tbuckley/cabot-search huggingface dataset:
Correlative study of EGFR mutations or protein expressions of EGFR, phosphorylated EGFR, HER2, phosphorylated HER2 and IGFR-1 with gefitinib sensitivity in patients with non-small cell lung cancer: Results of West Japan Thoracic Oncology Group trial (WJTO)
Authors: T. Hirashima, K. Nakagawa, T. Kashii, A. Kubo, J. Sasaki, K. Tanaka, S. Sato, T. Kurata, K. Tamura, M. Fukuoka
Journal: Journal of Clinical Oncology (2007)

14008 Background: Both epidermal growth factor receptor (EGFR) mutation and gene copy number of HER2, a member of EGFR family, are associated with gefitinib sensitivity. We carried out a correlative study to determine the relationships between EGFR mutations, EGFR or HER2 protein expressions, their activation status (pEGFR, pHER2) or insulin-like growth factor receptor 1 (IGFR-1) protein expressions and clinical outcomes after gefitinib treatment in advanced NSCLC. Method: Tumors from patients (pts) were evaluated for EGFR mutations by DNA sequence, and for protein expressions of EGFR, pEGFR, HER2, pHER2 and IGFR-1 by immuno-histochemistry. Time to progression (TTP) was calculated by the Kaplan-Meier method; groups were compared using the log-rank test. Risk factors associated with TTP were evaluated with Cox proportional hazard regression modeling. Correlation between EGFR mutation and response was evaluated by Fisher’s direct method. Relationship between each protein expression and response was tested by two-sided. Primary endpoint was to detect biomarkers to predict gefitinib sensitivity. Results: From Dec. 2003 to Dec. 2005, 103 consecutive pts were enrolled onto the study, and received gefitinib until disease progression. Median age was 68 years, female (58%), adenocarcinoma (83%), never smoker (55%) and no previous chemotherapy (49%). 98 pts were evaluable for efficacies, toxicities and gene analyses. Forty-one pts (42%) had EGFR mutations; 14 pts had deletional mutation in exon 19, 27 pts had missense mutation (L858R) in exon 21. EGFR mutations were significantly related to response (62 vs. 26%; P = 0.001), disease control rate (92 vs. 65%; P = 0.003) and TTP (median, 10.1 vs. 5.1months; hazard ratio = 0.64; P = 0.048). Both pEGFR (0, +1 vs. =+2; P = 0.002,) and pHER2 (0 vs. =+1; P = 0.001) expressions are significantly associated with incidence of EGFR mutation. Conclusions: EGFR mutation was a significant predictive biomarker of response to gefitinib. Phosphorylated EGFR protein expression is a potent replaceable biomarker for EGFR mutation. No significant financial relationships to disclose.
Population-based analysis of multimodality treatment of gastric cancer.
Authors: P. Cen, Y. Xing, C. J. Wray, M. B. Fallon, V. I. Machicao, D. Dougherty, R. J. Amato
Journal: Journal of Clinical Oncology (2011)

124 Background: Limited data is available for the role of multimodality management for gastric adenocarcinoma and its outcome in the community. Methods: We retrospectively reviewed the outcomes for 341 patients (pts) who were diagnosed with gastric cancer in a community-based health-care system, including 9 hospitals, from 2000 to 2009. Results: 148/341 pts had undergone surgery and were included in the analysis. Median age at diagnosis was 68 year (range: 32-96), 56% were male, 55% were Caucasian and 25% were black. The stage distribution was as follows: 27% (40 pts) localized, 61% (90 pts) locally advanced and 12% (18 pts) with distant metastasis. 98 pts (66%) received surgery alone, 22 pts (15%) received perioperative chemotherapy, and 28 pts (19%) received perioperative chemo-radiation. After a median follow-up time of 5.2 yrs, the median OS for the entire group was 1.9 years, and 88 deaths had occurred at the last follow up. By stage, the median OS was 7 yrs, 2.3 yrs, and 0.3 yrs for localized stage, regional stage, and metastatic disease, respectively. The 5-yr survival was significantly better in pts who received perioperative chemo-radiation (68%), compared to those who received with surgery alone (33%) or perioperative chemotherapy (0%) (p=0.002). The 5-yr survivals by stage and treatment are shown in the table. Conclusions: Perioperative chemo-radiation was associated with a significantly better OS compared to surgery alone. Trimodality therapy for gastric cancer appears to be underutilized in the community setting described here. The survival advantage of surgery plus chemoradiation compared to surgery plus chemotherapy remains controversial and should be investigated in clinical trials. [Table: see text] No significant financial relationships to disclose.
Recurrence patterns following a negative sentinel lymph node biopsy in patients with early-stage breast cancer
Authors: B. Taback, N. Hansen, K. Conway, A. Giuliano
Journal: Journal of Clinical Oncology (2004)

