tbuckley/cabot-search huggingface dataset:
Activity of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in chemotherapy-pretreated non-small cell lung cancer (NSCLC) patients (pts) prospectively selected according to specific molecular predictive factors
Authors: C. Nuzzo, A. Marchetti, M. Mottolese, A. M. Cianciulli, M. Rinaldi, F. L. Cecere, E. Bria, A. Ceribelli, M. Milella, F. Cognetti
Journal: Journal of Clinical Oncology (2007)

18006 Background: EGFR TKIs are effective in a small proportion of chemotherapy-pretreated NSCLC pts. A number of molecular alterations along the EGFR pathway have been proposed as predictors of response to EGFR TKIs, but to date none of them has been prospectively validated. Methods: Advanced, chemotherapy-pretreated, NSCLC pts were screened for the following EGFR pathway alterations: EGFR gene mutations (by SSCP and sequencing) and/or increased copy number (by FISH), EGFR protein expression (by IHC), and HER-2, phosphorylated AKT (pAKT), and total AKT protein expression (by IHC). Upon progression, pts were then assigned to treatment with an EGFR TKI (Iressa™ or Tarceva™) according to one of the following groups: A) mutated (regardless of any other parameter); B) non-mutated, amplified (either true gene amplification or high-grade polysomy in &gt; 40% of the tumor cells); C) non-mutated, non-amplified, EGFR positive (IHC score = 1+); D) Adk or BAC histology and no smoking history (non-mutated, non-amplified, EGFR-negative pts or unknown EGFR status). Results: From January 2005, 129 pts were screened for EGFR pathway alterations, while undergoing chemotherapy. Thirteen pts were identified in group A (6 with exon 19 deletions, 6 with exon 21 point mutations, 1 with both); 39 pts in group B (including 7 pts with true gene amplification); 32 pts in group C (including 19 pts with a pAKT IHC score = 1+); 7 pts in group D (including 2 pts with BAC histology). Treatment results in the different subgroups are reported in Table 1 . Conclusions: Based on the data available so far, there seems to be a continuum of response/ disease control rate that progressively declines from group A to group C. Accrual to the study will be continued in all 4 subgroups until computer simulations using a continual reassessment method will allow to confidently exclude a true response rate = 10% in any of the groups. [Table: see text] No significant financial relationships to disclose.
Oral magnesium oxide for treatment of hot flashes in women undergoing treatment for breast cancer: A pilot study.
Authors: J. Herrada, A. Gupta, A. F. Campos-Gines, L. S. Noble, M. M. Landeros, S. Moghaddam, R. Badillo
Journal: Journal of Clinical Oncology (2010)

e19530 Background: Breast cancer patients (pts) have limited options for the treatment of hot flashes. A recent clinical observation (Smith TJ, J Clin Oncol. 2009 Mar 1;27(7):1151-2. Epub 2009 Jan 26) has suggested a potential role of oral magnesium in the management of menopausal hot flashes. The aim of this pilot trial was to assess the efficacy and safety of magnesium oxide for the treatment of hot flashes in this patient population. Methods: Prospective evaluation. The average number of hot flashes per day reported by each pt was recorded before and after 4 weeks of oral magnesium oxide (400 mg TID). Results: Between March 2009 and early May 2009, 22 women on active treatment for breast adenocarcinoma and with bothersome hot flashes were evaluated. The median age was 48 years (34-75 years). All pts had normal creatinine levels. Active treatment for breast cancer included: tamoxifen (11), systemic chemotherapy (6), anastrozole (2), letrozole (2), and fulvestrant (1). The number of hot flashes per day reported by each patient was recorded before (median 10; range 20-3) and after 4 weeks of treatment with oral magnesium oxide (400 mg TID). No toxicity from magnesium oxide was observed. Ten (45%) pts achieved a complete resolution of hot flashes. Ten (45%) pts experienced at least a 50% reduction in the number of hot flashes per day. In two (10%) patients, no changes in the number of hot flashes were noted. Conclusions: In our small study, a symptomatic improvement was noted with a relatively nontoxic, simple intervention. Further clinical trials are warranted. No significant financial relationships to disclose.
To compare the results of Adjuvant Online and Oncotype DX in estimating risk for relapse in hormone receptor positive stage I breast cancer patients
Authors: K. Anwar, K. Edmiston, A. Khan, W. Walsh
Journal: Journal of Clinical Oncology (2008)

