tbuckley/cabot-search huggingface dataset:
First analysis of SWOG S0221: A phase III trial comparing chemotherapy schedules in high-risk early breast cancer.
Authors: G. T. Budd, W. E. Barlow, H. C. F. Moore, T. J. Hobday, J. A. Stewart, C. Isaacs, M. Salim, J. K. Cho, K. Rinn, K. S. Albain, H. K. Chew, G. V. Burton, T. D. Moore, G. Srkalovic, B. A. McGregor, L. E. Flaherty, R. B. Livingston, D. Lew, J. Gralow, G. N. Hortobagyi
Journal: Journal of Clinical Oncology (2011)

1004 Background: AC+G (doxorubicin 24 mg/m2/week x 15, cyclophosphamide 60 mg/m2/day po, and filgrastim daily except on the days of doxorubicin administration) produced encouraging results in a SWOG Phase II trial of pre-operative chemotherapy in locally advanced breast cancer. S0221 is a SWOG-coordinated Phase III adjuvant chemotherapy intergroup trial in node-positive and high-risk node-negative operable breast cancer, which hypothesized that the AC+G regimen is superior to ddAC (doxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2 IV and pegfilgrastim q 2 weeks x 6) and that weekly paclitaxel is superior to q 2 week paclitaxel. Methods: Between December 2003 and November 2010, 2716 patients were randomized in a 2x2 factorial design to 1) AC+G vs ddAC and 2) paclitaxel 80 mg/m2/week x 12 vs paclitaxel 175 mg/m2 q 2 weeks x 6. If there was no significant interaction between the factors, the trial was powered to find a disease-free survival hazard ratio (HR) ≤ 0.82 for weekly vs q 2 week for each factor. Results: By September 8, 2010, 349 events (161 ddAC, 188 AC+G) had occurred among 2,477 patients with follow-up, prompting the first planned interim analysis at 30% of the expected events. The arms were balanced for standard prognostic factors, and a Cox model adjusting for the paclitaxel arms had a HR = 1.21 (95% CI 0.98−1.50; p=0.071) favoring ddAC. The prescribed boundary for futility was the 99.5% CI (0.90−1.64) excluding the original alternative hypothesis that HR=0.82. No boundary was crossed for the paclitaxel comparison and there was no significant interaction of the two factors. Therefore, the Data Safety and Monitoring Committee recommended stopping randomization to the AC+G arms due to futility. Analyses by nodal-, hormone-receptor-, and HER2 status found no subset in which AC+G appeared superior. S0221 has re-opened and randomizes patients to the two paclitaxel arms after only 4 cycles of ddAC. Conclusions: Accrual will continue to 3,250 patients and ancillary studies remain ongoing. We conclude that AC+G is not superior to ddAC x 6, and do not recommend AC+G for routine use. Support: NCI grants CA32102, CA38926, CA21115, CA21076, CA77597, CA25224, CA77202, CCSRI15469, and Amgen, Inc.
Hormone replacement use, age, and prognosis for women with non-small cell lung cancer
Authors: A. Robinson, M. Ayeni
Journal: Journal of Clinical Oncology (2007)

18099 Background: Lung cancer is the leading cancer cause of mortality in women. A recent report by Ganti et al, presented at ASCO, suggested that women who had been taking hormone replacement therapy (HRT) had significantly decreased survival after a lung cancer diagnosis. In addition, in women fit enough to be enrolled on randomized controlled trials in advanced lung cancer, younger women (under age 60) may have a worse prognosis than older women. The purpose of this current study was to do an institutional review on women diagnosed with lung cancer to determine whether these novel prognostic factor results could be duplicated. Methods: All female patients who were diagnosed with lung cancer between January 1999 and December 2003 were reviewed for age at diagnosis, stage, treatment, smoking history, hormonal therapy, performance status, weight loss, age at menopause, and overall survival. Patients were excluded if they had small cell lung cancer, were unknown primary, or had previous or synchronous non-lung, non-skin, cancers. Statistics were performed using Chi- Squared tests for categorical variables, while the Kaplan-Meier method and Cox-Regression models were used for univariate and multivariate analysis of overall survival. Results: Of 397 patients, the majority (68%) were stage 3 or 4. There were very few never smokers (5%). Twenty-nine percent of patients had prior HRT, with no effect on overall survival, with median survivals of 13 months in the non- HRT group and 14 months in the HRT group. The most powerful predictors of overall survival were: Stage, Performance Status, and Weight Loss. Patients aged 60–75 did as poorly as younger patients (median survival 10 months for stage 4 disease). Conclusions: Stage, performance status, and weight loss, are the most powerful predictors of survival for women with lung cancer. Patients with prior HRT use do not have inferior outcomes compared to non-HRT users. In a non-clinical trial population, patients under age 60 have similar outcomes as women aged 60 to 75. No significant financial relationships to disclose.
Costs of administration of intravenous (IV) therapies in early versus late stage breast cancer in a US population
Authors: G. B. Kruse, M. M. Amonkar, D. Skonieczny, G. L. Smith
Journal: Journal of Clinical Oncology (2007)

