bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of relapse and second malignancy after adjuvant external beam radiation therapy for stage I-II seminoma.
Authors: Anderson Erik Steven , Folkert Michael Ryan , Zelefsky Michael J. , Alektiar Kaled M. , McBride Sean Matthew , Feldman Darren R. , Sheinfeld Joel , Kollmeier Marisa 
Published: March 2017

428 Background: To determine relapse rate, patterns of relapse and risk of second malignancy (SM) from a large single institution experience of adjuvant external beam radiation therapy (RT) for stage I-II seminoma. Methods: 463 patients with clinical stage I (n = 339) and II (n = 124) seminoma underwent adjuvant RT (median 25.5Gy) between 2/1990 and 11/2015. Data was gathered by retrospective chart review. Patients with > 5 years of follow-up (n = 312) were included in analysis of SM risk. Of stage II patients, 72% (89/124) received a boost to gross disease (median 4.5Gy). Field design was para-aortic nodal region only (n = 96), para-aortic and ipsilateral pelvic nodal region (n = 351) or para-aortic and bilateral pelvic nodal region (n = 8). Field design was not available for 8 patients. Patients were followed with clinical exam, serial imaging, and tumor markers. Relapse and SM were confirmed pathologically. Results: At median follow-up of 7.9 years, there were 20 relapses (median 13.2 months; range 2.5-55.3 months). There were 9 and 11 relapses in stage I and II patients, respectively, with 7/20 (35%) occurring > 2 years after RT. Relapses were identified by clinical symptoms (n = 7), imaging (n = 9), or elevated serum markers (n = 4). Sites of relapses included the lung/mediastinum (n = 10), retroperitoneum/pelvis (n = 5), bone (n = 3) and inguinal nodes (n = 2). 15 (3 pelvic) occurred after para-aortic and ipsilateral pelvic lymph node RT, while 5 (2 pelvic) occurred after para-aortic RT alone. 19/20 patients received cisplatin-based chemotherapy for relapse and were without evidence of disease at last follow-up (median 123 months). Of 35 total non-testicular SM (33 patients), 17 (48.6%) were in the RT field, 4 (11.4%) were marginal and 14 (40%) were out of field. Common SM were prostate (10), lymphoma (4), bladder (3) and kidney (3). The 5 and 10 year overall survival for the cohort is 99.2% and 97.9%, respectively. Conclusions: Stage I-II seminoma patients have a low risk of relapse and SM following adjuvant RT. Relapse is less common in patients treated with para-aortic and pelvic fields. More than 1/3 of relapses occur more than 2 years after adjuvant RT, necessitating long term clinical, radiographic and biochemical follow-up.
Intermediate-term outcomes from the DISSRM registry: A prospective analysis of active surveillance in patients with small renal masses.
Authors: Alam Ridwan , Patel Hiten D. , Riffon Mark F. , Trock Bruce J. , Uzosike Akachimere , Chang Peter , Wagner Andrew J. , McKiernan James M. , Allaf Mohamad , Pierorazio Phillip M. 
