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Purpose: Clinical biomarkers to identify patients unlikely to benefit from CDK4/6 inhibition (CDK4/6i) in combination with endocrine therapy (ET) are lacking. We implemented a comprehensive circulating tumor DNA (ctDNA) analysis to identify genomic features for predicting and monitoring treatment resistance. Experimental Design: ctDNA was isolated from 216 plasma samples collected from 51 patients with hormone receptor–positive (HR+)/HER2-negative (HER2−) metastatic breast cancer (MBC) on a phase II trial of palbociclib combined with letrozole or fulvestrant (NCT03007979). Boosted whole-exome sequencing (WES) was performed at baseline and clinical progression to evaluate genomic alterations, mutational signatures, and blood tumor mutational burden (bTMB). Low-pass whole-genome sequencing was performed at baseline and serial timepoints to assess blood copy-number burden (bCNB). Results: High bTMB and bCNB were associated with lack of clinical benefit and significantly shorter progression-free survival (PFS) compared with patients with low bTMB or low bCNB (all P < 0.05). Dominant APOBEC signatures were detected at baseline exclusively in cases with high bTMB (5/13, 38.5%) versus low bTMB (0/37, 0%; P = 0.0006). Alterations in ESR1 were enriched in samples with high bTMB (P = 0.0005). There was a high correlation between bTMB determined by WES and bTMB determined using a 600-gene panel (R = 0.98). During serial monitoring, an increase in bCNB score preceded radiographic progression in 12 of 18 (66.7%) patients. Conclusions: Genomic complexity detected by noninvasive profiling of bTMB and bCNB predicted poor outcomes in patients treated with ET and CDK4/6i and identified early disease progression before imaging. Novel treatment strategies including immunotherapy-based combinations should be investigated in this population.

Purpose:Clinical biomarkers to identify patients unlikely to benefit from CDK4/6 inhibition (CDK4/6i) in combination with endocrine therapy (ET) are lacking. We implemented a comprehensive circulating tumor DNA (ctDNA) analysis to identify genomic features for predicting and monitoring treatment resistance.Experimental Design:ctDNA was isolated from 216 plasma samples collected from 51 patients with hormone receptor–positive (HR+)/HER2-negative (HER2−) metastatic breast cancer (MBC) on a phase II trial of palbociclib combined with letrozole or fulvestrant (NCT03007979). Boosted whole-exome sequencing (WES) was performed at baseline and clinical progression to evaluate genomic alterations, mutational signatures, and blood tumor mutational burden (bTMB). Low-pass whole-genome sequencing was performed at baseline and serial timepoints to assess blood copy-number burden (bCNB).Results:High bTMB and bCNB were associated with lack of clinical benefit and significantly shorter progression-free survival (PFS) compared with patients with low bTMB or low bCNB (all P < 0.05). Dominant APOBEC signatures were detected at baseline exclusively in cases with high bTMB (5/13, 38.5%) versus low bTMB (0/37, 0%; P = 0.0006). Alterations in ESR1 were enriched in samples with high bTMB (P = 0.0005). There was a high correlation between bTMB determined by WES and bTMB determined using a 600-gene panel (R = 0.98). During serial monitoring, an increase in bCNB score preceded radiographic progression in 12 of 18 (66.7%) patients.Conclusions:Genomic complexity detected by noninvasive profiling of bTMB and bCNB predicted poor outcomes in patients treated with ET and CDK4/6i and identified early disease progression before imaging. Novel treatment strategies including immunotherapy-based combinations should be investigated in this population.

Gene alterations associated with shorter PFS.

Supplementary Methods

PredicineATLAS gene panel.

DNA sequencing data summary.

Patient demographics.

Supplementary Figure S1. High bTMB is associated with the presence of specific mutations. Supplementary Figure S2. ROC analysis to determine optimal bTMB cutoff. Supplementary Figure S3. High correlation between bTMB determined from WES and a 152- gene targeted sequencing panel. Supplementary Figure S4. Association between high cfDNA yield and shorter PFS. Supplementary Figure S5. High baseline tumor fraction is associated with shorter PFS. Supplementary Figure S6. bTMB scores are not associated with sites of metastatic spread. Supplementary Figure S7. Specific oncogenic signaling pathways are more frequently altered in patients with high bTMB and bCNB scores. Supplementary Figure S8. Genomic landscape of all patients at baseline. Supplementary Figure S9. bTMB and bCNB at baseline vs. progression. Supplementary Figure S10. Correlation between baseline bCNB and bTMB. Supplementary Figure S11. Comparison of ctDNA dynamics as measured by ctDNA fraction and bCNB during treatment and progression. Supplementary Figure S12. Genome-wide plots of copy number changes across treatment time points. Supplementary Figure S13. Copy number changes detected for RB1 and BRCA2 genes across treatment time points. Supplementary Figure S14. Relationship between ctDNA fraction and bTMB and bCNB Supplementary Figure S15. Relationship between tumor fraction and bCNB.

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. These NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of ductal carcinoma in situ and the workup and locoregional management of early stage invasive breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visitNCCN.org.

