tbuckley/cabot-search huggingface dataset:
A retrospective analysis of clinical factors influencing response to treatment with cabazitaxel in patients with metastatic castration resistant prostate cancer.
Authors: Daniel Yokom, Nimira S. Alimohamed, Eric Winquist, Scott R. Berry, Stacey Hubay, Jean-Baptiste Lattouf, Helene Leonard, Carla Girolametto, Fred Saad, Srikala S. Sridhar
Journal: Journal of Clinical Oncology (2015)

281 Background: The TROPIC trial demonstrated that cabazitaxel improves overall survival (OS) in mCRPC patients progressing on or after docetaxel; a setting where both abiraterone and enzalutamide are also approved. We evaluated baseline factors that may help predict prostate specific antigen (PSA) response or PSA progression defined as per the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria and OS in mCRPC patients treated with cabazitaxel. Methods: Forty patients from five centres participated in an early access program and were retrospectively reviewed to capture baseline characteristics, disease history, prior and subsequent treatments, PSA response, and OS. The influence of selected variables on PSA response and OS were evaluated by univariate and multivariate stepwise regression analysis. Results: At cabazitaxel initiation, median age was 65, ECOG 0-1 (90%), median PSA was 216 ng/mL, 25% had visceral disease and 70% had pain. Median number of prior docetaxel cycles was 9 and median time from treatment was 9.6 months (5-14.2). Median number of cabazitaxel cycles was 7 (1-27). Fourteen patients received abiraterone before cabazitaxel. In patients with prior abiraterone treatment there was no impact on PSA response compared to patients with no prior abiraterone. In the multivariate regression analysis, presence of visceral disease, low albumin (≤40g/L), low hemoglobin (&lt;100 g/L) and longer time between last docetaxel dose and start of cabazitaxel were correlated with PSA response to cabazitaxel (p&lt;0.10). Age &lt; 65, BMI ≥ 30kg/m2 and presence of pain were linked to an increased likelihood of PSA progression. None of the factors selected were significantly associated with OS. Conclusions: In routine clinical practice, this study suggests that mCRPC patients with visceral disease and a longer time elapsed between last docetaxel dose and start of cabazitaxel may experience a greater PSA response with cabazitaxel.
Final results of the Montpellier prostate cancer intensity modulated radiotherapy pilot study.
Authors: Marie Charissoux, Pascal Fenoglietto, Norbert Ailleres, Simon Thézenas, Xavier Rebillard, Carmen Llacer Moscardo, Rodolphe Thuret, Meng Huor Hay, Bruno Segui, Antoine Faix, Jean-Bernard Dubois, David Azria
Journal: Journal of Clinical Oncology (2014)

105 Background: Thirteen hundred prostate cancer patients have been treated with Intensity modulated radiotherapy (IMRT) since 2001. We present the final results of the pilot study concerning the first 373 patients with a median follow-up of 72.7 months (range 0 to 130). Methods: All patients received the entire treatment course to a prescribed total dose of 80 Gy. No pelvic irradiation was applied. Androgen ablation therapy was delivered for 6 months and 2 to 3 years in intermediate and high-risk patients, respectively (n=142, 38%). Prostate-specific antigen (PSA) failure was defined as nadir + 2. Toxicity was assessed according to the National Cancer Institute (NCI)/Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Multivariate analysis using the Cox model was performed to assess factors that may impact on PSA relapse. Logistic regression was used to correlate clinical and physical parameters with grade 2 or higher gastro-intestinal and genitourinary toxicities. Results: Median age was 69 (range 40 to 81). One hundred thirty nine (37.3%), 167 (44.8%), and 67 (18%) patients were classified as low (group 1), intermediate (group 2), and high-risk (group 3) patients, respectively. The 5 year biochemical relapse-free survival (5y-biochemical recurrence-free survival [bRFS]) was 85.7% (95% CI, 0.81-0.89). For the three prognostic groups, 5y-bRFS was 91% (95% CI, 0.85-0.95), 82% (95% CI, 0.75-0.87), and 80% (95% CI, 0.67-0.88) for groups 1, 2, and 3, respectively. Multivariate analysis showed that the absence of hormonotherapy in the group 2 and the number of positive biopsies impact on PSA relapse (p=0.04, HR 1.8 and p=0.01, HR 2.13, respectively). The incidence of late grade 2 or higher rectal and urinary toxicities were 10.5% and 12.7%, respectively. The dose received by 50% (D50) of the rectum was the only factor significantly correlated with late grade 2 or higher rectal toxicities (p = 0.04). Similarly, the dose received by 50% (D50) of the bladder was the only factor significantly correlated with late grade 2 or higher bladder side-effects (p = 0.02). Conclusions: IMRT to 80 Gy can provide good to excellent carcinologic results and low late toxicity rates in all prostate cancer subgroups. Hormonotherapy combined to high dose IMRT seems to be a serious option to consider in intermediate-risk patients. Clinical trial information: ICM 2001-13.
Effect of metastasectomy on survival in patients with metastatic Renal Cell Cancer: 10 years experience in 240 patients
Authors: M. Staehler, J. Kruse, N. Haseke, T. Stadler, A. Karl, C. Bruns, C. Graeb, K. Jauch, C. G. Stief
Journal: Journal of Clinical Oncology (2008)

