bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of dose-dense modified TCF regimen (TCF-dd) in metastatic or locally advanced gastroesophageal cancer (GEC).
Authors: Toppo Laura , Tomasello Gianluca , Liguigli Wanda , Ratti Margherita , Poli Rossana , Negri Federica , Curti Alessandra , Vismarra Marco , Maltese Mariangela , Delfrate Roberto , Donini Maddalena , Colombi Chiara , Brighenti Matteo , Panni Stefano , Perrucci Bruno , Lazzarelli Silvia , Passalacqua Rodolfo 
Published: March 2020

4112 Background: TCF is a standard first line option for GEC. The Norton-Simon hypothesis suggests that chemotherapy efficacy can be enhanced by decreasing intervals between cycles. We previously reported on the high activity of TCF-dd in GEC (Tomasello 2010). The aim of this study is to investigate the efficacy and safety of this intensified dose-dense regimen in a single-center large cohort of patients (pts). Methods: 150 pts with measurable or evaluable GEC, PS 0-2, with adequate organ function, treated in our center from 2004 to 2012 received TCF-dd: Docetaxel (60-85 mg/m2 d 1), Cisplatin (50-75 mg/m2 d 1), l-Folinic Acid (100 mg/m2 d 1-2), 5-FU (400 mg/m2 bolus d 1-2, and 600 mg/m2 as a 22 h continuous infusion d 1-2), plus Pegfilgrastim 6 mg d 3, every 14 days. Pts aged ≥ 65 years received the same schedule with a dose reduction by 30%. Analysis was based on the intention to treat population. Results: At a median follow-up of 44 months, 128 pts were evaluable for response, all for survival. Median age 65 (range 31-81), M:F 112:38. 17 pts (11%) with locally advanced inoperable GEC, 133 pts (89%) with metastatic GEC. Metastatic sites: liver 40%, peritoneum 31%, bone 14%, lung 12%. A median of 4 cycles (range 1-7) per patient was administered. 33% required a dose reduction. 33% were treated without any delay. 10 CR, 74 PR, 24 SD and 20 PD were observed, for an ORR of 66% (95% CI 57-74). Median OS was 13 months (95% CI 9.7-14.2). Most frequent grade 3/4 toxicities: neutropenia (34%), asthenia (28%), thrombocytopenia (17%), hypokalemia (16%), diarrhea (11%), febrile neutropenia (10%), anemia (9%), and stomatitis (4%). 11 pts (7%) [7 metastatic, 4 locally advanced] became operable after TCF-dd and underwent surgery. We identified 12 metastatic pts (8%) with overall survival > 3 years and 7 (5%) still maintaining a long lasting CR at the time of the current analysis. Conclusions: TCF-dd in GEC is very active and may be an option for conversion therapy. Toxicity can be relevant and requires a careful monitoring.
A nationwide cohort study of surveillance for stage I seminoma.
Authors: Mortensen Mette Sakso , Gundgaard Maria Gry , Lauritsen Jakob , Agerbaek Mads , Holm Niels Vilstrup , von der Maase Hans , Daugaard Gedske 
Published: March 2020

4502 Background: The standard treatment for stage I seminoma remains a topic for discussion. Survival rates are excellent irrespective of treatment modality (radiotherapy, carboplatin or surveillance). However, late effects might differ between treatment options. Only smaller surveillance studies with limited follow-up have previously been published. We present data from a large nationwide cohort study on surveillance in stage I seminoma patients. Methods: A nationwide and population based clinical database covering germ cell cancer patients diagnosed 1984-2007 was constructed. The database included 4,683 cases. All stage I seminoma patients followed by surveillance were identified. Possible prognostic factors for relapse were collected from patient files and pathology reports. By merging our data with the national patient registry we were able to collect data on late relapses, vital status and cause of death on all patients up to December 2012. Results: 1,822 patients with stage I seminoma were followed on a surveillance program. The median follow-up time was 15.4 years. Ten year cancer specific survival (CSS) was 99.6%. A total of 355 (19.5%) patients had a relapse after a median time of 13.7 months (range 1.2-173.7 months). Within 2-5 years after orchiectomy, 72 patients (4.0 %) had a relapse and 26 patients (1.4 %) had a relapse more than 5 years after orchiectomy. Invasion of blood or lymphatic vessels, tumor size > 4 cm and serum human chorionic gonadotropin > 200 IU/L were all predictive factors for relapse in both univariate and multivariate analyses (p<0.01). Invasion of rete testis was significant in the univariate analysis but not in the multivariate analyses (p=0.53). Conclusions: We present the largest cohort ever published of stage I seminoma patients followed on a surveillance program. The prognosis was excellent with a 10 year CSS of 99.6%. Prognostic factors for relapse were identified. The relapse rate after 5-years of follow-up was 1.4%. Surveillance should be the preferred option of management in stage I seminoma patients. Several international guidelines are now in agreement with this statement.
A phase II study of intermittent sunitinib (S) in previously untreated patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Rini Brian I. , Wood Laura S. , Elson Paul , Zhu Hui , Chittoria Namita , Mittal Kriti , Dreicer Robert , Gilligan Timothy D. , Shah Shetal N. , Garcia Jorge A. 
Published: March 2020

