bluuebunny/crossref_metadata_2025_split huggingface dataset:
Axitinib (AG-013736; AG) in patients (pts) with metastatic renal cell cancer (RCC) refractory to sorafenib
Authors: Rini B. I. , Wilding G. T. , Hudes G. , Stadler W. M. , Kim S. , Tarazi J. C. , Bycott P. W. , Liau K. F. , Dutcher J. P. 
Published: March 2020

5032 Background: Sunitinib and sorafenib, tyrosine kinase inhibitors (TKIs) of the VEGF and PDGF receptors (VEGFR, PDGFR), are FDA-approved treatments for advanced RCC. AG is a potent inhibitor of VEGFRs 1, 2 & 3 and showed substantial efficacy in a previous phase II study in pts with cytokine-refractory RCC (Rini et al. ASCO 2005). The activity of AG in metastatic RCC patients refractory to prior TKI therapy is of interest. Methods: Pts with sorafenib-refractory RCC were enrolled in this multicenter, open-label, phase II study. Eligibility criteria included measurable disease, ECOG performance status of 0 or 1, controlled CNS metastases (if present) and adequate organ function. All pts received a starting dose of AG 5 mg orally BID, titrated according to tolerance. The primary endpoint was RECIST-defined objective response (OR) with a null hypothesis of OR = 8% versus = 20% under the alternative hypothesis. Pts underwent radiographic staging at baseline and every 8 weeks and were treated until progressive disease or unacceptable toxicity. Results: All planned 62 pts have been enrolled. Median age of 42 evaluable pts was 60 years (range 35–77); 29 pts (69%) were male; 41 pts (98%) had prior nephrectomy. Median number of prior therapies was 2 (range 1–8); all pts had received prior sorafenib and 9 pts also received prior sunitinib. Partial response was observed in 6/42 evaluable pts (14%; 95% CI: 5–29%), stable disease in 15 pts (36%), 12 pts (29%) experienced progressive disease, and 9 pts (21%) withdrew due to adverse events. Overall, 57% of pts experienced some degree of tumor regression. With a median follow-up of 5.3 months, the median progression-free survival (PFS) was not reached. Preliminary analysis indicates overall median PFS > 7.1 months. No ORs have yet been observed in patients with prior sunitinib treatment, although tumor regression was demonstrated in 55% of pts with median PFS > 6.1 months. Treatment-related grade 3/4 AEs included hypertension (16%), fatigue (14%) and hand foot syndrome (14%). Overall, 36 pts remain on study. Conclusions: AG has substantial antitumor activity in pts with sorafenib-refractory, metastatic RCC. Toxicity is typical of TKI VEGFR inhibitors and generally manageable. [Table: see text]
Health-related quality of life (QoL) in patients with seminoma stage I treated with either adjuvant radiotherapy (RT) or two cycles of carboplatinum chemotherapy (CT): Results of a randomized phase III trial of the German Interdisciplinary Working Party on Testicular Cancer
Authors: Schoffski P. , Höhn N. , Kowalski R. , Classen J. , Meisner C. , Fechner G. , Dieckmann K. , Winkler C. , Bamberg M. 
