bluuebunny/crossref_metadata_2025_split huggingface dataset:
SWOG 0514: A phase II study of sorafenib (BAY 43–9006) as single agent in patients (pts) with unresectable or metastatic gallbladder cancer or cholangiocarcinomas
Authors: El-Khoueiry A. B. , Rankin C. , Lenz H. J. , Philip P. , Rivkin S. E. , Blanke C. D. 
Published: March 2020

4639 Background: There are no standard chemotherapeutic regimens for incurable biliary adenocarcinomas. Gemcitabine and fluoropyrimidine- based chemotherapy results in occasional responses and a median survival approaching 6 months. Given the presence of b- raf mutations and overexpression of VEGF in biliary cancers, we initiated a study to evaluate the efficacy of sorafenib, a multitargeted tyrosine kinase inhibitor of c and b-Raf, VEGFR-2/3 and PDGFR, in pts with metastatic biliary cancers. Methods: Pt eligibility included adequate organ function and no prior treatment for metastatic disease. The primary end-point was objective response rate (RR). Secondary endpoints were overall survival (OS) and progression free survival (PFS). A two-stage design was used to detect a difference in the null hypothesis of 5% response probability and the alternative 20% response probability. If at least one confirmed response occurred after the first 25 pts, another 25 were to be accrued. Sorafenib was administered at 400 mg PO BID continuously. A cycle was defined as 28 days of therapy, and radiological assessment was done every 2 cycles. Results: 36 pts were enrolled during the first stage of accrual. 5 pts were ineligible. 52% were female. Median age was 57.8 years (range 33.8–81.5). Adverse events: 1 pt died with grade 4 supraventricular tachycardia and venous thromboembolism. Grade 3/4 toxicities were noted in 20 pts (66.7%) and included hand-foot syndrome in 4 pts (13%), while thrombosis/embolism, elevated liver transaminases, and abdominal pain were each seen in 3 pts (10% for each). Reversible posterior leukoencephalopathy syndrome, GI perforation, and GI hemorrhage were each seen in 1 pt (3% for each). 2 pts (6%) had an unconfirmed partial response and 9 pts (29%) had stable disease. 27 pts have progressed. Median PFS was 2 months (95% CI: 2–4 months). 14 pts have died, with a median survival estimate of 6 months (95% CI: 4–10 months). Conclusions: Sorafenib did not result in a clinically significant objective RR in pts with gallbladder and cholangiocarcinoma but demonstrated an impact on survival that may be comparable to commonly used chemotherapy regimens. No significant financial relationships to disclose.
A phase II study of neoadjuvant chemotherapy with docetaxel, capecitabine and cisplatin (DXP) in patients with advanced unresectable or intra-abdominal metastatic gastric cancer
Authors: Sym S. , Chang H. , Ryu M. , Lee J. , Kim T. , Yook J. , Oh S. , Kim B. , Kang Y. 
