bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term outcomes of radiotherapy for stage II testicular seminoma: The Mayo Clinic experience.
Authors: Hallemeier Christopher Leigh , Pisansky Thomas Michael , Davis Brian , Choo Richard 
Published: February 2017

327 Background: To report long-term outcomes of patients (pts) treated with radiotherapy (RT) for stage II testicular seminoma. Methods: Between 1974 and 2007, 52 pts received RT for clinical stage II testicular seminoma after radical inguinal orchiectomy; 3 pts were excluded due to no clinical follow-up. CT staging was used for 46 pts (94%). Estimates of overall (OS), relapse-free (RFS), and cause-specific (CSS) survival were determined using the Kaplan-Meier technique. Major cardiac event (MCE) was defined as myocardial infarction, coronary artery bypass grafting or stenting, or valve replacement. Second malignancy (SM) was defined as biopsy-confirmed malignancy occurring in the RT field. Results: The median pt age was 35 years. AJCC stage was IIA (n=23), IIB (n=7), IIC (n=15), and unknown (n=4). Three pts were treated for paraortic recurrence during surveillance for stage I seminoma. Four pts with IIB (n=1) or IIC (n=3) disease were treated with chemotherapy in addition to RT. The median total RT dose was 30.4 Gy. Prophylactic mediastinal/supraclavicular (MSCV) RT was given to 24 pts (49%). The median follow-up was 18 years (range 0.4-37). Estimates of OS, RFS, and CSS at 10 and 20 years were 94% and 81%, 79% and 70%, and 96% and 96%, respectively. OS, RFS, and CSS were not significantly different between stage groups. Recurrence occurred in 9 pts (18%); sites were MSCV (n=6), para-aortic (n=1), lung (n=1), and peritoneal cavity (n=1). Seven pts were successfully salvaged, while 2 pts died of seminoma. No patient with stage IIA/B that received prophylactic MSCV RT (n=11) experienced MSCV relapse. Among patients that did not receive prophylactic MSCV RT, 2 of 13 (15%) with stage IIA and 3 of 6 (50%) with stage IIB experienced MSCV relapse. MCE occurred in 10 pts (20%) at a median of 18 years (range 7-30) after RT. SM occurred in 5 pts (10%) at a median of 27 years (range 20-34) after RT. Conclusions: Infradiaphragmatic RT alone was associated with a significant risk of MSCV failure, particularly in patients with stage IIB disease, suggesting that chemotherapy may be the optimal treatment in this patient cohort. Most MCE and SM events occurred more than 20 years after RT, highlighting the importance of vigilant long-term follow-up.
Genetic variants in antioxidant genes, Gleason grade, and prostate cancer recurrence after radical prostatectomy.
Authors: Richman Erin L , Weinberg Vivian K. , Sosa Eduardo V , Song Xiaoling , Carroll Peter , Witte John S , Chan June M. 
Published: February 2017

33 Background: Laboratory and genomic data suggest that the antioxidant defense system is important in prostate carcinogenesis, and that this relation may vary by plasma antioxidant status. Methods: Among 567 radical prostatectomy (RP) patients with non-metastatic prostate cancer (CaP), we examined genetic variants in SOD1(5 SNPs), SOD2(6), SOD3(6), TXRND1(5), TXRND2(21), GPX1(3), GPX3(8), GPX4(5), CAT(9), XRCC1(2), SELENBP1(5), SEP15(4), SEPP1(4), SEC14L2(8), and TTPA(4) and risk of high pathologic Gleason sum (8+ or 7 with primary 4+) using logistic regression, and CaP recurrence (PSA rise, second treatment, metastasis) using Cox proportional hazards regression. We also examined whether the genetic variants interacted with plasma selenium, alpha-tocopherol, or gamma-tocopherol in relation to risk of high grade CaP. Results: 21% (n = 117) of men had high grade CaP, and 47 recurrences occurred (median follow-up of all participants = 3 y). Men with 1+ of the less common allele (CT or TT) in rs4880 (SOD2) had a 49% reduced rate of recurrence (hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.28, 0.92), independent of grade, stage, and PSA. In contrast, men with 1+ of the less common allele in 3 of the TXRND1, 4 of the TXRND2, and 1 of the SEP15 SNPs had 2-fold increased rate of recurrence (HRs: 1.93-2.95; p-values: 0.002-0.04), and men with 2 of the less common allele in 2 of the GPX3 SNPs had 3-fold increased rate of recurrence (p-values from additive models: <0.01). For high grade CaP, men with 1+ of the less common allele in 1 of the SOD3 SNPs or 2 of the less common alleles in 2 of the TXRND2 SNPs had 2-fold increased risk (p-values = 0.007-0.02), while men with 1+ of the less common allele in 1 of the GPX1 SNPs had 37% reduced risk (p-value = 0.04). Among men with certain genotypes in 3 TXRND2, 1 GPX3, or 2 CAT SNPs, high plasma selenium reduced risk of high grade CaP by 50-76%. Among men with certain genotypes in 1 SOD1 or 1 SOD2 SNP, high plasma alpha-tocopherol reduced risk of high grade CaP by 65-68%. Conclusions: Genetic variants in antioxidant genes may be associated with CaP recurrence after RP, and may interact with plasma selenium and alpha-tocopherol in relation to risk of high grade CaP.
Adjuvant surgery in patients with testicular cancer undergoing post-chemotherapy retroperitoneal lymph node dissection.
Authors: Djaladat Hooman , Nichols Craig R. , Daneshmand Siamak 
Published: February 2017

