tbuckley/cabot-search huggingface dataset:
Racial variation in the reliability of prostate cancer indicators in men undergoing subsequent prostate biopsy.
Authors: Robert Scott Libby, Hoang Mt Nguyen, Jordan J. Kramer, Allison H. Feibus, Raju Thomas, Jonathan L. Silberstein
Journal: Journal of Clinical Oncology (2017)

115 Background: Many men with an initial negative prostate biopsy have a persistently elevated prostate specific antigen (PSA) prompting physicians to perform repeat biopsies. African American men (AA) are at particular risk as they have a greater prostate cancer (PCa) incidence and mortality, yet traditional PSA testing may be less reliable in this cohort. We sought to determine the predictors of PCa and PCa severity in a racially diverse population on subsequent biopsy following an initial benign biopsy. Methods: Upon receiving Institutional Review Board approval, a retrospective analysis was performed on men with repeat prostate biopsies at Tulane Medical Center and Southeast Louisiana Veterans Health Care Services in New Orleans, Louisiana from 2003-2015. Inclusion criteria included patients with a benign initial prostate biopsy and underwent subsequent repeat prostate biopsy within 5 years. Race, age, serum PSA, PSA density (PSAD), and prostate volume by transrectal ultrasound (TRUS) were evaluated to determine if they correlate with the presence and severity of PCa. Aggressive PCa was defined as Gleason score &gt;6. Results: A total of 209 men were included; 127 (61%) were AA, and 82 (39%) were Caucasian American men (CA). The two groups were similar with respect to PSA, PSAD, and TRUS. More AA (25.2% vs. 17.1%) had a repeat biopsy showing any PCa. Of those with PCa, 28.1% of AA and 28.6% of CA had aggressive PCa. PSAD positively correlated with any PCa (p=.015). TRUS negatively correlated with any PCa (p=.008). PSA levels (p&lt;.001) and PSAD (p&lt;.001) positively correlated with aggressive PCa in CA but not in AA. Conclusions: The goal of prostate biopsy particularly for those with a prior negative biopsy is to detect aggressive PCa. PSA and PSAD positively correlated with finding any PCa in both AA and CA but not with aggressive PCa in AA. PSA and PSAD are less accurate predictors of aggressive PCa in AA, and novel biomarkers are needed. [Table: see text]
Clinical features and outcome of B-cell acute lymphoblastic leukemia in patients older than 9 years: A single center experience of 241 cases from AIIMS, New Delhi, India.
Authors: Atul Sharma, Sunu Lazar Cyriac, Siddharth Kumar Sahai, Sameer Bakhshi, Ritu Gupta, Lalit Kumar, Rajive Kumar, Sobuhi Iqbal, Vinod Raina
Journal: Journal of Clinical Oncology (2013)

7082 Background: Data on B cell Acute Lymphoblastic leukemia (ALL) in the poor prognostic age group of &gt; 9 years from India is minimal. Methods: This is an analysis of patients of above 9 years that were diagnosed and treated from January 2000 to December 2010 at a single institute . All patients who completed at least 4 weeks of induction therapy were analysed for various outcomes. Results: Of the 241 newly registered patients, the median age was 19 years (Range 10-78 years) with an M:F ratio of 1.9:1. Out of this 47%, 25% &amp; 28% patients belonged to 10-18, 19-30 &amp; &gt; 31 years age group respectively. Twenty seven (11.6%) and 5(2%) had CSF and testicular involvement respectively. Thirty nine per cent had a total leucocyte count (TLC) of above 30x10 9 /L. Philadelphia chromosome (Ph) positivity was seen in 27% and was equally distributed among the different age groups. Patients available for outcome analysis were 213(88.4%). Complete remission rate (CRR) was 66.6% and induction mortality was 26.3%.At a median follow up of 65.8 months 5 year leukemia free survival was 30.5%. Seventy eight (55%) patients relapsed (median relapse time of 13.5 months, range 1.7 to 53.4 months) , 55% during maintenance phase. The 5 year overall survival (OS) was 30.3% with a median OS of 15.8 months. The OS was similar in 10-18 and 19-30 age groups (5 year OS 35% vs. 27.5%, p=0.641) but it was significantly lower in &gt;31 years (5year OS 21%, p=0.008). Apart from this, extramedullary disease, not attaining a CR in 1 st induction, albumin at presentation below 3.5gm% and TLC of &gt;100x10 9 /L were significant poor prognostic markers for survival. Conclusions: This is a large study of B-ALL outcomes in patients above 9 years from a single center in India. Patients above 30 years had a worse prognosis while the prognosis of 10-18 and 19-30 years age group were similar. Induction mortality was higher mainly because of advanced disease and poor performance status at presentation.
Oxaliplatin (OXA), 5-fluorouracil (5-FU) and leucovorin (LV) in patients with advanced or metastatic gastric cancer (A/MGC)
Authors: L. Cavanna, A. Zaniboni, F. Artioli, A. Lazzaro, A. Rizzi, M. Mazzocchi, P. Bernuzzi, R. Bertè, L. Bidin, M. Palladino
Journal: Journal of Clinical Oncology (2004)

