tbuckley/cabot-search huggingface dataset:
Gene expression profiling (GEP) of cd 138-purified plasma cells (pc) in previously treated multiple myeloma (PTMM): Validating prognostic models developed in newly diagnosed MM (NDMM)
Authors: Y. Alsayed, J. Haessler, B. Barlogie, J. Crowley, J. Shaughnessy
Journal: Journal of Clinical Oncology (2009)

8598 Background: We have previously reported on the strong discriminatory power in NDMM of GEP-derived 70-gene risk in CD138-purified plasma-cells developed in 351 patients enrolled in TT2 and validated in 441 patients enrolled in two TT3 trials and in PTMM treated with single agent high-dose dexamethasone or bortezomib. Here we report on the overall survival outcomes in 137 patients with PTMM. Methods: Treatment regimens included further autotransplantation and novel agent combinations. The purpose of the investigation was to determine whether PTMM OS was also governed by GEP features, such as high-risk (HR) score, proliferation score (PS), proliferation (PR) molecular subgroup, gain/amplification of chromosome 1q (amp1q) and deletion of the short arm (del1p) and TP53 deletion. Results: Compared with NDMM, PTMM was characterized by greater proportions with HR (32% v 16%, p&lt;0.001), PS (20% v 10%, p=0.002) and PR (24% v 11%, p &lt; 0.001); no difference was observed for TP53 deletion (21% v 30%, p=0.11); amp1q/del1p was more common in PTMM (17% v 9%, p=0.01). OS was 60% at 8yr in NDMM compared to a median of only 2.4yr in PTMM. According to HR, 4-yr OS estimates were 80% for LR v 37% for HR in NDMM (p&lt;0.0001) and 52% for LR v 24% for HR in PTMM (p&lt;0.01). On multivariate analysis of both standard prognostic factors and GEP HR, OS in PTMM was adversely affected by HR status (HR=2.00, p=0.047) and albumin &lt;3.5g/dL (HR=2.66, P=0.013), accounting for a cumulative R2 value of 20%. Conclusions: GEP-derived high-risk features are more prevalent in PTMM relative to NDMM in terms of HR, PS, PR and amp1q/del1p status. As in NDMM, HR status confers poor OS in PTMM. Consistent with serial sampling where LR to HR transformation routinely occurs, these data support the concept that HR in PTMM is derived from clonal evolution. Treatment strategies that presume the existence of underlying HR cells even in LR disease, should be pursued. [Table: see text]
Breast cancer screening in 10.000 women of an underserved population in South Brazil: The NMAMAPOA cohort
Authors: M. Caleffi, P. Ashton-Prolla, B. Weber, J. M. Zignani, E. C. Dias, L. P. Antunes, A. Bedin Junior, E. Lisboa, M. Graudenz, P. R. Pohlmann, D. Duarte Filho
Journal: Journal of Clinical Oncology (2005)

1020 Background: Porto Alegre city has the highest increased rate of breast cancer incidence and mortality in the last 20 years in Brazil. It is the main cause of death among 20–49y-o women. Collaboration among public and private institutions to attend underserved communities might help to determine risk factors and to control the disease. Methods: NMAMAPOA cohort was launched in 2004, to follow 10,000 women (>14y-old) for 10 years. When breast complains and/or physical findings are present, patient is considered symptomatic and referred to diagnosis/treatment. Asymptomatic patients within 40–69y of age are selected for annual mammography screening. Translational research is planned. Results: So far 2,256 women were enrolled over a 7 month period, 1,598 (70.8%) are considered asymptomatic and 1,000 (44.3%) are asymptomatic within 40–69y of age, being subject of the present analysis. Demography: median age 51y-o, menarche age 7–20 (13y-o), no. babies 0–16 (3.6), menopause 50%, age at menopause 23–60 (47y-o), no familial breast cancer risk 919 (91.9%), BMI≥30 51.9%. Hormonal replacement therapy was ever used by 8% of asymptomatic women, and 29.7% are smokers. BI-RADS I-II findings were present in 98% of women and 85% had breast density <50%. Five biopsies were performed, with 4 atypical hyperplasia and 1 breast cancer (T1micN0M0). Conclusions: So far demographics do not explain the increased incidence of breast cancer in Porto Alegre. Breast density and BMI may be different from American and European populations. If confirmed, this finding might have influence in the screening results and local policies. Diagnostic, therapeutic and biological issues must be validated for local population. Environmental aspects are also being included in our research. Collaboration among private, public and NGO institutions to carry on a cohort in the South of Brazil is feasible and this can be a partnership model to be used in countries with limited resources to help to control breast cancer mortality. No significant financial relationships to disclose.
Development of a PD-L1 companion diagnostic assay for treatment with MEDI4736 in NSCLC and SCCHN patients.
Authors: Marlon Rebelatto, Amita Mistry, Costi Sabalos, Jill Walker, Anita Midha, Keith Steele, Paul B. Robbins, Xia Li, Li Shi, John A. Blake-Haskins, Ramy A. Ibrahim, Laura Richman
Journal: Journal of Clinical Oncology (2015)