Published: March 2020

4640 Background: The prognosis of gastric cancer is dismal once R0 resection is impossible due to local invasion or distant metastasis. Previous studies have suggested the possible efficacy of neoadjuvant chemotherapy for the patients with locally advanced gastric cancer (AGC). The aim of the present study was to evaluate the feasibility, the impact on R0 resection of neoadjuvant chemotherapy in locally advanced, unresectable or intra-abdominal metastatic gastric cancer Methods: Patients with advanced gastric cancer, clinically unresectable because of local invasion or intra-abdominal metastasis in paraaortic lymph nodes and/or peritoneum based on CT scan were entered into this study. Preoperative chemotherapy consisted of docetaxel 60 mg/m2 IV on day 1, cisplatin 60 mg/m2 IV on day 1, and capecitabine 1,875 mg/m2/day PO on days 1 - 14 every 21 days. After 2 cycles of chemotherapy, the tumors were evaluated. Unless disease progression was encountered, surgery was performed after total 3 - 6 cycles of chemotherapy and followed by two cycle of adjuvant therapy with the same regimen if R0 resection was done. Results: Total 49 patients were accrued. Among them, 36 (74%) could undergo surgery, and 31 (63%) had R0 resection. R0 resection was possible in 15 (71%) of 21 patients with initially unresectable T4 lesions and in 12 (70%) of 17 patients with paraaortic lymph node enlargement, while only in 3 (42%) of 7 patients with suspicious peritoneal seeding. After a median follow up of 18.2 months for the surviving patients, median overall survival and progression free survival of total enrolled patients were 19 months (95% C.I, 10.5 - 27.4) and 11.6 months (95% C.I, 9.6 - 13.7), respectively. Among 31 patients who underwent R0 resection, median OS was 33.4 months and median PFS was 18.2 months. Major toxicity was neutropenia and grade 3/4 neutropenia occurred in 77% of patients, but there was only 4% of neutropenic fever and no treatment related mortality. Postoperative morbidities were observed in 4 patients. Conclusions: These data suggested that neoadjuvant DXP chemotherapy could offer a reasonable chance for curative surgery in AGC patients with local invasion or paraaortic lymph node enlargement. No significant financial relationships to disclose.
Increased foxp3+ regulatory T cells predicts for superior relapse-free and overall survival in early stage hepatocelullar carcinoma
Authors: Toh H. , Phoon Y. P. , Quek R. , Banham A. H. , Tan S. Y. 
Published: March 2020

4642 Background: Hepatocellular carcinoma (HCC) endemic in Asia is aggressive and mainly hepatitis B-related. In ovarian and breast cancer, higher levels of foxp3+ regulatory T cells predicts for a poorer clinical outcome. The reverse is true with follicular lymphoma and Hodgkin’s disease. We hypothesize that foxp3+ CD4+ regulatory T lymphocyte (Treg) frequency predicts for clinical outcome in HCC. We also examined the recently identified IL17-producing, RORγt-expressing, CD4+ pathogenic Th17 cells in HCC. Methods: We analyzed Treg cells (n=116) and CD8+ T cells (n=24) expression by CD3/Foxp3 double immunoenzymatic using a anti-Foxp3 murine monoclonal antibody (Nuffield Department of Clinical Laboratory Sciences, Oxford University, UK) and CD3/CD8 double immunofluorescence, respectively. Treg cells and CD8 cells expression were reported as a percentage of CD3+ T cells. RORγt (for Th17) and Foxp3 mRNA were measured using real-time PCR. Results: Median age (n=116) was 62 years, 65.5% were hepatitis B+ (n=76), 4.3% were hepatitis C+ (n=5), 1.7% were both hepatitis B+ and C+ (n=2) and 28.4% were not virus-related (n=33). Treg numbers were significantly higher in all 116 HCC (median 9.3% of CD3+ T cells) compared to paired adjacent liver (median 1.9%) (p<0.001). Conversely, CD8+ T cell numbers were significantly lower in 24 HCC (median 21.1%) vs paired liver (median 49.5%) (p<0.001). Stage 1 and II HCC patients (n=24) with superior overall survival (= 6 years) compared with stage I and II patients (n=29) with inferior survival (≤ 1 year) had a significantly higher Treg frequency (median 10.9% versus 8.4%) (p=0.035). Stage I and II HCC patients (n=66) who were relapse-free at ≥ 1 year vs Stage I and II HCC patients (n=21) who were relapse-free at ≤ 0.5 years had higher Treg frequency (median 10.2% vs 6.8%) (p = 0.005). Hepatitis B+ HCC patients (n=76) had significantly higher Treg (median 10.2%) compared to non-viral associated HCC patients (n=33) (p=0.013). No correlation was seen between ROR and foxp3 mRNA. ROR mRNA was over-expressed (> 1 fold) in 20 (54%) HCC (analysis ongoing). Conclusions: Treg expression was significantly higher in HCC compared to paired liver. Increased Treg frequency predicts for a superior relapse-free and overall survival in HCC. No significant financial relationships to disclose.
