bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of primary biopsy mutational landscape to pre-docetaxel LDH for prediction of docetaxel therapeutic response.
Authors: Hiew Kenneth , Hart Claire Alexandre , Ali Adnan , Lau Maurice , Ramani Vijay A.C. , Sangar Vijay , Maddineni Satish , Elliott Tony , Clarke Noel , Brown Mick D. 
Published: February 2018

220 Background: There is a lack of biomarkers to predict docetaxel response. Here we assess the potential of pre-treatment LDH, associated to the mutational background of the primary biopsy taken prior to 1st line therapy with ADT, to predict docetaxel response in the castrate resistant setting. Methods: Clinical and associated primary biopsy targeted next-generation sequencing data from matched training (n = 150) and test (n = 120) sets of retrospective progressive mCRPC patients (diagnosed 1996-2006) treated with docetaxel therapy were analyzed. LDH thresholds were determined and validated on the training and test sets respectively. Clinico-pathological associations with LDH were assessed using student t-test, Wilcoxon test and Chi-square test and predictive value of LDH determined by linear regression analysis for PSA and radiologic response. Time to event outcomes (PFS & OS) was evaluated by Kaplan-Meier. Meta-analysis of LDH association with DNA repair genes in the MSKCC and SU2C/PCF was conducted using cBioPortal Results: Using pre-docetaxel serum LDH of ≥450U/L as a prognostic threshold (AUC:0.75 (SD 0.054, 95% CI, 0.650–0.864, P < 0.001)) patients with LDH ≥450U/L were poorer PSA responders, with shorter PFS (213 vs 372 days, HR 1.876 (95% CI, 1.289-2.730)) and OS (362 vs 563 days, HR 1.630 (95% CI, 1.127-2.357)). LDH was also an independent surrogate marker for prediction of poor radiologic response and survival following docetaxel chemotherapy (P = 0.043). Genomic analysis showed that patients with LDH ≥450U/L (9/14 (64.3%)) have a higher tumour mutational burden (TMB) at the point of primary pre-ADT biopsy (mean, 46.2 vs 6.2 mutations/MB; p = 0.129) and that they were more likely to have DNA repair gene mutation(s) (BRCA1/2, ATM, CHEK2 and Fanconi’s anemia gene). Meta-analysis of the large MSKCC and the SU2C-PCF patient genomic databases confirmed the positive correlation between the LDH gene LDHA and PARP1 gene (r = 0.667, p < 0.01) expression and expression of other DNA repair genes. Conclusions: High pre-treatment serum LDH coupled with mutations in the DNA repair pathway in primary pre-ADT biopsy correlates with poor docetaxel response and overall survival in the castrate resistant state.
The importance of non-regional lymph nodes in assigning risk in primary metastatic prostate cancer.
Authors: Clarke Noel , Ali Adnan , Mistry Hitesh , Hoyle Alex 
Published: February 2018

227 Background: Patients diagnosed with non-regional lymph nodes (NRLN) in isolation exhibit a more prolonged clinical course than those with bone or visceral metastases in trial data, but evaluation of survival data in general populations is sparse and their presence doesn’t feature in risk estimations based on tumour volume. Methods: The evaluation and prognostic relevance of NRLN metastasis presenting synchronously with osseous or non-ossesous metastasis in hormone-naive prostate cancer was evaluated using the Surveillance, Epidemiology and End-results (SEER) database. Patients with stage M1a-c PCa diagnosed between 2004 and 2009 were identified and included within the analysis. Kaplan Meier was used to estimate overall (OS) and cancer specific survival (CSS) rates in relation to metastatic distribution. Multivariate cox-regression models were used to identify predictors of OS and CSS. Results: Of 4869 metastatic PCa patients identified, osseous metastasis was the most common finding (65.1%); followed by non-osseous (17.5%), osseous + NRLN (7.8%), NRLN (4.9%), non-osseous + osseous (±NRLN) (2.9%) and non-osseous + NRLN (1.8%). Median follow-up was 93 mo. Median OS and CSS were 28 and 34 mo respectively. Patients with osseous + NRLN metastasis had a significantly worse median OS (30 mo vs 25 mo, p = 0.001) and CSS (37 mo vs 29 mo, p < 0.001) compared to osseous only metastasis. On multivariate cox regression, osseous + NRLN metastasis was an independent predictor of OS and CSS when compared to osseous only metastasis (both p-values < 0.01). Conclusions: NRLN metastasis in the presence of osseous metastasis represents a poor prognostic feature when compared to osseous metastasis alone. The current therapeutic stratification of “low vs high volume” disease does not account for this phenomenon and patients requiring aggressive therapy may not receive maximal therapeutic benefit as a consequence.
Comparison of enzalutamide and bicalutamide in patients with non-metastatic castration-resistant prostate cancer: Number needed to treat to achieve one additional patient free of clinical progression events.
Authors: Karsh Lawrence Ivan , Penson David F. , Concepcion Raoul , Flanders Scott , Brown Bruce A. , Yang Hongbo , Ramaswamy Krishnan , Schultz Neil M. 
Published: February 2018

