tbuckley/cabot-search huggingface dataset:
Predictive and prognostic implications of KRAS genotype in patients with metastatic colorectal cancer (MCRC) treated with FIr-B/FOx association.
Authors: G. Bruera, K. Cannita, D. Di Giacomo, G. Troncone, A. Marchetti, G. Coletti, J. Sabourin, M. Tosi, C. Ficorella, E. Ricevuto
Journal: Journal of Clinical Oncology (2011)

457 Background: FIr-B/FOx association, consisting of triplet chemotherapy (FIr/FOx) plus bevacizumab, increases activity, efficacy, and resection rate of liver metastases in MCRC patients (Bruera G et al, submitted 2010). Even if bevacizumab-containing chemotherapy is also active in KRAS m MCRC patients, ORR, PFS, and OS seem to be lower compared to KRAS wt patients (Hurwitz et al, Oncologist 2009). Present data evaluates activity and efficacy of FIr-B/FOX according to KRAS genotype. Methods: Treatment schedule: weekly alternating bevacizumab (5 mg/kg days 1,15)/irinotecan (160 mg/m 2 ) or oxaliplatin (80 mg/m 2 ) associated to weekly 5- fluorouracil (12h-timed-flat-infusion, 900 mg/m 2 /d 1-2, 8-9, 15-16, 22-23); every 4 weeks. KRAS genotype was analyzed by direct sequencing or SNaPshot (Di Fiore et al, BJC'07) for KRAS codon 12 and 13 mutations. Results: Forty-two (84%) out of 50 enrolled patients (pts) in the FIr-B/FOx phase II study were evaluated: ORR 86% (C.I. ± 11), median PFS 13 months (3-46+), median OS 28 months (8-47). Liver metastasectomies (LM) were performed in 11 pts (26%): 42% of the 26 liver-MCRC pts; 58% of the 19 pts with liver-only MCRC pts. Twenty-five pts (59.5%) were KRAS wild-type (wt), 17 pts (40.5%) KRAS mutated (m). Clinical features were balanced. Among the 25 KRAS wt pts: ORR 88% (C.I. ± 14); median PFS 14 months (3-46+); median OS 31 months (8-47). LM were performed in 9 KRAS wt pts (36%): 56% of the 16 liver-MCRC pts; 82% of the 11 liver-only MCRC pts. Among the 17 KRAS m pts: ORR 82% (C.I. ± 19); median PFS 12 months (4-37+); median OS 19 months (8-44). LM were performed in 3 KRAS m pts (18%): 30% of the 10 liver-MCRC pts; 37.5% of the 8 liver-only MCRC pts. Conclusions: Triplet chemotherapy plus bevacizumab (FIr-B/FOx association) shows equivalent high activity (ORR) and efficacy (PFS) in KRAS wt and KRAS m MCRC pts; a trend toward a worse prognosis (OS) is confirmed in KRAS m pts. No significant financial relationships to disclose.
Phase I/II study of GTI-2040 plus docetaxel as 2nd-line treatment in non-small cell lung cancer (NSCLC) and other solid tumors
Authors: N. B. Leighl, S. A. Laurie, J. J. Knox, P. M. Ellis, F. A. Shepherd, R. L. Burkes, M. Vincent, G. R. Pond, J. A. Zwiebel, M. J. Moore
Journal: Journal of Clinical Oncology (2005)