Clinical and pathologic factors associated with development of hepatocellular carcinoma in patients with hepatitis virus-related cirrhosis: A long-term follow-up study
Authors: Morales-Espinosa D. , Martínez-Velasco A. , Cerón-Lizárraga T. , Rosas-Camargo V. , Rodríguez-Díaz J. L. , Flores- Estrada D. , Gamboa-Domínguez A. , Arrieta O. 
Published: March 2020

4646 Background: Hepatocellular carcinoma (HCC) represents >90% of primary liver neoplasms and develops mainly in patients with liver cirrhosis. Risk factor identification for development of HCC in patients with cirrhosis is of great relevance due to its high incidence and poor prognosis when detected at advanced stages. The aim of our study was to identify HCC development-associated risk factors in a cohort of patients with hepatitis virus-related chronic liver disease and cirrhosis. Materials and Methods: Patients with diagnosis of hepatitis virus-related cirrhosis from January 1980 to January 2000 were included. Patients were followed with abdominal US and determination of AFP levels, physical examination, and biochemical tests every 3–6 months. The endpoint in this study was defined as development of HCC. Liver histology was evaluated according to the METAVIR. Results: 282 patients met the inclusion criteria; most (86%) had a serologic diagnosis of hepatitis C virus, and only 14% had hepatitis B virus at the time of diagnosis of cirrhosis, while 56 and 37% were classified as Child A and B, respectively; only 7% as Child C. Histological activity was mild in 59% of patients; moderate and severe in 41%. Mean annual incidence was 1.87%; 22 and 35% of patients developed HCC at 10 and 15 years of follow-up, respectively. Diagnosis of HCC was made by histopathology in 37% and by tumoral lesion-associated AFP elevation confirmed by imaging studies in 63%. In multivariate analysis, 3 variables were associated with HCC: moderate to severe histological activity; platelet count <105 103/mm3, and alpha- fetoprotein >5 ng/mL. We divided patients into two groups according to regression coefficient: low and high-risk; patients assigned to the low-risk group showed 5, 10, and 15-year HCC incidences of 3.4, 6.4, and 6.4%, respectively, in contrast to patients from the high-risk group, who showed incidences of 17.8, 33.5, and 56.8%, respectively. Conclusions: We found three HCC-associated variables: histological activity; platelet count and alpha-fetoprotein levels. Patients considered as high-risk for developing hepatocellular carcinoma must be considered candidates for closer follow-up. No significant financial relationships to disclose.
Concomitant and adjuvant androgen deprivation (ADT) with external beam irradiation (RT) for locally advanced prostate cancer: 6 months versus 3 years ADT—Results of the randomized EORTC Phase III trial 22961
Authors: Bolla M. , van Tienhoven G. , de Reijke T. M. , van den Bergh A. C. , van der Meijden A. P. , Poortmans P. M. , Gez E. , Kil P. , Piérart M. , Collette L. ,   EORTC Radiation Oncology and Genito-Urinary TractCancer Groups
Published: March 2020

5014 Background: After EORTC trial 22863, 3 years of endocrine treatment has become standard adjuvant treatment to RT for locally advanced prostate cancer. EORTC 22961 tests if similar survival can be achieved in patients who underwent EBRT (to 70 Gy) and 6 months of combined ADT without further ADT (SADT arm) as in patients with 2.5 years of further treatment with luteinizing hormone-releasing hormone agonist monotherapy (LADT arm). Methods: Eligible patients had T1c-2b N1–2 or pN1–2, or T2c-4 N0–2 (UICC 1992) M0 prostate cancer with PSA <150ng/ml. Non-inferior survival was defined as a morality hazard ratio (HR) = 1.35 for SADT vs LADT. Non inferiority at 80% power and 1-sided a=0.05 required 275 deaths. A stopping boundary was applied at 1-sided a=0.018. Results: 970 patients were randomized (483 SADT and 487 LADT). At 5.2 years median follow-up, 173 patients had died (100 vs 73). An Independent Data Monitoring Committee