Background:ER positive, HER2-negative breast cancer is the most common subtype in both early and late stages. Previous studies have demonstrated a subset of patients may derive benefit from immune check point inhibitors in combination with endocrine therapy. We hypothesize that Pembrolizumab in combination with fulvestrant will demonstrate anti-tumor activity measured by frequency of response. Trial Design: This is a non-randomized, multi-site, open-label Phase II trial for subjects with metastatic, hormone receptor positive, HER2 negative breast cancer. The study will enroll 47 patients to evaluate the anti-tumor activity of pembrolizumab with fulvestrant as measured by RECIST 1.1 and irRECIST tumor response and by progression free survival. (ClinicalTrials.gov Identifier: NCT03393845) Eligibility Criteria: Patients with advanced non-resectable/metastatic breast cancer that is estrogen receptor positive (ER+) and/or (PR+), HER2 negative (HER2-), with no more than two lines of prior hormonal therapy or no more than two lines of prior chemotherapy. Specific aims: To evaluate the overall response rate (ORR) of pembrolizumab plus fulvestrant in patients with hormone receptor positive, HER2 negative advanced/metastatic breast cancer. Secondary aims include safety and tolerability of the combination. Tumor genomic profiling on solid and/or liquid specimens using next generation sequencing assays to help identify biomarkers of response to immunotherapy. Statistical Methods: This is a phase II study that will enroll a total of 47 patients to evaluate the anti-tumor activity of pembrolizumab with fulvestrant as measured by RECIST 1.1 tumor response and by progression free survival in patients with breast cancer. For maximal 47 patients, 21 will be accrued during stage I and 26 during stage II. If 6 or fewer responses are observed during stage I, then the trial is stopped early for futility. If there are 7 or more responses during stage I, the trial will go on to stage II, in which an additional 26 patients will be accrued. If a total of 21 or more responses are observed by the end of stage II, then the trial will be considered successful, and the combination therapy considered worthy of further investigation. Present accrual and target accrual: The study is currently enrolling patients at Rutgers Cancer Institute of New Jersey, Michigan State University, and University of Nebraska. 20 of 47 patients have been enrolled on study to date. Citation Format: Nancy Chan, Dirk Moore, Pavankumar Tandra, Jatin Rana, Coral Omene, Mridula George, Jairam Krishnamurthy, Shruti Desai, Nayana Patel, Yue Wang, Marc Bicomong, Xiao-wei Tan, Kim Hirshfield, Shridar Ganesan, Deborah Toppmeyer. A phase II study of pembrolizumab plus fulvestrant in hormone receptor positive, HER-2 negative advanced/metastatic breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-17-02.

Background: CDK4/6i combined with ET improves survival for pts with HR+, HER2- MBC. However, biomarkers to predict efficacy and resistance are needed. We hypothesized that a comprehensive next-generation sequencing (NGS)-based liquid biopsy assessment of ctDNA mutation and copy number analysis may identify novel prognostic and predictive biomarkers. Methods: We collected serial blood for ctDNA testing from the 51 pts with HR+, HER2- MBC enrolled in the Alt Dose Palbo trial (NCT03007979), a single-arm phase II study of palbociclib plus letrozole or fulvestrant at 5 days on/2 days off weekly schedule as the first- or second-line ET. The median follow up was 38.2 months at data cutoff for this analysis. Plasma collected at baseline (BL) from all 51 pts, at progression (PD) from all 20 pts who have progressed, and at additional interim timepoints from 2 pts to explore longitutinal changes, with paired germline DNA, were subjected to the PredicineWES+ assay and low-pass whole-genome sequencing (lpWGS). The PredicineWES+ assay provides deep sequencing of 600 genes in the PredicineATLAS panel combined with whole-exome sequencing (WES) of all exonic regions of 20,000 genes enabling genome-wide detection of somatic single nucleotide variation (SNV), indels, copy number variation (CNV) and determination of bTMB. LpWGS offers an unbiased and high-throughput assessment of CNVs and tumor fraction in cell free DNA to derive bCNB. Statistical associations of bTMB, bCNB, and individual alterations with clinical benefit (CB), defined as no PD at 24 weeks by RECIST 1.1, and progression-free survival (PFS) were examined by Fisher’s exact test, Kaplan-Meier analysis, and Cox model. P values were adjusted to control false discovery rate (FDR). Results: The BL median bTMB was 1.6 mutations per megabase pair [IQR 0.6-3.5]. Pts with CB (N=41, 80%) had significantly lower bTMB scores (median [IQR] 1.2 [0.6-2.6] vs. 8.3 [2.4-21.4], (P Citation Format: Andrew Davis, Jingqin Luo, Tiantian Zheng, Lu Tan, Amy Wang, Rama Suresh, Foluso Ademuyiwa, Caron Rigden, Timothy Rearden, Katherine Clifton, Katherine Weilbaecher, Ashley Frith, Pavan K Tandra, Tracy Summa, Brittney Haas, Shana Thomas, Leonel Hernandez-Aya, Lindsay Peterson, Shujun Luo, Bonnie L King, Shidong Jia, Jianjun Yu, Pan Du, Jairam Krishnamurthy, Cynthia X Ma, C Dai. Blood tumor mutational burden (bTMB) and blood copy number burden (bCNB) by genome-wide circulating tumor DNA (ctDNA) assessment predict outcome and resistance in hormone-receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer (MBC) patients (pts) treated with CDK4/6 inhibitor (CDK4/6i) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-07-01.

The NCCN Guidelines for Breast Cancer include up-to-date guidelines for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, male breast cancer, and breast cancer during pregnancy. These guidelines are developed by a multidisciplinary panel of representatives from NCCN Member Institutions with breast cancer–focused expertise in the fields of medical oncology, surgical oncology, radiation oncology, pathology, reconstructive surgery, and patient advocacy. These NCCN Guidelines Insights focus on the most recent updates to recommendations for adjuvant systemic therapy in patients with nonmetastatic, early-stage, hormone receptor–positive, HER2-negative breast cancer.