7253 Background: Median survival in advanced NSCLC with systemic therapy is 8 to 10 months, with modest benefits from 1st-, 2nd-, and 3rd-line therapy. GTI-2040 (Lorus Therapeutics, Canada), an antisense oligonucleotide complementary to mRNA encoding the RNR R2 subunit, demonstrates preclinical activity against lung cancer cell lines, synergy with taxanes, and disease stabilization as a single agent in a phase I trial. Objective: To determine the recommended phase 2 dose (RP2D) of GTI-2040 plus docetaxel, and the objective response rate and toxicity at RP2D as 2nd-line therapy in advanced NSCLC. Methods: Advanced solid tumor (phase I) and NSCLC (phase II) patients (pts) with performance status 0–2, adequate renal, hepatic, and hematologic function, and ≤ 1 prior chemotherapy regimen were treated with escalating doses of GTI-2040 by 14-day continuous venous infusion (CVI) plus IV docetaxel on one day every 21 days. Pts in Phase II were treated at RP2D. Results: 18 pts have been treated, 11 at RP2D (7 NSCLC). Dose escalation is shown below, with GTI-2040 5 mg/kg by CVI for 14 days plus docetaxel 75 mg/m2 IV q21days as the RP2D. Dose-limiting toxicity was not seen in cycle 1 at any dose level. Toxicities included neutropenia, sepsis, fatigue, and GI toxicity. Pts received a median of 2 cycles at RP2D (1–7); 2 pts at RP2D developed grade 4 or 5 febrile neutropenia; 3 developed grade 3 thrombosis related to central venous catheters; 2 experienced grade 3 hyperglycemia (likely dexamethasone-related); 1 developed grade 3 anemia after cycle 2. Stable disease (SD) was seen in 10 (6 NSCLC, 2 prostate, 1 SCLC, 1 H&N), including 4 minor responses (3 NSCLC, 1 prostate) and 1 minor PSA response (prostate). 15 patients have come off treatment, 1 after 6 cycles, 7 for progressive disease (PD), 2 for toxicity (including toxic death), 3 at investigator discretion and 2 pts withdrew; 3 remain on treatment, 1 on cycle 7. Accrual, response, survival and toxicity will be updated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
Correlation of 18F-FDG uptake and EGFR/KRAS mutations in surgically resected lung cancer.
Authors: K. Takamochi, S. Oh, M. Fukui, K. Suzuki
Journal: Journal of Clinical Oncology (2011)

10547 Background: The mutation status of both the epidermal growth factor receptor (EGFR) and KRAS genes have been reported to be important predictors of the efficacy of EGFR tyrosine kinase inhibitors such as gefitinib or erlotinib. 18F-fluoro-2-deoxy-glucose (18F-FDG) positron emission tomography (PET) is a functional imaging modality based on glucose metabolism, which has recently been used as a common staging tool for non-small cell lung cancer. We investigated the correlations between the standardized uptake value (SUV) of 18F-FDG and the mutation status of the EGFR and KRAS genes in lung cancer. Methods: We conducted a retrospective review of 189 patients with surgically resected lung cancers (167 adenocarcinomas and 22 non-adenocarcinomas) who underwent 18F-FDG PET/computed tomography scans preoperatively and who were examined for EGFR/KRAS mutations using surgically resected specimens. Correlations between the EGFR/KRAS mutation status and the clinicopathological factors including SUVmax were examined by the chi-square test and a logistic regression analysis. Results: EGFR and K-ras mutations were detected in 82 (44%) and 21 (11%) of the 189 lung cancers, respectively. The univariate analyses showed that EGFR mutations were more frequently observed in females (61%), non-smokers (56%), adenocarcinomas (49%), tumors ≤3 cm (51%), tumors without lymph node involvement (49%), lymphatic permeation (53%) and blood vessel invasion (53%), and with SUVmax <10 (51%). In the multivariate analyses, gender and SUVmax were the significant predictors of EGFR mutation. In the 75 female patients with a tumor with SUVmax <10, 49 (65%) patients had EGFR mutations. The univariate analyses showed that KRAS mutations were more frequently observed in males (17%), smokers (16%), and tumors with SUVmax ≥10 (21%). In the multivariate analyses, only gender was a significant predictor of KRAS mutations. Conclusions: The probability of EGFR mutation was inversely correlated with the SUVmax. In contrast, the probability of KRAS mutation was directly correlated with the SUVmax. EGFR mutated lung cancer may therefore be biologically less aggressive than KRAS mutated lung cancer.
G2/M Arrest Sensitizes Chronic Myelogenous Leukemia Cells to TRAIL-Induced Apoptosis
Authors: David Devlin, Eva Szegezdi, Paavilainen Tanja, Orsolya Orosz, Michael O'Dwyer, Michael Carty, Afshin Samali, Séverine Cruet Hennequart
Journal: Blood (2010)
The face of cancer: public perception versus cancer statistics
Authors: J. Tam-McDevitt, S. Lichtman, R. Hauser, H. Thomas, L. Balducci
Journal: Journal of Clinical Oncology (2008)

