bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicative value of [18F]-FDG PET scan for pathological complete response to neoadjuvant chemotherapy in breast cancer
Authors: Favier L. , Berriolo-Riedinger A. , Coudert B. , Touzery C. , Riedinger J. , Toubeau M. , Arnould L. , Brunotte F. , Fumoleau P. 
Published: March 2020

505 Background: To evaluate, in breast cancer patients treated by neoadjuvant chemotherapy, the early predictive value of the FDG uptake decrease for the assessment of the pathological complete response (pCR). Methods: Forty seven women with non metastatic with conventional imaging, non inflammatory, large or locally advanced breast cancer were included. Pathological tumour regression determined on surgical resection specimens served as the gold standard for the assessment of the neoadjuvant chemotherapy response. According to the Sataloff classification, patients were classified in two groups: patients with a pathological complete response (pCR) and patients with a pathological non complete response (non pCR). FDG uptake of breast lesions was evaluated before and after the first course of neoadjuvant chemotherapy, using Standard Uptake Value maximum (SUV) corrected by body surface area and glycaemia. Relations between baseline [18F]-FDG uptake and clinical, histopathological and biological parameters were assessed by Mann-Whitney test. Predictive value of the FDG decrease for the assessment of the pCR was studied with logistic regression analysis. Results: An elevated baseline SUV was found independently associated with a high mitotic activity (p<0.002), tumour grading (p<0.004), high score of nuclear pleomorphism (p= 0.03) and positive hormonal receptor status (p<0.005). After completion of chemotherapy, 11 (23%) of the 47 breast tumours examined at surgery showed a pCR while 36 (77%) showed a non pCR. The relative decrease (ΔSUV) after the first course of neoadjuvant chemotherapy was significantly greater in the pCR group than in the non pCR group (p< 10-4). A SUV decrease of 85.4% ± 21.9% in pCR patients versus 22.6% ± 36.6% in non pCR patients was found. ΔSUV<-60% predicted pCR with an accuracy of 87%. With multivariate logistic regression analyses, ΔSUV<-60% was the only predictive factor of the pCR Conclusions: In breast cancer patients treated by neoadjuvant chemotherapy, the FDG uptake decrease, after only one course of treatment, is an early and powerful predictor of the pCR. No significant financial relationships to disclose.
Damage of bone metabolism and osteoporosis in testicular cancer patients
Authors: Mardiak J. , Ondrus D. , Spanikova B. , Ostatnikova B. 
Published: March 2020

5052 Background: Improved survival of testicular cancer (TC) patients leads to rising of interest on late toxicity. Treatment-related bone loss is well recognized in breast and prostate cancer, but there has been little information in long-term survivors from other tumors. The aim of the study was to assign the damage of bone metabolism in TC patients. Materials: Bone mineral density (BMD) was measured by dual energy photon x-ray absorptiometry in the lumbar spine and hips. BMD was classified as osteopenia (T score ranging from -1 to -2,5) and osteoporosis (T score less -2,5). C-terminal cross-linked telopeptides of type I collagen (CTX) were measured using ELISA. Additionally serum total testosterone was measured. Comparison was made with matched control data. Relationships between baseline characteristics (age, treatment type and time from orchiectomy) and BMD were assessed using univariate and multivariate analysis tools. Results: We included 257 patients in the study (17 - 72 yrs old, median: 36 yrs) who were treated for GCT since 1982. 29 (11%) of them had bilateral orchiectomy (OE) due to bilateral TC. 23% of pts were treated by OE alone, 17% by subsequent radiotherapy of para-aortic field and 59% by subsequent chemotherapy. Median time since the OE was 4 years (1–36 yrs). Pts after bilateral OE had significantly lower BMD comparing with pts with unilateral OE. We didn’t find any differences between TC pts and matched control data regarding incidence of osteopenia and CTX, but the incidence of osteoporosis was considerably higher in TC pts. The incidence of osteoporosis appeared to increase with age and slightly correlated with time since OE, particularly after 10 years after OE. Type of therapy did not prove to have significant impact on the appearance of osteoporosis. Serum testosterone level did not correlate with BMD. Conclusion: The long term survivors from GCP have significantly higher risk of osteoporosis than healthy matched population. No significant financial relationships to disclose.