5107 Background: The aim of this study was to evaluate the efficacy of metastasectomy in metastatic renal cell carcinoma (mRCC). Methods: We included n=240 patients with potentially resectable mRCC between 1995 and 2006 at the University Hospital Munich Großhadern. All patients underwent nephrectomy, in n=183 patients metastasectomy was performed (Mx). The control group consisted of n=57 patients who denied surgery (M). Sites of metastases were liver (L), lungs (Lu), lymph nodes (Ln) and other (O). Surgery was performed in n=68 LMx, n=121 LuMx, n=87 LnMx, n=141 OMx, with controls of n=20 LM, n=41 LuM, n=29 LnM and n=36 OM. Patients were evaluated according, to MSKCC prognostic score, grading, histological subtype, and administration of systemic therapy. Results: The 5-years overall survival rate (5OSR) was 52.6% (±6.9). The 5OSR was significantly higher in Mx patients than in M patients, 57.8% (±5.9) vs. 35.3% (±9.2) respectively (p < 0.001). In Mx patients significant survival benefit compared to M patients was found to be independent from the metastatic site (see table). No benefit for Mx was found in G3/G4 patients. All other parameters, such as histological subtypes and prognostic score showed a significant survival benefit for MX patients. Conclusion: The 5-years OSR was significantly higher in patients who underwent metastasectomy. The only negative prognostic factor for surgery was grading with G3/4 tumours not showing a survival benefit with MX. Thus, in patients with G1 and G2 mRCC metastasectomy should be standard of care if technically feasible. Parameter Mx M p L 60.6 29.3 0.03 Lu 58.0 33.8 <0.001 Ln 49.4 32.3 0.013 O 57.0 35.4 <0.001 G1/G2 69.3 35.3 <0.0001 G3/G4 27.8 33.8 n.s. Clear Cell 61.9 44.7 0.002 Other Histology 26.5 0.0 0.022 MSKCC Score low/ intermediate 66.9 32.9 0.022 MSKCC high 54.0 32.4 0.0006 Systemic therapy 57.8 34.9 0.002 No systemic therapy 57.5 35.4 0.003 No significant financial relationships to disclose.
Outcome analysis of primary liver carcinomas.
Authors: Maria Majella Doyle, Neeta Vachhajarani, Nael Saad, Kathryn Fowler, Benjamin R. Tan, Elizabeth Brunt, William C. Chapman
Journal: Journal of Clinical Oncology (2016)

438 Background: Treatments for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCCa) are established. Significant debate exists over optimal treatment for biphenotypic primary liver carcinomas (PLC) with combined HCC and IHCCa (B-PLC) and is considered to be a contraindication for transplantation. The purpose of this analysis is to determine single center outcomes of patients with B-PLC compared to HCC and IHCCa. Methods: A prospective database was reviewed to determine treatments and survivals of patients with HCC, IHCCa and B-PLC. Results: From 1/1/2009 to 12/31/2014, 810 patients with PLC were treated with resection (LRx) (n = 117), liver transplant (OLT) (n = 224) or liver directed therapy (LDT) (n = 469). 723 patients had HCC, 34 had IHCCa and 53 had B-PLC. Overall Survival (OS) in the LDT group, was similar comparing all tumor types at 1 yr (61.7%) and 3 yrs. (23.8%) (p =.3) Median survival (MS) was 16.2 months. OS in the LRx group was also similar between tumor types (1yr 81.1% and 5yrs. 41.1%, p =.2) and MS was 40.9 months. Comparing OLT patients with HCC (n = 212, 77% within Milan) to B-PLC (n = 10, 70% within Milan), OS (1yr 92.5% and 5 yrs. 77.0%, p =.8) was comparable and so also were disease-specific (1yr 99.0% and 5yr 97.3%, p =.6) and disease-free (1yr 88.7% and 5yrs. 73.5%, p =.4) survivals. OS for patients with B-PLC was significantly greater in patients receiving OLT vs. LRx or LDT (p =.005). Conclusions: Biphenotypic PLC has a poor prognosis and has been considered a contraindication for OLT. In this limited series, however, outcomes with transplantation appear acceptable.
SCAT trial: Phase III Spanish customized adjuvant treatment according BRCA1 mRNA levels in stage II-IIIA non-small cell lung cancer.
Authors: B. Massuti, U. Jimenez, J. M. Rodriguez Paniagua, Y. W. Pun, M. Cobo, E. Carcereny Costa, R. Arrabal, J. Astudillo, I. C. Barneto, R. De Las Penas, C. Baamonde, G. Sales, J. Gonzalez-Larriba, G. Lopez-Vivanco, F. Hernando-Trancho, J. Pac, A. Artal-Cortes, J. Rivas, R. Rosell, J. M. Sanchez
Journal: Journal of Clinical Oncology (2011)

