tbuckley/cabot-search huggingface dataset:
Treatment of relapsed/refractory multiple myeloma with weekly cyclophosphamide plus bortezomib plus prednisone or dexamethasone (CyBor-P/D): Updated experience at Princess Margaret Cancer Centre (PMCC).
Authors: Donna Ellen Reece, Young Trieu, Esther Masih-Khan, Christine Chen, Vishal Kukreti, Giovanni Piza Rodriguez, Rodger Edwin Tiedemann, Suzanne Trudel
Journal: Journal of Clinical Oncology (2014)

e19568 Background: We previously defined the efficacy of CyBor-P, a 28-day regimen consisting of cyclophosphamide 300 mg/m2 (days 1,8,15, 22), bortezomib 1.5 mg/m2 (days 1,8, 15) and prednisone 100 mg q 2 days in a phase I/II trial involving patients (pts) with relapsed/refractory multiple myeloma (rel/refr MM) [Reece et al, JCO 2008; 26; 4777]. Variations of this regimen have since been reported (bortezomib weekly and replacement of prednisone with dexamethasone), along with its use as first-line therapy. Methods: We now retrospectively review our PMCC experience with CyBor-P/D in rel/refr pts who received ≥ 1 cycle of this regimen to gauge its effectiveness in the real-world setting. Results: Between 2007 and 2013, 98 pts with rel/refr MM received CyBor-P (prednisone 50-100 mg q 2 days) or CyBor-D (dexamethasone 20-40 mg/wk). Median age was 64 yrs (36-86); median # prior regimens was 2 (1-6), including ASCT (75%), bortezomib (28%) and IMiDs (85%). Median creatinine was 94 umol/L (range 53-900). Pts received a median of 5 cycles (range 1-47). Overall response rate (ORR) was 68%, with 42% achieving ≥ VGPR; 24% had stable disease. Median PFS was 14.9 mos (95% CI 12-17.9) and OS 24.2 mos (95% CI 20.2-28.1). Reasons for discontinuation included: progression (44%), planned 2ndASCT (11%), neuropathy (5%), cytopenias (4%), other (5%). The Table shows outcomes according to prior bortezomib exposure. There were no significant outcome differences between bortezomib-naïve pts, or pts treated at first vs. > first relapse. Cytogenetic data was incomplete but 9/15 (60%) del13q and 3/6 (50%) t(4;14) pts responded. Conclusions: 1) The ORR of 68% and PFS of 14.5 mos seen with CyBor-P/D in the real-world setting compare favorably with other 3-drug regimens; 2) CyBor-P/D is well-tolerated; 3) This regimen is effective as re-treatment in bortezomib-exposed pts. Patient Group N ORR (VGPR) Median PFS, mos Median OS, mos No prior bortezomib 61 68% (43%) 14.5 24.3 CyBor-P/D as induction before 2nd salvage ASCT 9 89% (33%) 20.8 Not reached Re-treatment after prior CyBor-P/D 13 53% (38%) 13.0 12 Re-treatment after other bortezomib regimen 14 72% (50%) 15.9 11.1
Dihydropyrimidine dehydrogenases (DPYD), and cytidine-deaminase (CDA) gene polymorphisms as genomic predictors of clinical outcome in resected gastric cancer patients (GCP) treated with fluoropyrimidine-based adjuvant chemotherapy
Authors: J. J. Grau, M. Monzo, C. Muñoz, J. A. Bombi, J. Domingo-Domenech, S. Jansa, L. Lema, R. Palmero
Journal: Journal of Clinical Oncology (2006)

4052 Background: Single nucleotide polymorphisms (SNPs) of DPYD gene induces DPD deficiency resulting in decreased activity of 5-fluorouracil derivatives in treatment of colorectal cancer patients (pts). In GCP has not been previously analysed. Methods: We analysed paraffin-embedded biopsies from 50 consecutive resected GCP who received adjuvant chemotherapy with four cycles of Mitomycin C (MMC), 20 mg/m 2 iv day 1 plus oral Tegafur (TG), 500 mg/m 2 day 1 to day 45 every six weeks, for SNPs of genes DPYD1 (A/G; Ile/Val), DPYD2 (C/T; Arg/Cys) and CDA (A/C; Lys/Gin). The status of alleles (wild type or at least 1 polymorphism) was correlated with outcome, overall survival (OS) and toxicity. Results: The status of SNPs frequencies according to the classification between wild type/non-wild type, were 36/14 in DPYD1; 26/24 in DPYD2; and 17/23 in CDA or between homozygous/heterozygous were 39/11 in DPYD1; 33/17 in DPYD2 and 26/24 in CDA respectively. After 77 months of median follow-up, 18 pts died of tumor relapse, (7 in peritoneum and 11 in distant organs). Difference in survival was observed in DPYD1 pts only, for non wild-type over wild-type (p = 0.0283) and in any of the 3 genes tested heterozygous over homozygous pts (p = 0.0463). In 10 pts (20%) total dose was reduced by toxicity (5 diarrhea, 2 neutropenia, 2 hepatotoxicity, 1 vomiting), only 3 of them were homozygous. Conclusions: SNPs of DPYD1, DPYD2 and CDA predict outcome, survival and toxicity of GCP treated with 5-FU-based adjuvant chemotherapy. No significant financial relationships to disclose.