4515 Background: S as initial treatment in mRCC is limited by balancing acute and chronic toxicity with clinical benefit. Pre-clinical and retrospective clinical data support that extended treatment breaks are feasible without a reduction in efficacy. Methods: Pts with treatment-naïve clear cell mRCC were enrolled on a prospective phase II trial and initially treated with 4 cycles of S (50 mg 4/2). Pts with ≥ 10% reduction in tumor burden (TB) following 4 cycles had S held, with CT scans approximately every 10 weeks. S was re-initiated for 2 cycles in those pts with an increase in TB by ≥ 10% and again held with ≥ 10% TB reduction. This intermittent S dosing continued until RECIST-defined disease progression while on S. The primary objective was feasibility of intermittent S, defined as the proportion of eligible pts who underwent intermittent therapy. The alternative hypothesis was a feasibility of > 80% vs. a null hypothesis of < 50% (a=0.05; power 80%). Results: Thirty-six pts were enrolled; 70% male, median age 60, 95% PS 0/1 and 32% favorable/65% intermediate by Heng criteria. Twenty pts were eligible for intermittent therapy and all pts (100%) entered the intermittent phase. Pts were not eligible for intermittent S due to PD (n=13); toxicity (n=1) or w/d of consent (n=2) prior to end of cycle #4. Sixteen pts (80%) had ≥ 10% TB increase off S with a median (range) increase of 1.5 cm (1.1-2.5) compared to the TB immediately prior to stopping S, considering all off periods.Four pts did not have ≥ 10% TB increase off S (3 pts after the 1st off period; off for 12, 8 and 5 months to date and 1 pt after the 2nd off period; off for 8 months prior to restarting S). Most pts exhibited a stable saw tooth pattern of TB reduction on S and TB increase off S. No pt had RECIST-defined PD while on S, but 2 pts were taken off extended breaks due to gradual TB increase over time, and 1 pt developed new CNS mets during the 2nd off period.The objective response rate was 53%. Toxicity was typical for S and completely resolved during treatment breaks. Conclusions: S dosing with periodic extended time off drug is feasible and associated with reduction in toxicity during the off periods. Clinical efficacy does not appear to be compromised. Clinical trial information: NCT01158222.
A phase II clinical trial examining the impact of neoadjuvant axitinib on primary tumor response in patients with locally advanced clear cell renal cell carcinoma.
Authors: Karam Jose A. , Devine Catherine E , Lozano Marisa , Tannir Nizar M. , Ahrar Kamran , Tamboli Pheroze , Wood Christopher G. 
Published: March 2020

