tbuckley/cabot-search huggingface dataset:
Factors affecting survival in laparoscopic vs. open surgery among stage III colon cancer patients.
Authors: Yang Zhang, Ryan W Walters, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2017)

e15095 Background: The role of laparoscopic surgery (LS) in the cure of advanced non-metastatic colon cancer is controversial. The study aims to define long-term survival of LS and open surgery (OS) of stage III colon cancer as well as to examine factors that influence the choice in surgical approaches. Methods: We abstracted 22,821 patients from the National Cancer Database who were diagnosed with stage III colon cancer from 2010 to 2012 who had undergone surgery of their primary site by either LS or OS; we only included patients who had also received adjuvant chemotherapy. The probability of undergoing a LS or OS was estimated using multivariable marginal logistic regression model, whereas the between-procedure survival difference was estimated with the Kaplan-Meier method with associated log-rank test and a multivariable marginal Cox regression model. Results: Holding the patient- and facility-level characteristics constant, significantly greater odds of receiving LS was associated with private insurance, patients living in areas with higher socio-economic status, patients receiving care at academic facilities, and patients living in the northeast United States. Kaplan-Meier results indicated that patients undergoing LS had significantly longer survival compared to patients undergoing OS (χ 2 1 = 111.6, p &lt; .001). Table 1 shows three-year survival estimates. After adjusting for the patient- and facility-level covariates, patients who underwent LS had 26.7% lower risk of death compared to those undergoing OS (95% CI: 21.7% to 31.4%, p &lt; .001). In general, lower adjusted risk of death was observed in patients who were younger, female, as well as patients with fewer comorbid conditions and those with private insurance (all p&lt; .05). Conclusions: In this largest, most recent analysis of surgical treatment of stage III colon cancer, our data suggest that long-term survival after LS is superior to conventional OS. Identification of associated demographic factors may prove useful for future allocation of treatment resources. [Table: see text]
Determination of optimal dose and treatment schedule of the immunotherapeutic vaccine, DPX-Survivac, for combination immunotherapy treatment of ovarian, fallopian tube or peritoneal cancer (OC): A phase Ib study.
Authors: Jeannine A. Villella, Michelle K. Wilson, Neil Lorne Berinstein, Mohan Karkada, Tara Quinton, Marcus O. Butler, Stephanie Lheureux, Victoria Mandilaras, Neesha C. Dhani, Genevieve Weir, Lisa MacDonald, Rita Nigam, Marianne Stanford, Marc Mansour, Amit M. Oza
Journal: Journal of Clinical Oncology (2016)

e14577 Background: Survivin is an important protein that regulates apoptosis, proliferation, and angiogenesis of tumors. Increased expression of survivin in various tumors correlates with progression and drug resistance. DPX-Survivac vaccine contains a mix of survivin HLA class I peptides contained in a novel formulation designed to evoke a cytotoxic T cell response against survivin. A phase 1 study (Berinstein et al, Oncoimmunology, 2015) has demonstrated the immunogenicity of DPX-Survivac in combination with metronomic low dose oral cyclophosphamide (mCPA). This study was designed to explore additional dosing schedules that maintain immunogenicity while limiting local injection site reactions in OC. Methods: Stage IIc-IV OC patients with a complete or partial response after first (adjuvant) or second line chemotherapy and with minimal disease were enrolled. Various vaccination schedules as well as boosting without the oil component of DPX-Survivac were tested. Adverse events and dose limiting toxicities were defined by CTCAE v4.03. Vaccine-induced T cell immunity (ELISpot; tetramer analysis) was assessed in purified PBMC. Clinical response was assessed by CT and CA125 using standard RECIST criteria. Results: 36 patients have been treated with different doses and schedules DPX-Survivac vaccination together with mCPA. Several modifications of the dose and schedule resulted in sustained immune responses of varying magnitude and duration. DPX-Survivac was well tolerated. Conclusions: DPX-Survivac in combination with mCPA results in sustained immune responses. This study will allow us to balance the immune response and site of injection profile for different indications including early prevention of recurrence or treatment of small volume active disease. Clinical trial information: NCT01416038.Cohort Pts (n) Priming DPX Boost DPX/Aq Skin ul ceration Grade (n) Immune ELISpot Re sponse 256 to >4000 SFU/ 106 PBMC n (%) Dose (mL) n Freq wks Vol (mL) n Freq wks 1 6 0.25 2 3 0.1 DPX 4 8 2 (2), 3 (1) 6 (100) 2 9 0.25 2 3 0.1 DPX 4 8 3 (1) 4 (44) 3 6 0.25 3 8 N/A 0 0 1 (1) 5 (83) 4 7 0.25 2 6 0.25 DPX 3 6 TBD TBD 5 8 0.25 2 4 0.5 Aq 4 4 TBD TBD
A single institution retrospective review of characteristics and outcomes of patients requiring chronic dose reduction of TKIs given as front-line therapy for chronic phase CML.