Rhinovirus species/genotypes and interferon-λ: subtypes, receptor and polymorphisms – missing pieces of the puzzle of childhood asthma?
Authors: Annika Bergauer, Nina Sopel, Bettina Kroß, Tytti Vuorinen, Paraskevi Xepapadaki, Scott T. Weiss, Ashley Blau, Himanshu Sharma, Cornelia Kraus, Rebekka Springel, Manfred Rauh, Susanne Mittler, Anna Graser, Theodor Zimmermann, Volker O. Melichar, Alexander Kiefer, Marek L. Kowalski, Anna Sobanska, Tuomas Jartti, Heikki Lukkarinen, Nikolaos G. Papadopoulos, Susetta Finotto
Journal: European Respiratory Journal (2017)

The correspondence from C. Scagnolari and co-workers raises some interesting points that we could not address in a single manuscript, but were otherwise addressed in our Predicta study and will therefore be reported on in future. Analysis of systemic IFN-lambda, during asthma exacerbations, should complement IFN analysis in the airways <http://ow.ly/DkhV309HL6e>
Virtual weight loss program for African-American breast cancer survivors: Preliminary results.
Authors: Jeanne M. Ferrante, Michelle Doose, Alicja Bator, Katie Devine, Pamela Ohman Strickland, Alessandra Angelino, Jennifer Lee, Alison Koransky, Kevin Hwang, Elisa Bandera
Journal: Journal of Clinical Oncology (2017)

163 Background: Obesity is associated with higher breast cancer recurrence and death, and poorer health and quality of life. African-American (AA) women have the highest prevalence of obesity, obesity-related comorbidities, and breast cancer mortality compared with other racial/ethnic groups. Weight loss after breast cancer diagnosis may lower rates of recurrence and improve fitness, fatigue, and quality of life. Methods: This 6-month randomized controlled trial pilot-tests the use of a Fitbit activity tracker (Fitbit only group) versus Fitbit plus SparkPeople, a free web-based weight loss program (combined group) among 70 AA breast cancer survivors. Paired t-tests assess changes from baseline to 6-months among each participant in primary (weight, body mass index [BMI], percent body fat) and secondary (24-hour caloric intake, daily number of steps, quality of life, self-monitoring strategies, self-efficacy) outcomes. Two-group t-tests assess differences in outcomes between the two groups. Results: Currently, 36 of 46 (78.3%) eligible participants have enrolled and completed baseline assessments. Mean age of participants is 61.7 years (SD 8.7) and mean BMI is 36.9 (SD 7.0). Analyses of the first 25 participants who completed 3-month assessments (Fitbit only N = 12; combined group N = 13) show significant weight loss in both groups; Fitbit only: mean weight change -6.73 pounds, SD 4.61, p &lt; 0.001; mean BMI change -0.96 kg/m 2 , SD 0.84, p = 0.002; combined group: mean weight change -5.95 pounds, SD 5.84, p = 0.003; mean BMI change -1.03 kg/m 2 , SD 0.77, p &lt; 0.001. All participants significantly increased tracking of diet (Fitbit only p = 0.016; combined group p &lt; 0.001) and physical activity (Fitbit only p &lt; 0.001; combined group p = 0.001). Though not significant, combined group participants showed greater increases in self-efficacy for eating healthy and reducing fat and calories, and increases in daily steps (+1308 vs. +285 for Fitbit only group). Preliminary analyses show no statistically significant difference in changes in outcomes from baseline to 3 months between the two groups. Conclusions: Both programs show potential as convenient and efficient weight loss methods for African-American breast cancer survivors. Clinical trial information: NCT02699983.
