Short- and Long-Term Survival of Metastatic Biliary Tract Cancer in the United States From 2000 to 2018.

INTRODUCTION: Information about survival outcomes in metastatic biliary tract cancer (BTC) is sparse, and the numbers often quoted are based on reports of clinical trials data that may not be representative of patients treated in the real world. Furthermore, the impact of more widespread adoption of a standardized combination chemotherapy regimen since 2010 on survival is unclear. METHODS: We performed an analysis of the Surveillance, Epidemiology, and End Results database to determine the real-world overall survival trends in a cohort of patients with metastatic BTC diagnosed between the years 2000 and 2017 with follow-up until 2018. We analyzed data for the entire cohort, evaluated short-term and long-term survival rates, and compared survival outcomes in the pre-2010 and post-2010 periods. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard models were used to evaluate factors associated with survival. RESULTS: Among 13, 287 patients, the median age was 68 years. There was a preponderance of female (57%) and white (77%) patients. Forty-one percent died within 3 months of diagnosis (short-term survivors) and 20% were long-term survivors (12 months or longer). The median overall survival (OS) for the entire cohort was 4.5 months. Median OS improved post-2010 (4.5 months) compared to pre-2010 (3.5 months) (P < .0001). On multivariate analysis, age <55 years, intrahepatic cholangiocarcinoma, surgical resection, and diagnosis post-2010 were associated with lower hazard of death. CONCLUSION: The real-world prognosis of metastatic BTC is remarkably poorer than described in clinical trials because a large proportion of patients survive less than three months. Over the last decade, the improvement in survival has been minimal.

Time to treatment initiation and its impact on real-world survival in metastatic colorectal cancer and pancreatic cancer.

BACKGROUND: Given the dearth of data regarding the time to treatment initiation (TTI) in the palliative setting, and its impact on survival outcomes, we sought to determine TTI in a real-world cohort of metastatic colorectal cancer (mCRC) and metastatic pancreatic cancer (mPC) patients and evaluate the impact of TTI on real-world survival outcomes. METHODS: We collected survival and treatment data for mCRC and mPC from the Flatiron Health electronic health records (EHR) derived database. We divided TTI into 3 categories: < 2 weeks, 2-< 4 weeks, and 4-8 weeks, from diagnosis to first-line therapy. Outcome measures were median TTI, real-world overall survival (RW-OS) based on TTI categories by Kaplan-Meier method, and impact of TTI on survival using cox proportional hazard models. RESULTS: Among 7108 and 3231 patients with mCRC and mPC treated within 8 weeks of diagnosis, the median TTI were 28 days and 20 days. Median RW-OS for mCRC was 24 months; 26.9 months versus 22.6 and 18.05 months in the 4-8-week, 2-< 4 week (control) and < 2-week groups, respectively (p < 0.0001). For mPC, median RW-OS was 8 months, without significant difference in RW-OS among the groups (p = 0.05). The 4-8-week group was associated with lower hazard of death (HR 0.782, 95% CI 0.73-0.84, p < 0.0001) and the < 2-week group was associated with a higher hazard of death (HR 1.26, 95% CI 1.15-1.38, p < 0.0001) in mCRC. The 4-8-week group was associated with lower hazard of death for mPC (HR 0.88, 95% CI 0.8-0.97, p = 0.0094). CONCLUSION: In a real-world cohort of patients treated within 8 weeks of diagnosis, and with the limitations of a retrospective study, later TTI did not have a negative impact on survival outcomes in mCRC and mPC.

Comparison of Tissue Molecular Biomarker Testing Turnaround Times and Concordance Between Standard of Care and the Biocartis Idylla Platform in Patients With Colorectal Cancer.