Authors: Jamie Lynn Koprivnikar, James K. McCloskey, Yucai Wang, Genique Stanislaus, Stuart L. Goldberg, Stefan Faderl
Journal: Journal of Clinical Oncology (2016)

e18544 Background: Dosing of TKIs is standardized and is not altered based on BSA, sex, or other patient characteristics. Long-term data on the effects of dose-reduction of TKI therapy based on toxicity is lacking and there is little data on risk factors for TKI intolerance. We sought to identify characteristics of patients requiring dose reductions as a part of first-line TKI treatment for chronic phase CML and to determine the long-term outcome of these patients. Methods: We identified all patients seen at our institution for first-line treatment of chronic phase CML between 11/1/10 and 7/16/15 and reviewed their records to identify individuals requiring chronic dose reductions. We identified a control group by capturing all patients tolerating full dose first-line TKI therapy during a pre-specified period. Results: A total of 18 patients were identified who required dose reduction with a median follow up time of 34.72 months (12.47-124.07). The median time spent on reduced dose therapy was 26.37 months (4.90-118.93). 89% of patients remained in a major molecular response 4 (MR4) despite dose reduction. Median progression free survival (PFS), as defined by loss of MMR, of dose-reduced patients had not yet been reached. One, two, and three year PFS rates were 100%, 93.8%, and 85.2% respectively. When compared to the control group of patients tolerating front line therapy at full-dose, patients requiring dose reduction were more likely to be female: 78% vs 48% (P = 0.045) and have a lower BSA: 1.77 versus 1.99 mg/m2 (P = 0.010). Conclusions: Important risk factors for TKI dose reduction include female sex and lower BSA. The majority of patients remained in MR4 despite dose reductions. Both of the 2 patients (12.5%) who did not were able to regain MR4 status after switching to an alternate TKI. Our data suggest the possible utility of dose adjustments based on BSA for patients who are intolerant of TKI therapy. Risk factors for TKI dose reduction. Full dose group Dose reduction group P value Number 29 18 Gender 15 4 0.045 (chi-square) Male 14 14 Female BSA 1.99±0.28 1.77±0.25 0.010 (t test) BMI 30.27±6.34 27.20±4.28 0.084 (t test)
Upper tract urothelial carcinoma is non-basal and T-cell depleted.
