tbuckley/cabot-search huggingface dataset:
Analysis of outcomes in patients (pts) with relapsed/refractory acute promyelocytic leukemia (APL) treated with and without high-dose chemotherapy and hematopoietic stem cell transplantation (HCT).
Authors: N. Pemmaraju, F. Ravandi, G. Rondon, S. Giralt, J. Chen, S. Pierce, R. E. Champlin, M. De Lima, M. Qazilbash
Journal: Journal of Clinical Oncology (2011)

6608 Background: Outcomes of pts with APL have dramatically improved, especially with availability of all-trans retinoic acid (ATRA), arsenic trioxide, and better supportive care. However, a small but significant number of pts relapse despite optimal upfront therapy. Methods: We reviewed pts with APL treated at our institution (1980-2010). Outcome of pts who received autologous (auto) or allogeneic (allo) HCT for relapsed disease was compared with those who did not. Results: We identified 42 pts with relapsed/refractory APL. 25 (60%) pts received auto (8) or allo HCT (17: related 5, unrelated 12). Median (med) age of pts receiving HCT: 29 years (range 6-61). RT-PCR was negative for PML/RARα at time of HCT in 6 of 6 evaluable auto pts and in 6 of 8 evaluable allo pts. Of the 8 auto pts, 5 were in CR2 and 3 in ≥ CR3. Preparative (prep) regimen: Busulfan (Bu) + Cyclophosphamide (CY) in 7 pts and Bu + Fludarabine (Flu) in 1 pt. Of the 17 allo pts, 12 were in CR2 and 5 in ≥CR3. Prep regimens for allo HCT: Bu + Cy 7, TBI-based 4, Bu + Flu 4, Flu + Melphalan 2. Successful engraftment: 24 (96%) HCT pts; only 1 pt (auto) died of graft failure after 2.7 months. Grade 2-4 acute GVHD: 6/17 pts (35%); limited or extensive chronic GVHD in 10/17 pts (59%). Med follow up (f/u): 82 months. Transplant-related mortality after auto or allo HCT: 37% and 41%, respectively. 7-year progression-free survival (PFS) after auto and allo HCT: 50% and 33% (p=0.66), respectively. 7-year overall survival (OS) after auto and allo HCT: 50% and 41% (p=0.65), respectively. At last f/u, 11/25 (44%) were alive, with 9/25 (36%) pts alive and in remission, between 2 to 19 years post HCT. Most common causes of death (COD): relapse 4, GVHD 5, infection 2. In the 17 pts who did not undergo HCT, med age was 45, pts received a med of 2 lines of therapy with 7 pts receiving ≥3 lines of therapy. APL relapse was most common COD (6 of 9 pts who died). 7-year OS from diagnosis: 40%, in contrast to 45% in pts receiving auto or allo HCT (p=0.48). Conclusions: In this retrospective study, both auto and allo HCT are associated with durable remission and prolonged survival. OS was not significantly different from pts who did not receive HCT.
Prevalence of cardiovascular disease (CVD) risk factors and receipt of preventive care among prostate cancer (CaP) survivors in the United States.
Authors: Kevin Alexander Pearlstein, Laura H. Hendrix, Trevor Joseph Royce, William A. Stokes, Ronald C. Chen
Journal: Journal of Clinical Oncology (2013)

185 Background: CVD is a major cause of mortality in CaP survivors. Prior claims-based studies have reported underutilization of preventive care in cancer survivors, but most CVD preventive care items are not available in claims data. We directly examined the prevalence of CVD risk factors and receipt of care in patients with these risk factors in two population-based data sources: National Health and Nutrition Examination Survey (NHANES) and National Health Interview Survey (NHIS) – both commonly used to examine patterns of care in the US. Methods: 2,938 (NHANES) and 452 (NHIS) men with CaP diagnosed from 1999 to 2011 were included. Statistical analysis accounted for sampling weight, and was stratifiedby Caucasian (CA) vs. non-CA. Results: CVD risk factors are highly prevalent (Table), and appear more so in non-Caucasian survivors. Further, 32% of survivors reported history of actual CVD (prior stroke, myocardial infarction, angina, or coronary heart disease). Overall, the majority of survivors receive preventive care. 89%of CA and non-CA survivors visited a primary care physician in the past 1 year. Among survivors with hypertension or hyperlipidemia, &gt;80% received blood pressure or cholesterol checks within past 1 year. Rates of tobacco cessation and exercise were lower. Conclusions: CVD and associated risk factors are prevalent in CaP survivors. However, the majority of these survivors visit a primary care physician and receive CVD preventive care. [Table: see text]
A pragmatic approach for measuring and monitoring hospitalizations in patients receiving chemotherapy for pancreatic cancer.
