tbuckley/cabot-search huggingface dataset:
Evaluation of an online, skill-building, group intervention for patients with cancer: Pillars4Life.
Authors: Jonathan David O'Donnell, Amy Pickar Abernethy, Greg Samsa, Tina Staley, Kristin MacDermott, Sophia Smith
Journal: Journal of Clinical Oncology (2014)

239 Background: Psychosocial distress is common for those with cancer; new interventions are needed. Pillars4Life is an online educational program that teaches coping skills in a group format. What is the relationship between participation in the LiveStrong-funded Pillars4Life program and personal psychosocial outcomes? Methods: This was a longitudinal observational cohort study. Cancer patients participating in the Pillars4Life program were recruited from the 17 hospitals that received the LiveStrong Community Impact Award. Consenting participants participated in 10 weekly sessions and completed electronic surveys at baseline and 3 months. Patient reported measures included: distress [Distress Thermometer (DT), Patient Care Monitor (PCM)], depression [Patient Health Questionnaire 9 (PHQ9)], anxiety [Generalized Anxiety Disorder 7 (GAD7)], posttraumatic stress [PTSD Checklist-Civilian (PCLC)], despair (PCM), fatigue [Functional Assessment of Chronic Illness Therapy (FACIT)], and cancer-related wellbeing [Functional Assessment of Cancer Therapy-General (FACTG)] outcomes. Results: Patient participants (n=130) were: mean age 56±11 years; 87% female; 89% white; 61% married; 48% employed; 51% had breast cancer; and 63% were receiving treatment. Mean scores significantly improved from baseline to month 3 on all patient-reported outcome measures: DT (-0.9), PCM Distress (-3.0), PHQ9 (-2.3), GAD7 (-2.3), PCLC (-4.3), PCM Despair (-2.9), FACT-G (4.7), all p&lt;.001; and FACIT-Fatigue (3.3, p=.001). Patients who reported distress at baseline (DT≥4; n=70) had clinically significant improvements (moderate to strong effect sizes ranged from 0.5 to 1.0 standard deviation units) in DT; PCM Distress, Quality of Life, and Despair; PHQ9; GAD7; PCLC; FACTG, among others. Conclusions: Participation in Pillars4Life was associated with statistically and clinically significant improvements on key psychosocial and quality of life patient-reported outcomes measures. Importantly, distressed patients experienced meaningful improvement.
Recurrence and morbidity in patients undergoing sentinel lymph node biopsy in Japanese breast cancer patients
Authors: I. Fujiwara, H. Nakajima, N. Mizuta, K. Sakaguchi, Y. Hachimine
Journal: Journal of Clinical Oncology (2007)

11062 Background: Aim of this study was to determine the axillary lymph nodes recurrence rate in breast cancer patients with tumor less than 5 cm (T2), who did not have axillary node dissection with negative sentinel lymph node (SLN). Methods: SLN biopsies were performed in 403 consecutive patients with breast cancer up to 5 cm and clinically negative axillary node from May, 2000, to December, 2005. SLN were identified using the combined method with sulfan blue dye and technetium 99m-labelled stannous phytate. SLN were examined with H&amp;E staining. In patinets with negative SLN, additional axillary nodes dissection were avoided. Results: The SLN identification rate was 99.8% (402 out of 403). Three-hundred forty-one (341) patients (84.8%) who were found to have no metastatic disease, were observed and followed without further axillary dissection. At a mean follow-up of 35.7 months (range, 12–79 months), five of these patients (1.5%) developed an axillary recurrence. SLN biopsy was not associated with morbidity such as arm lymph edema. Conclusion: With intermediate-term follow-up, the axillary recurrence rate was low and there was none of morbidity. We conclude that SLN biopsy is a promising alternative to axillary lymph node dissection in patients with breast cancer up to 5 cm in Japanese women. No significant financial relationships to disclose.
Clinical validation of a comprehensive cancer genomics analysis for lung cancer patients.