Published: March 2020

5050 Background: RT and CT are efficient adjuvant therapies in seminoma stage I and were compared in this trial. Clinical results will be reported elsewhere. Secondary endpoint was to assess QoL. Materials and Methods: Pts were randomized to receive RT (5x2 Gy/wk, 26–30 Gy total dose) or carboplatinum (300–460 mg/m2, 1 h iv d 1, 29). The QLQ C30 vs. 2.0 (15 QoL dimensions) and the Testicular Tumour Questionnaire (TTQ, 16 domains) were completed at randomization (0) and 1, 4, and 12 months (m) after trial entry. QoL was compared over time within the two arms (Wilcoxon) and between treatments (Mann-Whitney) by intent-to-treat. Results: 807 pts were randomized. Questionnaire compliance was 72% at 0, 75% at 1, 69% at 4 and 70% at 12m. Sign. variation (p<0.05) in QoL over time in both treatment arms (no. of Qol domains with deterioration over time): QLQ C30: RT: m1 vs 0 9, m4 vs 0 2, m12 vs 0 0 , CT: m1 vs 0 6, m4 vs 0 3, m12 vs 0 1; TTQ: RT: m1 vs 0 4, m4 vs 0 2, m12 vs 0 3, CT: m1 vs 0 1, m4 vs 0 2, m12 vs 0 1. (¼ improvement over time): QLQ C30: RT: m1 vs 0 0, m4 vs 0 6, m12 vs 0 8, CT: m1 vs 0 2, m4 vs 0 6, m12 vs 0 10; TTQ: RT: m1 vs 0 1, m4 vs 0 2, m12 vs 0 3, CT: m1 vs 0 2, m4 vs 0 4, m12 vs 0 6. Sign. variation in QoL comparing treatment modalities: QLQ C30: Better QoL in RT: at m1 in 0, at m4 in 0 and at m12 in 0 domains, Better QoL in CT: at m1 in 11, at m4 in 2 and at m12 in 5 domains; TTQ: Better QoL in RT: at m1 in 4, at m4 in 1 and at m12 in 0 domains, Better QoL in CT: at m1 in 3, at m4 in 0 and at m12 in 2 domains. Discussion and Conclusions: Adjuvant RT has a more negative impact on self-reported QoL of seminoma pts than CT, as determined by two instruments over a period of one year. RT negatively affects more dimensions of QoL as compared to CT, especially during the early phase. Pts rapidly adapt to QoL impairment, with little change persisting at m12. Not all observed differences are clinically relevant. Potential bias and methodological limitations will be discussed. Given the presumed clinical equivalence of both modalities, pts should be aware of the more negative impact of RT on the well-being. Treatment recommendation should be based on objective outcome parameters, toxicity, logistics and QoL considerations. No significant financial relationships to disclose.
Does progression-free-survival (PFS) correlate with overall- and cancer-specific survival (OS/CSS) in randomized clinical trials (RCTs) exploring the addition of hormonal therapy (HT) to radiotherapy (RT) for early prostate cancer (EPC)? Analysis of six RCTs
Authors: Ruggeri E. M. , Bria E. , Carlini P. , Cuppone F. , Milella M. , Nisticò C. , Sperduti I. , Terzoli E. , Cognetti F. , Giannarelli D. 
Published: March 2020

5056 Background: Although PFS is considered the standard primary end-point in EPC, the correlation with OS has never been explored in RCTs randomizing patients (pts) to HT plus radiotherapy (RT) versus RT. Given the relatively long prognosis in this disease setting, the correlation between PFS and CSS should be investigated as well. Methods: All phase III trials reporting all outcome’ data were considered eligible. The correlation has been explored according to a linear regression model considering both each single outcome pair (PFS, OS and CSS rates) for all arms, and each reported Hazard Ratio (HRs). The correlation was estimated according to both the Pearson- (r) and R2-coefficient (parametric) and the Spearman coefficient (Rho, non-parametric). A sensitivity analysis in 2 subgroups (long- and short-term HT) to test for effect robustness has been accomplished as well. A model to determine the target sample size to determine CSS benefit of 3%, 4%, 6% and 7% months, respectively, was calculated as well. Results: Six RCTs (4,212 pts) were collected (follow-up range: 4.5–7.6 years). In the overall population, when considering the crude rates, a linear stronger correlation was found between PFS and CSS (r=0.71, R2=0.51, p=0.003; Rho=0.75, p=0.005), rather than with OS (r=0.55, R2=0.30, p=0.06; Rho=0.78, p=0.11). Again, when considering HRs, a linear stronger correlation was found between PFS and CSS (r=0.87, R2=0.76, p=0.02; Rho=0.94, p=0.005), rather than with OS (r=0.75, R2=0.56, p=0.08; Rho=0.77, p=0.07). Similar correlations were found whatever subgroups was explored. The sample size model (on the basis of the beta-coefficient=0.71), calculate 4,575, 2,006, 1,115 and 700 pts to improve PFS of 4%, 6%, 8%, and 10% months, which means to improve CSS of 2.8%, 4.3%, 5.7% and 7.1%, respectively. Conclusions: The correlation between PFS and CSS in RCTs exploring the benefit of adding HT to RT for EPC is significant, and suggests its further investigation as surrogate end-point. The natural history of the disease clearly explains the stronger correlation of PFS with CSS rather than with OS. No significant financial relationships to disclose.
