tbuckley/cabot-search huggingface dataset:
Cetuximab with or without sorafenib in recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN).
Authors: Jill Gilbert, Michael J. Schell, Xiuhua Zhao, Barbara A. Murphy, Tawee Tanvetyanon, David N. Hayes, Missak Haigentz, Nabil F. Saba, Jorge J. Nieva, Jimena Perez, Justin A. Bishop, Christine H. Chung
Journal: Journal of Clinical Oncology (2013)

6047 Background: For patients with R/M SCCHN, cetuximab, a monoclonal antibody against EGFR, is approved as a single agent and has a survival benefit when combined with chemotherapy. We hypothesized that addition of sorafenib, a multi-kinase inhibitor of targets including VEGFR, to cetuximab may have greater clinical benefit than cetuximab alone. Methods: This trial was designed as a blinded, randomized phase II, placebo-controlled study of cetuximab at 400 mg/m 2 IV on day 1 followed by 250 mg/m 2 IV weekly plus placebo bid (Arm A) or cetuximab at the same dose and schedule plus sorafenib 400 mg po bid (Arm B), each in 21 day cycles. After 19 patients were enrolled, the trial was amended to remove the placebo (and blinding) due to issues with placebo tablet solubility. Target sample size was 84 patients with 83% power to detect a 2-month increase in PFS, the primary study endpoint. Interim analysis was planned at midpoint, requiring hazard ratio &lt; 1 to proceed to the second stage of study. Serum cytokine and tumor HPV ISH and p16 analyses were performed. Results: Of 56 patients (ages 26-74, 80% male) enrolled, 53 patients received treatment and 41 were evaluable for response. Of the patients who received therapy, 26 received cetuximab only (Arm A). For Arm A, the mean number of cycles delivered was 4.3 (range 1-16) and the mean for Arm B was 3.3 (range 1-11). The most common grade 3/4 AEs were fatigue (2 A, 1 B), hypertension (3 B), infusion reaction (both arms), and diarrhea (2 B). Arm A had 2 PRs and Arm B had 4 PRs. Median OS was 7 mo and 5.9 mo respectively. Median PFS was 3.1 mo for both arms. 24 patients had pre-treatment cytokine measurements. Of the 12 measured cytokines, high TGFB1 level was significantly correlated with inferior PFS (4.6 mo vs 1.6 mo), regardless of arm (p=0.015). 38 patients had tumors available for p16 staining (31 neg and 7 pos). 3 of 7 p16 pos were also HPV ISH pos. The p16 neg patients had significantly improved PFS (3.5 mo vs 1.6 mo) regardless of arm (p=0.032) but no difference in OS (p=1.0). Conclusions: Both arms demonstrated clinical activity although no significant difference was observed. However, a subset of patients with p16 neg tumors or low serum TGFB1 may have a greater benefit with cetuximab-based therapy. Clinical trial information: NCI-2012-02847.
Nonguideline concordant treatment of testicular cancer.
Authors: Pia Paffenholz, David Pfister, Axel Heidenreich
Journal: Journal of Clinical Oncology (2017)

407 Background: The management of testicular cancer requires a complex multimodal therapeutic approach. Despite the availability of regularly updated national and international guidelines on testicular cancer, treatment still differs between the institutions probably affecting the patients’ outcome. Our study aims to investigate frequently occurring errors regarding the diagnosis and therapy of testicular cancer in consideration of the current EAU guidelines. Methods: We performed a retrospective analysis including 129 patients diagnosed with testicular cancer that were referred to our department between 09/2015 and 10/2016. Patients’ age, histology, clinical stage, IGCCCG risk classification, treatment (surveillance, chemotherapy, radiotherapy, surgery) and follow-up were investigated and compared to the EAU guidelines’ recommendations. Results: Of the eligible 129 patients, 34 (26%) patients displayed a non-guideline concordant care. The most common error was undertreatment (47%), mostly due to missing chemotherapy cycles. Modified treatment and overtreatment occurred in 20% and 16% respectively, while inappropriate treatment (9%) and misdiagnosis (6%) were rarely seen. In secondary treated patients, non-guideline concordant therapy was observed more frequently compared to those patients receiving primary therapy (59% vs. 41 %). Almost all patients (93%) receiving a non-guideline concordant therapy suffered a relapse in contrast to 67% of patients that were treated according to the EAU guidelines. Conclusions: Non-adherence to the current EAU guidelines on testicular cancer appears to be a major problem in various testicular cancer treating institutions. In our study, the most frequent error was undertreatment, followed by modified treatment and overtreatment. Inappropriate therapy leads to a higher relapse rate and morbidity associated with a worse curative outcome.
Treatment patterns and impact of race in patients receiving first-line therapy for advanced penile squamous cell carcinoma (PSCC).
Authors: Charity Morgan, Gregory Diorio, Philippe E. Spiess, Guru Sonpavde
Journal: Journal of Clinical Oncology (2017)