Bone abnormalities in male germ-cell cancer survivors
Authors: Willemse P. M. , van Wulften L. , van Steijn A. Q. , Hamdy N. A. , Osanto S. 
Published: March 2020

5053 Background: Survival of men with testicular cancer is long due to successful therapeutic intervention, which usually includes orchidectomy. Therefore, we studied the prevalence of osteoporosis in a single center cohort of long term survivors of germ cell cancer. Methods: In a cross-sectional study design, we studied 186 male patients with a mean age of 39.6 years (range 18.1–66.8), who were treated between 1977 and 2006 for germ cell cancer. 181 (97.3%) patients underwent an unilateral, 3 (1.6%) a bilateral orchidectomy and in 2 (1.1%) patients no orchidectomy but retroperitoneal or mediastinal tumor biopsy was performed to confirm the diagnosis. 141 (75.8%) patients received cisplatin-based combination chemotherapy for metastases or primary extra-gonadal tumor at a mean age of 29.4 years (range 14.2- 62.6). Between 2003 and 2006, bone mineral density (BMD) was measured at the lumbar spine and femoral neck by DXA and Z-scores calculated. Vertebral deformities were evaluated by a semi-quantitative measurement on lateral x-rays of the spine. Non-vertebral fractures were evaluated by questionnaire and confirmed by x-ray. All patients had normal total testosterone, estradiol, parathyroid hormone, 25(OH)- vitamin D and 1,25(OH)2-vitamin D concentrations, evaluated by fasting blood samples. Results: BMD was low in 59 (31.7%) patients; 46 (24.7%) patients had Z-scores between -1 and -2 SD, while thirteen (7.0%) had Z-scores below -2 SD. Vertebral deformities were present in 57 of 151 (37.7 %) evaluated patients, sixteen of whom also had low BMD. There was no relationship between vertebral deformities and either age, chemotherapy or testosterone/estradiol levels. No correlation was found between vertebral deformities and low BMD. Eight of 114 (7.0%) patients who responded to the questionnaire had non-vertebral fractures at a mean age of 44.9 years (range 33.1–54.2); 1–17 years after the initial diagnosis of testicular cancer. Conclusions: More than one third of the eugonadal male survivors of germ cell cancer survivors have vertebral abnormalities which are not related to age, chemotherapy or genital hormone concentrations. The underlying mechanism remains unknown. This high prevalence of bone abnormalities indicates that screening should be advocated in all germ cell cancer survivors. No significant financial relationships to disclose.
Coordinated modulation of sonic hedgehog (Shh) signaling and androgen receptor (AR) in the prostate tumor microenvironment by chemo-hormonal therapy
Authors: Efstathiou E. , Troncoso P. , Wen S. , Do K. , Pettaway C. A. , Logothetis C. J. 
