tbuckley/cabot-search huggingface dataset:
Identification of a gene signature that can predict lone-term survival in patients with high-grade late stage serous ovarian cancer
Authors: T. Bonome, D.-C. Park, K. Hao, H. Donninger, M. Radonovich, J. Brady, J. C. Barrett, W. H. Wong, W. R. Welch, S. C. Mok, M. J. Birrer
Journal: Journal of Clinical Oncology (2005)

5032 Background: Though most patients with late stage serous ovarian cancer die within 2 years of diagnosis, a subset of patients, even with clinically and morphologically indistinguishable diseases, develop a more chronic form of ovarian cancer, and may survive 5 years or more with treatment. We hypothesize that these cancers may have a prognostic signature that can be used to predict the clinical course of the disease. Methods: To discover the prognostic signature, expression profiling was performed on 53 microdissected high-grade late stage serous tumors using the Affymetrix U133 plus2 oligo array platform. We applied a “semi-supervised” dimension reduction method, and (1) identified the genes associated with cancer survival and (2) established a predictive model. In brief, univariate Cox regression with Jackknife safeguard were conducted and pinpointed the 200 most significant genes. The first 6 principal components of these genes, representing >90% of total variance, entered a multivariate Cox model, based on which the relative hazard of future patients can be predicted. To confirm our finding, the microarray data underwent leave-one-out validation. In each iteration, we reserved one sample, and used the remaining 52 patients to carry out the gene selection and model building, which furthermore predicted the relative hazard of the reserved patient. To further validate the gene signature, quantitative PCR was performed on the 10 most significant genes in 44 patients. Results: According to the prediction, the patients were equally divided into low- and high- risk groups and the non-parametric Kaplan-Meier plot and log rank test showed the two groups were significantly different in survival (p = 0.0089). Quantitative PCR validation demonstrated the accuracy and robustness of the prognostic gene signature and the prediction model. Conclusions: These genes contribute to the differential survival of ovarian cancer patients, and may serve as unique targets for the management of the disease. No significant financial relationships to disclose.
The role of surgical staging in grade 1 endometrioid corpus cancer
Authors: J. K. Chan, H. Guo, M. K. Cheung, K. Osann, A. Husain, N. N. Teng, J. S. Berek, D. S. Kapp
Journal: Journal of Clinical Oncology (2006)

5009 Background: To evaluate the role of surgical staging of patients with grade 1 endometrioid uterine cancer. Methods: Data including stage, histology, grade, lymph nodes involvement and disease-specific survival were extracted from Surveillance, Epidemiology, and End Results Program from 1988 to 2001. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors for survival. Results: 12,712 women were diagnosed with endometrioid carcinoma which included 3,867 (30.4%) with grade 1, 5,285 (41.6%) with grade 2, and 3,560 (28%) with grade 3 disease. The 5-year disease specific survival of patients with grade 1, 2, and 3 disease was 97.78% ± 0.29, 92.14% ± 0.45, and 78.04% ± 0.82, respectively. Of all the patients with nodal involvement, 10% had grade 1, 39% had grade 2 and 51% had grade 3 disease (p &lt; 0.001). Positive nodes were found in 3% of grade 1, 9% of grade 2 and 18% in grade 3 tumors (p &lt; 0.001). Of the 3,867 patients with grade 1 disease, 3,281 (84.9%) had stage I, 317 (8.2%) had stage II, 166 (4.3%) had stage III, and 103 (2.7%) had stage IV disease. Fifteen percent of the patients with grade 1 disease had extra-uterine spread, including 8% to the cervix, 4% to the pelvis and 3% to the upper abdomen or distant metastases. Conclusions: Grade 1 uterine cancers have a risk of extra-uterine spread. Given that the information obtained from a thorough staging procedure clearly influences adjuvant treatment decisions, complete surgical staging is recommended. No significant financial relationships to disclose.
