tbuckley/cabot-search huggingface dataset:
Improved outcome after sequential brief induction conventional chemotherapy, concurrent chemoradiation (cCRT), consolidation high-dose chemotherapy (HDCT) or further conventional chemotherapy for early stage CD56+ natural killer (NK)/T-cell lymphoma
Authors: H. Yiu, R. K. Ngan, H. Cheng, K. Wong, M. Cheung, W. Lau
Journal: Journal of Clinical Oncology (2007)

8075 Background: Nasal NK/T lymphoma is uncommon but prognosis is universally poor even in early stage disease. Chemotherapy is often added to radiation for improving outcome although its role has not been well defined. Methods: Since 1998, an intensive protocol has been introduced for pts with stage I or II disease, which consists of 3 cycles of anthracycline-based (CHOP or ProMACE-CytaBOM) chemotherapy to be followed by cCRT (50–54Gy radiotherapy with weekly cisplatin at 40mg/m 2 ) for pts with adequate renal function, and then consolidation HDCT. Cyclophosphamide, BCNU &amp; Etoposide HDCT was offered to pts &lt;60 years with adequate organ functions. Otherwise, 3 more cycles of conventional chemotherapy were given. Results: Out of the 27 pts recruited into the intensive protocol up till 2005, 23 completed cCRT &amp; 14 received HDCT. Six pts had failed either locally or systemically, among whom 2 local failures were salvaged by further local radiotherapy. Eight patients had died with 4 related to lymphoma progression, 3 due to treatment complications and 1 died of prevailing medical illness. A preceding cohort of 35 pts intended to be treated with combined sequential conventional chemotherapy and radiotherapy only (sCRT: n=35) from 1986 to 1997 was also analyzed and compared with the current cohort (cCRT: n=27). Pts in both groups had similar characteristics. The type of intended treatment was a statistically significant factor for 6-year failure-free survival (sCRT 22.9%, cCRT 65.9%; p=0.0049, log-rank test) and overall survival (sCRT 36.4%, cCRT 69.8%; p=0.05, log-rank test), so are B symptoms (present Vs absent) and stage (I Vs II). Conclusions: The intensive protocol with sequential brief induction conventional chemotherapy, cCRT, and consolidation HDCT / conventional chemotherapy in appropriate pts was feasible, leading to better outcome than the combination of sequential conventional chemotherapy and radiation alone. The relative contributions of cCRT and HDCT to the improved outcome should be further explored. No significant financial relationships to disclose.
Risk stratified analysis improves prediction of treatment (Rx) benefit over subgroup analysis: Findings from Intergroup N9741
Authors: H. K. Sanoff, M. E. Campbell, H. C. Pitot, R. M. Goldberg, D. J. Sargent
Journal: Journal of Clinical Oncology (2008)

4018 Background: Risk stratified analysis (RSA) is advocated as a better method for predicting patient (pt) specific rx benefit over subgroup analysis [Kent Haywood, JAMA 2007]. RSA uses existing risk models to explore if rx benefit differs by pt risk. We performed RSA of N9741, a phase III trial of FOLFOX, IROX, and IFL in metastatic colorectal cancer (MCRC), using the risk model of Kohne [Ann Oncol 2002]. Methods: 1,682 subjects were grouped by baseline white blood cell (WBC) count, # of metastatic sites, alkaline phosphatase (ALK), and ECOG performance score (PS). Low risk: PS 0/1 and 1 site. Intermediate risk: PS 0/1, >1 site, ALK < 300 U/L; or PS >1, WBC< 10 x 109/L and 1 site. High risk: PS 0/1, >1 site, ALK ≥ 300 U/L; or ECOG >1, >1 site; or WBC count > 10 x 109/L. WBC was estimated from absolute granulocyte count (AGC) based on AGC= -0.7 + 