tbuckley/cabot-search huggingface dataset:
Bayesian analysis of the International Adjuvant Lung Trial (IALT): Should it change practice?
Authors: R. A. Miksad, T. G. Roberts, M. Gonen, T. J. Lynch
Journal: Journal of Clinical Oncology (2004)

6038 Background: IALT (2003) demonstrated that cisplatin-based adjuvant chemotherapy (CBAC) provides a 4% absolute survival benefit at 5 years for patients with resected stages I-III non-small cell lung cancer (NSCLC). These results must be interpreted in the context of conflicting data from prior randomized trials. We used Bayesian analysis to determine if the IALT results are convincing enough to change clinical practice or if additional trials are required. Methods: We developed three curves that estimate the probabilities of survival benefit prior to IALT's results. These estimates were based on: 1) a formal survey of 18 thoracic oncology experts; 2) a 1995 meta-analysis of adjuvant chemotherapy; and 3) a ‘skeptical’ curve, which downweights prior positive trials. The primary endpoint was difference in five-year survival. Analysis using Bayes Theorem incorporated IALT results into each curve to yield updated probabilities of survival benefit. Results: Survey respondents estimated a CBAC survival benefit, prior to IALT, of 2.94% (95% CI: 1.78–4.11%); only 11% of the experts offered CBAC at that time. The table shows the probability for each level of survival benefit before and after prior estimates were updated by IALT. Each updated curve supports an overall survival benefit for CBAC in NSCLC. However, the level of benefit supported varies. The probability of at least a 3% survival advantage was 80%, 71%, and 54%, for the meta-analysis, survey, and skeptical curve, respectively. The chance of a survival decrement for CBAC was below 1% for each curve. Conclusions: The preponderance of evidence supports at least a 3% survival advantage for CBAC. It is, therefore, ethically difficult to support additional randomized trials that include an observation-only arm. Future efforts should focus on incorporating targeted agents into adjuvant regimens for NSCLC as well as selecting patients most likely to benefit. No significant financial relationships to disclose.
Utility of PET imaging in predicting the aggressiveness and histopathology of lymphoma
Authors: S. R. Chandana, S. Movva, M. Arora, T. Singh
Journal: Journal of Clinical Oncology (2007)

8085 Background: F (18)-fluorodeoxyglucose positron emission tomography (FDG-PET) is widely used in the staging and restaging of non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). Few studies have investigated whether the intensity of tumor FDG uptake, measured by standard uptake value (SUV), a semiquantitative measure, could differentiate between indolent and aggressive disease. The clinical utility of SUV in determining the aggressiveness of NHL and HD and in differentiating histopathological subtypes was investigated in the present study. Methods: FDG-PET studies and histopathology of patients with NHL and HD were evaluated retrospectively. Inclusion criteria include PET before any therapy or on relapse of the disease, no diagnosis of diabetes mellitus or other types of cancer and time interval of &lt; 90 days between PET and biopsy. After reviewing the PET scans, the SUV of biopsy site were measured by drawing regions of interest. Mean ± SD of SUV was calculated for HD and various histopathological subgroups of NHL. Results: Fifty-five patients (mean age 58.1 ± 17.2 years, 30 males, 25 females, 13 patients with HD, 42 with NHL, among which 24 with aggressive and 18 with indolent NHL) were included. The mean SUV was 9.9 ± 7.8 for aggressive NHL, 4.1 ± 2.6 for indolent NHL and 11.5 ± 7.3 for HD. Mean SUV was statistically different between aggressive and indolent NHL (p &lt; 0.001) and HD and indolent NHL (p &lt; 0.001), but not between aggressive NHL and HD (p = 0.4). The SUV for the aggressive NHL can be subdivided further as follows: anaplastic (n =3, 15.1 ± 1.7), diffuse large cell (n=19, 9.6 ± 5.3) and follicular grade III (n=2, 8.1 ± 2.2). Indolent NHL included: mantle cell (n=1, 4.3), marginal zone (n=1, 6.3), small cleaved (n=12, 4.2 ± 3.5), low grade follicular (n=4, 3.2 ± 1.4) and small lymphocytic NHL (n=1, 2.3). Conclusions: Our study suggests that FDG- PET can distinguish aggressive from indolent lymphomas. There was a considerable overlap between HD and aggressive NHL.A SUV of seven or less indicates indolent lymphoma. PET could potentially differentiate between different histopathological subgroups of lymphomas. Future studies with greater sample size are warranted. No significant financial relationships to disclose.
Evaluation of epidermal growth factor receptor (EGFR) as a predictive marker in patients with non-small-cell lung cancer (NSCLC) receiving first-line gefitinib combined with platinum-based chemotherapy
Authors: L. R. Bailey, M. Janas, K. Schmidt, N. Bindslev, M. Wolf, J. Grous, J. Askaa, R. Herbst, D. H. Johnson, G. Giaccone
Journal: Journal of Clinical Oncology (2004)