8033 Background: A high quality PD-L1 companion diagnostic may help predict which patients are more likely to respond to PD-1/PD-L1 antibody-based therapy. Here we describe a PD-L1 immunohistochemical (IHC) diagnostic test developed by Ventana Medical Systems for use with MEDI4736. Methods: An anti-human PD-L1 rabbit monoclonal antibody (SP263) was optimized for use with Ventana OptiView DAB IHC Detection Kit on the automated BenchMark ULTRA platform. The PD-L1 IHC assay was validated for use in formalin-fixed, paraffin-embedded samples of NSCLC and SCCHN in a series of studies addressing sensitivity, specificity, robustness, and precision. MEDI4736 is a human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80 with high affinity and selectivity. A subset of clinical trial samples from a Phase 1/2 study of MEDI4736 (NCT01693562) was analyzed to determine optimal cut-off for enriching response to MEDI4736. Inter-reader precision was established by 3 pathologists who evaluated 81 NSCLC and 100 SCCHN samples across the range of expression levels. Results: The Ventana PD-L1 IHC (SP263) assay met all pre-defined acceptance criteria. The scoring algorithm was defined using statistical analysis of clinical response data and PD-L1 staining parameters observed in a set of NCT01693562 clinical trial samples. Samples of both cancer types are considered test positive when the membrane of ≥ 25% of tumor cells stain for PD-L1 at any intensity. Inter-reader precision in determining PD-L1 status resulted in an overall percentage agreement of 97% and 92% for NSCLC and SCCHN, respectively. For both NSCLC and SCCHN, PD-L1+ patients identified by the scoring algorithm had a higher response rate than PD-L1- patients. Conclusions: These results highlight the robustness and reproducibility of the PD-L1 IHC (SP263) assay in a clinical setting. In NSCLC and SCCHN patients treated with MEDI4736, PD-L1+ patients identified by the scoring algorithm had a higher response rate than PD-L1- patients. The clinical utility of the PD-L1 diagnostic assay will be further validated in a prospective manner using additional patients in this study and in other MEDI4736 studies. Clinical trial information: NCT01693562.
Factors predicting time-to-progression (TTP) and overall survival (OS) in patients with unresectable hepatocellular carcinoma (uHCC) treated by combination gemcitabine (G) and pegylated liposomal doxorubicin (PLD) chemotherapy.
Authors: G. Lombardi, D. Pastorelli, F. Zustovich, M. Farina, L. Furini, A. Cappetta, V. Zagonel
Journal: Journal of Clinical Oncology (2010)

e14618 Background: The aim of this study was to identify factors that could predict TTP and OS for patients with uHCC treated by combination G and PLD chemotherapy. G was administered before PLD because G induces an increase of topoisomerase II expression, and a subsequent anti-topoisomerase II drug (PLD) causes a more relevant cytotoxic effect. Methods: We examined 41 consecutive patients with uHCC treated from November 2003 to May 2008, in a prospective study. All patients underwent gemcitabine 1,000 mg/m2 on day 1 and 8, PLD 30 mg/m2 on day 1, once every 4 weeks up to a maximum of eigth cycles. Univariate and multivariate analyses of patient and disease characteristics were used to identify factors predicting TTP and OS. Results: The median TTP was 5.8 months (95% CI 2.6-8.9), the median OS was 22.5 months (95% CI 4.6-40.3). According to univariate analysis, the following variables were related to a longer TTP: good performance status (PS) (p = 0.004), Child-Pugh A (p < 0.001), earlier stage disease (Okuda stage, p < 0.001), AFP < 400 ng/mL (p = 0.04); PS (p = 0.04) and Okuda staging (p < 0.001) were found to be independent predictors for TTP on multivariate analysis. On univariate analysis: good PS (p = 0.003), Child-Pugh A (p = 0.03), earlier stage disease (Okuda stage, p < 0.001), previous hepatic resection (p = 0.04), AFP < 400 ng/mL were related to OS; good PS, earlier stage disease and AFP < 400 ng/mL were associated with a longer OS on multivariate analysis. Among patients with elevated serum AFP (> 400 ng/mL) before the treatment, a decrease in AFP of more than 20% after two cycles of chemotherapy was independent favourable predictor for TTP (p < 0.001) and OS (p = 0.02). Conclusions: Patients with uHCC who have a good PS and earlier stage disease have a better chance of prolonged TTP; because of the greater probability of survival, patients with good PS, earlier stage disease and AFP<400ng/ml might be good candidates for G and PLD chemotherapy. AFP response is an indipendent predictor for TTP and OS. This treatment should be tested in combination with targeted agents such as sorafenib, erlotinib and bevacizumab. No significant financial relationships to disclose.
A pilot study of preoperative, single-dose ipilimumab (Ipi) and/or cryoablation (Cryo) in women (pts) with early stage/resectable breast cancer (ESBC).
Authors: Adi Diab, Stephen Barnett Solomon, Virgilio Sacchini, Christopher Comstock, Majid Maybody, Jeremy C. Durack, Janice S. Sung, Brian Blum, Deirdre A. Neville, Alan Kotin, Jianda Yuan, Sujata Patil, Elizabeth Ann Morris, Edi Brogi, Monica Morrow, Jedd D. Wolchok, Clifford Hudis, James Allison, Larry Norton, Heather L. McArthur
Journal: Journal of Clinical Oncology (2013)

