tbuckley/cabot-search huggingface dataset:
Comparative health care (HC) costs in patients (pts) with metastatic melanoma (mM).
Authors: Chun-Lan Chang, Yeun Mi Yim, Julie Munakata, Prina Z Donga, Carolina M. Reyes, Vernon F Schabert
Journal: Journal of Clinical Oncology (2014)

9007 Background: Advances in mM have increased treatment (tx) options, where previously, few therapies were available. This study compares HC and adverse event (AE) costs in a U.S. managed care population of mM pts. Methods: This retrospective study used a large claims database comprised of 55 U.S health plans. mM pts who initiated treatment with vemurafenib (VEM), ipilumimab (IPI), dacarbazine (DTIC), paclitaxel (PAC) or temozolomide (TMZ) from 7/2009-9/2012 were identified. A treatment episode (TE) was defined as time from index date to addition or switch to different study drug, or a gap >45 days (>112 days for IPI). Adverse events (AEs) were selected if reported in package inserts (Grade 3/4 occurring ≥5%) and identified by ICD-9 codes occurring within TEs and 30 days after end of TEs. All-cause costs for TEs and AEs were normalized as monthly costs. Multivariate regression models with repeated measures were used to estimate adjusted monthly HC and AE costs. Results: The study identified 541 mM pts with mean (SD) age of 57.5 (11.5) years; 62.1% were male; 49.0% had >3 sites of metastases. A total of 809 TEs (VEM:143; IPI:147; DTIC:89; PAC:139; TMZ:291) were identified. Total mean (SD) all-cause costs for VEM were $77,687 (60,329); IPI $153,062 (134,048); DTIC $35,243 (33,641); TMZ $42,870 (41,384); PAC $58,991 ($81,306). Adjusted mean monthly TE costs for VEM was significantly lower than IPI and comparable to other mM drugs. VEM had significantly lower monthly AE costs than all other study drugs (Table). Conclusions: HC costs were highest for IPI, followed by TMZ, VEM, PAC and DTIC. This study is amongst the 1st economic analyses to include recently approved therapies in mM. In combination with safety and efficacy findings, these results may assist clinicians, policy makers and managed care organizations with treatment strategies in mM. VEM IPI DTIC TMZ PAC TE length, mean (median) days 138 (124) 72 (73) 69 (54) 87 (63) 100 (76) Adjusted monthly costs, mean (95% CI) TE $17,223 ($16,966−$17,480) $65,313 ($64,338−$66,288) $16,123 ($15,882−$16,363) $17,885 ($17,618−$18,152) $16,941 ($16,688−$17,194) AE $2,259 ($2,209-$2,309) $4,628 ($4,526-$4,730) $9,415 ($9,207-$9,622) $3,189 ($3,118-$3,259) $8,261 ($8,079-$8,444)
Identification of pharmacogenetic target genes associated with chemotherapy-induced peripheral neuropathy.
Authors: Masaaki Komatsu, Heather E. Wheeler, Claudia Wing, Shannon Delaney, M. Eileen Dolan
Journal: Journal of Clinical Oncology (2013)

e13541 Background: Chemotherapy-induced Peripheral Neuropathy (CIPN) is a dose-limiting toxicity of many anticancer drugs, including taxanes, vinca alkaloids and platinating agents. There are no effective means to predict which patients are at risk for CIPN nor are there effective treatments. Therefore, we have used a whole genome approach in lymphoblastoid cell lines (LCLs) alone or combined with clinical study data to identify target genes associated with CIPN that we tested further in Neuroscreen-1 (NS-1: rat pheochromocytoma) cells and human neurons derived from induced pluripotent stem cells (iCell neurons). Methods: For selecting candidate target genes, we compared published genome-wide association studies (GWAS) results of sensory peripheral neuropathy in cancer patients receiving paclitaxel with GWAS results of pharmacologic phenotypes in LCLs after paclitaxel treatment. We evaluated neurotoxic drug-induced cell growth inhibition using Cell Titer Glo and neurite parameters of outgrowth, processes and branching through imaging following transient knockdown of target genes in NS-1 cells and iCell neurons. Results: After treatment of paclitaxel, vincristine and cisplatin, iCell neurons showed decrease of neurite outgrowth, processes and branching. Whereas, these parameters did not decrease for hydroxyurea, which is not reported to induce neuropathy. Through transient knockdown in NS-1 cells of RFX2, a gene identified through clinical and preclinical studies to be associated with paclitaxel-induced neuropathy, sensitivity to paclitaxel increased as measured by a decrease of neurite outgrowth. Conclusions: These findings imply our model system could identify pharmacogenetic target genes associated with CIPN. These genes have potential for biomarkers or therapeutic targets and enable future personalized treatments for cancer patients at risk for CIPN.
Randomized study of tailored neoadjuvant chemotherapy according to the expression of tau, topo II α, and ERCC1 versus standard chemotherapy in HER2-negative breast cancer.
Authors: Yen-Shen Lu, Dah-Cherng Yeh, Ling-Ming Tseng, Shou-Tung Chen, Huang-Chun Lien, Hong-Tai Chang, Yuan-Ching Chang, Shu-Min Huang, Ching-Hung Lin, Ann-Lii Cheng, Chiun-Sheng Huang
Journal: Journal of Clinical Oncology (2015)

