tbuckley/cabot-search huggingface dataset:
Non-invasive detection of EGFR T790M in gefitinib/erlotinib resistant NSCLC
Authors: Y. Kuang, A. Rogers, L. Wang, M. Makrigiorgos, K. Vetrand, S. Thiede, R. Distel, P. A. Janne
Journal: Journal of Clinical Oncology (2008)

8075 Background: Fifty percent of NSCLC patients (pts) that develop a partial (PR) or complete (CR) response to gefitinib (G) or erlotinib (E) will develop a secondary EGFR T790M mutation as a mechanism of drug resistance. As most pts do not undergo repeated tumor biopsies, we evaluated the ability to detect EGFR T790M non-invasively from plasma DNA. Methods: NSCLC pts (n= 55) previously treated with G (n= 15) or E (n=36) or untreated (n=4) were included. Best response to prior treatment: CR/PR (n=28); SD (n=13); PD (n=10). EGFR mutant/wild type/unknown: 27/16/12. DxS real time PCR and WAVE technologies were used to screen for EGFR mutations in 72 plasma samples (median no. of samples per pt = 1; range = 1–5). Two methods of whole genome amplification (WGA) were explored to increase the yield of plasma DNA. Results: EGFR activating mutations were identified from plasma DNA in 32 (58%) pts. Concordance with primary EGFR tumor mutation was 70%. In 9 pts with a tumor EGFR mutation, we were unable to detect the mutation in plasma DNA. We detected EGFR T790M in 15/28 (53%) clinically resistant pts with prior CR/PR; 3/13 (23%) resistant pts with prior SD; and 0/10 (0%) resistant pts with prior PD. EGFR T790M was not detected in untreated pts. WGA was successful in 51/55 (93%) pts. There was no correlation between plasma DNA concentration and ability to detect EGFR activating or T790M mutation. Conclusions: We detected EGFR T790M from plasma DNA in 15 (53%) G or E resistant pts with prior CR/PR. This correlates closely with established estimates of EGFR T790M frequency (50%) from tumor biopsies in this pt population. Detection of EGFR T790M using non-invasive methods may aid in directing the course of subsequent therapy for G or E resistant pts. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca, Boehringer Ingelheim, Roche Pfizer Genzyme
Early outcome of a phase II study of yttrium-90 radioactive resin microspheres in the treatment of colorectal adenocarcinoma metastatic to the liver after failure of first-line combination chemotherapy (inSIRT Trial).
Authors: E. Roeland, K. A. Shimabukuro, P. T. Fanta, S. C. Rose, T. R. Reid
Journal: Journal of Clinical Oncology (2011)

626 Background: Liver metastases develop in at least half of the cases of colorectal cancer (CRC) and the liver is often either the dominant or the only site of metastases. It is estimated that up to 90% of patients with metastatic CRC die as a consequences of their hepatic metastases and resultant liver failure. We are evaluating the aggressive management of liver metastases through the incorporation of Yttrium-90 radioactive microspheres after evidence of progressive disease following a first-line FOLFOX based regimen with or without bevacizumab. Optimal timing for microsphere treatment relative to chemotherapy has not yet clearly been established. In this abstract, we present preliminary data of a phase II study evaluating tumor and biochemical response rates. Methods: Patients with disease progression despite first-line FOLFOX based therapy with or without bevacizumab are eligible for the inSIRT trial. Interventional radiology and nuclear medicine assess the liver lesions and the patient receives selective internal radiation therapy (SIRT) microspheres therapy. Bilobar hepatic disease requires a second treatment. 4-6 weeks after the final microspheres therapy, patients proceed to second-line chemotherapy with FOLFIRI. Results: To date, 3 metastatic CRC patients have been treated on this protocol and a total of 5 patients enrolled. No significant adverse events have been noted. Preliminary results for 3 patients show stable disease after failure of first-line combination chemotherapy up to 160 days after treatment. No significant financial relationships to disclose.
Influencing antiemetic prescribing practices and funding changes through evidence-based guidelines.
Authors: Kathy Vu, Michael Wan, Aliya Pardhan, Erin Redwood, Andrea Crespo, Nita Lakhani, Leonard Kaizer
Journal: Journal of Clinical Oncology (2016)