OBJECTIVES: Management of colorectal cancer warrants mutational analysis of KRAS/NRAS when considering anti-epidermal growth factor receptor therapy and BRAF testing for prognostic stratification. In this multicenter study, we compared a fully integrated, cartridge-based system to standard-of-care assays used by participating laboratories. METHODS: Twenty laboratories enrolled 874 colorectal cancer cases between November 2017 and December 2018. Testing was performed on the Idylla automated system (Biocartis) using the KRAS and NRAS-BRAF cartridges (research use only) and results compared with in-house standard-of-care testing methods. RESULTS: There were sufficient data on 780 cases to measure turnaround time compared with standard assays. In-house polymerase chain reaction (PCR) had an average testing turnaround time of 5.6 days, send-out PCR of 22.5 days, in-house Sanger sequencing of 14.7 days, send-out Sanger of 17.8 days, in-house next-generation sequencing (NGS) of 12.5 days, and send-out NGS of 20.0 days. Standard testing had an average turnaround time of 11 days. Idylla average time to results was 4.9 days with a range of 0.4 to 13.5 days. CONCLUSIONS: The described cartridge-based system offers rapid and reliable testing of clinically actionable mutation in colorectal cancer specimens directly from formalin-fixed, paraffin-embedded tissue sections. Its simplicity and ease of use compared with other molecular techniques make it suitable for routine clinical laboratory testing.

Accurate Therapeutic Response Assessment of Pancreatic Ductal Adenocarcinoma Using Quantitative Dynamic Contrast-Enhanced Magnetic Resonance Imaging With a Point-of-Care Perfusion Phantom: A Pilot Study.

OBJECTIVES: The aim of this study was to test the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with concurrent perfusion phantom for monitoring therapeutic response in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: A prospective pilot study was conducted with 8 patients (7 men and 1 woman) aged 46 to 78 years (mean age, 66 years). Participants had either locally advanced (n = 7) or metastatic (n = 1) PDAC, and had 2 DCE-MRI examinations: one before and one 8 ± 1 weeks after starting first-line chemotherapy. A small triplicate perfusion phantom was imaged with each patient, serving as an internal reference for accurate quantitative image analysis. Tumor perfusion was measured with K using extended Tofts model before and after phantom-based data correction. Results are presented as mean ± SD and 95% confidence intervals (CIs). Statistical difference was evaluated with 1-way analysis of variance. RESULTS: Tumor-size change of responding group (n = 4) was -12% ± 4% at 8 weeks of therapy, while that of nonresponding group (n = 4) was 18% ± 15% (P = 0.0100). Before phantom-based data correction, the K change of responding tumors was 69% ± 23% (95% CI, 32% to 106%) at 8 weeks, whereas that of nonresponding tumors was -1% ± 41% (95% CI, -65% to 64%) (P = 0.0247). After correction, the data variation in each group was significantly reduced; the K change of responding tumors was 73% ± 6% (95% CI, 64% to 82%) compared with nonresponding tumors of -0% ± 5% (95% CI, -7% to 8%) (P < 0.0001). CONCLUSIONS: Quantitative DCE-MRI measured the significant perfusion increase of PDAC tumors responding favorably to chemotherapy, with decreased variability after correction using a perfusion phantom.

Extramedullary Involvement by Chronic Myelogeneous Leukemia in Five Patients With Unusual Clinicopathologic Features: A Review of the Effectiveness of Tyrosine Kinase Inhibitors.

Chronic myelogeneous leukemia (CML) is associated with BCR-ABL1 fusion gene leading to an abnormal tyrosine kinase molecule. The accepted first-line treatment is imatinib mesylate (IM). CML uncommonly occurs in the extramedullary sites at initial presentation or relapse. Here we report five adult patients with CML who developed myeloid sarcoma (MS) while on treatment with IM. A retrospective medical chart analysis was performed to identify CML patients with MS who were diagnosed and treated at the University of Alabama at Birmingham. The age ranged between 21 and 36 years (median: 28.5) with a male to female ratio of 4:1. All of the patients were diagnosed with CML in chronic phase with initial treatment including IM. The median interval period between the initial diagnosis of CML and MS was 27 months (range 7 - 60 months). The sites of extramedullary involvement included lymph nodes (n = 2), central nervous system (n = 2) and hepatobiliary organs (n = 1). All patients were treated with either induction therapy or stem cell transplant (SCT) following the diagnosis of MS. The median survival was 16 months (range 1 - 72 months). The longest survival was observed in a patient who successfully received SCT therapy. IM is frequently used as the first therapeutic choice in new diagnosed CML; however, its penetration and effectiveness in extramedullary tissue is still unclear. The current report also supports the literature with less favorable prognosis of CML in younger individuals.