Survival of U.S. Medicare patients with advanced non-small cell lung cancer by line of therapy.
Authors: John R. Penrod, Beata Korytowsky, Allison Petrilla, Juan P. Wisnivesky, Chris Craver, Mark Salvati, Dionne Hines, Prina Z Donga, Christopher Blanchette, Rolin L. Wade, Lucinda Strycker Orsini
Journal: Journal of Clinical Oncology (2014)

6582 Background: Prior real-world (RW) studies of advanced non-small cell lung cancer (adv NSCLC) have described overall survival (OS) from diagnosis (Dx) for all patients (pts) as well as separately by whether chemotherapy was received. More recently, innovations in systemic anti-cancer treatment (SATx) have expanded to include oral targeted agents. Current RW data on OS of advanced pts in the US are limited, particularly by line of therapy (LOT). In this study, we use data from a recent cohort of SEER-Medicare pts to examine OS from adv NSCLC Dx for all pts and separately by SATx status. For treated pts, we also describe OS from initiation of each LOT. Methods: Fee-for-service pts aged ≥66 enrolled in Medicare Parts A/B/D with an incident Dx of adv NSCLC (Stage IIIB/IV) during 2007–9 were identified in the SEER-Medicare linked database. OS follow-up was available through 12/31/2011. We examined demographic and clinical characteristics, including histology, and the receipt of SATx (chemotherapy, tyrosine kinase inhibitors, or monoclonal antibodies). We performed descriptive and Kaplan Meier (KM) analysis of OS from adv NSCLC Dx for all pts and separately by receipt of SATx. KM OS analysis by LOT was performed from date of treatment initiation. Results: Of 7,080 eligible pts, 26% had squamous, 51% had nonsquamous, and 24% had not otherwise specified histology; 28% of pts were Stage IIIB and 72% were Stage IV. Overall, 44% of pts received SATx. For all pts, median OS from Dx was 4.9 months, and 1- and 2-year OS rates were 23% and 7%, respectively (Table). Median OS from adv NSCLC Dx was 2.8 months for pts not receiving SATx and 9 months for pts receiving SATx (P<.0001). From initiation of each LOT, OS declined with each successive line, with median OS of 6.6, 5.9, and 5.3 months for 1L, 2L, and 3L, respectively. Conclusions: Despite advances in SATx for adv NSCLC, more than half of RW pts do not receive such treatment and outcomes for both treated and untreated pts remain poor, with fewer than 10% of pts alive at 2 years following Dx or initiation of SATx. OS of adv NSCLC pts. N (%) Median OS (months) 1-yr OS, % 2-yr OS, % All pts 7,080 (100) 4.9 23 7 SATx (from adv Dx) Yes 3,131 (44) 9.0 37 11 No 3,949 (56) 2.8 11 3 LOT 1L 3,113 (44) 6.6 28 8 2L 1,320 (19) 5.9 25 7 3L 535 (8) 5.3 21 5
The Mevalonate Pathway As a Metabolic Target to Circumvent Multidrug-Resistance in Chronic Lymphocytic Leukemia Cells
Authors: Marta Coscia, Micol Rigoni, Chiara Riganti, Ivana Campia, Candida Vitale, Valentina Griggio, Silvia Peola, Barbara Castella, Patrizia Sciancalepore, Daniela Drandi, Marco Ladetto, Amalia Bosia, Mario Boccadoro, Massimo Massaia
Journal: Blood (2011)
Long-Term Survival Analysis of the North American Intergroup Study C9011 Comparing Fludarabine (F) and Chlorambucil (C) in Previously Untreated Patients with Chronic Lymphocytic Leukemia (CLL).
