tbuckley/cabot-search huggingface dataset:
Chemopredictive diagnostic project in patients (pts) receiving capecitabine (X) or 5-FU/leucovorin (LV) as first-line chemotherapy for metastatic colorectal cancer (MCRC)
Authors: J. A. Maroun, T. Moyana, C. Birnboim, K. Gloeckner-Hofmann, I. Gorn-Hondermann, D. Jonker, D. Vergidis, A. Wong
Journal: Journal of Clinical Oncology (2004)

9652 Background X (Xeloda®) is a tumor-activated oral fluoropyrimidine, with superior response rate and improved safety compared to bolus 5-FU/LV in 1st-line MCRC. Variation in tumor expression levels of thymidine phosphorylase (TP), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) may impact efficacy or toxicity of X-containing regimen. We are retrospectively evaluating the relationship of the expression of these enzymes to outcomes in a 1st-line MCRC phase III trial of X vs 5-FU/LV (Hoff, JCO 2001). 9 Canadian sites participated in the trial (N=164). Methods Pts were eligible if they received at least one dose of chemotherapy. We obtained informed consent through next-of-kin or Ethics Committee waiver. We obtained formalin-fixed, paraffin-embedded tissue from primary tumors +/- synchronous metastases. We analyzed TP, DPD and TS expression levels using immunohistochemistry (IHC) and quantitative reverse transcriptase - polymerase chain reaction (RT-PCR) kits, both from Roche Diagnostics. Overall IHC score was calculated using tumor and stromal staining intensity and pattern. IHC intensity and percentage of staining were scored blinded to pt treatment and clinical outcome.Results Tumor blocks from 37/164 pts have been analyzed to date, 34 primaries (see table), 4 metastases (not shown). Data on correlation of IHC and RT-PCR results to clinical outcomes will be presented at the meeting. Conclusions Retrospective sample collection was feasible in a large multicenter trial. Sophisticated molecular analysis of archival samples was performed with a success rate of 97%. Results of this biomarker analysis could generate a hypothesis to be tested in further prospective research with X, eventually allowing tailored therapy for the individual patient. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-La Roche Hoffmann-La Roche Hoffmann-La Roche
Molecular profiles of prostate cancer and its surrounding non-malignant tissue
Authors: V. Vuaroqueaux, M. Labuhn, R. Morant, P. A. Diener, C. Horica, T. Németh, M. Sulmoni, P. Urban, G. Fürstenberger, U. Eppenberger, S. Eppenberger-Castori
Journal: Journal of Clinical Oncology (2005)

9570 Background: In spite of complete resection of localized prostate cancer (CaP), some will recur and metastasize. New prognostic and predictive tools are needed to improve clinical management of adjuvant therapy. For this purpose we investigated 90 relevant genes in tumor and non-malignant adjacent tissue (NAT). Methods: Of 32 CaP patients, who underwent primary prostatectomy in 2003, fresh frozen samples of the tumor and respective NAT were asserved. The RNA extracted from cryocuts was tested on the Bioanalyzer 2100. The quantitative RNA expression levels were simultaneously determined on ABI 7000. Results: Unsupervised agglomerative clustering of the obtained molecular profiles clearly revealed different signatures in tumor versus NAT. Genes involved in proliferation as well as tumor markers such as PSA and prostate stem cell antigen were found at elevated levels in tumors, whereas high expression levels of other genes (e.g. cytokeratins, Glutathione S-transferase) were found in NAT. Interestingly, more expressed in NAT were certain markers of angiogenesis and cell matrix-remodeling. Conclusions: The molecular profile by quantitative RT-PCR is a powerful tool describing the biology of an individual tumor and its surrounding tissue, which in correlation with the Gleason score, pTNM staging and circulating PSA will help to predict clinical outcome and to identify at time patients who should receive hormone-deprivation. No significant financial relationships to disclose.
Outcome of patients (pts) with PDGFRA<sup>D842V</sup> mutant gastrointestinal stromal tumor (GIST) treated with imatinib (IM) for advanced disease.