Published: March 2017

430 Background: Active surveillance is an alternative to primary intervention aimed at reducing the overtreatment of small renal masses, defined as solid renal masses ≤4.0 cm (clinical stage T1a). Methods: Since 2009, the Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry prospectively enrolled 615 patients with small renal masses who chose to undergo primary intervention or active surveillance. Intervention was recommended to patients for masses with an elevated growth rate (>0.5 cm/year) or increased tumor diameter (>4.0 cm). Primary outcomes were cancer-specific survival and overall survival; secondary outcomes included progression-free survival. Progression was strictly defined as growth rate >0.5 cm/year, greatest tumor diameter >4.0 cm, metastatic disease, or elective crossover. Outcomes were evaluated using Kaplan-Meier survival analysis and comparisons were performed using the log-rank test. Results: Of the 615 enrolled patients, 298 (48.5%) chose primary intervention and 317 (51.5%) chose active surveillance. From the active surveillance cohort, 45 (14.2%) patients underwent delayed intervention. Median follow-up time for the entire registry was 2.9 years, with 203 (33.0%) patients followed for 5 years or more. At baseline, patients who chose active surveillance were older (p < 0.001) and had higher comorbidity status (p < 0.001) than those who chose primary intervention. There was no difference in cancer-specific survival at 7 years between primary intervention and active surveillance (99.0% vs. 100%, respectively, p = 0.3). However, overall survival was higher in patients with primary intervention when compared to active surveillance at 5 years (93.0% vs. 80.2%, respectively) and 7 years (91.7% vs. 65.9%, respectively, p = 0.002). The 5-year and 7-year progression-free survival rate in the active surveillance cohort was 76.7% and 48.4%, respectively. Conclusions: In the intermediate-term, active surveillance appears to be as safe as primary intervention for carefully selected patients with small renal masses. As the registry matures, further studies will elucidate the effectiveness of active surveillance in the long-term. Clinical trial information: NCT02346435.
Cryoablation of cT1 renal masses in the “healthy” patient: Early outcomes from Mayo Clinic.
Authors: Zaid Harras B. , Atwell Thomas D. , Schmit Grant , Boorjian Stephen A. , Parker William P. , Cheville John C. , Leibovich Bradley C. , Thompson Robert Houston 
Published: March 2017

433 Background: Current guidelines suggest that percutaneous thermal ablation (PTA) can be utilized in those with significant comorbidity who are unable to tolerate surgery (radical or partial nephrectomy). However, the use of PTA in healthy patients, who are otherwise candidates for surgery, has been limited. Here, we reviewed our institutional experience in healthy patients electing to undergo PTA, specifically cryoablation. Methods: We identified patients ≤65 years undergoing percutaneous cryoablation for solitary, non-metastatic renal masses <7cm (cT1). We further limited our cohort to patients with an ASA score of 1 or 2, and in whom pre-operative eGFR was >60. Clincopathologic characteristics and recurrence patterns (local recurrence within the kidney versus metastatic disease) were evaluated. Results: Between March 2003 and December 2015, 705 patients underwent cryoablation, of whom 43 (6.1%) were deemed to be “healthy”. Median age of this cohort was 57 years (IQR 52−62), with pre-ablation eGFR of 75.6 (IQR 69.0-86.3). Seven patients (16.3%) had a prior partial nephrectomy, and 5 (11.6%) had a solitary kidney. The majority (40, 93.0%) of ablated masses were cT1a, with 3 (7.0%) being cT1b. Median tumor size was 2.0 cm. 27 masses (63.7%) were biopsy-proven renal cell carcinoma (RCC) and 6 (13.6%) were benign; histology was unknown in 10 (22.7%). Follow-up imaging was available for 37 patients. Median radiological follow-up was 22 months (IQR 9-42), during which time 2 patients developed metastatic disease and 1 developed local recurrence; all events were in patients with biopsy-proven RCC. No patients died from RCC during this time period. Conclusions: In this single institution cohort of “healthier” patients with cT1 solitary renal masses, cryoablation offered reasonable short term oncologic control. While longer follow-up data are needed to evaluate for durability, cryoablation in healthy patients, particularly those with challenging surgical anatomy, warrants further study.
Expression of tyrosine kinase AXL receptor in patients with metastatic renal cell carcinoma treated with sunitinib and its association with clinical and pathological outcomes.
