tbuckley/cabot-search huggingface dataset:
Survival outcomes and patterns of utilization of cytoreductive nephrectomy in the tyrosine kinase inhibitors (TKI)-era in metastatic clear cell renal cell carcinoma (ccRCC) and non-clear cell renal cell carcinoma (nccRCC): Analyses from the National Cancer Database (NCDB).
Authors: Jeanny B. Aragon-Ching, Hongkun Wang, Donald L. Trump
Journal: Journal of Clinical Oncology (2017)

e16068 Background: Use of TKIs is standard of care for metastatic ccRCC and cytoreductive nephrectomy has improved survival even in metastatic ccRCC. The use of cytoreductive nephrectomy in the TKI era post-2005 for nccRCC histologies is unknown. We sought to determine trends and explore differences in characteristics of ccRCC and nccRCC, use of cytoreductive nephrectomy and survival outcomes for varying stages. Methods: Using a de-identified dataset acquired from the NCDB from 2004 to 2014, extraction of demographic information on patients divided into ccRCC versus nccRCC. Descriptive statistics was used for summarizing patients’ characteristics. Chi-Square test was used for comparing categorical variables. Two-sample t-test was used for comparing continuous variables. Kaplan-Meier method was used to analyze patients’ survival data. Results: 302,339 (82%) ccRCC and 66,530 (18%) nccRCC patients were identified. nccRCC included papillary (n = 42,251), sarcomatoid (n = 5769), chromophobe (n = 17,671) and collecting duct (n = 839). The median age for both groups was 63 years, more common in males (ccRCC = 61%; nccRCC = 69%), and mostly Caucasians (ccRCC = 86%; nccRCC = 75%). Most patients were treated in comprehensive community and academic research programs (ccRCC = 81%; nccRCC = 83%). Majority of patients were diagnosed with AJCC Stage I (ccRCC = 57%, nccRCC = 62%). Stage IV was diagnosed in 14% of ccRCC and 9% of nccRCC. The utilization of nephrectomy declined for ccRCC at 36% in the year 2014 compared to 44% in 2005, whereas it declined more for nccRCC with 47% in 2014 compared to 70% in 2005. The median survival time for Stage I was comparable in both groups (ccRCC = 140 mos, 95% CI 138.8 – 142.16; nccRCC = 140 mos, 95% CI 138 – unestimable). However, median survival was worse for stage IV in nccRCC (ccRCC = 9 mos; 95% CI 8.8 – 9.17; nccRCC = 7.43 mos; 95% CI 7.16 – 7.79). Conclusions: In stage IV patients with nccRCC, cytoreductive nephrectomy is used less often and overall survival appears inferior compared to ccRCC.
Racial differences of iron deficiency anemia in gastric cancer.
Authors: Stuthi Perimbeti, Erika Correa, Kathleen Degen, Shaun Bryan Hanson, William May Lee, Kevin Ye Hou, Maneesh Rajiv Jain, Kristine Marie Ward, Michael Styler, Neilanjan Nandi
Journal: Journal of Clinical Oncology (2017)

e15564 Background: One of the six domains of health care quality identified by the Institute of Medicine in 2001 was equitable care.1 While disparities in cancer are often expressed in terms of mortality, comorbidities such as iron deficiency anemia (IDA) that can be caused by less comprehensive or less timely treatment of gastrointestinal malignancies also impact quality of life and may be considered as a metric of equitable care. Methods: Using data from the Healthcare Cost and Utilization Project (HCUP), total numbers of U.S. admissions with gastric cancer listed as primary diagnosis were recorded for each year between 1999-2014. The subset of these numbers with IDA listed as a secondary diagnosis were recorded to derive a prevalence of IDA within this gastric cancer population. The relative rate of African American and Hispanic IDA prevalence were compared to Caucasians for each year. Within each ethnic subset, cost, length of stay, and inpatient mortality were compared. Results: The relative rate of iron deficiency in gastric cancer for African Americans versus Caucasians was 1.745 and for Hispanics versus Caucasians was 1.665. Hospital cost by ethnic group: Caucasians $55,359, African Americans $62,020, Hispanics $83,914. Length of stay in days by ethnic group: Caucasians 9.13, African Americans 10.12, Hispanics 10.17. Inpatient mortality by ethnic group: Caucasians 4.51%, African Americans 4.02%, Hispanics 2.29%. All values were significant (p &lt; 0.05). Conclusions: African American and Hispanic populations are at increased risk of iron deficiency anemia in the setting of gastric cancer as compared to Caucasians. This was associated with increased cost and length of stay to a lesser degree. Surprisingly, Caucasians still demonstrated the highest mortality rate, followed by African Americans and Hispanics. This suggests that though ethnic disparities are still evident as of 2014 they may not accurately reflect mortality but still continue to impact morbidity. As this comorbidity impacts quality of life, it may be a target for future metrics or interventions.
