tbuckley/cabot-search huggingface dataset:
Molecular testing guidelines for selection of colorectal cancer patients for targeted and conventional therapies.
Authors: Antonia R. Sepulveda, Stanley R. Hamilton, Wayne Grody
Journal: Journal of Clinical Oncology (2014)

600 Background: Molecular testing to enhance the response of colorectal cancers (CRC) to targeted and conventional therapies has been the center of many recent studies. While testing for KRAS mutations is generally accepted as a requirement to select patients for anti-EGFR antibody therapies, evidence-based guidelines for other markers are needed. The objective of this project is to establish evidence-based recommendations for the molecular testing of CRC tissues to guide EGFR-targeted therapies and conventional chemotherapy regimens. Methods: Three professional societies: American Society of Clinical Pathologists (ASCP), College of American Pathologists (CAP) and the Association for Molecular Pathology (AMP) have selected co-chairs, and multidisciplinary expert and advisory panels, which include specialists in pathology, GI oncology, surgery, gastroenterology and genetics. A systematic review was designed based on five overall key questions: (1) What biomarkers are useful for CRC management (selection of patients for targeted and conventional therapies)? (2) How should tissue specimens be processed for biomarker testing for CRC management?; (3) How should biomarker testing for CRC management be performed? (4) How should molecular testing of CRC be implemented and operationalized?; V: Should other genes/biomarkers be routinely tested? The expert panel will review title-abstract (TA) and full-text (FT) in DistillerSR software. Data extraction will then be performed and the panel will draft recommendations based upon evidence tables and the considered judgment process. Results: A systematic review was performed to capture published articles from January 2009 through August 2013, yielding 2,883titles to date. Currently the TA review phase is in course. Release of draft recommendations during an open comment period is anticipated in early 2014. Conclusions: The ASCP-CAP-AMP Molecular Testing Guidelines for Selection of Colorectal Cancer Patients for Targeted and Conventional Therapies will provide evidence-based guidelines for molecular testing of CRC. The final publication release is anticipated for the fall 2014.
Relief of bowel-related symptoms with telotristat etiprate in octreotide refractory carcinoid syndrome: Preliminary results of a double-blind, placebo-controlled multicenter study.
Authors: Thomas M. O'Dorisio, Alexandria T. Phan, Robert M. Langdon, Billie J. Marek, Nadeem Ikhlaque, Emily K. Bergsland, Joel Freiman, Linda Law, Phillip Lee Banks, Kenneth Frazier, Jessica Jackson, Brian Zambrowicz, Matthew Kulke
Journal: Journal of Clinical Oncology (2012)

4085 Background: Diarrhea associated with carcinoid syndrome has been attributed to tumor production of serotonin. Telotristat etiprate, (LX1032, LX1606), is an oral inhibitor of peripheral serotonin synthesis. This study explored the safety, tolerability, and efficacy of telotristat etiprate in carcinoid patients with octreotide-refractory diarrhea. Methods: Carcinoid patients with ≥4 bowel movements (BMs)/day on octreotide were randomized 3:1 to receive telotristat etiprate or placebo as double-blind treatment. Patients enrolled in sequential, escalating dose cohorts of 150, 250, 350, or 500 mg tid, followed by a 500 mg tid expansion cohort. Patients were followed for toxicity, 24-hr urinary 5-HIAA (u5-HIAA), BM frequency, and self-reported bowel-related symptoms. Subjects were asked “In the past 7 days, have you had adequate relief of your carcinoid syndrome bowel complaints such as diarrhea, urgent need to have a bowel movement, abdominal pain or discomfort?” Responses (yes or no) were analyzed as categorical variables. Results: 16 patients enrolled in the 4 escalating dose cohorts and 7 in the expansion cohort; 18 on telotristat etiprate and 5 on placebo. Median age: 62 yrs; mean 6.3 BMs/day (range, 4-10). AEs included primarily mild-moderate diarrhea, nausea, and abdominal discomfort. In treated subjects, adequate relief was reported as: Week 1 - 6/18 (33.3%), Week 2 - 5/16 (31.3%), Week 3 - 5/15 (33.3%), and Week 4 - 6/13 (46.0%). No placebo subjects reported improvement at any timepoint. Biochemical response (≥50%reduction in u5-HIAA) and BM response (≥30% reduction in daily BMs for 2 weeks) were associated with reporting of adequate relief. For evaluable telotristat etiprate-treated patients, 9/16 (56%) experienced a biochemical response and 5/18 (28%) experienced a clinical (BM) response; no placebo subjects achieved either biochemical or clinical response. Conclusions: Treatment with telotristat etiprate was associated with decreases in u5-HIAA and BM frequency, and with self-reported relief of bowel related symptoms. Treatment in an extension phase with open-label telotristat etiprate is ongoing.
Evaluation of tumour microvessel density &amp; pericyte coverage index following neoadjuvant chemotherapy in primary breast cancer
Authors: M. L. W. Ah-See, R. J. Burcombe, F. M. Daley, P. I. Richman, A. R. Padhani, S. M. Bentzen, S. B. Fox, A. L. Harris, A. Makris
Journal: Journal of Clinical Oncology (2005)

