tbuckley/cabot-search huggingface dataset:
Outcome of patients with KRAS exon 2 wildtype (KRAS-wt) metastatic colorectal carcinoma (mCRC) with cetuximab-based first-line treatment in the noninterventional study ERBITAG and impact of comorbidity and age.
Authors: Stephan Sahm, Thomas Goehler, Christiane Hering-Schubert, Jan Janssen, Ulf Peter Neumann, Michael Schwittay, Mark-Oliver Zahn, Karsten Guenter Stenzel, Alma Katharina Steinbach-Buechert, Friedrich Overkamp
Journal: Journal of Clinical Oncology (2016)

651 Background: Cetuximab in combination with irinotecan- or oxaliplatin-based chemotherapy has shown to increase ORR, PFS, OS of KRAS-wt mCRC patients (pts). ERBITAG aimed to evaluate safety and efficacy of cetuximab in combination with various first-line chemotherapy regimens in pts with unresectable KRAS-wt mCRC. Methods: KRAS-wt pts on a cetuximab-based first-line treatment with written informed consent could be enrolled in this prospective, non-interventional study. Primary endpoint was ORR, secondary endpoints were amongst others PFS, OS, TTF, and resection rate of liver metastasis. Comorbidities were documented and evaluated by the Charlson Comorbidity Index (CCI). Results: 817 eligible KRAS-wt mCRC pts were enrolled at 144 sites across Germany, documentations for 456 pts were finalised and evaluated. The median age was 65 [27-87] yrs, with 51.5% ≤65 yrs, 34.0% &gt;65-75 yrs, and 14.5% &gt;75 yrs. ECOG performance status was 0, 1, 2, or missing in 34.4%, 49.6%, 8.8%, and 7.2% of pts, respectively. CCI was 0 in 54.4%, and ≥1 in 45.6%. Resection of liver and/or lung metastases was done in 17.3% of pts, 13.4% were R0 resected. For pts with liver limited disease resection rate and R0-rate were 29.3% and 23.8%, respectively. Pts with CCI 0 had no different outcome regardless of age (table). Pts with CCI ≥1 and &gt;75 yrs had a lower ORR and decreased TTF, pts &gt;65-75 yrs had only a decreased TTF as compared to the ≤ 65 yrs age group (table). Conclusions: In this large observational trial outcomes (ORR and PFS) of KRAS-wt mCRC pts on a cetuximab-based first-line treatment were comparable to those reported in pivotal trials. Pts older than 75 yrs without comorbidities (CCI =0) showed no difference to younger pts in ORR, PFS, and TTF. Pts &gt;75 yrs with CCI ≥ 1 had a significant lower ORR and decreased TTF. Clinical trial information: http://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu-arzneimitteln/nisdb/nis-details/_455. [Table: see text]
Metabolic syndrome and breast cancer recurrence within the 21-gene recurrence score assay.
Authors: Jeanette Muniz, Kelley M Kidwell, Norah Lynn Henry
Journal: Journal of Clinical Oncology (2015)

104 Background: The 21-gene recurrence score (RS) assay (OncotypeDX) is prognostic in stage I-II, ER+, HER2-, node negative breast cancer (BC). While RS reflects tumor gene expression its interaction with host factors including metabolic syndrome (MS) is unclear. MS conditions such as obesity have been associated with increased risk of BC and worse prognosis. The aim of this study is to determine correlations between MS conditions and RS group or BC outcomes in both pre- and post-menopausal women. Methods: We retrospectively reviewed women with stage I-II, ER+, HER2- node negative BC evaluated with RS assay treated at University of Michigan since 2005. Demographic, pathologic and treatment data, MS criteria and menopausal status were abstracted from medical records. MS was defined as ≥ 3 of the following within 6 months of diagnosis: BMI ≥ 27.7kg/m 2 ; hypertension (HTN); impaired fasting glucose (IFG); HDL &lt; 50mg/dL; hypertriglyceridemia (trig). RS groups were defined as low ( &lt; 18), intermediate (18-30) and high ( &gt; 31). Results: Of 533 eligible women 74% had stage I disease and 61% were postmenopausal at diagnosis. MS criteria prevalence was 43% BMI, 42% HTN, 34% trig, 14% IFG and 13% HDL. MS was present in 22% and more common in post- vs pre-menopausal women (30% vs 9%; p &lt; 0.0001). RS groups were 55% low, 38% intermediate and 7% high. There was no significant association between RS group and overall MS status or any individual criterion, controlling for stage, and no association after stratification by menopausal status. Postmenopausal status was associated with higher RS group (p = 0.039), independent of stage. Over the 4.2 year median follow-up there were 7 deaths and 20 events, including 5 DCIS, 3 local and 11 distant recurrences and 1 second primary BC. There was insufficient power to detect associations between event rate and MS status. Conclusions: MS and comprising conditions are present in many early stage breast cancer patients, especially postmenopausal women. We were unable to identify associations between RS group and MS criteria. Thus the known worse BC prognosis with MS is not reflected in the RS. Identification of factors underlying this higher risk will be important for optimizing management of patients with breast cancer and MS.
Effect of neoadjuvant therapy in patients with resected pancreatic adenocarcinoma.
Authors: Noelle K. LoConte, Tabraiz Aijaz Mohammed, Emily Winslow, Heather B. Neuman, Maureen Smith, Glenn Allen, Jessica Schmacher
Journal: Journal of Clinical Oncology (2014)

