tbuckley/cabot-search huggingface dataset:
Identification of candidate tumor related genes using comprehensive gene expression analysis of neuroblastic tumors
Authors: J. Mora, C. Lavarino, G. Domenech, J. Rios, W. Gerald, C. De Torres, N. Cheung
Journal: Journal of Clinical Oncology (2006)

9051 Background: Neuroblastic tumors (NBTs) represent a heterogeneous and relatively well defined spectrum of neoplastic diseases. We performed gene expression analysis to molecularly characterize the distinct clinicobiological subtypes of NBTs. Methods: Gene expression analysis of 106 NBTs (10 ganglioneuromas, 10 stage 4s, 29 loco-regional (stages 1, 2, 3), and 57 stage 4) and 12 neuroblastoma cell lines was performed using Affymetrix Genechip Human Genome U95 Set Arrays. Differential expression between predefined groups of biological and clinical relevance was determined by differences &gt;3 standard deviations between the means for groups, step-down permutation and false discovery rate methods. Results: Gene expression analysis of clinically defined groups including stage 4 infants versus children, metastatic versus non metastatic, and stroma poor loco-regional versus stage 4, revealed that many differentially expressed genes mapped to chromosomal regions with well described recurrent abnormalities in NBTs (chromosomes 1, 11, 17, 19 and X). Pairwise comparison analysis of biologically defined groups, including triploid versus diploid/tetraploid NBTs, identified significantly discriminating genes that map to the same chromosomal regions. Gene expression analysis of MYCN-amplified versus MYCN non amplified NBTs, confirmed a functional overrepresentation for genes involved in protein biosynthesis. Conclusions: Gene expression profile analysis of clinically and biologically relevant subgroups of NBTs revealed differential expression of genes at specific chromosomal regions known to have strong association between genetic alterations and NBT clinical features. The identification of altered expression helps to define critical chromosomal regions and identify tumor related candidate genes within each region. No significant financial relationships to disclose.
Radiation therapy for Ewing’s sarcoma
Authors: T. H. La, P. A. Meyers, L. H. Wexler, J. H. Healey, M. P. La Quaglia, P. J. Boland, S. L. Wolden
Journal: Journal of Clinical Oncology (2005)

8555 Purpose: To evaluate the outcome of patients with Ewing’s sarcoma family of tumors (ESFT) treated with modern radiotherapy techniques using MRI imaging along with optimal chemotherapy. Materials and Methods: The records of all 60 patients with ESFT who received radiation to the primary site at MSKCC between 1990 and 2004 were reviewed. All patients received chemotherapy including vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide with or without surgical resection. All patients had MRI and CT scan based treatment planning and 43% received intensity modulated radiation therapy (IMRT). Radiation doses ranged from 30–60 Gy, median 51 Gy. Hyperfractionation was used in 35% of patients. We analyzed outcome and the effect of potential prognostic factors. Follow-up of surviving patients is 6–178 (median 41) months. Results: Median age was 16 (2–40) years with a male:female ratio of 1.1:1. Because of selection bias for radiotherapy, the majority of tumors were in the axial skeleton: spine (18), pelvis (15), extremities (12), chest wall (5), head and neck (5), and other (5) with 78% arising in bone and 22% in soft tissue. Metastases were present at diagnosis in 38% of patients and 52% of primary tumors were ≥ 8 cm. Actuarial 3-year local control was 77%. Time to local failure ranged from 8 to 32 months. The presence of metastases at diagnosis was an adverse prognostic factor for local control, 84% vs. 62% (p=0.04). No other predictive factors for local failure were identified including patient age, tumor size and site, as well as radiation dose, timing, fractionation or whether it was definitive or postoperative. In patients without metastatic disease, 3-year disease-free and overall survival were 70% and 87%, respectively, while in patients with metastases, they were both 21%. Conclusion: In this unfavorable cohort of ESFT patients, radiation therapy was an effective modality for local control, especially for patients without metastases. The presence of metastases at diagnosis is a predictive factor not only for death but also for local failure. Future strategies for metastatic patients may include short course, high dose per fraction regimens. No significant financial relationships to disclose.
Cell cycle regulators p16INK4a in metaplasia, dysplasia, and adenocarcinoma of Barrett's esophagus.
Authors: P. Torres-Galea, P. E. Stoemmer
Journal: Journal of Clinical Oncology (2010)