228 Background: Androgen receptor inhibitors enzalutamide (ENZA) and bicalutamide (BIC) are used to treat metastatic castration-resistant prostate cancer (mCRPC). The Phase 2 STRIVE trial included 35% non-metastatic (m0) and 65% metastatic CRPC patients (pts); ENZA reduced the risk of progression or death among pts, with an adverse event profile consistent with previous trials. The objective of this analysis was to compare ENZA with BIC using the number needed to treat (NNT) to achieve one additional pt with m0CRPC, with either a progression-free survival (PFS) event, radiographic PFS (rPFS), or free of prostate-specific antigen (PSA) progression at 1 year and 2 years. Methods: The 1- and 2-year event rates of PFS, rPFS, and progression-free PSA among pts treated with ENZA and BIC were obtained from the STRIVE trial report. The NNT was calculated as the reciprocal of the absolute risk reduction between ENZA and BIC at each time point. This represents the number of pts that need to be treated with ENZA, compared with BIC, to obtain one additional pt free of a clinical progression event. PFS was defined as the time from randomization to investigator-assessed radiographic (bone or soft tissue) progression, PSA progression, or death. The 95% confidence interval (CI) of the NNT was derived based on the 95% CI of the event rate difference. Results: The NNT to achieve one additional pt with PFS at 1 year, comparing ENZA with BIC, was 2.2 (95% CI 1.7, 3.4), suggesting that treating three pts with ENZA instead of BIC would result in one additional pt free of progression or death at the end of 1 year. The NNT to achieve one additional pt with PFS at 2 years was also 2.2 (95% CI 1.5, 3.7). For rPFS, the NNTs comparing ENZA with BIC were 4.7 (95% CI 2.8, 14.6) and 3.0 (95% CI 2.0, 6.1) at 1 and 2 years, respectively. For progression-free PSA, the NNTs were 2.0 (95% CI 1.5, 2.8) and 2.0 (95% CI 1.4, 3.3) at 1 and 2 years, respectively. Conclusions: This analysis supports the superior clinical benefit of ENZA versus BIC in men with m0CRPC. Pts treated with ENZA showed low NNT values across all clinical outcomes and time points. Clinical trial information: NCT01664923.
Treatment duration and utilization patterns in metastatic castration-resistant prostate cancer patients receiving enzalutamide or abiraterone acetate.
Authors: Kassabian Vahan , Flanders Scott , Wilson Samuel , Brown Bruce A. , Song Yan , Yang Hongbo , Lechpammer Stanislav , Schultz Neil M. 
Published: February 2018