4068 Background: Treatment options for advanced or metastatic gastric cancer (A/MGC) are limited and therefore inclusion of novel substances is necessary. Few studies have confirmed the activity and tolerability of the combination of oxaliplatin (OXA) and 5-fluorouracil (5-FU) modulated with leucovorin (LV) administered to patients (pts) with A/MGC. Methods: Thirty-five patients with A/MGC treated with FOLFOX-4 regimen. All patients had a pathologically confirmed A/MGC and at least one measurable lesion, 14 pts (40%) were previously untreated and 21 (60%) received prior chemotherapy. The regimen included: LV 200 mg/sqm/d as 2-hour infusion followed by bolus 5-FU 400 mg/sqm/d and a 22-hour infusion of 5-FU 600 mg/sqm/d, repeated for 2 consecutive days every 2 weeks, OXA 85 mg/sqm on day 1, given as a 2-hour infusion in 250 ml of 5% dextrose concurrent with LV (FOLFOX-4 regimen). Pts characteristics: males-21 (60%), female-14 (40%), median age-67 years (range 28–78), 16 pts (45.7%) had a performance status (PS) of 0 or 1 and 19 (54.3%) had a PS of 2 (WHO/ECOH scale), histology: adenocarcinoma in all cases. The 35 pts reported in this study received 283 cycles of therapy (median number 8, range 3–16). Median follow-up time is 7 months. The most common toxicities was haematological: grade 3 hematological toxicity included anemia in 16%, neutropenia in 18.5% and thrombocytopenia in 10%. Only one patient had a grade 4 neutropenia, while no other grade 4 hematological toxicities were observed; none pts experienced neutropenic fever. Only 3 pts (8.6%) had a grade 3 diarrea. No other grade 3 or 4 toxicities including peripheral neurophaty were reported in these pts and no toxic deaths occurred. Results: A complete response (CR) was achieved in 1 patient (2.9%), a partial response (PR) in 16 pts (45.7%), a stable disease (SD) for at least 12 weeks 10 pts (28.6%), and 8 pts (22.9%) showed tumor progression. Conclusions: This study, giving a 48.6% of best response rate (CR + PR) and a 28.6% of SD showing good activity with mild and acceptable toxicity of OXA/5-FU/LV regimen on patients with A/MGC; survival and response analyses will be presented. No significant financial relationships to disclose.
Clinical and biologic activity of soy protein powder (SPP) in healthy male volunteers: effect on testosterone and luteinizing hormone (LH)
Authors: S. Goodin, F. Shen, W. Shih, N. Dave', M. Kane, G. Lambert, M. Gallo, R. Dipaola
Journal: Journal of Clinical Oncology (2004)

4611 Background: Epidemiologic studies and a recent prospective trial have revealed a reduced risk of prostate cancer associated with consumption of soy foods, possibly due to the estrogenic properties of soy. To determine if a commonly used SPP can have estrogenic activity in men, we specifically evaluated supplementation with SPP in healthy male volunteers and the effect on testosterone and LH. Methods: Healthy volunteers recruited to this study were men 18 years of age or older that were in good health with no known allergy to soy or phenylalanine. Treatment consisted of consuming two scoops (56g) of pure SPP (Puritan's Pride, Oakdale, New York) daily for 28 days. Serum testosterone and LH levels were collected prior to initiation of supplementation with soy protein powder, throughout the 28 days, and 14 days after the completion of therapy. Patients maintained a food diary throughout the 28-day period. Results: Twelve healthy volunteers were enrolled with a mean age of 32 years (range 25 to 47). Serum testosterone concentrations decreased during the 4-week use of SPP and increased within two weeks after SPP was discontinued, with a statistically significant percent change in testosterone over the four-week period (P=0.021). At no time did the mean serum testosterone fall below the normal reference range. Serum LH concentrations decreased during the 4 week use of soy protein powder then increased within two weeks after soy protein powder was discontinued but the changes did not reach statistical significance (P =0.20). There were no side effects reported by any participants. Using a yeast based assay transfected with the alpha and beta estrogen receptor (ER), we found that the soy protein selectively activated ER-beta. Conclusions: Soy protein powder decreases testosterone levels in healthy patients, which is reversible upon removal of SPP from the diet. These data support further study of these hormonal effects as a mechanism in prostate cancer prevention. No significant financial relationships to disclose.
Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. Advanced Colorectal Cancer Meta-Analysis Project.
Journal: Journal of Clinical Oncology (1992)

