tbuckley/cabot-search huggingface dataset:
The clinical characteristics of <i>RET</i> rearranged lung adenocarcinoma patients.
Authors: Jeong-Oh Kim, Jieun Lee, Jung-Young Shin, Min Young Kim, Kyoung Hwa Son, Chan-Kwon Jung, In-Ho Kim, Jae Gil Park, Sook-Whan Sung, Sang-Ju Bae, Hyun-Jung Min, Jin Hyoung Kang
Journal: Journal of Clinical Oncology (2015)

e18528 Background: KIF5B-RET fusion genes are formed when part of the RET gene fuses with part of the KIF5B gene. This fusion gene induces the proliferation and differentiation of tumor cells by triggering abnormal activation of kinase domain in RET fusion protein, leading to lung adenocarcinoma. Methods: We constructed Tissue Micro Array (TMA) composed of 330 resected tumor tissues from lung adenocarcinoma patients and investigated the frequency of RET rearrangements using FISH analysis with break apart probe. We evaluated the protein expressions of RET and RET-related signal molecules including p-AKT, p-ERK, and VEGF using TMA-based immunohistochemical (IHC) staining. In addition, we examined the protein expressions of mutant EGFR and ALK rearrangement by IHC, and analyzed the association of RET rearrangements with clinical characteristics and outcome. Results: Among 330 patients, mean age was 62 yr. (range 20~84) and M: F ratio was 186:144. The frequency of RET rearrangement in 279 cases available for FISH analysis was 10.0%. Of 28 RET rearrangement-positive patients, EGFR mutations in exon 19 del and exon21 (L858R) were found with the frequency of 7.1% (2 cases) and 14.3% (4 cases), respectively. Median age of the RET-rearranged patients was 55 yr (range 41~74 years), M: F ratio 8:20. Seventeen patients were never-smoker. Median RFS was 29.4 mo. (range 20.7~60.9 mo.) and median OS was 41.1 mo. (range 29.5~152.7 mo). In statistical analysis of total 279 patients, the younger age ( < 62) and female gender were significantly associated with RET rearrangement (P = 0.011 and P = 0.004, respectively). The protein expression of RET (P = 0.551) as well as RET-related signal molecules including pAKT (P = 0.520), pERK (P = 0.311) and VEGF (P = 0.626) had no significant association with RET rearrangement. Conclusions: With strict criteria for interpretation of FISH data, the frequency of RET rearrangement was 10.0% in lung adenocarcinomas. Now, we are undergoing molecular study to identify a novel partner of RET fusion gene.
Effect of targeting the gp130 receptor rather than the IL-6 receptor on control of multiple myeloma growth.
Authors: Renate Burger, Andreas Guenther, Katja Klausz, Matthias Staudinger, Matthias Peipp, Martin Gramatzki
Journal: Journal of Clinical Oncology (2014)

e19576 Background: Due to the role of interleukin-6 (IL-6) in malignant plasma cell growth and survival, IL-6 and its receptor are considered potential targets for therapy of multiple myeloma. Monoclonal antibodies (mAb), such as elsilimomab (B-E8) and siltuximab (CNTO328), have already been evaluated in clinical trials, however, so far with limited success. The aim of this study was to evaluate the role of different gp130 cytokines in vivo in a cytokine-regulated xenograft tumor model mimicking growth regulation of malignant plasma cells. Methods: Cytokine dependent INA-6.Tu1 plasma cells were injected intraperitoneally into irradiated SCID or SCID beige mice and subsequently treated with murine mAb against IL-6 (clone B-E8), IL-6R (clone B-R6) and with two mAb recognizing the gp130 signaling subunit (clones B-R3 and B-K5). Treatment started one day after cell inoculation for 2 weeks and a total of 0.85 mg antibody per animal was injected. Survival was calculated by log-rank test (GraphPad Prism 6). Results: Treatment of mice bearing INA-6.Tu1 cells with antibodies B-E8 (IL-6) and B-R6 (IL-6R) modestly prolonged the time until plasmacytomas appeared, the differences to the PBS treated animal group, however, did not reach significance (p≥0.18). In contrast, plasmacytoma growth was completely prevented with the gp130 antibodies B-R3 and B-K5 (p<0.01). Importantly, complete tumor growth inhibition was also achieved using F(ab’)2 fragments of the B-R3 antibody without activity in antibody-mediated cellular cytotoxicity (ADCC). Among different gp130 cytokines that were provided in vitro, B-R3 and B-K5 were unable to block plasma cell growth stimulated by IL-6. Instead, their high efficacy in vivo argues for growth stimulation by oncostatin M (OSM) or leukemia inhibitory factor (LIF). Such cytokines of the gp130 family may provide the redundancy important for myeloma cell growth. Conclusions: For myeloma cell growthin vivo,gp130 activation mediated by other cytokines than IL-6 may be important and explain why IL-6 blockade appears rather incomplete and short lived. Targeting gp130 signaling may overcome this redundancy and gp130 antibodies may have a therapeutic window in such a situation.