31 Background: In 2013 Cancer Care Ontario released updated antiemetic recommendations supporting the use of aprepitant-based combinations as 1 st line therapy for highly emetogenic and 2 nd line therapy for moderately emetogenic chemotherapy and discouraging the prolonged use of 5-HT 3 antagonists. In 2014 changes were made in the Ontario drug formulary to align public funding to those recommendations. The impact of the changes in guidance and public funding on prescribing practices are now being analyzed. Methods: Using the Ontario Drug Benefit (ODB) database, data was extracted to analyze the prescribing practices of aprepitant, granisetron and ondansetron for chemotherapy-induced emesis between the pre-funding period (November 2013 to September 2014) and post-funding period (October 2014 to July 2015). Results: Prior to funding changes, an average of 197 prescriptions/month of aprepitant were billed to the ODB program totaling $22,422. After funding, an average of 1,165 prescriptions/month of aprepitant were billed totaling $132,145. This represented a 490% increase in utilization. The combined 5-HT 3 receptor antagonists prescriptions/month billed during the respective time periods were 5,592 ($405,604) and 5,536 ($402,628). This represented a 1% decrease in utilization. Conclusions: There was a significant increase in aprepitant utilization and total expenditure to the ODB program indicating strong uptake of the triple-drug recommendation for highly emetogenic regimens. However, there was minimal change in prescribing practices related to the 5-HT 3 receptor antagonists, indicating a reluctance to decrease utilization. Further work is necessary to discourage the prolonged use of 5-HT 3 receptor antagonists.
Baseline VEGF as a potential predictive biomarker of vandetanib clinical benefit in patients with advanced NSCLC
Authors: J. V. Heymach, E. O. Hanrahan, H. Mann, P. Langmuir, R. B. Natale, B. E. Johnson, R. S. Herbst, A. J. Ryan
Journal: Journal of Clinical Oncology (2008)

8009 Background: Vandetanib (V) is a once-daily oral agent that selectively inhibits VEGFR, EGFR and RET signaling. Three randomized Phase II studies of V in advanced NSCLC have demonstrated improved progression-free survival (PFS) with V: V300 mg vs gefitinib (6474IL0003) and V100 mg ± docetaxel (D) vs D (6474IL0006) in previously treated NSCLC; V300 mg ± paclitaxel (P) and carboplatin (C) vs PC (6474IL0007) in 1st-line NSCLC. However, in 6474IL0007, V300 mg monotherapy was inferior to PC in terms of PFS. An exploratory analysis of the potential relationship between baseline VEGF levels and PFS was investigated in patients (pts) from these 3 studies. Methods: Two baseline plasma samples were collected from 163/168 pts (6474IL0003) and 44/83 pts (6474IL0006). Two baseline serum samples were collected from 144/181 pts (6474IL0007). Mean baseline VEGF levels were determined for each pt by ELISA. High baseline VEGF values were above the immunoassay reference range for healthy subjects (>115 pg/mL in plasma, >707 pg/mL in serum) and low baseline VEGF values were within this reference range. Results: In 6474IL0003, pts with low baseline VEGF had a lower risk of disease progression when treated with V vs gefitinib (HR = 0.55, 95% confidence interval [0.35, 0.86]). Conversely, pts with high baseline VEGF had similar benefit from both agents (HR = 1.03 [0.60, 1.75]). In 6474IL006, pts with low baseline VEGF had a lower risk of disease progression when treated with V100 mg + D vs D (HR = 0.25 [0.09, 0.68]), whereas disease progression was similar in both treatment groups for pts with high baseline VEGF (HR = 0.95 [0.25, 3.61]). In 6474IL0007, pts with low baseline VEGF had a lower risk of disease progression when treated with V300 mg vs PC (HR = 0.72 [0.38, 1.38]) whereas those with a high baseline VEGF progressed more quickly when treated with V300 mg vs PC (HR = 1.62 [0.88, 2.98]). There was no evidence that pts with low or high baseline VEGF had differential benefits when treated with V300 mg + PC vs PC (HR = 0.77 [0.42, 1.40] {low}; HR = 0.66 [0.31, 1.43] {high}). Conclusions: These exploratory analyses suggest low baseline levels of circulating VEGF may be predictive of PFS advantage in pts with NSCLC receiving V300 mg monotherapy vs gefitinib or PC, or V100 mg in combination with D vs D alone. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca Oncology AstraZeneca Oncology AstraZeneca Oncology AstraZeneca Oncology
Concurrent chemoradiotherapy with protracted infusion of 5-fluorouracil (5 FU) and cisplatin for locally advanced resectable esophageal cancer: A retrospective study.
Authors: Khaldoun Almhanna, Sarah Hoffe, Ravi Shridhar, Jonathan R. Strosberg, William R. Dinwoodie, Kenneth Meredith
Journal: Journal of Clinical Oncology (2013)