Introduction: Palbo is approved in combination with an aromatase inhibitor or fulvestrant (FUL) for the treatment of HR+ HER2- MBC. The incidence of grade (G) 3/4 neutropenia (ANC) approaching 66% has been observed in phase 3 trials of palbo. We hypothesize that an alternative schedule of palbo, 5 days on/2 days off every 7 days, reduces the severity of neutropenia, therefore allowing continued weekly dosing and less dose reduction and discontinuation. Methods: A single arm phase II study (Alt Dose Palbo) was conducted in patients (pts) with HR+ HER2- MBC who had ≤1 prior systemic therapy in the metastatic setting (NCT03007979). Pts were treated with palbo 125 mg daily on a 5 days on/2 days off every 7-day schedule, along with letrozole (LET) or FUL per treating physician. Goserelin was administered if premenopausal. The primary objective was to determine the rate of G3/4 ANC within the first 29 days of treatment. Secondary objectives included determining the rate of G3/4 ANC during all cycles, rate of palbo dose reduction/interruption/discontinuation, adverse event (AE) profile per CTCAE v5, progression free survival (PFS), objective response rate (ORR) and clinical benefit rate (CBR) by RECIST 1.1. The sample size of 47 was calculated to provide 90% power based on one-sample binomial exact test at a 5% alpha level to test the one-sided null hypothesis of G3/4 ANC rate >62% versus the alternative of Table 1C1 D1-29 AEG1G2G3TotalWBC decreased26%50%17%93%ANC decreased10%43%21%74%Anemia38%12%0%50%Fatigue29%0%0%29%Platelets decreased14%0%2%17%Nausea12%2%0%14%All cycle AEG1G2G3TotalWBC decreased19%50%26%95%ANC decreased5%40%36%81%Anemia50%21%2%74%Fatigue36%5%0%40%Nausea26%2%0%29%Platelets decreased24%0%2%26%Alopecia21%0%0%21%Mucositis19%0%0%19%Hot flashes17%2%0%19%Constipation14%0%0%14%Arthralgia12%2%0%14%AST elevated10%0%2%12%Anorexia12%0%0%12%ALT elevated7%0%5%12% Citation Format: Jairam Krishnamurthy, Jingqin Luo, Foluso Ademuyiwa, Rama Suresh, Caron Rigden, Timothy Reardon, Katherine Weilbaecher, Ashley Frith, Anna Roshal, Pavan Tandra, Mathew Cherian, Tracy Summa, Shana Thomas, Leonel Hernandez-Aya, Lindsay Peterson, Cynthia Ma. A phase II trial assessing the safety of an alternative dosing schedule of palbociclib (palbo) in hormone receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer (MBC): Alt Dose Palbo [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-13.

The NCCN Guidelines for Breast Cancer include up-to-date guidelines for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, male breast cancer, and breast cancer during pregnancy. These guidelines are developed by a multidisciplinary panel of representatives from NCCN Member Institutions with breast cancer-focused expertise in the fields of medical oncology, surgical oncology, radiation oncology, pathology, reconstructive surgery, and patient advocacy. These NCCN Guidelines Insights focus on the most recent updates to recommendations for adjuvant systemic therapy in patients with nonmetastatic, early-stage, hormone receptor-positive, HER2-negative breast cancer.

Palbociclib 3-weeks-on/1-week-off, combined with hormonal therapy, is approved for hormone receptor positive (HR+)/HER2-negative (HER2−) advanced/metastatic breast cancer (MBC). Neutropenia is the most frequent adverse event (AE). We aim to determine whether an alternative 5-days-on/2-days-off weekly schedule reduces grade 3 and above neutropenia (G3 + ANC) incidence. In this single-arm phase II trial, patients with HR+/HER2− MBC received palbociclib 125 mg, 5-days-on/2-days-off, plus letrozole or fulvestrant per physician, on a 28-day cycle (C), as their first- or second-line treatment. The primary endpoint was G3 + ANC in the first 29 days (C1). Secondary endpoints included AEs, efficacy, and serum thymidine kinase 1 (sTK1) activity. At data-cutoff, fifty-four patients received a median of 13 cycles (range 2.6–43.5). The rate of G3 + ANC was 21.3% (95% CI: 11.2–36.1%) without G4 in C1, and 40.7% (95% CI: 27.9–54.9%), including 38.9% G3 and 1.8% G4, in all cycles. The clinical benefit rate was 80.4% (95% CI: 66.5–89.7%). The median progression-free survival (mPFS) (95% CI) was 19.75 (12.11–34.89), 33.5 (17.25–not reached [NR]), and 11.96 (10.43–NR) months, in the overall, endocrine sensitive or resistant population, respectively. High sTK1 at baseline, C1 day 15 (C1D15), and C2D1 were independently prognostic for shorter PFS (p = 9.91 × 10−4, 0.001, 0.007, respectively). sTK1 decreased on C1D15 (p = 4.03 × 10−7), indicating target inhibition. Rise in sTK1 predicted progression, with the median lead time of 59.5 (inter-quartile range: −206.25–0) days. Palbociclib, 5-days-on/2-days-off weekly, met its primary endpoint with reduced G3 + ANC, without compromising efficacy. sTK1 is prognostic and shows promise in monitoring the palbociclib response. ClinicalTrials.gov#: NCT3007979.

Breast cancer–related lymphedema (BCRL) is a potentially debilitating and often irreversible complication of breast cancer treatment. Risk of BCRL is proportional to the extent of axillary surgery and radiation. Other risk factors include obesity and infections. Given the 5-year survival rate of 90% and its potential impact on the quality of life of survivors of breast cancer, BCRL has become a significant financial burden on the health care system. Minimizing axillary surgery and radiation has been proven to reduce the risk of BCRL. Comprehensive multidisciplinary assessment at the time of initial diagnosis; early referral to physical therapy after surgery; and patient education regarding weight loss, skin, and nail care are cornerstones of the management of early-stage lymphedema. End-stage lymphedema may benefit from referral to a plastic surgeon specializing in lymphedema surgery. In this review, we attempt to review the incidence, risk factors, staging, prevention, and management of this complication of breast cancer treatment. We also describe our multidisciplinary approach for the prevention of this complication at the time of initial diagnosis.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non-muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non-muscle-invasive bladder cancer in the event of a bacillus Calmette-Guerin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.

The role of locoregional treatment (LRT) remains controversial in de novo stage IV breast cancer (BC). We sought to analyze the role of LRT and prognostic factors of overall survival (OS) in de novo stage IV BC patients treated with LRT utilizing the National Cancer Data Base (NCDB). The objective of the current study is to create and internally validate a prognostic scoring model to predict the long-term OS for de novo stage IV BC patients treated with LRT. We included de novo stage IV BC patients reported to NCDB between 2004 and 2015. Patients were divided into LRT and no-LRT subsets. We randomized LRT subset to training and validation cohorts. In the training cohort, a seventeen-point prognostic scoring system was developed based on the hazard ratios calculated using Cox-proportional method. We stratified both training and validation cohorts into two “groups” [group 1 (0–7 points) and group 2 (7–17 points)]. Kaplan–Meier method and log-rank test were used to compare OS between the two groups. Our prognostic score was validated internally by comparing the OS between the respective groups in both the training and validation cohorts. Among 67,978 patients, LRT subset (21,200) had better median OS as compared to that of no-LRT (45 vs. 24 months; p

Brain metastasis is a poor prognostic factor in breast cancer progression, and traditional treatment options have shown minimal response with overall low median survival rates. The incidence of brain metastasis has been increasing despite and, in part, due to advancements in treatment as a result of prolongation of survival. Targeted therapy such anti-HER2 agents have a lower efficacy in this setting compared to metastases elsewhere; however, novel therapies are emerging in this regard. In this comprehensive review, we discuss risk per subtype, special considerations for therapy selection, current focal and systemic treatments, and recent advancements and potential future targets for success. We present our treatment paradigm and multidisciplinary approach to brain metastases arising from breast cancer based on the available evidence, incorporating molecular characteristics.

