tbuckley/cabot-search huggingface dataset:
Use of a web-based app to improve breast cancer symptom management and aromatase inhibitor adherence.
Authors: Ilana Graetz, Caitlin N McKillop, Edward J. Stepanski, Gregory A. Vidal, Lee Steven Schwartzberg
Journal: Journal of Clinical Oncology (2017)

89 Background: For postmenopausal women with hormone receptor-positive breast cancer, long-term use of aromatase inhibitors (AI) significantly reduces the risk of cancer recurrence and improves disease free and overall survival. Despite the known benefits of AIs, many patients are nonadherent due to adverse side effects. We conducted a pilot randomized controlled trial of a web-enabled application (app) to provide real-time monitoring and better management of treatment-related adverse symptoms among patients with hormone-receptor positive breast cancer and a new AI prescription. Methods: Eligible patients who agreed to participate were randomized into either: App: had access to the app and received weekly reminders to use it; or Usual Care: had access to the app but did not receive reminders. Concerning responses and trends triggered email alerts to the patient’s providers, who then could review responses to manage ongoing treatment and make therapeutic adjustments. The main analyses compared overall AI adherence using the Morisky Medication Adherence Scale and quality of life using the Functional Assessment of Cancer Therapy Endocrine Symptoms (FACT-ES). Results: We enrolled 44 patients, 21 in the App and 23 in the Usual Care groups; 83% of patients approached agreed to participate, 23% were African-American, and 32% were over the age of 65. Overall, 74% of participants in the App group used the app at least once per week compared with 38% in the Usual Care group (p&lt;0.01). Reported AI adherence at 8 weeks after initiation was significantly higher among App compared with the Usual care group at 8 weeks (100% vs. 72%, p=0.01). Using a differences-in-differences analysis, we found a substantially larger decrease in quality of life in the Usual Care group compared with the App (-11.5 vs. -3.9, p=0.191), although this difference did not reach statistical significance. Conclusions: App use with weekly reminders significantly improved short-term AI adherence. If short-term gains in adherence persist, this low-cost intervention could improve survival outcomes for women with hormone-receptor positive breast cancer.
A single-arm, open-label, phase II study to evaluate the safety of vemurafenib (VEM) followed by ipilimumab (IPI) in BRAF V600-mutated metastatic melanoma (MM).
Authors: Asim Amin, David H. Lawson, April K. Salama, Henry B. Koon, Troy H. Guthrie, Sajeve Samuel Thomas, Steven O'Day, Montaser F. Shaheen, Bin Zhang, Stephen Francis, F. Stephen Hodi
Journal: Journal of Clinical Oncology (2015)

9032 Background: There is much interest in determining how to incorporate BRAF inhibitors with immune checkpoint inhibitors in the treatment of patients (pts) with BRAF-mutant MM. A phase I study showed that concurrent administration of IPI, an antibody that blocks cytotoxic T-lymphocyte antigen-4, and VEM, an inhibitor of BRAF V600-mutated kinase, caused significant dose-limiting hepatotoxicity in BRAF-mutant MM pts. An alternate strategy is to use these agents sequentially in order to minimize toxicities observed with concurrent administration and to improve efficacy over either agent alone. Methods: This single-arm, open-label, phase II study evaluated the safety of VEM followed by IPI in treatment-naïve MM pts harboring a BRAF V600 mutation. Pts initially received VEM for 6 weeks (960 mg twice daily) followed by IPI at 10 mg/kg (Q3W x 4 doses, then Q12W beginning at week 24 until disease progression or unacceptable toxicity) [VEM1-IPI phase]; VEM was then restarted. The primary objective was to estimate the incidence of grade 3–4 drug-related skin adverse events (AEs) during the VEM1-IPI phase. Results: Among 46 pts treated in the VEM1-IPI phase, 80% were male, 52% had stage M1c, and 54% had ≥ 5 sites involved. Grade 3–4 drug-related skin AEs occurred in 15 (33%) pts during the VEM1-IPI phase, the most common of which was rash in 9 (20%) pts. Grade 3–4 drug-related gastrointestinal AEs occurred in 10 (22%) pts (diarrhea in 5 [11%]) and hepatobiliary AEs in 2 (4%) pts (hepatitis; hyperbilirubinemia). There were no deaths due to study drug toxicity. At a median follow-up of 10.5 mo, the objective response rate was 30% (95% CI, 18%–46%) during the VEM1-IPI phase. Median progression-free survival was 4.4 mo (95% CI, 4.2–5.9). Interim median overall survival was 20.3 mo (95% CI, 11.1–NE). Conclusions: VEM followed by IPI at 10 mg/kg has a manageable safety profile with no significant signals of hepatobiliary toxicity, as seen with concurrent VEM and IPI; the incidence of grade 3–4 skin AEs was higher than with either agent alone. The benefit/risk of this sequence needs to be evaluated further based on individual patient characteristics and new treatment options. Clinical trial information: NCT01673854.
Post hoc analysis of association between treatment response and various indicators of efficacy and safety in a randomized phase III trial of decitabine in older patients with acute myeloid leukemia.
Authors: Mark D Minden, Chris Arthur, Jiri Mayer, Mark M. Jones, Peter G. Tarassoff, Hagop Kantarjian
Journal: Journal of Clinical Oncology (2012)