Genetic Heterogeneity in Therapy-Naïve Synchronous Primary Breast Cancers and Their Metastases
Authors: Charlotte K.Y. Ng, Francois-Clement Bidard, Salvatore Piscuoglio, Felipe C. Geyer, Raymond S. Lim, Ino de Bruijn, Ronglai Shen, Fresia Pareja, Samuel H. Berman, Lu Wang, Jean-Yves Pierga, Anne Vincent-Salomon, Agnes Viale, Larry Norton, Brigitte Sigal, Britta Weigelt, Paul Cottu, Jorge S. Reis-Filho
Journal: Clinical Cancer Research (2017)

Purpose: Paired primary breast cancers and metachronous metastases after adjuvant treatment are reported to differ in their clonal composition and genetic alterations, but it is unclear whether these differences stem from the selective pressures of the metastatic process, the systemic therapies, or both. We sought to define the repertoire of genetic alterations in breast cancer patients with de novo metastatic disease who had not received local or systemic therapy.Experimental Design: Up to two anatomically distinct core biopsies of primary breast cancers and synchronous distant metastases from nine patients who presented with metastatic disease were subjected to high-depth whole-exome sequencing. Mutations, copy number alterations and their cancer cell fractions, and mutation signatures were defined using state-of-the-art bioinformatics methods. All mutations identified were validated with orthogonal methods.Results: Genomic differences were observed between primary and metastatic deposits, with a median of 60% (range 6%-95%) of shared somatic mutations. Although mutations in known driver genes including TP53, PIK3CA, and GATA3 were preferentially clonal in both sites, primary breast cancers and their synchronous metastases displayed spatial intratumor heterogeneity. Likely pathogenic mutations affecting epithelial-to-mesenchymal transition-related genes, including SMAD4, TCF7L2, and TCF4 (ITF2), were found to be restricted to or enriched in the metastatic lesions. Mutational signatures of trunk mutations differed from those of mutations enriched in the primary tumor or the metastasis in six cases.Conclusions: Synchronous primary breast cancers and metastases differ in their repertoire of somatic genetic alterations even in the absence of systemic therapy. Mutational signature shifts might contribute to spatial intratumor genetic heterogeneity. Clin Cancer Res; 23(15); 4402-15. ©2017 AACR.
Aggressive surgical management of germ cell tumors with somatic-type malignancy: Pathologic features, prognostic factors, and survival outcomes.
Authors: Kevin R Rice, Martin J Magers, Stephen Beck, Lawrence H. Einhorn, Thomas M. Ulbright, Richard Foster
Journal: Journal of Clinical Oncology (2013)

4554 Background: Germ cell tumors (GCT) with somatic-type malignancy (SM) are rare occurring in approximately 3-8% of GCT cases. Prognostic factors and optimal management remain poorly-defined. Methods: The Indiana University (IU) testis cancer database was queried from 1979 to 2011 for patients demonstrating atypical histology at orchiectomy or subsequent resection of metastatic disease. Patients with transformation to PNET only were excluded due to distinct management. Chart review, pathologic review, and survival analysis were performed. Results: 122 patients met study inclusion criteria. Primary tumor site was testis in 112, retroperitoneum in 8, groin in 1, and pineal gland in 1. The most common SM histologies were sarcoma (71) and carcinoma (32). At GCT diagnosis, 24, 44, 45 patients had stage I, II, and III disease, respectively. Stage was unknown in 9. Median time from GCT diagnosis to SM was 13 months (Range, 0-397). This interval was longest for carcinomas (94.5 months) and sarcomatoid yolk sac tumors (113 months). Only 11 of 83 patients (13.3%) receiving cisplatin-based chemotherapy for measurable disease demonstrated an initial complete response. First resection at IU was reoperative in 45 patients (36.9%). 69 patients (56.6%) required extirpation of abdominal viscera/vascular structures or distant metastases. At a median follow-up of 71 months, the 5-year cancer specific survival (CSS) was 63%. Predictors of poorer CSS included SM diagnosed at late relapse (p = 0.014), referral to IU for reoperative RPLND (p = 0.022), and tumor grade (p = 0.043). SM histology subtype, stage, risk category, and number of resections for SM were not predictive of CSS. Conclusions: GCT with SM is associated with poorer CSS than traditional GCT. Established prognostic factors for GCT lose their predictive value in the setting of SM. SM can occur at any point in the course of GCT, but has a propensity for delayed presentation with later onset being associated with poorer CSS. Aggressive and serial surgical resections are often necessary to optimize CSS. Tumor grade is an important prognostic factor, particularly in sarcoma cases.
