bluuebunny/crossref_metadata_2025_split huggingface dataset:
Limitation of prostate-specific antigen doubling time as a predictor of outcome in hormone-naive prostate cancer
Authors: Nelson J. B. , Sleep D. J. , Isaacson J. D. , Carducci M. A. 
Published: March 2020

4566 Background: Prostate-specific antigen doubling time (PSADT) is used to monitor progression after primary therapy for prostate cancer. Increasingly in this population, PSADT is an efficacy measure in therapeutic trials, many of which are uncontrolled. Examination of PSADT response on placebo in a randomized controlled study may evaluate the utility of PSADT as an outcome measure in patients with hormone-naive prostate cancer. Methods: Patients with biochemical failure post radical prostatectomy were enrolled in a randomized, double-blind, placebo-controlled trial of atrasentan 10 mg. Eligibility criteria included baseline PSA between 0.4 ng/mL and 5 ng/mL with a PSADT ≤12 months based on two PSA values at least 2 weeks apart. On-treatment PSADT was compared between treatment groups in patients with at least 3 on-treatment PSA values collected every 12 weeks while on study drug. Categorical analysis comparing PSADT between groups was performed using Cochran-Mantel-Haenszel methodology. Mean change from baseline in PSA velocity (log PSA vs time) was analyzed using a one-way analysis of variance with treatment as the factor. Results: Of 222 patients enrolled, 209 had 3 PSA values on study: N=107 for placebo; N = 102 for atrasentan. Baseline PSA was lower for patients in the placebo arm than for those in the atrasentan arm (mean of 1.4 ng/mL [SE 0.1] vs 1.8 ng/mL [SE 0.1] P =.012). On-treatment PSADT was similar between treatment arms (P =.363); the proportion of patients whose PSADT was >1 year on study was 55% with placebo and 51% with atrasentan. More notably, PSADT lengthened on study for most patients in both arms (76/107, 71% for placebo and 68/102, 64% for atrasentan). PSA velocity was also protracted for patients in both treatment arms (placebo: slope = 1.47 at baseline to 0.96, P < .001; atrasentan: slope = 1.56 at baseline to 1.26, P =.017). Conclusions: The fact that over 70% of patients receiving placebo experienced lengthened PSADT suggests that, in the absence of a control arm, changes in PSADT from baseline are not a reliable measure of treatment effect in trials in early prostate cancer. PSADT data from trials in this population should be interpreted with caution. [Table: see text]
Long-term complications of platinum in testicular cancer survivors
Authors: Oh J. H. , Baum D. D. , Ensor J. , Pham S. , Muddiman M. D. , Nguyen S. , Chen I. 
Published: March 2020

4589 Background: Long-term medical complications of platinum have become a major priority in the care of testicular cancer survivors. This study aimed to describe the prevalence of these complications from platinum-based therapy in American testicular cancer survivors. Methods: Testicular cancer survivors with no evidence of disease for at least 2 years were interviewed, had lab tests, and charts reviewed. Demographics, comorbidities, blood pressure, treatment, and outcomes were compared between all treatment modalities. NHANES 2002 and NHIS 2004 were used to obtain national estimates. Results: The mean age was 41 years; 72.7 % had nonseminoma, 96.5% had orchiectomy, 21.0% received radiation (XRT), and 82.5% platinum. The mean follow-up was 8.4 years. There was no statistical difference in the rates of Coronary Artery Disease (CAD), hyperlipidemia, hypertension (HTN), renal insufficiency (RI), or hypomagnesemia (see table ). There was a trend toward an increase in hyperlipidemia at follow-up compared to initial visit in all treatment groups but HTN increased only in those who did not receive platinum. Conclusion: Excluding HTN, we observed a trend toward an increase in the prevalence of RI, hypomagnesemia, hyperlipidemia, and CAD among patients who received platinum when compared to their baseline rates. Similar to a recent study by Huddart et al, we saw a trend toward higher risk of developing CAD in those who received both platinum and XRT. These findings suggest that hyperlipidemia and HTN may be more related to orchiectomy or the germ cell tumor itself than being a complication of platinum. Further prospective cohort studies with a larger group of survivors who have not received platinum are warranted to determine if HTN and hyperlipidemia are true complications of platinum-based chemotherapy. [Table: see text] No significant financial relationships to disclose.
Predictors of survival in patients undergoing post-chemotherapy retroperitoneal lymph node dissection
Authors: Spiess P. E. , Brown G. A. , Liu P. , Tannir N. M. , Tu S. , Kamat A. M. , Pisters L. L. 
Published: March 2020

