tbuckley/cabot-search huggingface dataset:
Decision regret following treatment for localized breast cancer: Is regret stable over time?
Authors: Kathryn Anne Martinez, Ken Resnicow, Sarah T. Hawley
Journal: Journal of Clinical Oncology (2013)

19 Background: While studies suggest most women have little regret with their breast cancer treatment decisions, few (or no) studies have evaluated whether regret changes over time. Methods: Women diagnosed with breast cancer between August 2005 and May 2007 reported to the Detroit, Michigan, or Los Angeles County Surveillance Epidemiology and End Results (SEER) registry completed surveys at 9 months post diagnosis (time 1) and again approximately 4 years later (time 2). A decision regret scale (Brehaut, 2003) consisting of 5 items was completed at both time points. Item responses were summed to create a regret score at both 9 months and 4 years (scales of 5 to 25 points, with 25 being most regret). We used multivariable linear regression to examine change in regret from 9 months to 4 years. Independent variables included surgery type (breast conserving surgery, unilateral mastectomy, bilateral mastectomy), presence of invasive disease (yes/no), and recurrence status (yes/no) at follow-up. We included an interaction between surgery type and recurrence status. The model controlled for demographic and clinical factors. Results: The sample included 1,497 women. Mean decision regret at 9 months was 9.5 points and 10.1 points at 4 years (range 5-25) (NS). Two-thirds (64%) of respondents had breast conserving surgery, 26% had unilateral mastectomy, and 9% had bilateral mastectomy. We found no impact of surgery type on change in regret in the overall sample. However, among the, 86 (6%) women who recurred, those who underwent unilateral mastectomy reported significant reduction in decision regret over time relative to recurrent women who had breast conserving surgery (d= -6.76, p=0.024). Average change in regret among non-recurrent women was 0.52 points and was 2.7 points for women who recurred. Conclusions: Decision regret in breast cancer is generally stable over time, yet changes in regret appear to be associated with disease trajectory and treatment received. Our results suggest that more extensive treatment is associated with a reduction in regret only when women experience a recurrence. Understanding patients’ assessment of their decisions related to treatment may be useful for informing future decision making processes.
Engaging patients with their self-reported symptom outcomes trended data.
Authors: Scott Hartman, Diane Denny, Carmon Greene, Morgan Hannaford, Maurie Markman
Journal: Journal of Clinical Oncology (2016)

69 Background: Cancer Treatment Centers of America, Inc. (CTCA) is a national network of hospitals that specialize in the treatment of patients fighting complex or advanced-stage cancer. The Symptom Inventory Tool (SIT) is an assessment tool that captures the patients’ perceived symptom burden for real-time clinical intervention. Patients take a baseline SIT assessment at new patient intake and are eligible to take the SIT every 21 days. The SIT is comprised of the M.D. Anderson Symptom Inventory tool, a validated assessment instrument, along with additional questions and a free text box that were created by CTCA. The SIT became an integral part of patient care at CTCA beginning in 2012. Recognizing the value of the SIT data in real time patient intervention, a project was undertaken to engage the patient with his/her results and facilitate dialogue with his/her care team. Methods: Upon completing the SIT, patients were provided with their Symptoms-At-a-Glance (SAG) report, which is a graphical representation of trended outcomes of their SIT data, along with education on how to interpret the document. Patients were encouraged to review the SAG with their care team as a communication facilitation tool promoting open dialog on those symptoms identified as the most severe and or frequent. Pre and post evaluations of the process were completed via a brief questionnaire for patients and staff to evaluate efficacy of the exchange. Results: A total of 272 patients completed the SIT during the initial 30 days. 80.5% of patients utilized the SAG report during their Medical Oncology appointments and/or took their report with them for subsequent reference. Utilization of the SAG report by interdisciplinary teams for patient intervention showed an increase of 103%. Patients responded favorably to the project and reported that the SAG is a valuable tool which will be shared with their primary care physician and used to update family members. Conclusions: The project was successful in creating improved integration of the SIT outcomes and driving more focused and complete discussions between patients and their providers on a wide spectrum of quality of life issues.
IFCT0401-bio phase II trial: Gefitinib administered as 1st-line in non-resectable adenocarcinoma with bronchioloalveolar carcinoma features (ADC-BAC)—Predictive biomarkers of efficacy and survival
Authors: m. Wislez, M. Antoine, V. Poulot, L. Baudrin, M. Beau-Faller, J. Morere, E. Brambilla, M. Lebitasy, F. Coulet, J. Cadranel
Journal: Journal of Clinical Oncology (2008)