229 Background: Enzalutamide (ENZA) and abiraterone acetate (ABI) are approved hormonal therapies for men with metastatic castration-resistant prostate cancer (mCRPC). This study assessed real-world treatment duration and utilization patterns in patients receiving ENZA or ABI. Methods: Adult mCRPC patients initiating ENZA or ABI before or after cytotoxic chemotherapy were identified from the Truven MarketScan® claims database (2012–2015). The index date was the first initiation of ENZA or ABI; continuous insurance enrollment for ≥6 months prior to and ≥3 months after the index date was required. Treatment discontinuation was defined as a prescription gap of ≥45 days. Median treatment duration was estimated using Kaplan–Meier method. Treatment switching was defined as starting a new mCRPC-related therapy within 30 days before to 45 days after the discontinuation date. Analyses were separately conducted for chemo-naïve and chemo-experienced patients. Results: The study included 3230 chemo-naive (ENZA 920; ABI 2310) and 692 chemo-experienced patients (ENZA 262; ABI 430). Among chemo-naive patients, ENZA cohort was older (mean age 74.5 vs 73.5; p = 0.013), with a higher proportion of comorbidities vs ABI cohort. Treatment duration was longer for ENZA cohort than ABI cohort (log-rank p = 0.008; median = ENZA 10.7 vs ABI 8.8 months). Within 1 year of initiation, 55.7% of ENZA and 60.8% of ABI cohort discontinued treatment and 22.5% and 34.7%, respectively, switched to other mCRPC therapies. Results were consistent among subgroups with specific comorbidities. Treatment duration was shorter among chemo-experienced patients than chemo-naïve; the difference between ENZA vs ABI among chemo-experienced patients was not statistically significant (log-rank p = 0.255; median = ENZA 7.5 vs ABI 7.1 months). Conclusions: Despite a more complex profile at baseline, chemo-naive mCRPC patients in the ENZA cohort had a longer treatment duration and lower proportion of switching to other prostate-cancer-directed therapies vs the ABI cohort. The difference of treatment duration between the two cohorts was not statistically significant for chemo-experienced patients.
Androgen deprivation therapy and overall survival for Gleason 8 versus Gleason 9-10 prostate cancer.
Authors: Yang David Dewei , Mahal Brandon Arvin Virgil , Muralidhar Vinayak , Martin Neil E. , Orio Peter F. , Mouw Kent William , King Martin T. , Choueiri Toni K. , Trinh Quoc-Dien , Hoffman Karen E. , Spratt Daniel Eidelberg , Feng Felix Y , Nguyen Paul L. 
Published: February 2018

23 Background: While the addition of androgen deprivation therapy (ADT) to external beam radiotherapy is known to improve overall survival in Gleason 8-10 prostate cancer, it has been hypothesized that Gleason 9-10 disease, which is less differentiated than Gleason 8 disease, may be less sensitive to ADT. To investigate this idea, we examined the association between ADT and overall survival for Gleason 8 versus Gleason 9-10 prostate cancer. Methods: We identified 20,139 men in the National Cancer Database diagnosed with localized or locally advanced, Gleason 8-10 prostate cancer from 2004 through 2011 who received external beam radiotherapy. Patients with clinical evidence of nodal or metastatic disease were excluded. Cox proportional hazards regression was used to examine the association between ADT and overall survival. Results: Median follow-up was 4.0 years. 78.2% (9,509) of the 12,160 men with Gleason 8 disease and 86.6% (6,908) of the 7,979 men with Gleason 9-10 disease received ADT. On multivariable analysis, ADT was associated with a significant improvement in overall survival for Gleason 8 patients (adjusted hazard ratio 0.79, 95% confidence interval 0.71-0.88, P< 0.001) but not Gleason 9-10 patients (adjusted hazard ratio 0.96, 95% confidence interval 0.83-1.10, P= 0.532), with a significant interaction ( Pinteraction= 0.020). When considering Gleason 9-10 patients separately as Gleason 9 and Gleason 10, a higher Gleason score correlated with an increased adjusted hazard ratio for the association between ADT and overall survival ( Pinteraction= 0.012). Conclusions: In contrast to the significant survival advantage of ADT for Gleason 8 disease, our results strongly suggest that Gleason 9-10 disease may be less sensitive to ADT and that a higher Gleason score predicts lesser sensitivity. Consideration should be given to treatment intensification for Gleason 9-10 patients through enrollment in clinical trials or potentially adding novel antiandrogens or docetaxel, which have shown efficacy in both castration-resistant and castration-sensitive settings.
Health care resource utilization and costs in metastatic castration-resistant prostate cancer patients treated with enzalutamide or abiraterone acetate.
Authors: Kassabian Vahan , Flanders Scott , Wilson Samuel , Brown Bruce A. , Song Yan , Yang Hongbo , Lechpammer Stanislav , Schultz Neil M. 
Published: February 2018