6627 Background: In a recent, large phase III trial (NCT00260832; Kantarjian, JCO; in press), 485 patients ≥65y with newly diagnosed acute myeloid leukemia (AML) received, every 4 wks, treatment choice (TC) of either supportive care or cytarabine (20 mg/m 2 subcutaneous injection, 10 consecutive days) or decitabine (DAC) 20 mg/m 2 (1-h intravenous [IV] infusion, 5 consecutive days). This post hoc analysis investigated relationships between response to treatment and indicators of efficacy and safety. Methods: Response was defined as morphologic complete remission (CR), or CR with incomplete blood count recovery (CRi) or partial response (PR). Transfusions (red blood cell [RBC] or platelets [PLT]), IV antibiotic use, and dose modifications were tabulated for responders and nonresponders to DAC or TC during the treatment period. Results: Fewer responders than nonresponders had dose modifications (30.4% vs 64.5%, respectively; P&lt;.0001). Antibiotic use and transfusions were similar in both groups. Overall survival for responders was 16.1–18.5 mo vs 4.2–4.9 mo for nonresponders. Conclusions: These data suggest that response to DAC or TC treatment predicts clinically relevant benefits, with fewer dose modifications in older patients with newly diagnosed AML. The number of transfusions and antibiotic use was impacted by the longer survival time of responders vs nonresponders. Data on the impact of early response are being analyzed. [Table: see text]
A phase II study of lapatinib and capecitabine in second-line treatment of metastatic pancreatic cancer.
Authors: Zheng Wu, John Marshall, Jimmy J. Hwang, Michael J. Pishvaian, Anton Wellstein, Louis M. Weiner, Aiwu Ruth He
Journal: Journal of Clinical Oncology (2012)

e14569 Background: The anti-EGFR therapy erlotinib was FDA approved for the treatment of patients with advanced pancreas cancer. Human epidermal growth factor receptor 2 (HER-2), a member of the ErbB family of growth factor receptor tyrosine kinases to which EGFR belongs, is found overexpressed in 20% of pancreatic cancers . Targeting EGFR and HER-2 with separate specific monoclonal antibodies showed synergistic inhibition of pancreatic cancer tumor progression in mice bearing xenograft of human pancreatic cancer cell lines. We performed an open-label single arm phase II study to evaluate the combination of lapatinib, a dual tyrosine kinase inhibitor of EGFR and HER-2, and capecitabine in the second-line treatment of metastatic pancreatic cancer. Methods: Patients with metastatic, unresectable, gemcitabine-refractory pancreatic cancer with adequate performance status (ECOG 0-2) and normal hepatic and renal function were eligible. Patients received lapatinib 1,250 mg PO daily, and capecitabine 1,000 mg/m 2 PO twice daily on days 1-14 of each 21-day cycle. Restaging studies were performed every 2 cycles. The primary endpoint was median overall survival (OS). Secondary endpoints included response rate (RR) and progression free survival (PFS). Results: Between 9-2009 and 8-2011, 17 patients received treatment. Six of 17 patients (24%) had disease progression after 2 cycles, 2 of 17 patients (12%) progressed after 4 cycles and 4 of 17 patients (24%) had stable disease and received more than 6 cycles. The median number of treatment cycles was 3 (range 1-22 cycles). The median PFS was 9 weeks (95% CI 7.1-18.9). Median OS was 25 weeks (95% CI 11 -34). Grade 3 nausea, vomiting in 3 patients (17%), grade 3 diarrhea in 2 patients (12%), grade 3 limb edema in 1 patient (6%), and grade 3 fatigue in 1 patient (6%). Serum was collected at baseline, three weeks and time of disease progression for microRNA analysis to identify biomarkers correlated with clinical outcome. Conclusions: The combination of lapatinib and capecitabine is a tolerated regimen for patients with gemcitabine-refractory metastatic pancreatic cancer. Some patients were able to receive 6 or more cycles of therapy. Molecular analysis of patients’ biosamples is ongoing.
Protein overexpression and gene amplification of EGFR in esophageal squamous cell carcinoma: Relationship between malignant biologic behavior and EGFR status study.
Authors: Yaping Xu, Xiaojiang Sun, Jialei Gu, Wei Wu, Weimin Mao
Journal: Journal of Clinical Oncology (2014)