Authors: Panagiotis J. Vlachostergios, Brian D. Robinson, Bhavneet Bhinder, Rohan Bareja, Kyung Park, Peyman Tavassoli, Scott T. Tagawa, David M. Nanus, Juan Miguel Mosquera, Douglas Scherr, Mark A. Rubin, Olivier Elemento, Bishoy Faltas
Journal: Journal of Clinical Oncology (2018)

4525 Background: Urothelial cancer (UC) of the upper urinary tract (UTUC) accounts for 5-10% of UC. Despite sharing a common histology with bladder UC (UCB), staging and prognosis differences have been reported. Methods: To dissect the central biological features of UTUC driving its phenotype, we performed an integrated analysis of UTUC tumors using whole-exome (WES) and RNA sequencing (RNAseq). We compared the exome and transcriptome of UTUC to the TCGA UCB and an independent UTUC validation dataset (VALD). Results: We performed an integrated analysis of WES (n = 16) and RNAseq (n = 19) from biobanked nephroureterectomy archival specimens of 19 chemotherapy-naïve patients with UTUC. Patients' demographics are as follows: median age 71 (range 46-87); 11 men, 8 women; 11 former/current smokers; 13 renal pelvis, 6 ureteral; 17 high-grade, 2 low-grade; 8 low stage ( < pT2), 11 high stage (≥ pT2). Our analyses revealed several insights: 1) UTUC has a significantly lower frequency of TP53 mutations (3/16, 18.7%) compared to UCB patients (198/412, 48%) (p = 0.03) but similar frequency of mutations in chromatin modifying (KMT2C, KMT2D, KDM6A), transcription activation (CREBBP), receptor tyrosine kinase (FGFR3, PIK3CA, ERBB2, KRAS), and cell cycle regulation (RB1) genes. 2) UTUC is characterized by downregulation of the DNA mismatch repair genes (p ≤ 0.05) and APOBEC3A, APOBEC3B genes (p < 0.01) and a lower total mutational burden compared to UCB (2 vs 5 mutations per Mb, p = 0.01). 3) UTUC is intrinsically non-basal. UTUC is predominantly luminal by UNC (18/19, 95%) and the MD Anderson (MDA) (17/19, 89%) criteria, and luminal-papillary (16/19, 84%) by the TCGA criteria. All VALD UTUC tumors (n = 10) clustered with the luminal-papillary subtype. 4) UTUC tumors exhibit a T-cell depleted phenotype (17/19, 89%). 5) FGFR3 expression is a dominant transcriptional outlier in UTUC (7/19, 37%) and is associated with a T-cell depleted phenotype (p < 0.01). Conclusions: Our study demonstrates that UTUC is predominantly and intrinsically non-basal. We show that UTUC is characterized by a T-cell-depleted phenotype associated with FGFR3 overexpression. By dissecting the biology of UTUC, we provide the biological rationale for future UTUC-specific therapeutic strategies.
Creating simple solutions for safe naloxone use.
Authors: Jason Meadows, Kara McGee, Jessica Goldberg, Stacy Marie Stabler
Journal: Journal of Clinical Oncology (2017)

e18185 Background: Naloxone is sometimes required to reverse acute intoxication from opioid pain medications. Although clinical guidelines exist, naloxone dosing is variable in practice. Higher doses can cause pain crisis, acute withdrawal, and possibly increased patient risk. We developed a multi-faceted intervention to increase guideline-concordant naloxone dosing. Methods: We surveyed medical staff and retrospectively collected 6 months of naloxone prescribing data to assess knowledge and frequency of guideline-concordant dosing. We reviewed the electronic order for naloxone and interviewed experienced nurses to facilitate mapping of the process of naloxone administration. We then designed 4 interventions aimed at adult inpatients on medical oncology, general medical and ICU services: 1. Simplify wording of naloxone guidelines; 2. Create naloxone kit containing all necessary equipment and instructions; 3. Auto-populate dose into electronic naloxone order; 4. Administer 5-minute educational inservice to staff (RN, NP, PA, MD). To assess rate of guideline concordance, naloxone prescribing data was collected for the pre-intervention (12 months), intervention (6 weeks), and post-intervention (8.5 months) groups. The survey was repeated after the intervention. For analysis, a generalized linear regression with logit link function and a generalized estimating equation method were used. Results: Over the 22-month study period, 137 patients received 148 naloxone doses. Patients were mean age 63.1 y/o, 54.7% female, and 75.9% white. Of the 90 naloxone doses given pre-intervention, only 24.4% were guideline-concordant. The 10 doses of naloxone given during the intervention period were guideline-concordant in 40% of the cases. Of the 48 naloxone doses given post-intervention, 62.5% were guideline-concordant, a significant increase compared to the pre-intervention group (p &lt; 0.001). The improvement was most dramatic in the non-ICU services (26.4% to 73.5%, p &lt; 0.001). Increases were maintained at 8 months (median concordant rate 53.5%/month (range: 33%-100%). Conclusions: A simple, inexpensive intervention can be used to increase guideline-concordant naloxone dosing and potentially avoid adverse effects of naloxone.