232 Background: Cost of care is an important component of valuation of novel treatments in oncology. Enzalutamide (ENZA) and abiraterone acetate (ABI) are approved hormonal agents for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study compared healthcare resource utilization (HRU) and costs for patients treated with ENZA or ABI in the U.S. Methods: Adult mCRPC patients initiating ENZA or ABI before and or after cytotoxic chemotherapy were identified from the Truven MarketScan claims database (2012–2015). The first claim of ENZA or ABI was defined as the index date; continuous enrollment ≥6 months before and ≥3 months after the index date was required. HRU and costs were estimated during the post-index period for both cohorts. Generalized linear models compared HRU and costs between the cohorts and were adjusted for baseline demographic and clinical covariates. Analyses were separately conducted for chemo-naïve and chemo-experienced patients. Results: The study included 3230 chemo-naive patients (ENZA 920; ABI 2310) and 692 chemo-experienced patients (ENZA 262; ABI 430). Among chemo-naive patients, ENZA cohort was older (mean age: 74.5 vs 73.5; p=0.013), with a higher proportion of baseline comorbidities vs ABI cohort. During the post-index period, ENZA cohort had fewer all-cause inpatient admissions (IPA) [adjusted incidence rate ratio (IRR) 0.87; p=0.033], all-cause outpatient visits (OPV) [adjusted IRR 0.94; p=0.004], and PC-related OPV (adjusted IRR 0.92; p<0.001) vs the ABI cohort. Within 3 months of the index date, ENZA cohort was less likely to have an all-cause IPA (adjusted odds ratio [OR] 0.75; p=0.029). In addition, ENZA cohort had lower PC-related IPA and emergency department (ED) costs vs ABI cohort. The differences of HRU and medical costs between the 2 cohorts were not statistically significant for chemo-experienced patients. Conclusions: Despite a higher comorbidity burden at baseline, chemo-naive mCRPC patients treated with ENZA incurred less HRU and lower PC-related IPA and ED costs vs ABI cohort. Differences between the 2 cohorts were not statistically significant for chemo-experienced patients.
Detection of prostate cancer lesions using Gallium-68 PSMA-11 PET in men with biochemical recurrence following radical prostatectomy.
Authors: Gadzinski Adam J. , Greene Kirsten L , Carroll Peter , Ryan Charles J. , Feng Felix Y , Hope Tom 
Published: February 2018

236 Background: Conventional imaging techniques infrequently detect the site of prostate cancer disease in men with biochemical recurrence following radical prostatectomy (RP). We examine the use of Gallium-68 Prostate-Specific Membrane Antigen (PSMA) positron emission tomography (PET) to determine the site of disease recurrence in these men. Methods: We retrospectively reviewed men with persistently detectable prostate specific antigen (PSA) and those with formal biochemical recurrence (PSA ≥ 0.2 ng/mL) following RP who underwent PSMA PET scan under our institution's prospective trials (NCT02918357 & NCT02611882). We assessed the location of detected recurrences, and examined the distribution of recurrence location (prostate bed, pelvic lymph nodes (LN), and extra-pelvic disease) according to PSA at time of PET scan. Results: One hundred and fifty-eight men underwent PSMA PET after RP, 46% of men had previously undergone either adjuvant or salvage radiation therapy. Eleven men (7%) had the scan for persistently detectable PSA < 0.2 and 93% of men had biochemical recurrence. At time of RP, 66% of men had ≥pT3a disease, 40% had positive surgical margins, and 18% had positive lymph nodes. Gleason grade at RP was ≤3+3 in 5% of men, 3+4 in 27%, 4+3 in 32% and ≥4+4 in 36%. Overall, 77% of men had a lesion detectable on PSMA PET. Men with higher PSA at time of scan had a higher prevalence of lesions, with all men PSA > 6.0 having at least one lesion on PSMA PET (Table). Overall, we found extra-pelvic lesions in 44% of all men, and 58% of men with PSA ≥ 1.0. These are areas not typically covered by salvage radiation fields. Conclusions: PSMA PET detects lesions in a high proportion of men with biochemical recurrence following RP, with many lesions outside of the pelvis. This may facilitate more precise targeting of treatment areas for these patients. Clinical trial information: NCT02918357. Clinical trial information: NCT02611882. [Table: see text]
Impact of a geriatric oncology (GO) clinic on cancer treatment plans and supportive care for older adults with genitourinary (GU) cancer.
Authors: Alibhai Shabbir M.H. , Loucks Allison , Jin Rana , Puts Martine , Watt Sarah , Berger Arielle 
Published: February 2018