Authors: Kanti R. Rai, Bercedis L. Peterson, Frederick R. Appelbaum, Martin S. Tallman, Andrew Belch, Vicki A. Morrison, Richard A. Larson
Journal: Blood (2009)
First-line chemotherapy plus cetuximab in patients grouped according to prognostic risk factors: Analysis of the CRYSTAL and OPUS studies.
Authors: Gunnar Folprecht, Eric Van Cutsem, Carsten Bokemeyer, Michael Schlichting, Steffen Heeger, Claus-Henning Kohne
Journal: Journal of Clinical Oncology (2012)

3591 Background: Analysis of randomized trials has shown that mCRC patients (pts) can be divided into prognostic risk groups according to baseline clinical parameters including ECOG performance status, white blood cell count (WBC), alkaline phosphatase (ALP) and number of metastatic (met) sites (Köhne C, et al. Ann Oncol 2002;13:308-17). The effect of adding cetuximab to first-line chemotherapy (CT) on overall survival (OS) in these groups of KRAS wild-type mCRC pts was investigated in the CRYSTAL and OPUS studies. Methods: Pt risk groups were: low-risk (LRG= ECOG 0/1, 1 met site) intermediate-risk (IRG= ECOG &lt;1, &gt;1 met site, ALP &lt;300 U/L or, ECOG&gt;1, low WBC, 1 met site) and high-risk (HRG= ECOG&lt;1, &gt;1 met site, ALP&gt;300 U/L or ECOG&gt;1, high WBC, or ECOG&gt;1, low WBC and &gt;2 met sites). Exploratory analyses comprised estimates of effects using Cox‘s proportional hazards model for OS on individual pt data and comparison of treatment arms by log-rank test. Results: Data are shown in the table. In the pooled analyses, in both treatment arms OS was longest in LRG pts and shortest in HRG pts. Adding cetuximab to CT led to marked improvements in OS in the HRG (Hazard ratio [HR] 0.765, 95% CI 0.506–1.157, p=0.203) and IRG (HR 0.781, 95% CI 0.622–0.981, p=0.033), while improvements in LRG pts (HR 0.869, 95% CI 0.672–1.124, p=0.287) were observed only after prolonged follow up. Data were similar in the separate CRYSTAL and OPUS studies. Conclusions: The analysis confirms the concept of prognostic risk groups for OS according to baseline clinical parameters in pts with KRAS wt mCRC. Benefit from the addition of cetuximab to first-line CT in terms of OS appears to be more pronounced in the IRG and HRG. [Table: see text]
EGFR mutation status in cerebrospinal fluid of NSCLC patients who developed leptomeningeal metastasis after EGFR-TKI treatment.