SELECT: A multicenter phase II trial of adjuvant erlotinib in resected early-stage EGFR mutation-positive NSCLC.
Authors: Nathan A. Pennell, Joel W. Neal, Jamie E. Chaft, Christopher G. Azzoli, Pasi A. Janne, Ramaswamy Govindan, Tracey L. Evans, Daniel Botelho Costa, Rachel Pam Greenerger Rosovsky, Heather A. Wakelee, Rebecca Suk Heist, Alice Tsang Shaw, Jennifer S. Temel, Marc A. Shapiro, Alona Muzikansky, Michael Lanuti, Thomas James Lynch, Mark G. Kris, Lecia V. Sequist
Journal: Journal of Clinical Oncology (2014)

7514 Background: EGFR mutant NSCLC is exquisitely sensitive to EGFR tyrosine kinase inhibitors (TKIs). Retrospective data suggests adjuvant TKIs may improve outcomes. This trial is the first to prospectively test the efficacy of adjuvant erlotinib in EGFR-mutant NSCLC. Methods: Eligible pts had resected stage IA-IIIA NSCLC harboring a TKI-sensitizing EGFR mutation. Pts were treated with erlotinib 150 mg/day for 2 years after completion of standard adjuvant chemotherapy and/or radiotherapy. With a sample size of 100 pts the study was powered to demonstrate a primary endpoint of 2-year disease free survival (DFS) >85%, compared to a historical control of 76% in resected early-stage EGFR-mutant NSCLC. Results: 100 pts were enrolled at 7 sites between 1/08 and 5/12; 45% stage I; 27% stage II; 28% stage IIIA. 89 pts have reached 2 year follow-up (2 year follow-up on the entire cohort will be presented at the annual meeting). Toxicities were typical of erlotinib with no G4/5 events and 1 G2 pulmonary fibrosis. 40% of pts required dose reduction to 100 mg/day and 16% two dose reductions to 50 mg/day. 69% of pts completed at least 22 months of erlotinib. With median follow-up of 3 years, the 2-year DFS is 90% (97% stage 1, 73% stage 2, 92% stage 3). Median DFS and OS have not been reached. 24 pts have recurred, only 2 during erlotinib treatment and 22 after stopping erlotinib with a median time to recurrence of 12 months after stopping erlotinib. 63% (n=15) of pts with recurrence underwent repeat biopsy, and only 1 T790M was detected. 71% (n=17) of recurrent pts were re-treated with erlotinib with 10 pts remaining on erlotinib, treatment range 2-42 months. 8 pts have died. Conclusions: Pts with EGFR mutation-positive NSCLC treated with adjuvant erlotinib have an improved 2-year DFS compared to historical genotype-matched controls. Recurrences are rare on erlotinib and most occur in the 12m after discontinuation, suggesting longer duration of adjuvant treatment may be beneficial. Recurrent cases after adjuvant erlotinib remain generally sensitive to EGFR TKIs. Clinical trial information: NCT00567359.
