tbuckley/cabot-search huggingface dataset:
Epidermal growth factor receptor (EGFR) status in different stages of resected non-small cell lung cancer (NSCLC): Implications for treatment with EGFR-targeted monoclonal antibodies
Authors: R. Berardi, M. Scartozzi, M. Squadroni, A. Santinelli, A. Brunelli, S. Gasparini, G. Valeri, C. Marmorale, A. Fianchini, S. Cascinu
Journal: Journal of Clinical Oncology (2006)

20015 Background: Aim of our study was to verify potential changes in EGFR status in different stages of resected NSCLC. This was done in order to find out whether assessing the EGFR status could be considered an effective tool for planning therapy with EGFR-targeted monoclonal antibodies in different setting of patients. Methods: From January 1996 through December 2001, 439 patients underwent radical surgery for NSCLC at the Department of Thoracic Surgery of Università Politecnica delle Marche. EGFR expression was evaluated with an immunohistochemical technique on five micron-thick tissue sections obtained from specimens fixed in 10% (v/v) neutral buffered formalin and paraffin embedded.EGFR expression was detected as membranous and/or cytoplasmic brown staining of neoplastic cells with various intensity. Positivity for EGFR expression was defined as any membrane staining above background level. Both the primary and metastatic neoplasm were considered positive when ≥ 1% of the tumour cells had membranous staining. Results: Table 1 summarizes patients’ characteristics. Samples from 423 patients were available for EGFR analysis. EGFR immunohistochemical expression was found positive as follows: 15.8% in stage IIIB, 12.2% in IIIA, 2.3% in IIB, 5.3% in IIA, 4.8% in IB and 5% in IA. At multivariate analysis, EGFR status resulted indicator of prognosis both when considering all the patients and in the groups of patients with different stages of disease. Conclusions: Globally our findings seem to confirm the role of EGFR as a prognostic indicator in NSCLC. Furthermore the observation that EGFR is more frequently overexpressed in the advanced stages may suggest that EGFR-targeted treatment strategies could be more appropriated in this subgroup of patients. [Table: see text] No significant financial relationships to disclose.
High activity of the anti-IGF-IR antibody CP-751,871 in combination with paclitaxel and carboplatin in squamous NSCLC
Authors: D. D. Karp, L. G. Paz-Ares, S. Novello, P. Haluska, L. Garland, F. Cardenal, L. J. Blakely, P. D. Eisenberg, A. Gualberto, C. J. Langer
Journal: Journal of Clinical Oncology (2008)

8015 Background: CP-751,871 is a fully human, IgG2 monoclonal antibody against the Insulin-like Growth Factor type I Receptor (IGF-IR). We reported (ASCO 2007) a preliminary 46% Objective Response Rate (ORR) for the combination of CP-751,871 (I) with Paclitaxel (T) and Carboplatin (C) in 73 patients (pts) with advanced treatment-naïve NSCLC and performance status 0–1 enrolled in a multi-center phase 2 non-comparative study of TCI and TC with a primary endpoint of ORR by RECIST. The statistical hypotheses were 28% (null) versus 40% (response of interest). Methods: An additional 108 pts have been enrolled. Pts were randomized (2:1) to T (200 mg/m2), C (AUC of 6) and I (10 or 20 mg/kg), or TC alone every 3 weeks for up to 6 cycles; pts receiving TCI with response (PR) or stable disease were eligible to continue I as single agent until disease progression following discontinuation of chemotherapy. Pts progressing on TC alone were eligible to receive I as single agent or in combination with TC at the judgment of the investigator. Results: Safety and efficacy information are available for 178 and 143 pts, respectively (70% male, 45% ≥ 65 years old, 82% stage IV, 49% adenocarcinoma, 20% squamous cell carcinoma). Median number of treatment cycles was 4, with 24.6% of pts receiving single agent I beyond cycle 6. TCI was well tolerated. All causality grade 3,4 toxicity included (TCI, TC): hyperglycemia (11%, 4%), fatigue (9%, 7%), and neutropenia (14%, 14%). Forty-three of 85 pts receiving TCI (51%, p<0.001) and 21 of 58 pts (36%) on TC alone had objective responses. Of note, 13 of 18 TCI pts (72%, p<0.001) with squamous cell carcinoma responded to treatment, including 6 striking responses in pts with bulky disease, 2 pts with no further evidence of disease and a reversal of a superior vena cava obstruction. Five of 12 squamous pts (42%) responded to TC alone. Clinical benefit (PR/SD) was also observed in 3 squamous TC pts receiving I upon progression on TC alone. At present, only 38% of pts on study have progressed. Hazard ratio for progression free survival is 1.18 in favor of TCI. Conclusions: CP-751,871 appears safe and effective in combination with TC. The primary efficacy endpoint (ORR) has been met. Activity observed in squamous cell carcinoma deserves further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology Pfizer Oncology Pfizer Oncology Pfizer Oncology
RARE-13HYPERACUTE ADVERSE EVENTS OF HIGH-DOSE METHOTREXATE MONOTHERAPY IN PRIMARY CNS LYMPHOMA PATIENTS
Authors: Jae-Sung Park, Jae-Hyun Park, Sin-Soo Jeun, Yong-Kil Hong
Journal: Neuro-Oncology (2015)

