyses were adopted for searching prognostic ARGs, and an autophagy-associated signature for ORCA patients was constructed. Eventually, 4 desirable independent survival-related ARGs (WDR45, MAPK9, VEGFA, and ATIC) were confirmed and comprised the prognostic model. We made use of multiple ways to verify the accuracy of the novel autophagy-related signature for survival evaluation, such as receiver-operator characteristic curve, Kaplan–Meier plotter, and clinicopathological correlational analyses. Four independent prognostic DEARGs that formed the model were also associated with the prognosis of ORCA patients. Conclusions. The autophagy-related risk model can evaluate OS for ORCA patients independently since it is accurate and stable. Four prognostic ARGs that composed the model can be studied deeply for target treatment.

A Composite Ranking of Risk Factors for COVID-19 Time-To-Event Data from a Turkish Cohort

Having a complete and reliable list of risk factors from routine laboratory blood test for COVID-19 disease severity and mortality is important for patient care and hospital management. It is common to use meta-analysis to combine analysis results from different studies to make it more reproducible. In this paper, we propose to run multiple analyses on the same set of data to produce a more robust list of risk factors. With our time-to-event survival data, the standard survival analysis were extended in three directions. The first is to extend from tests and corresponding p-values to machine learning and their prediction performance. The second is to extend from single-variable to multiple-variable analysis. The third is to expand from analyzing time-to-decease data with death as the event of interest to analyzing time-to-hospital-release data to treat early recover as a meaningful event as well. Our extension of the type of analyses leads to ten ranking lists. We conclude that 20 out of 30 factors are deemed to be reliably associated to faster-death or faster-recovery. Considering correlation among factors and evidenced by stepwise variable selection in random survival forest, 10~15 factors seem to be able to achieve the optimal prognosis performance. Our final list of risk factors contains calcium, white blood cell and neutrophils count, urea and creatine, d-dimer, red cell distribution widths, age, ferritin, glucose, lactate dehydrogenase, lymphocyte, basophils, anemia related factors (hemoglobin, hematocrit, mean corpuscular hemoglobin concentration), sodium, potassium, eosinophils, and aspartate aminotransferase.