Correlation of deviation from intended cisplatin (CDDP) dose intensity with outcome in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) receiving concurrent chemoradiation (CRT)
Authors: C. S. Liu, C. Elser, S. Huang, G. R. Pond, B. O'Sullivan, E. X. Chen, J. N. Waldron, D. Goldstein, L. L. Siu, J. Kim
Journal: Journal of Clinical Oncology (2008)

6052 Background: CRT with high dose CDDP 100mg/m2×3 and radiation (RT) 70Gy/35f/7weeks is a standard treatment option in patients (pts) with LA-HNSCC. Whether the delivery of less than the intended doses of CDDP is associated with worse outcomes is unknown. Non-trial LA-HNSCC pts, definitively treated with CRT, were retrospectively reviewed to investigate correlates of outcome and toxicity. Methods: All non-nasopharynx LA-HNSCC pts treated between Jan 02 and Dec 06 whose treatment intent was CRT were reviewed. LA-HNSCC pts without bulky adenopathy were eligible for altered fractionated RT alone during this period. Pts on CRT study protocols or treated with RT alone were excluded. Data collected included baseline patient and tumour characteristics, chemotherapy and RT delivery details, toxicity and clinical outcomes. Results: A total of 257 eligible pts were identified: median age 57 (27- 80), male (75%), smokers (77%), ECOG 0 (63%), ≤1 co-morbidity (77%), pre-treatment weight loss (36%), oropharynx primary (54%), T3/4 (56%), N2/3 (83%), stage IV (92%: IVA=71%, IVB=21%). Median follow-up was 21.2 months. Of 257 pts, 242 (94%) received 70Gy and 122 (47%) received intensity modulated radiation therapy (IMRT), implemented as standard therapy after 2004. Only 97 (38%) pts received all 3 cycles of CDDP commonly due to acute hematologic toxicities and weight loss. The 2 year OS and PFS were 85.0% and 64.7%. On multivariate analyses, only poorer ECOG was significant for decreased OS (p<0.001). Lower PFS was associated with <3 cycles of CDDP (p=0.035), poorer ECOG (p<0.001), non-oropharynx primary (p<0.014), T3/4 (p=0.019) and stage (p=0.028). The delivery of <3 cycles of CDDP affected local but not regional or distant PFS. Increased late grade 3 (CTCAEv3) toxicity was associated with non- IMRT (p=0.017), poorer ECOG (p<0.001), low pre-treatment Hgb (p=0.024) and N0/1 (p=0.016). Conclusions: In these predominantly stage IV pts, about 2/3 could not receive the third cycle of CDDP and had decreased local control. Further study is required to validate this and other adverse factors identified for PFS. The implementation of IMRT was associated with less late grade 3 toxicity. No significant financial relationships to disclose.
Retrospective analysis of interleukin-2 therapy in patients with metastatic renal cell carcinoma who had received prior antiangiogenic therapy
Authors: T. Schwarzberg, M. M. Regan, V. Liu, J. W. Mier, D. Cho, H. Koon, R. S. Bhatt, V. Seery, K. Bradley, M. B. Atkins, D. F. McDermott
Journal: Journal of Clinical Oncology (2008)

5044 Background: Antiangiogenic therapy (anti-VEGF) has been advocated as frontline therapy for patients with metastatic renal cancer. The role of interleukin 2 (IL-2) therapy following development of resistance to anti-angiogenic therapy remains unexplored. We conducted a retrospective analysis of the tolerability and efficacy of IL-2 therapy in pts who had previously received anti-VEGF therapy. Methods: 16 consecutive pts median age 61; (range 48–70), ECOG PS 0/1/2:9/6/1, M/F: 12/4 who received salvage IL-2 therapy between 7/04- 5/07 were analyzed. All 16 pts were candidates for IL-2 prior to initiating anti-VEGF therapy. Prior anti-VEGF therapy included bevacizumab (B) alone (6), sorafenib (So) alone (2), sunitinib (Su) alone (2), So and Su (2), B and Su (3), and B and So (1). Treatment tolerability, as measured by IL-2 doses received, and toxicity, was compared to the HD IL-2 arm of a Cytokine Working Group Phase III trial (McDermott, et al, JCO 2005). Results: Median number of doses of IL-2 administered per intended 14 dose 5-day cycle was 11 (79%) for course (C)1, week (W) 1 and 8.5 (61%) for C1,W2. The median number of total doses for C1 was 18/28 (64%). 6/16 pts did not receive W2 of therapy (37.5%, 95% CI 15.2%- 64.6%). 6/10 pts with prior So or Su, compared to 0/6 with prior B alone, did not receive W2 of therapy (p=0.034). Expected toxicities were seen, such as hypotension, pulmonary edema and acute renal failure. Toxicities that precluded further treatment included: cardiomyopathy (1); myocarditis (1); atrial fibrillation with hypotension and bowel ischemia (1); severe angina (1); sudden fatal cardiac arrest (1), and bullous pemphigoid (1). The incidence of severe cardiac toxicities in pts receiving prior Su or So therapy was 50% (95% CI 18.7% to 82.3%) compared to 8.5% in the above mentioned Phase III trial. No partial or complete responses were seen. Conclusions: This retrospective analysis highlights unexpected and severe cardiac toxicities in pts receiving IL-2 after Su/ So failure. The assumption that IL-2 therapy can be safely administered following Su/So treatment may not be valid. Further examination of the safety of this sequential approach is necessary and more cautious patient selection appears warranted. No significant financial relationships to disclose.