Authors: P. Biron, P. A. Cassier, E. Fumagalli, A. Blesius, M. Debiec-Rychter, A. Adenis, J. Verweij, P. Hohenberger, J. Blay, P. G. Casali
Journal: Journal of Clinical Oncology (2010)

10051 Background: Approximately 85-90% of GIST are driven by oncogenic mutations of either KIT or PDGFRA. Mutations of exon 11 and 9 of KIT are the most frequents and tumors driven by KIT exon 11 mutations were shown to be the most sensitive to imatinib (IM). PDGFRA mutations are found in approximately 5-7% of advanced GIST, in most cases PDGFRA mutation are D842V substitutions. PDGFRAD842V mutant GISTs have been reported to be IM-resistant, however, IM efficacy in this subgroup has not been formally assessed due to the rarity of such pts. Methods: We conducted an international survey among GIST referral centers to collect clinical data on pts with advanced PDGFRAD842V mutant GISTs treated with IM for advanced disease. This dataset was completed with 7 patients from the EORTC trial database. Results: Twenty pts were included, 16 were male (80%), median age at treatment initiation was 63.4 (range 38.3-74.5) years. The primary tumor was gastric in 15 cases (75%), 17 patients had metastatic disease and 3 had locally advanced disease. Metastases involved the peritoneum in 7 cases and the liver in 12 cases. Fourteen pts received IM 400 mg/d and 6 received IM 800 mg/d up front in most cases in the context of clinical trials (EORTC 62001 and 62005 studies). Nineteen pts were assessable for response, none had a complete or partial response, 5 pts (26%) had stable disease (SD) and 14 pts (74%) progressed. Median progression-free survival was 2.8 (95%CI: 2.5-3.1) months. Of the 14 patients who received IM 400 mg/d, 7 were treated with 800 mg/d at progression, the subsequent median time to IM resistance, defined as the time from treatment initiation to definitive progression on IM (whatever the dose) for all patients (n=20) was 3.5 (95%CI: 0.0-8.3) months. Median overall survival was 12.7 (6.3-19.0) months. There were no significant differences in outcome between pts from the EORTC trials and the other pts included in this analysis. Conclusions: This study is the largest reported to date investigating the outcome of patients with advanced PDGFRAD842V mutant GIST treated with IM. Our data show that IM has little efficacy in this subset of patients, confirming data from previous reports. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Novartis Amgen, GlaxoSmithKline, Infinity, Johnson & Johnson, Lilly, Novartis, Pfizer, PharmaMar, sanofi-aventis, Schering-Plough Novartis
Is age at the time of surgery a predictor of biochemical failure following radical prostatectomy?
Authors: G. Badalato, L. Barlow, M. Benson, J. McKiernan
Journal: Journal of Clinical Oncology (2009)

e22110 Background: Preoperative PSA level, Gleason score, and tumor stage have all been shown to influence risk of recurrence after radical prostatectomy. Increasing age has been associated with more indolent behavior in some cancers. This study evaluates the effects of age at surgery on recurrence-free survival in prostate cancer patients at a single institution stratified by established preoperative risk factors. Methods: Using the Columbia Urologic Oncology Database, a retrospective analysis of 3,736 men treated with open or robotic-assisted laparoscopic radical prostatectomy for prostate cancer from 1988 to 2008 was conducted. Patients were divided into two groups by age at the time of surgery, and recurrence-free survival rates were analyzed using Kaplan-Meier survival curves. The subgroups were stratified by preoperative PSA level, biopsy Gleason score, and clinical stage; multivariate analyses with cox proportional hazards models were used to further identify independent predictors of recurrence. Recurrence was defined as a single PSA level of 0.2 ng/ml or greater at least 28 days after surgery. Results: 1,984 patients were divided into groups 1 (n=1,325 age 40–64) and 2 (n=659 age ≥65). Five-year recurrence-free survival rates were 80.6%(CI: 78.0–82.9%) and 75.6%(CI: 71.5–79.1%) for groups 1 and 2, respectively. In the univariate model, advanced age was significantly associated with an increased overall risk of recurrence (HR 1.30, p=0.012). However, in multivariate analyses accounting for PSA, Gleason score, and clinical stage, age was not shown to be an independent predictor of recurrence (HR 1.04, p=0.76). In a subset of patients with low-grade cancer (Gleason score 2- 6), advanced age was associated in a univariate analysis with an even greater relative risk of recurrence (HR 1.47, p=0.032). However, this was not significant in the multivariate model (HR 1.27, p=0.21). Conclusions: Older patients who undergo radical prostatectomy for prostate cancer appear to have an increased risk of recurrence, which is most notable in patients with low-grade disease. However, age is not an independent predictor of recurrence when accounting for PSA, grade, and stage. No significant financial relationships to disclose.
