bluuebunny/crossref_metadata_2025_split huggingface dataset:
mTOR inhibitor-associated noninfectious pneumonitis in patients with metastatic renal cell cancer: A single-center experience.
Authors: Cauley Diana H. , Atkinson Bradley J. , Ng Chaan S. , Millikan Randall E. , Xiao Lianchun , Corn Paul Gettys , Jonasch Eric , Tannir Nizar M. 
Published: March 2020

e15612 Background: Noninfectious pneumonitis (NIP) is a known adverse effect of mTOR inhibitors, with a reported incidence of 25-45%. The goal of this review was to characterize the incidence, onset, management, and clinical outcomes of pts with mRCC who experienced mTOR inhibitor-associated NIP at our tertiary cancer center. Methods: Retrospective review of 310 mRCC pts who received everolimus and/or temsirolimus between 6/1/2007 and 10/1/2010. Clinical correlation was made in conjunction with serial radiologic imaging studies. Results: 36 mRCC pts (12%) treated with an mTOR inhibitor developed NIP with a median time to symptom onset of 65 d (21-855) and radiographic appearance of 62.5 d (35-736). 23 pts (21%) received everolimus compared to 13 pts (6%) who received temsirolimus (P<0.0001). Median time to onset, radiographic appearance, and NCI CTCAE pneumonitis grade did not differ significantly between treatments (P=NS). Increased age (OR 1.04; 95% CI: 1.004-1.08) and everolimus (OR 4.106; 95% CI: 1.96-8.6) were associated with a greater risk of NIP. NCI CTCAE grade 2 NIP severity was most common (78%). mTOR inhibitor therapy was discontinued in 9 pts (25%); continued at same dose in 7 pts (19%), dose reduced in 2 pts (6%); held and resumed at lower dose in 2 pts (6%), and held and then resumed at same dose in 1 pt (3%). Median time on treatment was greater for pts who developed NIP; 4.1 vs 2 mo (P=0.035). Median OS was significantly greater for NIP pts; 15.4 vs 7.4 mo (P<0.0001). 3-yr survival of NIP pts was 35.4% vs 7.2% (P<0.0001). Predictors of improved OS included NIP (HR 0.315; 95% CI: 0.2-0.495; P<0.0001). Conclusions: A higher incidence of NIP was observed in mRCC pts treated with everolimus than temsirolimus. The finding of improved OS in pts who developed NIP is intriguing and should be further investigated.
Outcome of patients with nonmetastatic, muscle-invasive bladder cancer (MIBC), not undergoing cystectomy, after treatment with non-cisplatin-based chemotherapy and/or radiotherapy: A retrospective analysis.
Authors: Bamias Aristotelis , Tsantoulis Petros , Zilli Thomas , Koutsoukos Konstantinos , Caparrotti Francesca , Liontos Michael , Roth Arnaud , Lykka Maria , Stravodimos Kostas , Chrisofos Michael , Papatsoris Athanasios , Efstathiou Eleni , Wirth Gregory J , Mitropoulos Dionysios , Constantinides Constantinos A , Deliveliotis Charalambos , Iselin Christophe E , Miralbell Raymond , Dietrich Pierre-Yves , Dimopoulos Meletios A. ,   Hellenic Genito-Urinary Cancer Group
Published: March 2020

e15619 Background: Τransurethral resection of bladder tumor (TURBT), radiotherapy, chemotherapy or combinations can be used in patients with MIBC not undergoing cystectomy, but the optimal treatment is yet unknown. Cisplatin-based chemotherapy is the standard if systemic therapy is to be used. Nevertheless, unfitness for cystectomy is frequently associated with unfitness-for-cisplatin. We report the outcome of patients with MIBC who did not undergo cystectomy and did not receive cisplatin-based chemotherapy. Methods: Selection criteria: non-metastatic MIBC, no cystectomy, no cisplatin-based chemotherapy. Chemotherapy and/or radiotherapy should have been used apart from TURBT. Unfitness for Cisplatin was determined by: creatinine clearance < 50 ml/min, PS > 2, hearing loss, co-morbidities precluding adequate hydration. Carboplatin/gemcitabine was used in patients receiving chemotherapy. Tumor extent was evaluated by TURBT and CT. Patients consented to the use of their data. Results: 49 patients (median age 79), managed between 2/2003-2/2012 were included in this analysis (Table 1). 40 patients (82%) had T2 tumors. No factor for unfitness-for-cisplatin was present in 4 cases. During a median fup of 68 months 29 patients died (5 not due to disease). Treatment after TURBT and outcome are shown in the Table. Conclusions: Most patients with non-metastatic MIBC, not undergoing cystectomy, are also unfit-for-cisplatin, although comorbidities used as unfitness criteria do not always adhere to current guidelines. The outcome of these patients is poorer than that expected with cystectomy. Combining chemotherapy with radiotherapy produced numerically better outcomes and should be prospectively evaluated. [Table: see text]
Development of a nomogram to predict for all-cause and cancer-specific mortality in high-risk prostate cancer treated by external beam radiotherapy and androgen deprivation.
Authors: Tendulkar Rahul D. , Kattan Michael W. , Yu Changhong , Reddy Chandana A. , Stephans Kevin L. , Kupelian Patrick , Stephenson Andrew J. 
Published: March 2020