4593 Background: The majority of patients with testicular cancer have a favorable prognosis yet a subset of patients will succumb to this disease. The aim of this study was to identify the clinical and pathological parameters which predict the outcome of patients post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND). Methods: From 1980 to 2003, 236 patients with clinical stage IIA-III non-seminoma germ cell tumors (NSGCT) underwent a PC-RPLND. We retrospectively reviewed their medical records for pertinent clinical and treatment-related outcomes. The 5-year disease-specific and recurrence-free survival was 85% and 75%, respectively with the median length of follow-up following RPLND of 45 months (6 to 250 months). Results: The median age of patients at diagnosis was 28 years with all patients receiving systemic chemotherapy (median of 5 cycles) prior to RPLND. On multivariate analysis, predictors of disease-specific survival (DSS) included systemic symptoms at presentation (P = 0.05), elevated pre-RPLND serum alpha fetoprotein (AFP, P = 0.006) and ß-human chorionic gonadotropin (HCG, P = 0.004), post-operative complications (P = 0.03), and recurrence (P < 0.0001). Predictors of recurrence-free survival (RFS) included advanced clinical stage (IIC-III, P = 0.001) and presence of viable tumor in the RPLND specimen (P = 0.03). A pre-RPLND serum AFP > 9 ng/ml and HCG > 4.1 mIU/ml was found to predict DSS (P = 0.03 and 0.03, respectively). Conclusions: Survival of patients undergoing PC-RPLND can be predicted by pre-operative tumor markers, and by development of post-operative complications or recurrence. Advanced clinical stage and viable tumor in the surgical specimen predict RFS. No significant financial relationships to disclose.
A brief symptom index for renal cell carcinoma
Authors: Eton D. T. , Cella D. , Bacik J. , Motzer R. J. 
Published: March 2020

4595 Background: Renal cell carcinoma (RCC) occurs in over 30,000 Americans each year. Since it is often diagnosed in later stages and metastatic sites are variable, an array of symptoms and concerns affect patients with this disease. Our objective was to test a brief, symptom index for advanced RCC. Methods: We conducted secondary data analyses on patient-reported outcomes from a completed Phase III trial of 284 patients with metastatic RCC treated with interferon + 13-cis-retinoic acid or interferon alone (Motzer et al., 2000). Patient-reported outcomes were collected using the FACT-Biological Response Modifier (FACT-BRM) module at baseline, 2 weeks, and 8 weeks. We analyzed data from eight FACT-BRM items that were previously identified by clinical experts to represent the most important symptoms of advanced RCC. Items comprising the proposed Kidney Cancer Symptom Index (KCSI) assess nausea, pain, appetite, perceived sickness, fatigue and weakness, with higher KCSI scores indicating fewer symptoms. We determined the reliability and concurrent validity of the KCSI and estimated a minimally important difference (MID). Results: The KCSI had excellent internal reliability at all three time points (alphas = 0.85). Baseline KCSI scores were able to discriminate patients across Karnofsky performance status (KPS 80–90 > KPS 70; F (2, 210) = 15.5, p < .001), number of identified metastatic sites (0–1 site > 2+ sites; t (211) = 3.2, p < .01), and risk group categories (favorable or intermediate risk > poor risk; F (2, 205) = 9.9, p < .001). No differences were observed in KCSI change scores over time across two objective clinical indicators: response to treatment and time to progression. All patients evidenced declines in scores from baseline likely indicative of the toxic nature of the treatments. Distribution- and anchor-based methods converged on an MID estimate of 2 to 3 points for the KCSI. Conclusions: The 8-item KCSI appears to be a psychometrically sound measure of patient-reported symptoms of RCC. It is a brief, reliable, and valid measure that can easily be adapted for use in clinical trials and observational studies. [Table: see text]
Novel mutations in tyrosine kinase domain of epidermal growth factor receptor in prostate cancer
Authors: Douglas D. , Zhong H. , Ro J. , Oddoux C. , Pincus M. , Satagopan J. , Gerald W. , Scher H. , Lee P. , Osman I. 
Published: March 2020