6588 Background: There are significant costs associated with IV administration of cancer drugs ranging from adverse events associated with the administration to the need for specialized equipment, supplies and personnel time. This study utilized a novel provider-payer contract database to compare the cost components of providing IV therapy to women with early and late stage breast cancer. Methods: Women diagnosed with breast cancer (ICD-9 code 174) between 01/01/2003 and 05/31/2006 and receiving IV monotherapy were identified from an administrative claims database of &gt;60 multi-specialty medical practices/clinics (additional ICD-9 codes 196–198 used to identify late stage breast cancer). Costs were estimated on a per IV administration visit basis using the allowable amount for a claim which closely represents the actual amount paid to providers. Published literature was used to categorize the various billable cost components. Results: 1,393 early and 828 late stage breast cancer patients receiving any of 11 IV breast cancer drugs were identified. The costs breakdown by category for all drugs and for the 2 most commonly used drugs, per IV administration visit, is presented in the table . Conclusions: Costs associated with administration of IV therapies and other visit-related services constituted more than 36% of total costs for early stage and 41% of total costs for late stage breast cancer patients. These costs represent a significant cost burden to payers. Maximization of valuable resources could be effected by increased use of effective oral therapies for treatment of breast cancer. [Table: see text] [Table: see text]
Pemetrexed (Pem) plus gemcitabine (Gem) or carboplatin (Carbo) in patients (pts) with advanced malignant mesothelioma (MPM): A randomized phase II trial, E1B03.
Authors: M. M. Millenson, J. Lee, N. H. Hanna, C. J. Langer, T. Hoang, D. L. Graham, S. H. Okuno, J. H. Schiller
Journal: Journal of Clinical Oncology (2010)

e18053 Background: Pem and cisplatin have emerged as the standard combination in the treatment of MPM; but carbo is more commonly used in the US, and gem is also active in MPM. We therefore initiated a randomized phase II trial of pem combined with either carbo or gem. Methods: Fit, treatment-naive pts (PS 0-1) with measurable MPM were randomized 1:1 to pem 500 mg/m2 IV in combination with carbo AUC 5 every three weeks (Arm A) or to pem 500 mg/m2 d1 and gem 1,000 mg/m2 IV days 1 and 8 every q 3 wks (Arm B) for up to 6 cycles. All enrolees received prophylactic B12, folic acid, and dexamethasone. Primary endpoint using either modified RECIST or mesothelioma response criteria was minimum response rate (RR) of 40%. Secondary endpoints included assessment of progression-free and overall survival (PFS and OS) and toxicities. Results: 32 pts were enrolled between 11/01/05 and 7/12/07; study was terminated due to futility. 29 pts were eligible, 16 on arm A, 13 on arm B. Median age was 71; 90% were male, 76% PS 1. RR, Median PFS and OS for arms A and B were 18.8% (95% CI 5.4%-41.7%), 4.1 mos (90% CI 1.7-6.6 mos) and 13 mos (95% CI 5.6- 21.9 mos) and 0% (90% CI 0-20.6%), 3.3 mos (95% CI 1.6-5.2 mos) and 6 mos (95% CI 3.9-14.0 mos) respectively. The most common grade ≥ 3 toxicities in arms A and B included neutropenia (19% vs 77%), anemia (19% vs 15%) and fatigue (13% vs 23%). No neutropenic fever or fatal AEs were observed. Conclusions: There is no evidence to support further investigation of combination gem and pem in the first line treatment of MPM, and little likelihood that the pem-carbo combination will prove superior to pemetrexed-cisplatin, though it may have a more tolerable safety profile. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Lilly
Ki-67, p53, and clinical outcomes of patients with triple-negative breast cancer.
Authors: Yasuyuki Nishiyama, Reiki Nishimura, Tomofumi Osako, Yasuhiro Okumura, Nobuyuki Arima
Journal: Journal of Clinical Oncology (2012)