4516 Background: Previous studies have shown minimal impact of TKIs on primary renal tumor downsizing. Axitinib is a VEGFR TKI that has been recently approved for use in patients with metastatic clear cell renal cell carcinoma (RCC). In this prospective phase II trial, we sought to investigate the safety and role of axitinib in downsizing tumors in patients with non-metastatic renal cell carcinoma, prior to undergoing surgical resection. Methods: Patients with locally advanced (clinical stage T2-T3b N0 M0) biopsy-proven clear cell RCC were eligible for this phase II clinical trial. The primary outcome was objective response rate (using RECIST) following the administration of axitinib for 12 weeks prior to undergoing radical nephrectomy. Secondary outcomes included safety, tolerability, and feasibility of administration of axitinib in this patient population. Patients were given axitinib 5mg PO BID, and dose titration was allowed. Axitinib was continued until 36 hours prior to surgery. A dedicated radiologist independently reviewed all CT scans to evaluate for response using RECIST. Results: The study goal of enrolling 24 patients has been recently reached. At present, nineteen patients have completed the studies required for assessment of the primary outcome and are hereby reported. Fifteen patients were males, and four were females. Median age was 61 years (range 42-83 years). All patients had biopsy-proven clear cell RCC. All 19 patients continued axitinib for 12 weeks, and underwent surgery as planned without delay. Adverse events of any grade were: arthralgia in 6, hypothyroidism in 14, fatigue in 15, and hypertension in 16 patients. No wound complications occurred after surgery. Nine patients (47%) experienced a partial response by RECIST, and 10 patients had stable disease. There was no progression of disease while on axitinib. Conclusions: Axitinib is well tolerated in the neoadjuvant setting in patients with planned surgery for locally advanced non-metastatic clear cell RCC. The drug showed tumor downsizing activity when given for 12 weeks prior to surgery. Adverse events of any grade were common and easily manageable with routine care. Clinical trial information: NCT01263769.
Identification of predictive biomarkers of overall survival (OS) in patients (pts) with advanced renal cell carcinoma (RCC) treated with interferon alpha (I) with or without bevacizumab (B): Results from CALGB 90206 (Alliance).
Authors: Nixon Andrew B. , Halabi Susan , Shterev Ivo , Starr Mark , Brady John C , Dutcher Janice P. , Hopkins Judith O. , Hurwitz Herbert , Small Eric Jay , Rini Brian I. , Febbo Phillip G. , George Daniel J. ,   for the Alliance for Clinical Trials in Oncology
Published: March 2020

4520 Background: CALGB 90206 was a phase III trial of 732 pts with RCC comparing B+I versus I alone demonstrating no difference in OS. To date, there are no validated predictive biomarkers for B in RCC. For this reason, baseline plasma samples from CALGB 90206 pts were analyzed to identify and test predictive markers for B+I in RCC pts. Methods: Baseline EDTA plasma samples from 424 consenting pts were analyzed using an optimized multiplex ELISA platform for 32 candidate factors related to tumor growth, angiogenesis, and inflammation. The data were randomly split into training (n=286) and validation (n=138) sets. The proportional hazards model was used to test for treatment-marker interactions of OS. The estimated coefficients from the training set were used to compute a risk score (RS) for each pt in the validation set. The RS classified pts by risk in the validation set. The model was assessed for its predictive accuracy using area under the curve (AUC). Results: A statistically significant 3-way interaction between interleukin-6 (IL-6), hepatocyte growth factor (HGF) and treatment was observed in the training set (p<0.0001). The median levels of IL-6 and HGF in the training set were 8.4 pg/ml and 89 pg/ml, respectively. In the validation set, the RS was predictive of OS (p<0.001) with the high and low risk groups having a median OS of 10 months and 32 months, respectively. The AUC in the validation set was 0.82 (95% CI=0.77-0.88). The median OS (in months) by median levels of IL-6 and HGF stratified by treatment arm in the validation set is presented in the table with associated 95% CI (NR=not reached). Conclusions: IL-6 and HGF are predictive for OS in RCC patients treated with B+I and a RS based on these factors identified patients who benefitted most from B. If independently validated, this novel RS could guide clinical decisions and pt selection in future RCC trials. [Table: see text]
Pdl-1/pdl-3 (programmed death ligand-1/3) tissue expression and response to treatment with IL2 and antiangiogenic therapies.
Authors: Bailey Alexandra S. , Cheng SuChun , Kwon Eugene D. , Leibovich Bradley C. , Signoretti Sabina , Dutcher Janice P. , Appleman Leonard Joseph , Sosman Jeffrey Alan , Margolin Kim Allyson , Clark Joseph , Khushalani Nikhil I. , Curti Brendan D. , Ernstoff Marc S. , Pantuck Allan J. , Vaishampayan Ulka N. , Logan Theodore , McDermott David F. , Atkins Michael B. ,   Cytokine Working Group
Published: March 2020