TPS3120 Background: Intratumoral cryo combined with immune modulation generates a potent systemic anti-tumor immune response that might improve recurrence-free survival in ESBC. Cryo-mediated tumor destruction results in necrosis and immunogenic cell death which exposes dendritic cells (DC) to sufficient quantities of tumor antigens and inflammatory cytokines to induce their maturation and activation and elicit tumor specific T cell responses. To further amplify this immune response we use ipi, a human monoclonal antibody that blocks cytotoxic T lymphocyte antigen-4 (CTLA4). In preclinical murine models, the combination of cryo with CTLA4 blockade successfully mediates rejection of metastatic prostate cancer lesions and prevents growth of secondary tumors. We therefore hypothesize that this strategy could confer long-term immunity for pts with ESBC. In this study, we evaluate the safety of pre-op cryo and/or immune modulation with single dose ipi (at 10 mg/kg) in pts with ESBC. Methods: Pts are sequentially assigned to receive pre-op: cryo alone (Group A), ipi alone (B), or ipi with cryo (C). Cryo is administered 7-10 d prior to surgery. Ipi is administered 8-15 d prior to surgery (1-5 d prior to cryo). If at least 5/6 pts in each group proceed with surgery without delay, the regimen will be considered safe/tolerable.Primary aim: To evaluate the safety of pre-op cryo and/or ipi (10mg/kg) in pts with ESBC.Seconday aims: To characterize pre- and post-intervention radiographic and immunological (peripheral blood and tumor tissue) correlates. Eligibility: Pts ≥18y of age with operable ≥1.5 cm invasive ESBC, no history of autoimmune disease and planned mastectomy. Study status: As of January 25, 2013 7/7 pts were enrolled to Group A (expanded after 1 pt had suspected incomplete cryo) and 5/6 pts were enrolled to Group B. Enrollment to Group C will open when the pts in Group B meet the safety endpoint 30 d (+/-10 d) after surgery. Toxicity evaluation continues for 12 wks after ipi administration for Groups B and C. Clinical trial information: NCT01502592.
Phase I pharmacokinetic trial of docetaxel and thalidomide: A regimen based on anti-angiogenic therapeutic principles
Authors: M. M. Cooney, X. Li, R. J. McPeak, S. Ingalls, S. Krishnamurthi, J. Brell, A. Dowlati, B. Overmoyer, C. Hoppel, S. C. Remick
Journal: Journal of Clinical Oncology (2004)