OBJECTIVES: High-dose methotrexate chemotherapy (HD-MTX) is the mainstay in treatment of primary CNS lymphoma (PCNSL) and has been known to have acute or late toxicity on skin, gastrointestinal mucosa, liver, kidneys, and bone marrow. However, hyperacute adverse events (HADE), which occurred within one hour of HD-MTX administration, are rarely known in PCNSL patients. We report our HADE experiences with 9 consecutive cases. METHODS: Of 51 PCNSL patients, 38 immunocompetent adult PCNSL patients treated with HD-MTX at Seoul St. Mary's Hospital, The Catholic University of Korea between 2004 and 2015 were investigated. Our HD-MTX monotherapy regimen consists of induction period (8 g/m2 on day 1, 10, and 20 for 3 cycles) and maintenance period (3.5 g/m2, every 4 weeks for 3 cycles and then every 3 months for 3 cycles). Medical records were reviewed for each of the HADE events, retrospectively. RESULTS: Of 38 patients who received HD-MTX of 247 cumulative cycles, 9 patients (23.7%; 4 men and 5 women) presented 13 HADE. Median age of the patients was 58 years (range 47 to 64 years) at the time of the event. HADE developed during the maintenance period in 5 patients, at the early induction period in 1 patient and at the rechallenging period for recurrence in 3 patients. HADE symptoms were variable; most commonly skin rashes in 12 events (92.3%), abdominal pain in 2 events (15.4%), and most severely hypotension in 1 event (7.7%). HD-MTX monotherapy was discontinued in 4 patients, continued with corticosteroid premedication and symptomatic application of antihistamine with or without MTX dose modification in 5 patients, and completed in 2 patients. CONCLUSION: Although HD-MTX appears to be a relatively safe medication, greater awareness of possible HADE in HD-MTX chemotherapy is needed for its prevention, early diagnosis and management. Studies to clarify its mechanism should be warranted.
Combined high-dose carboplatin and cisplatin, and ifosfamide in previously untreated ovarian cancer patients with residual disease.
Authors: B Lund, M Hansen, O P Hansen, H H Hansen
Journal: Journal of Clinical Oncology (1990)