Background: The approved 3 weeks (wks) on/1 wk off schedule of PAL results in grade (G)3+ neutropenia (ANC) up to 66%. We hypothesized that an alternative schedule (Alt Dose Pal), 5 on/2 off every 7 days, reduces the rate of G3+ ANC, allowing continued weekly dosing. In addition, based on our previous study supporting sTK1, an E2F-dependent enzyme critical for DNA synthesis, as a pharmacodynamic indicator of CDK4/6 inhibition, we hypothesized that Alt Dose Pal inhibits sTK1 and sTK1 dynamics predicts PAL response. Methods: A single arm phase II trial was conducted in HR+ HER2- MBC, ≤1 prior endocrine therapy (ET) for MBC (NCT03007979). Pts received PAL 125 mg daily, 5 on/2 off weekly, plus letrozole (LET) or fulvestrant (FUL) per physician choice, on a 28-day cycle (C). Goserelin was added if premenopausal. Complete blood count and chemistry panel were done at baseline (BL), C1&2D15, and D1 of C2+. The primary objective was to determine the rate of G3+ ANC in C1 D1-D29. Secondary objectives were to assess the rate of all cycle G3+ ANC, PAL dose reduction/discontinuation, adverse events (AE) per CTCAE v5, progression free survival (PFS), objective response rate (ORR: CR+PR (complete and partial responses)) and clinical benefit rate (CBR: no progression (PD) in 24 wks) by RECIST 1.1. The sample size of 47 provides 90% power, 1-sample binomial exact test, 5% alpha, to test the 1-sided null hypothesis of G3+ ANC rate >62% vs the alternative of 10% or G3+. The ORR was 50% (2 CR, 13 PR, 95% CI: 33.15%-66.85%) in 30 pts with measurable disease (n=29) or non-measurable but CR (n=1). The CBR was 81.63% (95% CI: 67.5%-90.76%) in 40 (2CR, 13 PR, 25 SD ≥24 wks) of 49 evaluable pts. The median PFS (mPFS) was 24.3 mo (95% CI 15~not reached (NR)) overall. The mPFS was 33.5 mo (95% CI 17.3~NR) and 12 mo (95% CI: 10.4~NR), in ET sensitive and resistant population, respectively. sTK1 was significantly reduced, 80% down to undetectable, as early as C1D15 (p=7.77E-07). BL sTK1 levels correlated with PD vs non-PD (p=0.003) as best response and negatively correlated with PFS (p=0.002). sTK1 rose significantly at PD (p=0.0003). A median lead time of 80.6 (IQ range 6.8-189.2) days was observed for rising TK before RECIST PD. Conclusion: The Alt Dose Pal trial met its primary endpoint with reduced G3+ ANC. The efficacy data is comparable to prior reports. sTK1 shows promise for PAL response prediction and monitoring. Table 1 AEAEG1G2G3G4TotalC1 D1-29 (n=47)Leukopenia13 (27.6%)22 (46.8%)7 (14.9%)042 (89%)Neutropenia6 (12.8%)18 (38.3%)10 (21.3%)034 (72%)Anemia18 (38.3%)5 (10.6%)0023 (49%)Lymphopenia6 (12.8%)8 (17%)2 (4.3%)016 (34%)Fatigue13 (27.7%)00013 (28%)Hot flashes7 (14.9%)0007 (15%)Nausea6 (12.8%)1 (2.1%)007 (15%)Thrombocytopenia5 (10.6%)1 (2.1%)006 (13%)Alopecia5 (10.6%)0005 (11%)Dizziness1 (2.1%)01 (2.1%)02 (4%)All cycles (n=54)Leukopenia10 (18.5%)22 (40.7%)21 (38.9%)053 (98%)Neutropenia4 (7.4%)21 (38.9%)21 (38.9%)1 (1.9%)47 (87%)Anemia29 (53.7%)12 (22.2%)3 (5.6%)044 (82%)Lymphopenia8 (14.8%)16 (29.6%)10 (18.5%)034 (63%)Fatigue19 (35.2%)4 (7.4%)0023 (43%)Nausea19 (35.2%)3 (5.6%)0022 (41%)Alopecia18 (33.3%)00018 (33%)Thrombocytopenia15 (27.8%)01 (1.9%) *016 (30%)ALT elevated3 (5.6%)02 (3.7%)05 (9%)AST elevated4 (7.4%)01 (1.9%)05 (9%)*pt died from subdural hematoma (G5) Citation Format: Jairam Krishnamurthy, Jingqin Luo, Rama Suresh, Foluso Ademuyiwa, Caron Rigden, Timothy Reardon, Katherine Clifton, Katherine Weilbaecher, Ashley Frith, Anna Roshal, Pavan Tandra, Mathew Cherian, Tracy Summa, Shana Thomas, Leonel Hernandez-Aya, Mattias Bergqvist, Lindsay Peterson, Cynthia X Ma. Safety and efficacy of an alternative schedule of palbociclib (PAL) in hormone receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer (MBC) and the utility of serum thymidine kinase 1 (sTK1) activity in predicting PAL response [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-02.