4611 Background: We recently reported that EGFR protein overexpression is significantly more common in African American (AA) prostate cancer patients compared to White patients (Shuch et al. 2004 JCO, 22:4673–4677). In the current study, we further explore EGFR dysregulation in prostate cancer patients of different ethnicities by examining mutations in the EGFR tyrosine kinase (TK) domain. In addition to AA and White prostate cancer patients, we included South Korean patients in light of recent reports that EGFR mutations are more common in Asian patients with non-small cell lung cancer. Methods: Normal and tumor DNA from radical prostatectomy cases (n = 89: Koreans n = 36, AA n = 27, Whites n = 26) were studied for mutations in the EGFR TK domain using genomic DNA sequencing. Results: We identified 4/89 (5%) novel missense mutations in exons 19, 20 and 21 of TK domain: 3 in Koreans (8%, 95%, CI = 2%– 22%) and 1 in White (4%, 95% CI = 0.1%–20%) but none in AA. These mutations, which were not described before, are expected to affect TK activity based on the change of the amino acid phosphorylation pattern and the 3-dimensional structure of TK domain. We also identified 5 distinct synonymous DNA sequence changes in exons 20 and 21 in 31/89 (35%) patients. These synonymous sequence changes were not observed in the corresponding normal DNA in 8/31 (25.8%) patients, indicating the presence of de novo somatic mutation in those patients, and are likely to affect mRNA splicing leading to altered EGFR protein transcripts. Conclusions: Several independent mechanisms of EGFR dysregulation operate in prostate cancer including EGFR protein overexpression, missense mutations, and somatic synonymous sequence changes in the TK domain. Validation on a larger sample size in addition to functional studies are needed to determine the specific association between a patient’s ethnicity, EGFR dysregulation, and response to EGFR inhibitors in prostate cancer. No significant financial relationships to disclose.
Impact of zoledronic acid (Z) on pain in prostate cancer patients with bone metastases in a randomised placebo-control trial
Authors: Abetz L. , Barghout V. , Arbuckle R. , Bosch V. , Shirina N. , Saad F. 
Published: March 2020

4638 Background: Bone metastases occur in up to 80% of advanced prostate cancer patients and can results in painful Skeletal-Related Events (SREs). Z is the only biphosphonate approved for metastatic prostate cancer that decreases the occurrence of SREs which include pathologic fractures, severe bone pain requiring radiation therapy, spinal cord compression, surgery to bone and hypercalcemia of malignancy which may lead to daily activity limitations. We performed retrospective analyses on data from a placebo-controlled study of Z to investigate which items of the Brief Pain Inventory (BPI) were most sensitive to changes in patient’s pain due to treatment. Methods: Prostate cancer patients with bone metastases received Zoledronate 4 mg (n = 201) or placebo (n = 201). The BPI was administered at baseline (visit 2), and visits 3 (weeks 3–4), 4 (weeks 6–8), and then every second visit (every 6 weeks) until study end. Changes in BPI individual item scores and the Pain Severity and Pain Interference scale scores were compared between Z and placebo groups. Post-baseline missing data was replaced by Last Observation Carried Forward (LOCF). Results: Z was statistically significantly better than placebo for changes in BPI items ‘pain at its worst’, ‘pain at its least’, ‘pain on average’, and the BPI pain severity scale (p < 0.05) at visit 4 (weeks 6–8), and visit 6 (week 12). For ‘pain right now’ there were statistically significant differences at visit 4, but not visit 6. Z was also superior to placebo for ‘pain right now’ and the Pain Severity and Interference scales at visit 12 (week 30–32) (p < 0.05). Finally Z was superior to placebo for ‘interference with general activities’ at visits 12 (week 30–32), 16 (weeks 42–44), and LOCF (p < 0.05). Conclusion: Our findings suggest that Z significantly reduces bone pain and general activity limitations in prostate cancer patients with bone metastases. Several items in the BPI are more sensitive to Z treatment including ‘pain at its worst’, ‘pain at its least’, ‘pain on average’, and the BPI Pain Severity scale. [Table: see text]
Update on a phase II study of cyclophosphamide, etoposide and estramustine in patients with androgen independent prostate cancer
Authors: Moffett P. U. , Choudry M. A. , Ferguson L. A. , Williams D. A. , La Rocca R. V. , Hendler F. J. , Laber D. A. 
Published: March 2020