Carboplatin 200 mg/m2 day 1, cisplatin 50 mg/m2 days 2 and 3, ifosfamide 1,500 mg/m2 days 1 to 3, and mesna 900 mg/m2 days 1 to 3 every 4 weeks for six cycles were given to 37 previously untreated ovarian cancer patients with residual disease after the primary laparotomy. The median observation time was 17+ months (range, 9+ to 24+ months). Of all the patients, 81% had primary residual disease larger than 2 cm. The overall pathologic response rate (pathologic complete response [PCR] plus partial response [PPR]) in 36 assessable patients was 58%, PCR was 42%. Of the PCR patients, 53% had primary residual tumor larger than 5 cm. The substantial hematologic toxicity was manageable, but also the main reason for dose modifications. During treatment, 92% and 100% of the patients developed WBC and platelet nadir values corresponding to World Health Organization (WHO) grades 3 to 4. Dose-limiting encephalopathy, nephro- and neurotoxicity each occurred in 6% of the patients. The high PCR rate warrants further investigations of combined high-dose platinum and ifosfamide.
Assessment of quality of life using FACT-G survey in a phase I trial in cancer patients
Authors: G. Jung, D. Knight, A. Moadel, K. Desai, I. Chaudhary, S. Gajavelli, M. H. Ghalib, S. Mani, S. Goel
Journal: Journal of Clinical Oncology (2009)

e20709 Background: Quality of life (QoL) assessment in clinical trials has been gaining more attention. FACT-G surveys have been validated to assess QoL in clinical trials involving oncology patient (Cella DF et al, J Clin Oncol 11:570–579, 1993). However, there is paucity of evaluation of QoL in patients with advanced cancer participating in Phase I clinical trials. Methods: FACT-G surveys were conducted within the context of a Phase I trial to identify a safe dose and potential drug-drug interations of capecitabine and irinotecan combination (Goel, S et al, Invest New Drugs 25:237–245, 2007). The FACT-G survey consists of 28 questions in 5 sections, namely, physical well-being, social/family well-being, emotional well-being, relationship with doctor, and functional well-being). Patients were requested to complete the FACT-G surveys at baseline and every two cycles thereafter (each cycle of 3 weeks duration). Results: Forty-one of 47 patients with advanced solid tumors who participated in the clinical trial completed FACT-G surveys. Mean scores were calculated for each time point. The mean QoL scores at baseline and post cycle 2 were 53 and 58, respectively (p = 0.1). Post cycle 4, the mean QoL score was 62 [p = 0.01, (vs. baseline)]. Following cycle 4, the number of respondents decreased to the extent where we were unable to ascertain any further changes in the QoL scores. Conclusions: It is feasible to use FACT-G survey as a tool to assess QoL in patients participating in an oncology phase I clinical trial. Although the sample size of the patient population was not powered for any statistical significance, there was a trend toward improving QoL based on FACT-G survey scores. This suggests that phase I clinical trials may provide improvement of QoL for some patients. FACT-G is a useful tool in assessing QoL in oncology phase I trial study population. No significant financial relationships to disclose.
Correlation of quality of life with nutritional status and autonomy in elderly cancer patients according to standard geriatric evaluation.
Authors: C. Blanc-Bisson, M. Fonck, S. Mathoulin-Pelissier, C. Mertens, V. Brouste, M. Rainfray, P. Soubeyran
Journal: Journal of Clinical Oncology (2010)