recommended disclosure of results based on an interim analysis showing futility. Patient characteristics were well balanced: median age 69 years, WHO PS 0 in 83.4%, most patients had T2c-T3 N0 disease. Progression (mostly biochemical and/or bone progression) occurred in 220 cases (159 on SADT vs 61 on LADT) and was treated by secondary hormonal manipulation. The 5-year overall survival rate was 85.3% on LADT and 80.6% on SADT (HR=1.43, 96.4% CI: 1.04–1.98), and failed to prove non-inferiority. The 5-year clinical progression-free survival rate was 81.8% on LADT versus 68.9% on SADT arm and the 5-year biochemical progression-free survival rate was 78.3% on LADT versus 58.9% on SADT, indicating inferiority of SADT with HR=1.93 and HR=2.29, respectively. Conclusions: The study was designed to demonstrate non-inferior survival with 6 months ADT compared to 3 years adjuvant ADT after irradiation for patients with locally advanced prostate cancer, but observed survival data indicate that non-inferiority cannot be confirmed. Progression-free survival was also shorter on SADT. No significant financial relationships to disclose.
Results of a phase III randomized controlled trial of the safety and efficacy of atrasentan in men with nonmetastatic hormone-refractory prostate cancer (HRPC)
Authors: Nelson J. B. , Chin J. L. , Love W. , Schulman C. , Sleep D. , Qian J. , Steinberg J. , Hintzman P. , Dawson M. , Carducci M. 
Published: March 2020

5018 Introduction: Atrasentan is a potent oral, selective endothelin A receptor antagonist with biological activity in patients with HRPC. This randomized phase III trial of atrasentan vs placebo was conducted in 941 men with nonmetastatic HRPC whose prostate-specific antigen (PSA) was rising despite adequate androgen suppression. Methods: 467 patients were randomized to receive atrasentan 10 mg and 474 patients were randomized to receive placebo daily. Primary efficacy endpoints were time to disease progression (TTP) and progression-free survival, with progression defined as the onset of metastases. Secondary endpoints were overall survival, time to PSA progression, change from baseline in bone alkaline phosphatase (BAP), and PSA doubling time (PSADT). Results: In the intent-to-treat population, median TTP was 764 days with atrasentan and 671 days with placebo (hazard ratio [HR], 0.915; G1,1 P=0.288). More placebo- treated patients (267, 56.3%) than atrasentan-treated patients (227, 48.6%) experienced disease progression. Overall, 278 patients (29.5%) discontinued before reaching a protocol-defined endpoint (155, 40.8% US vs 123, 21.6% non-US). More placebo-treated patients (210, 44.3%) than atrasentan-treated patients (169, 36.2%) experienced new skeletal lesions. Median survival was 1,477 days for the atrasentan group and 1,403 days for the placebo group (HR, 0.909; G1,1 P=0.176). Mean change from baseline to final BAP was -1.51 IU/L with atrasentan compared with +2.20 IU/L with placebo (P<0.001). PSADT was lengthened with atrasentan relative to placebo (P<0.031). The incidence of peripheral edema, nasal congestion, headache, dyspnea, anemia, and heart failure was significantly greater in the atrasentan group (P<0.05). Most of these events were mild and nonserious and did not result in study discontinuation. Conclusions: Data from this study did not show a statistically significant difference in time to progression between atrasentan and placebo. However, the high discontinuation rate, especially among US patients, may have compromised the ability of the study to accurately determine the treatment effect of atrasentan in this population. No significant financial relationships to disclose.
Survival and secondary malignancy rates for adjuvant radiation therapy versus observation in stage I testicular seminoma: A Surveillance, Epidemiology, and End Results (SEER) analysis
Authors: Vudarla N. , Jawed I. , Kaya H. , Tward J. D. , Macdonald O. K. , Martincic D. , Gaffney D. K. , Shivnani A. T. , Odom- Maryon T. L. , Lee C. M. 