Authors: Catherine K. Foo, John A. St. John, Oscar Westesson, Nicholas J. Hahner, Aleah F. Caulin, Mitchell E. Skinner, Jeffrey P. Catalano, Kimberly Lung, Urvish G. Parikh, Anne S. Wellde, Jonathan K. Barry, George W. Wellde, Rafael Rosell, Jonathan S. Weissman, William Reilly Polkinghorn, Trever Grant Bivona, Petros Giannikopoulos
Journal: Journal of Clinical Oncology (2014)

e22122 Background: Despite recent advances in the understanding of the biology and genetics of lung cancer, and despite the introduction of multiplex somatic mutation testing in the clinic, the long-term survival for all lung cancer patients, particularly for those with advanced disease, remains low. In order to address the critical need for comprehensive profiling of these patients, we developed a CLIA-certified, whole exome sequencing assay that applies a disease-focused, integrated approach to identify therapeutically actionable drivers of disease in a clinically relevant timeframe. Methods: 12 surgically resected NSCLC specimens along with corresponding normal tissue underwent DNA extraction, and were prepared for whole exome sequencing using the using the Agilent SureSelectXT Human All Exon V5 kit and were sequenced on the Illumina HiSeq2500 platform at an average depth of >250X. Somatic variants and somatic copy number alterations (SCNAs) were identified and compared to results obtained by two independent CLIA laboratories. In addition, a well-characterized panel of 11 germline samples obtained from the 1000 Genomes Project were pooled to simulate a broad spectrum of somatic single nucleotide variant and indel allele frequencies. Analyses were also repeated by the same and different technolgists to establish intermediate precision. Results: Sequencing, data analysis and clinical reporting were completed for all 12 cases with an average turnaround time of less than 3 weeks. Somatic variants were identified with a sensitivity across the entire exome of > 95%, and a sensitivity of > 98% (98.7%) in cancer hotspots. The overall accuracy was > 99%, with a limit of detection of 10% mutant allele frequency. Somatic copy number alterations were detected with an overall accuracy of 99.2%. Concordance of mutation calls between repeated samples were > 99%. Conclusions: We demonstrate the feasibility of performing a comprehensive whole exome sequencing and copy number analysis in a clinically relevant timeframe with a high degree of accuracy and precision. Further validation studies are currently underway to clinically assess global gene expression and mutant allele-specific gene expression changes via total RNA-seq.
Phase I trial of extrapleural pneumonectomy [EPP], and intracavitary intraoperative hyperthermic [IOHC] cisplatin with amifostine cytoprotection for malignant pleural mesothelioma. [MPM]
Authors: L. Zellos, W. G. Richards, L. Capalbo, M. Jaklitsch, R. Bueno, B. Johnson, D. J. Sugarbaker
Journal: Journal of Clinical Oncology (2007)

18059 Background: Despite aggressive multimodality treatment, MPM remains a disease with poor survival. Innovative strategies that improve cytoreduction are needed. We sought to determine the maximum tolerated dose (MTD) and quantify the toxicity of cisplatin IOHC with amifostine cytoprotection in the setting of EPP for MPM. Methods: 42 MPM patients (pts) were enrolled in an IRB approved protocol. Those who underwent EPP with cytoreduction to &lt; 1 cm 3 received 910 mg/m 2 of amifostine followed by 1-hour perfusion of the chest and abdomen with cisplatin dose escalation (75–200 mg/m 2 ). Pts were monitored prospectively. Results: 13 pts were unresectable (9 with chest wall invasion, 3 with chest wall and mediastinal invasion and 1 with cardiac invasion). The 29 resected pts had median age 57 years; median stay 15 days, and mortality rate 6.8% (2/29 pts.). Complications were: atrial fibrillation 65.5% (19 pts.), deep vein thrombosis 31% (9 pts.), and grade 3 renal toxicity 31% (9 pts.). Renal toxicity was unrelated to cisplatin dose and no MTD was determined. Median follow-up was 17 months. Median survival (MS) for 42 enrolled pts was 17 months. The 13 unresected pts experienced a 10-month MS. The 29 resected pts had a 20-month MS while 24 epithelial pts experienced a 29-month MS and 5 non-epithelial pts 13 month MS (p=0.006). The 15 pts receiving higher cisplatin doses (175–200 mg/m 2 ) had a 26-month MS while the 14 pts receiving lower doses (75–150 mg/m 2 ) had 16-month median survival. (p=NS) The 10 pts with negative margins has a MS of 25.8 months while 19 pts with positive margins had a 13.4 month MS (p=NS). MS for 20 pts with N2 (-) nodes was 30 months and for 9 pts with N2 (+) 13 months (p= 0.0115). MS for 18 pts with BWH/DFCI stage 1–2 was 32 months and for the 11 stage 3 pts 14 months (p=0.0022). Conclusions: 1) IOHC was technically feasible with acceptable morbidity and mortality 2) Single dose amifostine was inadequate against cisplatin renal toxicity and MTD was not determined. 3) Stage 1–2, epithelial type or N2 (-) pts demonstrated survival greater that expected historic controls. No significant financial relationships to disclose.