338 Background: Retrospective data suggest that neoadjuvant therapy in patients with resectable pancreatic cancer may improve the R0 resection rate and potentially survival. We examined the impact of neoadjuvant therapy on survival rates at a population level for patients with resected pancreatic adenocarcinoma. Methods: Treatment and outcome data were obtained from the Surveillance, Epidemiology and End Results (SEER) Medicare database for patients with pancreatic adenocarcinoma, who underwent a curative intent pancreatectomy from 2001-2007. Patients were stratified by treatment (neoadjuvant vs no neoadjuvant therapy). Kaplan Meier curves were constructed to analyze survival. Cox proportional hazards regression models with and without propensity score weighting were performed to determine the effect of neoadjuvant therapy and race on mortality while adjusting for age, gender, race, marital status, SEER site, urban/rural location, income, education, year of diagnosis, and Charlson Comorbidity Score. Results: 2608 patients were included. 58.4% (n=1523) were between age 66-75 and 41.6% (n=1085) were age 76 or older. 94% (n=2459) did not receive neoadjuvant therapy and 6% (n=162) received neoadjuvant therapy. Patients undergoing neoadjuvant therapy were 28% less likely to experience death at one year (HR 0.72; 95% CI, 0.53-0.97; p=0.03). There was also a trend towards a lower risk of death in this group at 2 years (HR 0.82; 95% CI, 0.66-1.01; p=0.07). Conclusions: Patients with pancreatic adenocarcinoma who underwent neoadjuvant therapy followed by resection had an improved one-year survival relative to patients who did not receive neoadjuvant therapy in this cohort. This effect may partially reflect the role of neoadjuvant chemotherapy in allowing for better selection of patients likely to benefit from surgery. To our knowledge this is the first population-based study that suggests an improved survival in patients with pancreas cancer undergoing neoadjuvant therapy prior to resection. [Table: see text]
Are African American men adequately represented in prostate cancer randomized controlled trials? A systematic review.
Authors: S. Galeb, T. Reljic, B. Djulbegovic, C. Gwede, N. B. Kumar, A. Kumar
Journal: Journal of Clinical Oncology (2011)

6066 Background: African American (AA) men bear a disproportionate burden of incidence and mortality from prostate cancer compared with other racial groups (ACS Report, 2009). The clinical applicability (i.e., external validity) of results of randomized controlled trials (RCTs) depends on whether the sample of patients represents the disease population (NCI Report, 2004). Underrepresentation of AAs in clinical trials could impact the external validity of their findings leading to uncertainty about applicability of results to AA patients. A systematic assessment of participation of AA men in prostate cancer RCTs has not been done. Methods: We performed an electronic search of Medline and Cochrane databases to identify all prostate cancer RCTs for the years 2005-2009. Studies were included if they were phase III trials conducted in North America and evaluated prostate cancer prevention, screening, or treatment. Data were extracted on patient characteristics, interventions, controls, and outcomes. Dual extraction was undertaken for quality assurance. Meta-analysis using fixed effects model was performed to assess overall outcomes according to AA participation. Results: Our initial search identified 1206 citations of which 20 (29 comparisons) met the inclusion criteria. Overall, the methodological quality of included studies was high. Only 55% (11/20) of studies reported data on ethnic composition. Among those, 1 reported 30%, 4 reported 10-20%, and 6 reported <10% AA enrollment. Nine studies reported overall survival data. Pooling data according to the distribution of experimental versus standard treatments by participation of AA men showed no difference. The pooled hazard ratio in trials with >10% participation was 0.94 (95% CI; 0.87, 1.02), 0.97 (95% CI; 0.92, 1.03) in trials with <10% participation and 0.92 (95% CI; 0.80, 1.07) in trials with no reporting of ethnicity data. Conclusions: The results show AA men are underrepresented in prostate cancer RCTs in contrast to their disproportionate disease burden. Despite the conventional belief that AA men have poorer outcomes compared with other racial groups, our results show no difference in outcomes in prostate cancer RCTs.
Anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) or investigator’s choice of chemotherapy in subjects with relapsed or refractory adult T-cell leukemia-lymphoma (ATL).
Authors: Adrienne Alise Phillips, Paul Fields, Olivier Hermine, Graham Taylor, Maria L. Delioukina, Steven M. Horwitz, Juan Carlos Ramos, Jean CÃƒÂ´me Meniane, Stefan K. Barta, Karen M. Dwyer, Michael R. Kurman, Andrew Saunders, Dmitri O. Grebennik, Kevin Conlon
Journal: Journal of Clinical Oncology (2014)