4521 Background: Expression of PDL1 by RCC has been associated with aggressive histology and poor survival. Tissue obtained from the patients enrolled in the IL-2 Select Trial, a prospective, single arm, multicenter CWG study, was analyzed by IHC to determine if PDL1or PDL3 expression predicted for response to initial or subsequent therapy. Methods: Paraffin embedded tumor tissue was stained for PDL1 and PDL3 expression, and results were correlated with RECIST defined response to IL2 treatment. Tumor tissue was considered positive for PDL1 if >5% of the tumor membranes stained for the marker. A cutoff of 10% was used for PDL3. Duration of subsequent VEGFR/mTOR inhibitor therapy was also correlated with tissue PDL1/3 expression. Results: 120 eligible pts were enrolled; 115 had clear cell histology. The overall response rate (ORR) to IL2 was 25% (30/120) with a median OS of 40.6 months. 113 tumors were stained. 18 (16%) were PDL1+. ORR was 19% and 50% in the patients PDL1- and PDL1+ tumors, respectively (p=0.012). 85 (75%) tumors were PDL3+. ORR was 10.7% and 29.4% in the PDL3- and PDL3+ tumors, respectively (p=0.075). In the 17 patients who were positive for both PDL1 and PDL3, ORR was 52.9%. In the 27 pts who were negative for both PDL1 and PDL3, ORR was 11.1%. 69 patients received at least 1 dose of a VEGFR TKI as next therapy following IL2 treatment. 66 tumors were stained. Pts who were PDL1+/PDL3+ had a shorter duration on VEGFR TKI therapy compared to pts who were PDL1-/PDL3- (see Table). Conclusions: This small, retrospective analysis suggests that PDL1 and PDL3 tissue expression may predict for better response to IL2. PDL1 expression has been suggested as a possible predictor of response to anti-PD1 therapy. The current data suggests that its expression may predict for benefit to other immune therapies. PDL3 (+/- PDL1) expression appears to correlate to less benefit from subsequent VEGFR TKI therapy. Funded by NCI SPORE Grant # 5 P50 CA101942-08. [Table: see text]
Treatment patterns and outcomes in “real world” patients (pts) with metastatic urothelial cancer (UC).
Authors: Galsky Matt D. , Chowdhury Simon , Bellmunt Joaquim , Wong Yu-Ning , Recine Federica , Pal Sumanta Kumar , Moshier Erin L. , Ladoire Sylvain , De Giorgi Ugo , Yu Evan Y. , Niegisch Guenter , Crabb Simon J. , Mardones Mabel A , Necchi Andrea , Golshayan Ali Reza , Bamias Aristotelis , Mano Roy , Harshman Lauren Christine , Powles Thomas , Rosenberg Jonathan E. ,   RISC Investigators
Published: March 2020

4525 Background: Most studies reporting outcomes of pts with metastatic UC are derived from clinical trial data, potentially limiting the breadth/generalizability of the findings. To explore patterns of care/outcomes in “real world” pts, we initiated an international retrospective cohort study. Methods: Data were collected via an electronic data capture platform from 23 centers. Eligible pts had UC (at least muscle-invasive) and were initially evaluated from 1/1/2006-1/1/2011. Parameters were subjected to regression analysis to identify prognostic variables. Results: By 12/18/12, 1905 pts were enrolled. Among 1077 with metastatic UC, median age was 67 (IQR 60-75), 80% were male, 87% had bladder primary tumors, and 33% received perioperative chemotherapy. Only 758 (70%) received 1st-line chemotherapy for metastatic UC: cisplatin-based (51%), carboplatin-based (29%), non-platinum single-agent (16%), and non-platinum multi-agent (4%). The median survival from date of diagnosis of metastatic UC was 5.2 months (95% CI 4.4-6.5) and 16.1 months (95% CI 15.1-17.5) for pts who did and did not receive 1st-line chemotherapy, respectively [13.9 months (95% CI 12.78-14.98) from start of chemotherapy for latter group]. Among pts receiving 1st-line chemotherapy, univariable analysis revealed gender, primary tumor site, removal of primary, creatinine clearance, LDH, and hgb were not significantly associated with survival whereas smoking status, performance status, perioperative chemotherapy, metastatic sites, study site and chemotherapy regimen were. The multivariable analysis is shown in the Table. Conclusions: The current analysis identifies previously unrecognized prognostic factors in an international cohort of “real world” pts with metastatic UC treated with 1st-line chemotherapy. A large subset of pts with metastatic UC receives no chemotherapy. [Table: see text]
Randomized phase III trial of neoadjuvant chemotherapy (NAC) with methotrexate, doxorubicin, vinblastine, and cisplatin (MVAC) followed by radical cystectomy (RC) compared with RC alone for muscle-invasive bladder cancer (MIBC): Japan Clinical Oncology Group study, JCOG0209.
Authors: Kitamura Hiroshi , Tsukamoto Taiji , Masumori Naoya , Shibata Taro , Kunieda Futoshi , Fujimoto Hiroyuki , Hirao Yoshihiko , Kitamura Yasuo , Tomita Yoshihiko , Tobisu Kenichi , Niwakawa Masashi , Naito Seiji , Eto Masatoshi , Kakehi Yoshiyuki 
Published: March 2020