Autologous stem cell transplant (ASCT) for newly diagnosed multiple myeloma (MM) in the era of novel agents: A meta-analysis of phase III randomized controlled trials.
Authors: Binod Dhakal, Saurabh Chhabra, Mehdi Hamadani, Anita D'souza, Saad Zafar Usmani, Jeffrey Jackson, Parameswaran Hari
Journal: Journal of Clinical Oncology (2017)

8022 Background: Given the unprecedented deep response rates with the novel agent induction, the role of high dose therapy (HDT) followed by ASCT in MM pts. has been questioned, and was re-evaluated in a number of randomized clinical trials (RCTs). Although, the results of most studies suggest the continued benefit of HDT/ASCT, some RCTs suggest no overall survival (OS) benefit. We undertook a systematic review and meta-analysis of phase III randomized RCTs evaluating the role of HDT compared to standard therapy (SDT) in the context of novel agent induction Methods: We searched the PubMed, Scopus and Cochrane Collection of Controlled Trial databases using the term myeloma combined with autologous or transplant or myeloablative or stem cell from 2000-2016. A total of 2480 articles identified, of which 4 large phase III RCTs compared upfront HDT with SDT with novel agents use. Two individuals independently extracted the data. Reported hazard ratio (HR) and survival data were pooled using random effects models (STATA v14, College Station, Tx). Heterogeneity was assessed using I 2 . Results: Four studies comprising 2421 patients were included (Table 1). One study did not report the HR for death and hence OS analysis was limited to 3 studies. The combined hazard for progression with HDT was 0.55 (95% CI 0.40-0.71) (p &lt; 0.005). The combined hazard for death with HDT was 0.65 (95% CI 0.29-1.0) (p = 0.007). Sensitivity and sub-group analysis showed no difference in PFS (p = 0.06) and OS (p = 0.22) with HDT. Significant heterogeneity was demonstrated by I 2 of 71.4% for PFS (p = 0.01) and 68.4% for OS (p = 0.04). Conclusions: Based on our analysis, even in the novel agent era, HDT appears to be beneficial and should be considered standard of care for all transplant eligible MM pts. [Table: see text]
Trabectedin (T) as second line treatment option for patients with epithelioid malignant pleural mesothelioma (MPM) in progression following pemetrexed/platin-derivates chemotherapy: ATREUS trial.