335 Background: Up to 50% of patients who undergo induction chemotherapy for metastatic germ cell cancer have significant residual retroperitoneal disease in whom post chemotherapy RPLND is indicated with intent to cure. Since complete resection is a critical component in PC-RPLND, meticulous dissection of the retroperitoneum with resection of involved organs or structures (adjuvant surgery) should be considered whenever feasible to ensure optimal outcome. Methods: From 2004 to 2010, 85 testicular cancer patients underwent PC-RPLND by a single surgeon (SD). A bilateral template approach was utilized with nerve sparing technique whenever feasible. The clinico-pathologic and outcome of patients who underwent adjuvant surgery during PC-RPLND were reviewed. Results: Of 85 patients undergoing PC-RPLND, 28 (33%) required adjuvant procedures. Thirteen (15%) required vascular procedures including cavotomy/ caval resection in six, aortic resection in eight, common iliac vessels resection in four and renal vessels resection/reimplant in two. Twelve patients (14%) required adjuvant nephrectomy (10/12 left sided). There was 1 ureteral resection with appendiceal substitution, 1 partial duodenectomy, 2 cholecystectomy, 2 thoracotomies, 4 liver resection/ biopsy, and 1 neck dissection. There were 8 early complications (28%) including vocal cord paralysis, brachial plexus injury, lower extremities compartment syndrome, thigh numbness, UGI bleeding, retroperitoneal hematoma and alcohol withdrawal. No peri-operative death was reported. Retroperitoneal pathology revealed mature teratoma in 11 (39%), fibrosis in 8 (28%) and viable germ cell tumor (GCT) in 9 (32%) patients. 75%, 82% and 66% of patients with fibrosis, teratoma and viable GCT had no evidence of recurrence in mean follow up of 18 months. Conclusions: A significant number of patients undergoing PC-RPLND require adjuvant surgery including vascular procedures and nephrectomy. The excellent outcomes associated with low operative morbidity/mortality validate such aggressive surgical approaches performed by experienced surgeons.
Changes in body fat and lipid metabolism in testicular cancer patients undergoing curative chemotherapy.
Authors: Willemse Peter-Paul Michiel , van der Meer Rutger W. , van Elderen Saskia , Burggraaf Jacobus , Lamb Hildo J , de Roos Albert , Osanto Susanne 
Published: February 2017