142 Background: Triple-negative breast cancer (TNBC) tends to produce a poor prognosis because of aggressive tumor biology and lack of targeted agents. Breast cancer with a high Ki-67 value responds better to chemotherapy but is associated with lower relapse-free (RFS) and overall survival rates. The basal-like subtype overlaps with TNBC in approximately 70% to 80% of the cases, and the vast majority of basal-like subtypes have mutated p53. The aim of this study was to evaluate the clinical and prognostic significance of Ki-67 and p53 in patients with TNBC. Methods: We retrospectively reviewed 1,711 patients with pT1-3 invasive breast cancer diagnosed between 2001 and 2010. Of the 200 TNBC cases, 165 patients received adjuvant chemotherapy. Cases were classified as luminal (ER+ and/or PR+ and HER2-), HER2 disease (HER2+) and TNBC (ER-, PR- and HER2-) subtypes. Estrogen receptor (ER) and progesterone receptor (PR) positivity was defined as ≥10% positive tumor cells with nuclear staining. Ki-67 was classified into the following three groups: low (&lt;20%), intermediate (20-50%) and high (≥50%), and the p53 high group was indicated by ≥50% staining. RFS was compared according to the level of Ki-67 and p53. Results: Patients with a high Ki-67 value were frequently seen in 53% of the cases with TNBC (luminal: 6% and HER2 disease: 25%, p&lt;0.0001). The greatest proportion of patients in the low p53 group were the luminal type (luminal: 7%, HER2 disease: 49%, TNBC: 54%, p&lt;0.0001). A high Ki-67 value was not associated with poor RFS in TNBC (p=0.2734). A high p53 expression was associated with poor RFS (p=0.024). TNBC with adjuvant chemotherapy and a high p53 expression tended to produce poor RFS (p=0.0516). Conclusions: TNBC with a high Ki-67 value was not associated with poor prognosis in this study. However, p53 status could be a significant prognostic factor in TNBC patients, especially in adjuvant chemotherapy cases.
Management of cancer-related vertebral compression fracture: Comparison of treatment options: A literature meta-analysis
Authors: A. Bhargava, D. Trivedi, L. Kalva, M. Tumas, M. Hooks, J. Speth
Journal: Journal of Clinical Oncology (2009)

e20529 Objective: The objective of this review was to compare the efficacy and safety of treatment options for management of vertebral compression fractures (VCF) secondary to multiple myeloma and/or metastatic tumors based on a meta-analysis of the literature. Methods: A search was performed of published literature through November 2008. All articles reporting at least one clinical outcome were included. VAS pain scores and cement extravasation were the most common efficacy and safety outcomes reported in the included studies and were considered for analysis. The mean weighted difference in VAS scores or the effect size was calculated using the number of patients in each study as the weights. The paired t-test was used to assess significance of these differences. A 95% confidence interval (CI) was computed around these differences. The significance of difference (VAS and % cement extravasations) between different modes of treatment was assessed using a two sample t-test. Results: A total of 59 studies met the inclusion criteria and were included in the meta-analysis. The majority of the included studies (56 studies) were case series. No randomized controlled study was identified. The total sample size from the included study was 4,460 patients - 73% of patients had a diagnosis of tumor metastasis to the vertebral column; 18% had a diagnosis of multiple myeloma. Percutaneous vertebroplasty (VP) was described in 57.6% studies; balloon kyphoplasty (BKP) in 20.3%; conservative/combined (CC) therapy in 22%. Results are shown in the Table . Conclusions: This meta-analysis indicates that BKP is more effective than either VP or conservative therapy in relieving pain secondary to cancer-related VCF and that BKP is a safer intervention than VP based on the analysis of the rates of cement extravasation. [Table: see text] No significant financial relationships to disclose.
5′ Azacitidine in Combination with Valproic Acid Induces Complete Remissions in Patients with Advanced Acute Myeloid Leukaemia but Does Not Eradicate Clonal Leukaemic Stem/Progenitor Cells.
Authors: Charles Craddock, Nicolas Goardon, Mike Griffiths, James D. Cavenagh, Shamyla Siddique, Paresh Vyas
Journal: Blood (2008)
Autologous tumor-derived HSPPC-96 vs. physician’s choice (PC) in a randomized phase III trial in stage IV melanoma
Authors: J. Richards, A. Testori, E. Whitman, G. B. Mann, J. Lutzky, L. Camacho, G. Parmiani, A. Hoos, R. Gupta, P. Srivastava
Journal: Journal of Clinical Oncology (2006)

