tbuckley/cabot-search huggingface dataset:
A phase I study of PEG-intron, sunitinib and tarceva in patients with metastatic renal cell cancer (MRCC)
Authors: V. Vance, R. J. Amato, J. Jac, S. Saxena, J. P. Willis, S. B. Chiang
Journal: Journal of Clinical Oncology (2008)

14659 Background: Renal cell cancer (RCC) frequently overexpresses basic vascular endothelial growth factor, epithelial growth factor, and platelet derived growth factor. A phase I combination of pegylated interferon, sunitinib and tarceva to determine the maximum tolerated dose and provide an early indication of efficacy. Methods: Eligibility included: pathologic diagnosis of clear cell or papillary RCC, progressive measurable metastatic disease, no more than 3 prior therapies, adequate physiologic parameters and no active CNS involvement. The dosing schedule is: Results: Dose modifications were performed for toxicity per the National Cancer Institute toxicity criteria version 3.0. Patients were evaluated every cycle (6 weeks) using RECIST. 9 patients have been enrolled to date. 6 patients at dose level 0 and 3 patients at dose level +1. 5 patients have papillary and 4 clear cell. The most common treatment related adverse events; Grade 1: fatigue (44%), skin rash (44%), and diarrhea (33%). 2 patients experienced Grade 3/4: reversible thrombocytopenia and leukopenia. Partial responses were seen in 2 (22%) and stable disease for ≥ 3 months in 3 (33%). It is too early to establish progression free survival and overall survival. Conclusions: PEG-Intron, sunitinib, and tarceva has been well tolerated with reversible toxicities. We are presently enrolling an additional 3 patients at dose level +1. Signs of anti-tumor activity have been demonstrated. Safety data and anti-tumor activity will be presented. Dose Level Peg-Intron Ug/Kg/wk, Day 1 Weekly Sunitinib Mg Days 1–28, Days 29–42 Tarceva Mg Days 1–42 +0 1.5 37.5 75 +1 3.0 37.5 75 +2 3.0 50 75 +3 3.0 50 150 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Schering-Plough
Randomized, double-blind, phase II study of erlotinib in combination with placebo or R1507, a monoclonal antibody to insulin-like growth factor receptor-1 (IGF-1R), for advanced-stage non-small cell lung cancer (NSCLC).
Authors: S. S. Ramalingam, D. R. Spigel, M. Steins, J. A. Engelman, C. Schneider, S. Novello, W. E. Eberhardt, L. Crino, P. A. Janne, L. Liu, C. M. Brownstein, M. Reck
Journal: Journal of Clinical Oncology (2011)

7527 Background: R1507 (Hoffman LaRoche) is a selective, fully human, recombinant monoclonal antibody (IgG1 subclass) against IGF-1R. Based on strong pre-clinical evidence supporting co-inhibition of IGF-1R and epidermal growth factor receptors, we conducted a randomized study of R1507 with erlotinib (E). Methods: Advanced NSCLC patients with progression following 1 or 2 prior chemotherapy regimens, ECOG PS 0-2, and measurable disease were eligible. Patients were randomized to receive erlotinib (150 mg PO QD) in combination with either placebo, R1507 at 9mg/kg/week or R1507 at 16 mg/kg/Q 3 weeks, i.v. Treatment cycles were repeated every 3 weeks. The primary endpoint was comparison of the 12-weeks PFS rate. Results: 171 patients were enrolled, with the following characteristics: median age 61 years, female 33%, never-smokers 12%, stage IV 86%, PS 0/1- 88%, squamous histology 25%, adenocarcinoma 51%, and 1 prior regimen 74%. The median number of doses of R1507 was 6 and 3.5 for the weekly and Q3 week arms respectively. Grade 3/4 adverse events were noted in 37%, 44%, and 48% of patients with placebo, weekly, and Q3 week R1507 therapy respectively. The following biomarkers were evaluated in tissue specimens (n=165): Tumor tissue - expression of IGF-1R, and K-ras mutation status; Plasma-free IGF-1 level. In patients with high free IGF-1 levels, the 12-weeks PFS rate was higher with Q3 week schedule of R1507 compared to placebo (46% vs. 18%). The 12-weeks PFS rate in patients with K-ras mutation was 22% with R1507 compared to 0 with placebo. Conclusions: R1507 failed to improve the efficacy of erlotinib in an unselected group of advanced NSCLC patients in the 2nd/3rd line therapy setting. K-ras status and free IGF-1 bioactivity in serum demonstrated predictive potential in an exploratory analysis. Parameter E + Placebo E + R1507 (weekly) E + R1507 (Q 3 wks) N 57 pts 57 pts 57 pts Response rate 8.8% 8.8% 7% 12-weeks PFS rate 39% 37% 44% (NS) Median PFS 1.5 m 1.6 m 2.7 m (P=NS) Median OS 8.1 m 8.1 m 12.1 m (P=0.04) Gr 3/4 skin rash 8% 7% 10% Gr 3/4 fatigue 6% 10% 7% Hyperglycemia (any) 0 3% 9%
Role of nutritional status as predictor of survival in oesophageal cancer treated with definitive chemoradiation (dCRT): outcome from SCOPE1, a phase II/III randomised trial of dCRT +/- cetuximab.
Authors: Samantha Cox, Ceri Powell, Ben Carter, Chris Hurt, Somnath Mukherjee, Tom David Lewis Crosby
Journal: Journal of Clinical Oncology (2016)