TPS208 Background: Postop platinum-based CT improves outcomes in completely resected NSCLC with nodal involvement, (St II-IIIA). Standard adjuvant CT is still insufficient to provide optimal survival . Improvement could be obtained through better risk selection or customized therapy. mRNA BRCA1 levels are prognostic in early NSCLC (Rosell et al 2007) and could be a predictive marker for CT activity. BRCA1 expression level could acts as a differential modulator of CT. In advanced disease p with low BRCA1 benefit from cisplatin-doublets meanwhile p with high levels BRCA1 attained longer survival when were treated with taxanes (Rosell et al 2008). Pharmacogenomic customization is feasible in adjuvant setting due to tissue availability and timelines after surgery. Previous pilot trial p with high-expression levels treated with postoperative CT singel agent taxane do not showed inferior outcomes compared to the groups treated with cisplatin-doublets (Massutí et al 2009 WLCC). Methods: Phase III prospective randomized trial of 4 cycles selected vs non-selected adjuvant CT. Eligibility criteria: NSCLC, complete R0 resection, pN1 or pN2, KI > 70, recovered from surgery, ANC > 1,500/µL, Hb > 10 g/dL, platelets > 100,000/µL, bilirrubin < 1.0 mg/dL, GOT & GPT < 1.5 x UNL, creatinine clearance > 60 mL/min, no prior RT or CT, age > 18 y, signed informed consent. Stratification factors: N1 vs N2; Histology (squamous vs non-squamous), extent of resection (lobectomy vs pneumonectomy). Central lab for measurement of mRNA BRCA1 levels and quartile distribution. Primary end-point: Disease free survival. Secondary end-points: Survival, Toxicity profiles, Recurrence pattern. Tissue and serum samples collected for Translational research. Statistical hypothesis: Randomization: 1:3 (control/experimental arms); Accrual: 432 patients; 5-year survival rate 45% control group; Absolute improvement of 20% in experimental group; 80% powered; 2-sided type I error of 5%; Anticipated loss of 10% cases. Trial design is shown in the table. 1 Control arm Cisplatin-docetaxel x 4 N2 PORT Random 3 Experimental Arm Q1 cisplatin-gemcitabine x4 N2 PORT Q2-3 cisplatin-docetaxel x 4 Q4 docetaxel x 4 Opened June 2007. Current accrual; 272/432.
RAD001 and zoledronic acid in patients with renal cell carcinoma with bone metastases (RAZOR): A randomized phase II trial.
Authors: Reuben James Broom, Vicky Hinder, Katrina Sharples, Janie Proctor, Steven Duffey, Stephanie Pollard, Peter C.C. Fong, Garry Forgeson, Anne O'Donnell, Dean Laurence Harris, Sanjeev Deva, Michael B. Jameson, Richard T. North, Andrew Grey, Michael P. N. Findlay
Journal: Journal of Clinical Oncology (2013)