22069 Methods: Patients with Estrogen receptor positive, stage I, breast cancer that had Oncotype DX testing done were identified by retrospective review. 10 year relapse risk results obtained with Oncotype DX and Adjuvant Online were compared. The results were separated for T1b and T1c tumors. Cost comparison was done. Results: 30 patients with T1c and 8 patients with T1b disease were identified. All patients were females, age 29–73 years. Her 2 neu receptors were not over expressed in any case. T1c: For T1c tumors, 10 year tamoxifen adjusted relapse rate calculated from Adjuvant Online varied between 10.8–19.2%. Oncotype DX estimated rate of distant recurrence at 10 years in this group varied between 5–25%. 10 year relapse risk results calculated by these two methods were within 5 points of each other in 70% (21/30) cases, between 5–10 points in 23.3% (7/30) cases and > 10 point difference was seen in 6.7% (2/30) cases. Oncotype DX recurrence score identified 50% (15/30) patients in low risk group (Recurrence score < 18 and 10 yr relapse rate < 11), 40% in intermediate risk group (Recurrence score 18 - 30 and 10 yr relapse rate 11–21%), and 10% in high risk group (Recurrence score ≥ 31 and 10 yr relapse rate > 21%). Adjuvant Online results also showed three distinct groups with 26.6% patients in low risk group (10 yr relapse rate 10.8%), 63.3% in intermediate risk group (10 yr relapse rate 15%) and 10% in high risk group (10 yr relapse rate 19.2%). T1b: For T1b tumors, 10 yr relapse rate with Adjuvant Online varied between 9–15.6% and for Oncotype DX it varied between 10–23%. 10 yr relapse risk results calculated by two methods were within 5 points of each other in 62.5% (5/8) cases and difference was >10 points in 37.5% (3/8) cases. Oncotype DX testing assessed higher risk in 87.5% (7/8) cases. Cost Comparison: Oncotype DX cost $3,650 per test and total cost was $138,700. Adjuvant Online cost was 0. Conclusion: There was considerable variability in results of risk assessment provided by Oncotype DX testing and Adjuvant Online. Each method has been validated previously and there is need of a large longitudinal study to compare their risk assessment ability in cost effective fashion. No significant financial relationships to disclose.
Intraperitoneal(IP) 5’-fluoro-2’deoxyuridine(FUDR): Safety and outcome when administered prior to adjuvant chemoradiotherapy(chemoRT) following R<sub>0</sub> resection for gastric adenocarcinoma
Authors: D. J. Cohen, T. Ryan, E. Newman, S. Iqbal, M. Liu, M. Utate, S. Moore, M. Potmesil, H. Hochster, F. M. Muggia
Journal: Journal of Clinical Oncology (2007)