Nivolumab plus cisplatin/pemetrexed or cisplatin/gemcitabine as induction in resectable NSCLC.
Authors: Nathaniel R. Evans, Scott Cowan, Charalambos Solomides, D. Craig Hooper, Larry Harshyne, Grace L. Lu-Yao, Hushan Yang, Linda Phan, Dawn Poller, Benjamin Leiby, Maria Werner-Wasik, Bo Lu, Jennifer Maria Johnson, Rita Susan Axelrod, Athanassios Argiris, Ralph Zinner
Journal: Journal of Clinical Oncology (2018)

TPS8582 Background: For patients (pts) with stage IB (≥4cm)-IIIA Non-small-cell lung cancer (NSCLC), multi-modality therapy yields a modest improvement in 5 year post-surgical overall survival (OS), with comparable benefit for induction and postoperative adjuvant chemotherapy (chemo). Induction can speed the discovery of promising regimens by using pathologic response as a surrogate for OS. About 20% of pts treated with induction chemo have major pathologic response (MPR) ( < 10% viable tumor) at primary and lymph nodes while pathologic complete responses (pCR) average 4%. MPR was strongly associated with improved OS (Hellmann MD, Lancet, 2014). PD-1 checkpoint inhibitors (CI), nivolumab (nivo), pembrolizumab (pembro), and the PD-L1 CI, atezolizumab, are established in advanced NSCLC as 2nd line therapy, and pembro is approved as a single agent as 1st line treatment of pts with PD-L1 high expressing tumors. In a phase III 1st line NSCLC study, pts with high mutational burden tumors had superior OS with nivo plus ipilimumab compared to doublet chemo. Pembro plus carboplatin with pemetrexed (P) was approved as 1st line therapy based on a randomized phase II study in advanced NSQ NSCLC showing improved clinical response and PFS compared to chemo alone with no increase in grade III toxicity. We therefore hypothesize that the addition of nivo to induction cisplatin (C) P or C gemcitabine (G) will increase the MPR rate over induction chemo alone compared to historical controls. Methods: This is an investigator initiated trial for pts with newly diagnosed clinical stage I-IIIA (stage I ≥ 4cm) SQ and NSQ NSCLC. Induction is C 75mg/m2 IV q 3w x 3 plus either P 500 mg/m2 IV q 3wks x 3 or G 1250mg/m2 IV d1, d8 q 3 wks x 3 plus nivo 360mg IV q 3w x 3. Surgery is planned 3 wks after the last dose. The primary outcome is MPR. Secondary outcomes include safety, pCR, overall clinical response rate, clinical CR, 1 year PFS, OS and exploratory outcomes assessing markers of immune bias. Enrollment will be 34 pts. Clinical trial information: NCT03366766.
Comparative effectiveness and safety of monoclonal antibodies (bevacizumab, cetuximab and panitumumab) in the treatment of metastatic colorectal cancer: Systematic review and metanalysis.