560 Background: Breast cancer is one of the most frequently diagnosed malignancies among women. Early detection and multidisciplinary treatment including surgery leads to an overall excellent outcome. Axillary lymph node status is the most significant prognostic factor in these patients. We have demonstrated equivalent axillary staging using the technique of sentinel lymph node (SLN) biopsy, which is less invasive and allows a more focused assessment for occult metastasis. In 1995 we abandoned routine axillary dissection for patients with histologically negative SLNs by hematoxylin and eosin and immunohistochemistry staining. The purpose of this study was to determine the patterns of recurrence in patients following a negative SLN biopsy. Methods: The records of 732 breast cancer patients who underwent successful lymphatic mapping (LM) and SLN identification (approximately 70% of whom were operated on by a single surgeon) as part of standard practice at the John Wayne Cancer Institute between 1995 and 2002, and demonstrated a histopathologically tumor-free SLN were reviewed. Results: After a median follow-up of 46 months, 20 (2.7%) patients developed recurrent disease as follows: 9 local, 1 axillary, 8 distant and 2 local with distant recurrences. Among these patients 5 had received adjuvant chemotherapy, 10 received hormone therapy and 15 had postoperative radiotherapy. Median patient age was 54 years (range: 34 to 80 years) and median tumor size for this group was 1.4 cm (range 0.1 to 2.7 cm). Seven patients had poorly differentiated tumors, 18 were ER positive, 10 were PR positive and 5 were positive for HER2/Neu over-expression. All had negative margins following primary tumor excision. Conclusions: This study represents the most comprehensive prospective follow-up analysis to date of early-stage breast cancer patients following LM and SLN identification. These findings demonstrate that patients with histologically negative SLNs have extremely low rates of recurrent disease following multimodality therapy. More importantly, axillary failure following a successfully performed SLN dissection is remarkably uncommon. No significant financial relationships to disclose.
Phase I/II trial of CCI-779 and bevacizumab in stage IV renal cell carcinoma: Phase I safety and activity results
Authors: J. R. Merchan, G. Liu, T. Fitch, J. Picus, R. Qin, H. C. Pitot, W. Maples, C. Erlichman
Journal: Journal of Clinical Oncology (2007)

5034 Background: The mammalian target of rapamicin (mTOR) and vascular endothelial growth factor (VEGF) pathways are critically involved in the pathogenesis and progression of clear cell renal cell carcinoma. Methods: The goal of the phase I portion of the trial was to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combination of the mTOR inhibitor CCI-779 (C) and the anti-VEGF monoclonal antibody Bevacizumab (B). Patients with measurable stage IV clear cell RCC, performance status 0–2 and good organ function were eligible. Up to two prior treatment regimens were allowed. Treatment consisted of 25 mg IV weekly C and escalating IV doses of B (level 1= 5 mg/kg; level 2= 10 mg/kg) every other week. A cycle was defined as 4 weeks. Results: A total of 10 male and 2 female patients, median age 66 yrs (50–77) were enrolled to the phase I portion of the trial. PS: 0/1= 6/6; prior nephrectomy = 10; prior systemic therapy = 7 (prior cytokine therapy = 6); Number of metastatic sites: 1/2/≥3 = 2/2/8; one patient (out of 6) in dose level 1 experienced DLT which consisted of grade 3 hypertriglyceridemia. 1/6 patient in dose level 2 experienced DLT with grade 3 mucositis. Other grade 3 toxicities that were not DLTs included hypertension, proteinuria, hemorrhage, nausea/vomiting, dehydration, anorexia, pneumonitis, anemia, and hypophosphatemia. The best responses in the 12 evaluable patients included 7 PRs and 3 SDs. One patient had PD due to symptomatic deterioration and in one patient response information is not available at the time of this submission. Conclusions: Combination therapy with CCI-779 and Bevacizumab is safe and shows promising clinical antitumor activity. The recommended phase II dose is CCI-779 25 mg/week with bevacizumab 10 mg/kg every other week. The phase II study in stage IV renal cell cancer patients refractory to FDA approved receptor tyrosine kinase inhibitors is under way. The goals of the phase II portion are to determine the proportion of patients who have not had disease progression at 6 months, safety, response rates and correlative biomarker studies including determination of the tumor’s VHL-HIF-VEGF status, PTEN/AKT expression, plasma angiogenic activity and angiogenic cytokines. Supported by NCI N01-CM-62205 No significant financial relationships to disclose.
Detection of pulmonary metastases in patients with osteogenic and soft-tissue sarcomas: the superiority of CT scans compared with conventional linear tomograms using dynamic analysis.
Authors: H I Pass, A Dwyer, R Makuch, J A Roth
Journal: Journal of Clinical Oncology (1985)

