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.

Outcomes of sorafenib treatment of advanced renal cell carcinoma according to International Metastatic Renal Cell Carcinoma Data Consortium risk criteria: analysis of Japanese real-world data from postmarketing all-patient surveillance of sorafenib

Aim: To assess sorafenib survival outcomes in renal cell carcinoma patients using standard International Metastatic Renal Cell Carcinoma Data Consortium (IMDC) risk criteria. Patients & methods: The authors restratified a real-world cohort of 3255 advanced renal cell carcinoma patients, obtained from Japanese sorafenib postmarketing surveillance, to assess survival outcomes using IMDC criteria; intermediate risk was subdivided into Int-1 and Int-2 (one and two risk factors, respectively). Results: Overall, 2225 (68%) IMDC-evaluable patients were reclassified as favorable (17%), intermediate (62%) and poor (21%) risk, with median progression-free survival of 10.4, 8.1 and 3.4 months, respectively. Int-1 (36%) and Int-2 (26%) subgroups had median progression-free survival of 10.1 and 6.0 months, respectively. Sorafenib had acceptable safety/tolerability. Conclusion: Sorafenib effectiveness was promising for IMDC intermediate risk, particularly Int-1, warranting further investigation.

Impact of Treatment Modalities Upon Survival Outcomes in Skull Base and Clival Chordoma: An NCDB Analysis

Objectives: Skull base chordomas are locally aggressive malignant tumors derived from the notochord remnant. There are limited large-scale studies examining the role and extent of surgery and radiation therapy. Design: Analysis of the National Cancer Database (NCDB) was performed to evaluate the survival outcomes of various treatments, and to assess for predictors of overall survival (OS). Participants: Retrospective, population-based cohort study of patients diagnosed with a clival/skull base chordoma between 2004-2015 in the NCDB. Main Outcome Measures: The primary outcome was overall survival (OS). Results: 468 cases were identified. 49% of patients received surgery and 20.7% had positive margins. Mean age at diagnosis was 48.4 years in the surgical cohort, and 55% were male. Of the surgical cohort, 33.8% had negative margins, 20.7% had positive margins, and 45.5% had unknown margin status. Age ≥ 65 (HR 3.07, 95% CI 1.63-5.76, p<0.001), diagnosis between 2010-2015 (HR 0.49, 95% CI 0.26-0.90, p=0.022), tumor size >5 cm (HR 2.29, 95% CI 1.26-4.15, p=0.007) and government insurance (HR 2.28, 95% CI 1.24-4.2, p=0.008) were independent predictors of OS. When comparing surgery with or without adjuvant radiation, no survival differences were found, regardless of margin status (P=0.66). Conclusions: Surgery remains the mainstay of therapy. Advanced age over 65, large tumor size, and government insurance were predictors of worse OS. While negative margins and the use of adjuvant radiation did not appear to impact OS, these may very well reduce local recurrences. A multidisciplinary approach is critical in achieving optimal outcomes in this challenging disease.

Patient Characteristics and Survival Outcomes of Non-Metastatic, Non-Clear Cell Renal Cell Carcinoma

BackgroundNon-clear cell renal cell carcinoma (ccRCC) includes histologically and molecularly distinct subtypes such as papillary, chromophobe, collecting duct, and sarcomatoid RCC, with an incidence ranging from 20% to 25%. Oncologic outcomes and the role of adjuvant systemic therapy [vascular endothelial growth factor inhibitor (VEGFi) or immunotherapy] for non-ccRCC are not well-described.ObjectiveTo assess the incidence and survival outcomes of non-ccRCC subtypes in comparison to ccRCC.MethodsThe National Cancer Database was utilized to identify patients with non-metastatic RCC (T1–T4, N0–N1) between 2004 and 2015. The non-ccRCC cohort was further stratified by histologic subtype: papillary, chromophobe, sarcomatoid, and collecting duct RCC. Multivariable Cox regression models were used to compare overall survival (OS).ResultsThe 5-year OS for chromophobe, papillary, clear cell, collecting duct, and sarcomatoid RCC was 91%, 82%, 81%, 44%, and 40%, respectively. After adjusting for clinicopathologic and treatment characteristics, there was no significant difference in OS between papillary RCC and ccRCC (p = 0.17). Patients with collecting duct and sarcomatoid subtypes were at over two times increased risk of death compared to patients with clear cell (p &lt; 0.01 and p &lt; 0.01, respectively). Conversely, patients with chromophobe RCC were at 36% decreased risk of death compared to ccRCC (p &lt; 0.01).ConclusionsThis hospital-based analysis confirms that collecting duct and sarcomatoid histologic subtypes are uncommon and associated with poor survival after surgery when compared to the other RCC subtypes. Further studies are needed to evaluate the role of neoadjuvant and adjuvant systemic therapies in these subtypes to improve oncologic outcomes.

The impact of young age (< 40 years) on the outcome of a cohort of patients with primary non-metastatic breast cancer: analysis of 10-year survival of a prospective study

Background The role of young age (< 40 years) at diagnosis as an independent risk factor for adverse outcomes in female patients with breast cancer has been highlighted in several studies. In this prospective study, we assessed the difference in 10-year survival between two groups of patients diagnosed with non-metastatic breast cancer based on an age cutoff of 40 years. We also assessed the impact of factors including tumor characteristics, molecular markers and immunohistochemical markers on survival outcomes, highlighting the interaction of those variables with age. Methods A total of 119 female patients with newly diagnosed non-metastatic breast cancer were recruited at the American University of Beirut Medical Center (AUBMC) between July 2011 and May 2014. Patients were recruited and divided into 2 age groups (< 40 and ≥ 40 years). In addition to clinical characteristics, we assessed immunohistochemistry including estrogen, progesterone and HER2 receptors, p53, cyclin B1, vascular endothelial growth factor receptor (VEGFR), and ki-67. Germline BRCA mutations were also performed on peripheral blood samples. Patient and tumor characteristics were compared between the age groups. 10-year overall survival (OS) and disease-free survival (DFS) were estimated accordingly. Cox regression analysis was performed in order to assess the effect of the different variables on clinical outcomes. Results After a median Follow-up of 96 (13–122) months, the estimated 10-year OS was 98.6% for patients ≥40 as compared to 77.6% in patients < 40 (p = 0.001). A similar trend was found for 10-year DFS reaching 90% for patients ≥40 and 70.4% for those < 40 (p = 0.004). On multivariate analysis for DFS and OS, only younger age (< 40 years), higher stage and triple negative phenotype among other parameters assessed significantly affected the outcome in this cohort. Conclusion This prospective study confirms the association between younger age and adverse survival outcomes in patients with non-metastatic breast cancer. Future studies of the whole genome sequences may reveal the genomic basis underlying the clinical differences we have observed.