骨髄増殖性腫瘍の症状評価フォーム(MPN-SAF):患者402例における国際的プロスペクティブ・バリデーションおよび信頼性試験
Authors: Scherber Robyn, C Dueck Amylou, Johansson Peter, Barbui Tiziano, Barosi Giovanni, M Vannucchi Alessandro, Passamonti Francesco, Andreasson Bjorn, L Ferarri Maria, Rambaldi Alessandro, Samuelsson Jan, Birgegard Gunnar, Tefferi Ayalew, N Harrison Claire, Radia Deepti, A Mesa Ruben
Journal: Blood (2011)
Relative conditional survival in 41,476 patients with ovarian cancer.
Authors: R. Ware, L. Baldwin, B. Huang, T. Tucker, S. Goodrich, I. Podzielinski, C. P. DeSimone, F. Ueland, J. Vannagell, L. G. Seamon
Journal: Journal of Clinical Oncology (2010)

5090 Background: Although the overall survival (OS) for advanced ovarian cancer (OC) is poor, patients (pts) who survive the initial treatment period and beyond will have improved outcomes with each additional year survived. This concept is referred to as conditional survival (CS), and accounts for the change in the probability of survival over time. Our objective is to evaluate relative CS in OC, stratified by stage, classification of residence, and surgery as the first course of treatment. Methods: Using the Surveillance, Epidemiology, and End Results 1995-2006 database cases were identified using the International Classification of Diseases code for OC. Inclusion criteria included malignant behavior, first primary, actively followed, and age ≥ 20 years. Exclusion criteria included death certificate or autopsy only cases. Using the actuarial life table method, 5-year relative CS was calculated, stratified by stage, classification of residence, and surgery as the first course of treatment. Results: 41,476 pts met inclusion criteria. Stage distribution was 23%, 9%, 41%, and 28% for stages I, II, III, and IV, respectively. The first course of treatment was surgery in 76%. The overall 5-year relative CS improved over time (45%, 61%, 79% at diagnosis, 2, and 5 yrs, respectively). The largest improvement was noted in stage III and IV disease. Stage III relative CS was 36%, 43%, 50%, 56%, and 63% at diagnosis, 2, 3, 4, and 5 years after diagnosis, respectively. Stage IV relative CS was 17%, 28%, 33%, 39%, 48% at diagnosis, 2, 3, 4, and 5 years after diagnosis, respectively. Interestingly, patients living in a rural setting had lower relative CS than those in urban settings. Stage III disease pts undergoing surgery as their first course of treatment had a 5-year relative CS of 40% at diagnosis, 44% at 2 years, and 63% at 5 years following diagnosis compared to 9% at diagnosis, 28% at 2 years, and 52% at 5 years for those who did not have surgery as their first course of treatment. Conclusions: Relative CS is a more relevant estimate of survival for OC patients and provides more accurate prognostic information. Although advanced OC is associated with a poor prognosis (5 yr OS 33.5%), survival incrementally improves for every year survived. No significant financial relationships to disclose.