0.8(WBC) [Benson, Cancer 1985]. Overall survival (OS) and time to progression (TTP) were compared by risk group and PS. Cox models assessed the relative predictive utility of PS and risk group. Results: Kohne’s model was prognostic for OS. Median OS: low risk 20.7 mo, intermediate risk 17.4 mo, high risk, 9.4 mo, p < 0.001. TTP also varied by risk group: low risk 8.25 mo, intermediate risk 7.13 mo, high risk 5.4 mo, p < 0.001. Stratification by PS was similar to risk group, with median OS of PS 0=20.4 mo, PS 1=14.8 mo, and PS 2=9.1 mo. The high risk group was twice the size of PS=2 pts. FOLFOX resulted in longer OS and TTP than IFL and IROX in all risk groups. Despite a trend toward greater benefit of FOLFOX in low risk vs high risk pts, there was no rx by risk group interaction (p=0.08); rx benefit did not vary by risk group. In multivariate models, risk group provided additional prediction benefit compared to PS alone. Conclusions: The Kohne model was valid in our cohort of MCRC pts treated with modern Rx. FOLFOX was superior in all groups. RSA has utility for development of eligibility criteria and stratification factors as well as identifying population differences in cross trial comparisons. OS by risk group and treatment Risk Group Rx Arm N Median OS (95% CI) HR (95% CI) p-value LOW FOLFOX 247 27.5 (22.6, 29.9) 1 IFL 146 18.2 (15.8, 20.7) 1.68 (1.35, 2.08) <0.0001 IROX 135 19.7 (17.2, 23.3) 1.47 (1.18, 1.84) 0.0006 Intermediate FOLFOX 384 19.2 (17.9, 20.8) 1 IFL 227 13.8 (12.2, 16.4) 1.48 (1.25, 1.75) <0.0001 IROX 196 17.8 (16.1, 19.8) 1.29 (1.08, 1.55) 0.0047 High FOLFOX 60 10.7 (8.2, 12.4) 1 IFL 55 9.4 (6.3, 12.4) 1.27 (0.87, 1.85) 0.2086 IROX 49 9.1 (6.0, 12.3) 1.27 (0.87, 1.87) 0.2186 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology, sanofi-aventis Pfizer Oncology, sanofi-aventis Pfizer Oncology, sanofi-aventis
Docetaxel (DTX) and carboplatin (CP) followed by a dose-ranging study of oral capecitabine, weekly DTX, concomitant radiotherapy and surgery for the treatment of patients with stage II-III carcinoma of the esophagus
Authors: J. A. Bubis, I. Williams, K. H. Dragnev, J. E. Sutton, S. R. Gordon, B. I. Zaki, B. F. Cole, J. R. Rigas
Journal: Journal of Clinical Oncology (2004)

4049 Background: We previously reported promising phase I data using neoadjuvant weekly DTX and 5-fluorouracil (5-FU) with thoracic irradiation followed by surgery in patients with locally advanced esophageal cancer. This trial was modified in an attempt to improve the pathological complete response rate by increasing the 5-FU exposure during thoracic radiation with oral capecitabine (C). Here we report preliminary results from our dose escalation, trimodality trial. Methods: 18 patients with esophageal cancer (16 = adenocarcinoma, 2 = squamous) were consented and enrolled on this study. Patients (Pts) were staged with a CT scan and endoscopic ultrasound (EUS). Neoadjuvant therapy included DTX, 80 mg/M2, and CP, AUC 6, intravenously every three weeks for 2 cycles. Subsequently, concomitant chemoradiotherapy (CXRT) was initiated with DTX, 15 mg/M2, weekly for five doses and C (7 = 500 mg, 3 = 1000 mg, 8 = 1500 mg) orally prior to each fraction of irradiation (50.4 Gy in 28 fractions). Pts were then restaged with CT and EUS. Transhiatal esophagectomy was performed at 4–8 weeks post CXRT. Results: Patient characteristics: EUS stage, 1 = T3N0, 2 = T2N1, 15 = T3N1. Dose limiting toxicity (DLT), grade 3 dysphagia, occurred in 2 pts (1 = 300 mg, 1 = 1000 mg). No other grade 3 and no grade 4 toxicities were encountered. Only 3 pts required a feeding tube; 11 pts had weight gain over the course of therapy. Antitumor response following chemotherapy and CXRT was 78% (95% confidence interval: 52%–94%) by EUS. To date, 16 of 18 patients have had R0 resection. 