1025 Background: We hypothesized that selecting chemotherapy (CT) agents according to the expressions of drug sensitivity predictive biomarkers from tumor sample may improve the treatment efficacy for breast cancer (BC). Methods: Patients (pts) with stage II/III HER2 negative BC were eligible. Tumor biopsy samples were tested with immunohistochemistry study for the expression of tau, topo II α, and ERCC1. Four cycles of neoadjuvant CT were given after randomization, followed by operation. For control arm, Docetaxel (T)/ epirubicin (E) was given. For tailored arm, 1 of the 7 different CT regimens that containing 2 drugs among T, E, cisplatin, vinorelbine, and weekly high dose 5FU/leucovorin were given according to the expression of tumor biomarkers. After operation, 2-4 cycles of adjuvant CT were given and the choice of regimens were at investigators discretion. The primary endpoint was the primary tumor (T) pathological complete response (pCR) rate, and 268 pts were planned to be recruited. In the pre-planned interim analysis after recruitment of 60% of pts, the independent data monitoring committee decided to stop the recruitment because the difference between the two arms was too small to continue this study. Results: From April 2009 to March 2014, a total of 161 pts were enrolled, 78 and 83 of them were randomized to control arm and tailored arm, respectively. Median age was 49, 111 (68.9%) pts were ER positive, 65 (40.4%) pts were stage III. Among the tailored arm, 58 (69.9%), 41 (49.4%), and 64 (77.1%) of pts were positive for tau, topo II α, and ERCC1, respectively. The results of efficacy were listed in table. There were significantly higher incidence of grade 3/4 leukopenia (11.7% vs. 4.4%) and febrile neutropenia (2.9% vs. 0.3%) in control arm. Conclusions: Using the strategy of tailored CT according to the expression of tau, topo II α, and ERCC1 did not increase the efficacy neoadjuvant CT in BC. Clinical trial information: NCT00776724. T pCR T+N pCR Clinical response (CR+PR) 3-year event free survival Control arm 5 (6.4%) 5 (6.4%) 63 (80.8%) 74.6% Tailored arm 6 (7.2%) 3 (3.6%) 45 (54.2%) 77.5% p value 1.000 0.483 0.0004 0.858* *Log-rank test of median survival, median follow up 37.7 ms.
Pomalidomide (POM) with or without low-dose dexamethasone (LoDEX) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Outcomes in pts refractory to lenalidomide (LEN) and/or bortezomib (BORT).
Authors: Ravi Vij, Paul Gerard Guy Richardson, Sundar Jagannath, David Samuel DiCapua Siegel, Rachid C. Baz, Shankar Srinivasan, Gail Larkins, Mohamed H. Zaki, Mohamad A. Hussein, Kenneth Carl Anderson
Journal: Journal of Clinical Oncology (2012)

8016 Background: Response and survival outcomesare poor in pts with RRMM who are refractory to BORT and immunomodulatory drugs. POM+LoDEX has demonstrated activity in pts with advanced multiple myeloma who have received multiple lines of therapy. This analysis evaluates outcomes in pts with disease refractory to LEN, BORT, or both, as well in pts with disease refractory to both LEN and BORT who had received prior transplant. Methods: In the MM-002 phase II trial, pts received POM (4 mg/day on days 1–21 of each 28-day cycle) alone (n=108) or in combination with LoDEX (40 mg/week) (n=113). Refractory disease was defined as documented progression during treatment or within 60 days of the last dose of treatment. Response rates were assessed using European Group for Bone Marrow Transplantation (EBMT) criteria by independent adjudication committee. Results: Patients who received POM+LoDEX were refractory to LEN (77%), BORT (73%), or both (61%). Forty-two percent were refractory to both LEN and BORT and had received prior transplant. Overall, 20% of pts achieved ≥ PR, median PFS was 3.5 months, and 1-year survival rate was 59%. Response rates and duration were comparable in pts with disease refractory to LEN, BORT, or both, and in pts who had received prior transplant (response rate 25-34%, median duration of response 5.7-7 months). Survival outcomes were similar across the groups (median PFS 3.8-4.6 months; 1-year survival rate 60-67%). Conclusions: POM, given at 4 mg/day on days 1–21 of each 28-day cycle in combination with LoDEX, 40 mg/week, is effective in pts with RRMM refractory to LEN, BORT, or both, and including those with prior transplant. These results suggest a lack of cross-resistance between POM and LEN, and confirm activity not only in BORT-refractory pts but also those for whom transplant has failed. [Table: see text]
Baseline absolute neutrophil counts (ANC) and survival in second-line metastatic colorectal cancer (mCRC) patients (pts).
Authors: Axel Grothey, Josep Tabernero, Daniel S Mytelka, Li Li, Federico Nasroulah, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2017)