Authors: Zucca Luis Eduardo Rosa , Carcano Flavio Mavignier , Scapulatempo Cristovam , Oliveira Renato , Morini Mariana Andozia , Ribeiro Guilherme , Viana Cristiano Ribeiro , Reis Rui Manuel 
Published: March 2017

439 Background: Renal cell carcinoma (RCC) represents 2 to 3% of all cancers of the Western countries. Currently, sunitinib, an anti-receptor tyrosine kinase (RTK), particularly of PDGFR and VEGFR, is the first-line therapy for metastatic RCC (mRCC), with significant improvement in clinical outcome. However, there is a lack of predictive biomarkers of sunitinib response. Recently, we and others have suggested that the RTK AXL may modify the response to sunitinib. Objective: To study the expression of AXL in a series of mRCC patients treated with sunitinib and to correlate it with patient’s clinico-pathological features and therapeutic response. Methods: Sixty four mRCC patients (51 clear cell carcinomas and 13 non-clear cell carcinomas) were evaluated and AXL expression was assessed by immunohistochemistry in TMAs. Results: AXL positivity was observed in 47% of cases. The multivariate survival analysis showed that AXL expression was a poor prognostic factor in patients with mRCC (HR 2.007, 1.006 - 4.006, p=0.048). In addition to the positivity for AXL, other prognostic factors were absence of nephrectomy, more than one site of metastasis, and bone metastasis. Considering only the clear cell subtype, the univariate analysis showed that AXL expression was statistically associated with a poor prognosis, with a median overall survival of 13 months vs. 43 months in patients with negative AXL. In this subtype, along with the AXL positivity, other prognostic factors were absence of nephrectomy, KPS, more than one site of metastasis, and liver metastasis. Moreover, AXL expression was associated with shorter progression to sunitinib. Conclusions: AXL expression was correlated with worse clinical outcome and may be an important prognostic biomarker in sunitinib-treated metastatic renal cell carcinoma patients.
Combined abiraterone, salvage prostate bed radiotherapy and LH-RH agonists (CARLHA) in biochemically-relapsing prostate cancer patients following prostatectomy: A phase I study of the GETUG/GEP.
Authors: Supiot Stephane , Campion Loic , Pommier Pascal , Dore Melanie , Racadot Severine , Rio Emmanuel , Milano Gerard A. , Mahier - Ait Oukhatar Celine , Carrie Christian 
Published: March 2017

45 Background: Salvage radiotherapy (RT) plus 6 months LH-RH therapy (ADT) improves biochemical relapse free survival in men with rising PSA following prostatectomy. Abiraterone acetate (Aa) increases overall survival in metastatic prostate cancer. We aimed to establish the toxicity of adding Aa combined with salvage RT and 6 months goserilin (Gos). Methods: We enrolled pT2-pT4a pN0 prostate cancer patients (pts) with rising PSA (0.2 to <2.0 μg/l) following radical prostatectomy. The primary endpoint was to determine the Maximum Tolerated Dose and recommended dose of Aa during RT plus Gos, two dose levels tested : 1 (750mg) and 2 (1000 mg). Two different schemes were explored: Sheme A: Aa (1000 mg) and predisone (10 mg) were given orally during 1 month to salvage IMRT (66 Gy in 33 fractions). The first day of irradiation, Aa is reduced to level 1 or 2 and 10.8 mg Gos is injected (sc). In sheme B, Gos is injected the first day (1 month before starting RT). Results: We recruited 9 + 9 pts in scheme A and B respectively. In scheme A, Testosterone (Tst) levels declined to castration level (<0.5ng/ml) after 10 days . Two/9 pts did not achieve castration levels at 30 days. Median LH levels increased to 10.4 (D10) and 12.5 IU/l (D20). At dose level 1, 4/9 pts (44%) experienced grade 3 hepatitis, occurring prior to RT or during RT (8 Gy, 36 and 54 Gy). We hypothesized that this unexpected liver toxicity was related to the LH increase during the first month (Aa administration without Gos). Therefore, we modified LH-RH administration (scheme B) and recruited 9 more pts. Tst levels dropped to undetectable at day 6, while median LH levels decreased to 6.1 (D10) and 1.7 IU/l (D20). At dose level 1 (3 + 3 pts), no grade 3 liver toxicity was reported. No other grade 3 toxicity was recorded. At dose level 2, 2/3 pts had grade 3 hepatitis occurring during RT. CYP17 polymorphism did not correlate with liver toxicity. Conclusions: The recommended dose of Aa combined to short-term androgen deprivation and salvage RT is 750 mg. Aa alone did lead to castration levels in 22% of pts.An unexpected high frequency of grade 3 liver toxicity was observed. Clinical trial information: NCT01780220.