337 Background: Testicular cancer (TC) survivors are at increased risk to develop metabolic syndrome and cardiovascular disease. We assessed the utility of proton magnetic resonance spectroscopy (H1-MRS) and aortic Pulse Wave Velocity (aoPWV) with MRI to detect the early effects of chemotherapy-induced changes in lipid metabolism on liver fat storage and vascular function in testicular cancer patients undergoing curative treatment. Methods: Nineteen 19 chemo-naïve TC patients (age 20–54 years) were studied before, shortly after (<3 months), and 9 months after the start of three or four cycles of cisplatin-based chemotherapy. At each visit, fasting blood samples for serum glucose, insulin, HbA1c, and lipids were collected, and abdominal subcutaneous (scFat) and visceral fat (visFat) volume, hepatic triglyceride content (HTgC), and aoPWV were assessed by MRI. All measurements were performed using validated methodology. Data were analysed using RM-ANOVA. Results: Shorty after cessation of chemotherapy there was an increase in fasting serum insulin (5.7±4.4 vs. 9.6±6.3; p=0.05), HOMA-index (1.3± 0.3 vs. 2.3± 0.4; p=0.006), HbA1c (5.2±0.3 vs. 5.3±0.6; p=0.03), total cholesterol (4.88±1.31 vs. 5.61±1.50; p=0.002) and LDL-cholesterol (3.31±1.16 vs. 3.73±1.41; p=0.02). This coincided with relative volume increases of scFAT (6.9%; 95%CI 0.4–13.4%) and visFAT (18.7%; 95%CI 2.4–35.1%), a unsignificant increase in HTgC (47.4%; 95%CI −5.4–129.5%). AoPWV did not change (0.2%; 95%CI −0.5–0.8%). All parameters that were increased at 3 months returned to baseline at 9 months, but the increases in scFAT and visFAT remained. Conclusions: Cisplatinum-based chemotherapy in TC patients is associated with disturbances of glucose and lipid metabolism shortly after therapy but returns to baseline later. These changes did not translate into significant increases in HTgC and aoPWV, suggesting that these measures are of limited value to detect early chemotherapy-induced changes. Interestingly, scFAT and visFAT showed sustained increases, and this may explain the observed higher incidence in metabolic syndrome and (ensuing) cardiovascular disease in chemotherapy-treated TC patients.
Salvage treatment for metastatic penile cancer after first-line chemotherapy with paclitaxel, ifosfamide, and cisplatin: Analysis of response and survival outcomes.
Authors: Wang Jennifer , Pettaway Curtis A. , Pagliaro Lance C. 
Published: February 2017

340 Background: There are few effective salvage treatment options for men with advanced metastatic penile cancer. Patients who remain disease-free for 2 years after surgical removal of regional lymph node metastases are likely cured of the disease, but the survival is short for those who recur. Our objective was to estimate the efficacy of salvage treatments for metastatic penile cancer after neoadjuvant paclitaxel, ifosfamide, and cisplatin. Methods: Patients are from a 30-patient cohort who we saw between April 2000 and September 2008 presenting with stage TxN2-3M0 squamous cell carcinoma of the penis. All were treated with 1 to 4 courses of neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy prior to planned lymphadenectomy. For the patients who had progression or recurrence of disease, we retrospectively evaluated the salvage therapies given, response data, and survival times from the date of first progression. Results: Nineteen of the 30 patients (63.3%) had tumor progression and 17 received one or more salvage therapies. Median age at diagnosis was 57 years (range 24-72 years). The median survival from time of first progression was 5.8 months (range 3.7 to 30.9 months). Two of five patients (40%) who had received bleomycin, methotrexate, and cisplatin experienced an objective response (1 complete and 1 partial), and one (20%) developed pneumonitis. Two patients had received gemcitabine combinations without response. Two patients had received epidermal growth factor receptor-targeted therapy with gefitinib or cetuximab and cisplatin, both without response. Three patients had received chemo-radiotherapy, one with stable disease for 13.5 months and 2 with no apparent benefit. Five patients underwent salvage surgery, and they all progressed within 2 months with one case of fatal hemorrhage. Conclusions: Men with metastatic penile cancer that progresses through or recurs after front-line neoadjuvant chemotherapy have poor responses to the described salvage treatments, and median overall survival is less than 6 months. Emphasis should be placed on clinical trials for development of effective therapy in this setting.
Combination of paclitaxel, cisplatin, and gemcitabine (TPG) as third- to fourth-line therapy for male germ cell tumors (GCT).
Authors: Necchi Andrea , Nicolai Nicola , Giannatempo Patrizia , Raggi Daniele , Napoli Giuseppa , Catanzaro Mario , Biasoni Davide , Torelli Tullio , Milani Angelo , Stagni Silvia , Piva Luigi , De Braud Filippo G. , Gianni Alessandro M. , Salvioni Roberto 
Published: February 2017