Paraneoplastic syndromes, although rare, have been associated with lymphoproliferative disorders. Hodgkin’s lymphoma (HL) is the most common lymphoid neoplasm known to cause paraneoplastic syndromes. These syndromes can often be the earliest manifestation of the underlying malignancy, and treating the underlying lymphoma can cure the paraneoplastic disease. Paraneoplastic diseases reported in lymphoid malignancies can be broadly classified into hematological, neurological, and dermatological syndromes based on the organ systems that are predominantly involved. In addition, renal and hepatobiliary involvement has also been reported. The pathogenesis of the hematological paraneoplastic conditions primarily involves the production of autoantibodies by the neoplastic lymphocytes, which then subsequently leads to cytopenias. Cytoses are a result of cytokine produced by the neoplasms. The administration of corticosteroids along with chemotherapy for the underlying malignancy is the treatment of choice. Neurological paraneoplastic phenomena have been reported in both HL and non-Hodgkin’s lymphoma (NHL). They are thought to be secondary to an immune-related process that is triggered by the underlying process. Both the central and the peripheral nervous systems can be affected. Often, treatment of the underlying malignancy with chemotherapy can result in reversal of the paraneoplastic syndrome. In peripheral neuropathies, muscle relaxants and analgesics are often used for symptomatic relief. Dermatological manifestations, pemphigus vulgaris in particular, often precedes the malignancy. Renal and hepatobiliary manifestations, although rare, are also associated with lymphomas.

Von Willebrand disease (VWD) is the most common inherited bleeding disorder and is divided into three types, namely type 1, type 2 (2A, 2B, 2M, 2N), and type 3. We report a case of a 24-year-old Caucasian woman with a rare variety of type 2M VWD. Her von Willebrand factor versus antigen ratio was 0.44 (normal ratio is greater than 0.7) . She was asymptomatic and hence not treated but followed up regularly. VWD is not life-threatening when treated timely.

We present a case of a dialysis-dependent end-stage renal disease patient who originally presented with sepsis and later developed heparin-induced thrombocytopenia-related upper extremity deep venous thrombosis that rapidly progressed to phlegmasia. Argatroban, a direct thrombin inhibitor, was initiated without delay. Argatroban restored the venous patency completely but did not reverse his two gangrenous fingers. The patient finally underwent digital amputation. The management of this uncommon, but life-threatening, situation of upper limb phlegmasia cerulea dolens secondary to heparin-induced thrombocytopenia leading to gangrene is discussed in this case report.

Background: The incidence of melanoma in older patients is on the rise. Prior studies have shown disparities in surgical management and poor survival of older patients with melanoma. Methods: This is a retrospective study of adult patients diagnosed with cutaneous invasive and in situ melanoma between 2000 and 2011 in the National Cancer Data Base. Characteristics and management of older patients (≥60 years) were compared with younger patients (20–59 years) using χ2 testing. Results: Of 476,623 total cases, 54% ( n = 258,153) were diagnosed among older patients. The reported cases in the older patients increased by 1.74-fold between 2000 and 2011. The majority were white (96%), men (65%), with early-stage disease (76% stage 0-II), and superficial spreading melanoma histology (39%). Older patients, compared with younger patients, were more likely to be men (65% versus 49%, p < 0.0001), and have in situ melanoma (28% versus 21%, p < 0.0001); less likely to have nodal metastases (7% versus 9%, p < 0.0001), receive care in academic centers (30% versus 35%, p < 0.0001), undergo wide excision or major amputation for stage I–III disease (68% versus 72%, p < 0.0001) and systemic therapy for stage III (18% versus 45%, p < 0.0001) and IV disease (30% versus 50%, p < 0.0001). Conclusion: Older patients with melanoma are less likely to receive care in academic centers, undergo wide excision for stage I–III disease and receive systemic therapy for stage III–IV disease. Particularly, the utilization of systemic therapy is markedly low. This disparity is particularly important with the availability of less intense more effective therapies.

Lymphoma patients treated with autologous transplantation (ASCT) live an increasingly long life with the recent advancement in therapeutic modalities. This has resulted in an increase in the incidence of therapy-related myeloid neoplasms (t-MN), which is one of the leading causes of non-relapse mortality. Several observational studies have linked the development of t-MN after ASCT with the intensity and frequency of chemotherapy, particularly alkylating agents, use of total body irradiation (TBI), and peripheral blood progenitor cells. In addition, role of genetic factors is increasingly being identified. It is postulated that the use of chemotherapy prior to ASCT results in DNA damage of progenitor cells, mitochondrial dysfunction, and altered gene expression related to DNA repair, metabolism as well as hematopoietic regulation. Cytogenetic studies have shown the presence of abnormalities in the peripheral blood progenitor cells prior to ASCT. It is, therefore, likely that the reinfusion of peripheral blood progenitor cells, proliferative stress on infused progenitor cells during hematopoietic regeneration and associated telomere shortening ultimately result in clonal hematopoiesis and blastic transformation. Cytopenias, myelodysplasia, or cytogenetic abnormalities are common and can be transient after ASCT; therefore, only when present together, they do confirm the diagnosis of t-MN. Attempts to reduce the occurrence of t-MN should be directed toward minimizing the exposure to the identified risk factors. Although the median survival is few months to less than a year, studies have shown the promising role of allogeneic transplantation in select young t-MN patients without high-risk cytogenetics. In this review we will explain the recent findings in the field of t-MN in lymphoma patients that have implications for identifying the molecular and genetic mechanisms of leukemogenesis and discuss potential strategies to reduce the risk of t-MN in this patient population.

Background Salivary duct carcinoma (SDC) is a rare malignancy with a poor prognosis. Human epidermal growth factor receptor-2 (Her-2/neu) is overexpressed in SDC and, hence, HER-2/neu targeted therapy could be an option. Methods A 72-year-old man presented with parotid swelling and cervical lymphadenopathy. He underwent a parotidectomy, modified radical neck dissection, and postoperative chemoradiation with cisplatin. A year later, he developed metastatic disease in the contralateral neck that was treated surgically with right axillary lymphadenopathy. He received radiation to both sites, concurrent with carboplatin. Two years later, he underwent resection of a lung metastasis. He then had progression in the axillary and mediastinal lymph nodes and received 5 cycles of docetaxel and trastuzumab followed by maintenance trastuzumab. Results The patient had a partial response and restaging studies 9 months after therapy discontinuation did not show progression. Conclusion Trastuzumab-based therapy is a potential therapeutic option for patients with SDC. © 2013 Wiley Periodicals, Inc. Head Neck 35: E372–E375, 2013