7013 Background: In two Phase III trials (INTACT 1 & 2), gefitinib (‘Iressa’, ZD1839) in combination with first-line platinum-based chemotherapy regimens failed to show benefit in terms of survival when compared with chemotherapy alone in patients (pts) with NSCLC. The primary objective of this analysis was to evaluate if EGFR staining was predictive of survival. Methods: Pretreatment tumor biopsies were assessed by immunohistochemistry for EGFR using the DakoCytomation pharmDx assay™. The percentage of tumor cells was assessed using 4 levels of intensity: no staining, 0; weak, 1+; moderate, 2+; strong, 3+; as well as the presence of complete membrane staining. 516 pts (INTACT 1/2, 219/297) with tumor samples fully evaluable for EGFR were analyzed in the per protocol population of the combined trials. The analysis was stratified by trial and performed independently for pts randomized to placebo or gefitinib. A restricted backwards elimination Cox regression analysis was conducted to identify independent EGFR factors. Variables found to be significant (p<0.1) were also tested for treatment interaction to determine if they served as predictive factors. Results: The demographics of the analysis population were representative of the overall population in each trial as were common disease characteristics. The analysis showed that two EGFR-based variables are independent strong prognostic factors for both placebo- and gefitinib-treated patients. However, no interactions with treatment (ie no value for predicting benefit of gefitinib treatment) were indicated for either of these two variables (p=0.8688 and 0.4967) or for any other EGFR-based variables. Conclusion: Given the overall trial results for INTACT 1 & 2 showing no survival benefit between gefitinib and placebo, it was highly unlikely that EGFR variables would identify a subset of pts who receive survival benefit. The data presented support this hypothesis. 'Iressa' is a trademark of the AstraZeneca group of companies 'PharmDx assay' is a trademark of DakoCytomation Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca Pharmaceuticals; DakoCytomation AstraZeneca; DakoCytomation; Genentech AstraZeneca AstraZeneca AstraZeneca Pharmaceuticals
Litigation against oncologists: Lessons to be learned
Authors: M. B. Van Scoy-Mosher
Journal: Journal of Clinical Oncology (2004)

8172 Background: Though still infrequent, litigation against oncologists nonetheless is a significant problem. Most physicians do not understand the basic issues in malpractise litigation and will benefit from an explanation of the necessary elements of such litigation; this includes the concept of a breach of the standard of care, proximate cause, and the linkage of such a breach to damages. Methods: Specific exemplary cases will be reviewed, in each of which the author participated as an expert witness. Emphasis will be placed on how such a suit might have been avoided, or its defense assisted, by the defendant oncologist. Results: There are four broad categories of allegations brought against oncologists. Category I relates to unexpectedly severe toxicity secondary to chemotherapy, or for toxicity about which the patient was not properly informed or forewarned. Category II is for treatment based on a misdiagnosis. Category III is for treatment that appears to be unduly delayed. Category IV relates to cases wherein it is claimed the diagnosis of metastatic cancer was delayed. Conclusion: There are lessons to be learned from review of such cases, such that the risk of litigation can be decreased by the practising oncologist. No significant financial relationships to disclose.
p53 expression in breast cancer is more likely to predict survival in African-American than Hispanic or white women
Authors: K. A. Dookeran, K. Ferrer, M. Sekosan, X. Gao, Y. Wang, R. De La Torre, B. Lukaszczyk, L. Diaz de Leon, G. Roman, H. A. Zaren
Journal: Journal of Clinical Oncology (2006)