8002 Background: Vitespen (Oncophage; formerly HSPPC-96) is an autologous, tumor-derived, heat shock protein (gp96)-peptide complex vaccine that has shown signals of clinical activity in patients (pts) with metastatic melanoma, and colon and renal cancers. Methods: This phase 3 trial compares vitespen v. PC in AJCC stage IV melanoma. Pts had ECOG PS 0/1 and ≥7 g tumor tissue for vaccine production. Randomization was 2:1 favoring vitespen, and stratified by ECOG PS and AJCC substage (M1a, -b, -c). Vitespen was administered s.c. weekly for 4 weeks, then biweekly until vaccine depletion or disease progression (DP). PC treatment was any regimen including IL-2 and/or dacarbazine/temozolomide and/or tumor resection. Pts were evaluated every 3 months for 1st year, every 6 months for 2nd year, then annually until DP. Primary endpoint was overall survival (OS). OS data, based on ITT, were analyzed using 1-sided log-rank tests. Results: From Jan 2002-Sept 2004, 322 pts at 76 centers (US, Europe, Russia/Ukraine, Australia) were enrolled. 215 pts were randomized to vitespen, 107 pts to PC. Mean age was 55 y; 59% were male; ECOG was 0 in 71% of pts; 19% of pts were M1a, 24% M1b, 57% M1c. 62% of pts in vaccine arm received vitespen; median number of vaccines was 6 (range, 0–74). As of Sept 2005, 18 pts were in tumor evaluation phase, 53 in survival follow-up, 251 off-study (death, withdrew consent, lost to follow-up). Median follow-up time for vaccine and PC arms was 250 and 289 d, respectively. Estimated median survival for vaccine and PC arms was 281 and 322 d, respectively (P = .078). M1a pts in the vaccine arm survived longer than those in the PC arm (626 v. 383 d, P = .177). Survival was comparable in both arms for M1b pts (297 v. 320 d, P = .478), and longer in the PC arm for M1c pts (299 v. 226 d, P = .015). Impact of number of doses was examined using landmark analyses to correct potential biases. Pts who received ≥10 doses of vaccine survived longer than those who received PC (377 v. 478 d, P = .072). Conclusions: Vitespen confers qualitative survival benefit over PC for M1a melanoma pts. If 10 doses of vaccine can be administered, vitespen also appears to confer survival benefit over PC for M1b pts. A phase 3 trial evaluating vitespen in M1a and M1b pts is planned. [Table: see text]
Abstracts 1315 to 1481, LB6–LB15
Journal: Hepatology (2007)

Background/Aim This Phase 2b, active controlled study evaluated the efficacy and safety of albinterferon alfa-2b (alb-IFN)in IFN-naïve, CHC patients.The effects of alb-IFN on subject quality of life (QoL) and disability days were compared with those of PEG-IFNa-2a (PEG-IFN).Methods 458 patients were randomized and treated in 4 groups: PEG-IFN 180mcg Q1w or one of 3 alb-IFN arms (900mcg Q2w, 1200mcg Q2w or 1200mcg Q4w).The primary efficacy end-point was SVR.SF-36v.2 and the Hospital Anxiety and Depression Scale (HADS) were used to assess subject QoL and anxiety/depression.Subject disability days were evaluated by a number of missed work days or days with impaired activity.Missing data for patient reported outcomes were handled using LOCF (last observation carried forward).Results Based on ITT analysis, SVR rates were comparable (p=NS) across treatment groups.SVR in the 900Q2 was 58.5% and for PEG-IFN was 57.9%.Overall, QoL was similar or favorable for all albIFN arms compared to PEG-IFN at all timepoints assessed.At w12 and w24 on treatment, the 900Q2w cohort performed better in all 10 SF-36 domains relative to PEG-IFN.Statistically significant and clinically meaningful differences were observed in mental health (figure), bodily pain, vitality, and social functioning domains.Changes in mental health correlated strongly (r=0.7) with changes in HADS and by w12 post-treatment had recovered to baseline in 67% of 900Q2w subjects and 57% of PEG-IFN subjects.Subjects receiving alb-IFN 900Q2 experienced significantly fewer days of missed work: at w12 and 24, ~5% of 900Q2w subjects missed at least 7 days of work the previous month compared to ~20% for PEG-IFN.Conclusions The alb-IFN 900mcg Q2w dose was associated with the most favorable QoL and fewest missed work days while maintaining efficacy at least comparable to PEG-IFN.
Morphoproteomic depiction of constitutively activated mTOR and ERK pathways in adenocarcinoma of the large intestine: A pilot study
Authors: D. Tan, J. Yao, M. Javle, A. Law, R. Brown
Journal: Journal of Clinical Oncology (2007)