Cancer care near the end of life (EOL) has become more aggressive over the years. Palliative care services (PCS) may decrease this aggressive cancer care in terminally ill cancer patients. Our objective was to observe the aggressiveness of cancer care near the EOL among Veterans Affairs cancer patients before and after the institution of a PCS team. We also assessed the time taken prior to death to initiate a PCS consultation and its effect on the aggressiveness of cancer care near the EOL.This is a retrospective chart review analysis performed at the local Veterans Affairs hospital looking at the last 100 patients in each of the years, 2002 and 2008, who died with active cancer. Only patients in 2008 had access to a PCS team.In the last 30 days of life, compared to 2002, patients in 2008 had a higher incidence of: chemotherapy administration, more than one hospital admission, more than 14 days of hospital stay, intensive care unit admissions, and in-hospital deaths. Patients with timely PCS consults in 2008 appeared to have a lower incidence of: chemotherapy administration, more than one emergency department visit, more than one hospital admission, more than 14-day hospital stays, intensive care unit admissions, and deaths in the hospital. Timely PCS consults were associated with earlier and more frequent hospice referral.Cancer care near the EOL has become more aggressive with time at one of the hospitals in the Veterans Affairs healthcare system (VAHS). Institution of a PCS service was unable to completely decrease this trend of increasing aggressiveness of cancer care near the EOL. However, timely PCS consults may help attenuate this aggressiveness.

Background A long-term determinant of survival in resectable colon cancer is the involvement of regional lymph nodes. We evaluated the clinicopathologic factors associated with lymph node retrieval. Methods We conducted a retrospective analysis of patients with resected stage I–III colon cancer in the Veteran's Affairs Central Cancer Registry between 1995 and 2008. One-way ANOVA compared the differences between various groups. Multivariate logistic regression analysis was performed to determine the factors associated with the harvest of 12 or more lymph nodes for pathologic examination. Results There were 19,240 patients with resectable colon cancer included in our analysis. Mean number of lymph nodes retrieved increased with later year of diagnosis, higher overall stage, higher T descriptor, age

CD34+ cell dose calculations are usually based on actual body weight (ABW). We have shown that ideal body weight (IBW) may provide a better basis for this in a small population of patients with hematologic malignancies. This was studied further in 514 myeloma autografts. The CD34+ cell doses (10(6)/kg) by IBW and ABW were 1.37-39.36 (median 6.03) and 1.15-29.67 (median 4.84), respectively. IBW-based cell doses correlated slightly better with engraftment than ABW-based doses (higher r(2)): 0.5 x 10(9)/l neutrophils 0.83 versus 0.82, 1.0 x 10(9)/l neutrophils 0.78 versus 0.77, 20 x 10(9)/l platelets 0.54 versus 0.53 and 50 x 10(9)/l platelets 0.57 versus 0.55. When outliers (hematologic recovery in8 or16 days) were excluded, the findings were similar: 0.5 x 10(9)/l neutrophils 0.85 versus 0.84, 1.0 x 10(9)/l neutrophils 0.85 versus 0.84, 20 x 10(9)/l platelets 0.86 versus 0.85 and 50 x 10(9)/l platelets 0.85 versus 0.84. CD34+ cell doses based on IBW as well as ABW significantly affected engraftment when analyzed separately as continuous variables. However, when analyzed together, only the dose based on IBW retained significance. We conclude that calculation of CD34+ cell numbers for autotransplantation should be based on IBW.

BACKGROUND: CNS-PTLD is associated with inferior survival, compared to other forms of PTLD. Rituximab, high-dose methotrexate (HD-MTX) or cytarabine along with reduction of immunosuppression is the current standard of care. Although temozolomide has been used successfully in primary CNS lymphoma, its role in CNS-PTLD is unclear. METHODS: We retrospectively analyzed data for patients with CNS-PTLD, at the University of Nebraska Medical Center. RESULTS: We identified five females and one male. The median age was 53 years (range 18-67). Two had kidney transplants; two had kidney-pancreas transplants; one had a heart transplant and one had a heart-liver transplant. The immunosuppressive regimens included prednisone with either cyclosporine, tacrolimus, mycophenolate mofetil or sirolimus. The median interval between the transplant and CNS-PTLD diagnosis was 24 months (range 9-108). Patients presented with altered mental status (50%) or focal neurological deficits (83%). The radiographic appearance was solitary (33%) or multiple (66%) masses. Histology was polymorphic (33%) or monomorphic (66%). Tumor cells were positive for Epstein-Barr virus (EBV) and CD20 in all cases. Quantitative EBV DNA in blood was detected in five patients (

The risk factors, the optimal therapy and prognostic factors contributing to poor outcomes of neuroendocrine urinary bladder carcinoma are not fully elucidated because of its rarity. We reviewed the medical records of neuroendocrine bladder carcinoma patients treated at the University of Nebraska Medical Center between 1996 and 2011. Eighteen patients, 55% female with a median age of 77 years, had stage IV disease at diagnosis in 50% of cases. There was a high prevalence of smoking (78%), medical co-morbidities (94%), prior cancer history (22%) and family history of cancer (61%). Treatment modalities included surgery (72%), platinum-based chemotherapy (50%) and/or radiation (22%). Median overall survival was 18.5 months (95% confidence interval, 7-36 months). Patients with Stage II and III cancer who underwent radical surgery with or without neoadjuvant chemotherapy had a median survival of 37 months. In addition to smoking, for the first time, our study indicates that the personal or family history of cancer may increase risk to neuroendocrine bladder cancer. Advanced age and stage at diagnosis, and the presence of multiple co-morbidities contribute to poor overall survival. Patients with early-stage disease are likely to benefit from a combination of radical surgery and platinum-based neoadjuvant chemotherapy.