A phase I study of temozolomide (TMZ) and the farnesyltransferase inhibitor (FTI), lonafarnib (Sarazar, SCH66336) in recurrent glioblastoma
Authors: M. R. Gilbert, P. Gaupp, V. Liu, C. Conrad, H. Colman, M. Groves, V. Puduvalli, V. Levin, S. Hsu, J. Horowitz, W. Yung
Journal: Journal of Clinical Oncology (2006)

1556 Background: Farnesylation is essential for the post-translational modification of several proteins that play a role in cell proliferation and growth. FTIs demonstrate antiproliferative effects in a variety of tumor cell lines and xenograft models and enhanced efficacy by combining lonafarnib with TMZ compared with TMZ alone. Clinical studies show that dose-intense TMZ may have better efficacy then conventional dosing (Wick, Neurology 2004). Objective: Determine the maximum tolerated dose of lonafarnib when combined with a dose-intensified schedule of TMZ. Eligibility criteria: Histologically proven GBM; evidence of relaspe or progression; up to 2 prior chemotherapy regimens, prior TMZ permitted; KPS ≥ 60. No enzyme-inducing anticonvulsants. Methods: TMZ was given at 150 mg/m 2 days 1–7 and 15–21; lonafarnib escalated by cohort: 100 mg BID, 150 mg BID, 200 mg BID on days 8–14 and 22–28 of a 28-day cycle. Response: Toxicity measured after cycle 1 using NCI CTCAE v3. Patient (pt)accrual used a 3 + 3 design. Response was evaluated q2 cycles. Standard response criteria (MacDonald) were used. Results: 15 patients were accrued. Median age 47 yrs; median KPS 90. M:F ratio was 11:4. No DLTs in any dose cohort, a pt (cohort 1) died day 29 of unrelated cardiac disease. 4 pts demonstrated partial response, all with prior TMZ failure, 3 pts showed prolonged stable disease. 6-month PFS rate estimated at 33%, median PFS 14 weeks. Treatment was well tolerated: 1 episode each of grade 3 diarrhea, esophagitis, fatigue and hypokalemia; 3 episodes of grade 3/4 leukopenia, 2 episodes of grade 3/4 neutropenia, and 2 episodes of grade 4 thrombocytopenia. Seven pts had grade 3/4 lymphopenia, some with persistant lymphopenia from prior TMZ. 1 pt had grade 4 pneumonitis of uncertain etiology. Conclusions: The alternating week schedule of TMZ/lonafarnib was well tolerated. Preliminary results suggest anti-tumor activity even in pts who had failed prior TMZ. It is not certain whether this activity is due to the dose-intensified TMZ or the treatment combination. Studies are planned to evaluate potential predictors of response (i.e MGMT gene promoter methylation) and expand the trial to obtain pharmacokinetic and additional efficacy data. [Table: see text]
Myeloid Leukemogenesis Driven by Aberrant CDX2 Expression Involves Transcriptional Repression of KLF4 and Deregulated PPARγ Signaling
Authors: Katrin Faber, Lars Bullinger, Angela Garding, Daniel Mertens, Daniela Martin, Daniel Walcher, Konstanze Döhner, Hartmut Döhner, Stephen M. Sykes, Rainer Claus, Christoph Plass, Steven W. Lane, Claudia Scholl, Stefan Fröhling
Journal: Blood (2011)
Predictive value of EGFR mRNA levels assessed by quantitative RT-PCR in primary tumors of patients treated with cetuximab for metastatic colorectal cancer
Authors: E. C. Briasoulis, D. Papamichael, D. Tzachanis, C. Christodoulou, E. Samantas, E. Razis, P. Papakostas, C. Bakoyiannis, R. M. Wirtz, K. T. Kalogeras
Journal: Journal of Clinical Oncology (2007)

