tbuckley/cabot-search huggingface dataset:
A phase II study of gefitinib as a dirst-line therapy of advanced or metastatic adenocarcinoma of the lung in lifetime non-smokers
Authors: D. H. Lee, J. Y. Han, H. G. Lee, J. J. Lee, E. K. Lee, H. Y. Kim, H. T. Kim, E. K. Hong, J. S. Lee
Journal: Journal of Clinical Oncology (2005)

7072 Background: The analyses gefitinib trials suggested that gefitinib induced more responses in patients (pts) with adenocarcinoma of the lung who never smoked cigarettes. We conducted this study to evaluate the efficacy of gefitinib as a first-line therapy for this particular subgroup of pts. Methods: Eligible pts had stage IIIB or IV adenocarcinoma, ECOG PS of 0–2, adequate organ functions, measurable lesions and no smoking history. No pts received prior chemotherapy or radiotherapy to measurable disease. Treatment consisted of gefitinib 250 mg p.o daily x 28 days till disease progression, unacceptable toxicity or patient’s refusal. Objective tumor responses were assessed every 2 cycles. Results: Between 8/2003 and 8/2004, 55 pts were enrolled (median age: 55 years; M/F 4/51; ECOG PS 0/1/2 19/33/3; stage IIIB/IV 5/50); 54 were evaluable for response. The overall response rate was 61.1% (PR 57.4% & CR 3.7%) with SD in 11.1% and PD in 27.8% of pts. The response rate in female pts was 62.0% (31/50) but 50% (2/4) in male pts. There were 20 pts with evaluable brain metastases, 12 of whom had responses in both intracranial and extracranial lesions, and one had SD in intracranial metastases while extracranial lesions showed dramatic response. After a median follow-up of 36 weeks, the median progression-free survival was 26 weeks with 1-year survival rate of 78.5%. The median response duration for 33 responders was 30 weeks. Common toxicities were skin rash (95%), diarrhea (58%), and elevated liver enzyme (44%), and there was no significant hematologic toxicity. Significant toxicities included; G3 skin rash (2), G3 elevated liver enzyme (3), and G3 asthenia, vomiting, and neuropathy in one each. Conclusions: Gefitinib showed very promising antitumor activity and good toxicity profile for patients with advanced or metastatic adenocarcinoma of the lung and no smoking history. A further study is warranted in comparison with chemotherapy as a first-line therapy. (Supported in part by NCC grant 0210140) No significant financial relationships to disclose.
Clinical results of pharmacokinetic modulating chemotherapy (PMC) in combination with hepatic arterial 5FU infusion, continuous venous 5FU infusion and oral UFT as adjuvant chemotherapy after liver resection for hepatic colorectal metastases
Authors: M. Noda, H. Yanagi, R. Yoshikawa, M. Gega, H. Ikeuchi, T. Yamamura, M. Kusunoki
Journal: Journal of Clinical Oncology (2005)

3665 Background: We have presented the usefulness of pharmacokinetic modulating chemotherapy in combination with hepatic arterial 5FU infusion and oral UFT (HAI-PMC) as adjuvant chemotherapy after liver resection for hepatic colorectal metastases before. (ASCO Abst 556,2001) We also assessed the usefulness of PMC in combination with continuous venous 5FU infusion and oral UFT (CVI-PMC) as adjuvant chemotherapy for Dukes C colorectal cancer. (ASCO Abst 1175,2003) To decrease the recurrent rate at extrahepatic sites and improve prognosis we instituted PMC in combination with hepatic arterial 5FU infusion, continuous venous 5FU infusion and oral UFT as adjuvant chemotherapy after liver resection for hepatic colorectal metastases. Methods: Fifty-nine patients were randomly divided into 2 groups after liver resection. Group A (n=30 patients), underwent HAI-PMC in a combination of intra-arterial infusion of 5FU for 2 consecutive days per week at 600mg/m2/day and oral administration of UFT at 400mg/day for 5 days per week for 3 months. Group B (n=29), underwent CVI-PMC in a combination of continuous venous 5FU infusion per week at 600mg/m2/day and oral administration of UFT at 400mg/day for 5 to 7 days per week for 12 months after finishing HAI-PMC. Results: The five-year survival rate of patients in the A group was 61%, and in the B group 63%.(p=0.98) The five-year recurrence rate in remnant liver after hepatic resection was 12% and 11%, respectively (p=0.82); and the rate of extrahepatic recurrence was 38.1% and 34.6%, respectively (P-0.56). Conclusions: It is thought that further intensive systemic chemotherapy is necessary to decrease the rate of extrahepatic recurrence and improve prognosis. No significant financial relationships to disclose.