Clinicopathological and molecular features of myeloid sarcoma as initial presentation of therapy-related myeloid neoplasms: a single institution experience.

Therapy-related myeloid neoplasms (t-MN) have a common origin in prior cytotoxic therapy and/or radiation. These neoplasms include therapy-related acute myeloid leukemia, myelodysplastic syndrome (t-MDS), and myelodysplastic/myeloproliferative neoplasms (t-MDS/MPN). Myeloid sarcoma (MS), on the other hand, is a rare disease manifesting as an extramedullary collection of immature cells of myeloid lineage. Rarer still is therapy-related MS (t-MS), which has not been adequately studied due to its rarity and its lack of recognition as a unique entity among other t-MN. Here, we report what is to our knowledge the first case series of t-MS, with the aim of investigating and establishing salient clinicopathological and molecular features of this entity.

Update in systemic therapy of urologic malignancies.

Systemic therapy of advanced prostate and renal cancers has gained several recent additions to the therapeutic armamentarium. Treatment of patients with castration-resistant prostate cancer now includes additional immunotherapy (sipuleucel-T), chemotherapy (cabazitaxel), androgen-signaling inhibitors (abiraterone acetate, enzalutamide), and a radiopharmaceutical (alpharadin), based on extension of patient survival. Similarly, therapy for patients with renal cell carcinoma, a chemoresistant malignancy, has undergone dramatic changes based on an understanding of the role of angiogenesis. Multiple vascular endothelial growth factor inhibitors (sorafenib, sunitinib, pazopanib, axitinib, bevacizumab) and mammalian target of rapamycin inhibitors (temsirolimus, everolimus) have been added to the therapeutic arsenal. Additionally, immunotherapy retains an important treatment role, with a continuing application of high-dose interleukin-2 in select patients and the emergence of novel immunotherapeutic agents that may have significant benefit. Other major urologic malignancies, including urothelial, testicular, and penile cancers, have witnessed relatively few or no recent advances in therapy, although testicular germ cell tumors are one of the most curable malignancies. An agent for treatment of advanced urothelial cancer now has commercial approval, the chemotherapeutic agent, vinflunine, as second-line therapy in multiple countries-but not in the United States. Our review summarizes and updates the field of systemic therapy for advanced urologic malignancies, with a focus on castration-resistant prostate cancer and renal cell carcinoma.

Venous thromboembolic events with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a systematic review and meta-analysis of randomized clinical trials.

A trial-level meta-analysis was conducted to determine the relative risk (RR) of venous thromboembolic events (VTEs) associated with approved vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Eligible studies included randomized phase 2 and 3 trials comparing arms with and without a Food and Drug Administration-approved VEGFR TKI (sunitinib, sorafenib, pazopanib, vandetanib, and axitinib). Statistical analyses calculated the RR and 95% confidence intervals (CI), using random-effects or fixed-effects models based on heterogeneity. A total of 7441 patients from 9 phase III trials and 8 phase II trials were selected. The RR of all grade and high-grade VTEs for the TKI vs. no TKI arms was 1.10 (95% CI 0.73-1.66, p=0.64) and 0.85 (95% CI: 0.58-1.25, p=0.41), respectively. No difference in risk was found based on tumor type, age and trial design. The majority of trials exhibited high quality per Jadad scoring and no heterogeneity or publication bias was found.