A prospective serial evaluation in 19 patients with soft-tissue and osteogenic sarcomas was performed to determine whether computerized tomography (CT) or conventional linear tomography (LT) detected pulmonary metastases earlier. Analysis of the metastatic nodules was performed radiographically with histologic confirmation by obtaining serial CTs and LTs followed by metastasectomy. Nodules were classified as stable, growing, or developing and by detection on CT and/or LT. CT was the first positive study in a significantly greater number of patients (13 CT, 1 LT; P less than .005), and CT detected the nodules earlier than LT (56 CT first v 7 LT first; P less than .0001). Ninety of 166 nodules resected were detected by CT, LT, or both (54%). The median size of metastatic nodules documented at surgical exploration and first detected by CT was significantly smaller than that first detected by LT (7.6 mm for CT v 13.2 mm for LT; P less than .05). Of 55 histologically documented metastases detected initially either by CT or LT, CT was markedly superior to LT with 50 (91%) first detected only by CT (P less than .001). These data reveal that CT detects more pulmonary metastases earlier than LT and that developing or growing nodules in patients with sarcomas are usually metastases. Decisions regarding metastasis resection in sarcoma patients, therefore, should be based primarily on CT findings.
Survival benefit of TACE plus iodine-125 seed implantation in unresectable hepatitis b-related hepatocellular carcinoma with PVTT.
Authors: Mingsheng Huang, Qu Lin, HaoFan Wang, Long Wang, Mingjun Bai, Kangshun Zhu, Hong Shan
Journal: Journal of Clinical Oncology (2015)

408 Background: The aim of this study is to investigate the survival benefit of transarterial chemoembolization (TACE) plus Iodine-125 seed implantation on Hepatitis B-related hepatocellular carcinoma (HB-HCC) patients complicated with PVTT and the underlying prognostic factors. Methods: A retrospective matched cohort study was done on unresectable HB-HCC patients with PVTT at our hospitals between January,2011 and June, 2014. The treatment group enrolled 70patients receiving TACE plus Iodine-125 seed implantation. The control group included 140 case-matched HB-HCC patients receiving TACE. The factors that might affect the overall survival (OS) were examined. Results: There was no significant difference in the baseline demographic characteristics between the two groups (p&gt;0.05). Median survival time of the two groups was 11.0months and 7.5 months, respectively (P&lt;0.001). The OS at 6, 12, 24, and 36 months was 85% vs 55%, 50% vs 25%, 14.5% vs 9%, and 14.5% vs 5% in the treatment group and control group, respectively (all P&lt;0.001). The OS rate for type I+II PVTT patients, type III PVTT patients, patients complicated with arterial-portal-shunt (APS) or patients with mass/nodules in the treatment group was significantly higher than that in the control group (P=0.006, P&lt;0.001, P&lt;0.001,and P&lt;0.001, respectively). Multivariate analysis showed that type III PVTT [Hazard ratio (HR)=0.274; 95% confidence interval (CI): 0.187~0.400; P&lt;0.001], ECOG performance status 1~2 (HR=0.647; 95% CI: 0.428~0.979; P=0.039), diffusely infiltrating tumor subtype (HR=0.596; 95% CI: 0.417~0.852; P=0.005), and the presence of APS (HR=2.387; 95%CI: 1.594~3.574; P&lt;0.001) were independent predictors of poor prognosis. Treatment modality of TACE plus Iodine-125 seed implantation (HR=0.291; 95% CI: 0.185~0.456; P&lt;0.001) was independently associated with better survival. Conclusions: TACE plus Iodine-125 seed implantation can improve OS of unresectable HB-HCC patients with PVTT. Treatment modality, ECOG, PVTT type, presence of APS, and subtype of tumor were independent factors for predicting prognosis.
Myocardial expression of HER2 and HER4 in anthracycline-pretreated breast cancer patients
Authors: S. Landt, H. Bühler, N. Vorsteher, K. Evers, B. Duvnjak, H. Adam, N. Bangemann, J. U. Blohmer, G. Schaller
Journal: Journal of Clinical Oncology (2004)