Authors: Diego Luigi Cortinovis, Lital Hannah Hollander, Luciano Carlucci, Federica Grosso, Giovanni Luca Ceresoli, Ilaria Pacchetti, Paolo Andrea Zucali, Maurizio D'Incalci, Marcello Tiseo, Lorenzo Legramandi, Stefania Canova, Francesca Ugo, Maria Ida Abbate, Giacomo Taverna, Viola Cogliati, Paolo Bidoli
Journal: Journal of Clinical Oncology (2017)

8513 Background: Systemic chemotherapy in MPM is inevitably followed by relapse, and response rates to second line treatment are limited. T is an antineoplastic agent targeting both the malignant cells and the tumor microenvironment with demonstrated activity against a range of tumors. We aimed to study the activity and safety of T in advanced MPM. Methods: ATREUS, an Italian multicenter single arm phase II trial, assessed the activity T in MPM evaluating the proportion of patients responding to treatment and achieving progression free survival for 12 weeks (PFS12w). Pre-treated epithelioid and naive or pre-treated biphasic/sarcomatoid pts were treated until progression or unacceptable toxicity. Initial dose was 1.3 mg/m 2 , over 3 hours every 21 days, later reduced to 1.1 mg/m 2 to improve tolerability. In the epithelioid cohort, sample size was based on a Simon's Optimal Two-Stage Design. The study was set to reject, at an alpha error of 10% the hypothesis that PFS12w was ≤25% and to demonstrate, with a power of 85% the hypothesis that PFS12w was ≥40%. At least 20 out of 62 pts with assessed disease, no major protocol violations, either receiving ≥12 weeks of treatment or interrupting before for progression or death (per protocol – PP analysis) were to reach PFS12w in order to consider T effective. Results: 71 pts were enrolled and evaluable. Average age was 65.8 ± 8.75 years. 71.8% were male and 82.5% presented stage III or IV disease. 42.4% (25/59) of pts included in the PP analysis obtained PFS12w (95% CI: 29.6% - 55.9%). In a second, more conservative analysis, including pts withdrawn prematurely for toxicity or intercurrent illness as failures, PFS12w rate reached 38.5% (25/65 pts). The most frequent grade ≥3 treatment-related toxicities werehepatic toxicity (60.5%), non-febrile neutropenia (21.1%), and fatigue (6.6%). Five pts (7%) interrupted treatment for toxicities (2 liver, 1 multi-organ failure, 1 thrombocytopenia, 1 T intolerance). Conclusions: In pts with advanced epithelioid MPM, second line treatment with T showed an elevated rate of disease stabilization. Safety data is promising but require further evaluation. Clinical trial information: NCT02194231.
Functional classification of long non-coding RNAs by k-mer content
Authors: Jessime M. Kirk, Susan O. Kim, Kaoru Inoue, Matthew J. Smola, David M. Lee, Megan D. Schertzer, Joshua S. Wooten, Allison R. Baker, Daniel Sprague, David W. Collins, Christopher R. Horning, Shuo Wang, Qidi Chen, Kevin M. Weeks, Peter J. Mucha, J. Mauro Calabrese
Journal: Nature Genetics (2018)
Prognostic impact of 21-gene recurrence score in patients with node negative breast cancer in China.
Authors: Yinduo Zeng, Tao Qin, Qian Li, Kai Chen, Shunrong Li, Liang Jin, Jiannan Wu, Heran Deng, Nanyan Rao, Qiang Liu, Fengxi Su, Weijuan Jia, Herui Yao
Journal: Journal of Clinical Oncology (2018)

e24255 Background: The objective of this study was to determine whether the 21-gene Recurrence Score (RS) assay provides clinically meaningful information in node negative patients with hormone receptor positive/HER2negative (HR+/ HER2-) operable breast cancer. Methods: All data were extracted from the medical record from a prospective registry database in Sun Yat-sen Memorial Hospital. A total of 218 patients had primary tumor samples suitable for 21-gene RS analysis and were enrolled from January 2013 to July 2016. The prospective part of this study enrolled node-negative, hormone receptor-positive (HR+) patients who underwent 21-gene RS testing (Surexam, Guangzhou, China). Disease-free survival (DFS), distant metastases free survival (DMFS), and overall survival (OS) at 3-year were estimated by Kaplan-Meier with log-rank test. Results: Median age was 47.5 years (23 to 77 years). Of 218 patients, 64.7%, 30.3%, 5.0% had stage I, IIA and IIB. 133 (61.0%) with low RS ( < 18), 65 (29.8%) with intermediate RS (18 to 30) and 20 (9.2%) with high RS (≥31). There were 33.8%, 89.2% and 100% patients receiving chemotherapy in low-, intermediated- and high- RS groups. A total of 30% patients changed adjuvant chemotherapy decision after 21-gene RS test. After a median follow-up of 31 months, for entire cohort, the DFS and DMFS rate at 3 years were 93.3% and 95.2%, respectively. The OS rate at 3 years was 100% for each group. In addition, though tendency of high risk for recurrence in high RS group, the DFS rate at 3 years was no difference among low-, intermediated- and high- RS groups (95.9%, 91.3%, 87.4%, respectively, p = .579). Similar trend was observed in DMFS rate at 3 years (97.7%, 95.5%, 84.4%, respectively, p = .396). Conclusions: This is the first prospective study reported clinical outcome data from patients for whom the 21-gene RS assay in China. The 21-gene test might determine those patients with high risk for breast cancer recurrence, but needed longer follow-up duration.