238 Background: Older adults with cancer are complex due to multiple comorbidities, polypharmacy, and functional/cognitive impairments, leading to over-treatment and undertreatment. Studies examining the impact of geriatric assessment (GA) in older adults with various cancers found a median of 39% of treatment plans were revised after the GA ( Ann Oncol 2014; 25:307). Although these findings support the need for a GO clinic, whether such a clinic leads to changes in treatment in patients with GU malignancies is not clear. We examined the impact on the treatment plan of a GO assessment in GU patients, along with other enhancements to patient care for consecutive patients referred to the GO clinic in a tertiary care hospital. Methods: All referred older adults (age 65+) with a GU malignancy seen in the GO clinic at the Princess Margaret Cancer Centre, Toronto, Canada between July 2015 and June 2017 were included. Patients were seen by a geriatric oncologist and GO nurse and treatment recommendations were provided to the referring oncologist. Pre- and post-GO clinic treatment plans and enhancements to supportive care were recorded prospectively. Analyses were descriptive. Results: 98 patients (mean age 80) were seen in the GO clinic, of whom 35 were seen pre-treatment (25 prostate, 5 kidney, 5 bladder). 31 of 35 were referred for input on the treatment plan. The initial treatment plan included surgery (n = 6), radiation (n = 14), systemic therapy (n = 8), and hormonal therapy (n = 11). The final treatment plan was intensified in 1 patient, reduced in 6 patients, changed to best supportive care in 8 patients, and unchanged in 15 patients. Overall, GO resulted in a treatment modification in 52% of patients. Enhancements to care included comorbidity management (87%), educational support (94%), disease-related symptoms (39%), and peri-operative management (19%). Conclusions: The GO clinic results in modifications to the proposed treatment plan in over half of referred patients (predominantly a reduction in treatment intensity), and enhancements to care in the vast majority of patients. GO clinics have the potential to avoid overtreatment and improve care for older adults with GU malignancies.
Optimal timing of post-prostatectomy radiotherapy for prostate cancer with high-risk pathologic features: A multi-institutional analysis.
Authors: Hwang William L. , Tendulkar Rahul D. , Niemierko Andrzej , Agrawal Shree , Stephans Kevin L. , Spratt Daniel Eidelberg , Hearn Jason W.D. , Koontz Bridget F. , Lee W. Robert , Michalski Jeff M. , Pisansky Thomas Michael , Liauw Stanley L. , Abramowitz Matthew , Pollack Alan , Moghanaki Drew , Anscher Mitchell , Den Robert Benjamin , Zietman Anthony L. , Stephenson Andrew J. , Efstathiou Jason A 
Published: February 2018

24 Background: The use of radical prostatectomy (RP) as initial treatment of high-risk/locally-advanced prostate cancer is increasing but patients (pts) with adverse pathologic features such as positive surgical margins or T3 disease have up to 70% recurrence risk. These high-risk pts may be managed with adjuvant radiotherapy (ART) or early salvage radiotherapy (ESRT). The optimal timing of post-operative radiotherapy is unclear. Methods: Individual data from 1566 consecutive pts with pT2N0M0/R1 or pT3N0M0/R0-1 disease who underwent post-prostatectomy ART or ESRT (1987-2013) at 10 academic centers were pooled. Post-irradiation freedom from biochemical failure (FFBF), freedom from distant metastases (FFDM), prostate-cancer specific survival (PCSS), and overall survival (OS) were compared using Kaplan-Meier and multivariate competing-risks regression (MVA) analyses. Propensity score (PS) matching was used to account for covariates potentially associated with treatment allocation. All outcomes were measured from the date of surgery to address lead time bias. Results: After PS-matching, median follow-up after surgery was 66 vs. 73 months for the ART and ESRT groups, respectively, and baseline characteristics were well-matched. ART was associated with higher FFBF (12-yr: 69% vs. 43%; log-rank P < 0.0001), FFDM (12-yr: 95% vs. 85%; log-rank P = 0.03), PCSS (12-yr: 99% vs. 94%; log-rank P = 0.048), and OS (12-yr: 91% vs. 79%; log-rank P = 0.01). ART, lower Gleason score, lower T-stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on MVA for BF. Sensitivity analysis demonstrated that the decreased risk of BF associated with ART remained significant unless more than 56% of ART pts were cured by surgery alone. This threshold is greater than the estimated 12-yr FFBF of 46% after RP alone as determined by a contemporary nomogram. Conclusions: To the best of our knowledge, this represents the largest multi-institutional study to date comparing ART to ESRT. ART was associated with reduced biochemical recurrence, distant metastases, and death compared to ESRT for high-risk pts, pending prospective validation.