17503 Background: More than 60 percent of cancer diagnoses occur among people over age 65. Initiatives to address management of older adults with cancer are ongoing. In order to continue the efforts, public support for research in cancer and aging will be important. However, does the public perception of cancer and aging match what is reported in cancer statistics? Methods: A convenience sample was drawn to complete a 17-question pilot survey over a 1 month period. Demographics data were collected. The survey queried participants about their knowledge on the statistics associated with cancer and aging, participation of seniors in clinical trials, and other topics relating to cancer and aging. Results: One-hundred subjects who met study eligibility completed the survey. Demographics are as follows: 44 male, 56 female; 87% Caucasian; median age 45 (range, 19–91). Only 28% identified correctly 61–70 years as the median age at cancer diagnosis for many cancers. Only 11% answered correctly that 60% of cancer diagnoses occur among people over age 65. 72% subjects correctly answered that <10% of seniors participated in research studies. Only 18% felt doctors have enough information on the use of anti-cancer drugs in seniors with cancer, but 36% thought the government mandates testing of drugs in older adults before a drug can be used in this population. A high percentage (52%) surveyed also stated they felt drug companies do not try hard enough to find the best way to use their products in seniors, mainly due to insufficient financial incentives. Conclusions: Although 83% surveyed stated they knew someone age 65 or older with cancer, majority (66%) perceived the “face of cancer” to be more than a full decade younger compared with the actual cancer statistics. A future random sampling to verify our results is planned. The aging population highlights the continued need to address issues that may be unique to the older cancer adults. A public campaign to better educate the general public about cancer and aging may help to increase awareness and research for this long time under-served population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Geriatric Oncology Consortium Geriatric Oncology Consortium
Effect of age and ethnicity on the tumor location, nuclear accumulation of p53 and clinical outcome in colorectal adenocarcinoma.
Authors: Ravi Kumar Paluri, Michael Behring, James Posey, Upender Manne
Journal: Journal of Clinical Oncology (2016)

559 Background: The race/ethnicity based research in colorectal cancer (CRC) care continues to remain a high priority in developing personalized medicine, and to improve overall clinical outcomes. The role of p53 abnormalities in prognostication of CRC has been evaluated earlier. The incidence of nuclear accumulation of p53 (p53 nac ) and its prognostic relevance in African American (AA) and non-Hispanic white patients (pts) have been investigated, and it was suggested that the clinical consequences of p53 nac in CRC varies with anatomic location of the tumor and the race of the patient. However, the clinical value of p53 nac in relation to age, the tumor location, and race together is not assessed. Thus, we evaluated prognostic significance of p53 nac by considering the tumor location, age, race/ethnicity and p53 nac in CRCs in AA and white pts. Methods: Formalin fixed paraffin embedded CRC tissues from 242 AAs and 346 whites who underwent surgery were assessed for p53 nac by routine immunohistochemistry (IHC). The routine (not antigen retrieval) IHC will identify the majority of genetic alterations ( &gt; 95% missense point mutations) and have significant association with patient survival in CRC. The association between phenotypes, p53 nac status, clinicopathologic features, and overall survival were evaluated using the x 2 test and Cox regression analyses. Results: Approximately equivalent proportions of distal (52%) and proximal adenocarcinomas (48%) were positive for p53 nac in AA pts. In contrast, distal CRC from whites more frequently were positive for p53 nac than from the proximal colon (67% vs. 34%, x 2 P = 0.006). p53 nac was found to be a strong predictor of poor overall survival in young ( &lt; 65 yr) white pts with proximal tumors [hazard ratio (HR) = 2.8, 95% Confidence Intervals (CI):1.2-6.4] but not in AAs (HR = 0.7, 95% CI: 0.41-1.21). Conclusions: The findings of this study suggest that p53 nac is a strong prognostic marker for young white pts with proximal colon adenocarcinomas. Our findings are clinically relevant because several small-molecule inhibitors of mutant p53 are under investigation. These studies were supported by a pilot project grant by the UAB Comprehensive Cancer center.
Increased TACE (Tumor necrosis factor-alpha±-converting enzyme; ADAM17) Activity Associates with Decreased CD62L Expression, Increased Soluble CD62L Plasma Levels and Predicts Molecular Response to Nilotinib Therapy in Patients with Early Chronic Phase Chronic Myelogenous Leukemia (CML-CP): Results from an ENEST1st Substudy
Authors: Sieghart Sopper, Satu Mustjoki, Angelica Loskog, Bjorn T. Gjertsen, Guenther A. Gastl, Frank Giles, Andreas Hochhaus, Gert J. Ossenkoppele, Kimmo Porkka, Dominik Wolf
Journal: Blood (2015)
Frequency of c-Met, HGF, and HER-2 expression and evaluation of their association with clinicopathologic and prognostic factors in gastric cancer.
Authors: Suayib Yalcin, Yetkin Yildiz, Cenk Sokmensuer
Journal: Journal of Clinical Oncology (2015)

