tbuckley/cabot-search huggingface dataset:
Histological effect of prolonged hormonal therapy on prostate cancer
Authors: T. Nakamoto, Y. Inoue, K. Asano, Y. Hayashi
Journal: Journal of Clinical Oncology (2005)

4708 Background: To determine the histological effect of prolonged hormonal therapy on prostate cancer, we evaluated radical prostatectomy specimen after androgen ablation therapy. Methods: From January 2001 to December 2003, 36 patients underwent retropubic radical prostatectomy after several periods of hormonal therapy. The median period of hormonal therapy was 8 months (2 to 74 months) and 5 patients were given more than 3 years. Results: Seven of 36 patients (19.4%) had no residual cancer (pT0) in radical prostatectomy specimen. Periods of hormonal treatment of these patients were 6, 7, 8, 8, 16, 40, and 44 months, respectively. In the patient who was given the hormonal treatment for 74 months, only a small amount of degenerated, but viable cancer cells remained and this tumor was considered to be insignificant. Six of 7 tumors with pT0 were cT1c. There were no significant relationship between the histological effect and PSA level at diagnosis, however PSA level of all patients with pT0, except one, decreased less than 0.1 ng/ml before radical surgery. Tumors with high Gleason’s score, those received longer duration of hormonal treatment and those treated with a combined androgen blockade had a tendency to response to hormonal treatment well. Conclusions: In patients with localized prostate cancer whose PSA level kept less than 0.1 ng/ml for more than 3 years by androgen ablation, there was no significant cancer in surgical specimen. Theses findings suggest that some patients with localized prostate cancer may be cured by prolonged hormonal therapy alone. No significant financial relationships to disclose.
Phase II trial of veliparib (V) in patients (pts) with previously treated BRCA or PALB2-mutated (mut) pancreas adenocarcinoma (PC).
Authors: Maeve Aine Lowery, David Paul Kelsen, Sloane C. Smith, Malcolm Moore, Hedy Lee Kindler, Talia Golan, Amiel Segal, Ellen Hollywood, Hannah Maynard, Marinela Capanu, Mary Ellen Moynahan, Anne Fusco, Zsofia Kinga Stadler, Kinh G Do, Alice P. Chen, Kenneth H. Yu, Laura H. Tang, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2015)

358 Background: BRCA1, BRCA2, and PALB2 germline mutations are associated with an increased risk of PC. Other BRCA-associated cancers have demonstrated increased sensitivity to PARP inhibitors (PARPi) and early trials have shown activity of PARPi in untreated BRCAmut PC. We evaluated theactivity of V in patients with previously treated BRCA/PALB2mutPC. Methods: Eligibility: BRCA1/2, or PALB2mutPC, at least 1 and up to 2 prior treatment regimens, measurable stage III/IVPC; ECOG 0-1. Treatment Plan: V 300mg BID (N= 3 pts), then V 400mg BID day1- 28. Primary endpoint: RECIST 1.1 response rate (RR). Statistical plan: Single-arm, non-randomized, open-label, phase II, two-stage design, unacceptable RR 10%, promising 28%, type I, II error rates 10%. Secondary endpoints: progression-free survival (PFS), duration of response, overall survival, safety, tolerability and archival tumor analyses. Results: Between 05/12 and 12/13, N= 16 enrolled. Male= 8, Female= 8. Median age= 52 years (range 43- 77). BRCA1 mut=5. BRCA2 mut=11. N= 1AJCC stage III PC, N= 15 AJCC stage IV PC. N= 8 and N= 8 (50%) had 1 and 2 prior lines of therapy respectively. N= 13 (81%) received prior platinum therapy. Response: N= 1 unconfirmed PR (PR at 4 months (mo), POD at 6 mo), N= 4 stable disease (SD), N= 10 progressive disease (PD); N= 1 inevaluable (12 days of V only due to disease-related complications). Median PFS was 52 days (range 12 to 423). Three pts treated at 400mg V were dose-reduced for toxicity. Six pts had V related grade 3 toxicity including fatigue (N=3), hematologic (N=2) and nausea (N=1). No therapy-related grade 4-5 toxicities were observed. Conclusions: V was well tolerated. While no confirmed partial responses were observed, single-agent activity of V in previously treated PC was noted, and N= 4 (25%) remained on study with SD for ≥ 4mo (4, 6, 6, 9 mo). A randomized phase II trial evaluating cisplatin,gemcitabine +/- V is underway in untreated BRCA/PALB2mutPC (NCT01585805). Results of correlative studies will be presented. Acknowledgements: Lustgarten Foundation. NCI.AbbVie. Clinical trial information: NCT01585805.
The antiviral restriction factor IFN-induced transmembrane protein 3 prevents cytokine-driven CMV pathogenesis
Authors: Maria A. Stacey, Simon Clare, Mathew Clement, Morgan Marsden, Juneid Abdul-Karim, Leanne Kane, Katherine Harcourt, Cordelia Brandt, Ceri A. Fielding, Sarah E. Smith, Rachael S. Wash, Silvia Gimeno Brias, Gabrielle Stack, George Notley, Emma L. Cambridge, Christopher Isherwood, Anneliese O. Speak, Zoë Johnson, Walter Ferlin, Simon A. Jones, Paul Kellam, Ian R. Humphreys
Journal: Journal of Clinical Investigation (2017)