e14656 Background: p16INK4a is a cyclin-dependent kinase inhibitor, together with p21, p53 and p63 playing an important role in the regulation of the cell cycle and histomorphology in embryology, regeneration and in tumours. The variety of neoplastic and non-neoplastic types of epithelia and their architecture in Barrett esophagus may be associated with structural and functional proteins such as cell-cycle regulators. Loss of heterozygosity in p16INK4a/CDKN2A occurs in 75% of Barrett-carcinomas and is a amrker of better prognosis. Methods: Twenty formalin-fixed, paraffine embeded biopsies of Barrett esophagus with epithelia of specialised (colonic) type, twenty cases with metaplastic gastric foveolar type/cardiac type and ten cases of Barrett-associated adenocarcinoma (diffuse, intestinal and exophytic papillary type) were analysed for the expression and distribution of p16INK4a (Antibodies: mtm Heidelberg).All cases histologically and endopscopically confirmed (Munic Type C patients). Results: Nonneoplastic Barrett: Strong,expression of p16INK4a in the stratum spinosum cells of regenerative hyperplastic squamous epithelium: mostly coherent cells in columnar or reticulated arrangement. No expression in the foveolar cells of esophageal gastric heterotopia. Crypts and intestinal- metaplastic cardia-glands show slight to moderate nuclear and cytoplasmic expreession. Dysplasia and neoplasia in Barrett: Low p16INK4a positivity in colon-type specialized epithelium of low grade dysplasia. Moderarte positivity in high grade dysplasia. Most cases indeterminate for dysplasia are negative. Two different patterns of p16INK4a expression in invasive adenocarcinomas of Barrett epithelia: well-differentiated papillary and tubuloglandular cancers highly positive for p16INK4a; carcinomas of macroglandular or diffuse pattern or signet-cell-type no or low expression. Conclusions: Inactivation of CDKN2A /p16 and is an early event in Barrett
Clinical prognostic factors in advanced non-small cell lung cancer (NSCLC): Cox regression analysis based on 789 patients treated in three consecutive randomized trials
Authors: L. R. Pilz, N. Thatcher, C. Kortsik, G. Koschel, J. Mezger, K. Schott von Römer, C. Manegold
Journal: Journal of Clinical Oncology (2007)

7648 Background: Treatment efficacy and toxicity of the three studies have been presented at ASCO (2006, Abstract # 7035). Patients (pts) received gemcitabine or docetaxel either as single agents in different schedules and doses or as a platinum free doublet. Our retrospective analysis is to identify the clinical factors which would influence patient prognosis. Methods: Patients eligibility criteria included histologically confirmed stage IIIB or IV, performance status (PS) 0–2, and no prior chemotherapy. Overall survival (OS) was similar in all three studies. 819 pts were enrolled in 1998–2004 and 798 pts of them were evaluable for this analysis: 85% of pts had stage IV disease and PS=1. Univariate and multivariate (stepwise) Cox regression analyses were performed to evaluate the impact of baseline characteristics and quality of life (QoL) on OS. Results: Factors which have a significant impact on OS are the laboratory parameters hemoglobin (HGB) and LDH (p&lt;0.0001), WHO performance status (PS) (p=0.001) and the quality of life measure for lung cancer of the EORTC, LC13, (p=0.0006), respectively (see table ). Gender measured univariately also influences significantly OS (p=0.0085) but has less impact in the multivariate model (p=0.07). Age (&lt;65 vs 65 and older) is not of prognostic value with OS (HR=0.92, p=0.39), as well as histology (adeno/sqamous/other) (HR=0.99, p=0.90). Other factors as tumor stage (wet IIIB vs IV), presence of extra-thoracic metastases, number of co-morbidities, and surgical and radiological pretreatment also have no prognostic influence on OS. Analysis for the effect of smoking on OS could not be performed since only few pts never smoked. Conclusions: Our retrospective analysis confirms the prognostic value of serum HGB, and LDH, WHO-PS, and QoL LC13 as clinical determinants for OS. [Table: see text] [Table: see text]
Role of radiotherapy in combined modality treatment of locally advanced non-small-cell lung cancer.
Authors: K Kubota, K Furuse, M Kawahara, N Kodama, M Yamamoto, M Ogawara, S Negoro, N Masuda, M Takada, K Matsui
Journal: Journal of Clinical Oncology (1994)