655 Background: Angiogenesis is critical for the growth & metastasis of breast tumours & can be quantified using intratumoural microvessel density (MVD). Pericyte recruitment to the tumour microvasculature is thought to reflect vessel maturation & thus pericyte coverage index (PCI) provides a qualitative measure of tumour angiogenesis. Here we assess the effect of anthracycline-based neoadjuvant chemotherapy (NAC) on MVD & PCI in primary breast cancer (PBC). Methods: Paired pre- & post-treatment pathological specimens (diagnostic core biopsy & definitive surgical resection specimen respectively) from 80 women with PBC (median age 47 years; range 29 - 70) who received 5-fluorouracil, epirubicin & cyclophosphamide (FEC) NAC were analysed. Immunohistochemical double-staining was performed using the panendothelial marker, CD34, & alpha-smooth muscle actin (α -SMA). MVD & PCI were scored from random fields (median 9; range 2–31) at x200 magnification or, in the case of small samples (n=20), from all fields (median 2; range 1–12). Individual microvessels (CD34 positive) were counted per field & expressed per mm2. PCI was scored as the number of CD34 & α -SMA positive vessels & expressed as a percentage of all CD34 positive vessels within the field. Change in median MVD & PCI following NAC was evaluated using the Wilcoxon’s signed rank test. Results: The median (interquartile range) pre-NAC MVD & PCI values were 76.4/mm2 (46.5 - 106.6/mm2) & 17.3% (6.6 - 30.4%) respectively & post-NAC MVD & PCI values were 72.2/mm2 (50 - 100/mm2) & 25.5% (18.2 - 43.3%) respectively. There was no significant difference between the pre- & post-NAC MVD values (p = 0.48), however, there was a significant difference between the pre- & post-NAC PCI values (p<0.0001) with an increase in PCI following NAC. Conclusions: The MVD of breast tumours following FEC NAC is not significantly different to that measured in the pre-NAC diagnostic core biopsy samples. A significant increase in the PCI of the tumour microvasculature occurs following NAC. This would suggest a differential effect of NAC on the tumour microvasculature according to functional vascular status, with a reduction in the proportion of “immature” blood vessels. No significant financial relationships to disclose.
Timeliness of end-of-life (EOL) discussions for blood cancers: A national survey of hematologic oncologists.
Authors: Oreofe Olukemi Odejide, Angel Cronin, Nolan Condron, Craig Earle, Joanne Wolfe, Gregory Alan Abel
Journal: Journal of Clinical Oncology (2015)

13 Background: Although timely EOL discussions have been shown to positively impact EOL care for patients with advanced solid tumors, little is known about EOL discussions for patients with blood cancers. Methods: In 2014, we mailed a 30-item survey to a national sample of hematologic oncologists randomly selected from the American Society of Hematology clinical directory. The survey was developed through focus groups (n=20) and cognitive debriefing (n=5) with hematologic oncologists. We report preliminary data regarding timing of EOL discussions. Results: We received 349 surveys from 48 states (response rate: 57.3%). Median age was 52 years, median time in practice was 25 years, and 43% practiced primarily in tertiary centers. Of all respondents, 56% reported that EOL discussions with blood cancer patients typically occur “too late.” The great majority also reported conducting initialdiscussions regarding resuscitation status, desire for hospice care, and preferred site of death at times other than periods of disease stability (Table). In multivariable analysis adjusting for gender, years in practice, and self-reported confidence leading EOL discussions, respondents practicing in tertiary centers were more likely to report that such discussions occur “too late” (OR=1.91, 95% CI [1.22, 2.98]). Similarly, hematologic oncologists practicing in tertiary centers were less likely to report conducting timely initial resuscitation status discussions (before acute hospitalization or before death clearly imminent, OR=0.52, 95% CI [0.33, 0.82]). Conclusions: The majority of hematologic oncologists in our large national cohort reported late EOL discussions. Moreover, clinicians in tertiary centers were more likely to report late discussions, even when prompted about specific EOL topics. Our data suggest that physician-focused interventions to improve timing of EOL discussions for blood cancers should target those practicing in tertiary centers. [Table: see text]
Using a values assessment as a bridge to advance care planning: Results of 1286 patient reports.
Authors: John Russell Hoverman, Cynthia Taniguchi, Kathryn J Eagye, Susan Ash-Lee, Angela Kalisiak, Sabrina Q. Mikan, Nicole Hartung
Journal: Journal of Clinical Oncology (2016)

