bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-dose chemotherapy (HDCT) as second salvage treatment in patients with multiple relapsed or refractory germ cell tumors
Authors: Beyer J. , Hackenthal M. , Lorch A. , Neubauer A. , Dieing A. , Rick O. , Hartmann J. T. , Bokemeyer C. 
Published: August 2020

5082 Background: To determine the activity of high-dose chemotherapy (HDCT) as intensification of second salvage treatment (SST) in patients with multiple relapsed germ-cell tumors (GCT). Methods: Databases in Berlin and Marburg (Germany) on patients treated with HDCT between 1989 and 2008 for germ-cell tumors were screened. Among 534 patients overall, 71/534 (13%) patients were identified as scheduled for HDCT having failed at least one previous conventional-dose first-line and first-salvage chemotherapy regimen. Forty-nine patients who had received at least cisplatin- and etoposide as first-line as well as conventional-dose cisplatin as first-salvage treatment and were diagnosed after January 1, 1990, were further analyzed. Results: Median age at SST was 32 years (range 19 to 52 years). Median follow-up for surviving patients was 4 years (range 1,7 to 8,5 years). Histology was pure seminoma in 5/49 (10%) patients and non-seminoma or mixed histologies in 44/49 (90%). The median number of cisplatin-based treatment cycles prior to SST was 7 (range 5 to 11 cycles). Three of forty-nine (6%) patients either progressed or died prior to scheduled HDCT, the remaining 46/49 (94%) received either single or sequential HDCT. The rate of favorable responses to HDCT as intensification of SST was 27/49 (55%). Ten patients are alive without progression. One additional patient is lost-to-follow at four years without progression. The projected overall survival rate at five years after initiation of SST was 17%. Conclusions: HDCT can induce long term remissions even in patients with multiple relapsed GCT. No significant financial relationships to disclose.
Preliminary evaluation of chemotherapy plus residual tumor excision for testis conservation to provide justification for a randomized trial versus orchidectomy to reduce metabolic syndrome in patients with germ cell cancer
Authors: Oliver R. , Shamash J. , Nargund V. 
Published: August 2020

5087 Background: There is evidence that early andropause due to testicular atrophy may be playing a role in the increased metabolic syndrome and cardiac deaths seen with follow up of GCC patients even those on surveillance. In a randomized trial of 1,477 stage I seminomas a single course of carboplatin produced a 78% reduction of contra lateral testicular GC. This, has increased awareness of the effectiveness of chemotherapy on primary tumours This abstract updates our experience.assessing chemo-response of primary GCC in past 30 years. Methods: Testicular GCC patients receiving chemotherapy with primary tumour in situ during 1978–2001 have been reviewed. 62 had advanced disease and 20 had stage I. Results: In 30/82 (37%) the testis normalised and was retained. Median follow-up is 132 months. 7 of these patients developed second GCC. Actuarial 5, 10, and 15 year relapse free survival was 81% and 76%. All relapses are new tumours without evidence of metastasis and are disease free after orchidectomy alone (15, 17, 35, 45, 48, 72, and 156 months). 22 additional patients (28%) who underwent orchidectomy for apparent treatment failure had necrotic tissue/mature teratoma involving less than 50% of the testis and could have been candidates for tumour enucleation. Patients with stage 1 tumours and seminoma histology showed significantly higher preservation rate that approached 100% if one included those showing necrosis or mature teratoma involving less than 50% of the testis. There have been 6 pregnancies to date in wives of 3 patients. 5 of 6 patients studied in detail have recovered sperm, the highest count (100x106) being the only patient who was successfully treated for bilateral testis tumours. Conclusions: This preliminary study suggests that up to 50% of all cases and 90% of stage I seminoma cases with tumours small enough for tumour enucleation for incomplete responders could have successful testis preservation after chemotherapy safely up to 10 years though in the future a randomized patient preference driven trial is needed to establish its acceptability, safety and value in reducing androgen deficiency. No significant financial relationships to disclose.
Histopathology in surgically treated renal cell carcinoma: Is there a survival difference when stratified by stage?
Authors: Keegan K. A. , Hellenthal N. J. , Chamie K. , Koppie T. M. 
Published: August 2020