2 pts had pathologic CR. Conclusions: Response rates are encouraging using this tri-modality approach. Pts have tolerated combined modality therapy well with minimal side effects, thereby allowing for weight gain without the need for a feeding tube in the majority of enrollees. Capecitabine appears to be a safe agent in this combination up to a dose of 1500 mg. Patient accrual continues at 2000 mg dose level. Funded in part by CA23108, Aventis, and Roche. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis Abbott; Amgen; Aventis; Bristol-Myers Squibb; Genentech; GlaxoSmithKline; Ortho Biotech; Ligand; Merck; Pfizer; OSI; Roche
Update of the FL2000 randomized trial combining rituximab to CHVP-Interferon in follicular lymphoma (FL) patients (pts)
Authors: C. Foussard, N. Mounier, A. Van Hoof, V. Delwail, O. Casasnovas, E. Deconinck, H. Tilly, O. Fitoussi, R. Gressin, G. Salles, None Gela-Goelams
Journal: Journal of Clinical Oncology (2006)

7508 Background: The GELA-GOELAMS FL2000 trial investigated the role of rituximab in the first line treatment of FL pts. Methods: This prospective randomized study compared the CHVP regimen (12 courses) +18 months α2b-IFN (CHVP-I) to 6 CHVP courses combined with 6 rituximab infusions + 18 months IFN (R-CHVP-I). The primary endpoint was event-free survival (EFS). Inclusion criteria consisted in untreated stage II-IV FL pts; 18–75 years old; with a high tumor burden defined by at least one of the following criteria: B symptoms, ECOG PS&gt;1, LDH&gt;normal value, β2-microglobulin ≥3 mg/L, largest tumor ≥7 cm, 3 distinct nodes ≥3 cm, serous effusion, compression or symptomatic spleen enlargement. Results: From 05/00 until 05/02, 358 eligible pts were randomized (CHVP-I 183 pts and R-CHVP-I 175 pts) with the following characteristics: M/F = 1; median age = 60 years [25–75]; ECOG &gt; 1 = 8%; B symptoms = 27%; AA stage &gt; II = 87%; bone marrow involvement = 58%; β2-m ≥3 mg/L = 31%; LDH &gt; N = 37%; Hb &lt;12 g/dL = 18%; FLIPI score ≥3 in 57% of the pts. The first analysis [ASH 2004] showed a significant better treatment response in R-CHVP-I as compared to CHVP-I and a improvement of event free survival (EFS) in the R-CHVP-I arm (Log-Rang, P = .003). As initially planned, a second analysis on all pts has now been performed with a median follow-up of 3½ years, all pts with data &gt;01/01/05. The median EFS for the whole population has not yet been reached. In the CHVP-I arm, median EFS was 3 years and 46% of the pts are event-free at 42 months (mo.). In contrast, the median has not been reached in the R-CHVP-I arm and the EFS is 67% at 42 mo. (P &lt; .0001). This improvement in EFS was found both in the 150 pts with a low or intermediate FLIPI score (P = .019) and in those (n = 201) with a high score (P = .0005). When considering the 230 pts responders at the end of 18 mo. of therapy, 42 mo. EFS is 62% in CHVP-I arm versus 81% in R-CHVP-I arm (P = .002). Finally, the overall survival at 42 mo. of patients in the CHVP-I arm is of 84% versus to 91% in the R-CHVP-I arm (P = .029) with a reduction of death risk by approximately 2 (RR = 0.55). Conclusions: These results demonstrate that rituximab combined with CHVP-I has a durable benefit, in all FLIPI risk groups, allows to reduce the duration of chemotherapy and improves overall survival in high-tumor burden FL pts. [Table: see text]
Thymidine phosphorylase and cycloxygenase-2 expression in malignant melanoma.