10001 Background: Abnormal nuclear accumulation of p53 protein may predict poorer survival &amp; aggressive tumor biology in African-American (AA) women with breast cancer. We hypothesized that compared to Hispanics or whites, survival would be worse for AA women with p53 positive tumors. Methods: Tumors from 195 consecutive AA, 46 Hispanic &amp; 52 white women were evaluated for p53 expression with IHC, using antibody Pab1801 on paraffin embedded tissue, at the SHCC MBCCOP, in Chicago. Staining was scored on the UK Receptor Group 0–8 system with score ≥2 read as positive. Survival was computed by the Kaplan-Meier method &amp; correlated with p53 expression. Univariate analyses were done with two-sided log-rank test &amp; multivariate analysis was done with Cox proportional-hazards model. Results: There were no significant differences between racial groups regarding tumor size, grade, node status, stage, estrogen receptor (ER) status, treatment &amp; p53 expression. Hispanics were significantly younger (p=0.014). For AA, Hispanic &amp; white women respectively, p53 expression was 29.2%, 34.8% &amp; 18.8%. High grade (p=0.0001) &amp; negative ER status (p=0.006) were significantly associated with p53 expression in AA women; similar results were seen in whites (p=0.014 &amp; p=0.031 respectively), however although the trend for grade was similar, only negative ER status was significantly associated with p53 expression in Hispanics. AA women with p53 positive tumors had significantly worse survival compared to AA women with p53 negative tumors (Hazard Ratio=1.945; 95% CI=1.040–3.638; p=0.037). However, comparison of survival between races for women with p53 positive tumors (p=0.793) and also for women with p53 negative tumors (p=0.4027) was not different. Multivariate analysis demonstrated that there was no interaction (p=0.523) between p53 expression &amp; stage as predictors of poor survival in AA women. Conclusions: Analyses between racial groups demonstrated that AA, Hispanic &amp; white women with breast tumors with abnormal p53 expression had similar associations with high tumor grade, negative ER status and survival. However within racial groups, abnormal p53 expression was only able to predict significantly worse survival in AA women. This association appeared to be independent of stage. [Table: see text]
Molecular predictors for response to carboplatinum and paclitaxel (CP) chemotherapy in patients with ovarian cancer
Authors: A. Psyrri, A. Bamias, Z. Yu, S. Markakis, D. Kowalski, P. M. Weinberger, M. Harigopal, E. Efstathiou, D. L. Rimm, M. A. Dimopoulos
Journal: Journal of Clinical Oncology (2004)

5066 Backgound: The standard treatment of advanced-stage ovarian cancer includes cytoreductive surgery followed by CP chemotherapy. While this regimen is effective, emergence of resistance hinders successful outcomes. Our goal was to improve patient selection for this specific chemotherapy and develop strategies to overcome resistance by determining the molecular mechanisms associated with it. Methods: A tissue array composed of 40 advanced-stage ovarian cancer patients treated with surgery followed by CP chemotherapy has been constructed; clinical data are available. We measured protein expression levels of pro-apoptotic (p53, p27) and anti-apoptotic (c-MET, phospho-Akt) factors using conventional immunohistochemistry (IHC) and/or a novel method of in-situ quantitative analysis of protein expression. The results were analyzed with Mantel-Haenszel Chi-Square test. Results: Low p27 levels (p=0.005) and serous histology (0.016) were associated with chemosensitivity. p53, phosho-Akt and cMET did not correlate with sensitivity. Conclusions: Our results are consistent with reports implicating p27KIP1 as a mediator of adhesion-dependent drug resistance; cell-cell interactions may signal the upregulation of p27, which in turn causes growth arrest in the G1 phase of the cell cycle and resistance to apoptosis induced by anticancer agents targeting rapidly dividing cells. These results need to be confirmed; a tissue array composed of 300 advanced ovarian cancer cases treated with CP is being constructed and will be used to test this finding. No significant financial relationships to disclose.
A Phase 2 Randomized Controlled Trial of Personalized Peptide Vaccine Immunotherapy with Low-dose Dexamethasone Versus Dexamethasone Alone in Chemotherapy-naive Castration-resistant Prostate Cancer
Authors: Kazuhiro Yoshimura, Takafumi Minami, Masahiro Nozawa, Takahiro Kimura, Shin Egawa, Hiroyuki Fujimoto, Akira Yamada, Kyogo Itoh, Hirotsugu Uemura
Journal: European Urology (2016)