Circulating tumor cells in patients with castration-resistant metastatic prostate cancer
Authors: Danila D. C. , Leversha M. A. , Gonzalez-Espinoza R. , Anand A. , Gu B. , Gignac G. A. , Larson S. , Heller G. , Fleisher M. , Scher H. I. 
Published: March 2020

5076 Background: Blood-based assays are urgently needed to provide molecular information on the specific targets expressed in tumor cells to optimize treatment selection. Antibody-capture technologies have been applied to isolate circulating tumor cells (CTC) from small volumes of peripheral blood from patients with progressive castrate metastatic prostate cancer. It has been demonstrated previously that CTC isolated from these patients represent authentic prostate cancer cells. Methods: CTC, positive for EpCAM (epithelial cellular adhesion molecule) and nuclear DAPI, and CD45 negative, were isolated from 120 patients with clinical castrate metastatic disease. All patients had rising PSA levels and were on stable treatment regimens at the time of CTC sampling. We tested the association between CTC counts and PSA levels, and the extent of disease to bone, and soft tissue metastasis by Wilcoxon rank sum. Fluorescence in situ hybridization was performed for AR and ERBB2 genes by an adapted method in CTC. Results: The average age in this patient cohort was 69 years, and median PSA at the time when CTC were drawn was 111 ng/mL (range 0.86–12147 ng/mL). The patterns of metastatic spread included disease in soft tissue only in 12 patients (10%), in bone and soft tissue in 67 (56%), and in bone only in 41 patients (34%). CTC counts ranged from 0 to 1958 cells per 7.5 mL of blood. A large number of patients (54, 45%) had 10 or more circulating tumor cells, while only 33 patients (27.5%) had 1 or less CTC per sample of blood. Significantly higher numbers of CTC were detected in patients with bone metastasis compared to those without bone metastasis (11 vs. 2.5, p<0.01). In patients with marked amplification of AR locus (five patients), tetraploidy was noted in the majority of cases (four cases). Two patients without AR amplification showed apparent tetraploidy, while no analyzed samples (nine) had amplification of ERBB2. Conclusions: The analysis of cancer-related gene alterations in CTC is feasible in a hospital-based laboratory. Further gene expression studies focused on the patients with higher numbers of CTC in correlation with clinical outcomes, as well as the investigation of CTC gene expression during specific treatments are under way. No significant financial relationships to disclose.
Comparative analysis of bone marrow (BM) micrometastasis (M) with sentinel lymph node (SLN) status in early breast cancer (BRCa)
Authors: Patel M. P. , Saha S. , Ali S. , Iddings D. , Wiese D. , Sankaran H. , Arora M. , Singh T. , Branigin T. , Barber K. 
Published: March 2020

508 Background: While sentinel lymph node (SLN) metastasis (mets) and bone marrow (BM) micrometastases (M) provide prognostic information in breast cancer (BRCa) patients (pts), a definitive relationship between the two has not yet been proven. We hypothesize that the presence of BMM may not infer an increased risk of SLN mets due to differences in their mechanisms of spread. Methods: We conducted a 6-year retrospective study of 251 T1/T2 BRCa pts who underwent bilateral iliac crest bone marrow aspiration, SLN mapping, and either lumpectomy, partial mastectomy, modified radical mastectomy, or total mastectomy by a single surgeon. BM samples were examined for micrometastases by Automated Cellular Imaging System using Chroma Vision Cytokeratin Detection Kit to detect cells expressing CK 8 as defined by CAM 5.2 monoclonal antibody. Pts with BMM underwent repeat BM analysis after completion of adjuvant chemotherapy. Data was collected for SLN, BM, ER/PR and HER2/neu status. Results: There were 251 consecutive pts entered into the study. Of these, 27.5% (69/251) had SLN mets and 9.6% (24/251) had BMM. Of the pts with SLN mets, 11.6% (8/69) had BMM vs. 88.4% (61/69) with no BMM ( Table ). In pts with ER/PR negative (-ve) BRCa, 7.1% (2/28) had BMM vs. 92.9% (26/28) with no BMM and 25% (7/28) had SLN positive (+ve) vs. 75% (21/28) SLN -ve pts ( Table ). Of the pts with HER2/neu +ve BRCa, 13.1% (8/61) had BMM vs. 86.9% (53/61) with no BMM and 26.2% (16/61) were SLN +ve vs. 73.8% (45/61) SLN -ve pts. After completion of adjuvant chemotherapy all pts with BMM (n=24) converted to BM -ve status. Conclusions: No correlation was identified between BMM and SLN status in T1 and T2 BRCa pts. This study suggests that BMM can occur independently of SLN status. Furthermore, (-ve) ER/PR and (+ve) HER2/neu status did not have a direct correlation with either BMM or SLN mets. Pts with BMM status may benefit from adjuvant therapy. Long-term implications of BM (+ve) have to be evaluated by larger multi- center trials. [Table: see text] No significant financial relationships to disclose.