4121 Background: The epidermal growth factor receptor (EGFR) protein is the nominal target of the monoclonal therapeutic antibody cetuximab. Yet, repeated failure of EGFR immunohistochemistry (IHC) in predicting treatment outcome has questioned its value in colorectal cancer (CRC). Therefore search for a valid molecular predictor of cetuximab efficacy is highly justified. Methods: 64 CRC patients were treated with standard chemotherapy plus cetuximab in the metastatic setting. RNA was isolated from fixed tumor tissue samples employing an experimental method based on magnetic beads from Siemens Medical Solutions Diagnostics, followed by kinetic one-step RT-PCR for EGFR, HER-2, HER-3, and HER-4 analysis. EGFR protein levels were also assessed by IHC in 62 of the patients, using the 31G7 clone of the mouse monoclonal antibody (Zymed). Slides scored 1+, 2+ and 3+ were considered EGFR protein positive. Results: After a median follow-up of 17 months, median survival was 15.1 months, while median time to disease progression (TTP) was 6.6 months. For the RT-PCR results an objective cut-off at the 2nd quartile (median) for the HER family was chosen. EGFR RNA levels above the median value, demonstrated predictive value in terms of a prolonged TTP (9.3 vs. 5.5 months, p=0.017). No difference was found in terms of survival (24.6 vs. 12.6 months, p=0.106). EGRF assessed by IHC and the rest of the HER family markers assessed by RT-PCR failed to predict TTP outcome or survival. Finally, no agreement was found between the IHC and RT-PCR methods when assessing EGFR. Conclusions: The results of this retrospective study show a predictive value of EGFR RNA levels assessed by RT-PCR on TTP, as opposed to EGFR protein levels. Prospective validation studies are needed to prove if this biomarker is the missing molecular predictor of response to cetuximab. No significant financial relationships to disclose.
Pilot study of dronabinol for adult patients with primary malignant gliomas
Authors: J. J. Vredenburgh, C. H. Bohlin, D. A. Reardon, A. Desjardins, J. A. Quinn, J. N. Rich, D. A. Bota, K. J. Goli, H. S. Friedman, D. H. Allen
Journal: Journal of Clinical Oncology (2007)

19607 Background: Chemotherapy-induced nausea and vomiting (CINV) are common adverse effects from chemotherapy. While most treatments administered in patients with primary gliomas are not highly emetogenic, up to 50% of neuro-oncology patients report CINV despite 5HT 3 or steroid therapies. Adjuvant benzodiazepines frequently alter mental status. Dronabinol may provide a safe alternative option without compromise of neurological status. his study seeks to describe toxicities (TOX) associated with dronabinol administration in neuro-oncology patients. A secondary aim is to describe the impact that dronabinol has on their quality of life (QOL). Methods: This is an exploratory study of adult patients with WHO Grade III/IV primary gliomas on adjuvant chemotherapy. Power analysis determined a sample size of 34 subjects for 0.80 effect size. Enrollment is ongoing with 18/34 adult patients accrued. Patients take dronabinol 5 mg BID 24 hours prior to, during, and 48 hours after completion of oral/IV chemotherapy. Patients continue their established antiemetic regimen. Between chemotherapy doses, dronabinol is reduced to 2.5 mg daily. Intolerance of dronabinol is defined as 2 or more Grade 3 or greater non-hematologic TOX according to the CTC v.3 definition handbook. Modified Functional Living Index-Emesis (FLIE), Functional Assessment of Cancer Therapy-Brain Tumor (FACT-Br), Mini Mental Status Exam (MMSE), and CINV visual analog scales are collected at specific points for 2 cycles for TOX and QOL data. Results: Subjects are predominately male (n=10); mean age of 45.2 years. Four withdrew due to Grade 3 neurologic TOX of cognitive changes (n=3) despite decreasing dosages; Grade 3 persistent CINV (n=1) despite increasing dronabinol dosage. Increased dosages were required in 4 subjects to better manage CINV. Two required decreased doses for Grade 2 neurologic TOX. Most subjects (n=14) reported stable or improved QOL by FACT-Br and FLIE while the 4 withdrawn subjects reported worsening QOL related to TOX. Conclusions: Dronabinol is safe and effective for administration as an adjunct to standard antiemetic therapy during treatment for primary glioma. The dose may be titrated with minimal toxicities and improvement in QOL. No significant financial relationships to disclose.