Authors: Jing Zhao, Xin Ye, Yun Sun, Zhenfan Yang, Guanshan Zhu, Minjiang Chen, Wei Zhong, Yan Xu, Li Zhang, Longyun Li, Yi Xiao, Mengzhao Wang
Journal: Journal of Clinical Oncology (2014)

8081 Background: Prognosis for these patients with leptomeningeal metastasis (LM) is very poor due to the lack of therapeutic options. It was suggested that the leptomeningeal space is protected from the systemic chemotherapy as well as EGFR-TKIs. Therefore, it would be interesting to explore the EGFR mutation status in CSF of the NSCLC patients who developed LM after the initial response to EGFR-TKI. In this study, we attempted to address two questions: 1. what is the EGFR mutation status in CSF of this group of patients? 2. what is the difference of EGFR mutation status in CSF as compared to that in the concurrent plasma samples? Methods: A highly sensitive droplet digital PCR (ddPCR) method was used to detect EGFR mutation in 7 CSF samples which were collected from seven patients with NSCLC who initially responded to EGFR-TKI and developed LM afterwards. Concurrent plasma samples were collected and analyzed as well for comparison. Results: EGFR-sensitive mutations were detected in CSF of all 7 patients (4 of 19-del and 3 of L858R), one of which (1/7, 14.3%) carried T790M mutation as well (19-del&T790M). EGFR mutations were not detected in plasma from 5 of these 7 patients (5/7, 71.4%). In additional plasma samples from remaining 2 patients, who were positive for EGFR E19-del in CSF, E19-del and T790M double mutations were detected. Conclusions: With development of LM after EGFR-TKI treatment, CSF remained positive for EGFR mutations dominant by sensitive mutations only, even though the plasma were either negative for EGFR mutations or carried TKI-resistant T790M mutation. This is supportive of the protection of EGFR mutation positive tumor cells within leptomeningeal space from the exposure to current EGFR-TKIs. EGFR mutation status of matched CSF and plasma samples from NSCLC patients who developed LM after initial response to EGFR-TKI treatment. Patient ID EGFR mutation status CSF Plasma 1 19-del N 2 L858R N 3 L858R N 4 19-del&T790M N 5 L858R N 6 19-del 19-del&T790M 7 19-del 19-del&T790M
Zika Virus Transmission — Region of the Americas, May 15, 2015–December 15, 2016
Authors: Juniorcaius Ikejezie, Craig N. Shapiro, Jisoo Kim, Monica Chiu, Maria Almiron, Ciro Ugarte, Marcos A. Espinal, Sylvain Aldighieri
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Zika virus, a mosquito-borne flavivirus that can cause rash with fever, emerged in the Region of the Americas on Easter Island, Chile, in 2014 and in northeast Brazil in 2015 (1). In response, in May 2015, the Pan American Health Organization (PAHO), which serves as the Regional Office of the Americas for the World Health Organization (WHO), issued recommendations to enhance surveillance for Zika virus. Subsequently, Brazilian investigators reported Guillain-Barré syndrome (GBS), which had been previously recognized among some patients with Zika virus disease, and identified an association between Zika virus infection during pregnancy and congenital microcephaly (2). On February 1, 2016, WHO declared Zika virus-related microcephaly clusters and other neurologic disorders a Public Health Emergency of International Concern.* In March 2016, PAHO developed case definitions and surveillance guidance for Zika virus disease and associated complications (3). Analysis of reports submitted to PAHO by countries in the region or published in national epidemiologic bulletins revealed that Zika virus transmission had extended to 48 countries and territories in the Region of the Americas by late 2016. Reported Zika virus disease cases peaked at different times in different areas during 2016. Because of ongoing transmission and the risk for recurrence of large outbreaks, response efforts, including surveillance for Zika virus disease and its complications, and vector control and other prevention activities, need to be maintained.
Genetic variations in STK11, PRKAA1, and TSC1 associated with prognosis for patients with colorectal cancer.
Authors: Jong Gwang Kim, Yee Soo Chae, Byung Woog Kang, Soo Jung Lee, Jongwon Seo, Hyo-Sung Jeon, Gyu Seog Choi
Journal: Journal of Clinical Oncology (2014)

e22230 Background: Assuming an association between cancer and metabolism, oncogene-directed metabolic reprogramming in cancer has revealed new target strategies. For example, the LKB1-AMPK-mTOR signaling pathway genes are already known to alter the cell metabolism and to play a critical role in the malignant behavior of cancer. Accordingly, based on the assumption that genetic variations in the LKB1-AMPK-mTOR signaling pathway can change the intracellular signal in terms of metabolic reprogramming, the present study analyzed 18 single nucleotide polymorphisms (SNPs) of the STK11, PRKAA1, TSC1/2, and mTOR genes and their impact on the survival of patients with colorectal cancer. Methods: 772 consecutive patients with surgically resected colorectal adenocarcinoma were enrolled in the present study. 18 SNPs were selected from an in Silico analysis based on previous evidence of association. The SNP genotyping was performed using a Sequenom MassARRAY. Results: With a median age of 64 years, 433 (56.1%) patients were diagnosed with colon cancer and 333 (43.1%) with rectal cancer. The pathologic stages after surgical resection were as follows: stage I (n=139, 18.0%), stage II (n=318, 41.2%), and stage III (n=315, 40.8%). Among the 18 polymorphisms, three SNPs (PRKAA1 rs461404, STK11 rs741765, and TSC1 rs13295634) were significantly associated with disease-free survival (DFS). Moreover, a multivariate analysis showed that the TT genotype of PRKAA1 rs461404, GG genotype of STK11, and TG or GG genotype of TSC1 were identified as independent prognostic factors for a worse DFS (HR=1.408, 1.398, and 1.388; P=0.013, 0.030, and 0.002, respectively) and overall survival (OS) (HR=1.680, 1.431, and 1.394; P=0.001, 0.038, and 0.009, respectively). Conclusions: The present results suggest that genetic variants of the PRKAA1, STK11, and TSC1 genes could be used as prognostic biomarkers for Korean patients with surgically resected colorectal cancer.