PURPOSE For patients with locally advanced (stage III) non-small-cell lung cancer (NSCLC), radiotherapy (RT) has been used conventionally for many years. Few prospective trials have determined the role of RT. Recently, chemotherapy (CT) has been shown to produce excellent responses in regionally advanced disease. We therefore conducted a randomized trial using cisplatin (P)-based CT regimens with or without thoracic irradiation. PATIENTS AND METHODS We randomly assigned 92 patients with locally advanced NSCLC to receive one of three arms of P-based combination chemotherapy: vindesine (V) plus P, mitomycin (M) plus V plus P, or etoposide (E) plus P alternating with V plus M. After two cycles of CT, patients were reevaluated and those with stage III were again randomized to receive RT or not. RT consisted of 50 to 60 Gy in 5 to 6 weeks; 2 Gy was delivered once daily in conventional fractions. RESULTS Sixty-three patients were included in the second randomization. The patients in the CT/RT group (n = 32) and CT-alone group (n = 31) were comparable in terms of age, sex, performance status, histologic features, stage of disease, and induction CT regimen. The median durations of survival were similar for the two groups (461 days in CT/RT group and 447 days in CT-alone group). The survival rate in the CT/RT group was 58% at 1 year, 36% at 2 years, and 29% at 3 years, as compared with 66%, 9%, and 3% at 1, 2, and 3 years, respectively, in the CT-alone group. One patient in the CT/RT group died of pneumonitis, but there were no CT-related deaths. CONCLUSION In locally advanced NSCLC, P-based combination CT followed by chest irradiation significantly increases the number of long-term survivors as compared with CT alone. RT to bulky disease in the thorax is thus an important part of combined modality therapy, and a necessary part of further studies in locally advanced disease.
Prognostic implications of tumor-associated factors in resectable pancreatic adenocarcinoma
Authors: M. Gasser, M. Grimm, A. Thiede, D. Meyer, A. Waaga-Gasser
Journal: Journal of Clinical Oncology (2008)

15559 Background: Reproducible prognostic markers could potentially allow patients with pancreatic cancer to be stratified into treatment groups. In this study, we asked whether EGF, EGFR, erb B2, TGF-α and -β, p53, and PCNA expression might be useful in detecting different aggressive pancreatic cancers and if survival would be worse in high marker expressors. Methods: In this retrospective study a total of 282 patients with histologically verified pancreatic ductal adenocarcinoma were treated at our Department from 1993 to 2003. In addition, 93 patients were selected based on the availability of tissue specimens from the primary tumor and R0-resection (75% head, 13% corpus, 12% caudal). We used Elisa, immunohistochemistry and real time PCR to investigate expression of the different tumor associated factors. The values of morphological and molecular parameters were correlated with clinicopathological characteristics for their predictive value of tumor recurrence using chi-square test, Kaplan-Meier method, multivariate analysis by Cox regression, and Mann-Whitney-U- Test (follow-up period: 32±6.2 months). Results: A total of 34% of the patients underwent R0-resection, which significantly influenced their survival (78% stage UICC IIb, p<0.0001). Mean survival and time to progress were also influenced by N-stage (mean survival N1: 21.5 Mo vs. N0: 49.1 Mo) and tumor differentiation (G1: 63.7 Mo; G2: 26.3 Mo; G3: 15.2 Mo; p=0.009). The prognosis of patients undergoing curative R0-resection seems to be determined by perineural invasion (p=0.019) with a mean survival of 12 months (no invasion: 29 months). With exception of MIC-A all of the analyzed parameters showed an increased protein expression during tumor progression. A prognostic significance was observed for increased CD4+ and CD8+ T cell infiltration, and poor EGF, erb B2, and PCNA expression in the tumor (p<0.001). Conclusions: Our data suggest that patients, even if R0-resected and with no lymph node metastasis, may benefit from analysis of the prognostic markers EGF, erb B2, PCNA, and MIC-A in their tumors. Those nodal negative patients with increased marker expression profiles would potentially profit from chemotherapy combined with small molecules targeting intracellular signal transduction pathways. No significant financial relationships to disclose.
DOCTOR: A randomized phase II trial of preoperative cisplatin, 5-fluorouracil, and docetaxel with or without radiotherapy based on poor early response to standard chemotherapy for resectable adenocarcinoma of the esophagus and/or OG junction.
Authors: Andrew Barbour, Bernard Mark Smithers, Bryan Burmeister, John Raymond Zalcberg, Nigel Spry, Garrett Smith, Kate Wilson, Kate Roff, Sonia Yip, Euan Thomas Walpole
Journal: Journal of Clinical Oncology (2012)