4627 Background: ChemoRT after surgery for locally advanced gastric cancer improves overall and relapse-free survival (OS and RFS) compared to observation (NEJM 2000,345:725–30). However, loco-regional recurrences (&gt;50%) remain high and we hypothesized that adding IP FUDR would further improve outcome. Methods: Patients (pts) ECOG performance status (PS) 0–2, gastric/gastroesphogeal(GEJ) adenocarcinoma stage Ib-IV (M0) undergoing R 0 resection were eligible, and had insertion of IP catheters at surgery. IP FUDR(3gm/dose/day) was given on protocol days 1, 2, 3 and 15, 16, 17 prior to 5-FU/LV and external beam RT (45Gy) as in cited study. Simon 2-stage optimum design was used to demonstrate safety. Endpoints also included were loco-regional recurrence and survival. Results: 28 pts with gastric/GEJ adenocarcinoma (25/3) were enrolled from 2002 to 2006 at 2 institutions: median age 59.5 years (range 39–81), M /F (21/7). R 0 gastric resection was performed with dissection of median 22 (range 8–102) lymph nodes(LN’s). 22/28 pts were lymph node positive. Full dose IP FUDR was completed in 20/28 pts. 4 pts required dose reduction (1 for grade(gr) 2 hepatic enzyme elevation, 2 gr 2 neutropenia, 1 gr 4 neutropenia), 3 discontinued therapy (1 gr 3 abdominal pain, 1 GI abscess, and 1 bleeding arterial pseudoaneurysm). One pt received no IP treatment due to catheter failure. 24/28 pts completed chemoRT and had toxicity comparable to that previously reported in the Intergroup 0116 trial. At 26 month median follow up (range 2.8–43.4), of the 26 pts evaluable for response, 16 pts are NED, 6 alive with disease, 3 dead of disease, and 1 dead from other cause. 5 recurrences were intra-abdominal, 1 local, 2 distant, and 1 at multiple sites. At present analysis, the median RFS is 32.5 months. Conclusions: IP FUDR prior to chemoRT after R 0 gastric cancer resection is well tolerated. A randomized study to test its role in reducing regional recurrence and improving outcome is warranted. (FDA Orphan Products grant# FD-R-2150–04) No significant financial relationships to disclose.
Is cardiovascular screening in athletes justified? Inconsistent messages from the American Heart Association
Authors: Jonathan A Drezner
Journal: British Journal of Sports Medicine (2015)

Recent reports from the American Heart Association (AHA) and by lead authors of the 2014 AHA guidelines for cardiovascular screening in athletes present many inconsistencies that need to be critically examined. In three different AHA statements (1996, 2007, 2014), the AHA has endorsed cardiovascular screening: “Both AHA and ESC consensus panels have agreed previously that screening to detect cardiovascular abnormalities in asymptomatic young competitive athletes is justifiable in principle on ethical, legal, and medical grounds.”1 Furthermore, the AHA has not endorsed cardiovascular screening for young non-athletes: “Consideration for large-scale, general population, and universal cardiovascular screening in the age group 12 to 25 years with history-taking and physical examination alone is not recommended (including on a national basis in the United States) (Class III, no evidence of benefit; Level of Evidence C).”1

However, <1 year from publication, the AHA and leaders of the 2014 guidelines have called into question the very ethics of screening only young athletes, and recommended that all young persons be screened, with a cardiac history and physical examination as part of an …
Preoperative chemoradiotherapy with capecitabine and oxaliplatin in locally advanced rectal carcinoma: A phase II trial
Authors: V. Alonso, J. Lambea, A. Salud, J. Valencia, M. Mira, S. Polo, P. Escudero, E. Sierra, A. Monzon
Journal: Journal of Clinical Oncology (2007)