652 Background: Therapeutic benefits of the powerful combination of Trastuzumab and anthracyclines in the management of HER2-overexpressing metastatic breast cancer are limited by a dramatic increase in cardiac side effects. Many data indicate an important role of HER2 and its preferred cardiac heterodimerisation partner HER4 in mediating essential myocytes survival pathways. Gene targeting of either receptor leads to cardiomyocyte apoptosis and cardiomyopathy. An interaction between Trastuzumab and HER2/HER4 mediated signaling might therefore contribute to the cardiotoxic side effects. We therefore have examined possible changes in the protein expression levels of HER2 and HER4 after anthracycline treatment. Methods: We examined HER2 and HER4 protein expression as well as HER2 gene amplification in 35 cardiac specimens obtained from autopsy material of breast cancer patients with a history of anthracycline treatment. The mean cumulative Epirubicin dose was 662 mg. In addition 10 patients with anthracycline- free pretreatment were assessed. Three of them had received immunotherapy with Trastuzumab. HER2 and HER4 expression were analyzed immunohistochemically using the HercepTest (DAKO) and the polyclonal antibody c-18 (SantaCruz) respectively. Copy numbers of the HER2 gene were determined by fluorescence in situ hybridisation (Inform-Kit Ventana). Results: In the 54 cardiac biopsies with and without anthracycline pretreatment no HER2 staining could be detected. In addition, no HER2 gene amplification was observed in all specimens. A HER4 expression could be detected in 13 of the 25 anthracycline pretreated specimens witch was not significantly different from the cases without anthracycline history (6/10). No relation of HER4 expression with the cumulative anthracycline dose could be noticed. Conclusions: This study shows that an anthracycline treatment does not result in changes of the HER2 or HER4 expression levels nor in amplification of the HER2 gene in the myocardium as suspected to probably underlie the onset of heart failure in anthracycline pretreated patients receiving Trastzumab therapy. No significant financial relationships to disclose.
Patient-reported outcome (PRO)-assessed clinical benefit with panitumumab (Pmab) in metastatic colorectal cancer (mCRC) patients (pts)
Authors: A. Hendlisz, E. Van Cutsem, M. Peeters, Y. Humblet, B. Neyns, A. Sobrero, G. Devercelli, M. Wolf, R. G. Amado, S. Siena
Journal: Journal of Clinical Oncology (2007)

6560 Background: In a phase III study of mCRC pts, Pmab monotherapy significantly improved partial response (PR) rates and progression-free survival (PFS) compared with best supportive care (BSC). This analysis characterizes the clinical benefit of PR/stable disease (SD) and PFS in mCRC pts with respect to health-related quality of life (HRQoL) and CRC symptoms. Methods: Pts had documented disease progression (DP) after treatment (tx) with fluoropyrimidine-, irinotecan-, and oxaliplatin- containing chemotherapy regimens. Pts were randomized 1:1 to receive BSC + Pmab 6mg/kg Q2W. HRQoL (EQ-5D and EORTC QLQ-C30 Global QoL subscale) and CRC symptoms (NCCN/FACT CRC symptom index, FCSI) were assessed at baseline, at least Q4W during tx, and at the 30 day safety follow-up visit. Only pts with PFS ≥ 56 days were included in the analysis to minimize potential lead-time bias associated with response evaluation. T-tests and least square estimates were calculated for differences in PRO measures at 4, 8, 12, 16, and 20 weeks controlling for baseline score by best response (PR or SD vs. other) and by tx arm. Imputation of missing data incorporated each pt's rate of change to assign missing values. Results: In the Pmab arm (n=231), 36% of pts had PR or SD; in the BSC arm (n=232) 10% of pts had SD (no PRs). 109 Pmab pts and 63 BSC pts had at least 1 post-baseline PRO assessment and a PFS time ≥ 56 days. In the Pmab arm, pts with a best response of PR or SD (n=73) had significantly higher mean HRQoL scores at all 5 time points (indicating better HRQoL) compared to those with a best response of &lt; SD (n=36, p=0.03). Consistent results were observed between pts with a best response of PR/SD and CRC symptom scores (p=0.002), indicating less CRC symptomatology. However, in the BSC arm, pts with SD (n=20) had no significant differences in HRQoL or CRC symptoms at any time point compared to pts with &lt; SD (n=43, p=0.12). Results were consistent across all instruments and imputation methods used. Conclusions: These findings show that among Pmab pts with PFS ≥ 56 days, those who had a best response of PR or SD experience significantly higher HRQoL and less CRC symptomatology than Pmab pts without a response. These data suggest that delaying DP may result in clinical benefit. [Table: see text]
Survival predictors in advanced non-small cell lung cancer (NSCLC) patients with clinically proven sensitivity to gefitinib.
Authors: Y. Lee, T. Yun, J. Han, H. Kim, J. Lee
Journal: Journal of Clinical Oncology (2010)