CLL has been defined as presence of more than 5000 small mature appearing monoclonal B lymphocytes with a specific immunophenotype in peripheral blood. It is a well-known fact that CLL is associated with autoimmune cytopenias. CLL cells are CD5 + B lymphocytes, and usually are not the “guilty” cells which produce autoantibodies. T cell defect is another characteristic of CLL and the total number of T cells is increased, and there is inversion of the CD4/CD8 ratio. Autoimmune hemolytic anemia (AIHA) is the most common autoimmune complication of CLL and has been reported in 10-25% of CLL patients. However, the stage-adjusted estimated rate of AIHA in CLL is about 5%. Conversely, CLL is three times more common in patients who present with AIHA. Direct agglutinin test (DAT) is positive in 7-14% of CLL patients but AIHA may also occur in DAT negative patients. Autoimmune thrombocytopenia (AIT) is the second most common complication of CLL and has been reported in 2-3% of patients. DAT is positive in AIT but presence of antiplatelet antibodies is neither diagnostic nor reliable. Autoimmune neutropenia (AIN) and pure red cell aplasia (PRCA) are very rare complications of CLL and like other autoimmune complications of CLL may occur at any clinical stage. It is believed that most case reports of AIN and PRCA in CLL actually belong to large granular lymphocytic leukemia (LGL). Non-hematologic autoimmune complications of CLL including cold agglutinin disease (CAD), paraneoplastic pemphigus (PNP), acquired angioedema, and anti-myelin associated globulin are rare. Before starting any treatment, clinicians should distinguish between autoimmune cytopenias and massive bone marrow infiltration since autoimmune complications of CLL are not necessarily equal to advanced disease with poor prognosis. According to IWCLL guideline, steroids are the mainstay of treatment of simple autoimmunity. Intravenous immunoglobulin (IVIg), cyclosporine, and rituximab are used in complex, steroid refractory cases. Monotherapy with purine analogues and alkylating agents should be avoided as they may increase CLL associated autoimmune complications Normal 0 14 false false false EN-US X-NONE X-NONE

Interferon has been widely used in the management of patients with hematological malignancies such as polycythemia vera, myelofibrosis, chronic myeloid leukemia and viral infections such as chronic hepatitis C. Hematological adverse effects such as cytopenias have been observed, particularly in patients who receive a combination of interferon-α-2a and ribavirin for hepatitis C. Mild myelosuppression can be seen with pegylated interferon; however, bone marrow aplasia in patients with myelofibrosis has not been reported. It is important to be aware of such a serious complication since persistent bone marrow aplasia can be fatal. We describe a case of pegylated interferon-induced reversible bone marrow aplasia in a patient with primary myelofibrosis.

A long-term determinant of survival in resectable colon cancer is the involvement of regional lymph nodes. We evaluated the clinicopathologic factors associated with lymph node retrieval.We conducted a retrospective analysis of patients with resected stage I-III colon cancer in the Veteran's Affairs Central Cancer Registry between 1995 and 2008. One-way ANOVA compared the differences between various groups. Multivariate logistic regression analysis was performed to determine the factors associated with the harvest of 12 or more lymph nodes for pathologic examination.There were 19,240 patients with resectable colon cancer included in our analysis. Mean number of lymph nodes retrieved increased with later year of diagnosis, higher overall stage, higher T descriptor, age65 years, poorer differentiation and right-sided tumors (P 0.01 for all covariates). These aforementioned factors are also associated with an increased probability of retrieving 12 or more lymph nodes after surgical resection (P 0.01 for all covariates).Later year of diagnosis, younger patients, right-sided tumors, poorer differentiation, higher T descriptor and overall stage are associated with increased number of lymph nodes retrieved. These may indicate the presence of an immunological response of tumor versus host affecting lymph node retrieval.

Low CD34 + cell doses increase allograft-related mortality and very high doses increase the risk of graft-versus-host disease. The optimum CD34 + cell dose remains undefined. The effect of the CD34 + cell dose based on ideal weight was analyzed in 130 patients with hematologic malignancies undergoing reduced-intensity allogeneic blood cell transplantation in the context of factors known to affect the outcome: chemosensitivity, donor age, lactate dehydrogenase (LDH), human leukocyte antigen (HLA) match, performance status, and platelet count. The survival of patients receiving8 x 10(6)/kg CD34 + cells was not significantly different from those receiving6. The outcome of those receiving 6-8 x 10(6)/kg CD34 + cells was significantly better than the rest. This superiority was confirmed in multivariable analysis. Among patients receivingor=8 x 10(6)/kg CD34 + cells, an increasing number of infused cells was associated with higher overall survival in a continuous fashion (Risk ratio (RR) 0.8759; p = 0.045). Cell dose based on actual weight did not correlate with survival. The number of CD34 + cells infused, a potentially modifiable factor, affects survival after reduced-intensity allogeneic transplantation. We recommend a CD34 + cell dose of 6-8 x 10(6) per kg ideal body weight to optimize outcome. The possible adverse effect of higher cell doses (8) needs further confirmation.

“Stringent” complete remission in myeloma has been defined by a normal serum free light chain ratio (SFLCR) in addition to the standard criteria for CR. 2648 serial samples from 122 IgG or IgA myeloma patients were studied to explore the relationship between SFLCR and serum immunofixation electrophoresis (SIFE). SFLCR was normal in 34% of cases with positive SIFE and abnormal in 66%. SFLCR was normal in 69% of cases with negative SIFE and abnormal in 31%. When evaluated with SIFE as the benchmark, the sensitivity of SFLCR was 66% and specificity was 69%. These findings were unchanged when abnormal SFLCR values were classified as concordant (< 0.26 for λ disease and > 1.65 for κ) or discordant (< 0.26 for κ disease and > 1.65 for λ). Additional studies are required to determine the temporal relationship between SFLCR normalization and paraprotein clearance. Until then, the role of SFLCR in defining response remains controversial.

