bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salvage prostatectomy for prostate cancer (CaP): Data from the Surveillance Epidemiology and End Results (SEER) database
Authors: Johnstone P. A. , Goodman M. , Ward K. , Assikis V. , Ogan K. 
Published: March 2020

4622 Recent randomized data have established adjuvant radiation therapy (RT) as a standard of care approach for appropriately selected high-risk CaP patients after radical prostatectomy (RP). However, data on salvage prostatectomy (SP; defined here as radical prostatectomy, total prostatectomy, and cystoprostatectomy) after definitive RT are available only in single-institution reports of limited patient numbers. We analyzed data from the SEER database for the period 1988–1997. Specifically analyzed were data for patients undergoing various combinations of surgery and RT with or without hormonal therapy (HT; defined as medications, surgical castration or both) for localized (Stage I/II) CaP. Patients with multiple primary cancers were excluded. Demographic data for each case included age and diagnosis, race and year of diagnosis. Cancer-related variables included SEER summary stage and grade. Treatment information included surgery, RT, HT, and sequence of surgery with radiation. Using follow-up data through 2002, post diagnosis observed survival (OS) and relative survival (RS; defined as observed survival divided by that expected in a national age-, gender-, and race-matched cohort) was examined in four treatment groups: 44 patients with RT prior to SP, 1376 patients with RT following RP, 36344 patients with RP alone, and 30717 patients with RT alone. Mortality across treatment categories was compared using a Cox proportionate hazard model controlling for age, year of diagnosis, race, HT, SEER registry, and grade. Although infrequently performed, SP provides for 10-year relative survival of 82%. After controlling for potential confounding factors, data for RT followed by SP showed no appreciable benefit compared to RT alone. [Table: see text] No significant financial relationships to disclose.
Functional heterogeneity of prostatic intra-epithelial neoplasia: Length of hormonal therapy influences response
Authors: Kang T. , Nichols P. , Skinner E. , Groshen S. , Valin G. , Ye W. , Raghavan D. 
Published: March 2020

4648 Background: Prostatic intraepithelial neoplasia (PIN) is a premalignant lesion of the prostate etiologically linked to prostate cancer. While androgen deprivation therapy (ADT) has been used to reduce prostate cancer, there are controversial data regarding the effect of ADT on PIN. We hypothesized that PIN is a heterogeneous entity with respect to hormone responsiveness, that this may explain aspects of the heterogeneity in the natural history of this disease, and have used the clinical model of ADT followed by radical prostatectomy as a test of this hypothesis. Methods: We performed a retrospective study on a cohort of patients who underwent prostatectomy with biopsy proven prostate cancer. Study patients were those who must have received at least 3 months of ADT at the discretion of their surgeons. Patients from the same cohort who did not undergo ADT were used as controls. Patients were randomly selected from the database and their pathology slides were reviewed by a blinded pathologist looking for presence of PIN with an independent observer. Fisher’s exact test was used to compare the proportions of subjects who had residual PIN in the study group and the control group. Exact logistic regression was used to evaluate the duration of ADT in PIN regression. Results: Eighteen patients initially diagnosed with PIN who did not receive hormonal therapy were identified; 28 patients with PIN who underwent hormonal therapy were also studied. All patients who did not receive hormonal therapy had residual PIN whereas 7 of 28 patients undergoing ADT had no residual PIN (p = 0.043). Evaluation of hormonal therapy between responders and non-responders showed statistically significant association between PIN regression and hormone therapy duration (p < 0.001). However PIN response to ADT was not uniform as 16% of patients with ADT longer than 6 months had residual PIN, suggesting variable sensitivity of PIN to ADT. Conclusions: Our results demonstrate that ADT does cause PIN regression, and that there is heterogeneity in this effect with respect to hormonal duration. We propose for future prospective, multi-centered, randomized trials in which ADT impact on PIN is characterized further. No significant financial relationships to disclose.