8071 Background: A prospective multicentric trial evaluated gefitinib as 1st-line in non-resectable ADC-BAC. Tissue samples were collected to identify biomarkers associated with disease control, PFS and OS. Methods: Tumor samples were classified as BAC variants or ADC other types and as non-mucinous or mucinous/mixed. PAS staining and immunohistochemistry against TTF1 and EGFR were performed. Polysomy/amplification was examined for EGFR. EGFR 18–21 and KRAS 2 exons were amplified and sequenced. Results: Tumor samples were collected from 65/88 eligible participants. 50 (81%) were BAC (25 non- mucinous, 25 mucinous) and 15 (19%) ADC other types. EGFR high polysomy/amplification was present in 12/50 samples (24%), EGFR and KRAS mutations in 7/56 (12.5%) and 9/50 (18%) samples respectively. PFS was 3.21 mo [IC95%, 2.85–3.70] and associated with skin toxicity (p=0.01), low PAS-staining intensity (p=0.001), high TTF1 expression (p=0.01), non-mucinous BAC (p=0.0006), no KRAS mutation (p=0.003) and presence of high EGFR polysomy/amplification alone (p=0.008) or combined with mutation (p=0.002) in univariate analysis. In multivariate analysis, PFS was associated with no KRAS mutation (HR=0.46, p=0.06) and histology other than mucinous BAC (non-mucinous BAC: HR=0.31, p=0.003; ADC other types: HR= 0.19, p=0.001). OS was 14.0 mo [11.34–22.68] and associated with PS<2 (p=0.02), respiratory symptoms score (p=0.005), non-mucinous BAC (p=0.0006), low PAS-staining intensity (p=0.03), no KRAS mutation (p=0.004), high EGFR polysomy/amplification alone (p=0.008) or combined with mutation (p<0.002) in univariate analysis. In multivariate analysis, OS was associated with PS<2 (HR=0.06, p<0.0001), no KRAS mutation (HR=0.15, p<0.0002), high EGFR polysomy/amplification or mutation (HR=0.1, p=0.0006) and rash (HR=0.30, p=0.006). Conclusions: Molecular and cytological factors are independently predictive of PFS or OS in ADC-BAC treated with gefitinib. No significant financial relationships to disclose.
Screening for colorectal cancer in France: Third edition of the EDIFICE survey.
Authors: Jérôme Viguier, Jean F. Morere, Xavier B. Pivot, Yvan Coscas, Jean-Yves Blay, Claire Roussel, Francois Eisinger
Journal: Journal of Clinical Oncology (2012)

411 Background: In France, after a pilot population-based screening program (2002-2003), a national organized program targeting 17 million persons was progressively implemented starting in 2005 and generalized after 2009. The EDIFICE 3 survey was conducted in 2011, after EDIFICE 1 (2005) and EDIFICE 2 (2008), to provide a better understanding of the participation of the French population in the colorectal cancer screening program and to assess the evolution between the three periods. Methods: This third nationwide observational study, EDIFICE 3, was conducted through phone interviews among a representative sample of 1603 subjects aged between 40 and 75years, using the quota method. This analysis focused on the target population of the national screening program (50-74 years old). Results: In 2011, 59% of subjects between 50 and 74 years (N=946) declared having performed a screening test for colorectal cancer (including fecal test or colonoscopy) versus 38% in 2008 (p&lt;0.05) and 25% in 2005 (p&lt;0.05). Colorectal cancer screening increased significantly in all age groups, especially between 65 and 69 years, and for both sexes. Among the screened population, the recommended interval between two tests was respected in 51% of cases in EDIFICE 3. 62% of unscreened individuals plan to undergo a screening test in the near future. The main factors increasing the probability of screening were: being encouraged by one’s family, the existence of a case colorectal cancer in the family circle, higher frequency of medical consultation, better knowledge of the screening process and being reassured by the screening. The main reasons for not undergoing the screening were: not feeling concerned, fear of exams or results, no recommendation by the GP and carelessness. Conclusions: The European guideline objective rate of participation for colorectal cancer screening (65%) is not yet reached. This goal could be achieved by motivating the unscreened population already planning to perform a test. The trend for increasing testing will probably be confirmed in the future if the reasons for non-attendance in an organized program are addressed.
Clinician report as source of apathy information on cancer-related fatigue (CRF) patients.
Authors: M. A. Kallen, C. P. Escalante, J. D. Duffy, R. U. Valdres, T. Lam, E. F. Manzullo
Journal: Journal of Clinical Oncology (2010)