Authors: Wania Cristina Silva, Ellias Magalhaes Abreu Lima, Vânia Eloísa Araújo, Jéssica Barreto Ribeiro Santos, Michael Ruberson Ribeiro Silva, Francisco Assis Acúrcio, Mariangela Leal Cherchiglia, Eli Iola Gurgel Andrade
Journal: Journal of Clinical Oncology (2017)

e15008 Background: Biological agents have presented variable results in the treatment of metastatic colorectal cancer. This study aim to evaluate the effectiveness and safety of the monoclonal antibodies bevacizumab, cetuximab and panitumumab associated or not to chemotherapy in this scenario. Methods: A systematic review and metanaysis was performed based on observational cohort studies published in the following databases: MEDLINE/ Pubmed, LILACS, COCHRANE Library and EMBASE, up to march 2016. The effectiveness outcomes assessed in this trial were overall survival (OS), progression free survival (PFS), pos-progression survival (PPS), response rate based on RECIST criteria and metastasectomy rate. The safety outcome assessed was adverse events. Review Manager 5.3 software was used to perform the data metanalysis and the Newcastle-Ottawa scale evaluated the methodological quality of the observational trials included. Results: 16 trials were included in this metanalysis, 11 evaluating effectiveness and 8 assessing safety. Their methodological quality were considered moderate according to the Newcastle-Ottawa Scale. Basically, this study compared bevacizumab based therapies with no bevacizumab based therapies, once there was no enough data regarding cetuximab and panitumumab. Overall, the group treated with bevacizumab based therapies did better than those in the no bevacizumab group, with OS mean difference (MD) of 4,41 (95% CI 1.75 to 7.07; p = 0.001; I² = 86%) and PFS MD of 3.19 (95% CI 0.42 to 5.96; p = 0,02 I² = 96%). The PPS MD was also statistically significant (MD = 5.90; 95% CI 2.59 to 9.21; p = 0,0005; I² = 82%). When safety was the outcome concerned, the group treated with bevacizumab had more hypertension and gastrointestinal perforation. There was no statistical difference between the groups regarding others side effects. Conclusions: This study showed a potential benefit in using bevacizumab as a part of the treatment of mCRC. Bevacizumab improved PFS, OS and PPS and these differences were statistically significant. However, the drug also increased treatment related toxicities.
A phase I study of the safety and immunogenicity of a multipeptide personalized genomic vaccine in the adjuvant treatment of solid cancers.
Authors: Chrisann Kyi, Rachel Lubong Sabado, Ana Blazquez, Marshall R. Posner, Eric Michael Genden, Brett A. Miles, Hooman Khorasani, Peter Remsen Dottino, Hanna Irie, Elisa R. Port, Andrea S Wolf, Hearn J. Cho, Samir S. Parekh, John Mandeli, Matthew Galsky, William K. Oh, Sacha Gnjatic, Eric E. Schadt, Philip Adam Friedlander, Nina Bhardwaj
Journal: Journal of Clinical Oncology (2017)

TPS3114 Background: Mutation-derived tumor antigens (MTAs) arise as a direct result of somatic variations, including nucleotide substitutions, insertions, and deletions that occur during carcinogenesis. These somatic variations can be characterized via genetic sequencing and used to identify MTAs. We propose a platform for a fully-personalized MTA-based vaccine in the adjuvant treatment of solid tumors. Methods: This clinical trial is a single-arm, open label, proof-of-concept phase I study designed to test the safety and immunogenicity of the Personalized Genomic Vaccine 001 (PGV001). The single-center study will enroll 20 eligible subjects with histological diagnosis of the following tumor types: (a) head and neck squamous cell cancer, (b) non-small cell lung cancer, (c) ductal or lobular breast cancer, (d) serous carcinoma of the ovary, uterine adnexa, (e) urothelial carcinoma of renal pelvis or bladder, (f) cutaneous squamous cell cancer. Subjects must have no measurable disease at time of first vaccine administration, and 5-year disease recurrence risk of &gt; 30%. Patients will receive 10 doses of PGV001 as well as 10 doses of poly-ICLC (toll-like receptor-3 agonist, vaccine adjuvant), administered 1 day after PGV001 vaccination. Toxicity (endpoint 1) will be defined by Common Terminology Criteria for Adverse Events v5.0. Blood samples will be collected at various time points for immune response monitoring of MTA-specific humoral and cellular immune responses. For each patient, immunogenicity (endpoint 2) will be defined as an epitope-specific T cell response, detectable in peripheral blood samples after PGV001 vaccination. The change in the frequency of vaccine-induced epitope-specific T lymphocyte populations post-vaccination relative to baseline will be determined using mixed effects linear regression modeling. Conclusions: Our clinical trial will test for the first time the safety and immunogenicity of PGV001 in patients with multiple solid cancers. The information learned from this clinical trial will instruct the next generation of MTA-based vaccines, future development of immunotherapeutic approaches and rational combinations. Clinical trial information: NCT02721043.