Temozolomide therapy for patients with non-small cell lung cancer, breast cancer, or melanoma brain metastases.
Authors: D. R. Naskhletashvili, V. A. Gorbunova, M. B. Bychkov, G. E. Chmutin, V. B. Karahan, V. A. Aloshin, Z. P. Michina, S. B. Alieva, E. A. Moskvina, N. N. Blokhin
Journal: Journal of Clinical Oncology (2010)

e12539 Background: To assess the efficacy of temozolomide (TMZ) as monotherapy, RNMZ combined with whole brain irradiation (WBI), or combined chemotherapy of RNMZ and irinotecan (I) in patients (pts) with brain metastases (BM) from non-small cell lung cancer (NSCLC), breast cancer (BC), or melanoma. Methods: Pts with BM from NSCLC (21 pts), melanoma (16 pts) and BC (17 pts) were treated with WBI (3 Gy/30 Gy) and concomitant TMZ therapy (75 mg/m2/day orally on days 1-14). Pts with BM from NSCLC (7 pts), melanoma (16 pts) were treated with TMZ (150-200 mg/m2/day orally on days 1-5 every 4 weeks) as monotherapy. 11 heavily pretreated NSCLC pts (after I-II lines of chemotherapy and/or WBI) were treated with combined chemotherapy of I (250 mg/m2 day 6 intravenous, every 4 weeks) and TMZ (150 mg/m2/day orally on days 1-5, every 4 weeks). Results: Observations were as follows: in the TMZ + WBI treated pts with BM from NSCLC, 3 (14.3%) complete response (CR), 8 (38.1%) partial response (PR), 8 (38.1%) stabilization of disease (SD). The median overall survival (mOS) was 7.5 months. In the TMZ + WBI pts with BM from melanoma, 3 (18.8%) PR, 8 (50%) SD. The mOS was 6.6 months. Among pts with BC brain metastases, 2 (11.8%) CR, 11 (64.7%) PR, 3 (17.6%) SD .The mOS was 11 months. In the TMZ monotherapy pts with BM from NSCLC, there were 4 SD, 3 pts progressed. The mOS was 8 months. In the TMZ as monotherapy pts with BM from melanoma, 1 (6.3%) CR, 4 (25%) PR, and 6 (37.5%) SD. The mOS was 6 months. In the TMZ + I pts with NSCLC brain metastases, 7 (63.6%) SD. The mOS was 8 months. Conclusions: RNMZ with WBI showed high efficacy in pts with BM from NSCLC, BC and melanoma. RNMZ as monotherapy showed efficacy and good tolerability in pts with BM from melanoma and SD in pts with BM from NSCLC. Combined chemotherapy of TMZ and I in heavily pretreated pts with NSCLC BM showed prolonged SD and good tolerability. No significant financial relationships to disclose.