88 Background: Met and HER-2 are protoonkogenes encoding receptor tyrosin kinases c-Met and HER-2 respectively. HGF is c-Met’s ligand. We aimed to determine the frequency of c-Met, HGF and HER-2 overexpression in gastric cancer and investigated their association with clinicopathological factors and prognosis. Methods: Patients withstage 1-4 disease were analyzed. Overexpressions of c-Met, HGF and HER-2 were carried out with immunohistochemistry. Results: A total of 143 patients, 97 male 46 female were enrolled. C-Met score was 3(+) in 31.5%, 2(+) in 27.3% and 1 (+) in 10.5% of the patients. There was no statistically significant difference in age, sex, tumor location, differentiation, Lauren classification, TNM staging, presence of distant metastasis, depth of tumor invasion (T), lymphovascular invasion, and survival between c-Met subgroups. HGF positivity was 20.6%. HER-2 was 3(+) in 9.1%, 2(+) in 9.8%, and 1(+) in 16.1% of the patients. HER-2 overexpression was associated with better differentiation, intestinal subtype and advanced stage. C-Met overexpression was 84.6% in HER-2 overexpression positive group and 56,2% in HER-2 overexpression negative group. There was no statistically significant difference in survival between the c-Met overexpression positive and negative stage 3 and 4 patients and there was no statistically significant differences in survival between the HGF positive and negative groups. The median survival was 11.6±6.3 months in HER-2 overexpression positive stage 4 group and 11.9±6.8 months in HER-2 overexpression negative stage 4 group. There was no statistically significant differences in survival between the two groups. Conclusions: C-Met was not associated with any negative prognostic factors in gastric cancer. HER2 was associated with better differentiation, intestinal subtype, advanced stage and c-met overexpression. HGF expression was not asscociated with any clinicopathological factor.
Physician preferences and knowledge regarding the care of childhood cancer survivors in Japan: A mailed survey of the Japanese Society of Pediatric Oncology.
Authors: Y. Ishida, M. Takahashi, M. Maru, C. Daugherty, M. Mori, A. Manabe, T. O. Henderson
Journal: Journal of Clinical Oncology (2011)

e19522 Background: Japanese physicians’ attitudes regarding the health care needs of childhood cancer survivors (CCSs) are not well described. Thus we examined the self-reported preferences and knowledge of pediatric oncologists and surgeons concerning this population. Methods: A mailed survey was sent to 858 physician members of the Japanese Society of Pediatric Oncology in October 2010 according to the methods of Henderson et al (JCO 28 (5):878, 2010). Results: A total of 405 surveys were returned (47% response rate); of which 300/533 pediatric oncologists and 105/325 and surgeons responded, respectively. Respondents’ median age was 46 and 48 years, respectively; 79% and 84% men. There were no differences between physicians excluding living area distributions and educational opportunities of late effects. Less than one third of respondents (31%) report referring survivors to other physicians. When comfort levels in caring for CCSs were described (1 = very uncomfortable; 7 = very comfortable), physicians were most comfortable with CCS <= 21years (4.4 ± 1.3 and 3.8±1.4), less comfortable with CCSs > 21 years but < 30 years old (3.6 ± 1.4 and 3.6 ± 1.4), and least comfortable with CCS >30 years (2.8 ± 1.5 and 3.3 ± 1.6). Familiarity with long-term follow-up guidelines was quite lower in surgeons (2.8 ± 1.4 vs 1.5 ± 1.4). In response to a clinical vignette of a 25 year old woman treated at 1 year with prophylactic cranial radiation (24 Gy), 62 % of pediatric oncologists and 43% of surgeons answered 3 or more questions regarding follow-up frequency, Hepatitis C surveillance, and late effects of cranial radiation in concordance with Japanese recommendations. Logistic regression analysis limited to pediatric oncologists showed learning experience (OR= 1.75; 95% CI, 1.05 to 2.93); practicing in a children’s hospital (OR 5.11; 95% CI, 1.15 to 22.8); and practicing in a general hospital (OR, 0.55; 95% CI, 0.32 to 0.95) were associated with answering three or more questions correctly. Conclusions: Preferences and knowledge with regard to long-term follow-up care of CCSs differ between pediatric oncologists and surgeons in Japan; pediatric oncologists appear to be more comfortable.
Cancer team approach for prescreening and identifying breast cancer survivors as part of survivorship care plan implementation.
Authors: Oana Cristina Danciu, Sushma Bharadwaj, Kent Hoskins
Journal: Journal of Clinical Oncology (2015)