Disparities in supportive therapy for head and neck cancer and impact on missed radiation days and weight loss.
Authors: Stephen Ramey, Haley Perlow, Ben Silver, Adam Jaffe, Deukwoo Kwon, Felix Chinea, Stuart Samuels, Raphael Yechieli
Journal: Journal of Clinical Oncology (2017)

6077 Background: National guidelines emphasize the importance of speech and swallowing (SS) and nutrition services (NS) for head and neck cancer patients (pts). This study evaluates influences of demographic and treatment factors on receipt of SS and NS at a safety-net hospital (SH) and an adjacent private hospital (PH). It also examines associations between lack of these services and negative outcomes. Methods: This retrospective analysis included non-metastatic laryngeal or oropharyngeal cancer pts treated with radiotherapy (RT) at a PH or SH. Univariate (UVA) and multivariable (MVA) analyses utilized linear regression, logistic regression, and zero-inflated Poisson regression. Covariates included race, ethnicity, preferred language, insurance status, immigration status, gender, age, treating hospital, comorbidity score, primary treatment modalities, time to treatment initiation (TTI), and stage. Potential negative outcomes of not receiving SS and/or NS were analyzed only among pts treated with chemoradiation (CRT). Results: Of 239 pts (PH = 138 pts; SH = 56 pts), 28.6% of SH pts received SS pre-RT vs 54.1% at the PH (p &lt; 0.001). Receipt of pre-RT NS did not differ significantly between SH (14.3%) and PH (19.7%) but was low at both. On MVA, SH care (OR 0.29; p = 0.029) and longer TTI (OR 0.99; p = 0.033) were associated with decreased pre-RT SS. In contrast, surgery before RT (OR 10.1; p = 0.002) and surgery before CRT (OR 10.7; p = 0.001) vs RT alone were associated with increased pre-RT SS. No covariates were significantly associated with receipt of NS on MVA. For pts receiving CRT, pre-RT SS was associated with less weight loss during RT (mean difference = 2%; p = 0.036). Receiving both pre-RT SS and NS was associated with fewer missed RT days (RR 0.49; p = 0.004). Receipt of SS and/or NS were not associated with gastric tube placement, emergency room visits, or non-chemotherapy admission days during or within 90 days of CRT. Conclusions: SS was received less often at a SH vs a PH. NS were delivered at a low level at both centers. Lack of supportive services was associated with increased missed RT days and increased weight loss during CRT. Quality metrics to establish supportive care benchmarks may help reduce disparities.
Molecular and immunophenotypic predictors of response to azacitidine (aza) as frontline therapy for acute myeloid leukemia (AML).