PURPOSE A meta-analysis was performed on nine randomized clinical trials that compared fluorouracil (5-FU) with 5-FU plus intravenous (IV) leucovorin (LV) for the treatment of advanced colorectal cancer. DESIGN The analysis was based on the most recently updated individual patient data from all trials. The end points of interest were tumor response and overall survival. RESULTS Therapy with 5-FU plus LV administered either as weekly or monthly regimens showed a highly significant benefit over single-agent 5-FU in terms of tumor response rate (23% v 11%; response odds ratio (OR), 0.45; P less than 10(-7)). This increase in response did not result in a discernable improvement of overall survival (survival OR, 0.97; P = .57). The large number of patients who did not respond to treatment in both groups, and cross-overs from 5-FU alone to 5-FU plus LV are discussed as plausible explanations for the lack of a survival difference. CONCLUSION These results confirm the advantage of 5-FU plus leucovorin over 5-FU alone in terms of objective tumor response. They also suggest that in planning future trials, tumor response should not be considered a valid surrogate end point for survival in patients with advanced colorectal cancer.
Participation of teenagers and young adults (TYA) in cancer clinical trials (CCT): What can we learn from six years of accrual data in England?
Authors: Lorna Anne Fern, Jennifer Ann Lewandowski, Katy Marie Coxon, Elliann Fairbairn, Eileen Loucaides, Jeremy Whelan
Journal: Journal of Clinical Oncology (2012)

6115 Background: We reported underrepresentation of TYA in CTT in England, 2005-06. Since 2005 national healthcare policies and research initiatives aimed at increasing participation of TYA in CCT have been implemented. We aimed to determine if this has improved accrual rates (AR). Methods: We analyzed accrual by age during 2005-2010 to UK Cancer Research Network interventional trials recruiting newly diagnosed patients (pts) with leukaemia, lymphoma, bone/soft tissue sarcoma, central nervous system and germ cell tumours. AR were expressed as the ratio of pts entered onto trial compared to population incidence cases for 2005-08; for 2009-10, mean incidence of 2005-08 was used. Results: 2005-10 showed an AR increase of 10.3% for pts 10-14 yrs, 17.9% for pts 15-19 yrs but only 4.6% for pts 20-24 yrs (Table). In 2010 AR was 54.4% for pts 10-14 yrs, 43.3% for 15-19 yr olds and 20.6% for pts 20-24. Annual increases of AR were observed for pts 15-19 yrs, but in no other age groups, 0-59 yrs. We looked at AR for children and younger teenagers , 5-14 yrs, vs older TYA, 15-24 yrs. Overall, AR for 5-14 yr olds was greater, 53.7% vs 23.0% for pts 15-24 yrs; however, during 2005-10 AR increased by 9.7% for pts aged 15-24 compared to 7.8% for pts aged 5-14. Conclusions: AR for TYA has improved in between 2005-10. Most benefit is evident for older teenagers; AR for young adults remain disappointing. Changes relate to increased trial availability and access, centralisation of care for TYA, amendments to age eligibility criteria to reflect tumour biology and increased collaboration between adult and paediatric clinical research groups. Strategies to improve AR for young adults require further development. [Table: see text]
Continuing benefit of zoledronic acid for the prevention of skeletal complications in men with advanced prostate cancer
Authors: F. Saad, D. M. Gleason, R. Murray, N. S. S. Tchekmedyian, P. Venner, L. Lacombe, J. Chin, J. J. Vinholes, M. Zheng, Y.-J. Hei
Journal: Journal of Clinical Oncology (2004)