3135 Background: Preclinical models suggest that chronic, low-dose administration of anticancer therapy (cytotoxic agent and an angiogenesis inhibitor) may result in prolonged periods of freedom from progression (FFP) and tumor regression. This outcome may derive from continuous drug exposure and more pronounced anti-angiogenic rather than cytotoxic effects. Methods: Patients (pts) with advanced cancer for whom there is no curative or meaningful palliative therapy are eligible and enrolled in cohorts of 3. Pts are treated with a weekly dose of docetaxel (IV) with thalidomide (PO) given every 12 hours for 84 days (12 weeks) of continuous therapy. Since we sought to pilot a metronomic schedule over 12 weeks dose-limiting toxicity (DLT) was defined as ≥ grade 2 non-hematologic or ≥ grade 3 hematologic. Plasma concentrations of both drugs were determined by HPLC / MS-MS and pts were observed for response. Results: Sixteen pts have been enrolled; 5 are not evaluable [docetaxel hypersensitivity not considered DLT (3 pts) and 2 pts withdrew before 12 weeks]. All pts received thalidomide 100 mg bid. Docetaxel was escalated from 10, 20, 25, and 30 mg/m2 in 3, 3, 3, and 2 pts respectively. A total of 17 cycles have been completed. A single DLT (grade 3 fatigue) occurred at 30 mg/m2. There has been no myelosuppression. There has been 1 PR (SCLC), and 4 pts with FFP of >115 (prostate), 182 (papillary thyroid), >230 (prostate), and 321 days (melanoma). Measured trough plasma thalidomide concentrations of 466 ng/ml (range 344–682) have been achieved. Docetaxel plasma concentrations are consistent with previous reports of weekly schedules. Conclusions: The 12-week metronomic schedule of this regimen is feasible with a very acceptable safety profile. Clinical activity and prolonged FFP have been observed in a highly refractory population early in this study. (This trial is supported in part by the NIH grant MO1 RR00080, Aventis Oncology and Celgene.) No significant financial relationships to disclose.
Changes in serum P1NP, BAP, CTX-1, and YKL-40 following hormonal treatment for metastatic prostate carcinima are related to survival
Authors: K. Brasso, P. Iversen, J. Johansen, B. Teisner, P. Garnro, P. Pri Ce, I. J. Christensen
Journal: Journal of Clinical Oncology (2006)

20002 Background: Previously it has been demonstrated that elevated P1NP, BAP, CTX-1, and YKL-40 levels at the time of diagnosis in patients with metastatic prostatic carcinoma were associated with survival. This study presents a follow-up to evaluated the prognostic value of thes biomarkers in a time-dependent analysis. Methods: Serum P1NP, BAP, CTX-1, and YKL-40 were determined in 106 patients with newly diagnozed metastatic prostatic carcinoma following start of either total androgen ablation or parenteral estrogen theraphy. Results: After 6 months of treatment significant decreases in P1NP, BAP, and YKL-40 were found. Univariate Cox analysis demonstrated that 6 month levels of P1NP, BAP, and CTX-1 were significantly associated with survival. In a multivatiate analysis using tumormarker levels at 6 months after start of treatment demonstrated that Soloway score (HR=3.9), WHO grade (HR=3.9), and P1NP (HR=2.2) all were significant predictors of survival. When using the biomarkers mentioned above as time-dependent co-variates in univariate COX regression analysis it could be shown that increasing levels og P1NP, BAP, and YKL-40 alle were significant predictors of early death. Conclusions: Serial monitoring of serum P1NP, BAP, CTX-1, and YKL-40 in patients with metastatic prostatic carcinoma during hormonal treatment provide information on prognosis. No significant financial relationships to disclose.
Providing audiotapes of primary adjuvant treatment consultations to men with prostate cancer: Impact on recall, mood, satisfaction, and quality of life
Authors: T. Hack, T. Pickles, B. Bultz, D. Ruether, L. Degner
Journal: Journal of Clinical Oncology (2004)

8009 Background: Previously we reported on the benefits of providing audiotapes of primary adjuvant treatment consultations to women with newly diagnosed breast cancer (Hack et al; Proc ASCO 2001). The purpose of this multi-site, randomized controlled trial was to use similar methods to examine the efficacy of providing men with prostate cancer with an audiotape of their primary adjuvant treatment consultation. Methods: A total of 429 men and 15 oncologists from cancer centres in three Canadian cities participated. The men were block randomized to 1 of 4 consultation groups: 1. Standard Care Control Group - Consultation not audiotaped (n=113); 2. Patient not given audiotape (n=98); 3. Patient given audiotape (n=120); and 4. Patient offered choice of receiving the audiotape (n=94 accepted tape, n=4 declined tape). Patients completed the Decisional Role Preferences Scale (Degner) before and after the consultation, a measure of communication satisfaction post-consultation, and measures of decisional role, audiotape use, information recall, communication satisfaction, mood disturbance (Profile of Mood States), and prostate cancer-specific quality of life (FACT-P) at 3 months post-consultation. A feedback questionnaire was mailed to all participating oncologists. Results: Analyses of covariance showed that patients who received the consultation audiotape reported having had significantly more discussion about treatment side effects (p<.01), treatment alternatives (p<.05), and treatment and disease information in general (p<.05) than patients who did not receive the audiotape. Patients rated the audiotape intervention positively, with an average score of 83.0 out of 100. Fifty-six percent of oncologists stated that most, if not all, patients should be provided with an audiotape of their primary adjuvant treatment consultations. Conclusions: Audiotapes of primary adjuvant treatment consultations are rated beneficial by prostate cancer patients and their oncologists, and aid patients by facilitating perception of being informed of treatment alternatives and treatment side effects. No significant financial relationships to disclose.
A phase II trial of calcitrol and naproxen in recurrent prostate cancer
Authors: S. Srinivas, L. C. Harshman, D. R. Feldman
Journal: Journal of Clinical Oncology (2008)