4044 Background: The aim of this phase II trial was to assess the impact of preoperative external radiation therapy combined with Capecitabine and Oxaliplatin on pathologic tumor response, sphincter preservation and tumor control in patients with locally advanced rectal carcinoma. Methods: Sixty-seven patients with locally advanced rectal carcinoma (T3/T4 or N+) received radiotherapy (50.4 Gy/28 fractions) and chemotherapy with Capecitabine 825 mg/m 2 /12 hours on days 1–5 + Oxaliplatin 50 mg/m 2 on day 1 every week (weeks 1–6). Surgery with TME was performed 6–7 weeks after the end of the treatment. Adjuvant chemotherapy was administered after surgery according investigator‘s crtiteria. Results: Patients have been recruited between February 2005 and June 2006. 47 male/20 female. Median age 67 years (range 38–79). Performance status (ECOG) 0 in 45 patients. Clinical stage (determined by EUS+CT or RMI): cT2 3p/cT3 58p/cT4 6p/cN+ 47p. Tumor location (from anal verge): = 5 cm in 27p. Median CEA level 3,69 ng/ml (0,7–391). Surgery (performed in 65 patients) consisted of low anterior resection in 37p, abdominal perineal resection in 28p. Tumor downstaging was observed in 52p (78%), 50 (76,9%) had negative lymph nodes, including 13p with complete pathological response (19,4%) and ten with only microfoci of tumor remaining (14,9%). 80% of the patients received adjuvant chemotherapy. Main adverse effects (NCI-CTC): diarrhea G3/4 25%, sensitive peripheral neurotoxicity G1 60%, skin G2 9%, skin G3 3%, nausea/vomiting G2 7.5%, fatigue G2 50%, fatigue G3 4%, neutropenia G3/4 4%. Conclusions: Those results show that preoperative chemoradiotherapy with capecitabine and oxaliplatin is a well tolerated regimen for locally advanced operable rectal cancer leading to a high probability of tumor downstaging. No significant financial relationships to disclose.
Venous thromboembolism and all-cause mortality in cancer patients receiving chemotherapy
Authors: N. M. Kuderer, C. W. Francis, E. Culakova, A. A. Khorana, T. Ortel, A. Falanga, G. H. Lyman
Journal: Journal of Clinical Oncology (2008)

9521 Background: Venous thromboembolism (VTE) is a common complication of cancer occurring with increasing frequency. A recent meta-analysis of anticoagulation as a form of cancer treatment reported a significant reduction in overall mortality (Kuderer et al. Cancer 2007). The aim of this analysis is to evaluate the impact of VTE on early mortality in cancer patients receiving chemotherapy. Methods: A prospective study of 4,458 adult cancer patients with solid tumors or malignant lymphoma initiating a new chemotherapy regimen was conducted between 2002 and 2006 at 115 randomly selected U.S. practice sites. Demographic, clinical and treatment-related measures were captured at baseline and during the first 4 cycles of chemotherapy including rates of documented VTE and deaths from all causes. Overall survival (OS) was estimated by the method of Kaplan-Meier and adjusted hazard ratios (HR) for OS were based on a Cox regression model incorporating VTE as a time-dependent covariate. Results: Average patient age was 60 years (range: 18 to 97). VTE occurred in 93 (2.1%) patients at a median of 38 days following initiation of chemotherapy. 137 patients died during the period of observation (median follow-up, 75 days). In multivariate analysis after adjusting for major confounders for mortality, including ECOG performance status, Charlson comorbidity index, age, body mass index, cancer type, stage, delivered chemotherapy dose intensity, study year and practice site, the occurrence of VTE was a significant independent predictor of early all-cause mortality [HR=6.98, 95%CI: 2.83–17.21; P<.0001]. Following additional adjustment for baseline laboratory abnormalities, including elevated serum creatinine, alkaline phosphatase or decreased serum protein, VTE remained significantly associated with early mortality [HR=4.50; 95%CI: 1.61–12.53; P=.004]. While 298 (6.7%) patients progressed or recurred during the period of observation, no significant relationship between VTE and tumor progression was observed. Conclusions: VTE is strongly associated with increased early all-cause mortality during the course of cancer chemotherapy. Further studies of the effect of anticoagulant treatment on cancer mortality are needed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eisai Eisai, sanofi-aventis
A prognostic indicator in rectal cancer surgery: Lymph node ratio in neo-adjuvant chemo-radiotherapy (CRTX)
Authors: K. Ong, S.S. Fong, G.S. Tay
Journal: International Journal of Surgery (2015)