The antiviral restriction factor IFN-induced transmembrane protein 3 (IFITM3) inhibits cell entry of a number of viruses, and genetic diversity within IFITM3 determines susceptibility to viral disease in humans. Here, we used the murine CMV (MCMV) model of infection to determine that IFITM3 limits herpesvirus-associated pathogenesis without directly preventing virus replication. Instead, IFITM3 promoted antiviral cellular immunity through the restriction of virus-induced lymphopenia, apoptosis-independent NK cell death, and loss of T cells. Viral disease in Ifitm3-/- mice was accompanied by elevated production of cytokines, most notably IL-6. IFITM3 inhibited IL-6 production by myeloid cells in response to replicating and nonreplicating virus as well as following stimulation with the TLR ligands Poly(I:C) and CpG. Although IL-6 promoted virus-specific T cell responses, uncontrolled IL-6 expression in Ifitm3-/- mice triggered the loss of NK cells and subsequently impaired control of MCMV replication. Thus, IFITM3 represents a checkpoint regulator of antiviral immunity that controls cytokine production to restrict viral pathogenesis. These data suggest the utility of cytokine-targeting strategies in the treatment of virus-infected individuals with impaired IFITM3 activity.
The prognostic value of CAIX and Ki67 in defining hypoxia in squamous cell cancers.
Authors: A. C. Klimowicz, P. Bose, S. K. Petrillo, S. Chandarana, N. Brockton, W. Matthews, P. S. Craighead, J. C. Dort, C. M. Doll, A. M. Magliocco
Journal: Journal of Clinical Oncology (2011)

e21139
Comparative effective analysis between enzalutamide and abiraterone in the treatment of metastatic castration-resistant prostate cancer.
Authors: Akhil Chopra, Benjamin Haaland, Gilberto Lopes
Journal: Journal of Clinical Oncology (2013)