Authors: Michael Keith Alister Zimmerman, Michael Richard Grunwald, James Thomas Symanowski, Jonathan Michael Gerber
Journal: Journal of Clinical Oncology (2016)

7024 Background: The hypomethylating agent aza has emerged as a frontline treatment option for elderly and unfit AML patients (pts). However, markers predictive of response to aza are lacking. We hypothesized that mutations in nucleophosmin 1 (NPM1) and isocitrate dehyrodgenase (IDH) – which are common in AML, as well as the expression status of the cell surface marker CD34, might correlate with response to aza. Methods: We reviewed the charts of all AML pts treated with first line aza at our institution over 2 years (2013-2015). NPM1, IDH1, and IDH2 mutational status were identified by PCR; and CD34 expression was determined by flow cytometry – all performed on clinical testing of patients’ leukemia cells. Pts’ response to therapy was assessed by achievement of hematologic remission (HR), defined by: absolute neutrophil count > 1000, platelet count > 100, red blood cell transfusion independence, and the absence of peripheral blasts. CD34, NPM1, and IDH status were evaluated as categorical variables; correlations with HR were examined using Fisher’s exact test. Results: A total of 19 pts were treated with aza as frontline therapy for AML. NPM1 mutations correlated with both achievement of HR and CD34- status. Specifically, 83% (5 of 6) of NPM1+ pts achieved HR, compared to only 20% (2 of 10) of NPM1- pts (p = 0.031). Similarly, 83% (5 of 6) of NPM1+ pts were CD34- (p = 0.005). Interestingly, all pts (n = 6, including the 5 NPM1+) with CD34- AML achieved HR, versus only 23% (3 of 13) of those with CD34+ AML (p = 0.003). IDH mutational status did not correlate with response. 50% (4 of 8) of IDH+ pts achieved HR, compared to 38% (3 of 8) of IDH- pts (p = 0.841). Conclusions: Our data support prior reports of a link between the NPM1 mutation and CD34- status in AML. The NPM1+ genotype and CD34- phenotype appear to predict responsiveness of AML to aza therapy. In contrast, IDH status did not seem to impact the response of AML to aza. While this work requires validation in a larger cohort, screening for NPM1 mutations and CD34 status may help to identify AML pts likely to benefit from treatment with aza. Status CD 34 + CD 34 - NPM1 + NPM1 - IDH + IDH - Number of Patients 13 6 6 10 8 8 Number Achieved HR 3 6 5 2 4 3 Percent Achieved HR 23 100 83 20 50 38
Balancing the risk and benefit of adjuvant chemotherapy for early breast cancer: A retrospective cohort study in New South Wales (NSW), Australia.
Authors: Hanna E Tervonen, Tina YT Chen, Enmoore Lin, Frances M. Boyle, Eugene J. Moylan, Stephen A. Della-Fiorentina, Jane McNeil Beith, David Christopher Currow
Journal: Journal of Clinical Oncology (2018)

e18841 Background: Both toxicity and effectiveness require consideration when estimating the net effect of chemotherapy. We examined emergency hospital admissions and 5-year survival following adjuvant chemotherapy for early breast cancer in 2008-2012. Methods: A unique set of linked data was used (NSW Cancer Registry, NSW Clinical Cancer Registry, NSW Admitted Patient Data Collection, NSW Registry of Births, Deaths and Marriages, and Pharmaceutical Benefits Scheme). Women aged ≥18 years receiving adjuvant cytotoxic chemotherapy for early breast cancer in public hospitals in NSW were grouped by index chemotherapy protocol. We calculated the percentage of women with emergency hospitalisation within 6 months following chemotherapy initiation. Odds ratios (OR) for hospitalisation were estimated using logistic regression and survival using Cox proportional hazards model. Results: 3,950 women were included and 30.6% (n = 1,209) had an emergency hospitalisation. Commonest principal diagnosis at