It is well known that the prognosis of castration-resistant prostate cancer (CRPC) is poor, and several immunotherapeutic strategies have been applied to the clinical trials. Research on immunotherapy has been of special interest for the treatment of CRPC for years.To evaluate the safety of personalized peptide vaccine (PPV) immunotherapy and its clinical outcomes.A phase 2 randomized controlled trial of PPV immunotherapy with low-dose dexamethasone versus dexamethasone alone for chemotherapy-naive CRPC began in 2008. Eligible patients (prostate-specific antigen [PSA] <10 ng/ml) were human leukocyte antigen (HLA) A02, A24, or A03 superfamily positive and had asymptomatic or minimally symptomatic CRPC. Patients were allocated (1:1) to PPV plus dexamethasone (1mg/d) or to dexamethasone (1mg/d) alone. A maximum of four HLA-matched peptides (each 3mg) was selected based on the preexisting immunoglobulin G responses against the 24 warehouse peptides and administered every 2 wk.PSA, progression-free survival (PFS), time to initiation of chemotherapy, and overall survival (OS) were analyzed using the Kaplan-Meier method, a log-rank test, and proportional hazard analysis.Overall, 37 patients received peptide vaccinations and 35 received dexamethasone alone. The primary end point was PSA PFS, which was significantly longer in the vaccination group than in the dexamethasone group (22.0 vs 7.0 mo; p=0.0076). Median OS was also significantly longer in the vaccination group (73.9 vs 34.9 mo; p=0.00084). The relatively small number of patients enrolled is the major limitation of the study.PPV immunotherapy was well tolerated and associated with longer PSA PFS and OS in men with chemotherapy-naive CRPC. A larger phase 3 study is needed to confirm our findings.We compared clinical outcomes of the treatment with personalized peptide vaccine plus dexamethasone versus dexamethasone alone. Our data provide promising evidence of clinical benefit for peptide vaccines.UMIN-CTR: 000000959.
Proportion of Adult AML Patient Population Receiving Allogeneic Stem Cell Transplantation and Long-Term Outcome: Real World Data From the Swedish National Acute Leukemia Registry.
Authors: Gunnar Juliusson, Lars Möllgård, Sören Lehmann, Åsa Rangert Derolf, Ulf Tidefelt, Dick Stockelberg, Mats L Brune, Vladimir Lazarevic, Petar Antunovic, Anders Wahlin, Martin Hoglund
Journal: Blood (2009)
The PACT trial: Interim results of a randomized trial of TNFerade biologic plus chemoradiation (CRT) compared to CRT alone in locally advanced pancreatic cancer (LAPC)
Authors: N. Senzer, A. Rosemurgy, M. Javle, T. Reid, M. C. Posner, K. J. Chang, M. Owens, M. Shirinian, J. Stephenson, J. R. Hecht
Journal: Journal of Clinical Oncology (2006)

4102 Background: TNFerade is a second-generation replication-deficient adenovector, carrying the transgene encoding human TNF-α, regulated by the stress-inducible promoter Egr-1. In a phase I trial of TNFerade + radiation in 36 patients with advanced or refractory solid tumors, a 47% objective tumor response rate was observed, including 100% complete responses in 3 stage 4 melanoma patients, with 2/3 disease-free at &gt;3.5 years. Methods: This controlled phase II trial randomizes 74 patients with newly diagnosed unresectable LAPC to 5-wks of TNFerade (4 × 10 11 pu via weekly intratumoral injection) + CRT (5-FU [200 mg/m 2 /day CIV × 5 days/wk] and 50.4 Gy radiation) or CRT alone. All patients receive maintenance gemcitabine. Endpoints: Progression-free survival, safety, radiographic tumor response, CA 19–9 and survival. Results: In dose escalation (n=50) dose-limiting toxicities occurred in 3 patients at 1 × 10 12 pu (pancreatitis in 2 and biliary obstruction), setting the MTD at 4 × 10 11 pu. Compared with the first two cohorts (n=30), the MTD (n = 11) was associated with greater locoregional control and progression-free survival, a higher rate of stable or decreasing CA 19–9, improved overall survival (median = 11.2), and a high (45%) resection rate. Accrual continues in the randomized phase of the study at 20+ centers. The most frequent adverse events in the first 16 enrolled patients have been nausea (75%), abdominal pain (63%), constipation (50%), anemia (38%), diarrhea (38%), vomiting (38%), and weight loss (38%), with no significant difference in severity or frequency between the TNFerade + CRT and CRT groups. No thromboembolic events have been reported. Serum TNF-alpha levels have remained low (peak = 45.3 pg/mL, in a CRT patient). CA 19–9 has been stable (no change &gt; 100 U/mL) or decreased in all but one CRT patient. Conclusions: These initial data indicate that TNFerade plus CRT, given as weekly intratumoral injections to patients with LAPC, is feasible and tolerable compared to CRT alone. With continued accrual, comparative tumor response and toxicity data will be available and updated. No significant financial relationships to disclose.
A phase I / II trial of docetaxel, capecitabine, and cisplatin as a first line chemotherapy for advanced gastric cancer
Authors: Y.-K. Kang, T.-W. Kim, H.-M. Chang, M.-H. Ryu, J.-H. Yook, S.-T. Oh, B.-S. Kim, J.-S. Lee
Journal: Journal of Clinical Oncology (2004)