12 Background: Recent studies have shown that formal Palliative Care (PC) improves care at the end of life for cancer patients. The role of communication in PC is not defined. Other studies have shown that communication alone can be associated with better end of life outcomes. The US Oncology Network developed and tested a Values Assessment (VA) instrument for routinely broaching difficult topics to facilitate more formal advance care planning (ACP). The results of the first 28 months of the program on over 1200 patients are reported here. Methods: The VA consists of 10 questions of the format “How valuable is it to me to….”, for example “know that I am not a burden to my family, friends or helpers?” Responses were on a 4 point scale from unsure to very valuable. The VA was completed either in person in the clinic or telephonically. VA participation by n = 1286 metastatic cancer patients treated at participating practices from 4/1/2013-7/31/2015 were extracted from the EHR and confirmed by chart review, as were demographic (age, gender, ethnicity), clinical (diagnosis and stage), chemotherapy treatment and outcomes (hospice enrollment and place of death). Demographics and outcomes were compared using the Chi-Squared or Fisher’s Exact Test, or Wilcoxon Rank Sums test for continuous variables. Results: 1268 patients completed the VA. 56.7% were 65 or over. 57.8% went on to complete Advance Directives (AD). 52% had colon or lung cancer. There were 438 deaths of which 431 had a date of last chemotherapy recorded. Of these 431 patients, 78% died at home or inpatient hospice, 14.6% in the hospital. Hospice enrollment with AD was 76.1%, without 60.9%. (p = .008) Median LOS in hospice was 21 days vs. 12.5 (p = .025). Chemotherapy in the last 14 days of life was 7.05% with AD, 13.4% without. The VA was well accepted by patients. Conclusions: A VA as a routine part of practice is feasible and scalable. It can be delivered successfully either face to face or telephonically. It facilitates ACP discussion leading to AD. The results suggest VA and ACP lead to less aggressive care at the end of life.
Prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC): Findings from a North Central Cancer Treatment Group (NCCTG) pooled analysis.
Authors: S. E. Schild, N. R. Foster, J. P. Meyers, K. R. Olivier, H. J. Ross, J. R. Molina, P. J. Stella, L. R. Past, Y. I. Garces, A. A. Adjei
Journal: Journal of Clinical Oncology (2011)

7074 Background: This pooled analysis was performed to evaluate the results of PCI in SCLC patients (pts). 739 pts with stable disease or better following chemotherapy+/-thoracic RT (TRT) were included to examine the potential advantage of PCI in a wider spectrum of pts than generally participate in PCI trials. Methods: 318 pts with extensive SCLC (ESCLC) and 421 pts with limited SCLC (LSCLC) participated in 4 NCCTG phase II trials. 459 pts received PCI (30Gy/15 or 25Gy/10) and 280 did not. Survival and acute events (AEs) were compared using a landmark analysis. Results: PCI pts had significantly improved survival as compared to pts who didn’t receive PCI (HR=0.61 [95% CI: 0.52, 0.72]; p<0.0001). The 1 and 3-year survival rates were 73% & 20% for PCI pts vs. 52% & 6% for no-PCI pts. PCI was still significant after adjusting for age, performance status, gender, stage, and number of metastatic sites overall (HR = 0.74 [95%CI:0.62, 0.88],p=0.0007) and in both ESCLC (HR=0.75,p=0.0175) and LSCLC pts (HR=0.69,p=0.0073). There were significantly more grade 3+AE’s associated with PCI (64%) compared to no PCI (50%) (p=0.0096) across all pts. Those AE’s associated with PCI were alopecia, anemia, esophagitis and lethargy. Esophagitis appeared to be related to treatment sequence and was found in pts who received concurrent TRT&PCI. Dose-fractionation could be compared only for LSCLC pts and 25Gy/10 was associated with better survival than 30Gy/15 (HR=0.72,p=0.0512). Conclusions: PCI was associated with a significant survival benefit for both ESCLC&LSCLC pts who had stable disease or a better response to chemotherapy+/-TRT. Dose-fractionation appears important. PCI’s use was also associated with an increase in overall and specific grade 3+ AE rates.
A comparison of patient characteristics and outcomes in elderly compared to younger patients with esophageal cancer (EC).
Authors: G. T. Watson, G. B. Russell, H. D. Klepin, E. A. Levine, A. Monjazeb, G. Mishra, A. W. Blackstock, M. Aklilu
Journal: Journal of Clinical Oncology (2011)