Published: March 2020

5066 Background: Shh and androgen signaling are implicated experimentally in prostate development, regeneration and neoplastic progression. We assessed expression of components of these pathways in pretreated and control high risk prostate cancers (PCa) in a hypothesis generating search for an association with resistance to therapy. Methods: Sixty-four men with high risk PCa were randomized to receive either complete androgen ablation (AA) or AA and ketoconazole, adriamycin, vinblastine and estramustine (KAVE) for 16 weeks followed by radical prostatectomy (RP). We constructed 3 tissue microarrays from RP specimens of: a) (AA) 26 men pretreated with AA, b) (CH) 27 men pretreated with AA + KAVE and c) (Control) 26 untreated men matched for clinical stage, biopsy Gleason Score and PSA. A total of 3,178 cores were obtained [median cores: 36 (range 18–90), median blocks: 5 (range 3–9) per specimen]. Immunohistochemical expression of Shh pathway components (Shh, patched, smoothened, gli2) and AR were assessed in the tumor epithelium and stroma and recorded as percentage of cells exhibiting staining. A mixed model was used for fitting the correlated data (multiple observations from a subject). Pearson’s correlations between biomarkers were calculated based on mean expression. Results: Shh signaling, as indicated by mean expression (standard deviation) of nuclear gli2, was observed in the residual tumor epithelium [AA: 79.9 (17.4), CH: 85.7 (12.2)] and adjacent stroma [ AA: 43 (18.2),CH: 53 (16.4)] following treatment, in parallel (0.78 by Pearson’s correlation), and higher than in untreated control tumor epithelium [39.9 (20.6)] and stroma [22.9 (15.2)] (P<.0001). Smoothened and Shh were expressed accordingly. AR expression was lower in the treated tumor epithelium [AA: 47.3 (20.8), CH: 46.8 (21.1)] (P<.0001), with a trend toward increased stromal AR [AA: 8.6 (10.4), CH: 10.5 (8.2)] compared to control tumor epithelium [60.1 (24.1)] and stroma [6.4 (11.7)]. Conclusions: Shh and androgen pathways are modulated in a manner that suggests they behave in a compensatory fashion, and are determinants of response to therapy. These data support the hypothesis that the tumor microenvironment is implicated in PCa therapy resistance. No significant financial relationships to disclose.
MRI of the breast before and after primary systemic therapy correlates with histopathological tumor size in patients with locally advanced breast cancer (LABC)
Authors: Russu V. , Lex B. , Popovich M. , Pfaffenberger K. , Volkholz H. , Tulusan A. 
Published: March 2020

507 Background: Primary systemic therapy (PST) is a widely accepted preoperative treatment for patients with locally advanced breast cancer (LABC). Different authors beside our study-group showed that MRI is a sensitive method in describing the remaining size of an invasive breast lesion after PST. The established methods for measuring the size of lesions and monitoring the tumour-response to chemotherapy are clinical palpation, mammography and ultrasound, but specificity of these methods is unsatisfactory. Our prospective data is to clarify the accuracy of MRI in monitoring the tumour-response to PST is presented. Methods: 207 female patients (range of age: 26a- 78a) with LABC (cT2 â€“ cT4) were examined with dynamic contrast enhanced MRI after PST. 173 (84%) patients have had MRI examination before and after PST. 145 (70%) patients had a ductal-invasive, 48 (23%) patients a lobular-invasive carcinoma. 70 (34%) patients were treated with sequential anthracyclin- and taxan-based chemotherapy and 137(66%) with only anthracyclin based chemotherapy. 51% patients were premenopausal. 70% had an ER-positive tumour. The measure of tumour-response to PST was graded in partial response (PR: >50% of tumour reduction mm2), no change (NC: <50%) and complete response (CR: no evidence of residual tumour-cells). Results: Comparing tumour-size measured by MRI before and after PST 119 (69 %) of the patients had PR and 25 (14.5%) CR. The histological tumour- size after PST strongly correlated with the size measured by MRI r = 0,758 (pâ€1 0.001). Analyzing the tumour-types ductal-invasive carcinomas were significant (p<0.001) better to monitor than lobular-invasive types (r=0.824/r=0.210). Conclusions: preoperative MRI seems to be a helpful tool in estimating the efficacy of the tumour-response to chemotherapy and for the operative planning in the patients with LABC after PST, especially for ductal-invasive tumours. No significant financial relationships to disclose.
Efficacy of neo-adjuvant gemcitabine plus cisplatin (GC) in muscle-invasive urothelial cancer (UC)
Authors: Dash A. , Pettus J. A. , Bochner B. H. , Dalbagni G. , Donat S. M. , Herr H. W. , Bajorin D. F. 