Authors: A. Minisini, G. Pascoletti, P. Driol, C. Di Loreto, D. Intersimone, C. Scott, F. Valent, R. Spizzo, G. Fasola, F. Puglisi
Journal: Journal of Clinical Oncology (2010)

e19014 Background: Cyclooxygenase-2 (COX-2) protein expression has been described in melanoma and it seems to be associated with tumor progression and angiogenesis. Thymidine phosphorylase (TP) is a proangiogenic factor overexpressed in several human malignancies; it is also involved in the multistep process that converts the prodrug capecitabine into 5-fluorouracile. Both enzymes could be induced by several factors and could represent potential target for anticancer treatments. The aim of the study was to evaluate COX-2 and TP expression in a cohort of primary malignant melanomas and to investigate the correlation between these enzymes and known prognostic factors. Methods: Immunoistochemical TP and COX-2 expression was evaluated in 35 consecutive paraffin-embedded samples of cutaneous melanoma diagnosed between 1999 and 2003. Pathologic features were reviewed by expert pathologists. Clinical data were retrieved from medical charts. TP and COX-2 mRNA expression and protein expression was evaluated in melanoma cell lines through RT-PCR and Western Blot. Results: TP and COX-2 were highly expressed in 11 and 11 cases, respectively. High TP expression was associated with ≤ 1 mm melanoma (p = 0.0005) and Clark levels I-III (p = 0.017). High COX-2 expression was significantly associated with decreased disease free survival in multivariate analyses (p= 0.029). No significant association between these two biomarkers and other classical prognostic features was evident; a marginal association between COX-2 expression and mitotic rate > 0/mm2 was evident (p = 0.06). TP expression in melanoma cell lines was low; conversely, COX-2 was differently expressed among cell lines. Conclusions: The present study showed an interesting association betweenTP expression and thin malignant melanoma. In addition, COX-2 expression resulted to be associated with worse outcome. Further molecular characterizations of this series of melanoma is ongoing. The potential role of TP and COX-2 as therapeutic targets in melanoma deserves further investigations. No significant financial relationships to disclose.
Emotional responses of oncologists when disclosing prognostic information to patients with terminal disease: Results of qualitative data from a mailed survey to ASCO members
Authors: J. A. Wallace, F. J. Hlubocky, C. K. Daugherty
Journal: Journal of Clinical Oncology (2006)

8520 Background: Prior studies describe physician reluctance to reveal prognostic information to advanced cancer patients (acp), but little data exists describing their actual disclosure practices. Methods: A mailed survey was conducted to assess medical oncologists’ (MOs) self-reported behaviors, beliefs, and attitudes regarding prognostic conversations with terminally ill acp. Following letter pre-notification, surveys were mailed to a systematic sample of 1,222 MOs with U.S. addresses listed in the 2004 ASCO Membership Directory. Surveys contained a $25 gift card. The survey included qualitative questions eliciting emotional responses when communicating prognostic information to acp. Results: 729 surveys were completed and returned (60% response rate) with 654 providing qualitative responses (90%). The median age was 51 (range, 34–80) with male predominance (80%). Practice representation was: 56% (private), 23% (academic-based) and 20% (other active practice). MOs most commonly (47%) expressed negative emotions including sadness, pain, depression, heartache, feelings of loss, guilt, anxiety, stress, and finally discomfort with how their patient might react. They reported these conversations as unhappy, unpleasant, frustrating, and bothersome. They also described them as difficult, hard, exhausting and/or draining. 31% of MOs reported empathy, sympathy, compassion, caring, supportiveness, comfort, or being calm during prognostic disclosure. 14% reported positive feelings including optimism, hope, helpfulness, gratification, reward, or relief. 11% related emotional objectivity, detachment, control, or neutrality. Finally, MOs responses listed younger acp age as being a determinant of negative emotions. Conclusions: Negative emotions are more commonly described by MOs when asked to discuss their feelings toward prognostic disclosure. A lesser proportion described objectivity or a lack of emotion. Some related positive emotions. This qualitative data provides a greater explanation for MOs reluctance to disclose prognostic information. No significant financial relationships to disclose.