e14595 Background: Neoadjuvant chemoradiation (CRT) or CRT plus surgery, otherwise known as trimodality therapy (TRI), are viable options for treatment of locally advanced EC. The broad applicability of these treatment options in the elderly population has not been clearly established. To better understand whether age plays a role in the type of therapy given as well as the outcomes experienced, we analyzed patient characteristics and outcome data in patients over and under 70 years of age. Methods: We conducted a prospective, IRB approved analysis of 161 patients (32 aged 70+) diagnosed between 9/14/98 and 4/18/08 with esophageal cancer treated with either CRT or trimodality therapy at Wake Forest University Medical Center. Patient characteristics analyzed included age, gender, performance status, tumor histology, and stage at presentation. Endpoints included time to recurrence, pattern of recurrence, and survival between four separate groups (<70 CRT, 70+ CRT, <70 TRI, 70+ TRI). Group comparisons were done using Fisher’s Exact Test for categorical data; for survival data, the log-rank test of the chi-square approximation was used to compare the survival among groups. Results: There were 161 patients total (73 CRT, 88 TRI). Patient characteristics between the age groups and treatment modalities showed no significant differences in gender, performance status, or histology, but did show a numeric imbalance in stage at presentation that was not significant. No significant differences were appreciated in patterns of recurrence or in relapse free survival between the groups studied. Overall survival (OS) for the analysis is listed in the table. Conclusions: Despite the obvious limitations of this analysis, there does not appear to be a benefit for the addition of surgery over definitive CRT in the 70+ age group. The lack of difference in relapse free survival suggests that other comorbid conditions may play a significant role in this age group. A randomized controlled trial in this age group is warranted. Measures <70 CRT 70+ CRT P value <70 TRI 70+ TRI P value N 55 18 74 14 OS 14.4 mo 9.2 mo 0.41 24.9 mo 11.7 mo 0.039 6-mo survival 82% 67% 95% 79% 1-year survival 54% 44% 76% 50%
Aberrant Methylation of SHP-1 (SH2-Containing Phosphatases 1) and SOCS-1 (Suppressor of Cytokine Signalling 1) Genes in Immunodeficiency-Related Lymphomas.
Authors: Davide Rossi, Clara Deambrogi, Monia Lunghi, Michaela Cerri, Sara Garbellotto, Valeria Spina, Lorenzo De Paoli, Paola Riccomagno, Annunziata Gloghini, Marco Lucioni, Daniela Capello, Marco Paulli, Antonino Carbone, Gianluca Gaidano
Journal: Blood (2006)
A survey of suspected familial breast cancer in Iraqi Kurdish women.
Authors: A. M. Saaed, A. K. Sheikha, S. S. Mohammed, H. A. M. Ameen, S. Y. Sheet, M. Khasraw
Journal: Journal of Clinical Oncology (2011)

1602 Background:Health services in Iraq are trying to catch up with the developed world. Breast cancer is the most common cancer in women and the second cause of cancer related deaths. Most of our breast cancer patients present with incurable, advanced disease. BRCA1 and BRCA2 mutations and other familial cancer syndromes are expected to account for a fraction of all cases and potentially, more than 10% of high-risk patients carry a genetic mutation. Genetic counseling is an evolving area and currently is non-existent in Iraq. Methods: After appropriate institutional approvals were obtained, 500 women with breast cancer who were seen at our center were interviewed using a questionnaire for the following: history of breast cancer, endogenous and exogenous hormonal history and family history of breast and ovarian cancer in first and second degree relatives. Patients were stratified into high-, moderate and average risk groups. High risk patients were compared to average risk patients in regard to hormonal history. Results: Two hundred and five women completed the questionnaire and had the required medical record data available. The median age was 48 years (range 23-92). Hormonal history in the high- and average risk groups were similar (12.8[SD1.3] vs. 13.1[SD1.2]; p=0.33), (25.8[SD4.9] vs. 24.2[SD5.1]; p=0.48) for menarche and first birth respectively. Forty six patients (22%) were < 40 years. Twenty-nine (14%) had positive family history, of those 23 (11%) were considered high-risk. Sixty-eight (33%) were considered candidates for genetic counseling. Conclusions: Hormonal risk factors in the average- and high-risk patient subsets seemed to be similar. The rates of patients having first and second degree relatives affected by breast and ovarian cancer are similar to that seen in Western countries. A third of our patients are candidates for genetic counseling. Therefore at least 3.3%, constituting one tenth of our 33% candidate patients may have a familial cancer syndrome, below the 5-10% quoted for Western women. These estimates are well within the rates seen in Western countries but Kurdish breast cancer patients are unusually young and estimates do not appear to reflect a lifetme risk extending into the postmenopausal population.
Development of effectiveness guidance documents (EGDs) as a stakeholder-driven process for informing study designs for comparative effectiveness research (CER).
Authors: M. R. Tiglao, S. Phurrough, C. D. Mullins, A. P. Abernethy, S. R. Tunis
Journal: Journal of Clinical Oncology (2011)