4066 Background: Combination of capecitabine and cisplatin (XP) was active and tolerable in advanced gastric cancer (AGC). We added docetaxel (D) to XP regimen and performed a phase I / II study of DXP combination. Methods: Patients (pts) with chemotherapy-naïve inoperable AGC were eligible for this study. For the phase I study, with the fixed dose of P (60 mg/m2 D1), the doses of X (D1–14) and D (D1) were escalated as following schedule: level 1: X 1,875 mg/m2/d, D 60 mg/m2; level 2: X 2,250 mg/m2/d, D 60 mg/m2; level 3: X 2,250 mg/m2/d, D 75 mg/m2; level 4: X 2,500 mg/m2/d, D 75 mg/m2. The cycle was repeated every 3 weeks. The phase II study was planned at the dose level just below the MTD in pts with measurable disease. Results: During 1st cycle, 1 DLT (neutropenic fever) among 6 pts at dose level 2 and 2 DLTs (asthenia) among 3 pts at dose level 4 were observed. During 2nd cycle, 2 DLTs were experienced among the 6 pts at dose level 3, which made the dose level 3 as MTD and the subsequent phase II study was begun at dose level 2. After total 17 pts were treated at dose level 2, frequent need for dose reduction made further phase II study performed at dose level 1. Total 40 pts with measurable disease, treated at dose level 1 (23) and 2 (17) were evaluated for phase II portion of the study. Four pts were not evaluable for response because of follow-up loss after 1 cycle of chemotherapy. After median 6 cycles of chemotherapy, there were 4 confirmed CRs and 23 confirmed PRs, with the overall response rate of 67.5% (95% C.I.: 52.7 – 82.3) in intention-to-treat analysis. There was no difference in response rate between the two dose levels. Ten pts underwent surgical resection after clinical response with 4 – 9 cycles of chemotherapy. Four pathologic CRs were identified. With a median follow-up of 14 mo. (range 1 to 28), median time to progression was 7.7 mo. (95% C.I.: 6.9 – 8.5), and median overall survival has not been reached. Conclusions: Asthenia and neutropenia were DLTs in this DXP combination. The dose of D (60 mg/m2, D1), X (1,875 mg/m2/D, D1–14), and P (60 mg/m2, D1) was recommended for the 3 weekly DXP combination. The DXP chemotherapy was highly active and tolerable for the 1st line chemotherapy of AGC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Korea Roche
Ovarian adenocarcinoma in teenagers and young adults: A clinical challenge
Authors: N. Gercovich, S. Carnaval, F. Negro, D. Santillán, M. Abal, E. Morgenfeld, E. Rivarola, E. Gil Deza, F. G. Gercovich
Journal: Journal of Clinical Oncology (2007)

16070 Background: Ovarian cancer (OC) appears at an average age of 63, and is uncommon in younger patients (pt), with only about 5% being diagnosed below 30 years of age. The aim of this study is to analyze the onset and prognosis of ovarian adenocarcinoma (OA) in teenagers and young adults treated at the IOHM. Methods: From Oct 87 through Nov 06, 467 pt were diagnosed with OC. Twenty six pt (5,35%) were young adults or teenagers. Ten out of the 26 pt had OA, while the other histological types were as follows: 7 pt Germ cell tumors- 5 pt Borderline - 2 pt stromal tumors - 1 pt neuroendocrine - 1 pt undifferentiated. Characteristics of the Population: Median age: 22 years (range 15–29). Symptomatology: 6 pt presented pain and pelvic tumor, two pt malignant ascites, and one skin nodules. Stages: I (4 pt), III (3 pt), IV (2pt), Not registered: 1 pt. Histological Subtype: Serous: 2pt, Endometroid: 1pt, Mucinous: 4 pt. Non-specified adenocarcinoma: 3 pt; Histological Grade: 1: 4pt; 2: 2pt, 3: 3pt. Not registered: 1 pt. Results: All pt were surgically treated (optimal surgical cytoreduction: 5/ 9). All pt received first line chemotherapy based on a Platinum combination. The average follow up time was 58 months (range: 4–162). Five pt are still alive (Median Duration of Survival 78 months (range 12–162) and four of them are free of the disease (Stage I: 3pt and Stage III: 1pt). Conclusions: 1- The OA in teenagers and young adults is uncommon and only stands for 2% of the total ovarian tumors (10/467). 2- In contrast with its adult counterpart, the ascites as an initial symptom was only present in two of our cases. 3-Three out of four stage I pt and one stage III pt are still alive and disease free after 60 months. No significant financial relationships to disclose.