Relationship of body mass index and other anthropometric measures and prostate specific antigen, NHANES 2001–2002
Authors: Saraiya M. , Werny D. , Thompson T. 
Published: March 2020

4649 Background: Obesity has been suggested to be a risk factor for prostate cancer. However, there has been limited information examining the relationship between body mass index (BMI) and other anthropometric measures such as triceps thickness (TT) and waist circumference (WC) and prostate specific antigen (PSA), a marker used in screening for prostate cancer. Methods: We analyzed data from the 2001–2002 National Health and Nutrition Examination Survey (NHANES), a cross-sectional survey of a nationally representative sample of the non-institutionalized civilian US population. Participants in this study were limited to men aged 40 years and older without previously diagnosed prostate cancer (n = 1320). Weighted analyses were done overall and within three racial/ethnic groups [non-Hispanic whites (white), non-Hispanic blacks (black), or Mexican Americans (Mexican)]. BMI, TT, and WC were examined as both as a continuous and as a categorical variable. Three linear regression models were fit to determine the individual effect of BMI, TT, and WC on PSA within each racial/ethnic group after adjusting for age. Results: Among white men, the median PSA was 1.09 ng/mL [95% CI (0.96, 1.30)] for men with a normal BMI, 0.80 [95% CI (0.70, 0.94)] for overweight men, 0.83 [95% CI (0.74,0.95)] for obese men, and 0.74 [95% CI (0.56,1.22)] for severely obese men. Among black men, the median PSA for men was 0.83 [95% CI (0.70, 1.94)] and remained constant across BMI levels. Among Mexican men, the median PSA was 0.92 [95% CI (0.82, 1.23)] for men with a normal BMI, 0.91 [95% CI (0.81, 1.07) ] for overweight, 0.73 [95% CI (0.54,1.14)] for obese, and 0.59 [95% CI (0.39,1.06)] for severely obese men. In linear regression models controlling for age, a significant non-linear relationship was seen with BMI and PSA for both white (p = 0.010) and Mexican men (p < 0.001) but not for black men (p = 0.167). Increased TT was associated with decreasing PSA for black and Mexican men. Increased WC was associated with decreasing PSA for white and Mexican men. Conclusion: These data do suggest racial/ethnic differences of PSA across BMI categories as well as other anthropometric measures. This finding may help inform practitioners about the relationship of anthropometric measures on PSA levels. No significant financial relationships to disclose.
Is biopsy Gleason sum an independent predictor of biochemical progression following radical prostatectomy after adjusting for the pathological Gleason sum?
Authors: Fitzsimons N. J. , Freedland S. , Presti J. , Amling C. , Kane C. , Terris M. , Aronson W. 
Published: March 2020

4652 Background: Biopsy Gleason sum is a known important predictor of PSA failure following radical prostatectomy (RP). However, it is unclear whether it remains predictive of outcome after surgery when the pathological Gleason sum is known. Methods: We determined the association between biopsy Gleason sum and biochemical progression after correcting for both pre-operative and post-operative characteristics including pathological Gleason sum among 1,931 men treated with RP between 1988 and 2005 within the SEARCH Database. Gleason sum was examined as a categorical variable of 2–6, 3+4, and ≥4+3. Results: Higher biopsy Gleason sums were associated with increased prevalence of extra-capsular extension (p < 0.001), positive surgical margins (p < 0.001), seminal vesicle invasion (p < 0.001), positive lymph nodes (p < 0.001), and biochemical progression (log rank, p < 0.001). After adjusting for only pre-operative characteristics, both biopsy Gleason sums of 3+4 (p = 0.004) and ≥4+3 (p < 0.001) were associated with increased risk of biochemical progression when compared to biopsy Gleason sums of 6 or less. After further adjusting for multiple pathological characteristics including pathological Gleason sum, the association between higher biopsy Gleason sum and risk of progression was little changed in that men with biopsy Gleason sums of 3+4 (p = 0.001) and ≥4+3 (p < 0.001) were significantly more likely to progress. Furthermore, when stratified by pathological Gleason sum, higher biopsy Gleason sums were associated with increased risk of biochemical progression within each pathological Gleason sum category (log-rank, p ≤ 0.007). Conclusions: Biopsy Gleason sum remains a strong predictor of outcome even when the pathological Gleason sum is known. If confirmed at other centers, incorporation of biopsy Gleason sum into post-operative nomograms designed to predict risk of progression might improve model precision. No significant financial relationships to disclose.