Impact of BRCA mutation status on the clinical phenotype and survival of hereditary breast cancer
Authors: M. Kiechle, C. Engel, R. Schmutzler
Journal: Journal of Clinical Oncology (2008)

22037 Background: In a multidisciplinary program supported by the German Cancer Aid in 1996–2006 a total of 3.408 women with a family history for breast and/or ovarian cancer were genetically counselled and tested for BRCA-1 and BRCA-2 mutations. Methods: The mutations were detected using DHPLC and direct sequencing. The family history of breast and/or ovarian cancer was proven by collecting medical reports of family members. The statistical analysis was done using standard procedures (Kaplan-Meier-analysis, t-test, chi-square-test). Results: Among the women with breast cancer 566 showed a deleterious BRCA1 and 313 a BRCA2 mutation. Four women were found to have mutations in both genes and 2.525 were BRCA-1/2 negative. In accordance with the literature we found the phenotype “hormone receptor negative and grade 3” as well as the medullary subtype significantly more often in BRCA1 associated breast cancers (74% vs. 24%, 63% vs. 42% and 10% vs. 5%). The median age of onset was significantly lower in BRCA1 mutation carriers (38 yrs) compared to BRCA2 mutation carriers (45 yrs) and women tested negative for BRCA1 and BRCA2 mutations (46 yrs) as well as sporadic breast cancer cases within these families (52 yrs). The median age of the 4 women with mutations in both genes was even lower (median age 33.5 yrs). Although BRCA2 associated breast carcinomas presented in more advanced stages (N+ in 44% [118/257] compared to BRCA-1 positive in 31% [166/519], p<0.01) there was no difference in overall survival between BRCA1 and BRCA2 mutation carriers. However, BRCA1 and BRCA2 negative cases showed a significantly better survival rate compared to the women with mutations (p<0.0001). Women from families with early onset breast cancer (<35 yrs) or bilateral breast cancer (<40 yrs) had a significantly better survival (p<0.0001) than women from families with a later age of onset. Conclusions: The BRCA mutation status has a significant impact on the clinical phenotype of hereditary breast cancer which is important for the clinical management, counselling and prevention. No significant financial relationships to disclose.
Characterization of comorbidities, functional status, and symptoms in patients 75–89 years of age at a cancer center
Authors: B. Saraiya, C. Bellomo, M. Gordon, S. Hudson, P. Ohman-Strickland, E. Poplin
Journal: Journal of Clinical Oncology (2008)

20677 Background: Elderly cancer patients (age > 65) have increased comorbid conditions, declining functional status and increased illness burden. Methods: Medical records for elderly patients, aged 75 to 89, seen in the medical oncology clinics of the Cancer Institute of New Jersey (CINJ) between July 2006 and June 2007 were reviewed (N=177). As part of the chart, patients complete a health history form (HHF) that documents their medical and social histories, health related quality of life, fatigue, anxiety, depression and distress. Data were abstracted by one investigator using a scannable data entry form created using Teleform 9.1 software. Data were aggregated and analyzed using SAS statistical software. Results: Of the 177 identified patients, 91 patients; either did not keep their appointment, did not complete the HHF forms or did not have charts available for analysis. The remaining 86 patient charts were analyzed and the characteristics are as below. Of note, 37% reported difficulty with at least one of the IADLs. On the Hospital Anxiety and Depression Scale, 23% scored borderline abnormal and 7% abnormal for depression and 12% scored borderline abnormal and 14% abnormal for anxiety. Conclusions: Patients analyzed in this study were older than other studies. The comorbidity and use of concomitant medications characterize our CINJ elderly patients is similar to other published data. Our patients reported high levels of fatigue, anxiety and depression. Age 75-79 45% 80-84 35% 85-89 20% Sex (M, F) 60%, 40% Median co-morbidities 2 (0-8) Median pill burden 7 (0-14) IADL compromise 37% Performance Status 1 (0-4) Symptoms Fatigue score on visual analog scale 32% moderate 32% severe HADS Depression score (range 0-21) 23% with 8-10 (borderline abnormal) 8% with >10 (abnormal) HADS Anxiety score (range 0-21) 12% with 8–10 (borderline abnormal) 14% with >10 (abnormal) No significant financial relationships to disclose.