413 Background: Treatment patterns and outcomes with first-line therapy for PSCC are unclear. We conducted a retrospective analysis of the NCDB to study this issue and evaluate prognostic factors in treated patients (pts). Methods: Data from the NCDB was obtained for pts diagnosed with clinical stage 4 PSCC from 1998-2011. The following variables were evaluated: age, Charlson Comorbidity Index (CCI), race, survival, socioeconomic status (SES) based on median income of area of residence and therapy. Treatment patterns were described. Multivariate analyses (MVA) were conducted to assess the impact of factors on survival of pts receiving therapy. Results: Of 14,395 pts with PSCC, 614 pts with stage 4 PSCC were evaluable with complete data. The mean age was 61.9 (range 22-90), 498 (81.1%) were white and 91 (14.8%) were black. 300 (48.7%) pts received no anti-cancer therapy, 245 (39.9%) received chemotherapy (+/- other therapy) and 69 (11.24%) received radiation (+/- non-chemotherapy agents). Pts in the chemotherapy group were significantly younger (mean age 58.8 years) than those in the radiation (63.5 years) or no therapy (64.1 years) group (p &lt; 0.001), but there were no significant differences in other variables between the 3 groups. The median survival from date of therapy of those in the chemotherapy and radiation groups were 9.75 and 8.65 months, respectively. MVA of pts who received therapy showed that non-white race (p = 0.006) and shorter time from diagnosis to therapy (p = 0.005) were significantly associated with poor survival, while chemotherapy, SES, age and CCI did not impact survival. Additionally, non-white race showed a trend for association with poor survival (p = 0.089) in those not receiving anti-cancer therapy. Conclusions: A minority of pts (39.9%) with stage 4 PSCC received chemotherapy in this large NCDB cohort, who were younger than those who received radiation or no therapy. The association of non-white race with poor survival suggests the impact of germline factors and disparities in therapy. The absence of significant impact of chemotherapy on survival in this real world PSCC cohort highlights unmet needs in this orphan disease and the need for discovery of effective agents.
Resource utilization (RU) and toxicities after carboplatin/etoposide/melphalan (CEM) and busulfan/melphalan (BuMel) for autologous stem cell rescue (ASCR) in high-risk neuroblastoma (HRNB).
Authors: Ami Vijay Desai, Yimei Li, Mallorie Heneghan, Yuan-Shung Huang, Brian Fisher, Adjoa Mante, Stephan A. Grupp, Nancy J. Bunin, Richard Aplenc, Rochelle Bagatell, Alix Eden Seif
Journal: Journal of Clinical Oncology (2015)

e21009 Background: High dose chemotherapy with ASCR is a key component of therapy for patients (pts) with HRNB, but the optimal ASCR regimen is not defined. CEM is the current US standard; however, European data suggest that BuMel may improve outcomes with less toxicity. Published data regarding toxicities associated with CEM and BuMel within current-era HRNB therapy are limited. Methods: Pts with HRNB who underwent single ASCR with CEM or BuMel from 6/1/10-6/30/13 were identified in the Pediatric Health Information System (PHIS) database. RU data for 60 days (d) from the start of BuMel or CEM were compared using a Wilcoxon 2-sample test. A retrospective chart review of contemporaneously treated pts was conducted at Children’s Hospital of Philadelphia (CHOP) to evaluate toxicities that could not be identified in PHIS, such as sinusoidal obstruction syndrome (SOS). Data were analyzed using Fisher’s exact test. Results: Total inpatient days were greater in the PHIS BuMel group (n=59) than in the CEM group (n=171; Table); there was no difference in ICU-level days. Total days of mechanical ventilation and diuretic use were higher after BuMel. Antibiotic and antihypertensive use was more frequent after CEM. There were no differences in opiate, parenteral nutrition, dialysis, or vasopressor days. In the CHOP cohort, 1/13 CEM (8%) and 5/21 (24%) BuMel pts developed SOS (p=0.37). Mean time from ASCR to SOS was 20d for BuMel and 13d for CEM. Pulmonary hypertension (PHTN) occurred only after BuMel (n=4; 19%). Nearly half of CEM pts (46%) and no BuMel pts developed creatinine ≥2x baseline (p=0.001). Time to engraftment and ASCR related mortality were similar. Conclusions: RU associated with pain control, nutrition, and ICU-level care was similar in HRNB pts receiving CEM and BuMel. CHOP data suggest that SOS and PHTN following BuMel may in part explain the longer hospital stays of BuMel pts. Evaluation of SOS in a larger cohort of BuMel pts is needed. Monitoring for PHTN after BuMel may be warranted. PHIS Mean RU days. Resource CEM BuMel p Inpatient days 31 35 0.01 Ventilation 1 3 0.02 Diuretics 7 12 0.04 Antibiotics 32 23 0.002 Antihypertensives 7 2 0.002
Can frequency of prostate biopsy on active surveillance be reduced without significantly increasing risk?
Authors: Gregory Auffenberg, Christine Barnett, Zian Cheng, Fan Yang, Jiachen Wang, David Christopher Miller, James E. Montie, Mufaddal Mamawala, Brian Denton
Journal: Journal of Clinical Oncology (2017)