713 Background: Exploratory analyses from RAISE (NCT01183780), FOLFIRI with ramucirumab or placebo in previously treated mCRC pts, suggested pts with treatment-emergent neutropenia may have improved overall survival (OS) compared to pts who did not experience neutropenia on study (Ciuleanu T, et al. abst. 2475, ESMO 2016). Subsequent analyses suggested an even stronger association between baseline ANC and OS, with high baseline ANC associated with shorter OS. A retrospective observational study was conducted to test this association as a pre-specified hypothesis. Methods: The IMS Oncology Database (electronic medical record data from US community practices) was used to identify pts ≥ 18 yrs with mCRC (ICD-9 code 153.x, 154.0 or 154.1) who initiated second-line fluoropyrimidine and irinotecan (+/- bevacizumab; bev) in 2007-2013, following progression during or after first-line fluoropyrimidine and oxaliplatin (+/- biologic). Eligible pts had ≥ 1 ANC in the 60 days prior to second-line therapy. Pts were stratified by second-line bev use and high/low baseline ANC ( ≥ or &lt; 5.5x10 9 /L) and matched by propensity scores. OS based on a validated proxy was analyzed using the Kaplan-Meier method and a Cox proportional hazards model, adjusted for age, gender, ECOG PS, stage, length of first-line treatment, and BMI. Results: 747 eligible pts were identified, of whom 617 were matched. Pts with baseline characteristic data had a median age of 59 yr, 57% were male, 67% were Caucasian, 74% had stage IV disease at diagnosis, and 63% had ECOG PS of 0/1 at start of second-line. Bev-treated pts with high baseline ANC (n = 122) had a median OS (mOS) of 7.7 mo vs 14.7 mo in pts with low baseline ANC (n = 323); adjusted HR 1.69 (95% CI, 1.35, 2.12; p &lt; 0.0001). Pts with high baseline ANC not treated with bev (n = 59) had a mOS 5.4 mo vs 14.4 mo in pts with low baseline ANC (n = 113); adjusted HR 2.73 (95% CI, 1.89, 3.93; p &lt; 0.0001). There was a modest interaction effect between bev treatment and baseline ANC (p = 0.012), indicating greater bev benefit in the high ANC group. Conclusions: Baseline ANC appears to be a strong prognostic factor and potentially a weak predictive factor for antiangiogenic therapy for OS in pts with previously treated mCRC.
Utilization of pelvic lymph node dissection for low-risk prostate cancer.
Authors: Parth K. Modi, Megan Bock, Sinae Kim, Eric A. Singer, Rahul Parikh
Journal: Journal of Clinical Oncology (2017)

86 Background: National guidelines suggest against pelvic lymph node dissection (PLND) for patients with low-risk prostate cancer (PCa). However, the actuarial rate of PLND in this population is unknown. This study aimed to characterize the use of PLND in contemporary cohort of men with low-risk PCa undergoing robotic assisted radical prostatectomy (RARP). Methods: The National Cancer Database was queried for PCa patients who underwent RARP from 2010 to 2013. Patients who underwent PLND were identified and patient clinicodemographic and hospital characteristics were abstracted. The primary outcome measure was receipt of PLND. Secondary outcome measures included number of lymph nodes evaluated and number of lymph nodes positive for cancer. Unadjusted and multivariate regression analyses were conducted to identify predictors of receipt of PLND. Analysis of clustered data was employed to account for hospital-level correlation in utilization. Results: Of 51,971 patients with low-risk PCa who underwent RARP, 19,059 (36.7%) received PLND. Lymph node positivity was identified in 0.4% of low-risk patients and 4.6% of intermediate/high risk patients. Predictors of PLND in low-risk patients included rural residence (OR 1.157), treatment at academic institutions (OR 1.492) or high-volume (OR 1.327) facilities. Mean number of lymph nodes obtained in low-risk patients was lower than in intermediate- or high-risk patients (4.74 vs 5.86, P &lt; 0.0001). In multivariate analysis, black race was associated with significantly fewer lymph nodes retrieved. Intermediate or high risk PCa; rural residence; and treatment at an academic, high-volume, or West region facility were independently associated with a higher yield of retrieved lymph nodes. Conclusions: PLND is performed for greater than one-third of low-risk PCa patients undergoing RARP in this large hospital-based data set. Our study demonstrated a low likelihood (0.4%) of detecting nodal metastasis in this population, thus validating the national recommendations against PLND. Rural residence and treatment at high-volume and academic centers are associated with receipt of PLND. Reasons for the variation in practice patterns should be investigated to improve the quality of PCa care.
Childhood cancer in families with and without germline BRCA1/2 mutations ascertained at a high-risk breast cancer clinic
Authors: G. A. Brooks, J. E. Stopfer, J. Erlichman, R. Davidson, K. L. Nathanson, S. M. Domchek
Journal: Journal of Clinical Oncology (2006)