5089 Background: The impact of renal cell carcinoma histopathology (RCC) on survival has been conflicting and limited to retrospective institutional studies. Therefore, we sought to determine the role of RCC histopathology on stage-specific survival rates in a population-based cohort. Methods: We utilized the National Cancer Institute's Surveillance, Epidemiology, and End Results database and identified 21,258 patients who underwent partial or radical nephrectomy for RCC between 1996 and 2004. Patients were stratified based on histopathologic diagnosis (clear cell, papillary, chromophobe, sarcomatoid, and collecting duct) and pathologic stage. We performed Cox-proportional hazard modeling and Kaplan-Meier survival analyses to determine overall- and cancer-specific survival. Results: Using univariate analysis, histopathology significantly impacted overall- and cancer-specific survival (p< 0.001). Specifically, patients with papillary and chromophobe variants had lower stage disease at the time of surgery and had improved survival compared to clear cell subtypes, (HR: 0.50; 95% CI, 0.42–0.60 and HR: 0.31; 95% CI, 0.22–0.44, respectively). When controlled for stage, improved outcomes for chromophobe and papillary histologies persisted, although it did not achieve statistical significance at all stages. On the other hand, patients with sarcomatoid disease were more likely to present with high stage disease and invariably had worse survival compared to clear cell carcinoma (HR: 8.74; 95%, CI 7.70–9.91). When controlled for stage, this difference achieved statistical significance across all stages (p< 0.001). Conclusions: Histopathologic subtype in patients with RCC does predict overall- and cancer-specific survival. Patients with sarcomatoid RCC, even those presenting with low-stage disease, have poor survival. These findings may give further value to recent data suggesting the increased utility of percutaneous renal biopsy and its potential impact on management. [Table: see text] No significant financial relationships to disclose.
Use of chromosome 9p status to identify a subset of high-risk localized renal cell carcinoma
Authors: LaRochelle J. C. , Dastane A. , Rao N. , Klatte T. , Shuch B. , Kabbinavar F. , Said J. , Belldegrun A. , Pantuck A. 
Published: August 2020

5090 Background: We investigated whether deletion of chromosome 9p in clear cell renal cell carcinoma (ccRCC) predicts worse disease-specific (DSS) and recurrence-free survival (RFS), and if it is associated with worse prognosis in tumors < 4 cm. Methods: 316 patients undergoing nephrectomy prior to 2001 were included on a tissue microarray in whom FISH analysis using the LSI p16/CEP 9 Dual Color Probe was performed to assess chromosome 9p deletion status. An additional 389 patients undergoing nephrectomy after 2001 had 9p status determined by standard cytogenetics. Tumor grade, stage, size, 9p status, nodal involvement, and the presence of metastasis were recorded. Disease-specific and recurrence-free survival were determined, and independence was assessed using Cox proportional hazards models. Results: 9p deletions were detected in 14% of tumors. 54% of 9p-deleted tumors were high grade (G3–4) vs. 38% without 9p deletions, and 60% of 9p-deleted tumors were T3–4 vs 38% without 9p deletions (p < 0.01). 55% of those with 9p deletions had positive nodes or metastases vs. 34% of those without 9p deletions (p < 0.01). Median DSS for those with and without 9p deletions was 80 months and 37 months, respectively (p < 0.01). In localized disease, median RFS for those with 9p deletions was 53 months and was not reached in those without 9p deletions (p<0.01). In 188 patients presenting with localized RCC < 4 cm, loss of 9p occurred in 3/7 (42.9%) of patients with post-nephrectomy recurrence vs. 13/168 (7.2%) of patients without disease recurrence (p = 0.001). DSS for patients with 9p deletion in tumors < 4 cm was significantly worse than DSS in those without 9p deletions (HR 6.18; p = 0.02), and an independent effect on RFS was seen for 9p deletions in localized RCC (HR 2.3, p < 0.01). 9p status was not a significant predictor in metastatic RCC. Conclusions: Deletion of chromosome 9p in ccRCC occurs in 14% of patients and is associated with higher grade and T stage, presence of nodal and distant disease, worse prognosis, and in patients with small NOMO tumors, 9p deletions but not tumor size was independently associated with RFS. Identifying high risk patients with 9p deletions will allow better risk stratification for surveillance protocols and for adjuvant trials. No significant financial relationships to disclose.
A nomogram predicting disease-specific survival after nephrectomy for papillary renal cell carcinoma
Authors: Klatte T. , Remzi M. , Said J. W. , Haitel A. , Kabbinavar F. F. , Waldert M. , de Martino M. , Marberger M. , Belldegrun A. S. , Pantuck A. J. 
Published: August 2020