TPS8622 Background: The receptor for macrophage derived chemokine (MDC) and thymus- and activation-regulated chemokine (TARC) CC chemokine receptor 4 (CCR4) is over expressed in several T-cell malignancies including HTLV-1 related ATL where approximately 90% of malignant cells have been shown to overexpress this chemokine receptor. The HTLV-1 transactivator gene (Tax) does not directly induce CCR4 expression. Rather, expression of CCR4 is controlled by the constitutive activation of several transcription factors in HTLV-1 infected cells. Inhibiting the expression of these transcription factors with small-interfering RNAs has been shown to block CCR4 expression and also reduce proliferation of the affected cells.2 Patients with CCR4 positive ATL are more likely to have skin involvement and shorter overall survival (OS; median 9.5 months) compared with CCR4-negative (20.6 months). Mogamulizumab is a defucosylated, humanized, monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity (Potelligent) against primary ATL cells that bind to CCR4. Methods: This study includes patients with previously treated ATL, excluding smoldering type, who have relapsed or are refractory after at least 1 prior systemic therapy. CCR4 expression is not required for eligibility. Patients are randomized (2:1 ratio) to either mogamulizumab or Investigator’s choice (pralatrexate; gemcitabine plus oxaliplatin; or dexamethasone, cisplatin and cytarabine) and stratified by disease type (ie, acute, chronic, and lymphomatous). Patients who progress on the Investigator’s choice regimen may cross over to treatment with mogamulizumab. The primary endpoint is the overall response rate. Efficacy evaluation is based on the Tsukasaki criteria and includes assessment of lymph nodes, extranodal masses, the spleen, liver, skin, peripheral blood, and bone marrow. Safety analyses and an exploratory evaluation of mogamulizumab exposure-response relationship will be performed. The study is being conducted in the US, Europe, and Central/South America. As of 24 January 2014, 44% of 70 planned patients have been randomized. Clinical trial information: NCT01626664.
Do cancer-specific variables improve risk-adjusted hospital quality comparisons?
Authors: Ryan P. Merkow, Thomas E. Kmiecik, David J Bentrem, Mark E Cohen, Bruce L Hall, Warren B. Chow, Clifford Y. Ko, Karl Y. Bilimoria
Journal: Journal of Clinical Oncology (2012)

585 Background: For patients undergoing surgery for cancer, it has been suggested that risk-adjustment with cancer-specific variables is needed when evaluating short-term outcomes. Our objectives were to assess the influence of cancer-related variables on postoperative complications and hospital quality comparisons. Methods: Patients from ACS NSQIP and NCDB who underwent colorectal resection for cancer were linked (2006-2008) to create a dataset containing robust information on comorbidities, complications, and oncologic variables. Three hierarchical models were developed predicting the NSQIP outcome 30-day mortality or any serious morbidity using variables from (1) NSQIP only, (2) NCDB only, and (3) a combined model using NSQIP and NCDB. Models were compared with fit statistics and hospital outlier agreement. Results: From 146 NSQIP hospitals, 11401 patients underwent a colorectal resection for cancer, of which, 1954 (17%) experienced a mortality or serious morbidity event. The first five variables selected in the NCDB-only model were Charlson comorbidity score, neoadjuvant therapy use, T stage, primary payer, and M stage (c-statistic, 0.64; AIC, 9886). The first five variables selected in the NSQIP-only model were ASA class, preop sepsis, albumin, surgical procedure, and COPD (c-statistic, 0.66; AIC, 9787). In the combined model, neoadjuvant therapy use was the only cancer-specific variable selected in the top five. The remaining variables were ASA class, preop sepsis, albumin, and wound class (c-statistic, 0.67; AIC, 9455). At the hospital-level, the NCDB-only model identified three high outliers (worse than expected) and one low outlier (better than expected). Both the NSQIP-only and combined models identified the same four high and two low outlying hospitals (kappa: 1.0), which agreed marginally with the NCDB-only model (kappa: 0.59). Conclusions: Addition of cancer-specific variables to NSQIP models slightly improved model fit; however, hospital outcome comparisons were identical. For patients with colorectal cancer undergoing resection, cancer-related factors have limited predictive ability for short-term outcomes and did not influence hospital quality comparisons.
Long-term health-related quality of life in patients treated for localized prostate cancer.
Authors: Sanoj Punnen, Janet E. Cowan, Peter Carroll, Matthew R. Cooperberg
Journal: Journal of Clinical Oncology (2013)