Neutrophil lymphocyte ratio (NLR) as a clinical biomarker predictive of outcomes with immune checkpoint inhibitor therapy in genitourinary cancers.
Authors: Jeyakumar Ghayathri , Bumma Naresh , Kim SeongHo , Landry Craig , Kim Heejin , Silski Cynthia , Suisham Stacey , Dickow Brenda , Heath Elisabeth I. , Fontana Joseph A. , Vaishampayan Ulka N. 
Published: March 2017

453 Background: Immune checkpoint inhibitors (ICI) have been approved in genitourinary cancers (GU) such as renal cell carcinoma (RCC) and urothelial carcinoma (UC). There is an unmet need to determine factors predictive of response, to guide therapeutic selection in these cancers. We evaluated NLR as a predictor of response, progression free survival (PFS), and overall survival (OS) in patients treated with ICI. Other known prognostic clinical factors assessed were age, race, and smoking status and for RCC the prognostic score per MSKCC (Memorial Sloan Kettering) and Heng criteria. Methods: Regulatory approval was obtained. A retrospective chart review of RCC and URC patients at Karmanos Cancer Institute, treated with ICI based therapy was conducted. Data was collected on demographics, smoking status, prognostic scoring, NLR pretherapy, and post 4 doses of ICI. Correlation with clinical PFS and OS was conducted by univariable and multivariable analyses. Log-rank test was used to compare PFS and OS. Results: 57 pts were evaluated with median age 62 yrs (range, 24-85). 11 (19%) were African American (AA) and 31 (54%) were smokers. Pretherapy NLR<4 and ≥4 was seen in 38 (67%) and 19 (33%) pts respectively. 13 (31%) RCC pts were treated with > 1 VEGF therapy and 24(57%) pt were treated for > 6 mths and 14/15 UC pts were pretreated. RCC pts treated with > 6 mths and > 12 mths of VEGF therapy had a shorter PFS (HR =2.31, p= 0.028; HR = 2.075, p= 0.051 respectively). AA had shorter PFS and OS with ICI in RCC but not in UC (HR=3.72, p=0.001; HR= 40.8; p=0.001; HR=0.49, p=0.5; HR=0.85, p=0.88, respectively). Conclusions: Pretherapy NLR ≥4 was a statistically significant predictor of shorter PFS and OS with ICI therapy in RCC. NLR is an easily applicable clinical predictive factor that can help guide therapy, after validation of these findings in a larger population dataset. [Table: see text]
Sunitinib dose escalation after disease progression in metastatic renal cell carcinoma.
Authors: Raphael Jacques , Thawer Alia , Bjarnason Georg A. 