Interim results of OPAL, a study of tosedostat in elderly relapsed/refractory AML.
Authors: E. J. Feldman, K. W. L. Yee, D. Rizzieri, A. S. Advani, A. Charman, A. Richardson, M. J. Toal, J. E. Cortes
Journal: Journal of Clinical Oncology (2011)

6517 Background: Tosedostat is a novel oral aminopeptidase inhibitor which has shown promising efficacy in elderly relapsed/refractory AML (Lowenberg 2010). OPAL will provide additional data from a more tightly defined patient population and explore different dosing regimens. Methods: OPAL is a single-arm study of 73 AML patients aged >60 years who had a previous CR lasting less than 12 months, or no CR (Estey 1996) after primary induction. Patients received oral tosedostat, either 120 mg once daily for 6 months, or 240 mg once daily for 2 months followed by 120 mg once daily for 4 months. The pre-specified interim analysis at 3 months was based on bone marrow responses (complete <5% blasts, partial 5 to 25% blasts). Results: There were 15 responders (21%); 8 (21%) in the 120 mg arm, and 7 (20%) in the 240 mg arm. 22 patients (31%) had a best response of stable disease. There were 23 (32%) unevaluable patients (no month 1 bone marrow). Tosedostat was generally well tolerated by patients. Conclusions: The data is in line with the previous study and provides further encouraging data. Final analysis of the study will take place at 6 months. Plans for a phase III program with tosedostat in AML are well advanced. Overall n = 73 120 mg n = 38 240 mg n = 35 Demographics Median (range) <75 years Male 72 (65-86) 50 (68%) 43/30 (59/41%) 73 (65-86) 24 (63%) 26/12 (68/32%) 71 (65-86) 26 (74%) 17/18 (49/51%) Prior AML Secondary/therapy-related 11 (29%) 14 (40%) 25 (34%) Prior AML therapy Ara-C + anthracycline Other Ara-C regimes Demethylating agents Other 26 (36%) 18 (25%) 23 (33%) 3 (7%) 13 (34%) 8 (21%) 15 (39%) 2 (5%) 13 (37%) 10 (29%) 8 (23%) 1 (3%) Previous remission experience No CR CR <6 months CR 6-12 months 38 (52%) 15 (21%) 20 (27%) 18 (47%) 7 (18%) 13 (34%) 20 (57%) 8 (23%) 7 (20%) Mean duration (days) 83 99 66 Safety Patients with >1 SAE Most common SAEs Febrile neutropenia Disease progression Pneumonia Atrial fibrillation 63 (86%) - 21 (29%) 8 (11%) 6 (8%) 6 (8%) 33 (87%) - 9 (24%) 5 (13%) 1 (3%) 1 (3%) 30 (86%) - 12 (34%) 3 (9%) 5 (14%) 5 (14%) Patient disposition Completed 4 weeks Completed 12 weeks 55 (75%) 25 (34%) 29 (76%) 12 (32%) 26 (74%) 13 (37%) Responses Overall response rate 15 (21%) 8 (21%) 7 (20%) Complete 6 3 3 Partial 9 5 4 Stable disease 22 14 8 Progressive disease 13 6 7 Unevaluable 23 10 13
A survey on insomnia in patients with non-small cell lung cancer (NSCLC).