BRAF mutation predicts MEK-dependence in non-small cell lung cancer (NSCLC)
Authors: C. A. Pratilas, E. Halilovic, A. Sawai, O. Grbovic-Huezo, N. Rosen, D. B. Solit
Journal: Journal of Clinical Oncology (2007)

10523 Background: Constitutive ERK signaling is common in human cancer and is often the result of activating mutations in BRAF, RAS and upstream receptors. Missense BRAF kinase domain mutations are frequently observed in melanoma, colon and thyroid cancers and less frequently in lung and other cancer types. The vast majority (&gt;90%) involve a glutamic acid for valine substitution at codon 600 (V600E), which results in elevated BRAF kinase activity. BRAF kinase domain mutations with intermediate and impaired kinase activity have also been identified, most frequently in NSCLC. We have previously reported that tumors with V600E BRAF mutation are selectively sensitive to MEK inhibition. Methods: Using the potent and selective MEK1/2 inhibitor PD0325901 (Pfizer), we examined a panel of NSCLC cell lines with mutant EGFR, KRAS, and/or low, intermediate and high-activity BRAF kinase domain mutations, with regard to MEK dependence. In all but one case, EGFR, KRAS and BRAF mutations were mutually exclusive. Results: Consistent with our prior results, NSCLC cells with V600E BRAF mutation were exquisitely sensitive to MEK inhibition (PD0325901 IC50 of 2nM). The proliferation of cells with non-V600E mutations, including those with high (G469A), intermediate (L597V) and impaired (G466V) kinase activities, was also MEK dependent with IC50's ranging between 2.7 and 80 nM. Inhibition of MEK in these cells resulted in downregulation of cyclin D1 and G1 growth arrest, with variable induction of apoptosis. Despite high basal ERK activity, NSCLC tumor cells with EGFR mutation were uniformly resistant to MEK inhibition (at doses of up to 500nM), despite effective inhibition of ERK phosphorylation. Tumor cells with RAS mutation had a more variable response, with some cell lines demonstrating sensitivity, while others were completely resistant. There was no correlation between basal ERK activity and sensitivity to MEK inhibition. A strong inverse correlation between AKT phosphorylation/ activity and PD0325901 sensitivity was observed. Conclusions: These results suggest that MEK inhibition may be useful therapeutically in tumors with V600E and non-V600E BRAF kinase domain mutations. The results also suggest that inhibition of both MEK and AKT signaling may be required in NSCLC tumors with high basal AKT activity. No significant financial relationships to disclose.
TBCRC 019: An open-label, randomized, phase II trial of nanoparticle albumin-bound paclitaxel with or without the anti-death receptor 5 (DR5) monoclonal antibody tigatuzumab in patients with metastatic, triple-negative (ER, PR, and HER2-negative) breast cancer.