Published: March 2020

5077 Background: Neoadjuvant chemotherapy with methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) plus radical cystectomy (RC) improves survival over cystectomy alone in urothelial cancer (UC); survival is greatest for patients achieving either pT0 or = pT1 after chemotherapy. GC is less toxic and achieves a similar response and survival to MVAC in metastatic UC, but is untested as neoadjuvant therapy. This study compared GC-induced pathological response in the bladder to that seen with neoadjuvant MVAC in an historic control series (1983–88) at our center (JCO 12:1394, 1994). Methods: We retrospectively reviewed records from muscle-invasive UC patients who received neoadjuvant chemotherapy from 11/2000 to 5/2006; 43 received GC (planned 4 cycles) followed by RC. Post-chemotherapy pathologic response was compared to neoadjuvant MVAC pts (planned 4 cycles) but whose post-chemotherapy surgery varied by surgeon’s discretion. 34 of 111 MVAC patients underwent post-chemotherapy RC and an additional 21 patients underwent partial cystectomy (PC). Pathologic outcomes of the GC cohort were compared to MVAC patients that underwent either RC (n=34) or to either RC or PC (n=55). IRB approval was obtained. Results: Baseline characteristics and treatment results were similar for both groups. The median time from start of GC chemotherapy to RC was 141 days (IQ range 123–155). Start of MVAC to RC (n=34) was 95 days (IQ range 76–163) and to either RC or PC (n=55) was 119 days (IQ range 89–175). Achieving = pT1 was similar for GC (15/43; 35%, 95% CI 21–51%) and MVAC followed by RC (6/34; 18%, 95% CI 7–35) or MVAC followed by either RC or PC (20/55; 36%, 95% CI 24–50). Achieving pT0 for GC patients (11/43; 26%, 95% CI 14–41) was also similar to MVAC plus RC (5/34; 15%, 95% CI 5–31) and MVAC plus either RC or PC (15/55; 27%, 95% CI 16–41). Conclusions: Neoadjuvant GC is similar to MVAC in both pathologic response in the bladder and time to cystectomy. The efficacy and tolerance of neoadjuvant GC warrants further study to assess overall survival. No significant financial relationships to disclose.
Combination chemotherapy with gemcitabine, oxaliplatin and paclitaxel in patients with cisplatin-refractory or relapsed germ cell tumors (gct)
Authors: Oechsle K. , Bokemeyer C. , Honecker F. , Mayer F. , Waller C. F. , Boehlke I. , Hartmann J. T. , Kollmannsberger C. 
Published: March 2020

5084 Background: Treatment of pts with cisplatin-refractory GCT remains a therapeutic challenge. The present phase II study investigates the toxicity and activity of triple combination of gemcitabine/oxaliplatin/paclitaxel (GOP) in pts with multiple relapse or cisplatin- refractory GCT. Patients and Methods: Between 04/03 - 10/06, 41 patients (pts) refractory to cisplatin-based chemotherapy or with relapse after high-dose chemotherapy plus autologous peripheral blood stem cell transplantation (PBSCT) received 800 mg/m2gemcitabine, 80 mg/m2 paclitaxel, both on days 1+8, and oxaliplatin 130 mg/m2 on day 1 of a three week cycle for at least 2 cycles. Treatment was continued until tumor progression or a maximum of 8 cycles. Results: Pts were pretreated with a median number of 2 previous lines of platin-based chemotherapy (range, 1 - 3) and 78 % had relapsed after either first- (39%) or second-line high-dose chemotherapy (39%) with PBSCT. Responses: 5% of the pts achieved a complete response (CR), 47% a partial response and 20% a disease stabilisation. 20% of the pts underwent a secondary complete tumor resection resulting in a total NED-rate of 22%. After a median follow up time of 5 months (mos) (0 - 20+) 17% of the pts are continuously disease-free with a median response duration of 8 mos (1–17+). Median progression free and overall survival was 3 mos (1–17+) and 6 mos (1–19+), respectively. Toxicity was acceptable. 51% of 150 cycles could be applied without dose modifications or delay. Leucocytopenia grade 3/4 was observed in 15%, anemia in 7%, and thrombocytopenia in 49% of the patients. Grade 3/4 nonhematologic toxicities (diarrhoea, nausea and neurotoxicity) occurred in one patient each (2%). Conclusion: The triple combination chemotherapy with gemcitabine, oxaliplatin and paclitaxel is feasible and effective in patients with cisplatin-refractory or multiply relapsed germ cell tumors exhibiting an overall response rate of >50% and prolonged survival in about 20% of the pts. Despite a significant rate of grade 3/4 thrombocytopenia the overall toxicity profile is acceptable. No significant financial relationships to disclose.