Cytokine gene polymorphism: Influence in the response of bladder superficial carcinoma to the immunotherapeutic with BCG
Authors: Silva M. V. , Calais da Silva F. , Ligeiro D. , Trindade H. 
Published: March 2020

5081 Background: Gene polymorphisms in key immunoregulatory molecules may contribute to the heterogeneity in outcome between individuals with bladder superficial carcinome receiving the immunotherapeutic treatment with BCG. This study aims to verify and identify cytokine gene polymorphisms that could influence the immune response to BCG and antitumoural action in those patients. Methods: We studied 90 patients, after turb and BCG intravesical, there where 72 responders (80 %), 18 non-responders (20%) all patients are multiple or recurrent except T1 G3 or Cis, the median follow up is 4,5 years The cytokines single nucleotide polymorphisms (SNP’s) (IL-1a (-889T/C), IL-1β (-511C/T), IL-1β (3962T/C), IL-1R (970 C/T), IL-1Ra (11100 T/C), IL-4 (-590 C/T), IL4-Ra (+576 G/A), IL-6 (-174 G/C), IL-10 (-1082GA/-819CT/-592CA), IL-12p35 (-916C/T), TGF-β (Codon 10 C/T), TNF-a (488GA/-238GA/-308GA), TNF-β (252 G/A), IFN-γ (+874 T/A)) genotypes were assessed by PCR with Sequence Specific Primers (PCR-SSP). Genotypes and allele frequencies of responders and non-responders (with tumour recidive) to the treatment were compared and evaluated by the two-sided Fisher’s exact test or Chi square and odds ratios (OR) were calculated as an estimate of relative risk. Results: It was found a correlation of cytokine gene polymorphisms to outcome of patients for both the genotype and haplotype TNF-a 488G/-238G/-308G frequencies, which are significantly higher in patients with tumour recidive after BCG treatment (non-responders 72,2% vs responders 42% OR=3,6; 95%CI 1.15 to 11.17 p=0.033). From the other genes studied, we could depict a weak association of the IL-1R 970 T/T genotype, with a higher frequency in non-responder patients (27,8% vs 4.2% in responders, p<0.05) and with IL-10 -1082 A allele also more frequent in non-responders to BCG (75% vs 54,8%; p<0.05). Conclusions: These results suggest that host genetics of immune regulatory molecules may play a role in predicting the antitumoural response after BCG treatment of bladder cancer. Confirmation of these findings in other populations is required. No significant financial relationships to disclose.
A controlled prospective randomized trial of adjuvant chemoradiotherapy following radical cystectomy in advanced high risk bladder cancer
Authors: Zaghloul M. S. , Khaled H. M. , Lotayef M. , William H. , Nazmy M. , Attia G. 