e18060 Background: Recent study reported the timing of EGFR tyrosine kinase inhibitors was lack of survival predictive value in pts with EGFR-mutant lung cancer. This study was designed to investigate survival predictors in advanced NSCLC pts with clinically proven drug sensitivity. Methods: We retrospectively reviewed 1,698 NSCLC pts treated with gefitnib at stage IIIB/IV between 2002 and 2008. We identified 130 pts eligible for the followings; 1) use of gefitnib off protocol as first- or second- line therapy, 2) tumor response or disease stabilization ≥ 6 months after gefitnib, 3) chemotherapy other than gefitinib ≥ 1, and 4) ECOG performance status (PS) 0-2 at diagnosis. Results: Median follow-up time was 23.4 months. Patient characteristics were as follows; median age (range), 59 (29-79); female, 79.2%; never smoker, 72.3%; adenocarcinoma, 93.1%; ECOG PS 0-1, 88.5%; no. of metastasis site < 2, 56.2%. Forty-four pts (33.8%) received gefitinib as first-line therapy and 86 (66.2%) as second-line therapy. Ninety-five pts (73.1%) had ever been treated with platinum-based chemotherapy. Progression free survival (PFS) from the start of gefitinib was similar according to age, gender, smoking history, histology type, and gefitinib timing. In second-line gefitnib group, previous platinum exposure had no effect on PFS for gefitinib (median PFS; 9.7 vs. 9.5 months without previous platinum exposure; p = 0.691). In analysis of overall survival (OS) from the start of first-line therapy, age, gender, smoking history, histology type, gefitinib timing, and platinum-based chemotherapy were not significant predictors but EGOG PS. Pts with ECOG PS 0-1 showed a longer OS than those with ECOG PS 2 (median OS; 30.2 vs. 18.4 months with ECOG PS 2; p = 0.002). There was no significant difference in OS between first- and second-line gefitinib group (median OS; 31.3 vs. 28.5 months with second-line gefitinib; p = 0.714). In first-line gefitnib group, never exposure to platinum had a trend to longer OS (median OS; 41.8 vs. 29.9 months with ever exposure to platinum; p = 0.123). Conclusions: The timing of gefitinib and platinum-based chemotherapy had no effect on survival outcome in pts with gefitinib-sensitive lung cancer. No significant financial relationships to disclose.
CD8 count measurement has independent prognostic significance in individuals with AIDS-Kaposi sarcoma
Authors: J. Stebbing, A. Sanitt, A. Teague, T. Powles, M. Nelson, B. Gazzard, M. Bower
Journal: Journal of Clinical Oncology (2007)

20500 Background: We recently published a prognostic index for Acquired Immunodeficiency Syndrome (AIDS)-associated Kaposi sarcoma (KS) diagnosed in the era of highly active antiretroviral therapy (HAART) based on clinical and routine laboratory characteristics. Because immune subset measurement is often performed in human immunodeficiency virus (HIV) positive individuals, we examined whether these were predictive of mortality independently of the prognostic index, or could predict time to progression of KS. Methods: We performed univariate and multivariate Cox regression analyses on a dataset of 326 individuals with AIDS-KS to identify immune subset covariates predictive of overall survival and time to progression. Adaptive (CD8 T cell and CD19 B cell) and innate (CD16/56 natural killer cell) immune parameters were studied by flow cytometry. Results: In univariate analyses all 3 immune subsets had significant effects on overall survival (p &lt; 0.025). In multivariate analyses including the prognostic index, only CD8 counts remained significant (p = 0.026) although its effect on the overall prognostic index is small. An increase of 100 cells/mm 3 in the CD8 count confers a 5% improvement in overall survival. Individuals with a higher CD8 count did not have an increased time to progression. Patients who were already on HAART at the time of KS diagnosis did not have a shorter time to progression than those who were antiretroviral naïve at KS diagnosis. Conclusions: The CD8 count appears to provide independent prognostic information in individuals with AIDS-KS. Measurement of the CD8 count is clinically useful in patients with KS. No significant financial relationships to disclose.