Impact of Severity of Aortic Valve Stenosis on Effect of Intensive Lipid-Lowering Therapy: The SEAS Study
Authors: Eva Gerdts, Anne B. Rossebo, Terje R. Pedersen, Kurt Boman, John B. Chambers, Kenneth Egstrup, Christa Gohlke-Baerwolf, Ingar M. Holme, Antero Kesaeniemi, Christoph A. Nienaber, Simon Ray, Terje Skjaerpe, Kristian Wachtell, Ronnie Willenheimer
Journal: Journal of the American College of Cardiology (2009)
Endogenous knock-down of survival genes improves chemotherapeutic response in a T-ALL cell line
Authors: D. Morrison, N. Moskowitz, D. Bhojwani, H. Lee, B. Patel, T. Horton, E. Raetz, W. Carroll
Journal: Journal of Clinical Oncology (2007)

9522 Background: New targets for more effective, less toxic therapeutic approaches to childhood acute lymphoblastic leukemia (ALL) can be developed by discovering pathways unique to the blast. Using microarray technology, we identified potential target genes that are up-regulated at relapse compared to diagnosis (Blood 2006;108:711–7). Two genes, survivin and securin, were selected for analysis because they are involved in cell cycle regulation, apoptosis and cellular transformation. We hypothesized that decreasing endogenous expression of these genes would increase apoptosis and sensitize cells to chemotherapy. Methods: Short hairpin RNA constructs (shRNA) targeting both transcripts and a control shRNA were engineered. LSN2181295 (sodium salt of LY2181308), an antisense molecule targeting survivin developed by Eli Lilly and its mismatch control (LSN2293329) were also tested. The T- ALL cell line Molt4 was transiently transfected with shRNA constructs or antisense oligos. Western blot and qRT-PCR were performed to determine the time course of target knock-down while apoptosis was assessed by annexin-V labeling. Following transfection, cells were also treated with varying doses of etoposide and doxorubicin for 24 hrs prior to FACS analysis. Results: The survivin and securin shRNAs blocked endogenous gene expression by 80–90%, with maximal effect achieved at 48 hrs. Transfection of Molt4 cells with survivin and securin shRNAs induced ∼13% and 35% apoptosis, respectively, as compared to a control shRNA. When used in combination with chemotherapeutic agents, the shRNA constructs potentiated the effect of both doxorubicin and etoposide at low dosages (≤100 nM and ≤0.4 uM respectively, p values &lt;0.01). The antisense survivin drug had a similar effect as the survivin shRNA and also potentiated the effect of vincristine. Conclusion: Targeting levels of survivin and securin in conjunction with standard chemotherapy maximizes leukemia cell kill and effectively lowers the amount of chemotherapy needed to achieve cell death. Such an approach may improve overall survival for patients at relapse and could also lead to the delivery of effective chemotherapy at less toxic doses. No significant financial relationships to disclose.