Sunitinib malate (SU) plus interferon (IFN) in first line metastatic renal cell cancer (mRCC): Results of a dose-finding study
Authors: Kondagunta G. V. , Hudes G. R. , Figlin R. , Wilding G. , Hariharan S. , Kempin S. N. , Fayyad R. , Hoosen S. , Motzer R. J. 
Published: March 2020

5101 Background: Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs and PDGFRs with anti-tumor activity in mRCC patients previously treated with cytokines (JAMA, 2006;295:2516). A phase 3 randomized trial showed superiority for SU over IFN in first-line mRCC (PROC ASCO 24,18S, 2006). Dose and safety for SU combined with IFN was investigated in this phase I trial. Methods: Patients (pts) with previously untreated clear-cell mRCC received SU in repeated 6-week cycles of 50 or 37.5 mg/day orally for 4 weeks, followed by 2 weeks off treatment. IFN was given continuously, starting at 3 MU SC 3x/week with intrapatient dose escalation weekly as tolerated, to a maximum of 9 MU. Pts not tolerating a dose combination received lower doses of SU or IFN, or had dose interruptions. Doses of SU plus IFN were considered tolerable if = 4/6 pts completed 2 cycles without dose reduction or interruption. Results: 25 pts were enrolled; 19 are evaluable for safety/response. 6 pts who started treatment at 37.5 SU and 3 MU IFN are too early. The median age of the 19 pts (16 M: 3 F) was 63 years (range 45–77). MSKCC risk group (JCO 20:289–96, 2002) was 37% good and 63% intermediate. 12 pts started treatment with SU 50 mg and dose escalated IFN to 6 or 9 MU TIW. 13 pts started treatment with SU 37.5 mg and dose escalated IFN at 3 MU or to 6 MU TIW. 4 of 19 pts tolerated two cycles. 68% of pts had dose interruptions of SU; 90% of pts had dose interruptions of IFN. 15/19 pts had grade 3 toxicity, 1 pt had grade 4 hypertension and 1 pt grade 5 toxicity (myocardial infarction). Most common grade 3 toxicities were neutropenia (26%), fatigue (26%), and hand-foot syndrome (16%). Although response was not a primary endpoint, at a median of 3 cycles, there were 2 PR, 14 SD, 2 PD and 1 pt was not evaluable. Conclusions: The adverse events seen with combination SU and IFN in mRCC, neutropenia and fatigue, were similar to those seen with single agent SU and IFN, and resulted in frequent dose modifications and interruptions. The safety and efficacy of 37.5 mg sunitinib and 3 MU IFN is being evaluated. No significant financial relationships to disclose.
Randomized phase II study of sorafenib with or without low-dose IFN in patients with metastatic renal cell carcinoma
Authors: Jonasch E. , Corn P. , Ashe R. G. , Do K. , Tannir N. M. 