e16004 Background: Men receiving high dose external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) for high risk prostate cancer (HRPC) have other competing causes of mortality, however predictive schema do not account for patient-related co-morbidities. We aim to create nomograms estimating all-cause mortality (ACM) and prostate cancer-specific mortality (PCSM) in this population. Methods: 660 patients with HRPC defined by NCCN guidelines were treated with EBRT ≥74 Gy and ADT from 1996-2009. The probabilities of death from prostate cancer and other causes were estimated by cumulative incidence function. Multivariable Cox proportional hazards regression and competing risks regression analyses were used for modeling ACM and PCSM respectively. Deaths from other causes were treated as competing risks for PCSM. Missing values in the predictors were multiply imputed before conducting multivariable regression analysis. Variables investigated were age, clinical T stage, prostate specific antigen (PSA), Gleason score, race, family history, duration of ADT, body mass index (BMI), Charlson co-morbidity index score, coronary artery disease, and smoking pack-years. The stepdown method was used to make parsimonious models based on the rank of the predictive ability of each variable with respect to each endpoint. The final nomograms were internally validated by assessing the discrimination and calibration with bootstrap resamples. Results: At last follow up, there were 199 deaths. The 10-year cumulative incidence of death from prostate cancer was 14% and from other causes was 26%. The variables that predicted for 10-year ACM included age, PSA, BMI, Charlson score, and smoking pack-years. The ACM nomogram achieved a concordance index of 0.672. The variables that predicted for PCSM included Gleason score, PSA, race, and duration of ADT. The nomogram concordance index for PCSM was 0.673. The calibrations for both ACM and PCSM appear reasonable. Conclusions: We have developed nomograms that predict for ACM and PCSM in men with aggressive prostate cancer and competing risks of death. External validation may be useful.
Prognostic value of various summary measures of prostate-specific antigen (PSA) kinetics for overall survival (OS) in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) who failed first-line chemotherapy (TROPIC trial).
Authors: Legrand Catherine , Oudard Stephane , Sartor A. Oliver , De Bono Johann Sebastian , Shen Liji , Machiels Jean-Pascal H. 
Published: March 2020

e16010 Background: PSA kinetic measures are often reported as prognostic factors for overall survival (OS) in mCRPC pts. The objective of this study is to investigate the prognostic value of various summary measures of pre- and post-treatment PSA kinetics on OS in patients treated with cabazitaxel or mitoxantrone following progression during or after docetaxel in the TROPIC trial. Methods: PSA data from the phase III TROPIC trial that randomized 755 docetaxel pre-treated mCRPC pts between cabazitaxel and mitoxantrone were used. Baseline was defined as the time of randomization. The prognostic value of pre- and post-baseline PSA kinetic measures (percentage decline (PSA-D) / increase (PSA-I) and PSA velocity (PSA-V) within 2 months (m) before and post-baseline (B)) was systematically assessed for OS according to several cut-offs. PSA-V was computed as the slope of individual regression line over at least 3 measurements. The Kaplan-Meier estimator was used to compute median OS [95% CI]. Uni- and multivariate analyses were based on the Cox model. Results: Pre-B PSA-I, and Post-B PSA-D/I were found to be significant prognostic factor for various cut-off, e.g. pts with a PSA-I above 25% within 2 months after randomization were significantly more at risk [median OS: 11.4m[10.0-12.7] vs. 14.6m [13.0-17.9], p=0.0005]. For Post-B PSA-D, all cut-offs between 20 and 70% were significant, but the 30% one led to the more significant p-value. OS for the 224 pts with a Pre-B PSA-V below the median (1.07) was significantly better than for the 228 pts with a value above (median OS: 16.3m[14.3-18.8] vs. 12.9m [11.4-14.1], p<0.0001). Post-B PSA-V below (n=325) or above (n=312) the median (-0.012) also led to a significantly different OS (median OS: 16.3m [15.2-18.8] vs. 12.3m [11.3-13.4], p<0.0001). All results remain significant while adjusting for ECOG-PS, measurable disease, baseline pain, time of last docetaxel infusion and treatment. Conclusions: Our data suggests that pre and post-treatment PSA velocity is an independent prognosis factor for OS in mCRPC pts treated with chemotherapy.
Use of supportive measures to improve outcome and decrease toxicity in docetaxel-based antiangiogenesis combinations in metastatic castrate resistant prostate cancer (mCRPC).
Authors: Karzai Fatima H. , Madan Ravi Amrit , Apolo Andrea Borghese , Ning Yangmin M. , Parnes Howard L. , Arlen Philip M. , Beatson Melony A. , Harold Nancy , Couvillon Anna , Wright John Joseph , Chen Clara , Dawson Nancy Ann , Gulley James L. , Figg William Douglas , Dahut William L. 
Published: March 2020