5091 Background: Whereas multiple nomograms have been developed to assess outcomes of patients with clear cell renal cell carcinoma, a model to assess prognosis of papillary renal cell carcinoma (PRCC) has not yet been developed. After data collection and slide review of a large cohort of patients, the aim of this study was to develop and to internally validate a nomogram for prediction of disease-specific survival for PRCC. Methods: Out of 2,687 patients who underwent surgery for a renal tumor between 1989 and 2008 at two institutions, 258 (10%) were found to have PRCC. H&E slides were reviewed by one uro-pathologist at each institution for papillary sub-type, tumor grade, microvascular invasion, sarcomatoid features, collecting system invasion and presence and extent of tumor necrosis. A nomogram was constructed as a graphical representation of significant variables of disease-specific survival in multivariate Cox proportional hazards regression analysis. The discrimination and calibration of the nomogram were assessed, both utilizing bootstrapping to obtain relatively unbiased estimates. Results: After a median follow-up of 35 months, 49 PRCC-related deaths (19%) had occurred. In univariate analysis, incidental detection, T, N, M stage, grade, microvascular invasion, collecting system invasion, papillary sub-type, sarcomatoid features, and necrosis were all associated with prognosis. Multivariate Cox proportional hazards analysis, however, identified incidental detection, T stage, M stage, microvascular invasion, and necrosis, but not papillary sub-type as independent prognostic factors of disease-specific survival. These variables formed the basis of the nomogram that predicted 5-year disease-specific survival probability. The nomogram predicted well, with a bootstrapped corrected concordance index of 0.93, and showed good calibration. Conclusions: A highly accurate tool utilizing basic clinical and pathological information for predicting disease-specific survival was developed specifically for PRCC. This tool should be helpful for identification of the subset of PRCC patients with aggressive clinical behavior, and may contribute to the ability to individualize postoperative surveillance and therapy. No significant financial relationships to disclose.
Association of percentage of tumor burden removed with debulking nephrectomy and progression-free survival (PFS) in metastatic renal cell carcinoma (mRCC) patients (Pts) treated with VEGF-targeted therapy
Authors: Barbastefano J. , Garcia J. A. , Elson P. , Wood L. S. , Lane B. S. , Dreicer R. , Campbell S. , Rini B. I. 
Published: August 2020

5095 Background: Debulking nephrectomy is a standard of care in mRCC, although data in patients subsequently treated with targeted therapy is lacking. The objective of this study was to determine if fractional percentage of tumor volume (FPTV) removed with debulking nephrectomy is associated with PFS on subsequent VEGF-targeted therapy. Methods: The Cleveland Clinic Urologic Oncology database from 2005–2008 was retrospectively reviewed to identify mRCC patients who had undergone debulking nephrectomy followed by VEGF-targeted therapy, defined as treatment with sunitinib, sorafenib, bevacizumab or sunitinib + bevacizumab. FPTV was determined by the diameter of the primary tumor divided by the total tumor burden (per RECIST criteria) by investigator re-review of imaging studies. PFS was defined from the start date of systemic therapy to disease progression per RECIST criteria. Results: Seventy-five Pts were identified; 76% male, median age 60 years (range, 34–84), 95% clear cell histology and 69% ECOG PS 0. Pts received treatment with bevacizumab (28 pts), sunitinib (23), sorafenib (20), or sunitinib + bevacizumab (4). Lung (76%) and lymph node (48%) were the predominant sites of metastasis. The median diameter of the primary tumor was 9.3 cm (range, 3.3–21 cm). The median FPTV removed was 95% (range, 80–99%). The median PFS was 12 months. In univariable analysis, the FPTV removed was associated with prolonged PFS (p < 0.001), as were low nuclear grade (p = 0.009), longer interval from diagnosis to treatment (p = 0.05), normal hemoglobin (p = 0.02), number of metastatic sites (p = 0.05), and lack of lung (p = 0.05) and brain (p = 0.05) metastasis. In multivariable analysis, the FPTV removed, as well as the interval from diagnosis to treatment (p = 0.03), were found to be independent predictors of PFS (< 0.001). Conclusions: Improved PFS on targeted systemic therapy is significantly associated with a greater percentage of tumor burden removed at debulking nephrectomy. No significant financial relationships to disclose.
Dosing patterns in patients with renal cell carcinoma treated with sorafenib or sunitinib: A retrospective claims database analysis
Authors: Keefe S. , Moyneur E. , Barghout V. , Flaherty K. T. 
Published: August 2020