93 Background: Few studies have reported long term quality of life after primary treatment for localized prostate cancer. The objective of this study was report 10 year sexual and urinary quality of life data for men undergoing various treatments in the Cancer of the Prostate Strategy and Research Endeavor database. Methods: Men who have been treated for localized prostate cancer and have baseline and follow up quality of life date made up the study cohort. Primary treatment modalities included radical prostatectomy (RP), external beam radiotherapy (EBRT), brachytherapy (BT), cryotherapy (CT), primary androgen deprivation therapy (ADT), and active surveillance/ watchful waiting (AS/WW). Sexual and urinary quality of life were assessed by the validated UCLA Prostate Cancer Index and measured on a scale from 0-100. Mixed model repeated measures analysis was used to assess the association between primary treatment modality and long term urinary and sexual quality of life. Results: 3, 772 men made up the study cohort. Among all men being treated for prostate cancer the mean urinary function score was 92 at baseline, 76 at 1 year, 81 at 5 years and 77 at 10 years. Urinary bother scores were 84 at baseline, 71 at 1 year, 82 at 5 years, and 78 at 10 years. With respect to sexual function the mean score was 49 at baseline, 23 at 1 year, 29 at 5 years, and 24 at 10 years. Finally, the mean sexual bother score was 59 at baseline, 37 at 1 year, 46 at 5 years, and 47 at 10 years. With respect to quality of life by primary treatment modality most treatments showed a similar pattern of decreased scores in the first year followed by an increased in the following two years and a plateau up to the 10 year mark. EBRT and BT showed a longer decline in sexual and urinary function post treatment while RP scores plateau after 3 years. Conclusions: Men undergoing primary treatment for localized prostate cancer experience declines in sexual and urinary function and bother in the first year which improves after 3 years and plateaus up to 10 years.
New biomarkers to predict response to oxaliplatin-based chemotherapy in metastatic colorectal cancer: KRAS and ERCC1.
Authors: Antonia Strippoli, Michele Basso, Armando Orlandi, Giovanni Schinzari, Alessandra Calegari, Olga Elisabetta Cursio, Rosalba Barile, Alessia Amoruso, Carmelo Pozzo, Alessandra Cassano, Carlo Barone
Journal: Journal of Clinical Oncology (2012)

500 Background: In the present study we have evaluated the possibility that KRAS mutational status might be predictive of the efficacy of oxaliplatin-based chemotherapy. In addition, we explored the possible role of excision repair cross complementing group-1 (ERCC-1) that is envolved in repair of oxaliplatin (OXA) produced DNA-adducts. Methods: We performed a retrospective analysis of 90 patients with metastatic colorectal cancer, who received FOLFOX-6 schedule and FOLFIRI schedule ± Bevacizumab, in first or second line therapy. In sixty out of 90 patients the expression of ERCC-1 was also determined by fluorescence-based real-time detection method. Results: Among 90 patients, 42 (47%) wild-type (wt) and 48 (53%) mutated (mt) KRAS tumors were found. Twenty-two out of 42 wt KRAS patients received FOLFOX-6 as first-line therapy and the other 20 patients as second-line treatment; in the mt KRAS population, 27 and 21 patients received FOLFOX-6 as front-line or second-line, respectively. One complete response (CR) and 10 partial responses (PR) were observed in the wt KRAS group (RR 26%), whereas 2 CR and 25 PR were obtained in the mt KRAS group (56%); the difference is statistically significant in the total sample (p=0.003) and when only patients receiving FOLFOX-6 in first-line are considered (p=0006). PFS was longer in mt than in wt KRAS patients in the entire group of patients (10 vs 8 months, respectively; p=0.001) and in those treated in front-line (10 vs 8 months, respectively; p=0.003). ERCC-1 was over-expressed in 30 out of 60 patients, but the efficacy of FOLFOX-6 was not different in patient showing high ERCC-1 levels in comparison to those with low level of the gene. In ERCC-1 over-expressing patients, however, RR and PFS were higher in mt than in wt patients (40% vs 13% and 10 vs 8 months, respectively); a similar, not significant, trend was also observed in patients not over-expressing ERCC-1. Conclusions: Our data, if confirmed in larger series and in a prospective setting, suggest that activating mutation of KRAS oncogene could be a predictive biomarker of response to oxaliplatin. Basal tumor expression of ERCC-1 doesn’t explain the high efficacy of FOLFOX-6 in mt KRAS patients.
Does oncology patient-reported healthcare experience vary by site of care (SOC)?
Authors: Dana Drzayich Jankus, Adrianne Waldman Casebeer, Sari Hopson, Joseph Dye, Zhuliang Tao, Andrew M. Howe, Stephen Stemkowski, Jeffrey Patton, Art Small, Anthony Masaquel
Journal: Journal of Clinical Oncology (2016)