e16017 Background: We have completed accrual of 63 patients (pts) to our study combining lenalidomide (L), with bevacizumab (B), docetaxel (D), and prednisone (P) (ART-P) in mCRPC. Due to the lack of improved survival and the increased toxicity of anti-angiogenic docetaxel combinations in the MAINSAIL and CALGB 90401 trials, we attempted to compare and contrast our studies with these failed phase III trials. Methods: Among the first 52 pts on ART-P, 3 received L 15 mg daily, 3 received 20 mg daily, and the others received 25 mg daily for 14 days of every 21−day cycle (C). We then enrolled 11 pts at L 15 mg. All pts received D 75 mg/m2 and B 15 mg/kg on day 1 with P 10 mg and enoxaparin daily. Pegfilgrastim was given on day 2. Patients on CALGB 90401 received D 75 mg/m2 and B 15 mg/kg on day 1, with P 10 mg. On MAINSAIL, pts received D 75 mg/m2, L 25 mg daily for 14 days of every 21−day cycle with daily P. Patients on CALGB 90401 and MAINSAIL did not receive enoxaparin or pegfilgrastim prophylactically. Results: The median number of Cs on ART-P is 18 (1-52). Median PFS is 19.1 months. Twenty-seven pts had a PR, and one pt with measurable disease had a CR. Two patients (3%) had deep vein thromboses. Of 1,334 Cs given, 14 cycles were complicated by febrile neutropenia (FN) (1%). There were no treatment related deaths. In comparison, median number of Cs in MAINSAIL L+DP arm was 6, with a PFS of 45 weeks and an OS of 77 weeks. Thirty-four pts (6.5%) developed pulmonary emboli and there were 2 deaths due to toxicity in the experimental arm. Nearly 12% of Cs were complicated by FN. In the experimental arm of CALGB 90401 trial, median OS was 22.6 months with median PFS of 9.9 months. The median number of Cs were 8 and 19 pts developed thrombosis/emboli (3.6%). In addition, 37 patients developed FN and treatment related deaths were reported at 4%. Conclusions: The use of supportive care allowed longer treatment duration with the ART-P combination as compared to D+L (MAINSAIL) and D+B (CALGB 90401), potentiating a longer PFS, RR and possibly OS with an improved safety profile. This data demonstrates the potential importance of supportive measures and is hypothesis generating for future combination studies. Clinical trial information: NCT00942578.
Computer-aided bone scan lesion area quantitation: Inter-reader measurement variability.
Authors: Chu Gregory H. , Brown Matthew S. , Kim Hyun J. , Kaplan Andrew , Yang Katherine , Allen-Auerbach Martin , Poon Cheryce , Levine Benjamin , Schiepers Christiaan , Verma Ramesh , Bridges Juliette , Vidovic Adria , Ramakrishna Bharath , Ho Judy , Scher Howard I. , Goldin Jonathan 
Published: March 2020