Authors: J. Subramanian, M. Q. Baggstrom, E. Gilstrap, T. De Shields, L. Boehmer, K. Williams, S. Devarakonda, F. Gao, R. Govindan
Journal: Journal of Clinical Oncology (2010)

e19553 Background: Patients with cancer report insomnia frequently. However the true prevalence of insomnia in patients with cancer in general and in patients with lung cancer in particular has not been adequately described. Therefore we conducted a prospective study to determine the prevalence of insomnia and identify associations between insomnia and other clinical variables in patients with lung cancer. Methods: Anonymous surveys based on the Insomnia Severity Index (ISI) were made available to lung cancer patients in the waiting rooms of the oncology clinics at Siteman Cancer Center. Results: Of the 152 patients, who completed the survey, the majority were women 87 (58.4%) and the median age was 63 years (range 16-85 years). The study population was predominantly Caucasians accounting for 78%. NSCLC was the most common lung cancer subtype 86 (56.6%), followed by SCLC 23 (15.1%) and unknown 43 (28.3%). Insomnia was reported by 68 (46.3%) patients. Seventy-nine (52.7%) patients reported suffering from at least one of the following: anxiety, depression and fatigue (ADF). Fifty-one (33.5%) patients were on treatment for ADF. In addition, 42 (28.4%) patients reported a pain score of ≥ 5 on a subjective scale of 1 to 10 and 92 (62%) were on medications for pain control. Significant clinical insomnia characterized by an ISI score of ≥ 15 was reported by 25 (12.2%) patients and severe insomnia (ISI score ≥ 22) was reported by 5 (3.4%) patients. Patients reporting depression were more likely to suffer from insomnia than patients without depression; 61.5% vs. 40.7%; p = 0.04. A similar relationship was identified between insomnia and patients reporting fatigue; 69.7% vs. 39.5%; p = 0.002. Current smokers were more likely to suffer from insomnia than never smokers with lung cancer; 64.1% vs. 47.1% (p = 0.002). Conclusions: Nearly half of all patients with lung cancer in this survey reported insomnia. In addition, patients who were depressed and current smokers were more likely to report insomnia in our survey than those without depression or current tobacco smoking. No significant financial relationships to disclose.
CYPTAM-BRUT 2: A prospective multicenter observational study in the neoadjuvant and metastatic setting investigating tamoxifen response between women with a favorable versus unfavorable endoxifen profile.
Authors: A. Dieudonné, H. Wildiers, D. Lambrechts, H. Guchelaar, V. O. Dezentje, M. Joerger, K. Zaman, I. B. Vergote, P. Neven
Journal: Journal of Clinical Oncology (2011)

TPS140 Background: Tamoxifen is widely used to treat hormone receptor positive breast cancers, in the (neo-)adjuvant setting as well as in the metastatic setting. Even though tamoxifen saved many lives worldwide, a lot of variation in clinical response and side effects is observed between women. One hypothesis is variation in the metabolism of tamoxifen through cytochrome P450 enzymes, which are needed to convert tamoxifen in the more active metabolite endoxifen. Several retrospective studies have been performed but results remain contradictory. This can be explained in part by the retrospective nature of all studies, selection bias, different inclusion criteria and different objectives between the studies, making them difficult to interpret and compare. Methods: This is a prospective multicentre open label single arm non randomized observational study (NCT00965939) including postmenopausal women receiving tamoxifen as first line therapy in the metastatic or neo-adjuvant setting. Prior endocrine therapy in the adjuvant setting is allowed if there is more than 12 months after completion of the adjuvant therapy. Primary objective is to analyse tumor response by endoxifen plasma concentrations. Secondary objectives are 1) efficacy in terms of the proportion of patients who are progression free at 6 months, 2) efficacy in terms of clinical benefit (CR + PR + SD), 3) tolerability of tamoxifen and 4) predictive value of the tamoxifen activity score, based on tamoxifen pharmacogenetics and interacting drugs. Patients with bone only lesions and no other measurable lesions will not be included in the analysis of the primary objective. Total sample size is 260 and currently (31-01-2011) we included 100 patients from 20 participating centres. Other collaborative groups consider to join this protocol.
Association of tumor PDGFR-α and PDGFR-β expression and survival after resection of hepatocellular carcinoma.
