Christos Kyriakopoulos

Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal carcinoma. These guidelines are developed by a multidisciplinary panel of leading experts from NCCN Member Institutions consisting of medical oncologists, hematologists and hematologic oncologists, radiation oncologists, urologists, and pathologists. The NCCN Guidelines are in continuous evolution and are updated annually or sometimes more often, if new high-quality clinical data become available in the interim.

Outcome of Patients With Metastatic Sarcomatoid Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium

BACKGROUND Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. PATIENTS AND METHODS Clinical, prognostic, and treatment parameters in metastatic renal cell carcinoma patients with and without sarcomatoid histology treated with targeted therapy were retrospectively analyzed. RESULTS Two thousand two hundred eighty-six patients were identified (sRCC: n = 230 and non-sRCC: n = 2056). sRCC patients had significantly worse IMDC prognostic criteria compared with non-sRCC (11% vs. 19% favorable risk; 49% vs. 57% intermediate risk, and 40% vs. 24% poor risk; P < .0001). Time from original diagnosis to relapse (excluding synchronous metastatic disease) was shorter in the sRCC group (18.8 vs. 42.9 months; P < .0001). There was no significant difference in the incidence of central nervous system metastases (6%-8%) or underlying clear cell histology (87%-88%). More than 93% of patients received VEGF inhibitors as first-line therapy; objective response was less common in sRCC whereas primary refractory disease was more common (21% vs. 26% and 43% vs. 21%; P < .0001, for both). sRCC patients had significantly less use of second- (P = .018) and third-line (P < .0001) systemic therapy. The median progression-free survival (PFS)/overall survival (OS) was 4.5/10.4 months in sRCC patients and 7.8/22.5 months in non-sRCC patients (P < .0001 for both). Sarcomatoid histology was associated with a significantly worse PFS and OS after adjusting for individual IMDC risk factors in multivariable analysis (hazard ratio, 1.5; P < .0001 for both). CONCLUSION Patients with sRCC have a shorter time to relapse, worse baseline prognostic criteria, and worse clinical outcome with targeted therapy. Additional insight into the biology of sRCC is needed to develop alternative therapeutics.

Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial.

Purpose Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume. Patients and Methods In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/m2 for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional analyses of the prospectively defined low- and high-volume disease subgroups were performed. High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Results At a median follow-up of 53.7 months, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2 months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P = .0018). For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50 to 0.79; P < .001). For those with low-volume disease (n = 277), no OS benefit was observed (HR, 1.04; 95% CI, 0.70 to 1.55; P = .86). Conclusion The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned.

Hormonal Therapeutics Enzalutamide and Abiraterone Acetate in the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Post-docetaxel-an Indirect Comparison.

Introduction This study aims to make an indirect comparison between enzalutamide and abiraterone acetate for mCRPC post-docetaxel. Methods A search for published phase 3 trials was performed with PubMed. Indirect comparisons of enzalutamide (AFFIRM) to abiraterone acetate (COU-AA-301) on outcomes overall survival (OS), time to prostate-specific-antigen (PSA) progression, radiographic progression-free survival (PFS), and PSA response were constructed in the context of log-linear regression models. Results There was no statistically significant difference in OS (hazard ratio (HR) 0.85, 95% CI 0.68–1.07). However, there was some evidence that enzalutamide may outperform abiraterone acetate with respect to secondary outcomes: time to PSA progression (HR 0.40, 95% CI 0.30–0.53), radiographic PFS (HR 0.61, 95% CI 0.50–0.74), and PSA response rates (RRs) (OR 10.69, 95% CI 3.92–29.20). Conclusion While there was no statistically significant difference in OS, enzalutamide may be advantageous for secondary endpoints. Findings of this indirect comparison serve to be hypothesis-generating for future head-to-head trials.

Persistent Tn polyagglutination syndrome during febrile neutropenia: a case report and review of the literature.

IntroductionTn polyagglutination syndrome is a rare disorder that has been reported on only a few occasions in the literature, and, to the best of our knowledge, never before in the context of febrile neutropenia.Case presentationWe report the case of a 26-year-old Caucasian woman who presented to our emergency department complaining of a persistent fever over the previous three days. She had a history of long-standing refractory pancytopenia with multi-lineage dysplasia and severe neutropenia, but she had rarely experienced infection. The results of a physical examination and multiple laboratory tests were unremarkable. While investigating the possible causes of the refractory, long-standing pancytopenia, the possibility of a polyagglutinable state was suggested. Blood samples were sent to the laboratory for an analysis of mixed-field seed lectin agglutination assay. A serum lectin panel confirmed the final diagnosis of Tn-activation.ConclusionsWe should include Tn-activation in our differential whenever we encounter cases of refractory long-standing idiopathic cytopenias and inconclusive bone marrow results displaying multi-lineage dysplasia. Novel genetic techniques have recently revealed the interesting pathophysiology of this phenomenon. The recognition and inclusion of Tn polyagglutination syndrome in our differential diagnoses has important clinical implications, given its main associated features, such as severe thrombocytopenia and neutropenia, which are usually linked to a benign clinical course and prognosis. Increased awareness of the polyagglutinable disorders will potentially decrease the need for invasive and costly medical interventions and also raises the need for monitoring of this specific sub-set of patients. In addition, the study of the expression and implications of Tn, and other similar antigens, offers a fascinating perspective for the study of its role in the diagnosis, prognosis and immunotherapy of solid tumors and hematological malignancies. The infrequency with which Tn polyagglutination syndrome is encountered, its clinical features and its pathophysiology make it a formidable diagnostic challenge.