5097 Background: Tyrosine kinase inhibitors (TKIs; sorafenib [SR], sunitinib [SU]) are FDA approved for the treatment of advanced renal cell carcinoma (RCC). Dose reduction may be needed for management of treatment-related adverse events. We analyzed the dose reduction patterns in pts with RCC treated with SR, approved Dec 05, or SU, approved Jan 06. Methods: A retrospective analysis was conducted using data from a US claims-based database (MarketScan MedStat) covering ≥18 million lives for 2002–2008 in all US census regions. Inclusion criteria were ≥2 claims for RCC (ICD9 189.0 or 198.0), continuous healthcare coverage, >180 days of coverage before RCC diagnosis, no claim for SR or SU prior to RCC diagnosis, initial standard daily RCC dose per package insert recommendation (800 mg for SR or 50 mg for SU), and ≥2 consecutive dispensings. Initial episode was defined as the time from the date of the first drug dispensing (index date) to the first switch to another TKI, end of healthcare coverage, end of treatment, or March 31, 2008. Pt and pt-time level analyses for dose reductions between treatments were conducted. Results: SR- (n = 189) and SU-treated (n = 304) pts met the inclusion criteria. No significant differences in baseline demographics existed between the groups except for a higher incidence of stroke (7.9% vs 3.6%, p = 0.037) and other cancer site (93.7% vs 87.8%, p = 0.036) in the SR group. Significantly more pts who received SU (23%) required dose reductions during the first 3 months of therapy and for all initial episodes than did pts who received (4.2%) SR (p < 0.001 for both). For all episodes, the mean time to dose reduction was 104 days for SU versus 162 days with SR (p = 0.0028). The majority (65%) of dose reductions with SU occurred within the first 3 months, whereas dose reduction with SR was 25% during this time (p < 0.001). After controlling for different lengths of exposure time, 2 to 6 times more dose reductions were observed in pts who received SU than with SR (p < 0.001). Conclusions: This US retrospective claims analysis showed more dose reductions, including number of patients and total number of days, in pts who initially received sunitinib compared with those who received sorafenib. [Table: see text]
Final 10-year analysis of prospective multicenter Chemo N0 trial for validation of ASCO-recommended biomarkers uPA/PAI-1 for therapy decision making in node-negative breast cancer
Authors: Harbeck N. , Schmitt M. , Meisner C. , Friedel C. , Untch M. , Schmidt M. , Lisboa B. , Sweep C. , Jänicke F. , Thomssen C. 
Published: August 2020

511 Background: Based on interim results of the prospective, randomized, multicenter Chemo N0 trial and an EORTC pooled analysis (n = 8,377), ASCO and AGO guidelines recommend invasion markers uPA/PAI-1 for risk assessment in N0 breast cancer. Methods: We present final analysis of the Chemo N0 trial (recruitment 1993–1998; n = 647; 12 centers) with 113 (5–167) months median follow-up. Patients (pts) with low tumor levels of uPA and PAI-1 (n = 283) were observed. Of 364 patients with high uPA and/or PAI-1, 242 were randomized to CMF chemotherapy (n = 117) vs. observation (n =125); 122 pts decided for or against CMF on their own. External quality assurance provided good ELISA standardization in 5 participating laboratories. Results: The actuarial 10-year recurrence rate (without any adjuvant systemic therapy) for high uPA/PAI-1 pts in the combined (randomized and not randomized) observation group was 23.0%, in contrast to only 12.9% in those with low uPA/PAI-1 (p = 0.011, log rank). High-risk pts randomized for CMF had a 26.0% lower estimated probability of disease recurrence than high-risk pts randomized for observation (intention-to-treat analysis: HR 0.74 (0.44–1.27); p = 0.28, log rank). In per-protocol analysis, the treatment benefit was significant: HR 0.48 (0.25–0.88), p = 0.019, adjusted for tumor stage and grading in Cox regression for DFS; for OS, HR was 0.64 (0.35–1.19); p = 0.162, adjusted for tumor stage and grading in Cox regression. Conclusions: Chemo N0 is the first prospective biomarker-based therapy trial in early breast cancer defining a patient group achieving good long-term DFS without any adjuvant therapy. This trial demonstrates that, using a standardized uPA/PAI-1 ELISA, about half of N0 pts, classified as low-risk, could be spared chemotherapy, while high-risk pts benefit from adjuvant chemotherapy. These 10-year results validate the long-term prognostic and predictive impact of uPA/PAI-1 at highest level of evidence (LOE I) and support their guideline-based routine use for risk-adapted individualized therapy decisions in N0 breast cancer. The ongoing NNBC-3 trial is evaluating optimal chemotherapy for uPA/PAI-1 high-risk patients. [Table: see text]
A phase I study of temsirolimus (TEM) and bryostatin (BRYO) in patients with metastatic renal cell carcinoma (RCC)
Authors: Plimack E. R. , Wong Y. , Von Mehren M. , Malizzia L. , Roethke S. K. , Li T. , Litwin S. , Hudes G. R. , Haas N. B. 
Published: August 2020