Sequencing of single-agent (SA) docetaxel (T) and gemcitabine (G) therapy for patients (pts) with advanced non-small cell lung cancer (NSCLC): Results of three consecutive randomized trials
Authors: C. Manegold, N. Thatcher, C. Kortsik, G. Koschel, J. Mezger, K. Schott Von Römer, L. R. Pilz
Journal: Journal of Clinical Oncology (2006)

7035 Background: Standard doublet chemotherapy (DCT) is often clinically inappropriate. Since T and G show efficacy and favourable toxicity as SAs in 1st- and 2nd-line setting, sequencing of T and G may be an equally effective alternative to DCT for palliation. Three studies (S1-S3) were conducted: two to identify an optimal SA-sequence (S1/S2), and one to compare sequential SA to a platin-free doublet (S3). Methods: Common eligibility criteria included histologically confirmed stage IIIB or IV, performance status (PS) 0–2, and no prior chemotherapy. S1/S2 examined treatment feasibility (TF) of G or T with introduction of the opposite agent in case of progression. TF was defined as pt ability to receive ≥2 cycles (cyc) of 1st-line and if progressive ≥2 cyc of 2nd-line therapy and to survive ≥7 months (mos). In S1, G 1000 mg/m 2 and T 35 mg/m 2 was given on days (d) 1, 8, 15 (q4w) and in S2, G 1250 mg/m 2 (d 1, 8) and T 100 mg/m 2 (d 1; q3w). In S3, pts received G 1000 mg/m 2 (d 1, 8) and T 75 mg/m 2 (d 1; q3w) either concomitantly (G+T; 6 cyc) or sequentially (G→T; 3 cyc each). Primary endpoint of S3 was clinically relevant haematotoxicity (CRHT) defined as thrombocytopenia with platelet transfusions, anaemia with RBC-transfusions or febrile neutropenia with i.v. antibiotics (IVAB). Results: 819 pts were included (1998–2004): 85% of pts had stage IV disease and PS≤1. In S1 and S2 for (G→T)/(T→G) respectively: TF was 28/20% and 38/49% (p=.04); median survival (MS) was 9.0/5.0 mos (p=.03) and 6.3/8.6 mos; and median time to progression (TTP) was 4.3/2.2 mos and 2.4/3.3 mos. In S3, CRHT occurred less frequently with SA therapy (p&lt;.001), transfusions and IVAB treatment days were less common. QoL also favoured SA therapy. For (G+T)/(G→T), MS was 7.3/7.4 mos, response rate was 33/22% (p=.05) and TTP was 6.3/4.9 mos (p=.04). Conclusions: Sequencing modern SA was effective and well tolerated. Weekly T and G regimens seem less feasible than 3-weekly but compared to the nonplatinum doublet CRHT and IVAB are reduced with better QoL and cost-effectiveness. [Table: see text]
The relevance of stable disease (SD) as a surrogate end-point in advanced non-small cell lung cancer (NSCLC) patients treated with erlotinib (E) as the second/third line.
Authors: Francesco Grossi, Claudio Sini, Giulia Barletta, Erika Rijavec, Carlo Genova, Maria Giovanna Dal Bello, Paolo Pronzato, Paola Venturino, Giovanni L. Pappagallo
Journal: Journal of Clinical Oncology (2012)

7577 Background: SD has often been viewed as a result with an uncertain clinical value.With the advent of E in advanced NSCLC, increasing numbers of patients (pts) achieve SD as a best response. A common observation in clinical practice is that a high proportion of patients receiving E have durable SD.The aim of this analysis was to compare the progression-free survival (PFS) and overall survival (OS) in pts with advanced NSCLC who achieved confirmed SD or complete/partial response (CR+PR) after second/third line treatment with E. Methods: Data from 684 Italian pts from the TRUST trial (Tiseo M et al. Lung Cancer 2008) were analyzed. E was administered orally at 150 mg per day and was continued until disease progression, development of unacceptable toxicity or patient’s refusal. We define confirmed SD (cSD) if the patients’ PFS was ≥5 months (response to E was evaluated per protocol every two months) and reconfirmed SD (rSD) if the patients’ PFS was ≥8 months. Results: Pts’ characteristics included the following: median age, 67 years (31-89); females/males= 219/465 pts (32%/68%); never/former smokers= 191/493 pts (28%/72%); squamous/adeno/BAC/large cell/NOS= 163/361/26/21/113 pts (24%/53%/4%/3%/16%); ECOG PS 0-1/2-3= 557/127 pts (81%/19%). In 83 pts (12%), E was administered as the first-line therapy in pts who were unable to receive chemotherapy; 305 pts (45%) had received 1 prior line of chemotherapy, and 296 pts (43%) had received 2 prior lines of chemotherapy. A total of 428 pts were evaluable for a response: 44 pts (10%) exhibited CR+PR, 226 pts (53%) attained SD, which consisted of 139 pts (32%) with cSD and 83 pts (19%) with rSD. The median PFS estimates (with 95% CI) were 13.1 months (9.8-16.4) for CR+PR pts, 9.9 months (8.2-11.4) for cSD pts and 14 months (12-16) for rSD. The median OS estimates (with 95% CI) were 24.0 months (17-31) for CR+PR pts, 17.9 months (14.4-21.5) for cSD pts and 24.9 months (18.1-31.7) for rSD. Conclusions: Our findings are the first to demonstrate the relevance of achieving stable disease with E treatment. Pts obtaining cSD or rSD had durable PFS and OS comparable, particularly for rSD, with PFS and OS of those having CR+PR.