Authors: A. Forero-Torres, N. U. Lin, M. C. Liu, H. S. Rugo, S. Puhalla, R. Nanda, I. A. Mayer, A. M. Storniolo, T. A. Traina, D. F. Hayes, M. F. Rimawi, M. P. Goetz, F. J. Esteva, W. J. Irvin, A. C. Wolff
Journal: Journal of Clinical Oncology (2011)

TPS128 Background: TNBC has poor prognosis and with no known therapeutic targets in clinical use. Tigatuzumab is a humanized anti-DR5, agonistic, monoclonal antibody with strong preclinical data showing in vitro and in vivo activity against basal-like breast cancer cells enhanced by chemotherapeutics like paclitaxel. Phase I studies show single-agent tolerability and when combined with paclitaxel. Methods: Randomized 2:1 phase II clinical trial of nanoparticle albumin-bound paclitaxel (nab-PAC) ± tigatuzumab in patients with TNBC with no limit in the number of prior metastatic chemotherapy agents (including paclitaxel or docetaxel). Patients will be stratified by prior exposure to any chemotherapy for metastatic disease and by prior taxane use for metastatic disease. Patients will receive nab-PAC weekly x 3 ± tigatuzumab every other week, repeated every 28 days. Primary endpoint is overall response rate (ORR). Patients randomized to nab-PAC alone may crossover to the combination upon disease progression. Planned enrollment = 60 patients (40 on the combination arm) and biopsy of an accessible metastatic lesion is required. Tissue obtained will be analyzed for comprehensive genomic analysis, and DR5/DDX3/IAP regulatory complex profile. Serial circulating tumor cell numbers and M30 expression will be correlated with ORR and progression-free survival. Serum levels of M30 will be obtained and correlated with the expression of the protein in CTCs. The trial will utilize a 2-stage Gehan design and accrual is projected over 12 months.
Association of genomic polymorphisms of metabolising and DNA repair enzymes on clinical outcome of patients with advanced gastric cancer - results of a first interim analysis of a randomised multicenter phase II study comparing fluorouracil, leucovorin and oxaliplatin (FLO) versus fluorouracil, leucovorin and cisplatin (FLP)
Authors: J. Stoehlmacher, E. Goekkurt, S. Al-Batran, V. Barxten, C. Bokemeyer, E. Jaeger
Journal: Journal of Clinical Oncology (2005)

2008 Background: To evaluate the impact of genomic polymorphisms of drug metabolising and DNA repair enzymes on response to FLO and FLP. Patients: Pts. were randomised to receive FLO: F 2600mg/m2 24h infusion, L 200mg/m2 and oxaliplatin 85mg/m2 every two weeks or FLP: F 2000mg/m2 24h infusion, L 200mg/m2, weekly and cisplatin 50mg/m2 every two weeks. Interim analysis was performed after 80 pts. were randomised. No significant differences between FLO and FLP in terms of response were observed (abstr. submitted by Al-Batran et al.). Methods: Genotypes were determined for TS-5’, TS-3’, ERCC1–118, GSTP1–105, ERCC2–751, MTHFR-677, MTHFR-1298 using a PCR based RFLP technique. Results: Blood samples from 52 out of 80 pts. were available for genotyping. No association between any of the polymorphisms analysed and response was observed for the entire group of 52 pts. However, pts. who received FLP were more likely to fail therapy when possessing a GSTP1–105 ILE/ILE genotype (n=10/10, 100%) as compared to patients with GSTP1–105 ILE/VAL or VAL/VAL genotype (n=8/13, 62%, p=0.038). Pts. treated with FLO showed a superior response possessing a ERCC1–118 CC genotype (n=3/3, 100%) if compared to pts. with ERCC1–118 CT or TT genotype (n=7/25, 25%, p=0.037). There was a trend for pts. with MTHFR-677 CC genotype to fail therapy (n=10/12, 83%) if compared to pts. with MTHFR-677 CT and TT genotype (n=8/16, 50%, p=0.068). Conclusion: Gastric cancer pts. who showed a genotype that is associated with enhanced drug accumulation (GSTP1–105 VAL variants), increased sensitivity to 5-FU (MTHFR-677 CC) or diminished DNA-repair (ERCC1–118 CC) appeared to be more likely to respond to 5-FU/platinum chemotherapy. These preliminary data further suggest that there might be important differences for prediction of response based on genotyping analyses between FLP versus FLO. These differences might become valuable tools to design tailored treatment plans for these patients if FLO and FLP will be proven to be similarly effective. No significant financial relationships to disclose.