Published: March 2020

5082 Background: High risk locally advanced bladder cancer patients experienced low survival rates, high local recurrence and high rate of distant metastasis. Postoperative radiotherapy (PORT) improved local control and survival, yet it did not affect distant metastasis. Methods: A prospective randomized trial was performed at NCI, Cairo, Egypt including 146 patients in 2 arms. Patients who underwent radical cystectomy and pelvic lymphadenectomy had to have one or more of the following: stage P3b or P4a, G3 or involved lymphadenopathy. Arm I (74 patients) received PORT 45 Gy/30 fractions/3 weeks. Arm II (72 patients) received 2 courses of adjuvant chemotherapy (Gemcitabine 1 gm/m2 D1 and D8 and cisplatin 70 mg/m2 D2), same PORT regimen followed by another 2 courses of Gemcitabine-cisplatin. Results: Chemotherapy and radiation were tolerated with grade 1/2 toxicities. Delayed toxicity was comparable in both arms. The 45-month DFS was 51 ± 12 % in the whole group. This was affected significantly by performance status (p = 0.0001), pathological stage (p = 0.0099), nodal involvement (p = 0.004) and number of risk factors (p = 0.16). Though there was improvement of 45-month DFS from 28 ± 20% in PORT group to 70 ± 6 % in chemoradiotherapy group, yet it did not reach to the level of statistical significance (p = 0.18). Patients having one risk factor, G3 or no nodal involvement in arm II experienced better DFS than those in arm I (p = 0.17, 0.11 and 0.17 respectively). Distant metastasis-free survival (DMF) rate increased with the addition of chemotherapy from 29±21% to 75±6%. This effect was intensified in patients having one risk factor, grade 3 and negative nodes. Conclusions: Adjuvant chemoradiotherapy using Gemcitabine-cisplatin and PORT was tolerable. There was DFS improvement and higher DMF rates with the addition of chemotherapy to PORT (not statistically significant yet). Patients with one risk factor, G3 or no nodal involvement seemed to benefit more from the added chemotherapy. No significant financial relationships to disclose.
Outcome in 41 patients with late relapse germ cell tumors (GCT) treated with high-dose chemotherapy (HDCT)
Authors: Lorch A. , Rick O. , Hartmann J. T. , Metzner B. , Glasmacher A. , Berdel W. , Schirren R. , Bokemeyer C. , Beyer J. 
Published: March 2020

5086 Background: The management of patients (pts) with late-relapse GCT and unresectable tumors or very high tumor markers is controversial. Methods: A total of 41 late-relapse pts were identified among a group of 216 pts with refractory or relapsed GCT who were treated in an open, prospective, randomized, multicenter phase III trial. Late relapse was defined as any relapse occurring more than 2 years after completion of initial chemotherapy for GCT. Treatment consisted of either one cycle cisplatin 100 mg/m2, etoposide 375 mg/m2 and ifosfamide 6 g/m2 (VIP) plus three cycles of high-dose carboplatin 1,500 mg/m2 and etoposide 1,500 mg/m2 (CE, arm A) or of three cycles of VIP plus one cycle high-dose carboplatin 2,200 mg/m2, etoposide 1,800 mg/m2 and cyclophosphamide 6,400 mg/m2 (CEC, arm B). Each HDCT was followed by reinfusion of autologous peripheral blood progenitor cells. Results: Overall 20 pts with late-relapse GCT received sequential HDCT and 21 pts single HDCT when the study was stopped due to excess treatment-related mortality in arm B; median time to late relapse in 41 pts was 5.4 years (range 2–18 years); 8/41 (20%) pts had seminomatous GCT, 32/41 (78%) pts had nonseminomatous GCT with or without teratoma; one pt (2%) had unknown GCT histology. No non-GCT histologies were included. The retroperitonum was most commonly involved in 30/41 (73%) pts. 29 of 41 (71%) pts had unresectable, multifocal disease and 20/41 (49%) pts also had very high markers. A complete remission to chemotherapy alone was achieved in 4/41 (10%) pts, 16/41 (39%) pts achieved a partial remission with negative tumor markers. The remaining 21/41 (51%) either had a transient or no response despite HDCT. Residual tumor resections were performed in 17/41 (41%) pts. Residual tumor histology was viable cancer in 8/17 (47%) pts, teratoma in 4/17 (24%) pts and necrosis in 5/17 (25%) pts. With a minimum follow-up of 1 year and a median follow-up of 3 years the estimated Kaplan-Meier rates are 17%, 20% and 32% for event-free, progression-free and overall survival. Conclusion: Treatment outcome after HDCT was inferior in late-relapse pts compared to the group of pts who relapsed within less than 2 years. Despite an overall poor prognosis, HDCT can still result in long-term remissions in selected late-relapse GCT pts. No significant financial relationships to disclose.