10013 Background: Germline mutations in the BRCA1 and BRCA2 genes (BRCA1/2) are associated with breast cancer, ovarian cancer and other malignancies. Biallelic mutations of BRCA2 are a cause of Fanconi anemia and characteristic childhood cancers. We undertook this study to evaluate the contribution of familial heterozygous BRCA1/2 mutations to childhood cancer in hereditary breast cancer families. Methods: We conducted a retrospective cohort study to compare the prevalence of childhood cancers among 379 families with BRCA1/2 mutations and 426 families without known mutations. All families were ascertained at a high-risk breast cancer clinic. Our study and comparison cohorts included first- through fourth-degree relatives of cancer-affected mutation carriers and cancer-affected individuals with negative full sequencing for BRCA1/2 mutations. The primary endpoint was any case of childhood cancer (diagnosed &lt;age 21) as recorded in the family history. Results were analyzed using Fisher’s exact test. Results: 20 cases of childhood cancer were observed in 379 families with BRCA1/2 mutations and 35 cases of childhood cancer were observed in 426 families with negative mutation testing (p = 0.12). Apart from two very early-onset breast cancers, the types of childhood cancers occurring in the BRCA1/2 mutation positive families were similar to those occurring in the mutation negative families and in the general population. Nine childhood cancers occurred in 240 families with BRCA1 mutations, and 11 childhood cancers occurred in 141 families with BRCA2 mutations (p=0.1). 13 of 18 BRCA1/2 mutation positive families with cases of childhood cancer (72%) and 13 of 31 families with childhood cancer cases and negative mutation testing (42%) met the Birch clinical criteria for Li-Fraumeni like syndrome (LFL); no individual has undergone testing for germline TP53 mutations. Conclusions: Heterozygous BRCA1/2 mutations do not appear to be a significant risk factor for childhood cancer in hereditary breast cancer families. This observation supports the current practice of delaying BRCA1/2 mutation testing until candidates reach adulthood. Although many families in both groups met criteria for LFL, the clinical significance of this finding is uncertain. No significant financial relationships to disclose.
Diagnostic and prognostic significance of a t(1;19)(q10;p10) in patients (pts) with low-grade oligodendroglioma and astrocytoma: NCCTG 94–72–53
Authors: R. B. Jenkins, K. V. Ballman, C. Giannini, R. M. Arusell, H. Blair, S. Passe, H. Flynn, P. Brown, E. G. Shaw, J. C. Buckner
Journal: Journal of Clinical Oncology (2006)