Background: The tumor lysis syndrome (TLS) has been reported to be common in hematologic malignancies, particularly those associated with a high proliferative index, high tumor burden, and highly effective therapy. The classification proposed by Cairo and Bishop (Cairo MS, Bishop M. Br J Haematol 2004; 127:3-11) provides criteria that define laboratory TLS (hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia) and clinical TLS (e.g., cardiac dysrhythmias, neuromuscular irritability, signs or symptoms clearly associated with hypocalcemia, seizures, sudden death, oliguria, elevations of creatinine above baseline). Patients with laboratory manifestations of TLS are considered to be at high risk for developing clinical TLS. It has been recommended that these patients receive rasburicase as part of initial management. The purpose of this restrospective study was to survey the incidence of laboratory/clinical TLS and to attempt to evaluate the role of allopurinol vs rasburicase for TLS prophylaxis and treatment at our institution. Methods: We reviewed a series of consecutive patients presenting to our institution for initial inpatient therapy who were considered to be at high risk for tumor lysis by virtue of their hematologic diagnosis and need for aggressive chemotherapy. ICD9 codes were used to identify patients at 19 years of age or greater with Burkitt lymphoma, high tumor burden diffuse large B cell lymphoma (DLBCL)/mantle cell lymphoma (MCL), acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)/lymphoma receiving their initial inpatient chemotherapy between 2007 and 2011. Electronic medical records were used to document demographic data, laboratory and clinical course information, including TLS prophylaxis/treatment strategies, from 3 days prior to 10 days post chemotherapy. Exclusion criteria were hypersensitivity to allopurinol or rasburicase or known glucose-6-phosphate dehydrogenase (G6PD) deficiency. Clinical and laboratory TLS was defined according to the method described by Cairo and Bishop. Results: A total of 149 patients met the inclusion criteria. One hundred thirty seven (92%) patients had no presenting clinical or laboratory manifestations of TLS (“prophylaxis group”) and 12 (8%) patients with manifestations of TLS at presentation were considered as the “treatment group”. In the prophylaxis group, 128 (93%) patients received allopurinol alone, 3 (2%) received rasburicase alone and 6 (5%) received both allopurinol and rasburicase. In the treatment group, all 12 patients received both rasburicase and allopurinol. Four patients in the prophylaxis group that received allopurinol alone (4/128, 3%) eventually developed TLS which was managed successfully without the addition of rasburicase. The median total dose of rasburicase in the treatment group was 12 mg (range 6-18) and repeated doses were administered on only 3 occasions. In this group, arrhythmias due to TLS were observed in 1 (8%), acute kidney injury in 8 (67%) and hyperkalemia in 3 (25%) patients. Two patients (17%) required nephrology consult and 1 (8%) received hemodialysis. Three patients (25%) in this group died - 2 from acute respiratory distress syndrome and 1 from acute subdural hematoma with herniation and pneumonia. The highest incidence of TLS was in patients with AML, in whom 11 out of 81 (13.5%) patients developed TLS. Conclusions: The incidence of TLS was approximately 11% in this high risk patient population. This study suggests that allopurinol as monotherapy can be effective as a prophylaxis strategy against TLS in a high risk patient population receiving initial chemotherapy. With appropriate monitoring, rasburicase may be added quickly in patients who develop progressive hyperuricemia during induction chemotherapy. Disclosures No relevant conflicts of interest to declare.

9059 Background: The incidence and mortality of elderly melanoma are expected to increase. Prior studies have shown poor outcomes in elderly melanoma patients. Methods: This is a retrospective stud...

8572 Background: Rituximab has revolutionized the treatment of lymphomas and has been shown to improve clinical outcomes in patients with follicular lymphoma. Our study evaluated the progression free survival (PFS) and overall survival (OS) in patients with grades I and II follicular lymphoma when rituximab was used as initial therapy, as salvage or if no rituximab was used. Methods: Patients with grades I and II follicular lymphoma treated between June 1981 and January 2010 were included. Disease and treatment related variables were compared based on type of treatment (No rituximab-Group I, rituximab as salvage-Group II, Rituximab as initial treatment-Group III) using the Kruswal Wallis or chi-square tests. Univariate probabilities of PFS and OS were estimated using the Kaplan Meier method. Multivariate analyses were performed using Cox proportional hazards regression analysis to evaluate differences in risk of treatment failure and mortality in the three groups while adjusting for covariates. Results: There were 226 patients in group I, 84 in group II and 110 in group III. Significant differences were found in some of the disease and treatment related variables. Univariate analysis is shown in the Table. The relative risk of treatment failure for group II was 0.82 (p=0.26) and 2.63 (p=0.0001) respectively in the first 10 years and after 10 years while it was 0.52 (p=0.0003) and 3.97 (p=0.001) respectively for group III in the first 10 years and after 10 years. The relative risk of mortality in group II was 0.63 (p=0.008) and group III was 0.32 (p

472 Background: Sarcomatoid differentiation is not a distinct histological entity and it can present in any of the subtypes of renal cell carcinoma (RCC). Although many studies were published in the literature about its aggressive clinical course, limited clinical data was available about its management and especially about the role of newer targeted therapies. At our institution, we looked at the prognostic factors in SRCC and the role of systemic therapy in its management. Methods: During the years of 1997 to 2012, we studied the records of over 400 patients diagnosed with RCC. Out of them, 43 were identified as having SRCC. Cox proportional hazards risk analysis was used to analyze the factors associated with the risk of mortality. Survival probability was estimated using Kaplan Meier method. Results: Median age at diagnosis was 58. Median tumor size was 9.75 cm. High Furhmans grades (III & IV) were seen in 67.44%. 68.29% patients presented with stage IV disease. 74.42 % patients had upfront nephrectomy. Of the systemic therapies given, 20.9% received cytokines, 16.2% received chemotherapy and 34.8% received target therapy. Probability of survival at 1 year was 50% (95% CI 33-65) and at 5 years was 24% (95% CI 10-41). Median time to progression was 13 months (95% CI 7 -23). Factors associated with risk of mortality were mainly the stage at diagnosis [HR 2.174, p = 0.0123, CI (1.184-3.992)], Nephrectomy [HR0.243, p = 0.0012, CI (0.104- 0.571)] and the use of target therapy [HR 0.313, p = 0.0070, CI (0.134-0.728)]. Conclusions: Our study confirmed that the SRCC is more aggressive than conventional RCC in its presentation and in its median time to progression. It responds poorly and unpredictably to systemic therapies. In our study, upfront nephrectomy and target therapy appeared to be independent predictors of survival. SRCC needs to be considered as a different disease entity and new treatment options need to be explored for this unfortunate subset of patients with kidney cancer.