402 Background: Bone metastases (BM) from renal cell carcinoma (RCC) are common, cause morbidity, and have been identified as an adverse prognostic feature. Previous trials have not assessed the effects of modern therapies on BM from RCC. Randomized data has demonstrated that zoledronic acid (Z) reduces skeletal-related-events (SREs) in RCC patients (pts). Bone turnover markers can identify pts at risk of SREs among those receiving Z. We sought to evaluate the effect on BM of RAD001 (R) (everolimus) alone compared to R+Z in the first-line setting. Methods: 30 treatment naïve pts with RCC and ≥ 1 BM were randomized 1:1 to R 10mg daily vs. R+Z 4mg IV 4-weekly (dose adjusted for creatinine clearance [CrCl]). Key eligibility criteria were ECOG PS ≤ 2, no bisphosphonates, or radiotherapy within 4 wks and CrCl &gt;35ml/min. Bone-specific assessments were performed at baseline, wks-1, 4, 8, and 12. Treatment was continued on allocated arm until progression (RECIST 1.1). The primary objective was to assess the difference in bone turnover markers over the first 12 wks. The primary endpoint was urine N-telopeptide (uNTX) level with secondary endpoints being plasma C-telopeptide (CTX), quality of life (FACT-BP, BPI), progression free survival (PFS), SREs, and safety. Results: Heng prognostic group poor, intermediate, and good risk was 20.0%, 46.7%, 33.3% in R+Z and 40.0%, 46.7%, 13.3% in R. Over first 12 wks, the reduction in mean: uNTX on R+Z relative to R was 68.4% (95% CI (60.1%, 74.9%); p&lt;0.0001); CTX on R+Z relative to R was 77% (95% CI (68%, 83%); p&lt;0.0001). For FACT-BP there was no evidence of a difference (p = 0.5) but addition of Z was favourable for BPI Severity -1.1 (-2.2, 0.23; p = 0.05) and BPI Interference -1.3 (-2.5, 0.03; p = 0.06). Median PFS was 7.5 mo (95% CI 3.4, 14.7) on R+Z and 4.6 mo (95% CI 3.2, 6.3) on R (p = 0.03). Median time to 1 st SRE was 9.6 mo (95% CI 4.3, 15.5) on R+Z and 5.2 mo (95% CI 1.6-8.2) on R (p = 0.03). Conclusions: Addition of Z to R significantly reduced bone resorption markers in this RCC population of pts with the adverse prognostic feature of BM. Pts receiving R+Z had prolonged time to 1 st SRE and PFS; larger studies are required to further evaluate the addition of bone-specific to targeted therapies in this disease. Clinical trial information: ACTRN12609000980235.
The role of reduced intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) in patients with acute myeloid leukemia (AML): a donor versus no donor comparison
Authors: M. Mohty, H. de Lavallade, C. Faucher, N. Vey, J.-A. Gastaut, D. Blaise
Journal: Journal of Clinical Oncology (2005)

6540 Background: Standard myeloablative allo-SCT is an established therapy for AML. However, because of the high incidence of procedure-related toxicity, this procedure is limited to younger pts. Methods: Using a genetic randomization through a “donor” vs “no donor” comparison, we assessed the benefit of RIC-allo-SCT among 95 adult high risk AML pts. Results: In an intention-to-treat analysis, the KM estimate of LFS was significantly higher in the “donor” group as compared to the “no donor” group (P=0.01; 54% versus 30% at 4 y). When restricting the analysis to pts who could effectively receive the RIC-allo-SCT, the difference in LFS was also significant between this group of 25 pts (“transplant” group) and the remaining 70 pts (“no transplant” group; P=0.001; 62% versus 31% at 4 y). In the “transplant” group, no grade 3 or 4 toxicities were encountered, and only 3 pts died from transplant-toxicity, for an overall TRM of 12% (95%CI, 3–32%). This relatively low TRM translated towards a significantly higher overall survival (OS) in the “transplant” group as compared to the “no transplant” group (P=0.01) Overall, 41 pts (43%; 95%CI, 33–53%) had relapsed at a median of 295 (range, 116–823) days after diagnosis, with the 4-y cumulative incidence of relapse being significantly higher in the “no transplant” group as compared to the “transplant” group (P=0.0002; 54% versus 12%). After controlling for all relevant factors [demographic characteristics, leukemia features, cytogenetics risk group, prior therapy, and number of chemotherapy induction courses to achieve first CR), identification of an HLA-identical sibling donor, and effective performance of RIC-allo-SCT], in the multivariate analysis, only an intermediate cytogenetic risk group (P=0.01; RR=1.2; 95%CI, 1.2–4.7) and effective performance of RIC-allo-SCT (P=0.001; RR=4.0; 95%CI, 1.7–9.6), were significantly predictive of an improved LFS Conclusions: If a matched related donor is identified, RIC-allo-SCT should be proposed for AML pts not eligible for standard myeloablative allo-SCT. No significant financial relationships to disclose.
Survival for patients with resectable lung metastatic colorectal cancer (mCRC).
Authors: Timothy Jay Price, Yoko Tomita, Carol Beeke, Robert Padbury, Amanda Rose Townsend, Guy Maddern, Amitesh Roy, David Roder, Christos Stelios Karapetis
Journal: Journal of Clinical Oncology (2015)