Metastatic Tumor Burden Does Not Predict Overall Survival Following Cytoreductive Nephrectomy for Renal Cell Carcinoma: a Novel 3-Dimensional Volumetric Analysis.

OBJECTIVE To compare 1-dimensional (1D) and 3-dimensional (3D) volume measurements and determine whether primary tumor (PT) burden is predictive of overall survival (OS) following cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS Records and imaging studies of patients with mRCC treated with CN from 2006 to 2015 were included, with tumor volumes measured by a faculty radiologist blinded to clinical outcomes using Advantage Workstation Volume Share (Ver 4.6, GE, Waukesha, WI). RESULTS Complete PT and metastatic tumor volumes were measured for 67 patients. For 15 (22.3%) patients, 1D volume was within ±10% of the measured 3D volume. In 40 (59.7%) patients, the 1D calculated PT volume was >10% of the actual 3D volume. Fractional percentage of tumor volume (FPTV) removed during CN was calculated using the formula PT volume/(PT + met volume). FPTV was not associated with OS when analyzed as a continuous variable. Patients were divided into 2 groups based on previously published cut point of 90% FPTV. No differences between cohorts in age, gender, grade, subtype, number of metastatic sites, performance status, Memorial Sloan Kettering Cancer Center risk group, or International Metastatic Renal Cell Carcinoma Database Consortium risk group were identified. OS was not different between cohorts (P = .38). CONCLUSION 1D measurements of PT diameter frequently overestimate mRCC PT volume. In patients with mRCC selected for CN, the ratio of primary to metastatic tumor does not predict OS.

Chemohormonal Therapy for Hormone-Sensitive Prostate Cancer: A Review.

AbstractEver since the critical role of androgen deprivation therapy for the treatment of metastatic prostate cancer was established, several trials aimed to show an improved outcome with the early introduction of chemotherapy in metastatic disease. Until recently, all these trials—including the GETUG-AFU 15 trial—failed to confirm an improvement in survival. The recently published CHAARTED and STAMPEDE trials showed a striking benefit and changed the standard of care for patients with newly diagnosed metastatic prostate cancer. We summarize the evidence that emerged from these trials that support the use of combined chemohormonal therapy in metastatic hormone-sensitive prostate cancer.

Treatment selection for men with metastatic prostate cancer who progress on upfront chemo-hormonal therapy

Androgen deprivation therapy plus docetaxel (D‐ADT) increases overall survival (OS) in men with high‐volume, metastatic hormone‐sensitive prostate cancer (mHSPC). Although the vast majority of men initially respond to D‐ADT, most will progress and develop castration‐resistant prostate cancer (CRPC). Little is known about the optimal treatment sequence for men with progressive disease on D‐ADT.

Surrogate end points in early prostate cancer clinical states: ready for implementation?

The prostate cancer disease continuum is best conceptualized as a series of clinical states starting from localized disease (which is curable, in some) and often progressing to biochemically-recurrent disease, to non-metastatic or metastatic castration-resistant disease, and finally to lethal prostate cancer (1). Accordingly, a major decrease in the recurrence rate or death from prostate cancer after primary definitive therapy could potentially be achieved with more effective adjuvant therapies. For patients with localized prostate cancer, treatment options for definite therapy include surgery or radiation, with approximately one-third of these men experiencing disease recurrence (2).

Phase 1/2a, open-label, dose-escalation and safety study of APC-100 in men with advanced prostate cancer.

234 Background: Normal human prostate epithelium and prostate carcinoma exhibit high levels of oxidative stress, which is thought to play a role in the pathogenesis of prostate cancer. APC-100 (2,2,5,7,8-Pentamethyl-6-chromanol) is an oxidative stress modulator that reduces reactive oxygen species (ROS) in prostate cancer cells and inhibits growth of cultured androgen-dependent and independent human prostate cancer cells. We aimed to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), adverse events (AEs), clinical activity and pharmacokinetic (PK) parameters of APC-100 in men with castrate-resistant prostate cancer (CRPC). Methods: This open label phase 1/2a study utilizes a time-to-event reassessment method (TITE-CRM) design. Patients (pts) in cohorts of 3 were treated with escalating doses of APC-100 (900mg-2400mg) orally once daily continuously in 150 mg capsules. Cycles were 28 days. All patients were evaluable with PSAs and imaging studies. Results: Twenty pts (median age 72 ...