Published: March 2020

5104 Background: An 80 patient randomized open label phase II study is underway evaluating the safety and clinical benefit of sorafenib with or without low-dose interferon (LD IFN) in patients with untreated metastatic conventional (clear cell) renal cell carcinoma (mRCC). Prior studies combining sorafenib and conventional dose IFN demonstrated a response rate (RR) in the 20–30 percent range, higher than the 2–10 percent RR seen with sorafenib monotherapy, but with increased toxicity. Prior data suggest equivalent efficacy between LD and conventional dose IFN with fewer side effects. We postulated that low-dose IFN will add to the clinical benefit of sorafenib in patients with mRCC with minimal additional toxicity. Methods: Eligibility included conventional mRCC, measurable disease, no prior systemic therapy, a PS of 0 or 1 and no brain metastases. Patients were treated with sorafenib 400mg PO BID or sorafenib at the same dose plus interferon alfa 0.5 million units SC BID. Primary endpoints included response rate and progression free survival (PFS). The probabilities of PFS and overall survival (OS) were estimated for each arm using Kaplan-Meier methods. Median PFS and OS were summarized, along with the 95% confidence intervals for each arm separately. Results: A total of 60 patients were enrolled as of January 8, 2007. Five patients were inevaluable, and 5 patients had not undergone first restaging. Treatment was well tolerated in both groups. Best response and PFS are summarized below. In the sorafenib arm, 13 out of 25 patients progressed or died. The median time to progression was 9.3 months (95% CI 5.8- not reached). In the sorafenib + IFN arm, 13 out of 25 patients progressed or died. Median time to progression was 9.3 months (95% CI 5.2- not reached). Median OS was not reached in either arm. Conclusions: These findings, although preliminary, suggest that adding low dose interferon therapy to sorafenib therapy does not provide superior cytoreduction of metastatic RCC, but provides equivalent PFS. [Table: see text] No significant financial relationships to disclose.
Cardiac involvement in patients with sorafenib or sunitinib treatment for metastatic renal cell carcinoma
Authors: Schmidinger M. , Vogl U. M. , Schukro C. , Bojic A. , Bojic M. , Schmidinger H. , Zielinski C. C. 
Published: March 2020

5110 Background: Tyrosine-kinase inhibitors (TKI) of the VEGF and PDGF-receptor have significant clinical activity in patients with renal cell carcinoma (RCC). These agents target the VHL-hypoxia-inducible gene pathway and lead to inhibition of hypoxia- inducible factor (HIF)-induced gene products. Physiologically, HIF-1 related gene products are important mediators of myocardial response to ischemia, myocardial remodeling, peri-infarct vascularisation and vascular permeability. The aim of this prospective observational study was to investigate clinical and biochemical signs of myocardial damage in patients undergoing TKI-treatment for RCC. Methods: 73 consecutive patients (median age 65, range 44–68) intended for TKI treatment were analyzed for medical history of coronary artery disease (CAD) and risk-factors. Measurements of biochemical markers of cardiac damage (creatine kinase MB -CK-MB- and cardiac troponin T -cTNT-) and electrocardiogram (ECG) were performed before treatment. In patients developing cardiac symptoms during TKI treatment and/or at occurrence of CK-MB or TNT elevations, changes in ECG were analyzed and patients underwent echocardiography. Results: All patients had normal CK-MB and TNT levels at baseline. 17 patients (23%) developed (week 2–32 of treatment) significant CK-MB elevation, (TNT n=5), with clinical symptoms in 7 patients. No patient had uncontrolled hypertension. Detailed ECG’s comparison before and during treatment revealed significant changes in 10 out of 17 patients, such as ST-segment depression or elevation, T-wave changes and symptomatic AV-conduction disturbance, requiring pacemaker-implantation. 3 patients underwent coronary angiography with one patient showing acute coronary artery occlusion and myocardial infarction. 6 out of 17 patients had abnormal findings on echocardiography, such as reduced left ventricular function Conclusions: TKI-induced HIF-inhibition may be associated with severe myocardial damage. The underlying mechanism may not necessarily be caused by overt coronary artery occlusion. ECG-changes and biochemical markers are the most important indicators in the preclinical stage. Therefore, careful cardiac monitoring during TKI-treatment is strongly recommended. No significant financial relationships to disclose.