Authors: Gabriel Brooks, Carole Kathleen Dalby, Saira Chaudary, Joseph O. Jacobson
Journal: Journal of Clinical Oncology (2016)

278 Background: Hospitalizations in patients receiving chemotherapy are common and costly. In order to test interventions to reduce hospitalizations in chemotherapy patients, efficient approaches are needed for monitoring the incidence of hospitalization. Methods: We evaluated the monthly frequency of hospitalization in patients receiving active chemotherapy for pancreas cancer. Two definitions were used to identify patients under “active” chemotherapy treatment in a given month; both definitions required that patients were alive on the first day of the evaluation month. For definition A, patients were defined as active if they received any chemotherapy treatment in the evaluation month or the preceding calendar month. Definition B included any chemotherapy during the evaluation month or the two prior months. Reporting functions of the electronic health record (EHR, Epic Systems) were used to generate reports of chemotherapy treatment history and hospital discharges. Data were then combined using statistical software (SAS). Outcomes included the number of active chemotherapy patients per month, the number of hospital discharges per 100 chemotherapy patients, and discharge disposition by hospitalization. Results: There were an average of 101 active chemotherapy patients and 11 hospitalizations per month, using definition A to identify active chemotherapy patients. Corresponding figures using definition B were 115 active patients and 13 hospitalizations per month. The mean number of hospital discharges per month per 100 patients was 10.5 (SD 3.9) vs. 10.9 (4.4). Hospital discharge dispositions (using the inclusive definition B population) included home (49%), home w/ services (19%), home hospice (14%), hospice facility (11%), and SNF (8%). Conclusions: EHRs permit efficient approaches for monitoring monthly hospitalization frequency across a population of active chemotherapy patients. The observed frequency of hospitalization was similar with both active patient definitions. Capability to monitor hospitalization frequencies in active chemotherapy patients will facilitate development of quality improvement programs to reduce hospitalizations.
Establishment and Characterization of Bortezomib-Resistant Myeloma Cell Lines: A Possible Role of Mutated Proteasome β5 Subunit in Preventing the Accumulation of Unfolded Protein, Which Is Otherwise Followed by Catastrophic Endoplasmic Reticulum (ER) Stress.
Authors: Masaki Ri, Shinsuke Iida, Takayuki Nakashima, Hideyuki Miyazaki, Fumiko Mori, Asahi Ito, Atsushi Inagaki, Shigeru Kusumoto, Takashi Ishida, Hirokazu Komatsu, Yukimasa Shiotsu, Ryuzo Ueda
Journal: Blood (2009)
Ventricular arterial coupling in early breast cancer patients following treatment with anthracycline-containing adjuvant chemotherapy.