341 Background: Rescue of patients (pts) who fail to be cured following 2–3 chemotherapy (CT) combinations ± high dose CT (HDCT) or who are cisplatin-refractory is still an unmet need. The identification of novel active agents/combinations is a priority. Methods: We reviewed the characteristics of consecutive pts who received TPG combination at our Institution for relapse/progression after 2 or 3 previous platinum-based CT lines. Treatment consisted of the administration of paclitaxel 80 mg/m2 IV, cisplatin 50 mg/m2 IV and gemcitabine 800 mg/m2 IV on days 1 and 8 q3w. Program provided up to 8 administrations of TPG followed by surgery of all resectable masses. Paraffin slides of all cases with residual viable cancer after TPG were retrieved: CD30 staining and somatic mutation analysis by Sequenom OncoCarta Panel v.1.0 were planned. Results: From 04/1999 to 07/2011, 74 pts have been treated with TPG, 64 in 3rd and 10 pts in 4th line. Median age was 32 (20–55), median number of prior CDDP cycles was 7 (4–10), 10 pts (13%) had already received HDCT, 4 pts had primary mediastinal GCT, 42 (57%) were CDDP-refractory/abs refractory, 25 pts (34%) had either liver, bone or brain metastases before TPG. 40% developed G3-4 hematologic and 2 pts G3 renal toxicity, none of them being dose-limiting. No treatment delays have been observed. Median number of administrations was 7 (1–10). 8 complete responses (CR), 28 partial responses with normal markers (PRm-) and 13 incomplete response/stable disease have been recorded, for a major response rate (CR+PRm-) of 49%. 34 pts (46%) underwent post-CT surgery which was radical in 15 cases (44%) and led to 7 pathologic CR. 3-, 6- and 12-month PFS was 68% (95% CI 55–76%), 31% (21–42) and 20% (12–30), respectively. 1-yr PFS after HDCT only was 24% (4–53). 12- and 24-month OS was 46% (34–57) and 26% (16–37), respectively. Median PFS and OS were 5 (1–104) and 12 mos (1–116). Conclusions: TPG combination rates first among salvage therapies for refractory GCT, even after failure of HDCT. Benchmark survival endpoints for trials on new agents/combinations have been set. Results of the biomarker analysis will be available in Feb 2012 and may help to corroborate a window of opportunity for targeted agents in GCT.
A prospective randomized phase II trial evaluating maintenance GM-CSF in an intermittent chemotherapy (chemo) regimen for metastatic castration-resistant prostate cancer (mCRPC): A DoD prostate cancer clinical trials consortium trial.
Authors: Small Eric Jay , Weinberg Vivian K. , Ryan Charles J. , Higano Celestia S. , Lin Amy Mimi , Maruca Yvonne , Alumkal Joshi J. , Yu Evan Y. , Rosenberg Jonathan E. , Beer Tomasz M. 
Published: February 2017

35 Background: The optimal number of cycles of docetaxel for patients (pts) with mCRPC is not known, and in practice, treatment breaks are common. The current study was designed to test the safety and efficacy of utilizing 6 cycles of standard docetaxel with chemo free intervals in patients who achieve and maintain a response to docetaxel. Methods: Pts with mCRPC, no prior chemo, and KPS > 60% were eligible. Pts were treated with “induction” docetaxel 75 mg/m2 q 3 weeks, and prednisone 5 mg po bid. PSAWG1 criteria were used to define response and progression. After 6 cycles, responding pts stopped chemo and were randomized to observation (Obs) or to GM-CSF, 250 mcg/m2 daily for 14 days out of every 28-day cycle. Pts were followed with monthly PSA and imaging every 2 cycles until progression, at which point docetaxel was reinitiated for another 6 cycles, followed by the same “off chemo” regimen. The primary endpoint was the time to progression while on chemo (time to chemo resistance). Results: 114 pts have been enrolled: 3 are undergoing induction, and 111 are therefore evaluable. Of these pts, 82 completed induction, (10 did not due to PD, 9 due to adverse events (AE), 10 due to pt or MD choice). Of 111 evaluable pts, 48 (43%) had a response to chemo and were eligible for randomization. 22 were randomized to Obs and 26 to GM-CSF. Of 48 randomized pts, 25 restarted chemo, all for PSA PD. (23 pts did not re-start chemo because of AE, other therapy being started, or pt choice; 1 pt is still on GM-CSF.) 6/25 (24%) pts experienced a response to the 2nd series of chemo, and 1/6 (17%) to the 3rd. The time to chemo re-initiation (n=25) was 3.1 mos in Obs pts and 4.2 mos in GM-CSF pts. Conclusions: 43% of patients met criteria for undergoing intermittent chemo. The response proportion to the 1st, 2nd, and 3rd series of docetaxel was 43%, 24% and 17%, respectively. GM-CSF may modestly delay the time to chemo re-initiation, but the sample size is small and insufficient to assess the impact of GM-CSF on time to chemo resistance.
A multicentered population-based analysis of outcomes of patients with metastatic renal cell carcinoma (mRCC) who do not meet eligibility criteria for clinical trials.
Authors: Heng Daniel Yick Chin , Choueiri Toni K. , Lee Jae-Lyun , Harshman Lauren Christine , Bjarnason Georg A. , Knox Jennifer J. , MacKenzie Mary J. , Vaishampayan Ulka N. , Tan Min-Han , Rha Sun Young , Donskov Frede , Agarwal Neeraj , Kollmannsberger Christian K. , North Scott A. , Rini Brian I. , Wood Lori ,   International mRCC Database Consortium
Published: February 2017