107 Background: Recommendations from the Institute of Medicine are that cancer patients receive individualized survivorship care plan (SCP)and treatment summary.SCP includes guidelines for monitoring and maintaining health and is a communication tool shared with families and health care providers. Offering SCP and treatment summary to cancer survivors remains challenging due to time and resource limitations, inadequate reimbursement and survivor access. Methods: Survivorship starts when completing the initial treatment (surgery, chemotherapy or radiation therapy). A team of medical oncologists, nurse practitioner and patient navigator created a process of pre-screening and identifying breast cancer (BC) survivors. SCP and treatment summary were pre-populated, individualized for each patient, then finalized and discussed with the patients during their medical oncology clinic visit.Pre intervention data was retrospectively collected, including all BC cases from March 2014 to March 2015. Post intervention data was prospectively collected over eight weeks. Pre and post intervention SCP completion rates were compared with chi square analysis. Results: A baseline one year review of 1124 encounters noted 23 of 90 (25%) BC survivors received SCP. Ninety-six encounters occurred during the 8 week pilot period. Sixteen (16.6%) cases met the definition of BC survivor. During the pilot period, 15 out of 16 (93.7%) survivors received the SCP and treatment summary (p &lt; 0.0001). Conclusions: We successfully piloted the implementation of SCP for BC survivors. Our team found that using clinic visit screening and pre-identifying patients that transition into the survivorship program resulted in improvement of compliance with survivorship measures. We plan to open a BC survivorship clinic to address survivorship issues and to review SCP and treatment summary.
Concurrent cisplatin and radiotherapy: Decision making, tolerability, and outcomes for patients treated in a multidisciplinary bladder clinic.
Authors: Nafisha Lalani, Sue Richter, Peter W. M. Chung, Neil Eric Fleshner, Michael A. Jewett, Alexandre Zlotta, Robert Glen Bristow, Michael Milosevic, Srikala S. Sridhar
Journal: Journal of Clinical Oncology (2014)

320 Background: For select muscle invasive bladder cancer (MIBC) patients, a multimodal approach using transurethral resection of the bladder tumor (TURBT) followed by concurrent cisplatin and external beam radiotherapy (EBRT) provides a curative bladder-sparing alternative to cystectomy. Our aim was to review decision making, tolerability and outcomes for patients treated in a multidisciplinary bladder clinic. Methods: Between June 1998-June 2011, MIBC patients treated with TURBT and concurrent cisplatin (40mg/m2 weekly) with EBRT (60-66Gy in 30-33 fractions to the bladder and pelvis) were identified. Post-treatment cystoscopy was performed every 3 months with regular imaging. Results: A total of 64 patients were assessed; mean age 73 (43-89), 83% were male. The decision to attempt bladder-sparing was based on patient preference (58%), nonsurgical candidate (25%), or unknown (17%). Patients received a mean 5/6 weeks of cisplatin with the most common toxicity being a 14% overall risk of grade 0-1 renal toxicity by NCIC CTC criteria. All patients completed the prescribed EBRT. No patients experienced acute toxicity requiring cystectomy or causing death. At a median follow-up of 3.5 years, 50/64 (78%) patients were alive and had their own bladders, 7/64 (11%) were alive after cystectomy for recurrence, 7/64 (11%) died. Of the 24/64 (38%) recurrences: 3/64 (5%) had positive cytology/carcinoma in-situ and received intravesicle therapy; 1/64 (2%) had local superficial recurrence and underwent TURBT; 7/64 (11%) had local invasive recurrence requiring cystectomy; 13/64 (20%) had distant recurrence, 6 received chemotherapy and 7 were observed. Estimated disease free survival was 51%, and overall survival was 90% at 3.5 years. Conclusions: Bladder-sparing therapy with concurrent cisplatin and EBRT is a well-tolerated and effective approach with outcomes comparable to cystectomy in carefully selected patients. Prospective trials are required to delineate clinical and molecular factors to further triage patients into sub-groups who may benefit from bladder sparing with neoadjuvant/adjuvant chemotherapy or molecularly-targeted agents to improve survival.