e19532 Background: Number of elderly people is growing and with them the possibility to develop cancer. Specific cares and particularly chemotherapy must allow to maintain their quality of life. Methods: From 2003 to 2006, cohort of 364 patients older than 70 years with cancer was evaluated by oncologist and geriatrician before chemotherapy in public and private hospitals in south-west of France. Quality of life of patients was appreciated by QLQ-C30 completion. Standard geriatric evaluation occurred and oncologic endpoints were collected . Global quality of life, functions and symptoms items were calculated according to Aaronson (JNCI 1993) using EORTC SAS Program provided. Results: Median age was 77.5 years [range 70-99.4] and sex ratio was 214/150 (M/F). Most of patients had metastatic status 65.6% (n = 231) among several cancer location. Creatinine clearance was <50ml/min in 42% (n = 153) and 29.9% presented one comorbidity grade 3-4 and 8.3% at least 2 comorbidities. Global quality of life was not related to age, cancer location and metastatic status. Global quality of life was associated with sex (p = 0.014), toxicities during treatment (0.014), weight loss (p<10-3), performance status (p<10-3) and death within 6 months of treatment beginning. Except for comorbidities, all elements from geriatric standard evaluation were linked significantly to global quality of life. All functions (physical, role, cognitive, emotional and social) were stronghtly associated with weight loss (<5%, 5 to 10%, >10%) (p<10-3) and MNA (≤23.5 vs >23.5) (p<10-3) as well as performance status (0-1 vs. >1) (p<10-3) and IADL (≤7 vs. >7) omitting emotion (p = 10-3). Most of symptoms were related to weight loss and MNA (excepted financial impact and dyspnea) (p = 10-3) and in majority (fatigue, pain, appetite loss) they were linked to poor performance status (p<10-3) and low IADL score (p = 10-3). Conclusions: Poor Global quality of life was correlated to poor scores of standard geriatric evaluation and early death. Altered functions and presence of symptoms were related to malnutrition status (weight loss, poor MNA) and loss of autonomy (poor performance status and low IADL). No significant financial relationships to disclose.
Out-of-pocket (OOP) spending burden for Medicare beneficiaries with cancer.
Authors: X. Ke, F. Hendrick, T. Shaffer, A. J. Davidoff
Journal: Journal of Clinical Oncology (2010)

9124 Background: The financial burden associated with out-of-pocket medical costs can be devastating for Medicare beneficiaries with cancer. Costs for cancer-related treatment are substantial, yet Medicare and supplemental coverage may not provide adequate financial protection. This may be particularly true for traditionally vulnerable groups, defined by race, income, and health status. Methods: We used data from the 2006 Medicare Current Beneficiary Survey (MCBS), a nationally representative survey of the Medicare population that reports beneficiary demographics, health status, and supplemental insurance coverage. Medical spending is based on self-report augmented by Medicare Parts A and B claims. We selected fee-for-service enrollees who reported that they ever had a cancer diagnosis (N=2,007). Bivariate analyses compared spending by patient characteristic. Results: 7.5 million or 17% of the Medicare population reported a cancer diagnosis, with 3% reporting incident cancer. 89% were age >=65, 8% black, 5% Hispanic, 45% low income, 33% in fair/poor health, 90% with supplemental medical coverage, 89% with prescription coverage; 50% were enrolled in Medicare Part D plans. Mean total spending was $16,854 (95% CI: $15,539-$18,169), and OOP was $2,753 (95% CI: $2,408-$3,098) for prevalent cases; total spending was $26,345 (95% CI: $22,439-$30,251) and OOP $4,062 (95% CI: $3,015-$5,109) for incident cases. At the median, OOP spending (including premiums) was 14% of income. Median OOP spending on prescription drugs was 42% of total OOP. Mean OOP spending was lower for black patients vs white, excellent vs fair/poor health, Medicaid vs no supplemental coverage (all at p<.01). Conclusions: Given the prevalence of major chronic illness in the Medicare population, our prevalent cancer cohort experienced a large, but not disproportionate financial burden. However patients with new cancer diagnoses, and those disadvantaged by socioeconomic and poor health status were particularly vulnerable. Additional research is needed to examine how financial resources and supplemental medical and prescription drug insurance affect cancer treatments, and access to preventive and primary care in this cohort. No significant financial relationships to disclose.
Primary Prostatic Extragastrointestinal Stromal Tumor on 18F-FDG PET/CT
Authors: Yachao Liu, Baixuan Xu
Journal: Clinical Nuclear Medicine (2015)

Extragastrointestinal stromal tumors are relatively rare soft tissue neoplasms originating from the extragastrointestinal tract. The present study reports an extremely rare case of primary gastrointestinal stromal tumor arising from the prostate. The final diagnosis was based on 18F-FDG PET/CT, enteroscopy, pathologic results, and immunohistochemical findings.
Detection of chromosomal anomalies in uterine endometrial carcinoma using fluorescence in situ hybridization (<i>UteroFISH</i>)
Authors: J. Qian, D. Weber, R. Cochran, D. Hossain, D. G. Bostwick
Journal: Journal of Clinical Oncology (2009)