Published: March 2020

5020 Background: The standard adjuvant treatment for men with stage I testicular seminoma remains controversial within the literature. We analyzed survival and secondary malignancy rates in men with stage I seminoma who underwent adjuvant radiation therapy (RT) or observation (OB) following orchiectomy. Methods: Data was obtained from the Surveillance, Epidemiology, and End Results program (SEER) of the U.S. National Cancer Institute from 1973 - 2003. The primary end points were overall survival (OS) and cause-specific survival (CSS). Multivariate Cox regression models were utilized to study the significance of clinical variables: age at diagnosis, laterality of primary disease, race (white, black, American Indian, Asian/pacific islander) and radiation group. Standardized incidence ratios (observed-to-expected [O/E] ratio) and absolute excess risks of secondary malignancies were also assessed for each subgroup. Results: Out of 6,764 patients eligible for analysis, 5,265 were treated with RT and 1,499 with OB. After a median follow up of 7.6 years, the 5-, 10- and 20- year OS rates for the RT versus OB were 97.9 vs. 95.0; 92.2 vs. 92.2; and 83.6 vs. 84.1 (p= 0.005), respectively. The CSS rates for the same time periods were 99.6 vs. 98.7; 99.2 vs. 98.7; and 99.2 vs. 98.7 (p= 0.002), respectively. Adjuvant RT was associated with improved CSS on multivariate analysis with HR 0.37 (CI 0.19–0.70, p= 0.002). Overall, 312 patients developed secondary malignancies which was significantly higher than the endemic rate (O/E 1.43, p<0.05). RT patients had an increased rate of secondary malignancies when compared with the OB population (O/E 1.93, p<0.05). RT population were at excess risk for contralateral testicular, pancreatic, and hematologic malignancies (p<0.05). Conclusions: Within this large United States population analysis, adjuvant RT was associated with improved CSS for men with stage I testicular seminoma. The incidence of secondary malignancies was also found to be significantly increased for the RT group. Further studies are needed to determine if modern RT techniques and field-size reductions may lead to improvements in the therapeutic ratio. No significant financial relationships to disclose.
Sunitinib versus interferon-alfa (IFN-α) as first-line treatment of metastatic renal cell carcinoma (mRCC): Updated results and analysis of prognostic factors
Authors: Motzer R. J. , Figlin R. A. , Hutson T. E. , Tomczak P. , Bukowski R. M. , Rixe O. , Bjarnason G. A. , Kim S. T. , Chen I. , Michaelson D. 
Published: March 2020

5024 Background: In a randomized phase III trial of patients (pts) with mRCC, sunitinib demonstrated a significant improvement in progression-free survival (PFS) and objective response rate (ORR) compared to IFN-a as first-line therapy (Proc ASCO 2006;24:2s [Abstract LBA3]). We present the most recent data from this trial and an analysis of prognostic factors. Methods: Untreated pts with clear-cell mRCC were randomized 1:1 to receive either sunitinib (repeated 6-week cycles of 50 mg/day orally for 4 weeks, followed by 2 weeks off treatment) or IFN-a (9 MU given subcutaneously three times weekly). The primary endpoint was PFS. Results: A total of 750 pts were randomized: 375 to sunitinib, 375 to IFN-a. The median duration of treatment is 11 months (range: <1–25) for sunitinib vs. 4 months (range: <1–22) for IFN-a. The updated ORR by investigator assessment is 44% (95% CI: 39, 49) for sunitinib vs. 11% (95% CI: 8, 15) for IFN-a (p <0.000001), including 4 complete responses for sunitinib and 2 for IFN-a. The median duration of response in the sunitinib group (n=165) is 12 months (95% CI: 10, 14) vs. 10 months (95% CI: 8, 17) in the IFN-a group (n=43). The median PFS is 11 months (95% CI: 10, 