4647 Background: Oral therapy offers the tremendous advantage of independence and avoids all the catheter-related complications. Cyclophosphamide (C), etoposide (E) and estramustine (E) are active against androgen-independent prostate cancer (AIPC). The optimal dose and schedule of these agents have not been defined. Methods: Objectives are to evaluate the efficacy and safety of this triple drug regimen (CEE). Each treatment cycle consists of cyclophosphamide 50 mg/m2 p.o., etoposide 50 mg/m2 p.o. and estramustine 280 mg p.o. administered on days 1–14, every 28 days. Response was assessed by changes in size of measurable and non-measurable lesions (RECIST JNCI 92(3):205–216, 2000), and PSA levels (JCO 17(11):3461–7, 1999). Results: Twenty-nine subjects with AIPC were enrolled. 25 patients, who completed at least 2 cycles, are evaluable for toxicity and response. Median baseline characteristics: age 68 years (52–86); ECOG performance status 2 (0–3); PSA 148 ng/ml (26–2268); and 8 had prior chemotherapy. Total number of cycles administered: 98 with median of 3 cycles/patient. Response: PSA response: Out of 25 subjects, 7 (28%) had >50% decrease and 5 (20%) had >75% decrease, for an overall PSA response of 58%. Measurable disease: 13 patients had measurable lesions by RECIST criteria. One pt had a complete response (8%), seven had SD (54%) and there were 5 PD (38%). 44% of the subjects experienced an improvement in their ECOG performance status and 64% reported improvement in their level of pain. Toxicity: Grade 3–4: 36% neutropenia, 12% thrombocytopenia, 5% anemia. Four patients (27%) developed a thrombotic event. 3 with DVTs, two spontaneous and one after a 14-hours car trip. One subject with a strong history of cardiac complications had a myocardial infarction. Neutropenic fever requiring antibiotic use occurred in 2 patients. Conclusions: CEE is a well-tolerated, all oral, easy to administer and effective triple drug therapy for patients with metastatic androgen-independent prostate cancer. No significant financial relationships to disclose.
Extended vs. limited laparoscopic pelvic lymph node dissection for prostate cancer: The value of Partin tables in selection of the need for and the extent of dissection
Authors: Touijer K. , Rabbani F. , Romero Otero J. , Secin F. , Guillonneau B. 
Published: March 2020

4654 Background: To determine if pelvic lymph node dissection (LND) can be omitted in prostate cancer patients at low risk of nodal metastases according to the Partin tables and to determine the yield on extended vs limited LND in patients at high risk to better define the appropriate template of dissection. Methods: A total of 577 patients with clinically localized prostate cancer underwent a laparoscopic radical prostatectomy (LRP). In the first 363 patients, a cutoff of 1% on the Partin tables’ predicted probability of lymph node invasion (PPLNI) was used to select patients for a limited LND (external iliac nodes only). In the subsequent 214 patients, all patients underwent an extended LND (external iliac, obturator and hypogastric nodes). Patients were classified into 4 groups: Group I, 186 patients with a PPLNI ≤1%, did not undergo a LND; Group II, 110 patients with PPLNI ≤ 1%, underwent an extended LND; Group III, 177 patients with PPLNI >1% underwent a limited LND and Group IV, 104 patients with PPLNI >1%, underwent an extended LND. We compared Group I and II to assess the value of the Partin tables in selecting low risk patients for nodal metastasis. Multivariate logistic regression analysis was performed to compare the node positivity rate between groups III and IV, controlling for preoperative and pathological parameters. Results: None of the patients in group II had a positive lymph node after an extended LND. On multivariate analysis, controlling for PSA, biopsy Gleason, clinical stage, pathological Gleason and stage, and seminal vesicle invasion, the extended LND independently impacted the rate of node positivity with a relative risk (RR) of 15.6 (95% CI 3.7 -66.4, p < 0.001). The median (mean) number of nodes retrieved was 9 (10) and 14 (15) after limited and extended LND respectively (p < 0.001). Conclusions: A lymph node dissection including the external iliac, obturator and hypogastric lymph node groups yields positive nodes more frequently and retrieves a higher total nodal count than the often-performed LND limited to the external iliac nodes. Decision to forgo LND in low risk patients needs to be validated by long-term biochemical recurrence data No significant financial relationships to disclose.
Does timing of androgen deprivation influence radiation-induced toxicity? A secondary analysis of Radiation Therapy Oncology Group protocol 9413
Authors: Bahary J. , Bae K. , Taussky D. , Roach M. , Sandler H. M. , Shipley W. U. 
Published: March 2020