Phase I/II study of preoperative (pre-op) short course chemoradiation (CRT) with proton beam therapy (PBT) and capecitabine (cape) followed by early surgery for resectable pancreatic ductal adenocarcinoma (PDAC) of the head.
Authors: Theodore S. Hong, David P. Ryan, Darrell R. Borger, Lawrence Scott Blaszkowsky, Beow Yong Yeap, Vikram Deshpande, Jennifer Yon-Li Wo, Raymond Couric Wadlow, Eunice Lee Kwak, Jill N. Allen, Jeffrey W. Clark, Andrew X. Zhu, Cristina Ferrone, Harvey J. Mamon, Judith A. Adams, Barbara Winrich, Tarin Grillo, Thomas F. DeLaney, Carlos Fernandez-del Castillo
Journal: Journal of Clinical Oncology (2012)

4021 Background: Standard adjuvant 6 week CRT may delay and reduce tolerability of adjuvant gemcitabine-based chemotherapy. We explore the safety and efficacy of a one-week course of pre-op CRT with PBT and cape followed by early pancreaticoduodenectomy (PD). Methods: Patients with radiographically resectable, biopsy-proven PDAC of the head were enrolled from May 2007-December 2010 on this prospective, NCI-sponsored clinical trial. Eligibility included no CT involvement of SMA or celiac artery; No metastatic disease. Dose level 1 consisted of PBT delivered 3 Gy x 10. Pts in subsequent dose levels received 5 Gy x 5 in progressively shortened schedules: level 2 (wk 1 M W F, wk 2 T Th), level 3 (wk 1 M T Th F, wk 2 M), level 4 (wk 1 M-F). PBT was targeted at pancreatic mass with elective nodal coverage. Pts received Cape 825 mg/m2 BID wk 1 and 2 M-F. Surgery was performed 1-6 wks after completion of cape. Patients were recommended to receive 6 mo of gemcitabine after surgery. Genotyping of 15 genes (including KRAS, PIK3CA, BRAF, NRAS, TP53, IDH1) was performed. Results: 50 pts were enrolled on study. 48 patients are eligible for this analysis. 3 pts were treated at each of dose levels 1-3. 6 pts were at dose level 4, which was selected as MTD. No DLTs were observed. 35 patients were treated in the phase II portion at the MTD. Gr 3 toxicity was noted in 2 pts (chest wall pain-1, colitis-1). 38 pts underwent PD. Reasons for no PD were: metastatic disease-9, unresectable tumor-1. Mean post-op length of stay was 7 days (range 5-47). 6/38 (16%) resected pts had positive margins. 28/38 (74%) had positive nodes. Median follow up is 21 months among the 19 patients still alive. 4/48 (8%) local failures in ALL patients. mOS and mPFS are 18 and 10 months respectively for ALL patients and 27 and 14 months for RESECTED patients. Of 28 patients with genotype data available, 22 (79%) had KRAS mutations. 10/22 KRAS mt and 4/6 KRAS wt pts are alive. Conclusions: Pre-op CRT with 1 wk of PBT and capecitabine followed by early surgery is well tolerated and associated with favorable local control. Complete genotype and DPC4 data will be presented at the meeting.