Authors: Graeme J Koelwyn, Nia C Lewis, Susan Ellard, Lee Jones, Jinelle C Gelinas, Douglass J Rolf, Bernie Melzer, Samantha Thomas, Pamela S. Douglas, Michel Khouri, Neil D Eves
Journal: Journal of Clinical Oncology (2014)

9591 Background: Use of anthracyclines is limited by dose-dependent cardiotoxicity. Research has focused on cardiac specific damage, although injury may extend beyond the heart to the vascular network. We sought to explore the utility of ventricular-arterial coupling (VAC), an integrative measure of heart and arterial function, at rest and during exercise, to evaluate cardiovascular function post therapy. Methods: Thirty ER+/HER2- breast cancer survivors (6.1 ± 2.4 yrs post anthracyclines) with normal left ventricular ejection fraction (LVEF) (59 ± 6) and 30 age-activity matched healthy controls were studied. Echocardiographic measurements were performed at rest and during exercise at 25%, 50%, and 75% of a predetermined maximal workload (Wmax) to determine arterial elastance (Ea), end systolic elastance (Ees) and VAC (Ea/Ees). Endothelial flow-mediated dilation (FMD), carotid intima-media thickness (CIMT), arterial stiffness and peak oxygen consumption (VO2peak) were also measured. Results: At rest, Ea, Ees, Ea/Ees and LVEF were not different between survivors and controls. The expected increase in Ees during exercise was attenuated in survivors compared to controls at 25% Wmax (5.28 ± 2.39 vs. 7.0 ± 2.11 mmHg/mL, p<0.001), 50% Wmax (5.94 ± 1.62 vs. 8.26 ± 2.76 mmHg/mL, p<0.001), and 75% Wmax (6.75 ± 2.29 vs. 10.26 ± 4.22 mmHg/mL, p<0.001). Accordingly, the Ea/Ees ratio was significantly higher at all exercise-related workloads in survivors compared to controls (p’s<0.05). Ea, diastolic relaxation and filling, endothelial independent and dependent FMD, CIMT, arterial stiffness and VO2peakwere not different between groups (p’s >0.05). Conclusions: While not detectable at rest, significant reductions in contractile performance (Ees) of the left ventricle were observed in survivors when the cardiovascular system was challenged by exercise. This subclinical cardiovascular dysfunction appears to be isolated to the heart as no differences in vascular function were observed at rest or during exercise. VAC assessment during exercise is a viable tool to evaluate late-occurring cardiovascular dysfunction in early breast cancer patients.
Hepatic arterial oxaliplatin salvage therapy for hepatobiliary tumors that have failed prior TACE
Authors: B. I. Carr
Journal: Journal of Clinical Oncology (2005)

4131 Background: Choice of effective drugs for multifocal bilobar primary tumors of the liver is limited. Usually, it is difficult to get any responses after failure of primary transarterial chemoembolization (TACE). This report concerns our initial experience of hepatic arterial oxaliplatin (Eloxatin) in patients (pts) with hepatocellular carcinoma (HCC), n=28; cholangiocarcinoma (CCC), n=14; gallbladder cancer (GB), n=3; or neuroendocrine tumors (NET), n=11; who had failed primary TACE, usually with cisplatin (HCC), gemcitabine (CCC) or doxorubicin (NET), respectively. Methods: Pts were treated with hepatic arterial oxaliplatin at 80 mg/m2, 100 mg/m2, 110 mg/m2 or 120 mg/m2 on successive cycles of TACE every 8 wks, blood counts and bilirubin permitting. Drug was administered together with partial arterial occlusion using Embogold microspheres, 300 - 500 microns. Complete blood count and liver function tests were performed weekly. A CAT scan was performed at each treatment. Results: A total of 56 pts have been treated. All were prior chemotherapy failures. Thus far, there have been PRs in 8 pts with HCC (28.5%), 3 pts with CCC (21.4%), 6 pts with NET (54.5%), and 1 of 3 with GB cancer. There have been minor responses or stable disease in 12 pts with HCC (42.8%), 5 pts with CCC (35.7%) and 4 pts with NET (36.3%). 6 HCC and 7 CCC thus far, pts are alive without tumor progression at 1 year. Toxicities have included 18 pts with cold-associated peraesthesiae (32%), 4 pts with dyspnea, 2 pts with laryngeal spasm (all transient) and 4 pts with grade I myelosuppression (7.1%), but none with grade II myelosuppression and none with elevated bilirubin over baseline. 2 pts also had transient hypotension. Conclusions: oxaliplatin appears to be hepatologically safe, and a promising drug for these otherwise chemotherapy resistant primary tumors in the liver. No significant financial relationships to disclose.