14580 Background: Preclinical studies have demonstrated a role for the mammalian target of rapamycin (mTOR) pathway in intestinal tumorigenesis. However, the mTOR and its related ERK pathway in human adenocarcinoma of the large intestine (ALI) have been little examined. Methods: To assess morphoproteomic alterations of ALI, tissue materials from three patients with ALI were analyzed in the present study. Antibody probes used included phosphorylated (p)-mTOR (Ser-2448) and one of its downstream effectors, p-p70S6K (Thr-389); bcl-2, which undergoes mTOR-dependent phosphorylative inactivation; and p-extracellular signal-regulated kinase (ERK)1/2 (Thr-202/Tyr-204), a co-activator of p-p70S6K. The intensity of the chromogenic signal and the cellular compartmentalization (plasmalemmal, cytoplasmic, and/or nuclear) were assessed and scored on a scale of 0–3+. Results: Moderate to strong (up to 2+ or 3+) expression of p-mTOR and its substrate, p-p70S6K, and p-ERK1/2 was present in all three cases. We also found plasmalemmal translocation of p-mTOR and nuclear translocation of p-p70S6K and p-ERK1/2, indicating constitutive activation of these protein analytes and their corresponding signal transduction pathways. We did not detect bcl-2 expression in any of these cases. Conclusions: Morphoproteomic analysis reveals constitutive activation of the mTOR and ERK pathways in ALI as evidenced by the collective commonalities of expression of p-mTOR, p-p70S6K, and p- ERK1/2 and the plasmalemmal translocation of p-mTOR and nuclear translocation of p-p70S6K and p-ERK1/2. The absence of bcl-2 expression in this context is noteworthy. These findings coincide with the preclinical data on the efficacy of rapamycin and a rapamycin analogue against colon cancer cell lines and xenograft models. Although preliminary, these observations of morphoproteomic alterations represent the first in primary human ALI specimens according to a review of the literature. The present pilot study offers a starting point for further studies (we are currently conducting a confirmatory study with larger series of cases) and the design of clinical trials using such small molecule inhibitors(e.g. rapamycin, RAD001) in a combinational strategy against ALI. No significant financial relationships to disclose.
Adult testicular lymphoma in the United States (1985–2004): Analysis of 3,669 cases from the National Cancer Data Base (NCDB)
Authors: S. Pingali, R. S. Go, J. D. Gundrum, L. Wright, G. Gay
Journal: Journal of Clinical Oncology (2008)

19503 Background: Because patients with testicular lymphoma are rare and generally excluded from clinical trials, data on clinical features,treatment and survival are limited. Methods: We retrospectively reviewed all cases of adult (age ≥18 years) testicular lymphoma registered with the NCDB from 1985–2004. Survival data were available only for patients diagnosed before 2001. The NCDB, a project of the American College of Surgeons Commission on Cancer, serves as a comprehensive clinical surveillance resource for all forms of cancer and captures approximately 75% of all cancer cases in the US. Results: We identified3669 cases of testicular lymphoma. This comprised 0.6% of all non-Hodgkin lymphoma. Major histological groups included diffuse large B-cell (DLBCL) (77.8%), other B-cell (21.1%), and T/NK/null cell (1.1%). Median age at diagnosis was 70 years (range, 20–101), with 34.9% under age 65. The right testis was as frequently involved as the left (46.4% v 44.2%). Bilateral testicular involvement occurred in 6.1%. Among those with complete staging work-up, the stage distribution was: I (59.1%), II (15.3%), III (6.0%), and IV (19.6%). Majority were cared for in the community(62.4%) and either had surgery plus additional treatment (59.9%) or surgery alone (23.8%). Median overall survival improved over time, 35.5, 37.6, and 49.5 months for those diagnosed in 1985–1989, 1990–1994, and 1995–2000, respectively (P= 0.01). Other significant predictors of better survival were age <65 years, non-black race, stages I/II at diagnosis, multi-modality treatment, and treatment at a non- Veterans Affairs facility. After multivariate analysis, only age, stage, race, and treatment modality remained independent predictors of survival. Conclusions: This is the largest reported clinical series of testicular lymphoma. Testicular lymphoma is rare and usually presents as early stage disease. Even prior to the introduction of rituximab, the prognosis of testicular lymphoma improved over time, perhaps due to the more frequent use of multimodality therapy. Notably, black race predicted for a worse outcome while DLBCL histology unexpectedly did not. No significant financial relationships to disclose.