e19540 Background: Interventions for CRF require patient commitment, particularly if incorporating lifestyle change. Apathy, or lack of motivation, may diminish prospects for a successful outcome, yet few studies have addressed apathy in cancer patients. We conducted an observational study in our CRF Clinic and report on 79 patients evaluated for apathy. Our objective was to determine the apathy information source (clinician vs. patient) most associated with fatigue-related symptoms. Methods: New CRF patients were evaluated for apathy using the Apathy Evaluation Scale (AES); its scores (range 18-72) can be used to classify patients as apathetic or not (≥38 = clinically significant apathy). Two AES versions were employed: Clinician (AES-C) and Patient (AES-S). Scores and reliability were compared, then scores correlated (Spearman's rho) with five symptoms commonly experienced by CRF patients (fatigue, pain, depression, anxiety, sleep disturbance). Apathetic patient symptoms were compared (Mann-Whitney U) to non-apathetic per apathy measure, and agreement on apathy classification assessed. Results: 79 new CRF patients were evaluated for apathy by both clinician and patient. Median age was 59 years (range 26-84), 72% (n = 57) were female, 76% (n = 60) white, and 71% (n = 56) married. Leading cancer diagnoses were breast (37%, n = 29) and leukemia/lymphoma/myeloma (16%, n = 13). Median AES-C was 25 (range 18-61), with 19% (n = 15) clinically apathetic. AES-S range was 18-61, but median was 31 and 27% (n = 21) classified apathetic. Alpha reliability was .96 (AES-C) and .89 (AES-S). AES-C was correlated (p<.05) with fatigue (.27), depression (.41), and anxiety (.29); AES-S was correlated with depression (.49), anxiety (.33), and sleep disturbance (.26). Apathetic patients (AES-C) had greater fatigue (p =.021), depression (p =.001), and anxiety (p =.014) than non-apathetic. Apathetic patients (AES-S) had greater depression (p<.001) than non-apathetic. Apathy classification discordance was 18%. Conclusions: Clinician-reported apathy exhibited symptom correlations and greater discrimination of apathetic vs. not symptom burden. This suggests clinician-reported apathy may have important clinical and research use. No significant financial relationships to disclose.
ARN-509 in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Dana E. Rathkopf, Emmanuel S. Antonarakis, Neal D. Shore, Ronald Tutrone, Joshi J. Alumkal, Charles J. Ryan, Mansoor N. Saleh, Ralph J. Hauke, Edna Chow Maneval, Howard I. Scher
Journal: Journal of Clinical Oncology (2013)

48 Background: ARN-509 is a novel second-generation anti-androgen that binds directly to the ligand-binding domain of the androgen receptor, impairing nuclear translocation and DNA binding. The Phase II portion of a multicenter Phase I/II study is evaluating the activity of ARN-509 in 3 distinct patient populations of men with CRPC: 1) non-metastatic treatment-naïve CRPC; 2) mCRPC treatment-naïve (tx-naïve); and 3) mCRPC abiraterone acetate pre-treated (AA). Preliminary results for the 2 cohorts of patients with metastatic CRPC are presented here. Methods: All patients had metastatic CRPC with progressive disease based on rising PSA and/or imaging. No prior chemotherapy for metastatic prostate cancer was allowed. Patients on the AA pre-treated cohort had to have been treated with AA for at least 6 months. All patients received ARN-509 at the recommended Phase II dose of 240 mg/day (Rathkopf et al, GU ASCO 2012). The primary endpoint was PSA response rate at 12 weeks according to the Prostate Cancer Working Group 2 Criteria in each of the treatment groups. Secondary endpoints included safety, time to PSA progression and objective response rates. PSA assessments were collected every 4 weeks and tumor imaging was performed every 16 weeks. Results: A total of 46 patients were enrolled: 25 on the tx-naïve and 21 on the post-AA cohorts. The combined median age was 68 (range 48-91) and at baseline, patients presented with ECOG performance status 0 (57%), Gleason Score 8-10 (52%), and median PSA of 14.7 (tx-naïve) and 58.4 (post-AA) ng/mL. All patients received prior treatment with a LHRH analog with or without a first-generation anti-androgen. To date, 15 patients discontinued the study due to disease progression (11), adverse events (2) and consent withdrawn (2). The most common treatment-related adverse events (AE) were fatigue (30%), abdominal pain (24%), nausea (22%), and diarrhea (17). There was only 1 treatment-related Grade 3 AE of abdominal pain. At 12 weeks, the PSA response was 88% (tx-naïve) and 29% (post-AA). Conclusions: In men with mCRPC, ARN-509 is safe and well tolerated, with robust PSA response in the tx-naïve cohort. Post-AA data suggests that ARN-509 has activity in a subset of patients that developed resistance to abiraterone acetate. Clinical trial information: NCT01171898.
Identification of signaling pathways involved in the mechanism of action of the immunomodulatory peptide gamma-D-glutamyl-L-tryptophan.
Authors: J. Papkoff, H. Lee, G. Singh, S. Singh, S. Chitta, K. Andrew, P. Quintel, J. S. Rosenberg, B. A. Watkins, S. T. Sonis, C. W. Tuthill
Journal: Journal of Clinical Oncology (2011)