e15043 Background: Epidermal growth factor receptor (EGFR) is widely distributed in human epithelial cell membrane, including esophageal squamous cell carcinoma (ESCC). The purpose of this study was to evaluate the relationship between malignant biological behavior and prognoses with EGFR overexpression and gene amplification in ESCC. Methods: Fifty-six patients with surgically resected ESCC were screened in our hospital between January 2004 and November 2010. Immunohistochemistry (IHC) was performed to analyze the expression of EGFR. Fluorescence in situ hybridization (FISH) was performed to assess the EGFR gene amplification. A chi-square test or Fisher exact test for independence was used to examine the correlation among the status of EGFR protein, gene and the several clinicopathological factors. Kaplan-Meier method and Cox regression analysis were employed to compare prognoses. Results: EGFR was overexpressed in 30 of 56 ESCC (53.6%) and was correlated with poorer grade differentiation (p=0.047). EGFR gene amplification was found in 13(23.2%) cases and was correlated with the presence of lymph node metastasis (p=0.002) and higher pathological tumor-node-metastasis (pTNM) stage (p=0.042). In univariate analysis, there was no correlation between the prognosis and EGFR protein expression, but EGFR gene amplification was a significant predictor of prognosis (p=0.031). However, the multivariate analysis revealed that there was only margin significant association between the EGFR gene amplification and overall survival (p=0.056). Conclusions: EGFR protein overexpression and gene amplification in ESCC were correlated with the malignant biological behavior, including tumor differentiation and lymph node metastasis. Further studies should be conducted to analyze the prognostic value of EGFR protein overexpression and gene amplification in patients with ESCC.
Field deployable platform for prognostic hepatic cancer screening.
Authors: Jill E. Shea, Jennifer H Granger, Mark D Porter, Courtney L. Scaife
Journal: Journal of Clinical Oncology (2017)

267 Background: Hepatocellular carcinoma (HCC) incidence rates are increasing in many parts of the world particularly in low- and middle-income countries (LMICs). Although treatable if identified in the early stages in many LMICs patients are identified later in disease. A low cost point of care system that could identify patients at a higher risk of having HCC could be used as a screening tool to identify patients at an earlier stage. We are currently developing a low cost point of care hand held platform that can simultaneously evaluate the blood levels of common HCC markers. We present our preliminary findings on the limit of detection (LOD) of our system. Methods: Our device combines the rapid but qualitative results of a vertical flow assay with the quantitative capabilities of surface enhanced Raman scattering spectroscopy. Our final product will be able to simultaneously measure the blood levels of the five most proven markers of HCC: alphafetoprotein (AFP), lens-culinaris agglutinin binding alphafetoprotein (AFP-L3), des-gamma-carboxy prothrombin (DCP), core antibodies to hepatitis B virus (HBV), and core antibodies to hepatitis C virus (HCV). In this pilot study we initially evaluated the LOD of our system by evaluating known concentrations of AFP in human serum samples. We then evaluated serum levels of AFP in HCC patient samples (n = 5) with our device and compared with values obtained using a standard ELISA. Results: The LOD of our system for the detection of AFP in spiked serum samples was 1 ng/mL. Our quantitative lateral flow assay measured AFP within 10% of the values of obtained by standard ELISA, with serum values ranging from 10-900 ng/mL. The quantitative vertical flow assay was able to provide results within 5 minutes at a cost of approximately $2/sample. Conclusions: Our inexpensive, portable and rapid test was able to measure serum levels of AFP at values comparable to standard clinical methods. Importantly, one blood marker would be insufficient to identify high risk patients, so further research will be required to expand the number of markers within the panel. The end goal will be to evaluate the ability of our point of care system to screen high risk population in LMICs, thereby identifying at risk patients earlier in disease progression.
Efficacy of Recombinant Erythropoietin + 13-cis Retinoic Acid + Dihydroxylated Vitamin D3 in the Treatment of Anemia of Low-Intermediate Risk Myelodysplastic Syndrome Patients.
Authors: Dario Ferrero, Chiara Dellacasa, Antonella Darbesio, Marilena Bertini, Patrizia Pregno, Mario Boccadoro
Journal: Blood (2004)
ALK and MET genes in advanced lung adenocarcinomas: The Lung Cancer Mutation Consortium experience.
Authors: Marileila Varella-Garcia, Lynne D Berry, Pei-Fang Su, Wilbur A. Franklin, A. John Iafrate, Marc Ladanyi, D. Ross Camidge, Edward B. Garon, Eric B. Haura, Leora Horn, Fadlo Raja Khuri, William Pao, Charles M. Rudin, Alice Tsang Shaw, Joan H. Schiller, Mark G. Kris, Bruce E. Johnson, John D. Minna, David J. Kwiatkowski, Paul A. Bunn
Journal: Journal of Clinical Oncology (2012)