Capecitabine and irinotecan in elderly patients with advanced or metastatic gastro-intestinal tumors
Authors: J. Kattan, J. Abou Yared, F. Farhat, G. Chahine, F. Nasr, W. Moukadem, F. Younes, M. Ghosn
Journal: Journal of Clinical Oncology (2006)

18619 Background: Capecitabine and Irinotecan exhibit single-agent activity in gastro-intestinal tumors. Their combination seems safe and effective. Adult patients with advanced or metastatic gastric or colorectal cancers were enrolled separately in 2 phase II trials dealing with the combination of both drugs. The aim of this study was to evaluate retrospectively the toxicities and the safety profile of this combination in elderly patients (≥ 65 years) as first line therapy for advanced or metastatic gastro-intestinal cancers. Methods: Patients with advanced or metastatic adenocarcinomas of the colon or the stomach aged 65 years or more were treated with the combination of: Irinotecan 80 mg/m 2 IV d1,8,15, and Capecitabine 1250 mg/m 2 orally d 1–14, Q 4w. Toxicities were graded according to the NCI common toxicities criteria version 3. Results: 24 naïve-chemotherapy patients were included. Median age was 68 years (extremes 65 to 88). Primary tumor was stomach, colon, and rectum in 13, 9, and 2 cases respectively. Frequent sites of metastases were liver (18), lymph nodes (8), peritoneum (7), and lung (5). They received 113 cycles with median number 4.7/patient, and extremes 1 to 14. Serious toxicities graded as IV were universally absent. Grade III anemia, diarrhea, and vomiting were encountered in 1, 1, and 2 patients respectively. Grade II anemia, leucopenia, diarrhea, alopecia, fatigue, and vomiting were recorded in 5, 2, 4, 2, 2, and 6 patients respectively. Hand-foot syndrome was observed as only grade I in 2 patients. There was no febrile neutropenia. In the other hand, objective response was encountered in 9 patients (37.5%), with median response duration of 6 months (extremes 1 to 15). After a median follow-up of 36 months, 19 patients died from progression of their disease with mean overall survival of 5.5 months (extremes 1 to 28). Conclusion: The combination of Irinotecan and Capecitabine according to our schedule revealed an excellent safety profile with easily manageable toxicities. This schedule is highly suitable for elderly patients. No significant financial relationships to disclose.
Radiation induced lung injury in survivors of childhood cancer
Authors: M. M. Stegner, P. M. Luckett, J. E. Fitzgerald, D. Eshelman, C. Cochran, P. J. Leavey
Journal: Journal of Clinical Oncology (2007)

20017 Background: The purpose of this study was to examine survivors of childhood cancer, treated with whole lung irradiation (WLI), for signs of pulmonary insufficiency and to correlate pulmonary function test (PFT) results to symptoms of pulmonary dysfunction as detected using the St. George’s Respiratory Questionnaire (SGRQ). Methods: A cross-sectional study was conducted on eligible patients (&gt;2 years from WLI and &lt;18 years at time of diagnosis) who are followed in our institution’s cancer survivor program. Participating patients had a history and physical examination and PFTs performed pre and post bronchodilator challenge. Patients (or their guardians) also completed the SGRQ. The SGRQ, validated for patients 17 to 80 years, generates four values that define respiratory dysfunction: a Symptoms score, an Activity Score, an Impact score, and a Total score. Results: Twenty eligible patients were identified, 12 of whom consented to participate in this study (11 Wilms, 1 Ewing sarcoma). The median current age was 18.4 years (7.5 to 43 years; n=6 &lt; 14 yrs), while patients received WLI (1,200 cGy n=10, 1500 cGy n=2) at a median age of 4.4 years of age (1.7 to 8.7 years). The median time from radiation therapy was 12.6 years (4.7 to 34.3 years). All patients denied smoking, 4 had a history of asthma and all had a normal lung exam. Ten patients had PFTs, 5 of whom (4/5 adults and 1/5 children) had a restrictive pattern noted by PFTs. One further patient (7.5 yrs of age) had a total lung volume 70% predicted but a forced vital capacity 86% predicted. In the pediatric patients (&lt;14 years currently) the FEF 25–75 (4/5) and SGaw (5/5) were increased following treatment with bronchodilator. Twelve participants completed the SGRQ, 4 had elevated total scores (22, 32, 37 and 64). 1 patient with echocardiographic evidence of a dilated cardiomyopathy had an elevated total score but normal symptom score. One patient with a recorded acute pneumonitis after WLI, now 18 years later had normal PFTs and normal SGRQ scores. No correlation was seen between PFT results and SGRQ scores. Conclusions: A restrictive lung function pattern is more common at a later age following WLI in childhood. Mid-expiratory flow and airway conductance following bronchodilator were increased in children. The functional significance of these findings requires further study. No significant financial relationships to disclose.