103 Background: Malnutrition is common in oesophageal cancer and may be related to the disease or treatment. We aimed to identify nutritional prognostic factors and the outcome of nutritional intervention in patients recruited to the SCOPE1 trial. Methods: 258 patients were randomly allocated to dCRT with or without the addition of cetuximab. Data was collected prior to induction chemotherapy (iCT) and before commencing concurrent CRT. Nutritional Risk Index (NRI) was calculated and categorised; ≥ 100 (no risk of malnutrition), 97.5-100 (mild risk), and &lt; 97.5 (moderate to severe risk). The maximal nutritional intervention (MNI) received was classified as: none, dietary advice, oral supplementation or major intervention (enteral feeding/tube placement). Univariate and multivariate analyses using Cox proportional hazard modelling were conducted to identify predictive factors and important interactions involving MNI. Results: An NRI score &lt; 100 at baseline strongly predicted reduced median overall survival (OS) in multivariate analysis (HR = 12.45, 95% CI 5.24 – 29.57; p = &lt; 0.001). Furthermore, OS was improved in this group if they received dietary advice (HR = 0.12, p = 0.004), oral supplementation (HR = 0.13, p = &lt; 0.001) or major intervention (HR = 0.13, p = 0.003) prior to commencement of iCT, but there was no benefit if intervention occurred after commencement of iCT. Patients on cetuximab arm undergoing major intervention had worse outcomes compared to control (13 months vs 28 months, p = 0.003). Conclusions: Assessment and correction of poor nutritional state at baseline may improve survival outcomes in oesophageal cancer patients treated with dCRT. The benefit of intervention is no longer observed once treatment has commenced, highlighting the need for early nutritional assessment and intervention. Reason for poor OS in patients on cetuximab requiring major intervention is unclear. Clinical trial information: 47718479.
Validation of blinded events review committee (ERC)-determined time to neurologic progression (TTNP) demonstrates correlation with survival, radiologic progression, and functional independence endpoints
Authors: W. R. Shapiro, J. A. Smith, R. A. Patchell, M. J. Glantz, L. D. Recht, M. P. Mehta, S. C. Phan, M. F. Renschler
Journal: Journal of Clinical Oncology (2005)

1534 Background: Survival is a standard endpoint for brain metastasis trials, but inadequately measures treatment benefit because of competing risks for death from systemic disease, and does not account for neurologic function, an important quality of life consideration. There is no standardized and validated tool to measure TTNP. The purpose of this study was to test the validity of ERC-determined TTNP. Methods: In a prospective, randomized phase 3 trial of whole brain radiation +/−motexafin gadolinium for patients (pts) with brain metastases, 401 pts underwent standardized neurologic exam, neurocognitive tests (NCT), evaluation of symptoms, functional independence (Barthel Index), and MRI. Using a pre-specified algorithm, the ERC reviewed blinded clinical data, excluding MRI, to score progression if 2 of 3 functional domains (NCT, neuro exam, neuro symptoms) showed progression on consecutive visits (Mehta J Clin Oncol 21:2529, 2003). TTNP was compared to survival, MRI progression, and time to loss of functional independence using log-rank tests and Kaplan-Meier plots. Results: Pts with TTNP ≤ 1, 2, 3, or 4 months (mo) had a decrease in median survival of 4.4, 3.9, 3, and 2.4 mo, respectively, compared with pts who did not have neurologic progression at those times (all p<0.001, see Table). Pts who experienced MRI progression at 2 mo had a significantly shorter TTNP by ERC than pts with stable or improved MRI (p<0.001). Pts with TTNP ≤ 1, 2, 3, or 4 mo lost their functional independence significantly more rapidly compared with pts who did not have neurologic progression at those times (p<0.001 for all). Conclusions: The validity of a blinded ERC-determined TTNP endpoint was demonstrated by high correlations with survival, radiologic progression, and loss of functional independence endpoints. ERC-determined TTNP measures clinical benefit. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pharmacyclics Pharmacyclics Pharmacyclics Pharmacyclics
Quantitative gene expression at the 8q24 prostate cancer risk locus
Authors: M. Pomerantz, C. Beckwith, M. M. Regan, W. Xie, P. Herman, J. Chan, K. Ardlie, W. K. Oh, P. W. Kantoff, M. L. Freedman
Journal: Journal of Clinical Oncology (2008)