1505 Background: Combined deletion of chromosomes 1p and 19q is associated with improved prognosis in pts with anaplastic oligodendroglioma. We recently discovered that the combined deletion is mediated by a chromosome 1;19 translocation: t(1;19)(q10;p10). The prognostic significance of this alteration in pts with low-grade gliomas is not known. Methods: Paraffin-embedded tumor tissue was obtained from 134 pts enrolled in two NCCTG trials for newly-diagnosed low-grade glioma: 86–72–51: a randomized phase III trial of 50.4 Gy vs 64.8 Gy radiation therapy (RT) and 93–72–02: a phase II trial of PCV for 6 cycles followed by RT. Interphase fusion of a CEP1 probe and a BAC contig probe for 19p12 was used to detect the 1;19 translocation. Analysis of 1p and 19q deletions had been previously performed by FISH. Kaplan-Meier distributions of overall survival (OS) and progression-free survival (PFS) for pts whose tumors did or did not exhibit CEP1/19p12 fusion were compared using the Wilcoxon test. Results: Of 134 pts, CEP1/19p12 fusion testing was informative for 92. CEP1/19p12 fusion prevalence was 55% among 42 oligodendrogliomas, 47% among 30 mixed oligoastrocytomas, and 5% among 20 astrocytomas. 91% of gliomas with and 11% without 1p/19q deletion had CEP1/19p12 fusion (p&lt;0.0001, chi-square test). The frequency of the t(1;19) by tumor histology, as well as median and 5-year progression-free and overall survival are provided in the table . Conclusions: Our results strongly suggest that a t(1;19)(q10;p10) mediates the combined deletion of 1p and 19q in human gliomas. Like combined 1p and 19q deletion, the 1;19 translocation is associated with superior progression-free and overall survival in low-grade oligodendroglioma patients. FISH analysis of the t(1;19) will likely be a more sensitive and specific means to assess 1p and 19q status in patients with gliomas. (Supported in part by CA85799, CA108961 and NCCTG grants CA25224 and CA114740) [Table: see text] No significant financial relationships to disclose.
Resminostat and sorafenib combination therapy for advanced hepatocellular carcinoma in patients previously untreated with systemic chemotherapy.
Authors: Masatoshi Kudo, Baek-Yeol Ryoo, Ho Yeong Lim, Do Young Kim, Takuji Okusaka, Masafumi Ikeda, Hisashi Hidaka, Jong-Eun Yeon, Eishiro Mizukoshi, Manabu Morimoto, Myung Ah Lee, Kohichiroh Yasui, Yasunori Kawaguchi, Jeong Heo, Sojiro Morita, Tae-You Kim, Junji Furuse, Kazuhiro Katayama, Takeshi Aramaki, Won-Young Tak
Journal: Journal of Clinical Oncology (2017)

252 Background: Resminostat is an oral hydroxamate-type inhibitor of class I, IIB, and IV histone deacetylases. A European Phase II study of second-line combination therapy with resminostat and sorafenib for hepatocellular carcinoma (HCC) in patients (pts) revealed a promising improvement in overall survival (OS). Here we report the findings on safety and efficacy of an Asian Phase I/II study on first-line combination therapy with sorafenib and resminostat in HCC pts. Methods: Pts with advanced or metastatic HCC considered Child-Pugh A and ECOG 0/1 were enrolled in Japan and Korea. Sorafenib was administered at 400 mg (bid) in both Phase I and II. Resminostat was administered on days 1 to 5 every 14 days. In Phase I, the dose of resminostat was escalated from 400 mg/day (DL1) to 600 mg/day (DL2). In Phase II, pts were randomly assigned to sorafenib monotherapy or sorafenib/resminostat combination therapy at a ratio of 1:1. The primary endpoint was time to progression (TTP). Tumor response was assessed according to RECIST version 1.1 every 6 weeks. Results: A total of 9 pts were enrolled in Phase I (DL1, 3 pts; DL2, 6 pts). Higher incidences of G3-4 toxicities, including one DLT (G4 thrombocytopenia), were observed at DL2. Therefore, DL1 was determined as the recommended dose for Phase II. A total of 170 pts were enrolled in Phase II. The median TTP was 2.8 months in the combination and control arm, respectively (HR: 0.984). No significant difference was observed in the median OS. Retrospective analysis revealed favorable results for the combination option in certain subgroups: for example, HBV+ (TTP: HR, 0.630; OS: HR, 0.846); no prior therapy (TTP: HR, 0.629; OS: HR, 0.590); and platelet count &gt; = 151.000 (TTP: HR, 0.646; OS: HR, 0.509). Conclusions: Although the primary endpoint was not reached in this Phase II all-comer HCC study, the results of the subgroup analysis suggest a population-specific effect for the combination therapy, especially in one which is HBV+. This warrants the further development of this combination as first-line therapy in a well-defined subset of pts with advanced HCC. Clinical trial information: NCT02400788.
Vitamin D, Calcium, and Cancer
Authors: JoAnn E. Manson, Shari S. Bassuk, Julie E. Buring
Journal: JAMA (2017)

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Molecular epidemiology of EGFR mutations in 7,953 non-small cell lung cancer of Chinese ethnicity.
Authors: Shun Lu, Ziming Li, Xiaomin Niu, Zhiwei Chen, Xiangyun Ye, Ding Ding
Journal: Journal of Clinical Oncology (2014)

e19009 Background: The incidence of EGFR mutations in east Asia population is around 30-40%. But the molecular epidemiology of EGFR mutations in Chinese ethnicity non-small-cell lung cancer (NSCLC)...