71 Background: Patients with cancer are increasingly receiving chemotherapy infusions in a hospital outpatient (HO) as compared to the physician practice setting (PO). Previous research has focused on SOC differences in economic measures, such as healthcare costs, in commercially insured populations. This study investigates SOC differences in patients’ reported healthcare experience for a mostly Medicare population. Methods: A convenience sample of 2,604 Humana members with cancer of the breast, lung, colon/rectum or NHL/CLL and treated in 2014 received a survey by mail to capture patient reported healthcare experiences. We implemented the Consumer Assessment of Health Care Providers and Systems (CAHPS) for Cancer Care survey’s 5 domains (“affective” communication, shared decision making, patient self-management, exchanging information and access to care and information) and ad hoc travel and wait time questions. Average composite scores for each CAHPS domain were weighted and adjusted by age and health status (1 = excellent - 5 = poor). Differences in responses were tested using chi-square and t-tests. Results: The response rate was 25.0% (N = 651). Survey respondents were mostly female (75.0%) and Medicare beneficiaries (87.9%) with a mean age of 68.7. HO patients reported slightly worse health status than PO patients (2.9 vs 3.0, p= 0.028) CAHPS for cancer domain scores indicated a similar patient perceived experience across all domains except for access to care and information (1-3 scale): HO = 2.6 vs PO = 2.5, p= 0.007. This difference was driven mainly by items related to contacting the health care team for certain symptoms and after hours care. More HO patients traveled &gt; 30 minutes for treatment (39.0% vs 25.9%, p= 0.004) and reported wait times &gt; 15 minutes (72.2% vs 63.8%, p= .054). Patient perceived acceptability of these travel and wait times were similar (HO: 61.9% vs PO: 66.7%, p= .782 and HO: 60.4% vs PO: 63.1%, p= .919). Conclusions: Analysis of the new CAHPS for cancer care survey showed comparable patient perceived experiences by site of care. However, access to the health care team for certain symptoms and after hours care was better for HO patients, though HO patients also had longer travel and waiting time.
In search of the optimal outcome measure for patients with advanced cancer and gastrointestinal obstruction: A qualitative research study.
Authors: Brian D. Badgwell, Loretta A. Williams, Eduardo Bruera
Journal: Journal of Clinical Oncology (2016)

100 Background: Gastrointestinal obstruction (GIO) is the most common indication for palliative surgical consultation in patients with advanced cancer. The purpose of this study was to delineate the symptom burden and experience of patients with GIO. Methods: Twenty patients with advanced cancer and GIO described symptoms at the time of surgical consultation. We used content analysis of interview transcripts and symptoms were ranked by frequency and compared to a general symptom assessment survey (MD Anderson Symptom Inventory). Results: Malignancy type included colorectal (N = 9), gastric (N = 4), urothelial/renal (N = 3), and other (N = 4), while site of obstruction was small bowel in 11 (55%), gastric outlet in 3 (15%), and large bowel in 6 (30%). Thirteen patients (65%) had received chemotherapy within 6 weeks. Imaging evidence of a primary/recurrent tumor, carcinomatosis, or ascites was documented in 13 (65%), 11 (55%), and 16 (80%) patients, respectively. Thirty symptoms were identified on qualitative interviewing. MD Anderson Symptom Inventory symptoms of pain, nausea, and vomiting were frequently noted. Frequently mentioned GIO-specific symptoms included bloating, cramping, not having a bowel movement, and inability to eat. Conclusions: Qualitative research methodology can identify symptoms of importance to patients which can be used to assess improvement after treatment of GIO. Expert panel rating will be used to develop the final symptom item list prior to psychometric testing of the survey.