5055 Background: The 8q24 chromosome locus has emerged as a genetic risk factor for prostate cancer. How the locus exerts its effect, however, is currently unknown because the risk variants are situated in non-coding regions. One hypothesis is that the risk alleles influence expression of one or more genes in the region. We sought to define the transcriptional landscape at 8q24 and identify the gene(s) influenced by the risk polymorphisms. More generally, we provide an approach for following up risk alleles from genome wide scans. Methods: DNA and RNA were isolated from 124 individuals from the Dana-Farber Cancer Institute/Gelb Center cohort. The DNA was isolated from blood samples and genotyped for 6 single nucleotide polymorphisms (SNPs) shown to contribute independently to prostate cancer risk. RNA was isolated from histologically normal tissue from radical prostatectomy specimens. To comprehensively evaluate transcription, a Nimblegen tiling array was constructed spanning 5 megabases across 8q24 at 8 base pair resolution. Twelve transcripts of interest were selected based on a cDNA/genomic DNA metric. Expression levels of these transcripts and 7 housekeeping genes in the 124 samples were measured using competitive PCR on the Sequenom mass spectrometry platform. Linear regression was used to test for association between risk allele status and transcript abundance. Results: Twelve distinct areas of transcription were observed on tiling array: 3 previously unannotated elements and 9 annotated genes or expressed sequence tags, including the oncogenes MYC and PVT1. Analysis of 48 individuals showed that MYC expression was unaffected by the total number of risk alleles inherited by an individual, but a non-significant increase in expression was seen among carriers versus non- carriers of risk alleles for SNP rs7000448. Expression of 3 transcripts in or near PVT1 (BM556507, M34431, and TMEM75), though not PVT1 itself, decreased as the total number of risk alleles carried by an individual increased (p <0.05). Analysis of all 124 individuals will be completed by February, 2008. Conclusions: We provide the first systematic analysis of the association between inherited prostate cancer risk alleles at 8q24 and transcript abundance in this region. No significant financial relationships to disclose.
Monitoring of the estimated glomerular filtration rate (eGFR) in patients with small cell lung cancer during chemotherapy: Equations based on serum creatinine or cystatin C?
Authors: X. Zhang, L. Ren, Y. Gong, M. Huang, L. Zhou, J. Zhu, Z. Ding, M. Hou, Y. Lu
Journal: Journal of Clinical Oncology (2011)

e19741 Background: Cystatin C (CysC) has been demonstrated as a new marker of glomerular filtration rate. This study compared the differences between eGFR calculated by the Cockcroft&Gault' (eGFRCG) and CysC-based formula (eGFRCysC) in monitoring renal function in patients with small-call lung cancer (SCLC) during chemotherapy. Methods: Besides the disease-specific parameters, serum creatinine and CysC were detected in 61 patients, and eGFRCG and eGFRCysC after each chemotherapy cycle were calculated and analyzed. Patients also were compared within different eGFR groups. Results: eGFRCysC correlated significantly with serum creatine and eGFRCG respectively (p<0.001). The decreases of eGFRCysC after each treatment cycle were more significant than those decreases of eGFRCG (-3.0634±10.651 vs -0.2274±10.298 ml/min/1.73m2, p=0.001). Single/multi-parameter analysis showed that patients having higher BMI (>23), Scr concentration (>77 μmol/L) and receiving more treatment cycles (>2) were in the increased risk of developing renal impairment with eGFR less than 60 ml/min/1.73 m2 during chemotherapy. Conclusions: The CysC-based formula seems more accurate in predicting eGFR as routine monitoring renal function in patients with SCLC receiving chemotherapy than the CG formula. More attention should be paid to specific patient groups on their renal function during treatment.
Local control in resectable and borderline resectable pancreatic cancer (PCa) treated with preoperative chemoradiation using IMRT or chemotherapy alone.
Authors: Jordan Kharofa, Tracy R. Kelly, Ben George, Paul S. Ritch, Susan Tsai, Kathleen K. Christians, Douglas B. Evans, Beth Erickson
Journal: Journal of Clinical Oncology (2013)