Published: March 2017

458 Background: Previous pharmacologic studies demonstrated that higher sunitinib ( S) exposure is associated with improved clinical outcomes in metastatic renal cell carcinoma (mRCC) patients. We aimed to assess the efficacy and toxicity of S dose escalation in mRCC patients progressing on the standard 50mg dose. Methods: A single institution retrospective review was conducted on mRCC patients, treated outside trials with a 50 mg S dose given on an individualized schedule between October 2009 and January 2016, who subsequently progressed on imaging. At progression, patients were dose escalated to 62.5 and 75mg on an individualized schedule if toxicity permitted. Median Progression and Overall Survival (PFS, OS) were analyzed using the Kaplan Meier method. PFS1 and 2 were defined as the time between the start of sunitinib and first progression and the time between dose escalation and second progression respectively. Results: Twenty-five eligible patients were identified, with a median follow-up of 40.3 months (11.1-66.6) and a mean age of 54 years (12.4). The majority of patients underwent cytoreductive surgery (92%) and were men (88%). Thirty two percent, 44%, and 24% had a good, intermediate, and poor prognostic Heng score respectively. At the 50 mg doses, 60% and 16% of patients had a partial response (PR) and stable disease (SD) respectively with a median time to progression (TTP) of 11.4 months (95% CI, 3-20.7). After progression, 36% and 28% had PR and SD on higher doses of S respectively with a TTP of 7.8 months (95% CI, 6.3-12.4). Three patients with progressive disease as best response on a 50 mg S dose achieved SD (2/3) or PR (1/3) after dose escalation. The median PFS1, PFS2, and OS were 6.1 months (95% CI, 2.3-19.4), 6.7 months (95% CI, 3.1-8.4), and 63.7 months (95% CI, 26-not reached) respectively. The most common adverse events after dose escalation were fatigue (56%), diarrhea (40%), and skin toxicity (28%). Conclusions: Patients with mRCC who progress on a 50 mg S dose, may derive a clinical benefit and prolonged survival from dose escalation with acceptable toxicity profiles. These results need to be confirmed in well-designed prospective studies with the aim to optimize the duration of benefit from S therapy.
Eligibility criteria and endpoints in metastatic renal cell carcinoma trials.
Authors: Wong Sarah , Quinn David I. , Bjarnason Georg A. , North Scott A. , Sridhar Srikala S. 
Published: March 2017

465 Background: Treatments for metastatic renal cell carcinoma (mRCC) are often compared across trials, but trial eligibility criteria and endpoints differ. In Sept 2015, DATECAN published recommendations for time-to-event endpoints in mRCC trials. The success of their efforts to harmonize endpoints has not yet been assessed. Methods: We assessed eligibility criteria and endpoints from 18 Phase III mRCC trials starting from 2003 onwards. We also assessed 4 Phase III trials submitted after Sept. 2015 for compliance with DATECAN recommendations. Results: Among the 18 trials, consistent criteria were: absolute neutrophil count ≥1,500/µL, platelet count ≥100,000/µL, and bilirubin ≤1.5xULN. However, the following differed in requirements and measures used: see table.The 4 newer trials did not entirely follow DATECAN’s recommendations. Although their primary endpoint is progression free survival (PFS) as recommended, 3/4 trials do not define PFS, and the one that does includes death from any cause instead of DATECAN’s “death from kidney cancer.” Conclusions: Key eligibility criteria were somewhat inconsistent across phase III mRCC trials, and newer trials’ endpoints did not align with DATECAN’s recommendations. Not only is greater standardization needed to facilitate meta-analyses and cross-trial comparisons, but as evident from lack of adherence to DATECAN’s recommendations, greater promotion and enforcement of recommendations is needed to harmonize trial design and improve comparability.[Table: see text]
The SUNPAZ study: Results of an open label, single arm trial to evaluate patients with mRCC treated with everolimus after failure of first line therapy with sunitinib or pazopanib.
Authors: Schostak Martin , Nusch Arnd , de Geeter Patrick , Decker Thomas , Resch Anna , Weiss Claudia , Schmitz Stephan H. 