Are men with larger prostates and bothersome voiding symptoms less likely to have significant prostate cancer?
Authors: Porter C. R. , Wright J. , Borden L. , Jason K. , Latchemsetty K. 
Published: March 2020

4656 Background: Gleason Sum (GS) predicts clinically significant prostate cancer (CAP) and prostate specific antigen (PSA) survival in men undergoing prostatectomy for CAP. BPH can also elevate PSA. Objective: evaluate prostate gland volume (PV) and American Urologic Symptom Score (AUASS) in men undergoing prostate needle biopsy (PNB) to detect CAP. Analysis endpoints: 1) CAP and 2) GS ≥7. Methods: From 1/2000–7/2005, 1,078 men undergoing PNB were prospectively examined. Urinary voiding symptoms were measured by AUASS. All men were examined by 1 surgeon: DRE and Transrectal Ultrasound (TRUS) were given levels of suspicion (LOS) from 1 = low suspicion (smooth DRE, homogeneous TRUS) to 5 = high suspicion (hard DRE, hypoechoic lesion). LOS ≥3 was abnormal. Prebiopsy parameters: PSA, DRE, age, race, biopsy history, prostate volume (PV), TRUS lesion, and AUASS. All men had 10-core biopsy. 1) Predictors for CAP were evaluated by Univariate (UVA) and multivariate (MVA) analysis (logistic regression) for 1,078 men. 2) Predictors for GS≥7 were evaluated in men with no prior biopsy (NOPB). Results: Median PSA = 5.4 ng/ml (mean 10.4), 38% and 52% had abnormal TRUS & DRE respectively. Mean patient age = 64 years. Mean AUASS = 10.4. Positive biopsy rate = 38%. AUASS: 47% had low symptoms scores (<7), 39% had moderate scores (8–19), and 14% had severe scores (20–35). UVA & MVA (N = 1,078) showed that PSA was not an independent predictor of CAP (p = 0.18), but abnormal DRE, age, low AUASS, no prior biopsy (NOPB), race (AA), abnormal TRUS, and low PV were all independent predictors (p < 0.03). Subset MVA analysis of men in PSA range of 2.5–10 (N = 738), demonstrated that low AUASS (p = 0.05) & low PV (p = 0.00001) were predictors of CAP, while DRE, NOPB, and age were also independent predictors. MVA of men with NOPB (N = 790), indicated that low PV, PSA, DRE, and Age were independent predictors for CAP (p < 0.0001). The multivariate risk of having GS ≥7 on biopsy was independently associate with both low PV (p = 0.001) and abnormal DRE (p = 0.001). The relationship between PV and GS ≥7 showed that for every 1 cc increase in gland volume the risk of GS ≥7 CAP decreases by 2.2%. Conclusions: Men with smaller prostates are more likely to have cancer and are more likely to have significant disease. No significant financial relationships to disclose.
A Gynecologic Oncology Group randomized trial of whole abdominal irradiation (WAI) vs cisplatin-ifosfamide+mesna (CIM) in optimally debulked stage I-IV carcinosarcoma (CS) of the uterus
Authors: Wolfson A. H. , Brady M. F. , Mannel R. S. , Lee Y. , Futoran R. J. , Cohn D. , Ioffe O. B. , Rocereto T. F. 