282 Background: The primary objective is to review local control and failure patterns in PCa patients treated with preoperative chemoradiation (chemoXRT) using IMRT compared to patients treated with chemotherapy alone. Methods: All patients with resectable and borderline resectable PCa treated between 1/1/2009 -11/1/2011 were reviewed. During the study period, 68 patients (40 borderline resectable, 28 resectable) were treated with preoperative chemoXRT (50.4 Gy [1.8 Gy/fx] with concurrent gemcitabine [n=59] or capecitabine [n=7]). 12 patients with resectable tumors received gemcitabine based chemotherapy alone and did not receive radiation therapy due to enrollment on chemotherapy only protocols (n=10) or to patient preference (n=2). Radiation was delivered to a CTV that includes the primary mass, the SMA and SMV, +/- the celiac axis. A 4D-CT and daily image guidance were used in all patients. The local failure free interval was defined as the time from surgical resection to local failure or last documented CT scan of the abdomen with no evidence of local disease progression. Results: Following preoperative chemoXRT, 48/68 patients underwent resection with 47(98%) R0 resections. 11/12 patients in the No XRT group undwerent resection with 10 (91%) R0 resections. In the No XRT group, 8/11 (73%) patients failed locally at the SMA/SMV or resection bed as a component of first failure compared to 1/48 (2%) patients who received preoperative chemoXRT (p&lt;0.001). Local failure was the sole site of first failure in 5/11 patients in the No XRT group and 0/48 patients who received preoperative chemoXRT. The actuarial rate of local failure 1 year from surgery was 5% in the preoperative chemoXRT group vs 27% in the No XRT group (p&lt;0.001). All local failures in the No XRT group would have been encompassed using the CTV target volumes used in patients treated with preoperative chemoXRT. Conclusions: IMRT-based, conformal, preoperative chemoXRT for resectable and borderline resectable PCa may facilitate margin negative resection and increase local control. Omission of radiation therapy may result in high rates of local failures at the SMA/SMV vasculature or in the pancreatic bed.
A blood-based gene expression signature of early-stage non-small cell lung cancer.
Authors: Melissa Rotunno, Nan Hu, Hua Su, Chaoyu Wang, Pier Alberto Bertazzi, Neil Caporaso, Phil R. Taylor, Maria Teresa Landi
Journal: Journal of Clinical Oncology (2012)

69 Background: Accurate blood-based biomarker for early cancer detection could be an easier and more convenient screening option than monitoring the target organ via tissue or imaging. We recently identified and validated eight genetic biomarkers of early-stage lung adenocarcinoma detectable in both peripheral whole blood (PWB) and lung tissue of smokers. Since biomarkers distinguishing benign disease versus lung malignancy across all cell types are needed in the diagnostic clinical setting, it is important to test the identified biomarkers in other lung cancer histologies, particularly in squamous cell carcinoma (SQCC), the second most common lung cancer histology after adenocarcinoma (AD). Methods: Using Real-Time Quantitative PCR (qRT-PCR), we measured mRNA levels for the eight candidate genes in PWB of 48 randomly sampled stage I SQCC cases, in addition to previously analyzed 82 AD cases and 130 age, sex, and smoking frequency matched healthy controls from the Environment And Genetics in Lung cancer Etiology (EAGLE) case-control study. The qRT-PCR data were analyzed using the 2 - ΔΔCt method to compare SQCC cases with controls. The area under the receiver operating characteristic curve (AUC) was computed to assess the predictive accuracy of the candidate biomarkers in SQCC separately, and in SQCC and AD together. Results: Expression of TGFBR3, RUNX3, TRGC2, TRGV9, TARP, and TSTA3 genes, significantly differentiated SQCC cases versus controls, while ACP1 and VCAN gene expression did not. The eight genes combined discriminated patients with lung cancer from healthy controls with similarly high accuracy in SQCC and overall (AUC = 0.80 ± 0.1). RUNX3 showed the highest single gene accuracy for SQCC (AUC = 0.78). Conclusions: We showed that the previously identified gene expression signature of early-stage lung AD also differentiated early stage SQCC from healthy controls and demonstrated its sensitivity and specificity as a potential diagnostic lung cancer biomarker. Since lung cancer is the most common cause of cancer mortality worldwide and current smokers are at very high risk, our smoking-specific findings, if confirmed and translated into screening approaches, have the potential to impact public health.
A multidisciplinary team approach to efficient breast cancer diagnosis.
Authors: Mary E. Cianfrocca, Melissa Shelby, Shefali Birdi, Stephanie Costa Byrum, Julie Annie Yee Billar, Kevin McCabe, Jignesh Patel, Vilert A Loving
Journal: Journal of Clinical Oncology (2016)