Bone marrow infiltration in infants with disseminated neuroblastoma
Authors: B. De Bernardi, S. Sorrentino, M. Pasino, A. R. Gigliotti, D. Dau, F. Scuderi, C. Rosanda
Journal: Journal of Clinical Oncology (2009)

10056 Background: The INSS definition of stage 4S neuroblastoma allows a bone marrow infiltration (BMI) no greater than 10%. More extensive involvement is to be consider stage 4. However, the degree of BMI may be difficult to establish, since tumor cells in the marrow commonly aggregate in clumps. So far, no studies have specifically investigated this issue. In this study we have reviewed the bone marrow slides of infants with disseminated neuroblastoma enrolled between January 1998 and July 2008 in the Italian Neuroblastoma Registry. Methods: BMI was arbitrarily considered &lt;10% when it consisted of a maximum of 5 tumor cell aggregates/slide in association to normal cellularity. Marrow was aspirated from iliac crests and slides were stained with Wright-Giemsa method. A minimum of 2 slides for aspirate were examined at low magnification. The same 2 hematologists (CR, MP) examined the slides independently along the study period, blind for clinical data. A third hematologist (FS) joined to perform the reviewing process. Results: Of 142 infants enrolled, we retrieved and reviewed bone marrow slides of 73. Before results of bone marrow study, 31 patients were defined as stage 4, and 42 as stage 4S. Following bone marrow study, 2 patients previously defined as stage 4S who had ≥10% BMI were moved to stage 4. The results of the revision are summarized ( Table ). Conclusions: In this study, only 2/42 infants with stage 4S clinical features had BMI ≥ 10% and were eventually labeled as stage 4. Whether chemotherapy for stage 4 is of advantage for these patients remains to be seen. [Table: see text] No significant financial relationships to disclose.
Colony stimulating factors secreted by irradiated autologous tumor cell vaccines inhibit immunity
Authors: Sruthi Ravindranathan, Sean G Smith, Khue Nguyen, David A Zaharoff
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Autologous tumor cell-based vaccines (ATCVs) have a number of potential advantages including multivalency and patient specificity. ATCVs contain many potential antigens, both known and unknown which potentiate polyclonal responses capable of responding to a more diverse population
A phase Ib trial of Bcl-2 inhibitor obatoclax in combination with carboplatin and etoposide for previously untreated patients with extensive-stage small cell lung cancer (ES-SCLC)
Authors: A. Chiappori, M. T. Schreeder, M. M. Moezi, J. Stephenson, J. L. Blakely, R. Salgia, Q. S. Chu, S. M. Malik, M. M. Modiano, M. S. Berger
Journal: Journal of Clinical Oncology (2009)

3576 Background: Obatoclax (Ob) is a small-molecule antagonist of all the Bcl-2 prosurvival proteins. In vitro it enhances the effects of the drugs cisplatin and etoposide. Bcl-2 family proteins are frequently expressed in SCLC, and SCLC cell lines are sensitive to Ob. Methods: This study was designed to find the maximal tolerated doses (MTD) of oOb when given on a 21 day (D) cycle together with carboplatin (AUC 5 D1) and etoposide (100 mg/m2 D1–3), in separate dose escalations using Ob as a 3-hr infusion D1–3 and as a 24-hr infusion D1–3. Eligible patients had ES-SCLC, measurable disease, ≤1 prior therapy, ECOG PS ≤1, and adequate hematological, renal and hepatic function. 3- 6 patients were enrolled into ascending dose cohorts with standard DLT rules evaluating safety in C1 to determine dose escalation. Results: 24 patients were enrolled into 5 dosing cohorts (14 males; median age 67). A total of 66 cycles (C) have been administered to date. There were no DLTs in the initial cohorts using Ob 15 mg over 3 hr or Ob 30 mg over 24 hr. Two DLTs occurred in the Ob 30 mg over 3 hr cohort - both due to myelosuppression in previously treated patients. As a result, the trial was amended to exclude previously treated patients. 