Authors: S. H. Patel, P. J. Kneuertz, M. Delgado, C. Cohen, J. Sarmiento, C. A. Staley, D. A. Kooby, A. B. Farris, S. K. Maithel
Journal: Journal of Clinical Oncology (2011)

220 Background: Hepatocellular carcinoma (HCC) proliferates through angiogenic pathways mediated, in part, by vascular endothelial growth factor receptor 2 (VEGFR2) and platelet-derived growth factor receptors (PDGFR) α and β. We hypothesized that overexpression of these proteins is associated with decreased survival after resection. Methods: 57 patients with available tissue for analysis who underwent liver resection for HCC between 8/00 and 3/08 at one institution were identified from a prospectively maintained database. Tumors were assessed by immunohistochemistry for VEGFR2, PDGFR-α, and PDGFR-β expression and were graded by a single pathologist. Primary outcome was overall survival (OS). Results: Median age was 64 yrs; 65% were male. Median F/U was 25 mo, and OS was 26 mo. Median tumor size and number were 7 cm and 1, respectively. Macro- and microvascular invasion were present in 9% and 42% of patients, respectively. 25% had tumors that met Milan criteria. 9% had positive resection margins. 35% of patients had cirrhosis and the median nonadjusted MELD score was 7.5. Tumors exhibited differential expression of VEGFR2 (low: 79%, high: 21%), PDGFR-α (low: 93%, high: 7%), and PDGFR-β (low: 96%, high: 4%). After excluding all 30-day deaths (n=7), high PDGFR-α and β expression were independently associated with decreased OS (8.7 vs 29.1 mo, p=0.01; 2.8 vs 28.8 mo, p&lt;0.001; respectively). When adjusted for tumor burden, margin status, and MELD score on independent multivariate analyses, both PDGFR-α and β expression were predictive of decreased survival (Table). Conclusions: High PDGFR-α and PDGFR-β expression are independently associated with decreased overall survival after resection of HCC. This finding may help to select patients who would benefit from targeted inhibitor therapy in the adjuvant setting. [Table: see text] No significant financial relationships to disclose.
Predicting invasive disease at excision of ductal carcinoma in situ in core biopsies: A predictive model.
Authors: C. McGathey, A. Fought, D. Scholtens, S. A. Khan
Journal: Journal of Clinical Oncology (2011)

580 Background: Several features have been identified in DCIS diagnosed by core biopsy (DCIS-core) which predict the presence of invasive carcinoma (IC) in the surgical specimen. However, these have not been combined into a model to predict which patients with DCIS-core will be found to have IC on excision, a tool that will be useful both for clinical management and to researchers designing neo-adjuvant trials for DCIS. We analyzed our experience with DCIS-core to develop such a model. Methods: DCIS-core patients treated at our center over the period 2008-09 were included and their pathologic and imaging characteristics reviewed. Univariate and multivariate logistic regression was performed to predict the presence of true IC (foci >1 mm) in the final surgical specimen. Variables examined include age, race, nuclear grade of DCIS, hormone receptor (HR) status, presence of comedo necrosis (CN) (present, absent, or focal), lobular extension (LE), size on mammography, and presence of mass on mammography or ultrasound. Results: 232 patients were identified, mean age was 56 years, 75% were Caucasian, 86% were HR positive and 51% had grade III disease. CN was present in 57% and LE was present in 29%. Mean size on mammography was 2.8 cm (SD 2.9) and 22% displayed a mass on mammogram or ultrasound. IC was seen in the surgical specimens of 30 women (13%). In univariate analysis, characteristics significantly predictive of IC were: presence of CN (odds ratio (OR) 7.4, 95% CI 1.7-32.5), LE (OR 2.5, 95% CI 1.1-5.4), and presence of mass (OR 2.7, 95% CI 1.2-6.1). In the age-adjusted multivariate model, two variables were retained: CN 9.7 (2.1-44.6), and mass on imaging 3.7 (1.5-9.1). Of the 22 women with both CN and a mass on imaging, 9 (41%) had IC in the surgical specimen. We are in the process of refining this model for use in the clinic and by researchers who wish to identify a uniform DCIS population based on imaging and core biopsy features. Conclusions: We have incorporated commonly available pre-operative pathologic and imaging characteristics into a predictive model that will inform decisions about sentinel node biopsy procedures and aid researchers as they set eligibility thresholds for future studies of neo-adjuvant treatments for DCIS.