4526 Background: Cisplatin-based NAC for patients (pts) with MIBC is considered to provide a 5–8% overall survival (OS) advantage, although several studies failed to prove the survival benefit of NAC. Methods: Eligibility criteria included histologically proven urothelial carcinoma, MIBC (T2-4aN0M0) within 8 weeks from TURBT, PS 0-1, and age 20-75 years old. Patients were randomized to receive 2 cycles of neoadjuvant MVAC followed by RC (NAC arm) or RC alone (RC arm). The primary endpoint was OS. Secondary endpoints were progression-free survival (PFS), surgery-related complications, adverse events during NAC, the percent with no residual tumor in the RC specimens (pT0), and QOL. The sample size was 180 pts in each arm with a one-sided alpha of 5% and a power of 80% to detect a 7% difference in 5-year OS, 45% in the RC arm, and 57% in the NAC arm. Results: From March 2003 to March 2009, 130 pts were randomized to the NAC arm (n=64) and RC arm (n=66). Fifty-nine patients in the NAC arm and 65 in the RC arm underwent cystectomy. The patient registration was terminated early because of slow accrual. At the 2nd interim analysis conducted after the completion of patient accrual, OS of the NAC arm was better than that of the RC arm, although the difference was not statistically significant (HR, 0.65; multiplicity adjusted 99.99%CI, 0.19-2.18; one-sided log-rank p = 0.07). Considering the current situation in which NAC with gemcitabine and cisplatin (GC) is widely used in clinical practice, the Data and Safety Monitoring Committee recommended early publication of the results. PFS of the NAC arm was better than that of the RC arm (HR, 0.61; 95% CI, 0.35-1.06, one-sided log-rank p=0.04). No differences in perioperative complications, other than lymph leakage, were observed between the arms. In the NAC arm and the RC arm, 34% and 9% of the patients had pT0, respectively (p<0.01). In subgroup analyses, OS in almost all subgroups was in favor of NAC. Conclusions: Although NAC with GC is widely used for MIBC, NAC with MVAC can still be considered promising. Clinical trial information: C000000093.
Prognostics factors in previously untreated urothelial cancer patients ineligible for cisplatin-based chemotherapy: An external validation of the Bajorin risk groups.
Authors: Collette Sandra , Sylvester Richard , Bellmunt Joaquim , Mead Graham , Kerst Jan M. , Leahy Michael Gordon , Maroto Pablo , Gil Thierry , Marreaud Sandrine , Daugaard Gedske , Skoneczna Iwona Anna , De Wit Ronald , De Santis Maria ,   EORTC GU Cancers Group
Published: March 2020

4529 Background: In patients with urothelial cancer who are unfit for Cisplatin chemotherapy, EORTC phase II/III trial 30986 investigated two carboplatin-based chemotherapy regimens: Gemcitabine/Carboplatin (GC) and Methotrexate/Carboplatin/Vinblastine (M-CAVI). The trial did not show any significant differences in efficacy (response rate, OS, PFS) between the treatments; however the incidence of severe acute toxicity was slightly higher on M-CAVI. We now investigate the prognostic factors for survival. Methods: 238 patients with impaired renal function (Glomerular Filtration Rate (GF) <60 mL/min) or poor performance status (PS 2) were randomized by 29 institutions between GC and M-CAVI. The median follow-up was 4.5 years and, with 218 deaths reported (progression of malignant disease in 72%), the overall survival median was 9.3 months in the GC arm and 8.1 months in the M-CAVI arm. Univariate and multivariate Cox prognostic factor regression models for overall survival were developed on the whole population stratified by treatment arm. Results: In the multivariate analysis, the risk of death significantly increased (p<0.10) with WHO-PS 2, hemoglobin ≤ 12 g/dl (women) or ≤ 13.6 g/dl (men), the presence of visceral metastases and even more with the presence of liver metastases. The risk of death was not influenced by the site of the primary tumour, white blood cell or platelet count. In addition, the prognostic factors had a stronger effect in the M-CAVI arm than in the GC arm. Conclusions: This prognostic factors analysis confirms the Bajorin classification based on visceral metastases and performance status. However, we were also able to show the importance of hemoglobin and that in the patients with visceral metastases, the subgroup of patients with liver metastases had a significantly worse prognosis than the patients with only other visceral metastasis. Clinical trial information: NCT00014274.