7589 Background: The Lung Cancer Mutation Consortium (LCMC) consisting of 14 US Cancer Centers was established to evaluate a panel of molecular mutations in advanced lung adenocarcinoma. ALK gene fusions and MET gene amplification were assessed by FISH in CLIA certified laboratories. Methods: Molecular tests were performed in stage IIIB or IV lung adenocarcinoma. To date, FISH assays have been completed in 901 patients for ALK (ALK break-apart, Abbott Molecular) and in 654 patients for MET (in house/Abbott Molecular reagents). ALK+ specimens were defined by split 3’ALK/5’ALK signals (gap &gt;2 signal diameters) or single 3’ALK signals in &gt;15% of tumor cells. MET gene amplification (MET+) was defined by ratio mean MET/mean CEP7 ≥2. Results: The ALK+ patient subset (N=75, 8.3%) compared to the ALK- had significantly lower age at diagnosis (52 vs. 60, p&lt;0.001) and less frequent heavy smoking history (61% never-smokers among ALK+ vs. 31% among ALK-, p&lt;0.001; pack-year for current/former smokers 17 vs. 40, p=0.003). Liver metastases were significantly more frequent among ALK+ than ALK- (23% vs.10%, p=0.004); no difference was detected in bone, brain and adrenal gland metastases. MET+ (N=29, 4.4%) was significantly associated with female sex (72% female among MET+ vs. 39% among MET-, p&lt;0.001) and marginally more frequent in patients with adrenal metastasis; no difference was detected for age at diagnosis and smoking history. Follow-up on 73 ALK+ patients indicated that 56% received crizotinib as targeted therapy. Response was unknown in 8% and unreportable in 22% patients enrolled in ongoing randomized trials. Among patients with evaluable response, complete response, partial response, stable disease, and progressive disease were found respectively in 3%, 66%, 28%, and 3%. Conclusions: The LCMC successfully tested ALK and MET FISH in a large number of lung adenocarcinomas. It was demonstrated that directing positive patients to specific interventions is feasible, and that grouping of testing and trials within consortia may maximise relevant trial accrual in rare molecular subtypes. Supported by NCI-GO award. Submitted on behalf of the LCMC.
Clinical outcome (CO) and predictive factors (PRE) evaluation of a cohort of castration resistant prostate cancer (CRPC) patients (pts) treated with abiraterone acetate (AA) in a named patient program (NPP): Preliminary results from a retrospective study.
Authors: Antonello Veccia, Lucia Fratino, Umberto Basso, Maddalena Donini, Alessandro D'Angelo, Francesco Massari, Giuseppe Procopio, Donatello Gasparro, Francesco Verderame, Caterina Messina, Fable Zustovich, Roberto Iacovelli, Anna Paola Fraccon, Giovanni L. Pappagallo, Francesca Maines, Orazio Caffo, Enzo Galligioni
Journal: Journal of Clinical Oncology (2013)