Local Staging of Adenocarcinoma of the Colon With Multislice Ct
Authors: Etienne Danse, Marie-Christine Nicaise, J. A. Jouret-Mourin, S. C. Sempoux, K. A. Kartheuser, G. L. Goncette, A. L. Annet, Jacques Jamart
Journal: Annals of Oncology (2010)
Potentiated B-Cell Antigen Receptor Signaling In Mantle Cell Lymphoma Is Associated With Overexpression Of Surface CD79B and IgM
Authors: June Helen Myklebust, Joshua Brody, Ash A. Alizadeh, Debra K Czerwinski, Arne Kolstad, Michael R Green, Roch Houot, Jan Delabie, Holbrook E Kohrt, Jonathan M. Irish, Ronald Levy
Journal: Blood (2013)
Time to ADT and chemotherapy initiation for treatment of metastatic prostate cancer (mPC).
Authors: Daniella J. Perlroth, Stephen F. Thompson, Yesenia Luna, Dana P. Goldman, Essy Mozaffari, Darius N. Lakdawalla
Journal: Journal of Clinical Oncology (2012)

41 Background: ADT and chemotherapy use in men with mPC may differ across regions in community practice. The extent of variation could indicate whether men with mPC have appropriate access to effective treatments. Methods: We identified 16,024 men diagnosed with mPC in the Surveillance, Epidemiology, and End Results (SEER) database from 2000-2005 linked to their Medicare claims. Patients were excluded if they had a second cancer or disenrolled from Medicare Parts A or B (n=6,155), or failed to initiate therapy with ADT (n=3,400). We identified demographic and clinical information from SEER and treatments and comorbidities from J-codes and ICD-9 codes in the Medicare claims. We used regression models to estimate the probability of advancement to chemotherapy, the time from diagnosis to first ADT use, and time from first ADT to chemotherapy. Then the patient-level predicted results from these models were used to generate summary statistics by hospital service area (HSA). Results: There were 6,469 patients remaining after exclusion who were treated with ADT, and 1,198 of those received chemotherapy (19%). The median age was 76 years old, most were white (77%), married (62%), and 50% had 1 other major comorbidity (most frequent was diabetes, 21%). Men who were younger, married, with fewer comorbidities, and higher Gleason scores were statistically more likely to both receive chemotherapy and use it earlier. After adjusting for clinical and sociodemographic factors, the average time to ADT by referral region was 2.7 months but varied from 1.3 to 5.6; probability of progression to chemotherapy averaged 19% but varied from 6% to 30%, and the time from first ADT to chemotherapy averaged 19.7 months but varied from 12.9 to 25.7 months. The difference in time to ADT between regions in the 10 th and 90 th percentiles of use was 2.6 months, whereas for chemotherapy initiation, it was 12.4 months. Conclusions: Our results suggest that living in different parts of the country has a substantial impact on how clinically similar patients are treated. There was substantial variation across regions in use of and time to initiation of chemotherapy for men with mPC, but not in ADT use.