5111 Background: TEM, an inhibitor of mTOR complex 1 (TORC1), is approved for the treatment of metastatic RCC. BRYO inhibits protein kinase C, a downstream effector of mTOR complex 2 (TORC2). We observed additive effects of TEM and BRYO against RCC in vitro. Methods: Four cohorts of 3–6 patients (pts) received weekly BRYO (20 mcgm/m2) and TEM (10, 15, 25, or 37.5 mg,) in 28 day cycles. DLT was defined as 1st cycle toxicity ≥ grade 3. Results: Twenty-three pts have been enrolled. Eighteen pts had RCC: clear cell (12), papillary (3), clear cell with sarcomatoid/spindle features (2), unclassified (1), Among RCC pts, 3 had no prior therapy. 15 had a median of 2 prior therapies (immunotherapy, TKIs, and/or bevacizumab). To date, 22 pts have received 103 cycles across 4 dose levels. Five non-RCC pts (4 sarcoma, 1 paraganglioma) received up to 3 cycles of treatment. Two of these pts (both had prior cytotoxic therapy) experienced DLT at 15 mg (Gr 3 neutropenia and Gr 3 hypophosphatemia) Subsequently, pts with prior cytotoxic therapy were excluded. One additional non-RCC pt (prior radiation) experienced DLT (Gr 3 neutropenia) at TEM 37.5 mg. Among RCC pts, there were no 1st cycle DLT's. Significant toxicities during later cycles included Gr 3/4 thrombosis at TEM 37.5 mg (2), Gr 4 thrombus/Gr 4 LV dysfunction at TEM 15 mg (1), and Gr 3 dyspnea/Gr 3 pneumonitis at TEM 10mg (1). Gr 4 hypercholesterolemia (1) and Gr. 4 triglyceride elevation (1) were seen at TEM 37.5 mg, both reversed with treatment. One RCC pt withdrew prior to receiving treatment. Of the 17 remaining RCC pts, 3 had PRs and 9 had SD. One treatment naïve pt (TEM 15 mg) continues with PR for 2+ years after discontinuing treatment. One pt (had progressed on sunitinib) continues in a PR at 14+ months. Twelve pts received ≥4 cycles and 3 received >10 cycles. PR was seen in both clear cell and papillary histologies. Median PFS was 7.8 months for all pts and 5.7 months for previously treated pts. Two pts, both with PR, remain on treatment, having received 18 and 8 cycles. Conclusions: The TEM/Bryo combination is feasible for multiple cycles on a weekly schedule at full doses of each agent with durable PR and SD in RCC refractory to other therapies. Enrollment continues to further characterize safety and efficacy. [Table: see text]
Survival gains needed to justify the side effects of treatment for localized prostate cancer
Authors: King M. T. , Viney R. , Hossain I. , Smith D. , Savage E. , Stockler M. R. , Armstrong B. 
Published: August 2020

5119 Background: Men diagnosed with localized prostate cancer face difficult treatment decisions. Evidence about the relative survival benefit of treatment options is lacking or piecemeal. Side-effects can vary widely with treatment, affecting some fundamental aspects of quality of life (QOL). Little is known about patients’ views of the relative tolerability of these side-effects or the survival gains needed to justify them. Methods: QOL data were collected prospectively 3 years post-diagnosis in a population-based cohort of men treated for localized prostate cancer (n=1642); these data were used to identify common side-effect profiles. A patient preference survey was conducted in a subset (n=357, stratified by treatment); hypothetical treatment alternatives were described in terms of side-effects and survival. Random parameter logit models were estimated. We adapted the concept of compensating variation from welfare economics to derive a parameter function for the value of changes in QOL in terms of survival time; i.e., the survival gains needed to justify persistent side-effects. Bootstrap confidence intervals (CI) were constructed. Results: The table shows the survival gains needed for a range of common treatment profiles, relative to the base case of active surveillance (in which men typically experienced mild loss of libido and mild fatigue). For example, radical prostatectomy often resulted in severe impotence and mild urinary leakage; men required an extra 8.0 months (95% CI 7.4–8.7) of life to make this worthwhile. Generally, urinary dysfunction and bowel symptoms were considered the least tolerable, hormonal symptoms and fatigue came next, and sexual dysfunction was considered relatively benign. This pattern was relatively consistent across treatment groups. Conclusions: These results highlight the need for better evidence about the actual survival benefits of alternative treatments. They also help to target supportive care to optimize patient QOL after treatment for localized prostate cancer. [Table: see text] No significant financial relationships to disclose.