Published: March 2017

473 Background: The VEGFR-TKIs Sunitinib and Pazopanib are the currently recommended 1st line agents for the treatment of renal cell carcinoma (RCC). Everolimus is a well-established treatment option after failure of a prior VEGFR-TKI. However, few prospective clinical data exist on the efficacy and safety of Everolimus after failure of a single line of VEGFR-TKI therapy and no clinical data exists on the efficacy and safety of Everolimus following Pazopanib treatment. Methods: This phase IV clinical trial investigated Everolimus 10 mg daily in patients who have progressed on or after 1st line treatment with Sunitinib or Pazopanib. Adult patients with advanced clear cell RCC and an ECOG 0-1 were included. The primary endpoint was the rate of patients progression-free after 6 months of treatment. Results: 16 and 13 patients who received prior Sunitinib and Pazopanib, respectively, have been enrolled at 13 German sites. The median age was 65 years in the Sunitinib (SUN) group and 74 years in the Pazopanib (PAZ) group. After 6 months of Everolimus treatment, 11/12 (92%) patients in the SUN group showed disease progression, whereas 6/13 (46%) patients in the PAZ group remained progression-free (FAS population). The median OS was 14.8 months in the SUN group (95% CI 9.4 – not reached (NR)) and 20.4 months in the PAZ group (95% CI 11.7 – NR). The most common adverse events (AE) regardless of any relation to study drug included anemia (31.1% (SUN group) vs. 53.8% (PAZ group)), nausea (25.0 vs. 46.2%), stomatitis (12.5 vs. 61.5%), peripheral edema (12.5 vs. 53.8%), and dyspnea (12.5 vs. 46.2%). Conclusions: Patients in the PAZ group showed a lower rate of tumor progression within 6 months and a longer PFS as compared to the SUN group. The results confirm Everolimus as an effective 2nd line treatment option with a favorable safety profile, especially following Pazopanib, and the sequence Pazopanib - Everolimus as effective treatment option for mRCC patients. However, due to the small number of patients enrolled in the study, results have to be interpreted with caution. The types of observed AE are consistent with the well-known toxicity profile of Everolimus. Clinical trial information: NCT01514448.
Long term overall survival (OS) in patients with primary metastatic kidney cancer: An analysis of 1468 patients from the Austrian National Cancer Registry (ANCR).
Authors: Marszalek Martin , Karim-Kos Henrike E , Madersbacher Stephan , Rauchenwald Michael , Hackl Monika 
Published: March 2017

489 Background: The introduction of thyrosinkinase inhibitors (TKI) changed the treatment of metastatic kidney cancer fundamentally. To elaborate the potential impact of TKI therapies, we studied trends in OS for patients with primary metastatic kidney cancer between 1998 and 2014 in Austria. Methods: All patients with primary metastatic kidney cancer aged ≥18 years, diagnosed from 1998-2009 were derived from the ANCR (n=2134). Patients diagnosed from 2004-2006 (n=316) were excluded (transition period of systemic therapies). To evaluate differences in OS between patients treated in preTKI-era and TKI-era, two periods were defined: 1998-2003 (before the introduction of Sunitinib in Austria, P1; n=926) and 2006-2009 (P2; n=542). Follow-up was complete until December 31st, 2014. OS rates were estimated by using the Kaplan-Meier method. The Cox proportional hazard model was used to calculate hazard ratios (HR). Results: A total 1468 patients was included in the analysis. The median age of the study population was 70 yrs (sd ±12) and did not differ between the two eras. The incidence of T1 tumors increased from 6.6% in P1 to 10% in P2 while T4 tumors decreased from 15% to 6.5% (p<0.001). Surgery rate remained stable at 48% (p=0.14). Five-year OS for patients undergoing surgery slightly increased from 16% in P1 to 20% in P2, although not significant (p=0.11). For patients without surgery 5-year OS improved from 4.3% in P1 to 7.9% in P2 (p=0.02). Apart from surgery, survival gain was observed for younger patients (<75 yrs) of 4% (p=0.04) and for T3/T4 tumors of 7% (p=0.008). The risk of death (HR) for patients treated in the TKI-era was reduced compared to the preTKI-era (HR 0.83, 95% CI 0.74-0.93) adjusted for sex, age, T-stage, and surgery. Survival advantage for patients undergoing surgery remained significant (HR: 0.50, 95% CI 0.45-0.57) after adjustment for TKI-era, sex, age, and T-stage. Conclusions: Patients with primary metastatic kidney cancer treated in the TKI era show improved OS compared to the cytokine era. Most benefit was observed in non-surgical patients, younger patients, and for T3/T4 disease. Surgery remains as an important therapy for additional survival benefit.