Eosinophil-cationic protein: A novel liquid prognostic biomarker in melanoma.
Authors: Alvaro Moreira, Annika Krueckel, Gerold Schuler, Lucie Heinzerling
Journal: Journal of Clinical Oncology (2018)

e21573 Background: The prognostic role of eosinophils is still unclear with a trend towards longer survival for melanoma patients with eosinophilia at any point in their course of disease. However, eosinophil count at initial diagnosis of metastatic disease does not predict survival. Since eosinophil cationic protein (ECP) might mediate anticancer effects, such as tissue remodeling and cytotoxic activity, this marker was investigated as early prognostic marker preceding eosinophilia. Methods: Serum of 56 melanoma patients was collected at the time of diagnosis of metastatic disease. ECP levels as measured by ELISA were correlated with overall survival (OS) in patients before systemic therapy with immunotherapy or chemotherapy. Statistical analyses were performed using the Log–Rank (Mantel–Cox) test and Gehan-Breslow-Wilcoxon test. Results: The median OS for patients with high serum ECP above 10 ng/ml was 13 months, compared to 32 months for patients with ECP below this threshold (p = 0.0001). This striking survival difference was observed independently of the consecutive therapy. ECP levels were not correlated with LDH levels. Conclusions: ECP is a novel prognostic serum marker for predicting the outcome of melanoma patients which is independent of LDH and easy to perform in clinical practice. The negative prognostic value of high ECP level is unanticipated.
Laparoscopic versus open surgery for advanced gastric cancer.
Authors: Guoxin Li, Jiang Yu, Changming Huang, Yihong Sun, Xiangqian Su, Hui Cao, Jiankun Hu, Kuan Wang, Jian Suo, Kaixiong Tao, Xianli He, Hongbo Wei, Mingang Ying, Weiguo Hu, Xiaohui Du, Yanfeng Hu, Ziyu Li, Hao Liu, Pingyan Chen, Jiafu Ji
Journal: Journal of Clinical Oncology (2018)

4058 Background: Laparoscopic distal gastrectomy for early gastric cancer is widely accepted with superiority to conventional open surgery. However, oncologic validation for advanced gastric cancer is still being debated. We conducted a multi-center, randomized, controlled trial to compare 3-year disease-free survival (DFS) rates after laparoscopic distal gastrectomy with D2 lymphadenectomy and open surgery for advanced gastric cancer. Methods: Between September 2012 and December 2014, we randomly assigned 1056 patients with clinical stage T2, T3, or T4a gastric cancer, without bulky nodes or distant metastases to undergo either laparoscopic or open distal gastrectomy with D2 node dissection in a 1:1 ratio. The primary end point was 3-year DFS rate. Results: At 3 years, the DFS rate were 76.5% in the laparoscopic group and 77.8% in the open group; the hazard ratio (HR) for recurrence was 1.069. The 3-year overall survival rates were similar in the two groups (83.1% in the laparoscopic group and 85.2% in the open group; HR for death, 1.162). The clinical recurrence types were comparable between two groups (P = 0.213). Conclusions: The long-term oncological outcomes of laparoscopic distal gastrectomy with D2 lymphadenectomy were non-inferior to those of the conventional open surgery for the patients with advanced gastric cancer. (CLASS-01 trial) Clinical trial information: NCT01609309.