TPS4145 Background: Surgery forms the mainstay of curative treatment for oesophageal and gastro-oesophageal junction adenocarcinoma (OAC). Preoperative chemotherapy (CTX) with or without concurrent radiotherapy (CRT) have resulted in modest improvements in outcome. Patients who demonstrate a histological response in the resected specimen following pre-operative therapy (CTX or CRT) have consistently better survival than non-responders. Recent data suggests that early metabolic response, assessed by FDG-PET scan performed 14+/-1 days after the start of CTX compared with a baseline PET scan, is predictive of a histological response and improved survival. Increasing the proportion of responders to pre-operative therapy remains one of the major challenges facing patients with localised OAC. Methods: 150 patients with resectable adenocarcinona of the oesophagus or GOJ will be registered and given 1 cycle of cisplatin and 5FU (CF). Patients will undergo a series of baseline tests including endoscopy, endoscopic ultrasound and 18FDG-PET. At Day 15 of the initial CF cycle the PET will be repeated. Patients with a PET response (≥ 35% reduction in SUV max ) to initial treatment will continue with CF as standard treatment prior to surgery. PET non-responders (&lt; 35% reduction in SUV max ) will be randomized equally to receive either docetaxel, cisplatin and 5FU (DCF) or DCF plus radiatiotherapy. Following completion of the preoperative chemotherapy /chemoradiotherapy patients will have their cancer surgically removed. The primary end point is major histological response (&lt;10% residual viable tumour) and secondary endpoints of progression-free and overall survival, toxicity, quality of life and feasibility of response-based therapy. Eligibility: T2 or greater tumours (by EUS or CT), or T1 tumours that are poorly differentiated, or T1 node positive, histologically proven invasive adenocarcinoma of the oesophagus or GOJ, technically resectable tumour which is sufficiently FDG avid on the initial PET staging scan. Status: Opened to accural 2009.
Effect of lobectomy on survival in early-stage small cell lung cancer: A retrospective analysis
Authors: J. M. Varlotto, A. Recht, J. C. Flickinger, A. Dyer, L. Medford-Davis, M. DeCamp
Journal: Journal of Clinical Oncology (2009)

7585 Background: Small cell lung cancer (SCLC) rarely presents as I/II Disease. In order to assess the incidence, treatment and prognosis of this early-stage SCLC, we used the Surveillance, Epidemiology and End Results database. Furthermore, since some investigators are irradiating growing and/or PET Scan positive nodules without biopsy, presenting characteristics of surgically-resected Stage I SCLC were compared to those of non-small cell lung cancer (NSCLC). Methods: The SEER 17 Database from 1988–2003 was accessed for all patients with early-stage SCLC. Presenting characteristics of surgically-resected Stage I SCLC were compared to those of resected Stage I NSCLC using chi-square and Wilcoxon Rank Sum tests. The logrank test was used to compare the differences in Survival(S) resulting from the various treatments options for early-stage SCLC. Results: 1,615 patients were identified with early-stage SCLC with greater than 3 months of follow-up. The median S was 20 months for the entire group. Over the time period of our study, the incidence of early stage SCLC as a percentage of all SCLCs and all lung cancers (SCLCs and NSCLCs) remained stable and ranged from 3.00–4.96% and 0.09–0.16% respectively. Surgically-resected Stage I SCLC did not differ from NSCLC in regards to patient characteristics (age, sex, race) or tumor location, but SCLC was found to have significantly smaller tumor size (p&lt; 0.0001). Lobectomy or greater resections without radiotherapy were associated with a greater median S than those treated with segmental/wedge resections and those treated with radiotherapy alone (44 vs 29 months, p=0.03 and 20 months, p &lt;0.0001). Furthermore, when lobectomy or greater resection was performed, adjuvant radiotherapy was associated with a shorter, but not significantly different median S (32 vs 44 months, p = 0.17). Segmental/wedge resections without radiotherapy were associated with significantly better S than patients who received radiotherapy alone, but no difference in S was found with the use of adjuvant radiotherapy (29 vs 20 months, p =0.003, and 35 months, p=0.31). Conclusions: The incidence of stage I/II small cell lung cancer was stable over the years of our study. Anatomic lobectomy without adjuvant radiotherapy appears to be the optimal therapy for patients without mediastinal nodal metastases. No significant financial relationships to disclose.
A phase I trial of tipifarnib, a farnesyltransferase inhibitor, and tamoxifen in hormone-receptor positive metastatic breast cancer
Authors: P. F. Lebowitz, J. Eng-Wong, F. Balis, B. Widemann, N. Jayaprakash, S. Gantz, C. Chow, M. Merino, J. Zujewski
Journal: Journal of Clinical Oncology (2004)