353 Background: Clinical trials have strict eligibility criteria to maintain internal validity. These criteria exclude many patients to whom the trial results are later applied to in clinical practice. Patients that do not meet eligibility criteria are poorly characterized. Methods: mRCC patients treated with VEGF targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky Performance Status (KPS) < 70%, brain metastases, non-clear cell histology, hemoglobin ≤ 9 g/dL, creatinine > 2x the upper limit of normal, platelet count of < 100x103/uL, neutrophil count < 1500/mm3 or corrected calcium ≤ 12 mg/dL. Results: 894/2076 (43%) patients were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression free survival (PFS) and median overall survival of first-line targeted therapy were 21% vs 29%, 5.2 vs 8.8 months and 14.5 vs 28.8 months (all p < 0.0001), respectively. Second-line PFS (if applicable) was 3.2 months in the trial ineligible vs 4.4 months in the trial eligible patients (p = 0.0074). When adjusted by the Heng et al prognostic categories, the hazard ratio for death between trial ineligible vs trial eligible patients was 1.621 (95% CI = 1.431–1.836, p < 0.0001). If only KPS, brain metastases and non-clear cell histology were used as exclusion criteria, 672 (32%) patients were excluded and the results were similar. Conclusions: The number of patients that are ineligible for clinical trials is high and their outcomes are inferior. Designing more inclusive clinical trials for this “ineligible” patient population are needed. [Table: see text]
Evolving trends in non-clear cell renal cell cancer (RCC) epidemiology: A large registry analysis of 4,483 patients.
Authors: Pai Ashok P. , Brown Monica , Pan Chong-xian , Lara Primo 
Published: February 2017

374 Background: Non-clear cell (ncc) RCC is uncommon but includes a heterogeneous group of histologic subtypes such as papillary, chromophobe (Chr), medullary (Med), and collecting duct (CD) cancers. We used a large cancer registry to define nccRCC clinical features and outcomes, identify prognostic variables, and to generate hypotheses for further study. Methods: Invasive RCC tumors in the California Cancer Registry from 1998–2009 among adults > 18 years of age (n=38,251) were analyzed. Baseline clinical and tumor variables were collected. Primary outcome measures were 3-year cause-specific (CSS) and overall survival (OS). Uni- and multivariate survival analysis were used to identify predictors of CSS and OS. Results: Of 38,251 RCC cases, 19,149 (50%) were of clear cell type; 14,619 (38.2%) were “unclassified”. Thus, 4,483 (11.7%) nccRCC cases were identified and included in this analysis. Of these, 3304 (73.7%) were diagnosed in 2004–09, suggesting a shift to more precise coding of histologic subtypes starting in the early 2000s. Histology distribution (n, %): papillary − 2,863 (63.9%); Chr − 1,507 (33.6%); and other including Med and CD − 113 (2.5%). Variables associated with significantly better OS and CSS (univariate analysis) were Chr histology, female sex, and higher socioeconomic status (SES). Significantly worse OS and CSS were seen in Med+CD, age > 65 yrs, no nephrectomy (Nx), and higher stage. Non-hispanic blacks had significantly worse OS and CSS, while the “targeted therapy era” (2004–2009) was associated with better OS. Multivariate analysis showed the following to be independently associated with outcomes (all p <0.001; Hazard Ratios [HR] shown for CSS and OS): Chr histology (0.48, 0.56), Med+CD histology (2.99, 2.42), no Nx (2.84, 3.18), regional stage (5.84, 1.98), distant stage (25.7, 7.67); and non-hispanic blacks (1.5,2 p=0.006; 1.25, p=0.03). Age > 65 yrs (HR 1.78, p<0.001) and high SES (HR 0.88, p=0.001) were associated with OS but not CSS. Conclusions: This is among the largest registry analyses of nccRCC ever performed, showing emerging trends in this uncommon RCC subset. Clinical variables associated with CSS and OS were identified that can inform the design of future clinical trials in nccRCC.