217 Background: Recently Abiraterone (A) and Enzalutamide (E), new drugs with different novel mechanisms of action, have been approved for the treatment of metastatic castration-resistant prostate cancer (CRPC) based on the COU-AA-301 and AFFIRM phase III trials, after docetaxel failure. The lack of direct comparative trials has introduced a new treatment dilemma for the practicing oncologist: is one drug more effective than the other? Methods: We performed an indirect comparative effectiveness analysis between E and A using the results of the AFFIRM and COU-AA-301 pivotal trials. Due to the lack of study-to-study replication of comparisons, these indirect comparisons are subject to the assumption that the relative effects of each drug relative to placebo are the same across studies. Results: 1) Overall survival (OS)- the respective hazard ratios (95% confidence intervals {CI}) in the AFFIRM and COU-AA-301 trials for OS for E vs. placebo and A vs. placebo were 0.63 (0.53-0.75) and 0.66 (0.56-0.79). The indirect estimate of the hazard ratio (HR) (95% CI; p-value) for E vs. A was 0.96 (0.75-1.22; 0.72) 2) Time to PSA progression- the respective HR(95% CI) in the AFFIRM and COU-AA-301 trials for time to PSA progression for E vs. placebo and A vs. placebo were 0.25 (0.20-0.30) and 0.58 (0.46-0.73). The indirect estimate of the HR (95% CI; p-value) for E vs. A was 0.43 (0.32-0.58; 4.3 × 10 -8 ). 3) Radiographic progression Free Survival (rPFS)- The respective HR (95% CI) in the AFFIRM and COU-AA-301 trials for time to PSA progression for E vs. placebo and A vs. placebo were 0.40 (0.35-0.47) and 0.67 (0.59-0.78). The indirect estimate of the HR (95% CI; p-value) for E vs. A was 0.60 (0.49-0.74; 7.1 × 10 -7 ). 4) PSA response- the respective odds ratios (95% CI) in the AFFIRM and COU-AA-301 trials for time to PSA progression for E vs. placebo and A vs. placebo were 77.08 (34.02-174.70) and 5.49 (3.84-7.84). The indirect estimate of the odds ratio (95% CI; p-value) for E vs. A was 14.04 (5.75-34.28; 6.6 × 10 -9 ). Conclusions: In this indirect comparative effectiveness analysis, E appears to be more effective than A in terms of time to PSA progression, rPFS and PSA response. OS was not different.
Clinical outcomes for special populations of patients treated with first-line bevacizumab-based therapy in an observational study (AVVA).
Authors: J. De Castro, M. Domine, J. Garcia-Bueno, S. Saura, R. García, M. Sereno, O. Juan Vidal, E. Pujol, B. Rubio-Viqueira, M. Cobo
Journal: Journal of Clinical Oncology (2011)

e18033 Background: More than 50% of cases of advanced NSCLC are diagnosed in patients (pts) older than 65 years. Furthermore, the majority of pts with NSCLC present at the time of the diagnosis one or more comorbidities. Both subgroups are often under-represented in clinical trials based on perceptions that they do not wish for and/or cannot tolerate active systemic therapy. Methods: AVVA is a multicenter, observational study in pts with advanced NSCLC (stage IIIB noncandidates for radiotherapy or IV) treated with first-line bevacizumab-based regimen. A subanalysis according to age ≥65 years and ≥1 comorbid condition was performed. Preliminary results are presented. Results: A total of 148 pts were evaluated. Median age 57.5 (50-64) years; male 64%; tumor histology: 77% adenocarcinoma, 14% large-cell carcinoma; disease stage IV/IIIB 93%/7%; ECOG 0/1/≥2 37%/56%/7%. 24% of pts were ≥65 years and 64% presented ≥1 comorbid condition at baseline, being the more frequent HTN (19%), dyslipidemia (16%), DM (12%), CVD (7%) and COPD (6%). Commonly used first-line chemotherapy (CT) regimens in combination with bevacizumab were carboplatin doublets in 71% of pts and cisplatin doublets in 26% for a median of 6 cycles. Treatment characteristics and outcomes are specified in the table. The main ≥grade 3 toxicity was DVT in 2.7% of pts. The incidence of ≥ grade 3 AEs of special interest were: haemoptysis <1%, proteinuria <1%, HTN 0%, thromboembolism <1%. DVT (2%) was the only ≥ grade 3 AE reported in elderly pts. In pts with ≥1 comorbidity, DVT (3%), neutropenia (1%) and infection (1%) were the only ≥ grade 3 AEs reported. Conclusions: First-line bevacizumab-based therapy was effective and safe in older pts and pts with at least one comorbid condition. No new safety signals have been indentified and efficacy results match with previously reported data. All patients (n=148) Age ≥65 (n=35) ≥1 comorbid condition (n=95) CT regimen (%) Carboplatin doublets Cisplatin doublets 71 26 68 26 73 25 Median no. of CT cycles 6 6 6 Median no. of bevacizumab cycles 8 6 8 Disease control rate (%) CR PR SD 85.0 1.3 51.3 32.4 85.6 2.9 51.4 31.4 84.1 2.1 52.6 29.5 PFS, months (95% CI) 7.6 (7.2-8.0) 6.6 (5.0-8.2) 7.4 (6.3-8.2)
Prognostic value of serum PSP94 (prostate secretory protein of 94 amino acids) and its binding protein (PSPBP) after radical prostatectomy
Authors: J. R. Reeves, H. Dulude, C. Panchal, L. Daigneault, D. M. Ramnani, J. W. Xuan
Journal: Journal of Clinical Oncology (2005)