644 Background: Farnesyltransferase inhibitors (FTIs) were initially developed to target oncogenic Ras and have clinical activity in a number of malignancies. Preclinically, FTIs have synergistic activity when used with tamoxifen in breast cancer cell lines. We conducted a phase I trial using tipifarnib with tamoxifen in patients with hormone-receptor positive breast cancer to determine acute and chronic toxicities and to identify a chronic dose for phase II testing. Methods: Patients with hormone-receptor positive metastatic breast cancer, performance status 0–1, and adequate organ function were entered in the study. Tipifarnib was administered at 2 dose levels (200 mg po BID and 300 mg po BID) for 21 out of 28 days. Tamoxifen (20 mg daily) was started after 1 week of tipifarnib alone thereby allowing comparison of pharmacokinetics and other correlative studies with tipifarnib alone versus tipifarnib and tamoxifen. Results: Pharmacokinetic analysis (n=9) demonstrated a median AUC of 3514 ng.hr/ml (range 1829–4803) with tipifarnib alone and 3093 ng.hr/ml (range 1417–3747) with tipifarnib and tamoxifen. Farnesyltransferase activity, measured at steady state in peripheral blood mononuclear cells (n=6), decreased by a median of 30% (range 14–57%) with tipifarnib alone, and by 41% (range 23–59%) with tipifarnib and tamoxifen. Grade 2 or 3 toxicities included diarrhea (1), nausea/vomiting (3), constipation (2), hot flashes (3), fatigue (1), and rash (1). Hematologic toxicities included grade 2 neutropenia (6), thrombocytopenia (1), and anemia (1). One patient had a pulmonary embolism. All patients treated at the 300 mg BID dose level had the tipifarnib dose decreased due to ≥ grade 2 toxicities. Although not a primary objective of the study, 4 of 11 (36%) evaluable patients had clinical benefit. Partial tumor responses were seen in 3 of 11 patients and one patient has stable disease at 8 months. Conclusions: The combined regimen of tipifarnib and tamoxifen is well-tolerated and exhibits promising initial clinical activity. A phase II trial is currently in progress using tipifarnib 200 mg BID and tamoxifen 20 mg QD. No significant financial relationships to disclose.
First line chemotherapy with FOLFOX 4 in elderly patients (&gt;65 years) with advanced or metastatic gastric cancer (A/MGC): A pilot study
Authors: D. Azzarello, C. Giuffrè, V. Panuccio, R. Giannicola, P. Del Medico, M. Zavettieri, M. Raffaele, R. Maisano, A. Falzea, M. Nardi
Journal: Journal of Clinical Oncology (2006)

14095 Background: Cisplatin/5-FU based regimens are considered therapies of choice for the treatment of A/MGC even if severe toxicities are reported especially in elderly pts. FOLFOX 4 regimen is standard chemotherapy in adjuvant and metastatic colorectal cancer and it is effective and well tolerated also in elderly population. Several trials have showed activity and safety of FOLFOX regimen in A/MGC. For these reasons, we carried out this pilot study in order to evaluate the feasibility of FOLFOX 4 in elderly pts (&gt;65 yrs) with A/MGC. Methods: From June 2003 to June 2005 we treated with FOLFOX 4 regimen 31 pts with median age of 70 yrs (range 66–79), 20 males and 11 females, ECOG PS 0–2 with MGC in 19 cases and AGC in 12 cases. All pts had measurable disease according to RECIST criteria, NCI-CTC was employed to grade toxicity except for neurotoxicity graded by specific scale. Results: We recorded 4 CR (13%), 6 PR (19%), 9 SD (29%) and 12 PD for an ORR 32% and median TTP of 6.8 months. A total of 281 courses were delivered with a median of 8 courses (range 4–15) per pt. No toxic deaths occurred and no therapy has been ended for toxicity or pt refusal. Pts did not receive G-CSF support. 43 courses were delayed for toxicity (maximum 2 weeks). Haematological adverse events were: 23 episodes of neutropenia G1/2, 8 episodes of G3 and 3 episodes of G4 neutropenia; G1/2 thrombocytopenia occurred in 15 episodes; anemia G1/2 was reported in 13 episodes. Besides, we recorded 12 episodes of emesis G2 and 2 episodes of G3; 24 episodes of G1/2 and 7 episodes of G3 oral mucositis were recorded; diarrhoea G1/2 was a common event (around 50% of cycles) while severe diarrhoea was a rare. Alopecia G1/2 was registered in 19 pts, G1neurosensorial toxicity (specific scale) occurred in 16 pts, G2 in 7 pts and G3 in one pt. One pt had hypersensitivity reaction at first infusion that did not occurred anyone by prolonged infusion of L-OHP. Conclusions: Our data show that FOLFOX 4 is active in the treatment of A/MGC and that toxicity profile is favourable in elderly population in comparison to standard regimens. No significant financial relationships to disclose.