Published: March 2020

5001 Background: Besides initial surgery, there has been no established consensus regarding adjunctive therapy for optimally debulked patients with uterine CS. This study was designed to compare progression-free interval (PFI), overall survival (OS), toxicity, and failure patterns using WAI vs CIM chemotherapy for this uncommon group of female malignancies. Methods: Patients with stage I-IV disease, ≤ 1 cm residual tumor, and no extra-abdominal involvement were randomly assigned to either WAI (approximately 30 Gy followed by pelvic boost) or cisplatin 20 mg/m2/d × 4, ifosfamide 1.5 g/m2/d × 4 and mesna 120 mg/m2 loading dose, then 1.5 g/m2/d × 24 h, repeated q 3 weeks × 3 cycles. Results: 224 patients were enrolled, of whom 207 (WAI = 105; CIM = 102) were eligible. Patient demographics and characteristics were similar between arms. FIGO stage (both arms) was: I = 64 (31%); II = 26 (12%); III = 93 (45%); IV = 24 (11%). GI toxicity ≥ grade 2 occurred frequently and similarly (31%, both arms). CIM was associated with more ≥ grade 3 anemia (11% vs 1%) and neurotoxicity (9% vs 0%) compared to WAI. Two deaths were attributed to RT-induced hepatitis. Sites of first recurrence in WAI vs CIM among the 97 (47%) patients who relapsed were: vagina, 4 vs 10; pelvis, 12 vs 12; abdomen, 23 vs 14; lung, 13 vs 13; other, 13 vs 9. The estimated probability of recurring within 5 years is 55% (WAI) and 49% (CIM). Adjusting for stage, the recurrence rate was 28.5% lower for CIM patients relative to WAI patients (hazard ratio [HR]: 0.715, 95% confidence interval [CI]: 0.474–1.077, p = 0.108, 2-tail test). The estimated death rate for CIM is 32.8% lower relative to WAI (HR: 0.672, 95% CI: 0.458–.986, p = 0.042). Conclusion: Compared to WAI, adjuvant CIM reduces the recurrence rate and significantly prolongs OS in optimally debulked uterine CS patients; however, due to a high relapse rate and poor OS, the imperative for new adjuvant therapies remains. No significant financial relationships to disclose.
Radiation ±cisplatin for bulky stage IB cervical carcinoma; Long-term follow-up of a GOG trial
Authors: Stehman F. B. , Ali S. , Gallup D. G. , Key H. 
Published: March 2020

5015 Purpose: To confirm that concurrent cisplatin (CT) with radiation (RT) is associated with improved long-term progression-free survival (PFS), overall survival (OS), and decreased morbidity compared to RT stage IB bulky carcinoma of the cervix, when both groups’ therapy is followed by hysterectomy. Methods: Three hundred seventy-four patients entered this trial. There were 369 evaluable patients; 186 were randomly allocated to receive RT alone and 183 to receive CT+RT. Radiation dosage was 40 Gray (Gy) in 20 fractions followed by a single low dose-rate intracavitary application of 30 Gy to Point A. Chemotherapy consisted of cisplatin 40 mg/M2 every week for up to six weekly cycles. Total extrafascial hysterectomy followed the completion of RT by 3–6 weeks. Results: Preliminary results have been published, at which time there many censored observations and limited follow-up. Patient and tumor characteristics were well-balanced between the regimens. The median patient age was 41.5 years; 81% had squamous tumors; 59% were white. Median follow-up is 101 months. The relative risk for progression was 0.61 favoring CT+RT (95% confidence interval [CI]: 0.43–0.85, p < 0.004). At 72 months 71% of patients receiving CT+RT were predicted to be alive and disease-free when adjusting age and for tumor size compared to 60% of those receiving RT alone. The adjusted death hazard ratio was 0.63 (95% CI: 0.43–0.91, p < 0.015) favoring CT+RT. At 72 months, 78% of CT+RT patients were predicted to be alive compared to 64% of RT patients. An increased rate of early hematologic and gastrointestinal toxicity was seen with CT+RT. There was no detectable difference in the frequency of late adverse events. Conclusion: Concurrent weekly cisplatin with RT significantly improves long term PFS and OS when compared to RT alone. Serious late effects were not increased. The inclusion of hysterectomy has been discontinued on the basis of another trial. Pending further trials, weekly cisplatin with radiation is the standard against which other regimens must be compared. Key Words: Cervical carcinoma, chemoradiotherapy. No significant financial relationships to disclose.