5 previously untreated patients receiving Ob 30 over 3 hr had no DLTs. There were no DLTs in the Ob 45 mg over 24 hr cohort but 2 patients in the Ob 24-hr infusion cohorts had infusion pump malfunctions while at home. There were 2 DLTs in the Ob 45 mg over 3 hr cohort (somnolence, euphoria, &amp; disorientation) establishing MTD of Ob 30 mg over 3 hr daily x 3. After C2 the 6 previously untreated patients on Ob 24-hr infusion cohorts had 3 PRs, 1 SD, 1 PD, and 1 Unk; the 2 previously treated patients had PRs. After C2 all 7 previously-untreated patients at 15 or 30 mg in the 3-hr infusion cohorts have PR; the 3 previously treated patients had SD. Conclusions: Ob can be combined with carboplatin and etoposide using either a 3-hr or a 24-hr infusion, and both regimens are associated with high early response rates in ES-SCLC, perhaps due to inhibition of mcl-1. Due to practical issues with the 24-hr infusion arm, the 3-hr 30 mg MTD dose will be utilized in a randomized phase II versus carboplatin and etoposide alone. [Table: see text]
Hyperthermia and radiation therapy for locally advanced or recurrent breast cancer
Authors: K. D. Kiel, T. Refaat, N. Navanandan, V. Sathiaseelan
Journal: Journal of Clinical Oncology (2009)

631 Background: Hyperthermia is a known radiation sensitizer. This retrospective series evaluates a single institutional experience with hyperthermia and radiotherapy (RT) for locally advanced/recurrent breast cancer, many referred for palliation. Methods: Records of 130 pts with locally advanced/recurrent breast cancers treated with hyperthermia and RT from 1991–2007 were reviewed. 40% had distant metastases. 168 different sites were irradiated to 16–76.4 Gy (median 50 Gy) with conventional fractions and treated with 1–11 hyperthermia sessions twice/wk (median 6). 58 pts required &gt;1 hyperthermia field to cover tumor. Intratumoral temperature goal was &gt;42.5°C for &gt;45 min. Thermal equivalent dose (TED) was calculated for each treatment (min above 42.5 and 43°C). Results: Median and mean FU of alive patients was 20 and 32 mos, respectively. 27 pts were treated for locally advanced and 103 for recurrent cancer on the chest wall, nearby skin, or nodes. Treated sites were: intact breast (21%), chest wall/skin (66%), nodes (12%). Disease volume was microscopic in 11%, less than 3 cm in 11%, and greater than in 78%. Various concurrent chemotherapy regimens were given in 56%. 40% of treated sites had prior RT (median 50 Gy). CR was seen in 52% and CR/PR in 79% in pts with measurable tumor. 5 mastectomies were done, with no residual cancer in 1. Local control (LC) at last FU was obtained in 58% of treated sites. Type (primary vs recurrent), location (breast/chest wall/node), extent of disease (3 cm), or prior RT were not associated with LC. Improved LC was seen with increased RT dose, 36%, 52%, and 70% for 16–39.6 Gy, 40–50 Gy, and 50+ Gy, respectively. LC also improved with more minutes of hyperthermia - median of 238 min and 147 min TED 42.5°C &amp; 43°C, respectively in pts with LC, and median of 180 min and 105 min TED 42.5°C and 43°C, respectively in pts without LC. All pts with microscopic disease are controlled. 16 pts (12%) are NED (mean 32 mos). Conclusions: Hyperthermia and RT improves local control and can palliate locally advanced or recurrent breast cancer, even in previously irradiated pts - a quality of life issue. Although the followup of this poor prognosis group is short, local control appears to be maintained to death for many pts. Pts with microscopic residual cancer after resection may benefit from the combination. No significant financial relationships to disclose.