e546 Background: The goal of this investigation is to use longitudinal Active Surveillance (AS) data to identify whether biopsies could be eliminated from a 10-year AS plan calling for annual biopsy without substantially prolonging the time to detection of prostate cancer (CaP) grade progression. Methods: With data from 1,500 men with very-low or low-risk CaP enrolled in AS at Johns Hopkins, we developed a hidden Markov model to estimate probabilities of progression to Gleason 7 or higher. We then simulated all potential AS biopsy strategies where it was assumed biopsy would be performed no more often than annually and either would or would not be performed each year after diagnosis. For every strategy the model was used to predict the average time from occurrence to the detection of grade progression. Potential alternatives to annual biopsy were identified. Results: The estimated 10 year probability of grade progression was 40.0% and the annual probability was 4.0%. Simulation of an annual biopsy strategy estimated that for men who experience grade progression the mean time from occurrence to detection would be 14.1 months. Alternative strategies that reduced the number of biopsies received over 10 years increased the time to detecting grade progression; however several strategies eliminated biopsies with only small increases in the time to detecting grade progression (Table). For instance, a strategy calling for 6 biopsies over 10 years (biopsies in years 1-3,5,7, and 8) would only increase the average time to detecting grade progression by 4.6 months while eliminating 4 biopsies. Conclusions: While annual biopsy was associated with the shortest interval to detecting grade progression, several alternative strategies may allow for less frequent biopsy without sizable increases in time to detecting grade progression. [Table: see text]
Treatment patterns and economic burden of illness in patients with advanced bladder cancer receiving second-line therapy.
Authors: Sumati Rao, Kyna McCullough Gooden, Pamela Landsman-Blumberg, Binglin Yue, Maria L. Lankford, Robert Dreicer
Journal: Journal of Clinical Oncology (2017)

320 Background: Second-line chemotherapies (SLCT) for bladder cancer (BC) are high in toxicity and yield low objective response rates resulting in low overall survival (OS). BC in general is an expensive malignancy to treat, but real-world SLCT treatment patterns and the associated burden of illness are absent from the published literature. The objective of this study was to describe chemotherapy regimens and evaluate the clinical and economic burdens of advanced BC in the second-line setting. Methods: Patients aged ≥18 years with newly diagnosed stage 3 or 4 BC (4/2011–9/2014) were identified from the Truven Health MarketScan Databases. Patients were continuously enrolled in health benefits 12 months before advanced diagnosis date through death, end of enrollment, or end of study period (12/2014) with no pre-diagnosis evidence of other primary cancers, HIV, or pregnancy. SLCT regimens, time on therapy, OS, and BC-specific resource use and costs were computed using the Kaplan-Meier sampling average method with bootstrap and reported from SLCT initiation to the end of available follow-up. Results: A total of 475 patients with advanced BC received SLCT (Table). Their median age was 64.0 years, 76% were male, and median duration of SLCT was 56 days. The median OS was 7.8 months from SLCT initiation and 15.8 months from the date of advanced diagnosis. Mean per-patient BC-specific medical costs from SLCT initiation were $54,226 (95% CI, $41,878–$63,055), of which 44% was attributable to chemotherapy and related services. Inpatient stays (35%) and other outpatient services (33%) were the other major contributors to medical costs. Conclusions: This is the first known study evaluating real-world advanced BC treatment patterns and costs in a nation-wide cohort of SLCT recipients.Immunotherapeutic agents recently approved and in development provide oncologists with additional treatment options for these patients. [Table: see text]
Presence of HLA-DR15, a Minor PNH Clone, or an Aplastic Anemia - Associated Autoantibody Do Not Predict a Favorable Response to Immunosuppressive Therapy in Children with Aplastic Anemia.
Authors: Hiroshi Yagasaki, Nao Yoshida, Naoto Hirano, Nobuhiro Nishio, Asahito Hama, Yue Wang, Yoshiyuki Takahashi, Seiji Kojima
Journal: Blood (2006)
Reduction in tumor size after the first course of cisplatin/etoposide (PE) in limited disease small-cell lung cancer (LD SCLC).
Authors: Bjørn Henning Grønberg, Nina Levin, Stein Sundstrøm, Øystein Fløtten, Odd Terje Brustugun, Paal Brunsvig, Roy M. Bremnes, Stein Kaasa, Tarje Onsoien Halvorsen
Journal: Journal of Clinical Oncology (2015)