e16078 Background: AA provided a survival advantage compared to placebo, in pts who had received docetaxel for CRPC. Before the regulatory authority approval, AA was made available in Italy through a NPP supervised by the local ethic committees. The present retrospective study is aimed to assess PRE and CO in an unselected CRPC population which received AA by NPP. Methods: We retrospectively reviewed the clinical records of all pts treated with AA by NPP in our Institutions. For each pt we have recorded the pre and post-AA clinical history, the treatment details and outcomes. We have assessed the ability of a series of selected 22 clinical factors to predict AA response through a logistic regression analysis. Continuous variables were categorized by quartiles and chosen for the initial model after a univariate chi-square analysis. Results: To date we have collected a consecutive series of 136 pts from 13 Italian hospitals. The median age was 72 yrs (range 52-87). The median baseline PSA was 154 ng/ml (range 0.33-&gt;100.000); 80% and 16.7% of the pts showed bone and measurable lesions respectively. The median duration of AA treatment was 15 wks (range 1-73); 59 treatments are ongoing. Grade 3-4 toxicities were anemia (5 pts), nausea (1 pt), fatigue (4 pts), bone pain (3 pts), and hypokaliemia (1 pt). A PSA reduction &gt; 50% was observed in 37.5% of the pts. Having a performance status (PS) 0-1 [(exp(beta) 4.541; p= 0.018], a previous ormonotherapy lasting &gt;40 months [(exp(beta) 3.299; p= 0.020], baseline hemoglobin &gt;12 g/dl [(exp(beta) 2.595; p= 0.074], no visceral organ involvement [(exp(beta) 1.929; p= 0.097] resulted to be independently predictive of a PSA reduction &gt; 50%. The median PFS and OS were 5 mos and 14 mos, respectively; the 1-year PFS and OS rates were 25.7% and 53%, respectively. Conclusions: Our preliminary results have confirmed the efficacy of AA in second line CRPC outside clinical trials. Pts with good PS, with good hemoglobin levels, with long-lasting hormosensitivity, and without visceral organ involvement have higher probability to achieve a biochemical response to AA.
The statistical distribution of involved axillary lymph nodes in breast cancer: A SEER population-based study
Authors: V. Vinh-Hung, A. Guern, G. Storme
Journal: Journal of Clinical Oncology (2007)

11031 Background: The number of involved lymph nodes in patients with breast cancer is highly variable. It might be important to examine the frequency distribution (FD) of these numbers in order to characterize their variability. This study examines the FD’s statistical properties and determines what they imply in terms of statistical analyses. Methods: The data was based on the National Cancer Institute’s Surveillance, Epidemiology and Ends Results (SEER). It covered 109618 patients, in whom axillary dissection had been performed between 1973 and 2002, in 9 states or towns of the USA. The involved lymph nodes were fitted to different statistical distributions adapted to count data using the maximum likelihood method (ML). The fittings were evaluated with the Kolmogorov-Smirnov (KS) statistic (KS close to 1 indicates lack of fit and KS close to 0 indicates good fit) and with the chi2 statistic (large chi2 indicates lack of fit). Results: The FD showed a logarithmically decreasing frequency, i.e. log-concave type. The mean number of involved nodes was 1.1465 and the variance was 9.54. The fit with a Poisson distribution gave a chi2=7.18*10 6 and the KS was 0.389. The fit with a negative binomial distribution using the ML gave a chi2=291.7, and the KS was 0.0086, i.e. 45-fold improved fit. Discussion: The FD’s variance 9-fold larger than the mean number of involved nodes indicates important overdispersion, i.e. the variability increases when the number of involved nodes increase. The Poisson distribution is inappropriate as was shown by the chi2 and KS. Overdispersion implies that nodal metastases are not independent random events. Overdispersion might be explained by 1) subsets of patients had a higher than expected propensity of nodal involvement, and/or 2) nodal involvement is a cascade process in which the likelihood of involvement increases when more nodes are involved. The implication for further analyses is that building predictive models of nodal involvement should take into account overdispersion and use appropriate modeling distributions such as the negative binomial. Conclusion: The FD characterization indicated a log-concave type with overdispersion. This might be important to gain an insight into the mechanisms of nodal involvement and to improve their analyses. No significant financial relationships to disclose.