4632 Background: With an increase in the number of patients diagnosed with early stage prostate cancer, there is need to identify new prognostic markers to aid in the selection of conservative or radical treatment options. Prostate secretory protein of 94 amino acids (PSP94) is one of the three most abundant proteins in semen and recently a blood binding protein was identified (PSPBP). Previous work has demonstrated the prognostic value of bound/free PSP94 in prostate cancer patients treated with radiation. Here we assess the prognostic value of total and free PSP94 and PSPBP in the pre-treatment serum of radical prostatectomy patients using new validated ELISA tests (Procyon Biopharma Inc). Methods: One hunderd and eighty five serum samples were obtained from patients with localized prostate cancer prior to treatment with radical prostatectomy at Virginia Urology (Richmond, VA, USA). Patients were followed up for a median of 48 months (range 1–66 months) and biochemical relapse was indicated as total prostate specific antigen (tPSA) rising to above 0.1 ng/ml. Available clinical variables included initial tPSA, Gleason score, surgical margin status and clinical stage. Total PSP94, free PSP94 and the PSPBP were quantified in the pre-treatment serum. Univariate and multivariate Cox regression was used to assess the ability of PSP94 and PSPBP to predict time to recurrence. Results: Thirty-one patients had biochemical recurrence. Gleason score, margin status, clinical stage, and initial tPSA significantly predicted time to relapse (all p < 0.001). In addition, low levels of PSPBP (hazard ratio 0.993) and, consistent with previous studies, a high bound/free PSP94 ratio (hazard ratio 1.113) were associated with rapid relapse (p = 0.005 and p = 0.008 respectively). Multivariate analysis demonstrated that PSPBP, as well as the bound/free PSP94 ratio, were independent predictors of time to relapse adjusting for tPSA, Gleason score and margin status. Conclusions: Bound/free PSP94 and PSPBP are novel and independent prognostic markers following radical prostatectomy for prostate cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Procyon Biopharma Procyon Biopharma Procyon Biopharma
Clinical benefit rate (CBR) of panitumumab monotherapy among patients with KRAS wild-type metastatic colorectal cancer (mCRC).
Authors: Hagen F. Kennecke, Howard John Lim, Balvindar Singh Johal, Muhammad Zulfiqar, Caroline Speers
Journal: Journal of Clinical Oncology (2012)