4575 Background: We previously reported the efficacy and safety of 4 mg zoledronic acid (Zol) at 15 months compared with placebo in patients with bone metastases from prostate cancer (Saad et al. J Natl Cancer Inst. 2002;94:1458–1468). We report here the results of an exploratory analysis of the 15- to 24-month extension phase of this study to evaluate the benefit of Zol treatment beyond 15 months.Methods: Data were collected during months 15 to 24 for patients who chose to enter the 9-month extension phase. Endpoints included the percentage of patients with a skeletal-related event (SRE), time to first SRE, skeletal morbidity rate (SMR), and multiple event analysis using the method of Andersen and Gill. Results: Of 422 patients randomized to the 4-mg or placebo treatment arms, 147 completed the 15-month core phase, and 133 elected to enter the extension phase. Among these patients, multiple event analysis revealed a 53% reduction in the risk of developing an SRE for patients treated with 4 mg Zol compared with placebo (risk ratio = 0.467; 95% CI = 0.243, 0.897; P = .022). Additionally, only 19% of patients treated with 4 mg Zol had an SRE during the extension phase versus 38% of patients treated with placebo (P = .017). Time to first SRE was significantly extended in the 4–mg Zol group compared with placebo (P = .036), and mean SMR was reduced approximately 2-fold (0.42 for 4 mg Zol versus 0.88 for placebo; P = .016). Conclusions: This exploratory analysis suggests that long-term treatment with Zol provides significant and ongoing clinical benefit in patients with bone metastases from advanced prostate cancer. Considering that patients who have an SRE are also at higher risk for a subsequent SRE, this analysis suggests that patients should continue on bisphosphonate therapy even after they have an SRE. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp.
A look back: Results from 1 year of routine clinical testing of both hematologic and solid tumors using two targeted next-generation sequencing (NGS) panels.
Authors: Robert D Daber, Corey J. Langer, Selina M. Luger, Lynn Mara Schuchter, D. Gary Gilliland, David Roth, Martin Carroll, Katherine L. Nathanson, Jennifer J. Morrissette
Journal: Journal of Clinical Oncology (2014)

e22099 Background: Molecular characterization of the genomic mutations underlining cancer continues to advance. At our institution we initiated a tumor genotyping program as part of routine care, screening both hematologic and solid tumors for a wide spectrum of mutations. Herein, we describe our initial experience. Methods: Upon clinician request, patient samples were analyzed using one of two NGS panels. DNA was extracted from either fresh tissue or from Formalin Fixed- Paraffin embedded tissue and target genes were enriched using the TruSeq Amplicon Cancer Panel (47 genes) or a TruSeq Custom Amplicon panel (33 genes) with subsequence sequencing on the Miseq. With slight alterations to the standard protocol, as low as 5 ng total input DNA was used to produce libraries with a mean depth of coverage over 2,000x. Using custom analysis pipelines, variants were detected to an allele frequency of 5% and indel size up to 90 basepairs. Results were returned with an average turnaround time of 7-10 days. Results: Initial launch was focused on four major indications, acute myelogenous leukemia (AML), melanoma, brain and lung tumors. During the first year of testing, over 1,000 samples were received, with 15% being cancelled for sample adequacy or appropriateness. Of the remaining 900 samples analyzed, over 71% were found to be abnormal with at least one disease associated mutation detected; 93 of which contained only TP53 mutations. 14% of cases were found to be mutation negative, 6% contained only unclear variants and 6% contained DNA that was insufficient for analysis. Over 1,100 unique variants were detected across the two panels, with each abnormal case containing on average, 1.6 disease associated mutations and 0.6 variants of uncertain significance. Conclusions: Multi-gene testing has shown rapid and widespread adoption across our institution. The advance of this technology has challenged the standards of current practice and demonstrated that ‘actionable’ mutations exist outside the genes currently considered as standard of care. The platform is now being extended to include actionable alleles in noncancer disease areas in our health care system.
Single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor (<i>VEGF</i>) family genes as predictive or prognostic biomarkers in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of the phase III MAX study.
Authors: Fiona J.M. Chionh, Val Gebski, Anderly C. Chueh, Sheren J Al-Obaidi, Andrew James Weickhardt, Chee Lee, David S Williams, Carmel Murone, Kate Wilson, Andrew Mark Scott, John Simes, Timothy Jay Price, John M Mariadason, Niall C. Tebbutt
Journal: Journal of Clinical Oncology (2014)