A genotype-based dose-escalation study of irinotecan in advanced colorectal cancer patients treated in second-line of chemotherapy
Authors: E. Marcuello, L. Paré, D. Páez López-Bravo, E. del Río, A. Barnadas Molins, A. Altés, M. Baiget
Journal: Journal of Clinical Oncology (2008)

14599 Background: The dose-limiting toxicities of Irinotecan are diarrhea and neutropenia. The risk of developing these toxicities is related to polymorphisms in the gene coding for the enzyme UGT1A1 that inactivates the active metabolite of Irinotecan (SN-38). The efficiency of UGT1A1 is inversely correlated to the number of TA repeats in the promoter region of the UGT1A1 gene being the most common repeat numbers 6 and 7. Patients with a 7/7 genotype are at high risk of toxicity and a dose reduction can be appropiate in these cases. In the remaining patients (6/7 and 6/6) higher doses of Irinotecan can theoretically be administered. Methods: 25 patients with advanced colorectal cancer (with a 6/6 or 6/7 genotype) treated with different escalated doses of Irinotecan (see table) in second-line chemotherapy have been studied. Irinotecan was administered alone. Dose limitimg toxicity (DLT) at cycle 1 was defined when one or more of the following side effects appeared: grade IV neutropenia lasting more than 7 days, febrile neutropenia, grade III diarrhea, grade III-IV other toxicities. Maximum tolerable dose (MTD) was defined when 2–3 of 5–6 patients experienced DLT. Results: See table. Conclusions: In this group of colorectal cancer patients with UGT1A1 genotypes 6/6 and 6/7, we have defined (see table) the maximun tolerated dose (MTD) of Irinotecan. UGT1A1 Genotype Irinotecan dosis (mg/m2) Patients with DLT/Total patients TA6/TA6 350 0/3 425 3/8 TA6/TA7 210 0/3 250 1/6 300 2/5 No significant financial relationships to disclose.
Decreased distant recurrence and preserved local control using dose dense induction weekly paclitaxel (P) and carboplatin (C) followed by concurrent paclitaxel, carboplatin and radiotherapy (CRT) in locally advanced head and neck squamous cell cancers (HN-SCC)
Authors: A. Nadeem, S. Desai, P. Chougule, H. Wanebo, C. Ruhl, D. Joyce, J. Tarro, T. Kennedy, N. Ready
Journal: Journal of Clinical Oncology (2004)

5545 Background: Many groups have reported a higher rate of distant vs local failures after CRT for locally advanced HN-SCC. We evaluated dose dense induction chemotherapy (IT) prior to CRT to decrease distant relapse Methods: Treatment consisted of IT (P 135mg/m2, C AUC 2) for 6 weeks and a 2 week rest followed by CRT weekly (P 40mg/m2, C AUC 1) and daily RT 1.8 Gy (total dose 66–72 Gy). Inoperable patients received 8 weeks CRT. Operable patients underwent primary site biopsy after 5 weeks. Biopsy positive patients underwent surgery and post op RT. Biopsy negative received 3 more weeks of CRT Results: 38 patients enrolled 3/99–11/01(accrual closed), median age 61 years, PS 0–1. 34 evaluated for efficacy. Inevaluable:1 allergic reaction 1st dose, 3 declined treatment after consent. Major nonhematologic toxities:1 died during IT (sepsis), 1 died during CRT (cardiac event), 2 gr 3 neuropathy, and 18 gr 3–4 mucositis. Dose intensity during IT was 92% of planned doses: P (680mg/m2) and C (AUC 10.2). Median follow up is 30 months. Response for pts completing therapy IT: n=32; ORR 72% (3 complete, 20 partial, 5 stable, 1 progression, 3 unknown). CRT (n=32); 10/13 (77%) operable patients had pathologic CR upon biopsy, 2 operable patients not biopsied (1 refused, 1 died). Inoperable group (n=17); 9 CR, 5 PR, 2 SD, 1 progression. 23/32 (72%) pts are NED. Local failure/recurrence is 11/32 (34%); (2 pts with local failure are NED after salvage surgery). Distant relapse rate is 2/32 (6%), compared to 14/70 (20%) historical controls treated with CRT alone on BrUOG trials HN 53 and 67. Conclusions: Dose dense weekly IT with P/C prior to CRT has acceptable toxicity. IT did not delay CRT and had no adverse effect on locoregional control. IT followed by CRT resulted in complete responses in the majority of patients. The rate of distant metastases was decreased compared to historical controls. No significant financial relationships to disclose.