e16617 Background: Each year, more than 18,000 randomized control trials are published and thousands of other clinical studies conducted. Despite this, systematic reviews intended to inform clinical and health policy decisions routinely conclude that evidence is inadequate or insufficient to draw conclusions. The Center for Medical Technology Policy (CMTP) developed a stakeholder-driven process to create EGDs to provide specific recommendations to product developers, sponsors and clinical researchers on designing CER studies. Methods: Since 2008, CMTP has piloted several EGD initiatives and worked with a team of trial and systematic review experts to better establish and standardize a formal EGD process, outlining specific steps to explicitly engage stakeholders (e.g., patients, payers, clinicians, technical experts, professional societies, regulatory agencies, federal scientific bodies, industry, compendia publishers, advocates) throughout the development phases. Results: As of 2011, CMTP has produced two oncology EGDs and others in cardiology, wound care and genomics. Development of these EGDs involved an iterative, stakeholder-driven process. Project staff conducted interviews with designated stakeholders prior to convening asymposium that: (1) discussed findings from a literature review and the interviews, (2) developed and vetted recommendations, and (3) generated a summary policy document. Draft recommendations were revised by participants and others through email, phone calls, and public comment. Conclusions: The CMTP stakeholder-driven EGD process generates recommendations for designing CER studies aimed at generating evidence for post-regulatory decision makers. Studies that follow these guidelines provide decision-makers with reasonable confidence in understanding the comparative relationships between interventions and health outcomes, consistent with Patient Centered Outcomes Research Institute’s (PCORI) mission and goals.
A randomized phase II study of axitinib in combination with pemetrexed/cisplatin (pem/cis) as first-line therapy for nonsquamous non-small cell lung cancer (NSCLC).
Authors: Chandra Prakash Belani, Nobuyuki Yamamoto, Igor Bondarenko, Sergey V Orlov, Jie Tang, Andreas G. Niethammer, Antonella Ingrosso, Sinil Kim, Giorgio Scagliotti
Journal: Journal of Clinical Oncology (2012)

7551 Background: Axitinib is a potent and selective second-generation inhibitor of VEGF receptors 1, 2, and 3 that has promising single-agent activity in advanced NSCLC. Efficacy and safety of axitinib (in 2 dosing schedules) combined with pem/ciswere evaluatedfor non-squamous NSCLC. Methods: Patients with confirmed stage IIIB, IV, or recurrent non-squamous NSCLC and ECOG performance status (PS) 0 or 1 were stratified by gender and PS, and randomized 1:1:1 to receive six 21-day cycles of axitinib continuously plus pem/cis (arm I); axitinib on Days 2 through 19 followed by a 3-day interruption plus pem/cis (arm II); or pem/cis alone (arm III). Axitinib was administered at a starting dose of 5 mg BID. Pem/cis (500/75 mg/m 2 ) was infused on Day 1 of each cycle. Primary endpoint was progression-free survival (PFS). Results: Baseline characteristics of patients in arm I (n=55), arm II (n=58), or arm III (n=57) ranged between 59–62 yr median age; 62–65% male; 71–85% White; 73–85% current/ex-smokers; and 43–47% PS 0. There were no significant differences in PFS or overall survival (OS) between axitinib-containing arms I and II compared with pem/cis alone, but objective response rates (ORR) were higher (Table). Most common all causality grade 3 adverse events (AEs) in arm I, II, and III, respectively, were hypertension (20%, 17%, 0%); neutropenia (18%, 10%, 9%); nausea (16%, 5%, 7%); vomiting (13%, 5%, 4%); fatigue (11%,16%,16%); and anemia (7%, 14%, 9%). Grade 4 AEs observed in &gt;1 patient were asthenia and pulmonary embolism (2 patients each in arm II). Conclusions: Axitinib combined with pem/cis was generally well tolerated, but efficacy was not significantly better than pem/cis alone in non-squamous NSCLC. [Table: see text]