s / International Journal of Surgery 23 (2015) S15eS134 S23 Results: 76 patients underwent lung resection in the year prior to the ERP and 80 patients in the following year. Median agewas 72 years (IQR 64-77) and 69 years (IQR 64-75) before and after programme commencement, respectively (p 1⁄4 0.120). The proportion of patients undergoing VATS resectionwas 55.3% and 66.3% in the consecutive years (p1⁄4 0.160). LOS for all approaches prior to and following the introduction of ERP was 6 days (IQR 4-8) versus 5 days (IQR 3-8), respectively (p 1⁄4 0.126). The non-significant reduction in LOS was observed in both open and VATS cases. Overall, the reduction in LOS represented a cost reduction of £26880(14%). Conclusion: The benefits of a thoracic surgery ERP may be difficult to measure in terms of hard end-points due to the staged nature of ERP implementation. A trend towards reduced LOS was observed following the introduction of the thoracic surgery ERP. 0308: A PROGNOSTIC INDICATOR IN RECTAL CANCER SURGERY: LYMPH NODE RATIO IN NEO-ADJUVANT CHEMO-RADIOTHERAPY (CRTX) K. Ong , S.S. Fong , G.S. Tay . University of Glasgow, UK; 2 Tan Tock Seng Hospital, Singapore Aim: This study aims to identify which variables -lymph node yield (LNY), LN ratio (LNR) and LN involvement (LNI)are significant predictors of overall survival (OS) in patients who had neo-adjuvant CRTx for rectal cancer. Methods: This is a retrospective study of patients who had surgical resection for rectal cancers from January 2006-December 2011 in TTSH (Singapore). LNY, LNI and LNR from histopathology are recorded. Correlation and multiple regression analyses were conducted to examine relationship between OS ( 3-year follow-up) and potential predictors (LNY, LNI, and LNR). Results: A total of 200 patients were included, of which 80 had neoadjuvant CRTx. A reduction in mean LNY and LNI were found in the neoadjuvant group (from 23.4 to 15.0, p < 0.01 and 3.45 to 1.86, p 1⁄4 0.163 respectively). There was no reduction in mean LNR (both 0.11). OS is negatively and significantly correlated with LNI (p 1⁄4 0.019) and LNR (p 1⁄4 0.011). The stepwise multiple regression model showed LNR as best predictor of survival (R2 1⁄4 0.072, F (1, 71) 1⁄4 5.495, p < 0.05). Conclusion: Neo-adjuvant CRTx reduces LNYand LNI but not LNR. LNI and LNR are inversely related to OS. LNR is the single best predictor of prognosis for patients who had neo-adjuvant CRTx for rectal cancer. 0339: A COMPARISON OF TWO DIGITAL MAMMOGRAPHY SYSTEMS AT BREAST TEST WALES e WHAT DOES IT MEAN FOR SURGEONS? G. Devonish, T. Evans, B. Burlton, D. Bailey, K. Gower-Thomas. Breast Test
HER2, p95HER2, and HER3 expression and treatment outcome of lapatinib plus capecitabine in HER2-positive, trastuzumab-refractory metastatic breast cancer.
Authors: S. Han, J. Ro, A. Paquet, W. Huang, J. Weidler, K. S. Lee, I. Park, D. Oh, S. Im, T. Kim
Journal: Journal of Clinical Oncology (2010)