5533 Background: Endometrial cancer is the most common pelvic gynecological malignancy. The diagnosis of well-differentiated endometrial adenocarcinoma, atypical hyperplasia, and marked hyperplasia is often challenging. We sought to investigate the utility of chromosomal anomalies for the detection of uterine endometrial carcinoma using multitarget fluorescence in situ hybridization (FISH). Methods: Samples were collected by endometrial brush and processed by liquid-based thin-layer cytological preparation protocol. For study, we collected cytology slides from consecutive cases to include 50 benign, 50 hyperplasia without atypia, 50 atypical hyperplasia, and 50 endometrial cancers. Each was hybridized using fluorescence labeled DNA probes to chromosomes 1, 8, and 10 (UteroFISH). The FISH signals were enumerated in 100 cells per case, and the chromosomal anomalies were correlated with pathologic findings, including histologic diagnoses on endometrial tissue samples. Results: Numeric chromosomal anomalies were found in 0% (0/50) of benign, 20% (10/50) of hyperplasia, 76% of atypical hyperplasia (38/50), and 86% (43/50) of carcinoma specimens. The mean percentage of cells with chromosomal changes was 54% in cancer specimens, significantly higher than that in hyperplasia without atypia (13%, p&lt; 0.0001) and atypical hyperplasia (34%, p&lt; 0.0001). The most frequent chromosomal anomaly was gain of chromosome 1. FISH anomalies had an overall sensitivity of 81% and specificity of 90% for the detection of atypical hyperplasia and/or endometrial carcinoma. There was no association with grade of endometrial carcinoma. Conclusions: Multi-target UteroFISH appeared to be useful for the differential diagnosis of reactive hyperplasia, atypical hyperplasia, and endometrial adenocarcinoma, with a high level of sensitivity and specificity. Endometrial hyperplasia with FISH-detected chromosomal anomalies may require close clinical follow-up. No significant financial relationships to disclose.
Randomized Controlled Trial on the Skin Toxicity of Panitumumab in Third Line Treatment of Kras Wild-Type Metastatic Colorectal Cancer: Hgcsg1001 (Japanese Skin Toxicity Evaluation Protocol with Panitumumab: J-Stepp): Additional Analysis of Qol and Skin Toxicity
Authors: M. Nakamura, Y. Kobayashi, S. Yuki, H. Nakatsumi, H. Hayashi, I. Iwanaga, Y. Tsuji, K. Hatanaka, H. Okuda, J. Konno, F. Yamamoto, K. Iwai, M. Onodera, T. Takagi, H. Hisai, M. Koike, R. Abe, K. Oba, Y. Sakata, Y. Komatsu
Journal: Annals of Oncology (2014)
Is hepcidin involved in anemia of advanced non-small cell lung carcinoma (NSCLC) patients treated with platin-based chemotherapy? An exploratory study
Authors: J. De Castro, P. Cejas, C. Belda-Iniesta, N. Ramirez-Merino, J. Barriuso, E. Hernandez-Agudo, J. Feliu, V. Moreno-Garcia, V. Martinez-Marin, M. Gonzalez-Baron
Journal: Journal of Clinical Oncology (2009)