708 Background: Hepatic resection for CRC metastasis is now considered a standard of care and perioperative chemotherapy may improve outcomes. Resection of metastasis isolated to lung is also considered potentially curable, although there is still some variation in recommendations and no evidence for perioperative or adjuvant chemotherapy. Here, we explore patient characteristics and outcomes for patients undergoing lung resection for mCRC, with the liver resection group as the comparator. Methods: SA mCRC registry data were analysed to assess patient characteristics and survival outcomes between patients suitable for lung or liver resection. K-M survival analysis was used to assess OS. Results: 3,241 patient are registered on the database. 102 (3.1%) patients were able to undergo a lung resection compared to 420 (12.9%) a liver resection. Of the lung resection patients, 21% initially presented with liver only disease, 11% both lung and liver, and 7% brain or pelvic disease. 62 (61%) presented with lung only disease. Of these patients, 79% went straight to surgery and 34% had lung resection as the only intervention. When comparing the groups, they were balanced for age and sex, liver v lung; 67.7 years v 69.5 years, 63.6% v 57.8% male. There was no difference in pathological grade or KRAS MT rate when tested (36% liver v 32% lung). Compared to patients undergoing liver resection, those having lung resection were more likely to be metachronous (75.5% v 44%, p=&lt;0.0001) and have a rectal primary (43.1% v 30.7%, p=0.017). Chemotherapy for metastatic disease was given more often in liver resection patients (76.9% v 53.9%, p=0.17). Median overall survival is not reached for both arms and the lower hazard rate for lung than liver resection does not approach statistical significance (HR 0.82, 95% CI 0.54-1.24, p=0.33). The 3 and 5 year survival liver v lung as follows; 77% v 81% and 62% v 70%. Conclusions: Lung resection occurs less frequently than liver resection for metastatic disease as expected. There was no statistical difference in overall survival in patients suitable for lung or liver resection. These data support the potential for long term survival with resection of both lung and liver metastasis in mCRC.
Examining control of biological processes in testis tumors using RTQ-PCR.
Authors: A. Riecke, M. Port, H. U. Schmelz, C. Ruf, C. Sparwasser, M. Stockinger, J. Lu-Hesselmann, V. Meineke, M. Abend
Journal: Journal of Clinical Oncology (2010)

e15082 Background: In order to get further insights into biological processes of testis tumors we examined key biological processes in seminoma and non-seminoma testis tumors simultaneously. The focus was on biological functions like cell death, cell-cycle control, repair and stress response, which represent key functions and a focus in the field of tumorigenesis. Methods: Ten pure seminomas, ten nonseminomas (T1N0M0 to T3N2M1) and corresponding biopsies from normal tissues were examined. Expression of 37 genes related to cell death (n=12), cell cycle (n=8), repair (n=10) and stress response (n=7) were measured in duplicate using RTQ-PCR. Statistical measures such as coefficient of variation (CV), quantil calculations and Chi-square statistics (in univariate logistic or linear regression analysis) were performed using SAS. Results: Methodological variability was low (mean CV=12.3%, +11.6%) and inter-individual gene expression variability (CV) did not exceed 100% for 93% of the genes examined. Gene expression normalised by the housekeeping gene 18SrRNA decreased with age at operation, a trend which became significant for 14 from 37 genes in particular in normal tissues, but not in tumor tissues. Differential gene expression (normal tissue served as the individual reference) did not differ significantly between both entities (except for Clusterin, p=0.05). Genes controlling cell cycle checkpoints (cyclines, cdks) in part were upregulated and the key cell cycle inhibitor p21 downregulated. Cell death control was characterized by an up-regulation of certain key pro-apoptotic stimuli (TNFa, FasL, Fas-receptor, Bax, Caspase 3 and 4) and a down-regulation of anti-apoptotic stimuli (Bcl2, Bag1). Different repair processes (NER, NHEJ, HEJ) and stress response genes partly appeared down-regulated or showed control values. Conclusions: In summary, upregulated differentially expressed genes coding cell cycle control together with downregulated repair genes could promote tumorigenesis in testis tumors which becomes counteracted by upregulated proapototic and downregulated antiapoptotic genes. The integrity of this mechanism could explain the high curability rate inherent in these tumors. No significant financial relationships to disclose.