1088 Background: Lapatinib (L) is a dual tyrosine kinase inhibitor of EGFR and HER2. Lapatinib plus capecitabine (C) is an effective treatment option in trastuzumab (T)-refractory HER2-positive (+) metastatic breast cancer (MBC). However, predictive biomarkers for this treatment are not known. This study sought to investigate correlation of quantitative measurements of HER family proteins and treatment outcome in HER2+, T-refractory MBC patients (pts) treated with L plus C. Methods: Total HER2 (H2T), HER2 homodimer (H2D), p95HER2 (p95), and total HER3 (H3T) expression were quantified in formalin-fixed paraffin-embedded samples using the VeraTag assay (Monogram Biosciences, CA). HER2+ (either IHC 3+ or FISH+) MBC pts who had progressed after prior therapy including anthracycline, taxane, and T were included. Patients received L 1,250mg/day D1-21 and C 2,000mg/m2/day D1-14 every 21 days according to Lapatinib Expanded Access Program. The association between protein expression levels and clinical outcomes was analyzed. Results: 59 pts with tissues available for testing were included. H2T, H2D, p95, and H3T were assessable in 52, 51, 49, and 47 pts, respectively. Best overall response according to RECIST in the study population was PR in 11 (21.2%), SD in 30 (57.7%) and PD in 11 (21.2%). Median time-to-progression (TTP) was 4.4 months (mos) and overall survival 14 mos. H2T (median 63.9 in PR, 45.5 in SD, and 17.3 in PD; p > 0.026) and H2D (median 36.7 in PR, 32.3 in SD, and 27.9 in PD; p > 0.014) levels were significantly higher in responders. Longer TTP was associated with high H2T [high (>14.95), 5.0 mos vs. low (≤14.95), 1.4 mos; p > 0.026]. Pts with both high H2T and high H3T showed disease control rate (PR+SD) at 3 mos of 84.2% (16/19) vs. 46.4% (13/28) in the others (p > 0.009) and median TTP of 5.2 mos vs. 3.0 mos in the others (p > 0.010). No significant association between p95 and response or survival was observed. Conclusions: These data suggest a correlation between high H2T and H3T levels and treatment outcome of L plus C in the study population, while clinical outcomes were similar regardless of p95 expression level. These results require confirmation in further studies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Monogram Biosciences
Effect of nivolumab (NIVO) on quality of life (QoL) in patients (pts) with treatment-naïve advanced melanoma (MEL): Results of a phase III study (CheckMate 066).
Authors: Georgina V. Long, Victoria Atkinson, Paolo Antonio Ascierto, Caroline Robert, Jessica Cecile Hassel, Piotr Rutkowski, Kerry J. Savage, Fiona Taylor, Cheryl Coon, Isabelle Gilloteau, Homa Dastani, Ian Waxman, Amy Pickar Abernethy
Journal: Journal of Clinical Oncology (2015)

9027 Background: While treatments exist that extend survival in advanced MEL, the quality of that survival is not often evaluated. There is a need for treatments that demonstrate increased survival while preserving long-term QoL. In a phase III, randomized, double-blind study, NIVO (a PD-1 immune checkpoint inhibitor; 3 mg/kg every 2 weeks [wks; Q2W]) improved overall survival compared with dacarbazine (DTIC; 1,000 mg/m2 Q3W) in treatment-naïve pts with advanced MEL. Methods: In this study, QoL measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EuroQol-five dimension questionnaire (EQ-5D) was evaluated at baseline (BL) and at treatment cycles Q6W. Mean changes and non-parametric comparisons are reported. Further analyses are planned to examine longitudinal QoL and the relationship between clinical and pt outcomes. Results: A total of 418 pts were randomized to NIVO (n = 210) or DTIC (n = 208). Adjusted completion rates at BL for EQ-5D utilities were 69.5% with NIVO and 64.9% with DTIC, and those for EORTC QLQ-C30 were 70.0% with NIVO and 64.9% with DTIC. While rates remained similar throughout the study, analysis of QoL involving DTIC was not feasible after wk 13 due to a high attrition rate in the DTIC arm (n ≤ 41). Mean BL QoL scores were similar for NIVO versus DTIC (EQ-5D utilities: 0.778 vs 0.711; EQ-5D visual analog scale [VAS] scores: 70.9 vs 69.1; EORTC Global Health: 68.9 vs 66.2). No QoL change was noted for DTIC prior to study dropout. For NIVO, improvements from BL were noted in EQ-5D utilities from wk 7 (0.027; n = 132; P= 0.011) through wk 49 (0.045; n = 38; P= 0.034), and in EQ-5D VAS scores at wks 25, 31, 37, 49 and 61 (P≤ 0.03). EORTC subscale scores did not change over time. Conclusions: These results demonstrate that NIVO does not impair QoL and may enhance it compared with BL, while also conferring survival benefits, in treatment-naïve pts with advanced MEL. Dropout rates with DTIC after wk 13 limited QoL data interpretation for this treatment group. Clinical trial information: NCT01721772.