admissions was neutropenia (30.8%). Women receiving docetaxel/carboplatin/trastuzumab (TCH) and docetaxel/cyclophosphamide (TC) were most likely to be hospitalised. After adjusting for key demographic and clinical factors, 5-y survival was 92.7% (95%CI 91.9-93.6) for the whole cohort and largely similar for women receiving different protocols. There were no deaths during index chemotherapy. Women who were or were not hospitalised had similar 5-y survival (92.0%, 95%CI 90.4-93.6 and 93.1%, 95%CI 92.1-94.1, respectively). Conclusions: Despite emergency hospitalisation being relatively common, survival was high and similar between women who were and were not hospitalised. Protocol Hospitalisation Survival % OR (95%CI)1 5-yr survival (95%CI) 1 AC (3wkl) 28.6 1 92.1 (90.3-93.8) TCH 43.4 1.8 (1.4-2.5) 94.1 (91.2-97.1) TC 35.4 1.4 (1.1-1.8) 94.9 (92.6-97.3) FEC-D 30.6 1.1 (0.9-1.4) 93.4 (91.8-95.0) FEC-100 29.8 1.1 (0.8-1.5) 93.9 (90.6-97.3) TAC 27.9 1.0 (0.8-1.3) 89.7 (86.7-92.7) AC+PAC (3wkl) 22.3 0.7 (0.5-1.0) 92.1 (89.2-95.0) 1 Adjusted for age, node positivity, TNM stage, surgery type, and hormone receptor status proxy Protocol information: www.eviq.org.au
A phase I study of novel dual Bcl-2/Bcl-xL inhibitor APG-1252 in patients with advanced small cell lung cancer (SCLC) or other solid tumor.
Authors: Nehal J. Lakhani, Drew W. Rasco, Anthony W. Tolcher, Yingjie Huang, Jiao Ji, Hengbang Wang, Qi Dong, Lichuang Men, Timothy J. O'Rourke, Sreenivasa R Chandana, Alex Amaya, Yvette Cole, Brianne Kaiser, Theresa A. Mays, Amita Patnaik, Kyriakos P. Papadopoulos, Dajun Yang, Yifan Zhai
Journal: Journal of Clinical Oncology (2018)

2594 Background: We have developed a unique strategy to tactically reduce on-target platelet toxicity with APG-1252, a novel dual Bcl-2/Bcl-xL inhibitor, while maintaining strong in vivo antitumor activity. APG-1252 potently inhibits tumor growth in human cancer xenograft models including SCLC models while trigged significantly less platelet killing APG-1252 demonstrated a higher therapeutic index than ABT-263 in preclinical studies. Methods: This Phase I study (NCT03080311) enrolled patients with advanced SCLC or other solid tumors. In dose escalation, the patients received APG-1252 (10–400 mg) intravenously twice weekly for 3 weeks in a 28-day-cycle, until disease progression. Study objectives include safety (primary endpoint), pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity assessed every 8 weeks per RECIST v1.1. Results: As of Jan 31, 2018, 13 patients (including 6 pts with SCLC) have been treated in 5 cohorts of APG-1252. Current dose level being explored is 160 mg. The median number of prior systemic anti-cancer therapies was 2 (range 1-6). The pts received a median of 2 cycles of APG-1252 (range 1-6). MTD has not been identified yet. TRAEs were reported in 10 pts (77%). The most common AE’s (reported in ≥10% of pts) included: arthralgia, AST/ALT increased, vomiting, and fatigue. All TRAEs were grade ≤ 2 in severity. There were no AEs leading to treatment discontinuation. No thrombocytopenia or other cytopenias have been observed six pts had ≥1 on-treatment tumor assessment. One confirmed partial response was observed in 1 patient with metastatic SCLC at the 40 mg dose, and the duration of response lasted for more than 6 cycles. PK analyses indicate that AUC and Cmax increase dose proportionally over 10-40 mg range on day 1, while AUC increases more than dose proportionally on Day 22. AUC at 40 mg on Day 22 is close to in vivo efficacious exposure. Conclusions: APG-1252 was well-tolerated across all dose levels tested. No hematologic toxicity has been reported so far. Dose escalation and further evaluation of APG-1252 in patients with SCLC and other advanced solid tumors is ongoing. Clinical trial information: 03080311.