Analysis of the VEGF family and their receptors in serum/plasma of patients with pre-invasive and invasive cervical cancer
Authors: Landt S. , Thomas A. , Fueger A. , Jeschke S. , Korlach S. , Adam H. , Ulm K. , Schmid P. , Blohmer J. , Lichtenegger W. , Kuemmel S. 
Published: March 2020

5016 Background: The vascular endothelial growth factor (VEGF) family and their receptors are essential regulators of angiogenesis and lymphangiogenesis. This study examined the significance of circulating VEGF, VEGF-C, VEGF-D and their receptors VEGFR-1 and VEGFR-2 in patients with preinvasive and invasive cancer in relation to conventional prognostic parameters. Methods: Blood samples were obtained from 125 women before initial treatment (CIN I-III n = 50; FIGO stage I-IV n = 51; relapse n = 24). Plasma (p) and serum(s) levels of pVEGF, sVEGF-D, sVEGFR-1, sVEGFR-2 (R&D Systems, USA) and sVEGF-C (IBL, Japan) were determined by using a quantitative sandwich enzyme-linked immunosorbent assay (ELISA). Results: The highest level of pVEGF (p = 0.007) and sVEGFR-2 (p = 0.014) were detected in patients with recurrent disease, whereas the highest level of sVEGF-D (p = 0.046) were measured in patients with preinvasive lesions (CIN I-III). Furthermore, significantly elevated levels of sVEGF-C (p = 0.021) were detected in early stages (FIGO I-II) in comparison with advanced stages (FIGO III-IV) of cervical cancer. No significant difference in concentration was observed between the various grades of cervical intraepithelial neoplasia (CIN I-III). Correlations between conventional prognostic markers such as lymph node status (N0/N1), lymphangioinvasion (L0/L1), angioinvasion (V0/V1) and grading (G1/G2/G3) were investigated. Increased plasma levels of VEGF (p = 0.036) correlate with the dissemination of tumor cells to regional lymph nodes (N1),whereas serum VEGF-D levels were significantly decreased in women with lymph-node involvement (N1) (p = 0.045) and vascular invasion (L1) (p = 0.019). None of these members of the VEGF family were found to correlate significantly with histological subtype (squamous cell carcinoma, adenocarcinoma, adeno-squamous cell carcinoma) or grading of the tumor cells (G1/G2/G3). Conclusions: These results show that circulating concentrations of VEGF are associated with the stage of disease. In an early stage of cervical cancer a switch to a lymphangiogenic phenotype (VEGF-D, VEGF-C) might be possible. No significant financial relationships to disclose.
Molecular markers for lymph node involvement in locally advanced cervical carcinomas
Authors: Kristensen G. B. , Lyng H. , Svendsrud D. H. , Holm R. , Knutstad K. , Brøvig R. , Sundfoer K. , Oksefjell H. , Stokke T. 