Anaplastic large cell lymphoma (ALCL) ALK positive and ALCL ALK negative uniformly treated with intensive alternating chemotherapy at a single institution.
Authors: Joanna Romejko-Jarosinska, Katarzyna Domanska-Czyz, Beata Ostrowska, Ewa Paszkiewicz-Kozik, Lidia Poplawska, Grzegorz Rymkiewicz, Jan Andrzej Walewski
Journal: Journal of Clinical Oncology (2012)

e18512 Background: Anaplastic large cell lymphoma ALK positive (ALCL ALK+) is frequently referred to as easily curable disease, however, patients with more than 1 IPI risk factors have a poor outcome. ALCL ALK negative (ALCL ALK-) have usually higher IPI score and there is no general consensus on what treatment is the optimal. We evaluated data on 26 consecutive patients with ALCL ALK+ and ALCL ALK- treated uniformly at our institution between July 2004 and April 2011. Methods: 26 patients with ALCL ALK+ or ALCL ALK- were treated according to GMALL B-ALL/NHL 2002 protocol (Hoelzer D et al. Blood 2007; 110: Abstr. 518) without rituximab. Kaplan-Meier method and Cox’s model were used to analyze overall survival time and progression free survival time. Results: ALK protein expression was tested in 26 patients, 19(73%) were positive, 5(27%) were negative. Median age was 33 years (range 16-53). 14 pts (54%) were male, 20 (77%) were in clinical stage (CS) III or IV, 16 (61,5%) had B symptoms, 10(38,5%) had bulky disease, 10 (38,5%) had LDH &gt; N, and 20 (77%) had IPI score &gt;1. The overall response rate (ORR) was evaluated in 23 of 26 patients. The ORR was 87% (20/23 patients). After median follow up of 26 months (range; 6-90) overall (OS) and progression free survival (PFS) at 2 years was 67%: 95% C.I.=[48%, 86%] and 65%: 95% C.I.=[48%, 82%], respectively. On multivariate analysis none of factors: CS III and IV, B symptoms, bulky disease, IPI score&gt;2, LDH&gt;N, ALK expression influenced OS and PFS. The major toxicity was reversible myelosuppression: grade 4 neutropenia occurred after every cycle. Other complications included mucositis and infection. Two toxic deaths (7,6%) from sepsis occurred during neutropenia after first cycle of treatment. Conclusions: These results suggest that GMALL- B-ALL/NHL 2002 protocol is an effective treatment for both ALCL ALK + and ALCL ALK-, however, toxicity is remarkable, with neutropenia and infection being most frequent complications.
Modulation of insulin-like growth factors following exercise in breast cancer: A meta-analysis of randomized controlled trials.