Health concerns of long-term survivors of gynecologic cancers
Authors: C. C. Sun, S. N. Westin, R. A. Lacour, L. A. Meyer, C. S. Tung, D. L. Urbauer, M. M. Frumovitz, D. M. Gershenson, K. H. Lu, D. C. Bodurka
Journal: Journal of Clinical Oncology (2008)

20535 Background: Survivorship-related issues are recognized as a key component of the complete care of cancer patients. Our study surveyed gynecologic cancer survivors to identify significant health concerns at specific times from diagnosis. Methods: As part of an ongoing study, a stratified group of women with gynecologic cancers seen at our institution from 1997–2007 was systematically sampled. Health concerns were quantified and categorized by personal importance according to time from diagnosis. Results: To date, 2,286 women received surveys; 781 surveys (34%) were completed and analyzed. Median age was 59 years; median time from diagnosis was 4.8 years (range 0.5 - 58 yrs). Similar numbers of women with cervical, endometrial, and ovarian/peritoneal/fallopian tube cancers responded ( 29 vs 25 vs 27%, respectively). The remaining 18% had vulvar/vaginal cancer. Top 5 rankings by personal importance and frequency according to time from diagnosis are shown in the table. Fatigue was the most frequent health issue among all groups. However, all patients reported sexual, bowel and urinary problems as their most important personal health concerns. The likelihood of having fatigue, sexual and urinary problems increased with time from diagnosis. Compared to < 2 yrs, odds ratios (OR) for 5–10 yrs and 10+ yrs were OR=1.7; 95% CI (1.0, 2.6) and OR=2.4; 95% CI (1.4, 4.1), respectively, for fatigue; OR=1.8; 95% CI (1.1, 3.1) and OR=2.8; 95% CI (1.5, 5.2) for sexual; and OR=2.9; 95% CI (1.7, 4.9) and OR=3.3; 95% CI (1.8, 5.9) for urinary concerns. Conclusions: Our data illustrate a discrepancy between frequency of health concerns and personal ranking of the importance of these issues in gynecologic cancer survivors. As healthcare providers, we must address common health concerns as well as issues of specific importance to individual women and recognize that time from diagnosis may influence the severity of health issues. Effective patient-physician communication is critical to identifying, understanding, and treating survivorship issues. Survivor group by time from diagnosis Rank 0 to < 2 yrs (n=129) 2 to < 5 yrs (n=273) 5 to < 10 yrs (n=260) 10 + yrs (n=119) Personal importance Fre-quency Personal importance Fre-quency Personal importance Fre-quency Personal importance Fre-quency 1 Sexual Fatigue (34%) Sexual Fatigue (44%) Urinary Fatigue (44%) Bowel Fatigue (49%) 2 Fatigue Neurologic (26%) Bowel Neurologic (37%) Sexual Urinary (42%) Sexual Urinary (44%) 3 Bowel Bowel, Sleep (25%)* Urinary Sexual (36%) Bowel Sexual (39%) Cardiac Sexual, Sleep (38%) 4 Urinary Sexual (24%) Fatigue Memory, Sleep (33%)* Fatigue, DJD Sleep (36%) Urinary Neurologic (35%) 5 Sleep, Cardiac* Depression (21%) Memory Bowel (31%) Sleep, cardiac* Memory (32%) DJD Bowel (34%) * denotes tie No significant financial relationships to disclose.
Risk factors for surgical complications after D2 gastrectomy following neoadjuvant chemotherapy for gastric cancer.