5591 Background: Gamma-D-glutamyl-L-tryptophan (SCV-07) is being studied for attenuation of oral mucositis (OM) in head and neck cancer patients receiving chemoradiation therapy. In a pilot study SCV-07-treated subjects had delayed onset of ulcerative OM (Adkins 2009) which correlated with changes in circulating cytokines (Alterovitz 2010). In animal studies SCV-07 inhibits growth of different xenografted tumor types. SCV-07 acts via immune modulation; initial evaluation of SCV-07 signaling demonstrated inhibition of cytokine induced STAT3 transcriptional activity. In this study we explored further the molecular mechanisms by which SCV-07 interferes with mucositis pathobiology and concurrently exhibits anti-tumor activity. Methods: Tyrosine phosphorylated STAT3 (STAT3 PY) was evaluated by Western blot of Jurkat or CD45 mutant Jurkat cells with or without IL-10 or IFNα stimulation and SCV-07. Global phosphorylation profiles were analyzed using phosphoprotein detection array kits. C57/B6 mice inoculated with B16F0 tumor cells were treated with vehicle or SCV-07 and plasma cytokines analyzed by multiplex assay when tumor inhibition was evident. Results: SCV-07 significantly inhibited IL-10- and IFNα-induced STAT3 PY in Jurkat cells which was blocked by pervanadate treatment, implicating tyrosine phosphatase activity. Phosphatase CD45 was not required since STAT3 PY inhibition was seen in CD45 mutant Jurkat cells. However, SCV-07 induced activating phosphorylation of the phosphatase SHP-2 and altered phosphorylation of Src family kinases and STAT5a/b, known substrates for SHP-2. SCV-07 also decreased IFNα stimulated phosphorylation of SHP-2 associated immunoreceptors Siglec3 (CD33) and SIRPbeta1 (CD172B). SCV-07-treatment of B16 bearing mice slowed tumor growth and significantly decreased the STAT3-induced cytokines MCP-1 and IL-12p40 which are implicated in immune pathology. Conclusions: These data suggest a model where SCV-07, via SHP-2 activation and STAT3 inhibition, could shift macrophage subsets from M2 to M1 and T cells from Th2 to Th1, thereby promoting an immune regulatory environment that inhibits both mucositis and tumor progression.
A Multicenter Phase I/II Trial Evaluating the Safety and Efficacy of Lenalidomide [Revlimidä (R), CC-5013] in Combination with Doxorubicin and Dexamethasone (RAD) in Patients with Relapsed or Refractory Multiple Myeloma.
Authors: C. Gerecke, S. Knop, M.S. Topp, S. Kotkiewitz, H. Gollasch, P. Liebisch, G. Hess, K. Watters, H. Einsele, R.C. Bargou
Journal: Blood (2005)
Treatment of neuroendocrine tumors (NETs) with combination of everolimus and lu-177 radiolabeled somatostatin analogue.
Authors: Ali Husain Aljubran, Mahmoud Tuli, Hussein Raef
Journal: Journal of Clinical Oncology (2015)