e18553 Background: Combined chemotherapy and early thoracic radiotherapy (TRT) is the recommended treatment of LD SCLC. The definition of “early” varies. Some start TRT concurrent with the first chemotherapy-course (PE1), while others start after the second (or later). Starting TRT along with the second PE may allow tumors to shrink before TRT. In case, less normal tissue will be irradiated which might reduce toxicity and enable higher doses of TRT – which is believed to improve survival. The aim of this study was to investigate the reduction in tumor size after PE1 in LD SCLC. Methods: Patients from a randomized phase II trial were analyzed. All patients received 4 PE and TRT of either 45 Gy/30 fractions (twice daily) or 42 Gy/15 fractions (once daily). Lesions on baseline CT scans (CT1) and CT planning scans (CT2) conducted 2-3 weeks after PE1 were measured and evaluated according to RECIST 1.1. Results: CT scans were available for 146/157 patients. Median age was 63, 51% men, 84% had PS 0-1, 81% stage III, and 45% received 45 Gy. Mean number of days from CT1 to PE1 and from PE1 to CT2 were both 19 days. Mean sum of diameters (SOD) on CT1 was 84 mm (range 20 to 230). SOD increased by 4 mm in 1 patient and decreased in 142 patients (97%). There was a significant reduction of SOD (p < .001) with a mean change of -20 mm (4 to -71) corresponding to -24% (4% to -74%). According to RECIST 1.1, 98 (67%) had stable disease (SD) and 48 (33%) a partial response (PR). Median overall survival (OS) for all patients was 22.7 mos. Those with the greatest reduction in SOD had a longer median OS: 0-15% reduction (n = 39): 19.9 mos, 15-30% (n = 58): 21.9 mos, ≥ 30% (n = 48): 29.5 mos. Median OS for those who achieved SD was 21.7 mos; for those with PR 29.5 mos. In multivariate analyses adjusting for gender, age, stage of disease, performance status and TRT-schedule there were significant associations between OS and % reduction of SOD (p = .017) and RECIST-response (p = .032). Conclusions: Almost all patients had a reduction in tumor size after the first chemotherapy course, and 33% achieved a PR. The reduction in tumor size appeared to be large enough to influence the extent of radiotherapy fields. Response to PE1 was a significant, positive prognostic factor for survival.
춘계학술대회 발표 : 포스터 발표 ; 바이러스성 간염, B&C형 : Peptide Nucleic Acid-clamped PCR 및 MALDI-TOF RFMP를 이용한 YMDD 돌연변이 바이러스의 검출 및 라미부딘 치료전 혈청내 YMDD 돌연변이 바이러스의 출현빈도
Authors: 박영민, 지승일, 홍선표, 김수옥, 박상종, 유왕돈
Journal: Clinical and Molecular Hepatology (2006)
Genetic variants of genes in CCL5/CCR5 pathway to predict regorafenib-induced hand-foot skin reaction in patients with refractory metastatic colorectal cancer: A report of ethnic difference.
Authors: Mitsukuni Suenaga, Marta Schirripa, Shu Cao, Wu Zhang, Dongyun Yang, Lisa Salvatore, Sara Lonardi, Roberto Moretto, Beatrice Borelli, Yan Ning, Satoshi Okazaki, Martin D. Berger, Yuji Miyamoto, Roel Gopez, Diana L. Hanna, Afsaneh Barzi, Takeru Wakatsuki, Toshiharu Yamaguchi, Fotios Loupakis, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2017)