3609 Background: Adding bevacizumab (B) to chemotherapy (CT) improves survival outcomes in pts with mCRC. Pt subgroups benefiting most from B need to be identified. SNPs in genes for VEGF-A and its receptors VEGF-R1/–R2 can affect their expression/production. We hypothesised these may be prognostic and/or predictive biomarkers for response and survival outcomes in pts treated with CT and B for mCRC. Methods: We analysed tissue from 325 of 471 pts (69%) randomised to capecitabine (C), or C + B, or C + B + mitomycin for mCRC. We performed Taqman SNP genotyping assays on available (in order of preference) normal (51%), adenoma (2%), or malignant (47%) FFPE tissue. 16 candidate SNPs in VEGF-A (n = 6), -R1 (n = 4), and -R2 (n = 6), all in Hardy-Weinberg equilibrium with minor allele frequency ≥ 10%, were analysed for associations between genotype and response rate (RR), progression-free survival (PFS) and overall survival (OS). We assessed if SNP genotypes were predictive of B efficacy using tests for B treatment - SNP genotype interactions. Results: Of the SNPs analysed, VEGF-A rs25648 major allele C was significantly associated with improved PFS and OS, including when adjusted for B treatment (Table), but not associated with RR (p= 0.30). Other than B treatment, no clinico-pathologic variables were associated with survival outcomes. There were no significant interactions between B treatment and any SNP genotypes. Conclusions: VEGF-A rs25648 was an independent prognostic biomarker for PFS and OS in pts with mCRC, with allele C conferring improved prognosis, but was not predictive of B efficacy. This finding is biologically plausible as rs25648 is in the VEGF-A 5’UTR, and in previous studies the CC genotype has been associated with lower VEGF-A levels/expression. rs25648 genotype Reference HR (95% CI), median (months HR (95% CI) adjusted for B treatment PFS OS PFS OS CC n = 236 CT/TT n = 82 0.66 (0.51 – 0.85), 8.6 vs 6.4 0.70 (0.52 – 0.92), 21.4 vs 17.3 0.61 (0.49 – 0.83) 0.70 (0.55 – 0.92) TT n = 69 CC/CT n = 249 1.66 (1.25 – 2.19), 6.0 vs 8.5 1.53 (1.13 – 2.06), 17.0 vs 21.4 1.72 (1.25 – 2.19) 1.53 (1.13 – 2.06)
Adoptive Cell Therapy for metastatic melanoma: A UK centre experience.
Authors: Manon Rhys Pillai, Ryan Guest, Natalia Kirillova, Shien Chow, Paul Lorigan, Robert E. Hawkins
Journal: Journal of Clinical Oncology (2015)

9060 Background: Adoptive cell therapy (ACT) with tumour infiltrating lymphocytes (TIL) has consistently demonstrated impressive clinical results in several international studies in the management of metastatic melanoma. We describe our experience as the only UK cancer centre providing TIL therapy. Methods: TIL are cultured from resected tumour samples as previously described. Infusion is preceded by non-myeloablative lymphodepleting chemotherapy (high dose cyclophosphamide and fludarabine) and followed by intravenous high dose interleukin 2 (HD-IL2). Results: Eleven patients have been treated to date: eight with cutaneous melanoma, two with ocular melanoma and one patient with mucosal melanoma. All patients had metastatic disease and were heavily pre-treated with a combination of targeted agents and immunotherapies (anti-CTLA4 and anti-PD1 antibodies). In the ten patients currently evaluable, 60% achieved an objective clinical response according to the response evaluation criteria in solid tumours. Five of eight patients with cutaneous melanoma achieved a response, including one ongoing complete response (30+ months) and four partial responses. All other patients showed disease stabilisation. One patient with ocular melanoma achieved a short lived partial response. Of eight patients with significant symptomatic progressive disease, six obtained clear symptomatic benefit. Treatment is well tolerated. All patients experienced anticipated toxicities associated with pre-conditioning chemotherapy and HD-IL2, which were short lived and manageable on the medical ward. Conclusions: We show that at our centre lympho-depleting chemotherapy followed by transfer of TIL and HD-IL2 is feasible and clinically effective, demonstrating tumour regression in over 60% of patients with metastatic cutaneous melanoma. Short lived responses were additionally seen in patients with ocular melanoma, where treatment options are limited, suggesting a potential role for TIL therapy in this group of patients also. Significant toxicities are attributable to HD-IL2 and further evaluation of TIL followed by low dose IL2 should be conducted to decrease treatment related complications and expand clinical participation in ACT.