TPS502 Background: Treatment of Grade 1 and 2 NET is complex and involves surgical, Locoregional and systemic modalities depending on the manifestations as well as extent of disease. Of the emerging new systemic modalities are everolimus and radiolabelled somatostatin analogue. everolimus is FDA approved for advanced pancreatic NET whereas radiolabelled somatostatin analogue is still not standard therapy in the USA. However, it is gaining popularity especially in Europe as effective systemic therapy for somatostatin receptor positive tumors. Subclinical animal model research showed synergistic effect of the combination of everolimus and the Lu-177 radiolabeled somatostatin analogue. The goal of this study is to assess the safety and efficacy of the combination of Everolimus and the intravenous radiolabeled Lu-177 DOTATOC Therapy in the treatment of unresectable G1-2 neuroendocrine tumors of all gastrointestinal, lung and pancreatic origins. Methods: This is a phase 1 – 2 study. The phase 1 part involves finding the maximum tolerating dose (DLT) of everolimus and accordingly to recommend dose for the phase II part. The second part is a standard phase II trial assessing the efficacy and toxicity of the regimen at the recommended dose. A total of 30 patients will be enrolled, based on the expected response of the combination to be 20% with power of 80 and type 1 of.05, compared to the known everolimus alone overall all response of 5%. In phase 1, three patients will be treated with 5mg daily with expansion to six patients if one of the three patients experienced DLT. If DLT occurred in none of three or no more than one of six patients, everolimus dose will be escalated to 10 mg and will be considered the recommended dose for phase 2 part. Otherwise, everolimus dose will be kept at 5 mg daily and will be considered the recommended dose for phase II part. DLT in more than two of six patients will be considered unacceptable, and the trial will be closed because of high toxicity.
Long-term follow-up of dose-dense neoadjuvant chemotherapy in patients with stage II/III breast cancer.
Authors: S. Nimmagadda, L. Nabell, J. T. Carpenter, C. I. Falkson, H. Krontiras, J. F. De Los Santos, M. M. Urist, K. I. Bland, A. F. LoBuglio, Y. Li, A. Forero-Torres
Journal: Journal of Clinical Oncology (2011)

e11048 Background: Prior studies have shown that women with operable breast cancer had no improvement in disease free survival (DFS) or overall survival (OS) having received chemotherapy (AC) either pre or postoperatively. However, they were able to delineate a subset of women who had improvement in DFS and OS. Achieving a pathological complete remission (pCR) was directly proportional to DFS and OS. Dose dense adjuvant chemotherapy (ATC) has shown a statistically significant improvement in DFS and OS. Methods: We performed a single institution review of patients (pts) enrolled in a neoadjuvant trial who received dose dense neoadjuvant chemotherapy (doxorubicin 60mg/m2 IV Q2wks x4, paclitaxel 175mg/m2IV Q2wks x4 and cyclophosphamide 600 mg/m2 IV Q2wks x4) to asses response rates, safety and DFS. Women with newly diagnosed breast cancer T > 3cm, any N, and M0 were enrolled. Results: Since 2/2003, 48 pts were enrolled in a trial at UAB (mean age 48.7, range 28-64) and received dose dense chemotherapy. The median follow up is 67.9 months (range 8-88 months). Forty one pts completed dose dense chemotherapy and underwent surgery. Seventeen (41.4%) pts achieved a pCR in the breast and of those 14 (34%) pts were also pathologically negative in axillary lymph nodes. Ten of the 17 pts with pCR in the breast were triple negative. Nine pts have had disease relapse including one pt (HER2+) who had achieved a pCR. Two pts had febrile neutropenia, 2 pts had grade 3 anemia and none with grade 4 thrombocytopenia or anemia. Non hematological grade 3 or 4 toxicity included: venous thrombosis 3 pts, hyperglycemia 2 pts, syncope 1 pt, varicella zoster 1 pt and neuropathy in 2 pts. Conclusions: Our results show that dose dense neoadjuvant chemotherapy is effective, achieving high number of pCRs (breast and node) in triple negative and HER2+ breast cancer subtypes as opposed to hormone receptor positive cancers, with tolerable toxicity. Achieving a pCR is an important factor predicting the subsequent risk of relapse across all tumor types. Triple-negative HER2+ ER+ Total Number of cases (%) 17 (41) 6 (15) 18 (44) 41 (100) Breast pCR 10 (59) 5 (29) 2 (12) 17 (100) Breast/node pCR 8 (57) 4 (29) 2 (14) 14 (100) Relapses 4 2* 3 9 pCR in relapses None 1 None 1