Authors: Takaki Yoshikawa, Toru Aoyama, Tsutomu Hayashi, Kazuaki Tanabe, Kazuhiro Nishikawa, Yuichi Ito, Haruhiko Cho, Satoshi Morita, Yumi Miyashita, Akira Tsuburaya, Junichi Sakamoto
Journal: Journal of Clinical Oncology (2014)

164 Background: The feasibility and safety of D2 surgery following neoadjuvant chemotherapy (NAC) has not yet been fully evaluated in patients with gastric cancer. Moreover, the risk factors for surgical complications after D2 gastrectomy following NAC are also unknown. The aim of the present study was to identify risk factors for postoperative complications after D2 surgery following NAC. Methods: This study was conducted as an exploratory analysis of a prospective randomized phase II trial of NAC. This randomized phase II trial compared two and four courses of neoadjuvant S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) using a two-by-two factorial design for locally advanced gastric cancer. Sample size was set at 60 to 80 to achieve 10% improvement of 3-year OS by four courses or by PC with approximately 80% probability of the correct selection. The surgical complications were assessed and classified according to the Clavien-Dindo classification. The uni- and multivariate logistic regression analyses were performed to identify risk factors for morbidities. Results: Among the 83 patients who were registered in the phase II trial, 69 patients received NAC and D2 gastrectomy. Postoperative complications were identified in 18 patients, and the overall morbidity rate was 26.1%. The results of the univariate and multivariate analyses of various factors potentially affecting the overall surgical morbidity identified a creatinine clearance (CCr) &lt; 60ml/min (P = 0.016) as the sole significant independent risk factor for overall morbidity. The incidence of pancreatic fistula was significantly higher in the patients with a low CCr than in those with a high CCr. Conclusions: A low CCr was found to be a significant risk factor for surgical complications associated with D2 gastrectomy after NAC. Careful attention is therefore required for these patients. Clinical trial information: UMIN000002595.
Reverse-phase protein array marker evaluation of protein expression patterns related to anti-angiogenesis treatment in renal cell carcinoma
Authors: D. Tsavachidou, N. M. Tannir, C. Thomas, G. B. Mills, E. Jonasch
Journal: Journal of Clinical Oncology (2008)

16016 Background: Renal carcinoma patients treated with anti-VEGF therapy (bevacizumab) typically exhibit 10–15% partial responses with detectable primary tumor shrinkage in 70% of the cases (Rini B.I., Clin Cancer Res, 2007). It is not well known which factors determine response or are modulated by therapy. In this study, primary tumors from patients treated with bevacizumab-erlotinib were screened for protein expression of markers representing a broad spectrum of signaling pathways, including AKT, MAPK, angiogenesis, cell growth and apoptosis pathways. Methods: 32 patients with metastatic clear-cell renal carcinoma received bevacizumab 10mg/kg IV Q14 days for a total of 4 infusions plus erlotinib 150mg PO daily for 8 weeks. Nephrectomies were performed 2 weeks after last dose of erlotinib, 4 weeks after last dose of bevacizumab. Tumor and matched normal renal tissue specimens were histologically confirmed and subjected to protein extraction. Lysates were serially diluted and spotted on protein array slides. The arrays were stained with 47 specific antibodies for protein detection. Data were normalized and analyzed according to unsupervised hierarchical clustering approaches, for detecting patterns of protein expression across samples. VHL status (deletions and mutations) was also assessed for each tumor. Results: The protein array method clearly separated normal renal tissue from tumor samples according to their protein expression patterns, as demonstrated by unsupervised hierarchical clustering. Furthermore, duplicate and replicate preparations clustered tightly with their tumor specimen of origin, demonstrating marked reproducibility of the technique, and limited intra-tumor heterogeneity of the biomarkers being analyzed. Treated primary tumors with more than or equal to 10% shrinkage grouped into a distinct protein expression cluster. This cluster was driven mainly by 8 factors (p<0.001) with PTEN being the most prominent (increased expression in the ≥10% shrinkage cluster, p<1.3*10-7). This response group correlated with VHL copy loss (p<0.02). Conclusions: Bevacizumab-erlotinib treated renal tumors reveal distinct protein expression signatures according to the degree of primary tumor response. No significant financial relationships to disclose.