e19086 Background: Anemia is a common complication in NSCLC patients. Hepcidin, a liver-produced peptide, acts to cause a block on cellular iron export by internalisation and degradation of ferroportin.This results in iron sequestration and interrupts iron delivery to erythroid precursor cells thus causing anemia. To date there are no studies addressing whether hepcidin expression contributes to the anemia in NSCLC. Methods: to investigate whether hepcidin is implicated in NSCLC anemia, hemoglobin (Hb), iron metabolism and serum hepcidin levels, were studied in newly diagnosed advanced NSCLC patients. Blood samples of each patients were collected before starting cisplatin based chemotherapy treatment. Serum was separate by centrifugation at 2,500 g for 10 min at 4ºC. Hepcidin was detected by a solid phase enzyme-linked immunosorbent assay (ELISA) on the serum of each patient. The ELISA test is based on the principle of competitive binding. The microtiter wells are coated with a polyclonal antibody directed towards an antigenic site on the hepcidin prohormone molecule. Endogenous hepcidin prohormone of patient sample competes with a hepcidin prohormone biotin conjugate for binding to the coated antibody. Hepcidin absolute quantitation was achieved using a standard curve. Hepcidin results were correlated with serum parameters related to iron metabolism. Results: In a exploratory analysis, 20 patients with advanced NSCLC were selected for hepcidin prohormone detection. Only 10% were anemic at the diagnosis but 70% developped anemia during the treatment. 50% of the patients had iron deficiency. 70% received treatment for anemia (40% erythropoetin and iron, 20% iron, 10% erythropoetin). Median serum hepcidin levels was 151 ng/ml (range 99–308). The serum hepcidin level correlated with serum ferritin but no correlation was found with other iron metabolism parameters. An inverse correlation was seen between serum hepcidin level and Hb evolution after 4 cycles of chemotherapy. Conclusions: These results support a potential relationship between hepcidin expression and anemia in NSCLC patients. Further confirmatory study is ongoing and final results will be presented in the meeting. No significant financial relationships to disclose.
A randomized phase II trial investigating the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive early breast cancer (GeparSixto).
Authors: Gunter Von Minckwitz, Andreas Schneeweiss, Christoph Salat, Mahdi Rezai, Dirk Michael Zahm, Peter Klare, Jens U. Blohmer, Hans Tesch, Fariba Khandan, Sebastian Jud, Christian Jackisch, Keyur Mehta, Sibylle Loibl, Michael Untch
Journal: Journal of Clinical Oncology (2013)

1004 Background: Use of carboplatin in neoadjuvant chemotherapy (NACT) has never been prospectively examined in breast cancer. Cohort studies suggest a high sensitivity to DNA-damaging agents (e.g., carboplatin in triple negative breast cancer [TNBC]), which have a high prevalence of BRCA mutations. Two trials examining carboplatin in HER2+ metastatic disease have shown conflicting results, but one was biased by different dosage of docetaxel in treatment arms. GeparSixto investigates the impact of carboplatin in addition to an identical, optimized cytotoxic-targeted regimen on pathological complete response (pCR) in these two breast cancer subtypes. Methods: In GeparSixto trial (NCT01426880) patients were treated for 18 weeks with paclitaxel 80mg/m² q1w and non-pegylated-liposomal doxorubicin (NPLD) 20mg/m² q1w. HER2+ patients received concurrently trastuzumab 6(8) mg/kg q3w and lapatinib 750mg daily. TNBC patients received concurrently Bevacizumab 15mg/kg i.v. q2w. All patients were randomized 1:1 to receive concurrently carboplatin AUC 1.5-2 q1w vs not, stratified by subtype. Primary objective is pCR rates (ypT0 ypN0), secondary objectives are pCR rate in predefined subgroups or by other definitions, clinical response rate, compliance and tolerability of carboplatin. Carboplatin dose was reduced from AUC 2.0 to 1.5 by an amendment after 330 patients due to carboplatin-related toxicity at pre-planned safety analyses. Results: 595 patients were recruited (8/2011 - 12/2012) in 51 German centers, 299 did not receive carboplatin. Median age was 47/48 years (no carb/carb), 36.8/36.5% were postmenopausal; 14.0/13.3% had T3, 5.0/3.7% T4, 41.8/37.6% N+, 93.0/92.9% ductal invasive, 64.5/65.3% G3 tumors; 46.2/46.3% had HER2+, 53.8/53.7% TNBC. 225 patients had a SAE (149 no carb/177 carb) and 3 died (postoperative pneumonia; reduced general condition; acute myocardial infarct), all in no carb arms. Final analysis on primary endpoint will be presented. Conclusions: This is first study, evaluating efficacy and safety of the addition of carboplatin to anthracycline-taxane containing NACT in patients with primary HER2+ and TNBC. Clinical trial information: NCT 01426880.