615 Background: CCL5/CCR5 pathway is involved in VEGF-A production and a recent study reported that serum CCL5 levels predict onset of hand-foot skin reaction (HFSR) due to regorafenib. We therefore tested whether genetic polymorphisms in the CCL5/CCR5 pathway predict onset of HFSR in patients with refractory metastatic colorectal cancer (mCRC) receiving regorafenib. Methods: Two independent cohorts treated with regorafenib were included in this study: a training cohort from Japan with 79 patients (median age 62 years, male 47%); and a testing cohort from Italy with 150 patients (median age 62 years, male 54%). Single nucleotide polymorphisms (SNPs) of genes in CCL5/CCR5 pathway ( CCL5, CCR5, PRCKD, CCL3, CCL4, KLF13, HIF1A) were selected for analyses using PCR-based direct sequencing. Adverse events were graded according to the CTCAE version 4.0. Comparisons of variants’ and adverse events’ distributions across two cohorts, and association between SNPs and adverse events were analyzed using contingency tables and Fisher’s exact test. Results: Grade 3 ≤ HFSR was more frequent in Japanese patients compared with Italian patients (32.9% vs. 16.0%, P= 0.004). The frequency of homozygous variant in CCL5 SNPs varied between Japanese and Italian patients (G/G variant in rs2280789, 21.5% vs. 1.3%, P&lt; 0.001; T/T variant in rs3817655, 22.8% vs. 2.7%, P&lt; 0.001). In the training cohort, patients with the G/G variant in rs2280789 had a higher incidence of grade 3 ≤ HFSR compared to those with any A allele (53% vs. 27%, P= 0.078); and the T/T variant in rs3817655 was significantly associated with onset of grade 3 ≤ HFSR compare to any A allele (56% vs. 26%, P= 0.026). These findings were not confirmed in the testing cohort, and no significant differences for toxicities were observed in the other candidate SNPs. Conclusions: Germline CCL5 polymorphisms in the CCL5/CCR5 pathway may serve as predictor of onset of severe HFSR in refractory mCRC patients receiving regorafenib. The different percentage of homozygote of CCL5 SNPs confers the ethnic difference in developing severe HFSR between Italian and Japanese patients.
Association of physical activity with cardiorespiratory fitness and cardiac function in cancer survivors with chemotherapy-related heart failure.
Authors: Karen Basen-Engquist, Carol Harrison, Daniel C Hughes, Elie Mouhayar, George Baum
Journal: Journal of Clinical Oncology (2014)

9598 Background: Studies have shown that physical activity can have a positive effect on cancer survivors, but there is scant research that addresses whether physical activity is beneficial to survivors who have chemotherapy related heart failure (CRHF). Methods: The purpose of this study was to evaluate the association between physical activity and cardiac function in cancer survivors with CRHF. There were 24 survivors, 20 were female, with a mean age of 54, 42% where white and the most common cancer site was breast (62.5%). The mean BMI was 30.5 and mean peak V02 was 13.1. B-type natriuretic peptide (BNP), troponin, ejection fraction and peak VO2 were measured at a baseline assessment. Patients also filled out the CHAMPS physical activity questionnaire. Correlations and regression models were used to determine if physical activity measured by the CHAMPS was associated with the CRHF measures and peak VO2. All regression models included gender, age, race and BMI. Separate models were run for CHAMPS total hours and CHAMPS hours of moderate or greater intensity activity. Results: Both total hours and hours of moderate or greater activity from the CHAMPS were significantly correlated with peak V02 (Total: R = .473, P = .026; Moderate or greater: R = .538, P = .010). There was no significant relationship between the CHAMPS activity variables and ejection fraction, BNP or Troponin. The regression models showed that BMI was a significant predictor of peak VO2 (B = -.253, P = .014) and CHAMPS moderate or greater intensity hours approached significance (B = .458, P = .062), but CHAMPS total hours was not a significant predictor. Age was the only variable to significantly predict BNP (B = 6.54, P = .017) and race (P = .05) was a significant predictor of ejection fraction with white subjects having higher values. There were no significant predictors of troponin. Conclusions: In this study, patients’ current physical activity levels were not related to measures of cardiac function. Current exercise and BMI were related to peak VO2 suggesting that despite the CRHF, cardiorespiratory fitness may improve with exercise. Future randomized trials should test the effects of exercise in survivors with CRHF.