Published: March 2020

5049 Background: Lymph node involvement is the first indication of cervical cancer spread and a strong prognostic factor. The aims of the present study were to identify genes associated with lymph node involvement. Methods: The nodal status and tumor volume were determined from MR images in 48 patients with FIGO stage 2a to 4a at the time of diagnosis. cDNA microarray technique was used to identify genes that differed in expression between node positive and negative tumors. Biopsies enriched for carcinoma tissue were co-hybridized with a common reference sample in a dye-swap design. Quantitative real time PCR (qRT PCR) and immunohistochemistry were used to validate microarray results and determine protein expression of selected genes. Results: Pathologic lymph nodes were seen in 29 patients and normal nodes in 19. We identified 16 genes with higher and 15 with lower expression in node positive tumors as compared to the negative ones. QRT PCR data of 4 genes were consistent with these findings. CKS2, MRPS23, MRPL11, LSM3 and PDK2 were upregulated in node positive tumors suggesting high proliferation activity and oxygen consumption. MSN, KLF3 and TBX3 were downregulated. CKS2, MRPS23, MRPL11, PDK2, LSM3, TBX3, KLF3 and MSN were significantly related to progression free survival in univariate analysis. Protein expression, determined for CKS2 and MSN, was significantly correlated to survival, consistent with these results. In multivariate analysis including only gene variables, MRPL11, PDK2 and TBX3 were significant. Including also clinical and MRI variables, tumor volume, KLF3 and TBX3 were significant. NEK1, CSTA, ANX4 and DDOST were upregulated indicating activated DNA damage repair (NEK1) and resistance to apoptosis (CSTA, ANX4, DDOST). NTN4 and HYAL1, which are involved in cell-matrix interactions, were downregulated, suggesting mechanisms for increased cell migration and invasive growth. Conclusions: Our findings are consistent with known phenotypic characteristics of node positive cervical tumors, such as hypoxia and high lactate content. They point to molecular mechanisms for development of hypoxia, deregulation of glucose metabolism, activation of survival strategies and interactions between carcinoma cells and tumor stroma that may promote metastasis formation. No significant financial relationships to disclose.
A multi-institutional study of radiation therapy for isolated para-aortic lymph node recurrence in uterine cervical carcinoma: 84 subjects out of over 5,000 population
Authors: Niibe Y. , Hayakawa K. , Michimoto K. , Kenjo M. , Kazumoto T. , Takayama M. , Yamauchi C. , Kataoka M. , Suzuki K. , Oguchi M. 
Published: March 2020

5052 Background: Most patient who had any recurrent sites of cancer, have been considered to be last-stage of life. However, recent advances of clinical research reveal some patients achieve long-term survival even in recurrence cases. Furthermore, patients who had only one recurrent region, even radiation therapy could play an important role. As for uterine cervical carcinoma, the most common recurrent site other than pelvis is para-aortic lymph node. Furthermore, improvement of diagnostic imaging enables us to detect more frequently isolated para-aortic lymph node recurrence. Thus, we conducted the current study. Methods: Between 1994 and 2003, over 5000 uterine cervical carcinoma patients treated with curative intended treatments at sixteen Japanese major hospitals. Out of them, 84 patients developed para-arotic lymph node recurrence as the only site of initial tumor progression. Seventy-four patitents had squamous cell carcinoma and 5 had adenosquamous cell carcinoma and 5 had adenocarcinoma. These patients were treated with external beam radiation therapy prescribing 1.7–2.0 Gy per fraction, 5 fractions per week and median total dose was 50 Gy (25–60 Gy). Thirty-two patients received adjuvant systemic chemotherapy. Results: Median follow-up time of all patients was 20 months (2–92 months). Three- and 5-year overall survival rates of all patients were 49.5% and 31.3%, respectively. Stratified by patients with or without chemotherapy, 3-year overall survival rate of patients with chemotherapy group was 37.7% and those without group was 56.7% (p = 0.69). Moreover, stratified by symptom sign, 3-year overall survival rate of symptom positive group was 27.6% and those of negative group was 56.1% (p = 0.018). Three-year overall survival rates of the total dose ≥ 51Gy and that of ≤ 50 Gy were 58.0% and 42.8%, respectively (p = 0.07). AS for morbidity, no patients received G3 or greater late toxicity (CTCAE ver. 3.0). Conclusions: The current study suggested that radiation therapy for isolated para-aortic lymph node recurrence in uterine cervical carcinoma could have significant impact on overall survival. Furthermore, no symptom group and over 51Gy irradiation group could achieve better prognosis. No significant financial relationships to disclose.