Cytogenetic changes in renal cell carcinoma: Basis for sensitivity and resistance to everolimus.
Authors: Imogen Rose Caldwell, Paul Oei, Daniel Ng, Peter C.C. Fong, Reuben James Broom
Journal: Journal of Clinical Oncology (2012)

403 Background: The mTOR inhibitors have improved outcomes for pts with metastatic renal cell carcinoma (mRCC) but the duration of benefit is variable. Currently there are no predictive biomarkers for pre-selecting pts who are likely to respond to these agents. We undertook an exploratory translational study evaluating cytogenetic changes in the context of response to everolimus therapy. Methods: 10 pts with mRCC treated with everolimus therapy were enrolled. Pre-treatment paraffin-embedded tissue specimens were analysed for cytogenetic changes using fluorescence in situ hybridisation (FISH) and clinical data including PFS (RECIST 1.1) were obtained. The gene probes chosen for this analysis were; VHL, FHIT, FGFR1/3, PDGFb, PDGFRb, EGFR, MYC and IGH@. Results: Results are displayed in the table below. The median PFS was 8.25mo (months). Eight pts were treated 1 st -line (on clinical trial), one 2 nd -line and one 3 rd -line. The longest responder (PFS 25.5mo, 3 rd -line) had a normal VHL status but loss of FHIT. Two pts with the longest PFS and one with a PFS of 5.5mo had gain of both PDGFb and PDGFRb. Gain of FGFR1 and FGFR3 was seen in two and three pts respectively. Two specimens were unsuitable for full analysis. Conclusions: Loss of FHIT but a normal VHL status was seen in one pt with mRCC who had an enduring response to everolimus. Concomitant gain of PDGFband PDGFRb was observed in three pts with a good response. FGFR1/3 may be of relevance in the setting of alternative targeted therapies. Further research evaluating the utility of these potential biomarkers is required. [Table: see text]
Radiation therapy practice patterns for elderly patients with early-stage breast cancer.
Authors: Erin Healy, Lihong Qi, Jason Vuong, Richard J. Bold, Dominique Rash, Jyoti Mayadev
Journal: Journal of Clinical Oncology (2013)

82 Background: Controversy exists regarding the benefit of whole breast radiation (RT) after breast conservation surgery (BCS) in elderly early stage breast cancer patients. We investigated the clinical and pathological characteristics that influence referral patterns and consent for RT. Methods: Between 2006 and 2011, 93 women, aged ≥ 70 were treated with BCS at the University of California Davis Medical Center (UCDMC). Electronic medical records were reviewed to identify pathological and clinical tumor characteristics, including stage, nodal involvement, lymphovascular invasion, margin status and molecular subtype. Patient factors including Karnofsky performance status, Charlson comorbidity index, and distance from UCDMC were recorded. Adjuvant therapy recommendations regarding RT, radiation dose and fractionation, hormonal and chemotherapy, and the ultimate treatment plan were noted. Descriptive statistics were used to characterize the referral pattern data. Patient and tumor characteristics were compared between those referred and not referred for RT using chi-square tests for categorical variables and Student’s t tests for continuous variables. Similar comparisons were also conducted for those who consented and declined RT. Results: Of the 93 women eligible for adjuvant whole breast radiation, 79 (85%) were referred to radiation oncology. Sixty five patients had stage I, 16 had stage II, and 4 had stage III breast cancer. Seventy four patients had a luminal A molecular subtype, 11 of whom declined RT. Hormonal therapy was recommended for 78 patients, of which 11 were not referred to RT. The mean age of those referred to RT was significantly less than those not referred, 76 vs. 81 years, P = 0.006. Mean distance to UCDMC was 17.2 miles for those not referred and 34.4 miles for those referred, P = 0.02. There were no significant correlation between stage, molecular subtype, margin status or lymph node involvement and referral to RT. Conclusions: The majority of elderly patients are referred to RT but increased age and comorbidity were associated with non-referral. Patients’ perception of their own comorbidity, previous experience with RT and the decision to pursue hormonal therapy contributed to patients’ decisions to decline RT.