Authors: Jose F Meneses-Echavez, Robinson Ramirez-Velez, Jorge Enrique Correa Bautista
Journal: Journal of Clinical Oncology (2015)

e22012 Background: Insulin resistance,Insulin-like growth factor 1 (IGF-1), IGF-2 and IGF binding protein-3 (IGFBP-3) are associated with breast cancer risk, cell growing, apoptosis and other tumoral mechanisms. This study aimed to determine the changes on IGF system following exercise in women with breast cancer. Methods: PRISMA statement and the Cochrane Handbook were followed. We searched MEDLINE, Ovid, EMBASE and Cochrane Central Registers to identify randomized controlled trials published between 1990 and October 2014. Primary outcomes measures were: Insulin resistance,IGF1, IGF-2 and IGFBP-3, whilst waist circumference was evaluated as a measure of body composition. For pooled analysis, mean difference (MD) (p < 0.05 with 95% Confidence interval). Results: Seven studies (n = 321) were included. There was high quality and a low risk of bias. Pooled analyses demonstrated that exercise training resulted in significant changes on IGF-I (MD = -12.9, 95%CI -16.73 to -9.14), IGF-II (MD = -43.4, 95%CI -58.5 to -28.3), IGFBP-3 (MD = -0.61, 95%CI -0.69 to -0.53) and waist circumference (MD = -1.13, 95%CI -2.20 to -0.05). Conversely, non-significant differences were found for Insulin Resistance (MD = 0.64, 95%CI -0.01 to 1.29), Insulin (MD = 0.04, 95%CI -0.24 to 0.34) and Glucose (MD = 0.22, 95%CI -0.32 to 0.78). Reporting bias was not observed. Conclusions: The serum levels of insulin like growth factors (IGF1-IGF2) and IGFBP3 were positively modulated by exercise training in breast cancer survivors, enhancing the physiological basis of exercise in regulating cellular proliferation and other tumoral mechanisms in breast cancer.
Activity of abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) previously treated with ketoconazole (keto): A prospective phase II study from the Prostate Cancer Clinical Trials Consortium.
Authors: Won Kim, John Wilton, Li Zhang, Amy M. Lin, Lawrence Fong, Andrew Caleb Hsieh, Terence W. Friedlander, Rahul Raj Aggarwal, Vivian K. Weinberg, Allison Morse, Jeffrey Bozeman, Arturo Molina, Gerald J. Fetterly, James Mohler, Russell Zelig Szmulewitz, Eric Jay Small, Charles J. Ryan
Journal: Journal of Clinical Oncology (2014)

5039 Background: AA, like keto, inhibits CYP17, the rate-limiting enzyme in androgen synthesis. Since pts with prior keto were excluded from the pivotal phase III AA trials, the utility of AA following keto is not well understood. This prospective study evaluated the efficacy of AA in pts previously treated with keto. Methods: Pts with progressive mCRPC, prior keto ≥28 days, and normal baseline organ function were treated with AA 1000mg PO daily and prednisone 5mg PO BID. Pts with prior chemotherapy were excluded. Serum androgen levels, including dehydroepiandrosterone (DHEA), were measured by liquid chromatography/mass spectrometry (LC/MS) at baseline and during treatment for exploratory analyses. Radiographic progression-free survival (rPFS) was defined as freedom from death, radiographic progression, or unequivocal clinical progression. Results: 42 pts were enrolled. Median duration of prior keto was 38 weeks (wks). 40 pts discontinued keto due to disease progression, and 2 due to toxicities. AA resulted in ≥30% PSA decline at 12 wks in 20 pts (48%, 95% CI 32-63%), and ≥50% PSA decline at 12 wks in 16 pts (38%, 95% CI 24-54%). Median time on prior keto was significantly shorter in pts who had ≥30% PSA decline compared to those who had <30% decline (20 vs. 58 wks, p=0.003). Median time to PSA progression (TPP) was 16 wks (range, 4-64). Median rPFS was 24 wks (range, 1-88). Baseline serum DHEA levels were measured in 40 pts. 9 pts had DHEA < limit of quantitation (LOQ, 0.250ng/mL), and 31 pts had DHEA ≥LOQ. 1 pt with DHEA <LOQ (1/9, 11%) had PSA decline ≥30% at 12 wks, compared to 17 pts (17/31, 55%) with DHEA ≥LOQ (p=0.027). Median TPP was 6 wks (range, 4-32) for pts with DHEA <LOQ, compared to 16 wks (range 4-64) for pts with DHEA ≥LOQ (p=0.017). Median rPFS was 12 wks (range, 4-36) for pts with DHEA <LOQ, compared to 31.5 wks (range, 1-88) for pts with DHEA ≥LOQ (p=0.0009). 4 pts remain on AA. Conclusions: AA retains clinical activity in a significant proportion of pts previously treated with keto. DHEA levels via LC/MS merits further study as a biomarker in pts treated with androgen synthesis inhibitors.