Clinical and biological effects of gefitinib in EGFR FISH positive/phospho-akt positive or never smoker non-small cell lung cancer (NSCLC): Preliminary results of the ONCOBELL trial
Authors: F. Cappuzzo, L. Toschi, R. Trisolini, L. Bemis, M. Sujita, I. Domenichini, W. Franklin, L. Crino, F. Ciardiello, M. Varella-Garcia
Journal: Journal of Clinical Oncology (2006)

7023 Background: Effectiveness of gefitinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), in never smokers and/or EGFR FISH positive NSCLC patients has been evaluated only in retrospective studies and few data exist on the biological effects of gefitinib therapy in tumor samples. Methods: The ONCOBELL trial is a multicenter prospective phase II study designed to include 39 patients EGFR FISH positive/phospho-Akt (p-AKT) positive and/or never smokers with advanced or metastatic NSCLC. Gefitinib is given at the daily dose of 250 mg. When feasible, primary tumor biopsy was repeated immediately before therapy, during therapy and at progression. Specimens were evaluated for EGFR and HER2 gene copy number by FISH, EGFR gene mutation by DNA sequencing, and EGFR and p-AKT protein expression by immunohistochemistry. Results: Data from the first 28 enrolled patients are available: median age was 60 years (range, 43–80); male/female: 7/21; stage IIIB/IV: 2/26; ECOG PS 0/1/2: 18/6/4; 25 patients had a diagnosis of adenocarcinoma and/or bronchioloalveolar carcinoma; 13 patients had brain metastases, and in 10 cases gefitinib was offered as first-line therapy. Twenty-four patients were never smokers and 19 were EGFR FISH positive. Overall response rate was 54%, including 1 complete and 14 partial responses. Median time to progression was 6.45 months, and median survival was not reached. Response to therapy was not influenced by previous therapies or presence of brain metastases. Toxicity was mild, and consisted in grade 1–2 skin rash (68%) and diarrhea (57%). One patient developed grade 3 diarrhea and another patient was hospitalized for acute interstitial lung disease. In patients exposed to previous chemotherapy, no difference in EGFR or HER2 FISH results were observed in specimens collected at the time of original diagnosis compared to specimens collected immediately before gefitinib therapy. In 14 cases primary tumor biopsy was repeated during gefitinib therapy. Conclusions: These preliminary data indicate that gefitinib is highly effective in patients with trial characteristics. Clinical and biological data for the entire cohort will be available in June 2006. No significant financial relationships to disclose.
Carcinoma of the Ampulla of Vater: Follow-up 24 years period
Authors: J. L. Gonzalez-Trujillo, C. A. Ramirez-Alvarado, E. León
Journal: Journal of Clinical Oncology (2008)

15677 Background: To assess the management and outcome of carcinoma of the Ampulla of Vater in a single tertiary referral center. Methods: The notes of all patients with a diagnosis of carcinoma of the Ampulla of Vater referred to our unit for over 24-year period were identified and retrospectively reviewed. Presentation, management and outcome were assessed. Results: Eighty-six patients were identified. The median age was 57 years (range 20–94 years). Female to male ratio was 1.1:1. Fifty one patients underwent pancreaticoduodenectomy (operative morbidity 51% and mortality 15.7%), thirteen patients underwent palliative surgery, four patients local resection and eighteen patients weren't surgical treatment. Sixteen patients in 51 Whipple's procedure received adjuvant treatment (eight radiotherapy, three chemo-radiotherapy and five chemotherapy). The median duration of survival was 14 months for the treatment group and 16.7 months for the observation group (p=0.26). According to the Log rank test and Cox analysis, T3 or T4 tumors (p<0.001), poor histologic grade (p<0.001), positive margins (p<0.001), surgical morbidity (p=0.22) were prognostic factors for disease-free survival. Positive lymph nodes metastases (p<0.001), positive margins (p<0.001), pour differentiated tumors (p<0.001), surgical morbidity (p=0.04) and T3 or T4 tumors (p<0.001) were prognostic factors for global survival. At a median follow-up of 12 months (range 1–198 months), 25 patients (49%) are alive and 22 patients (43%) are disease-free. In the palliative setting, radiotherapy in non-resection patients (4) and chemotherapy in metastasic patients (6) and best care support in the other patients. At a multivariaty analysis in palliative treatment, minor mortality risk were female [HR 0.29 (CI 95% 0.11–0.78), p=0.014] and radiotherapy treatment [HR 0.14 (CI 95% 0.03- 0.72), p=0.018]. Median survival for patients treatment with radiotherapy were better 324 days and 44 days without radiotherapy (p=0.019). Conclusions: Adjuvant treatment for unfavorable carcinoma of the Ampulla of Vater might equally survival in patients with unfavorable features. No significant financial relationships to disclose.