e14176 Background: Panitumumab (Pmab) improves progression free survival as first-, second- and third-line therapy for KRAS wild-type (wt) metastatic colorectal cancer (mCRC). Only in the third-line setting is there evidence of benefit of Pmab monotherapy. In this analysis of an exploratory biomarker study of Pmab monotherapy, the clinical benefit rate of Pmab according to previous lines of therapy is described. Methods: Patients (pts) with KRAS non-mutated, measurable MCRC previously treated with or ineligible for oxaliplatin/5-FU and irinotecan were treated with Pmab 6mg/kg IV q2w until progression or toxicity. The primary endpoint is clinical benefit rate (complete (CR) or partial response (PR) + prolonged stable disease (PSD) &gt; = 24 weeks) by RECIST criteria. Results: The study completed accrual and (40) evaluable patients were treated between September 2009 and December 2011 of which 32 were evaluable for the primary endpoint. Median follow-up was 8.8 months, median age was 64.5 years and 90% were ECOG 0/1. Previous therapy was: 5-FU/Capecitabine(C) only in 12 pts, Irinotecan/5-FU/C only in 2 patients, Oxaliplatin/5-FU/C only in 3 pts, Oxaliplatin/Irinotecan/5-FU/C in 23 pts. 22 patients received prior Bevacizumab. Median number of cycles was 8 and 6 pts required a dose modification. There were 7 (22%) PRs and 7 (22%) pts experienced PSD &gt;=24 weeks. Clinical benefit rate (PR+PSD) according to previous therapy was 33% (3/9) for 5FU/C only, 100% (2/2) Oxaliplatin/FU/C only, 0% (0/2) Irinotecan/FU/C only, and 47% (9/19) for Oxaliplatin/Irinotecan/5FU/C. Conclusions: Pmab monotherapy is well tolerated and response rates vary according to previous lines of therapy. Patients ineligible for irinotecan and/or oxaliplatin experience a high clinical benefit rate with single agent Panitumumab and should be considered for such therapy. Updated study results will be presented.
The incidence of adverse pathologic characteristics in small renal masses as size increases.
Authors: Cayce Nawaf, James Rosoff, Adebowale Adeniran, Peter Humphrey, Brian M. Shuch
Journal: Journal of Clinical Oncology (2016)

596 Background: The AUA guidelines include active surveillance (AS) as an option for patients with the cT1a renal mass (≤4 cm). We evaluate how increasing tumor size (≤4 cm) correlates to the incidence of adverse pathologic features (APF) found on nephrectomy. Methods: We queried a single institution database of nephrectomy specimens from subjects undergoing surgery for renal cell carcinoma (RCC). From a total of 898 consecutive cases, 389 patients had primary tumors that were ≤4 cm and N0, M0. All cases were centrally reviewed for the following adverse pathologic features: high nuclear grade (Fuhrman grade 3 or 4), lymphovascular invasion (LVI), histologic tumor necrosis, sarcomatoid features, rhabdoid features, papillary type II histology and advanced stage (≥pT3). Tumor size categories were compared in 1 cm increments. Relationships between the variables were analyzed by chi-square, Fisher’s exact, and ANOVA tests. Results: There was a significant increase in tumor grade (p=0.006) and stage (p=0.04) seen as size increased. APF were found in 157 (40.4%) of tumors ranging from 22.2% for tumors ≤1 cm to 50.8% of tumors &gt;3 to ≤4. There was a significant increase in the presence of one or more of any APF as size increased (p=0.013). Conclusions: Tumors ≤4 cm that could be considered for AS still show frequent aggressive characteristics at nephrectomy. As over half of tumors 3-4 cm have APF, caution is advised when placing patients with larger tumors on AS. Renal tumor biopsy may identify several aggressive histologic characteristics and could be considered to aid the selection of patients considering AS. [Table: see text]
Preoperative breast MRI and MR-guided surgery of invasive breast cancers with and without DCIS components.
Authors: Christiane K. Kuhl, Heribert Bieling, Kevin Strobel, Eva Wardelmann, Walter Kuhn, Nikolaus Maass, Simone Schrading
Journal: Journal of Clinical Oncology (2015)