Human epidermal growth factor receptor-2 (HER2) Ile655Val single nucleotide polymorphism (SNP) is associated with gender-specific outcome in patients with metastatic colorectal cancer (mCRC) treated with cetuximab in a phase II study (IMCL-0144).
Authors: A. Gerger, P. O. Bohanes, D. Yang, T. Winder, Y. Ning, M. J. Labonte, D. J. Mauro, C. Langer, E. K. Rowinsky, H. Lenz
Journal: Journal of Clinical Oncology (2011)

441 Background: HER2 pathway is an important growth-regulatory pathway in many malignancies. In-vitro data from various cell lines suggest that activation of HER family members predicts resistance to cetuximab. HER2 also interacts with hormone receptors and estrogen, promoting tumor proliferation in breast cancer models. We previously demonstrated that polymorphisms in HER1 and ER-β were associated with gender-specific survival in colorectal cancer patients. HER2 Ile655Val (rs1136201) SNP's functionality was shown in breast cell lines with Val-expressing cells exhibiting increase growth capacity. We tested whether this SNP may predict gender-specific clinical outcome in mCRC treated with cetuximab. Methods: Tissue samples of 130 patients, 64 males and 66 females, with mCRC, enrolled in a phase II trial of cetuximab monotherapy were analyzed. Genomic DNA was extracted from FFPE tumor tissue. K-Ras mutation status and HER2 Ile655Val (rs1136201) SNP were analyzed using direct DNA-sequencing and PCR-RFLP. 23 out of 130 patients were still alive at the time of data analysis with a median follow-up of 12.3 months. Results: Females with the low activity HER2 Ile/Ile (n = 41) genotype had better progression-free survival (PFS) when compared to Ile/Val or Val/Val (n = 21) genotypes (median PFS = 2.4 vs. 1.2 months; HR = 2.06 (95% CI: 1.08-3.92), p = 0.0281) based on the multivariable Cox regression model adjusting for KRAS, performance status and severity of skin rash and stratified by race. In KRAS wild-type females, 15 patients out of 20 (75%) with HER2 Ile/Ile genotype responded or had stable disease when compared to 4 out of 12 (33%) Ile/Val or Val/Val genotypes (exact conditional test p = 0.143). In males, HER2 Ile655Val SNP is not associated with outcome. HER2 Ile655Val SNP is not associated with gender-specific overall survival. Conclusions: Our data suggest that HER2 Ile655Val SNP may identify females with mCRC likely to experience better outcome when treated with cetuximab. Prospective biomarker-embedded clinical trials are needed to validate our results. [Table: see text]
Incidence of esophageal cancers among oral cavity and pharynx cancer patients: A review of the SEER database (1973-2007).