119 Background: Neoadjuvant CCRT has become the standard treatment for esophageal cancer. Most clinicians use a conventional cisplatin/5 FU combination which is associated with moderate to severe toxicity. For the last 15 years we have used contiuous low-dose 5-FU combined with two doses of cisplatin. Methods: Between July 1997 and June 2012, 155 patients with locally advanced esophageal cancer (T3 or N1 and higher), received CCRT consistent of cisplatin 75 mg/m2 on day 1 and day 29 and continuous infusion of 5-FU (225 mg/m2/day) on the days of radiation. Results: Median age of patients was 63 year (30-76).Seventeen percent of pts were female and 85% had adenocarcinoma. (3, 34, 86 and 31 pts had stage I, II, III and IVa disease respectively. One hundred and twenty seven pts had N1 disease. Radiation dose (RT) ranged from 45-60 Gy (median 56Gy). Median weight loss was 6.5%. All patients completed treatment. 20% of patients had &gt;=grade 3 toxicity, with 29 patients requiring hospital admission. 53% of patients had surgical resection between 37-149 days following CCRT (median 62 days). R0 resection was achieved in 96% of patients. A pathological complete response was achieved in 38 of 83 pts (45%) who underwent surgical resection. With a median follow up of 26 months (1.2 -144 months), 36% of pts recurred and total of 50% died. Conclusions: Compared to conventional chemotherapy regimen, our CCRT regimen for locally advanced esophageal cancer is well tolerated and associated with a high pathological response rate.
Impact of chemotherapy (CT) related anemia on functional/cognitive capacity in elderly non-small cell lung cancer (NSCLC) patients
Authors: A. Mancuso, P. Beccaglia, M. R. Migliorino, S. de Santis, A. Saponiero, F. de Marinis
Journal: Journal of Clinical Oncology (2005)

8176 Background: In elderly cancer patients (≥ 65 years) no trial defines exactly the impact of CT on functional status and cognitive functions of these patients. AIM: Considering that anemia is a common finding in this setting of cancer patients and its prevalence increases after 65 years, we performed this study to find whether any association exists between haemoglobin level (Hb) and Comprehensive Geriatric Assessment (CGA) variables. (Mini Mental State Examination [MMSE], Activities of Daily Living [ADL]/Instrumental Activity Daily Living [IADL], Geriatric Depression Scale [GDS], Cumulative Illness Rating Scale [CIRS]). Patients and Methods: We enrolled 42 consecutive NSCLC elderly patients (male/female = 31/11, median age = 77, PS 0/1/2/3 = 14/20/7/1, stage III/IV disease = 20/22) undergoing CT (platinum based CT: 55% of cases). After the baseline evaluation (V0), all patients were interviewed after each cycle of CT (Vx) receiving multidisciplinary CGA at least till cycle 2. Hb was checked weekly and its association with these indexes was expressed using Spearman’s non-parametric coefficient r. Results: Mental and functional capacity, depression and comorbidities were found to be associated to Hb value; Spearman’s r calculated over all visits (V0-V5) was: MMSE and Hb +0.52 (p < 0.0001), ADL and Hb: +0.55 (p < 0.0001), IADL and Hb: +0.27 (p < 0.0003), GDS and Hb: -0.50 (p < 0.0001), CIRS and Hb: -0.33 (p < 0.0001). For all visits since V1, ADL, MMSE and CIRS changes from V0 were related with concomitant Hb changes, Spearman’s r being +0.54 (p < 0.0001) for ADL, +0.47 (p < 0.0001) for MMSE, and -0.45 (p< 0.0001) for CIRS. In 14 patients given erythropoietin in the interval V0-V2, mean Hb increased from 9.2 to 10.8 g/dL, and ADL (+0.57), MMSE (+3.4), CIRS (-1.7) mean values were improved. On the contrary, in 18 patients not given erythropoietin Hb varied from 13.0 to 11.2 g/dL and a parallel worsening in ADL (-0.94), MMSE (-3.3) and CIRS (+6,2) has been observed. Conclusion: Chemotherapy related anemia is associated with reduction of ADL, MMSE and increase of CIRS. In elderly cancer patients anemia correction or maintenance could be useful to preserve or improve functional independency and mental decay. No significant financial relationships to disclose.
Preoperative triage and multidisciplinary consultation for patients with breast cancer: A pilot study between surgery and medical oncology.
Authors: Rachel Adilman, Christine E. Simmons, Maryam Eslami, Caroline Illmann, Rebecca Warburton, Elaine McKevitt
Journal: Journal of Clinical Oncology (2016)