11) for sunitinib vs. 4 months (95% CI: 4, 5) for IFN-a. The median PFS for pts with 0 risk factors is 14 months (95% CI: 11, 16) for sunitinib vs. 8 months (95% CI: 7, 10) for IFN-a; 9 months (95% CI: 8, 11) vs. 4 months (95% CI: 4, 4), respectively, for pts with 1- 2 risk factors; 4 months (95% CI: 2, 10) vs. 1 month (95% CI: 1, 2), respectively, for pts with =3 risk factors. The sunitinib benefit in PFS extends across all MSKCC prognostic risk factor groups (HR=0.488; 95% CI: 0.406, 0.586). The baseline features that predict longer PFS (by investigator assessment) for the sunitinib group are hemoglobin =LLN (p=0.0043), corrected calcium =10 mg/dL (p=0.001), ECOG score of 0 (p=0.0005), number of metastatic sites 0 or 1 (p=0.0064), and time from diagnosis to treatment =1 yr (p=0.0002). Conclusions: Sunitinib is a reference standard for first-line treatment of mRCC, with significant improvement in PFS and ORR compared to IFN-a. The benefit of sunitinib extends across all subgroups of pts with mRCC. Previously defined MSKCC risk factors for mRCC predict longer PFS with sunitinib. No significant financial relationships to disclose.
Randomized phase II trial of first-line treatment with sorafenib versus interferon in patients with advanced renal cell carcinoma: Final results
Authors: Szczylik C. , Demkow T. , Staehler M. , Rolland F. , Negrier S. , Hutson T. E. , Bukowski R. M. , Scheuring U. J. , Burk K. , Escudier B. 
Published: March 2020

5025 Background: This trial investigated the efficacy and safety of sorafenib (SOR) vs interferon (IFN) in treatment-naïve patients with clear-cell renal cell carcinoma (RCC). Methods: Previously untreated patients with advanced RCC were randomized to continuous oral SOR 400 mg bid or IFN 9 million units tiw (part 1), with an option of dose escalation to SOR 600 mg bid or crossover from IFN to SOR 400 mg bid upon disease progression (part 2). The primary endpoint was progression-free survival (PFS). Results: Baseline characteristics (ITT, n=189) were similar in SOR (n=97) and IFN (n=92) groups. In the IFN arm, 90/92 patients received treatment; 56 had disease progression, of which 50 crossed to SOR. All 97 patients in the SOR arm received SOR 400 mg bid; 65 had disease progression, of which 44 were dose escalated to 600 mg bid. In part 1, 5% vs 9% patients had complete/partial response, disease control rate (complete/partial response + stable disease) was 79% vs 64%, and median PFS was 5.7 months (CI: 5.0–7.4 months) vs 5.6 months (CI: 3.7–7.4 months) for SOR vs IFN, respectively. Progression-free rates for SOR vs IFN were 90.0% vs 70.4%, 45.9% vs 46.5%, and 11.5% vs 30.4% at 3, 6, and 12 months, respectively. A total of 11% vs 15% of patients receiving SOR or IFN, respectively, discontinued due to adverse events. Overall, the incidence of adverse events was similar between both treatment arms, although skin toxicity (rash and hand-foot skin reaction) and diarrhea occurred more frequently in the SOR group, and flu-like syndrome occurred more frequently in the IFN group. In part 2, median PFS was 5.3 months (CI: 3.6–6.1 months) in patients (n=50) who crossed from IFN to SOR. The median PFS for patients (n=44) with dose escalation to 600 mg bid was 3.6 months (CI: 1.9–5.3 months). The 600 mg bid dose was well tolerated. Conclusions: Although the primary endpoint (PFS) was not reached, SOR showed activity in first-line treatment of RCC based on disease control rate. PFS benefit was observed in patients who crossed to SOR 400 mg bid after progression on IFN. Patients who were dose escalated to 600 mg bid after progression had disease stabilization for a further 3.6 months. Further analyses of possible benefit from SOR dose escalation are required in a larger number of patients. [Table: see text]