16103 Background: Although commonly used as second-line treatment for patients with progressing prostate cancer, hormonal therapy is associated with unpleasant side effects, and has not unequivocally been shown to prolong survival. To this date, in vitro and in vivo studies, as well as early phase clinical trials, have shown a promising role for both calcitriol and nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of prostate cancer. Because calcitriol and NSAIDs interfere with PG pathways by different mechanisms, there is reason to believe that their combined effects to inhibit PG action may be synergistic and this was in fact demonstrated in cultured human prostate cancer cells. We combined calcitriol and naproxen (a non-selective NSAID) to delay the growth and progression of early recurrent prostate cancer. Methods: Patients with biochemical relapse after local therapy for prostate cancer were treated with a very large dose of calcitriol (DN101) (45 micrograms/once per week) and naproxen (400 mg bid) for one year. Patients were followed with serum PSA levels as well as imaging studies. Progressive disease was defined as a decrease in PSA doubling time (PSADT) from baseline, or initiation of hormonal therapy, and/or formation of new bone lesions on bone scan. Results: Twenty-one patients were enrolled in the trial from 4/05–10/07. Sixteen had radical prostatectomy as primary therapy and 12 of these had subsequent radiation for a rising serum PSA. Median Gleasons score was 7, and median number of cycles of therapy was 6. Eighteen patients were evaluable for response. Four patients met criteria for progression, with a PSADT that decreased while on therapy. Fourteen patients had a prolongation of PSADT compared to baseline. The prolongation was greater than a 2-fold increase in 50% of the patients. Three patients had a greater than 5-fold prolongation of the PSADT. One patient developed an asymptomatic kidney stone and was taken off study. Conclusions: Preliminary results show that weekly administration of calcitriol and naproxen is well tolerated in most patients with recurrent prostate cancer, with improvement in PSADT noted in 75% of patients. The combination therapy was successful in delaying the rate of progression in a majority of patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novacea, Inc
Off-label prescribing of chemotherapy among older cancer patients.
Authors: Carlos Hernando Barcenas, Ning Zhang, Jiangong Niu, Yufeng Zhang, Hui Zhao, Sharon Hermes Giordano
Journal: Journal of Clinical Oncology (2013)

130 Background: Off-label chemotherapy prescribing is thought to be common, but little data exist on the current patterns and predictors of off-label treatments for cancer patients. Methods: Patients from the Surveillance Epidemiology and End Results-Medicare database with a first cancer diagnosis between 1995 and 2009, age &gt;65 years, who had claims for intravenous chemotherapy were included. Off-label chemotherapy use was evaluated for the following invasive cancers: breast (BC), n=26,702; colorectal (CRC), n=37,727; non-small cell lung cancer (NSCLC), n=49,263; small cell lung cancer (SCLC), n=13,364; and ovarian cancer (OV), n=8,552. Patients were considered as having received off-label treatment if they had at least one claim for an intravenous chemotherapy drug that did not have a Food Drug Administration labeled indication for the specific cancer on the date of administration. Generalized estimating (GEE) multivariable models were created for each cancer site to evaluate predictors of off-label chemotherapy use. Results: Patients with OV and CRC were older compared to patients with other tumor types. Distant stage disease was present in 12.5% of patients with BC, 26.7% with CRC, 55.5% with NSCLC, 63.2% with SCLC, and 82.7% with OV. Off-label chemotherapy use varied widely across tumor types. Overall, 23.8% of patients with BC, 14.6% with CRC, 86.2% with NSCLC, 97.7% with SCLC, and 46.7% with OV had at least one claim for an off-label chemotherapy agent. The GEE models showed that distant stage disease was significantly associated with increased off-label use for patients with BC (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.57-1.88), CRC (OR 1.44, 95% CI 1.32-1.58), OV (OR 1.85, 95% CI 1.54-2.21), and NSCLC (OR 1.07, 95% CI 1.00-1.14). Off-label use was more common among patients age &gt;80 years with BC, but was significantly less common for older patients with CRC, NSCLC and OV. Conclusions: The use of off-label chemotherapy is common among patients with different cancer types, particularly among those patients with NSCLC and SCLC, but use varies between specific cancer types, stage of disease, and by age.