Authors: E. Kim, N. Chandra, J. Kim
Journal: Journal of Clinical Oncology (2011)

5545 Background: Although patients may benefit from improvement in local control after treatment of oral cavity and pharynx cancers (OPC), they may be at increased risk for second primary malignancies such as esophageal cancers (EGC). Literature regarding EGC among patients with OPC is limited. Our aim was to examine the incidence of second primary EGC among patients with OPC in the SEER database. Methods: The study cohort consisted of 9 population-based tumor registries within the Surveillance Epidemiology and End Results (SEER) database of North America (1973-2007). Second primary EGC were analyzed for incidence and relative risk to the general population. Standardized incidence ratios (SIRs) were calculated by comparing the second cancer incidence in OPC patients to the first primary cancer incidence in non-cancer populations. Incidence of EGC was also stratified by subsites within the oral cavity and pharynx, age, race, and sex. Results: Of 74,893 OPC patients, 760 (1%) developed EGC. Compared with age-adjusted, gender, and tumor-specific rates in the general population, OPC patients had higher risks of developing EGC overall (observed-to-expected ratio [O/E] = 8.49, 95% confidence interval [CI] = 7.89-9.11). Advanced at age diagnosis was correlated with decreased risk of EGC (p<0.05). Among 5 year survivors in the 40-44 year age group, ([O/E] = 45.86, 95% CI = 23.7-80.11). Relative risk was higher among black patients ([O/E = 20.77, 95% CI = 16.39-25.96) compared to whites ([O/E] = 8.67, 95% CI = 7.55-9.92). Females had increased risk [O/E] = 16.90 compared to males [O/E] = 7.18 (p<0.05). Relative risk was higher among various subsites within the oral cavity and pharynx at 5 years (oropharynx [O/E] = 23.0, 95% CI = 12.24-39.32, hypopharynx [O/E] 31.50, 95% CI = 24.15-40.38). Conclusions: Patients with OPC are at increased risk for development of EGC. The positive correlation may be in part due to the common risk factors of tobacco and alcohol use. This risk was increased with younger age at diagnosis, female sex, black race, and specific subsites such as oropharynx and hypopharynx. Early screening for EGC among these patients may be indicated.
Correlation of SPARC expression and primary tumor site response(PTSR) and relapse to nab-paclitaxel vs docetaxel-based induction chemotherapy (IC) in patients(Pts) with HNSCC.
Authors: Jon Chatzkel, James S. Lewis, Jessica C. Ley, Loren S. Michel, Tanya Marya Wildes, Jason Rich, Brian Nussenbaum, Douglas Adkins
Journal: Journal of Clinical Oncology (2015)

e17079 Background: SPARC may facilitate uptake of albumin-bound drugs (nab-pac). In 1 study, SPARC+ HNSCC responded more robustly to nab-pac. We hypothesized that SPARC expression would predict better PTSR and lower relapse rates with nab-pac- vs docetaxel-based IC in HNSCC. Methods: Pts received 3 IC cycles then CRT (cisplat). Two regimens were employed: nab-pac- (APF-C: nab-pac, cisplat, FU, and cetux, 29 pts) and docetaxel-based groups (TPF-C, 32 pts). PTSR was assessed visually by otolaryngologists after 2 IC cycles. Complete PTSR was classified as a positive visual responder. The APF-C group also underwent FDG-PET: PTSR was assessed categorically (CR, PR, SD, or PD) and as the average % change in 1-3 tumor target lesions (% PET response). SPARC expression was evaluated by IHC in pre-treatment tumor stroma and cells and each assigned a score of 0, 1 ( < 25% +), 2 (26-50% +), 3 (51-75% +), or 4 ( > 76% +). Tumors in which the average of the two scores was > 2 were classified as SPARC positive. Regression analyses were performed separately for both the APF-C and TPF-C groups to assess whether PTSR- visual (or relapse) was significantly associated with SPARC expression (+/-). The effect of the interaction between SPARC expression and APF-C on PTSR-visual was assessed in the entire population. We assessed if SPARC expression was associated with either categorical or % PET response in the APF-C group. In all analyses, P16+ oropharyngeal tumors were denoted with a dummy variable. Significance was assessed at the p < .05 level. Results: SPARC expression was not associated with categorical PET response (Odds Ratio [OR] for SPARC = 4.9, p = .10), % PET response (OR .75, p = .33), PTSR-visual (OR 3.3, p = .16) or relapse (OR 2.0, p = .58) in the APF-C group. SPARC expression was not associated with PTSR-visual (OR 1.7, p = .55) or relapse (OR .30, p = .19) in the TPF-C group. Interaction of SPARC and treatment with APF-C was not associated with PTSR-visual (OR for the interaction = 2.2, p = .52) or relapse (OR 6.4, p = .22) in the entire study population. Conclusions: SPARC expression did not predict for better tumor response nor lower relapse risk to nab-pac- vs docetaxel-based IC in HNSCC.