e16019 Background: Bone scan is essential for response assessment in subjects with metastatic prostate cancer. However, visual assessment is subjective and prone to inter-reader variability. A commercial computer-aided (CAD) system for bone scan lesion area (BSLA) calculation has been developed (MedQIA, LLC). BSLA provides an objective and sensitive measure for response assessment. New VEGF treatments showing promising results in reducing lesion burden on bone scan present an urgent need for validated systems capable of accurately assessing treatment response. Measurement of inter reader variability is fundamental to such a validation. In this work we measure inter-reader variability in quantitation of BSLA change using the CAD system. Methods: In a multi-center clinical trial of cabozantinib (Exelixis, Inc), bone scans were acquired according to a standardized imaging protocol. Scans at baseline and Week 12 were available for 113 subjects for this analysis. Automated CAD lesion detection was performed following image intensity normalization to increase consistency between subject time points. Two nuclear medicine physicians independently edited and approved the CAD result as needed, primarily to remove false positives due to degenerative joint disease. The system then calculated the percent change in BSLA at Week 12 from baseline (BSLAPCT). The BLSAPCT values from the two readers were compared to assess inter-reader variability. Additional analytic validation of the BSLA measure was performed in which the readers provided a categorical assessment of responder vs non-responder, using the CAD-normalized images, and the classification performance of BSLAPCT was assessed using ROC analysis. Results: The median (IQR) difference in BSLAPCT between the two readers was -1.8 (20.0) percentage points. The absolute difference was 9.4 (23.9) percentage points. The BSLAPCT response classification had an ROC area under curve (AUC) of 0.96 for both readers. Conclusions: Computer-aided quantitative assessment of change using bone scan lesion area demonstrated low variability between two readers. This is an important step toward the validation of an objective, quantitative, and sensitive response assessment technique.
Skeletal-related events (SREs), baseline comorbidity, and survival among elderly patients (pts) with metastatic (M1) prostate cancer (PCa) in SEER-Medicare.
Authors: Onukwugha Ebere , Yong Candice , Mullins C. Daniel , Seal Brian S. , Hussain Arif 
Published: March 2020

e16027 Background: The prevalence of comorbidities increases with age in older men diagnosed with M1 PCa. However, the relationship between comorbidities, PCa, SREs, and mortality is not well understood. Methods: We analyzed pts aged 66+ diagnosed with M1 PCa between 2000 and 2007 from the linked Surveillance, Epidemiology, and End Results (SEER) and Medicare dataset. Pts surviving at least 30 days post-diagnosis were identified and followed until death or censoring in December 2009. Pathologic fracture, spinal cord compression, and bone surgery were identified from Medicare claims based on three measures: 1) SRE claim occurred after claims with a bone metastasis (BM) ICD 9 code; 2) BM ICD 9 code directly coincided with SRE claim; 3) SRE was not anchored to BM. Cox proportional hazards regression models controlled for demographic and clinical factors, including interaction terms involving indicators for comorbidities. Regression models were estimated using all-cause and PCa-specific mortality as outcomes. Results: Application of inclusion/exclusion criteria resulted in 7,062 pts. PCa-specific and all-cause mortality were 54% and 80% at a median (mean; min; max) follow up of 609 days (837; 30; 3,653). The proportion with any SRE was 17% (Measure 1), 9.7% (Measure 2), and 17.1% (Measure 3). Joint tests indicated statistically significant interaction terms using Measure 1 for PCa-specific mortality and Measure 3 for all-cause mortality. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) on the SRE indicators are shown in the Table. Conclusions: The association between SREs and death among elderly M1 PCa patients is affected by comorbidities. [Table: see text]
Impact of the USPSTF D recommendation: Early assessment of referrals for elevated PSA and prostate biopsies in a LUGPA following statement revision.
Authors: McGinley Kathleen F. , Brown Gordon Andrew 
Published: March 2020

e16041 Background: In October 2011, the U.S. Preventative Services Task Force (USPSTF) posted for public comment the draft of their recommendation against PSA-based prostate cancer screening. Extensive media coverage and discussion within the medical community ensued. The USPSTF released their formal statement of a D recommendation in May 2012. While the potential implications of the USPSTF recommendation upon prostate cancer screening will take years to manifest, the early impact of their recommendations upon the market is evaluable. Methods: The electronic medical record of a large urology group practice composed of 32 providers was queried for two variables: the number of referrals for an elevated PSA and the number of individuals who underwent a prostate biopsy. A control period of October 2010-September 2011 was selected and compared to October 2011-September 2012, the twelve month period beginning with release of the USPSTF draft against PSA-based prostate cancer screening. Results: From October 2010 to September 2011, 28,698 patients were evaluated for an elevated PSA by 32 urologists; from October 2011 to September 2012, 25,075 patients were evaluated by the same number of physicians, a difference of 12.6% following release of the USPSTF recommendations. From October 2010 to September 2011, 2465 patients underwent a prostate biopsy; from October 2011 to September 2012, 1989 had a biopsy, a difference of 19.3%. Conclusions: A marked decrease in the number of patients referred to a large urology group practice for evaluation of an elevated PSA, and an even greater decrease in the number of prostate biopsies performed, occurred in the 12 months following release of the USPSTF recommendations against PSA-based prostate cancer screening.
Castrate-resistant prostate cancer (CRPC): Prognostic and predictive value of testosterone levels in patients receiving chemotherapy.
Authors: Gomez De Liano Lista Alfonso , Reig Óscar , Mellado Begoña , Martin Lorente Cristina , Cillan Elena , Macias Ismael , Sancho Gemma , Palou Joan , Maroto-Rey Pablo 
Published: March 2020