208 Background: Breast cancer management has become exceedingly collaborative across specialties. Preoperative multidisciplinary input in particular is increasingly needed as indications for neoadjuvant therapy (NAT) continue to expand. In British Columbia, as in many other regions, breast cancer surgery is typically performed by community surgeons working in settings away from medical and radiation oncologists, making preoperative multidisciplinary input challenging. Methods: This prospective pilot study was designed to enhance and streamline preoperative breast cancer care at the BC Cancer Agency Vancouver Centre (BCCA) and Mount Saint Joseph’s Hospital (MSJ). Patients with a new diagnosis of breast cancer at the MSJ Breast Clinic are included in this pilot triage project if tumors meet one or more of the following criteria: triple negative, HER2+, clinically palpable ≥ 2cm, or present with positive/palpable nodes. Before the patient has consulted with a surgeon, the pathology, imaging, and GP’s assessment is faxed by a MSJ nurse navigator to BCCA for preoperative triage by a medical oncologist. A BCCA navigator facilitates this confidential electronic triage process, and communicates the medical oncologist’s recommendation [a) urgent referral for NAT, or b) upfront surgery] back to MSJ for appropriate booking and management. Results: Since inception in November 2014, 42 patients have undergone electronic preoperative triage through this pilot project. Of those, 47.6% were recommended to have, and did have, a preoperative medical oncology consult to discuss NAT. 90% of patients who had a NAT consult ultimately received NAT compared to a 66% uptake of NAT through the traditional referral process (P = 0.029). Median wait time from ‘biopsy result’ to ‘start of chemotherapy’ was significantly reduced by 9 days through this novel triage process (P = 0.047). Conclusions: This preoperative multidisciplinary triage project has significantly reduced treatment wait times and improved patient selection for and uptake of NAT for breast cancer. Breast cancer care benefits from increased preoperative navigation to help streamline and expedite care for high-risk patients.
Twenty years treating early-stage epithelial ovarian carcinoma patients with adjuvant platinum-based chemotherapy. A single institution’s experience
Authors: J. A. García-Saénz, A. Casado, J. Puente, S. López-Tarruella, J. C. Camara, P. Coronado, J. A. Vidart, I. de la Gandara, M. Martín, E. Díaz-Rubio
Journal: Journal of Clinical Oncology (2005)

5167 Background: One-third of epithelial ovarian cancer (EOC) patients (pts) present with localized disease and have a 50–70% ten-year survival. Prognostic factors and adjuvant strategies have been explored. Platinum-based chemotherapy (QT) is the mainstay of therapy. Aims: To describe Disease-Free Survival (DFS) and Overall Survival (OS) in EOC stage I-II pts receiving adjuvant platinum-based QT at our institution in the last 20 years. To determine prognostic factors and the role of paclitaxel addition. Methods: Retrospective analysis including all incident early-stage EOC pts receiving adjuvant platinum-based QT from 1984 to 2003. Well differentiated FIGO stages I were excluded. Demographic-data, surgical procedures, histological features, toxicities, follow-up and outcome were recorded. Up to 1997 pts received QT: CDDP 80mg/m2-CTX 750mg/m2, CBDCA 300mg/m2-CTX 600mg/m2, CDDP 80mg/m2-ADM 50mg/m2-CTX 500 mg/m2, every 3–4 w x 6. From 1997: Paclitaxel 175 mg/m2 and CBDCA AUC5 every 3 w x 4–6. Results: 140 pts (40 with paclitaxel) were compiled. Median age: 53.7 years (19–81). Completed surgically staged patients: 67.1%. Medium follow-up: 82.5 months; DFS 75.7%, OS 79.3%. No survival difference was found between pts receiving or not paclitaxel. Statistically significant prognostic factors were: ECOG 0 (p<0,003; OR 0,29; 95% CI 0,13–0,67); FIGO I stage (p<0.0001; OR 0.11; 95% CI 0,04–0,32); I-II grade (p<0,003; OR 0,3; 95% CI 0,14–0,68); non-mucinous excluding clear cell histology (p<0,01; OR 0,27; 95% CI 0,09–0,79). Pts who underwent most comprehensive surgery were likely to have a better prognosis (liver inspection (p<0,048; OR 0,45; 95% CI 0,21–1,0); paracolic-gutters inspection (p<0,023; OR 0,40; 95% CI 0,18–0,89)). The multivariate analysis will be reported at the meeting. Conclusions: Our data represent an actual approach to the impact of platinum-adjuvant QT in early-stage EOC, and might serve for reference to future trials. Paclitaxel’s impact on the outcome cannot be addressed due to the number of patients. Effective therapies are required for stage II, undifferentiated and mucinous tumours. Quality of surgery carries prognostic value. No significant financial relationships to disclose.
Survival effects of erythropoiesis-stimulating agents (ESAs) in patients with breast cancer: A meta-analysis.
Authors: Brian Leyland-Jones, Matti S. Aapro, Volker Moebus, Ulrike Nitz, Joyce O'Shaughnessy, Paolo Pronzato, Michael Untch, Dianne Tomita, Gerry C. Bohac
Journal: Journal of Clinical Oncology (2013)