Can we improve the outcome of patients with advanced non-seminomatous germ cell tumors (NSGCT): 16 years experience of a single institution
Authors: Tryakin A. , Tjulandin S. , Fedyanin M. , Titov D. , Bulanov A. , Garin A. , Figurin K. , Kanagavel D. , Sergeev J. , Zakharova T. 
Published: March 2020

5092 Background: We performed an analysis to review the outcome of patients (pts) with advanced NSGCT treated in Russian Cancer Research Center, since the introduction of modern chemotherapy (CT) at 1987. Moreover, we analyzed whether the results had improved over the last 6 years. Methods: 589 CT-naive pts with advanced NSGCT received induction etoposide- and cisplatin-based CT from 1987 to 2003. 534 (91%) pts had primary testicular tumor. Most commonly used CT regimens were EP (36%), BEP (52%), and C-BOP-3BEP (9%). Median follow-up was 60 months (range, 2–210) for the pts who survived. Pts survival was compared in accordance with two treatment periods, ‘before 1997’ and ‘after 1997’. Results: Survival rate differed significantly among the IGCCCG prognostic groups. There was a trend toward improved results over the last 6-year period (see table ). The poor prognostic group attained the most pronounced improvement in both PFS and OS (absolute benefit 14%). This fact could be explained by CT intensification (decrease in the number of reasons for treatment delay or dose-reduction on next cycle of CT) and by increase in the rate of post-CT resections of residual tumors. Conclusions: Despite the absence of major changes in advanced NSGCT treatment during the last two decades, there still exists opportunity to improve the outcome of the pts. [Table: see text] No significant financial relationships to disclose.
A phase I study to evaluate safety, immunogenicity and anti-tumor activity of the multi-peptide vaccine IMA901 in renal cell carcinoma patients (RCC)
Authors: Staehler M. , Stenzl A. , Dietrich P. Y. , Eisen T. , Haferkamp A. , Beck J. , Mayer A. , Walter S. , Singh-Jasuja H. , Stief C. 
Published: March 2020

5098 Background: IMA901 is a therapeutic cancer vaccine based on multiple synthetic tumor-associated peptides confirmed to be naturally presented by analysis of primary RCC tissues. IMA901 consists of 9 HLA-class I-binding and 1 HLA class II-binding peptides with the capacity to activate cytotoxic T cells (CD8+ T cells) and T helper cells (CD4+ T cells). Methods: 30 patients with stage III/IV RCC were enrolled in a single arm, multi-centre study. The endpoints were safety, T-cell responses, pharmacokinetics of the intradermal application of GM-CSF and anti-tumor activity according to RECIST. Patients had to be HLA-A*02 positive and received 8 intradermal vaccinations on days 1, 2, 3, 8, 15, 22, 36 and 64 each consisting of 4.5 mg IMA901 and 75 μg GM-CSF. Results: The most prevalent adverse events (AEs) were fatigue, cough and headache. Aseptical lymphadenitis and injection site reactions such as erythema, edema and pruritus were the most frequent possibly drug-related AEs. All possibly drug-related adverse events were mild to moderate. No patient experienced any possibly drug-related serious adverse events or deaths during the study. Pharmacokinetic data provided no evidence for accumulation of GM-CSF upon repeated i.d. administration. 74% of patients showed a vaccine-induced specific T-cell response and 30% of patients responded to multiple peptides contained in IMA901. The overall tumor assessment in patients with measurable disease revealed that 8 patients (35%) demonstrated a clinical benefit (1 PR + 7 SD). Most encouraging, patients who elicited multiple T-cell responses showed a statistically significant higher clinical benefit rate. Conclusions: IMA901 is safe, very well tolerated and immunogenic. Clinically observed tumor growth control in RCC patients may imply anti-tumor activity strongly supported by two patients with tumor regression (1 PR and 1 patient with 27% shrinkage in target lesions). The mode of action is strongly supported by the finding that multiple T-cell responders were significantly more likely to have a clinical benefit. These data clearly support the further development of IMA901. No significant financial relationships to disclose.