88 Background: System inefficiencies result in delayed breast cancer diagnoses. Inefficiencies include any non-value added steps between symptom onset/imaging abnormality to cancer diagnosis and treatment. Diagnostic delays can lead to more advanced disease and may negatively impact survival. Further, optimizing the efficiency of diagnostic evaluation models can reduce barriers to care and improve patient satisfaction. To achieve these efficiency goals, Banner MD Anderson Cancer Center (BMDACC) instituted the Undiagnosed Breast Clinic (UBC). The UBC expedites patient evaluation through a multidisciplinary diagnostic team of internists, surgeons, pathologists and radiologists. Patients with an abnormality on physical exam or imaging are promptly evaluated by the UBC team and any necessary diagnostic tests are performed. If malignancy is diagnosed, the BMDACC breast team swiftly institutes multidisciplinary care. Methods: We conducted a retrospective chart review of patients seen in the UBC from 12/2012 - 12/2013. We tallied patient demographics, diagnostic data, and treatment information. Results: 177 patients (174 females; 3 males) were identified. Mean age was 54 years (range: 16-91). Patient racial breakdown was 144 (81%) Caucasian; 8 (5%) Black, 6 (3%) Latina, 4 (2%) Asian, and 15 (8%) Other. Malignant diagnoses (invasive carcinoma or ductal carcinoma in situ) were found in 28 patients (16%), and high-risk lesions (atypia or lobular carcinoma in situ) were found in 8 patients (5%). Of the 46 patients who underwent needle biopsy as part of the UBC evaluation, 28 (61%) underwent biopsy the same day as the initial visit. An additional 5 patients (11%) underwent biopsy the next day.Genetics consults were obtained in 11 patients (6%). Of these 11 patients, one tested positive for BRCA 1 and one for BRCA2. Conclusions: A multidisciplinary team approach to breast cancer diagnosis is feasible. The resultant evaluation eliminates non-value added steps in the patients’ workup, thereby expediting time from presentation to diagnosis and, if needed, treatment.
A phase II trial of trastuzumab combined with irinotecan in patients with advanced HER2-positive chemo-refractory gastric cancer: OGSG1203 (HERBIS-5).
Authors: Kazuhiro Nishikawa, Daisuke Sakai, Junji Kawada, Ryohei Kawabata, Tomono Kawase, Yoshio Oka, Naotoshi Sugimoto, Takeshi Shimizu, Junichi Nishijima, Hiroko Hasegawa, Shunji Endo, Yutaka Isozaki, Yutaka Kimura, Jin Matsuyama, Yukinori Kurokawa, Toshio Shimokawa, Kazumasa Fujitani, Taroh Satoh
Journal: Journal of Clinical Oncology (2016)

128 Background: Irinotecan is a key drug in second- or further-line chemotherapy for patients with advanced gastric cancer. Continuous administration of trastuzumab beyond first progression is expected to contribute to the benefit of chemotherapy for HER2-positive gastric cancer. We assessed the efficacy and safety of combination chemotherapy with trastuzumab and irinotecan in Japanese patients with advanced HER2-positive chemo-refractory gastric cancer. Methods: Intravenous infusion of irinotecan every 2 weeks at a dose of 150 mg/m 2 ; intravenous infusion of trastuzumab at a dose of 8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks. Administration of irinotecan and trastuzumab were repeated in independent schedules. The primary endpoint was disease control rate. The secondary endpoints were adverse events, response rate, time-to-treatment failure, progression-free survival, overall survival, and response rate stratified by prior trastuzumab use. This study was conducted by the Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG). Results: From October 2012 to Augst 2014, 30 patients were enrolled and one patient withdrew before study treatment. Accordingly, 29 patients were assessable for efficacy and safety. The disease control rate was 65.5% [95% C.I. 45.7 - 82.1%], and the response rate was 20.7% [95% C.I. 8.0 - 39.7%]. The median progression free survival and the median overall survival were 3.7 and 7.5 months, respectively. The major grade 3/4 toxic effects were neutropenia (24%); anemia (24%); leucopenia (21%); anorexia (11%); fatigue (14%); hypoalbuminemia (24%); and hypokalemia (14%). One death (NOS) was considered to be related to the study. Conclusions: The results of combination Trastuzumab with irinotecan showed feasible and promising efficacy against advanced HER2-positive chemo-refractory gastric cancer. These findings indicated that trastuzumab continuation use might be beneficial. Clinical trial information: 000008626.