e20616 Background: New data are available from two trials of ESA use in patients with breast cancer receiving chemotherapy. We conducted a meta-analysis of trials of ESA use in this population. Methods: A literature search identified reports from 1997-2012 that included mortality data from controlled ESA trials (epoetin alfa, epoetin beta, darbepoetin alfa, biosimilars) in patients with breast cancer receiving chemotherapy. We used data from company databases for Amgen Inc. or Janssen Products LP studies and published data for other studies. Random-effects odds ratios (OR) were calculated to compare results for patients randomized to ESA to patients randomized to control. Analyses were stratified by metastatic stage; mixed stage or treatment; and adjuvant/neoadjuvant treatment. Results: We analyzed 9 studies (N = 4713; ESA n = 2346, control n = 2367) (Table).The overall stratified random-effects OR for death was 1.17 (95% confidence interval, 0.99-1.39). Details are presented in the Table. Conclusions: Overall survival OR remains consistent with prior data after including recent results. [Table: see text]
Effect of first-line molecular targeted agents on the efficacy of second-line bevacizumab-containing regimen for metastatic colorectal cancer.
Authors: Hiroko Hasegawa, Hiroya Taniguchi, Seiichiro Mitani, Azusa Komori, Toshiki Masuishi, Yukiya Narita, Shigenori Kadowaki, Takashi Ura, Masashi Andoh, Kei Muro
Journal: Journal of Clinical Oncology (2016)

748 Background: Bevacizumab (BV)-containing regimen is a standard second-line chemotherapy(CTX) for patients (pts) with metastatic colorectal cancer (mCRC) regardless of the prior use of BV in the first-line CTX. However, little is known about the efficacy of the second-line BV-containing regimen after first-line CTX with anti-EGFR agents. Methods: We retrospectively evaluated the efficacy of a BV-containing regimen as the second-line CTX for mCRC. The eligibility criteria for the pts included in the study were as follows: ECOG PS 0–2, KRAS wild-type tumors, and refractory to first-line CTX with fluoropyrimidine and oxaliplatin or irinotecan from March 2007 to March 2015. The Kaplan–Meier method with a log-rank test and Cox regression analysis were performed to evaluate the progression-free survival (PFS) of the pts. Results: A total of 123 pts were eligible. The pts’ characteristics were as follows: males/females 73/50, median age 59 years, PS 0-1/2 118/5, LDH levels &lt; 400IU/l / ≥ 400IU/l 91/32, second-line CTX regimen FOLFIRI+BV/FOLFOX+BV 111/12. The patients were categorized into the following 3 cohorts according to the prior use of molecular targeted agents: anti EGFR agents (cohort E, 35 pts), BV (cohort B, 58 pts), no molecular targeted agents (cohort C, 30 pts). There was hardly any difference in the baseline characteristics of the 3 cohorts; however, LDH levels in cohort E were higher than those in the other cohorts. Treatment efficacies were as follows (cohort E/B/C): response rate, 30%/10%/20%, with a significant difference between cohort E and B (OR = 1.50, p = 0.035) and median PFS, 8.6/5.9/6.9 months, with a significant difference between cohort E and B (p = 0.025). Multivariate analyses for PFS were adjusted for baseline characteristics such as histology, PS, chemotherapy regimen, presence of peritoneal metastasis, LDH levels, and duration of PFS in the first-line CTX. The PFS of cohort E was better than that of cohort B (HR = 2.180, p = 0.0025) and was not much different from that of cohort C (HR = 1.682, p = 0.64)in multivariate analyses. Conclusions: The second-line BV-containing regimen is effective regardless of the prior use of anti-EGFR agents.
Genome Wide DNA Methylation Analysis Identifies a Characteristic Methylation Profile for Patients with Acute Promyelocytic Leukemia and FLT3-Internal Tandem Duplication
Authors: Mark Reinwald, Anjulie Haag, Eva Lengfelder, Maximilian Mossner, Benjamin Hanfstein, Verena Nowak, Marion Klaumuenzer, Florian Nolte, Julia Oblaender, Stephanie Fey, Thomas Büchner, Karsten Spiekermann, Wolf-Karsten Hofmann, Daniel Nowak
Journal: Blood (2012)