4655 Background: We conducted a secondary analysis of RTOG 9413 to compare if the timing of antiandrogen-therapy, concomitant versus adjuvant, influences the incidence of rectal toxicity in whole pelvic radiotherapy. Methods: For the purpose of this secondary analysis, we analyzed the 2 of the 4 arms of the study, in which all patients received radiotherapy to the whole pelvis followed by a boost to the prostate and excluded the two arms that received prostate only radiotherapy. The 2 arms differed only in the timing of the total of 4 months of total androgen deprivation (TAD): arm I (320 patients), TAD was begun 2 months before the start of radiotherapy and continued during radiotherapy. Arm III (319 patients), TAD started immediately after the completion of radiotherapy. Both acute rectal and acute urinary toxicities (CTC v.2.0), testosterone (measured at baseline and yearly after) and other patients data were modeled using the multivariate logistic regression and the multivariate Cox-proportional hazards regression. Results: Median follow up for all patients is 6.0 and 5.8 years (arm I and II, resp.). 43 (13%) patients in each arm had abnormally low testosterone before start of TAD. Late grade 2 - 5 rectal toxicity occurred in 16% and 13% and urinary toxicity in 18% and 20% (arm I and II, resp.). Frequency (or occurrence) of late rectal toxicity (grade 0–1 vs. 2–5, p = 0.2170) and late urinary toxicity (grade 0–1 vs. 2–5, p = 0.4204) are not significantly different between the two arms. The only risk factors for late rectal toxicity in a multivariate regression model was acute rectal toxicity (OR 1.48, p = 0.025), but not abnormal testosterone level at baseline (p = 0.718) or treatment arm (p = 0.874). For late urinary toxicity: age (OR = 1.588, p = 0.010), RT field size (OR 1.004, p < 0.025), baseline testosterone (OR 1.718, p = 0.028), and acute (grade 2–4) toxicity (OR = 1.664, p = 0.006) but not treatment arm (p = 0.928) were risk factors. Conclusions: While late toxicity was not different for concomitant vs. adjuvant hormonal therapy, an abnormally low testosterone level at baseline is a risk factor for late urinary toxicity and not late rectal toxicity. No significant financial relationships to disclose.
Cytochrome P450 2D6 status predicts breast cancer relapse in women receiving adjuvant tamoxifen (Tam)
Authors: Knox S. K. , Ingle J. N. , Suman V. J. , Rae J. M. , Flockhart D. A. , Zeruesenay D. , Ames M. M. , Visscher D. W. , Perez E. A. , Goetz M. P. 
Published: March 2020

504 Background: CYP2D6 genetic variants and concurrent administration of potent inhibitors (Inh) of the enzyme markedly reduce the plasma concentrations of endoxifen (Jin. JNCI 2005;97:30–9). We have shown that genetic variation in CYP2D6 is associated with a higher risk of relapse in Tam treated patients (pts) (Goetz. JCO 2005;23:9312–18), but the impact of CYP2D6 inhibition on Tam clinical outcome is unknown. Methods: Using the North Central Cancer Treatment Group 89–30–52 adjuvant Tam trial (1989–1994), we evaluated the effect of co-administration of CYP2D6 Inh and CYP2D6*4 genotype on relapse in pts receiving tam alone. Patient charts were reviewed at each randomizing site to record the following known CYP2D6 Inh: fluoxetine (F), paroxetine (P), sertraline (S), cimetidine (C), amiodarone (A), doxepin (D), ticlopidine (T) and haloperidol (H). Poor metabolizers (PM) were defined as pts who were CYP2D6 *4/*4 and/or known to receive a CYP2D6 Inh. Intermediate metabolizers (IM) were defined as WT/*4 without CYP2D6 Inh, and extensive metabolizers (EM) as WT/WT without CYP2D6 Inh. The association between CYP2D6 status and Tam clinical outcome was determined using the log-rank test. Multivariate Cox modeling was performed using traditional prognostic factors. Results: CYP2D6*4 genotype was obtained in 190 of 256 eligible pts, with a CYP2D6*4/*4 genotype frequency of 6.8% as described previously (Goetz JCO 2005). Medication history was available in 171/256 eligible pts and in 143/190 pts with CYP2D6 genotype. Eleven of 173 patients were concomitantly administered these CYP2D6 Inh: F(2), P(2), S(2), H(1), C(4), and D(1). The median duration of use was 2.5 yrs. Twenty-four pts met criteria for PM [13 by *4/*4 genotype and 11 by CYP2D6 Inh (7 WT/WT, 1 WT/*4, and 3 unknown genotype)], 21 for IM, and 102 for EM. Compared with either IM or EM, PMs had significantly worse time to recurrence and disease free survival in both the univariate (HR 2.5, p=0.02; and 2.2, p=0.01) and multivariate (HR 2.7, p=0.01; and HR 2.2 p=.02) analyses utilizing tumor size, nodal status, and tumor grade. Conclusion: Our data indicate that CYP2D6 status can be used to identify pts who should receive tam therapy and tam treated pts should not be co-administered potent CYP2D6 inhibitors. No significant financial relationships to disclose.