e16049 Background: Recent development of new second line therapies in patients with CRPC upon progression to docetaxel has raised the question of who benefit most of either a salvage hormonal treatment (HT) or chemotherapy. Objectives: To analyze the prognostic value for survival of the absolute levels of serum testosterone (TL) in patients under definition of CRPC (PSA and/or clinical progression with a TL <50 ng/dL). To analyze the probability of response to salvage HT upon failure to docetaxel. Methods: 101 patients with metastatic CRPC were included in 9 different non-hormonal first line phase II-III trials in two single institutions from August 2006 until September 2012. Inclusion criteria of those trials required castrate levels of testosterone. TL was determined by automated immunoassay. Survival was calculated since the date of entrance in the trial to death. Results: Median age was 70 years (41-89). 22% of the patients had visceral metastases. Median PSA was 51 U/L (0.04-1284). Median Hemoglobin was 13 g/dL (9.3-15.6). Median TL was 11.53 ng/dL (range undetectable to 48.9). First line chemotherapy was Docetaxel (alone or in combination) in 71/101 patients (70%). Median overall survival (OS) was 24.51 months. Patients with TL under median value (N=49) had an OS of 22.4 months, compared to 32.7 months in those whose TL was higher (N=52) (p=0.0162 , HR 0.52). Anemia (Yes vs NO) was an adverse prognostic factor (OS 20.6 vs 28.4 months, p=0.0025, HR 2.4). Patients presenting both factors (anemia and lower TL) had a worse outcome compared to those who had only one or none of them (OS: 17.9 vs 22.4 vs 38.1 m; p=0.0024). 41 patients (40.6%) were treated with salvage hormone therapy after chemotherapy failure. Baseline TL was associated with PSA response to salvage HT. Only 5/23 patients (21.74%) with TL below median value showed PSA response, vs 10/18 (55.6%) if TL was over median value. Conclusions: Testosterone even under castration level (< 50 ng/dL) was a prognostic factor for survival in patients with metastatic CRPC. PSA response to salvage hormonotherapy differed depending on testosterone levels. TL could help us in treatment decision after first line chemotherapy failure.
Analysis of docetaxel therapy in elderly (≥70yrs) castration resistant prostate cancer (CRPC) patients enrolled in the Netherlands Prostate Study (NePro).
Authors: Los Maartje , Gerritse Frank L. , Meulenbeld Hielke Jodie , Roodhart Jeanine M.L. , van der Velden Ankie M.T. , De Wit Ronald ,   on behalf of the NePro Study group
Published: March 2020

e16059 Background: Prostate cancer truly is an age-associated disease, approximately half of prostate cancer patients in the Netherlands are aged 70 years or older at the time of diagnosis. However, age above 70 years has been an exclusion criterion in many clinical trials. Hence the knowledge about chemotherapy tolerance and toxicity in patients aged 70 years and above is limited. In this study we evaluated the influence of age on docetaxel chemotherapy in elderly (≥70yrs) castration resistant prostate cancer (CRPC) patients. Methods: Prostate cancer truly is an age-associated disease, approximately half of prostate cancer patients in the Netherlands are aged 70 years or older at the time of diagnosis. However, age above 70 years has been an exclusion criterion in many clinical trials. Hence the knowledge about chemotherapy tolerance and toxicity in patients aged 70 years and above is limited. In this study we evaluated the influence of age on docetaxel chemotherapy in elderly (≥70yrs) castration resistant prostate cancer (CRPC) patients. Results: We analyzed 568 patients (median age 68.1yrs, range 46-89yrs, 44.5% aged ≥70yrs). There was no relation between dosage and age (p=0.60). We found no significant differences between the number of dose reductions, TTP, overall survival, chemotherapy tolerance and toxicity up to the age of 80 years. However, when compared to younger men, men aged 80 years or above more frequently experienced grade 3/4 toxicity, were five times less likely to complete the first three treatment cycles at the intended dose (OR5.34, p=0.0052) and showed decreased overall survival (15.3mos versus 24.5mos in <80yrs group, p=0.020). Conclusions: In mCRPC, and possibly other cancer patients, up to the age of 80 years docetaxel chemotherapy is well tolerated with toxicity levels, tolerance and TTP comparable to that of younger patients. However, for chemotherapeutic treatment of patients aged 80 years and above an individual assessment should be made.