58 Background: DCIS-components of invasive breast-cancers are a major cause for positive margins and reoperations in women undergoing breast-conserving-surgery. We investigated whether breast-MRI, through improved diagnosis of such DCIS-components, combined with MR-guided needle biopsy and pre-operative MR-guided lesion bracketing where appropriate, would help reduce reoperation-rates for invasive breast cancers. Our hypothesis was that with improved diagnosis of local disease extent through MRI and MR-guided surgery, reoperation rates should be low, and should be independent of the presence or absence of a DCIS-component. Methods: Prospective study in two academic breast-centers on consecutive patients with newly-diagnosed invasive breast-cancer. Women underwent breast-MRI in addition to conventional imaging (CI; digital-mammography/breast-ultrasound), and MR-guided needle-biopsy and preoperative MR-guided lesion bracketing where appropriate. Accuracy of breast-MRI for diagnosing DCIS-components was compared with that of CI, stratified by nuclear-grade and relative size of DCIS-components. Surgical outcomes (reoperation and mastectomy-rates) were recorded, stratified by presence or absence of DCIS-components. Results: 593 women were included. Surgical-pathology documented DCIS-components in 139/593 (23.4%) women. Sensitivity of MRI (84.9%) for demonstrating DCIS-components was significantly higher than that of CI (36.7%) (p &lt; 0.0001); over half (51.1%) of DCIS-components were only detected by MRI. The sensitivity advantage of MRI over CI increased significantly with increasing relative size and nuclear-grade of the DCIS-component. Reoperation-rates were equivalent for women with vs. without DCIS-components (10.1% vs. 9.9%); mastectomy rates were 10.8% and 8.1%, respectively. Similar Positive-Predictive-Values were achieved with CI and MRI. Conclusions: Breast-MRI significantly improves depiction of DCIS-components of invasive breast-cancers prior to surgery. Use of breast-MRI and MR-guided surgery translates into low reoperation rates for women with operable invasive breast-cancer, which were similar for women with or without DCIS-components.
Association between tobacco use, pain expression, and maladaptive coping among patients with advanced cancer.
Authors: Rony Dev, Yu Jung Kim, Akhila Sunkepally Reddy, David Hui, Kimberson Cochien Tanco, Diane D Liu, Minjeong Park, Janet L. Williams, Cindy L. Carmack, Eduardo Bruera
Journal: Journal of Clinical Oncology (2016)

65 Background: Cancer patients who smoke have been reported to have higher pain expression and increased risk for opioid abuse. The purpose of our study is to evaluate the association between tobacco use, symptom expression, and maladaptive coping in advanced cancer patients. Methods: We prospectively enrolled advanced cancer patients evaluated in an outpatient Supportive Care Center and collected data on patient demographics, cancer diagnosis, morphine equivalent daily dose (MEDD), cigarette smoking status using Behavioral Risk Factor Surveillance System, symptom expression as measured by Edmonton Symptom Assessment Scale, Cut down/Annoyed/Guilty/Eye opener (CAGE alcoholism questionnaire), short form Screener and Opioid Assessment for Patients with Pain (SOAP-SF) survey, and Brief COPE Questionnaire. Results: Among399 patients, 195 (49%) were never smokers, 158 (40%) former smokers, and 46 (11%) current smokers. The most common malignancies were gastrointestinal (21.1%) and breast (19.5%). Never smokers were more likely to be female (p = 0.005). Current smokers expressed significantly higher pain scores at consultation than former or never smokers [median 7 vs. 6 vs. 5, respectively (p = 0.015)], increased MEDD (median 90 vs. 60 vs. 50, p = 0.002), and more likely to screen CAGE positive (33% vs. 24% vs. 8.7%, p &lt; 0.0001). Compared with former and never smokers, current smokers were significantly more likely to cope with substance use (p = 0.02), denial (p = 0.007), and self-blame (&lt; 0.0001), while both current and former smokers significantly more likely to use venting (p = 0.04). In addition, current smokers compared with former and never smokers were significantly more likely screen positive (≥ 4) on the SOAP-SF survey (74% vs. 13% vs. 9.3%, p = &lt; 0.0001) and clinicians rated patients to be at higher risk for maladaptive coping (6.5% vs 2.5% vs. 1.5%, p = 0.003). Conclusions: In advanced cancer, current and former smokers were significantly more likely to have higher pain expression, CAGE positivity, and increased MEDD at consultation. In addition, a history of current or past tobacco use in advanced cancer patients was associated with increased risk of maladaptive coping.