bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conditional survival in gallbladder carcinoma: Results from the SEER 11 dataset
Authors: Thomas C. R. , Fuller C. D. , Starling G. D. , Wang S. J. 
Published: March 2020

4130 Background: Traditionally, survival is reported as 5-or10-yr survival from diagnosis. However, the 5-yr probability of demise changes considerably with each year survived in many cancers. Clinicians may utilize conditional survival to estimate risk over time. Gallbladder cancer is a rare neoplasm with little extant data with regard to risk assessment for patients with one or more years survival post-therapy. The specific aim of this study is to assess the conditional survival of patients with gallbladder adenocarcinoma using data extracted from the Surveillance, Epidemiology, and End Results (SEER 11) Program. Methods: Cumulative observed survival rates were calculated by the life-table method using SEER data for 3744 patients with histologically confirmed gallbladder adenocarcinoma (diagnosed from 1973 to 2001). On the basis of the cumulative survival estimates, we derived the conditional survival, defined as the calculated probability of survival having already survived a specified number of years from diagnosis, with sub-stratification by extent of disease. Results: Conditional survival calculations reveal dismal 5-year survival at diagnosis (Figures 1 and 2), with increasing probability of survival per each year survived. However, conditional survival plateaus at approximately 60–70% at 4 years post-diagnosis, with little change in conditional survival until 10 years. Conclusions: This dataset represents the largest pooled data for gallbladder carcinoma, and is markedly larger than any given institutional series. Consequently, while imperfect, this data represents a useful estimate for patients with considerable post-diagnosis survival. Although the disease-free survival outcomes for patients with gallbladder adenocarcinoma remain low, for those patient surviving even 1 year post-diagnosis, conditional survival estimates increase rapidly. [Table: see text] No significant financial relationships to disclose.
New feasibility study design with hepatocellular carcinoma: A phase I/II study of TSU-68, an oral angiogenesis inhibitor
Authors: Kanai F. , Yoshida H. , Teratani T. , Sato S. , Tateishi R. , Obi S. , Yamashita M. , Kawabe T. , Shiina S. , Omata M. 
Published: March 2020

4145 Background: Hepatocellular carcinoma (HCC) is a devastating disease with limited treatment options at advanced stages. HCC is a highly vascular tumor in which angiogenesis contributes to its pathogenesis. TSU-68 is an oral anti-angiogenesis compound that blocks VEGFR-2, PDGFR, and FGFR. Methods: This is an open-label phase I/II study to characterize the safety, tolerability, pharmacokinetic (PK) profile and efficacy of TSU-68 at 800mg/po daily in adults with unresectable HCC. Patients (Pts) previously treated with surgery, radiofrequency ablation, transcatheter arterial embolization, chemotherapy, or radiotherapy were eligible. Pts were stratified into three groups based on hepatic function: level 1 (no cirrhosis), level 2 (Childs-Pugh A) or level 3 (Childs-Pugh B). The safety, tolerability and PK of TSU-68 were assessed sequentially from level 1 by enrolling 3 pts in each level. The response was evaluated based on RECIST. Results: 15 pts were enrolled: median age = 67 years (range 53–74 years), male/female = 11/4, cirrhosis/no cirrhosis = 12/3, HCV/HBV/alcohol = 12/2/1. 2 pts at level 3 who received 800 mg/d experienced DLTs (CTC grade 3 abdominal pain and ascites). The dose was reduced to 400 mg/d in an additional 3 pts at level 3 (no DLT observed). The most common adverse events were: hypoalbuminemia, diarrhea, abdominal pain, fever, and AST/ALT elevation. PK data from 12 pts (3 at level 1; 3 at level 2; 6 at level 3) indicated that the area under the curve (AUC) of TSU-68 was similar from level 1 to 3, and biologically active levels of TSU-68 could be reached at a dose of 400 mg/d. One pt had a partial response, 7 pts had stable disease (2 pts for over 12 months) and 7 pts had progressive disease. Tumor necrosis was observed in 8 pts. Conclusions: The study design based on hepatic function is useful to assess the safety of anti-tumor agent in pts with impaired liver function. A dose of 400 mg/d TSU-68 is well tolerated in pts with HCC. While the study is still on going, the preliminary results suggest that TSU-68 has anti-tumor activity against HCC. No significant financial relationships to disclose.
Endoscopic thermal ablation therapies for hepatocellular carcinoma; multi-center study
Authors: Sakaguchi H. , Seki S. , Iwai S. , Kadoya H. , Ido K. , Isoda N. , Tsuji K. , Teramoto K. , Suzuki M. , Kioka K. 
Published: March 2020

4147 Background: Differences of efficacy between radiofrequency ablation (RFA) and microwave coagulation (MWC) for hepatocellular carcinoma (HCC) is still unknown. So we performed multi-center study to assess factors contributing to survival among patients treated by endoscopic thermal ablation for single HCC. Methods: 396 patients in six institutions with single HCC who were firstly treated by endoscopic thermal ablation were enrolled in this study and assessed retrospectively. Among 396 patients, 347 were treated under general anesthesia and 49 were treated local anesthesia. 144 were treated by MWC and 252 were treated by RFA. 383 were ablated laparoscopically and 13 were done thoracoscopically. 230 HCCs were located superficial position of liver and 166 were deep position. Classification with Child-Turcotte-Pugh score, the Japan Integrated Staging score, and the Cancer of the Italian Program scoring system were performed. All patients were analyzed survival rates by Kaplan-Meier method and differences among groups were compared by the log-rank test. Results: Five year survival rates of all 396 patients were 63% and ten year survival rates were 42%. Differences between general and local anesthesia were not significant (p = 0.28). Differences between MWC and RFA were not significant (p = 0.77). Location of HCCs were not significant (p = 0.89). Differences among groups classified by Child-Turcotte-Pugh score were significant (p = 0.017). Classification by the Japan Integrated Staging score was not significant (p = 0.24). However, classification by the Cancer of the Italian Program scoring system were significant (p = 0.001). Conclusions: Endoscopic thermal ablation therapies for HCC was effective. Differences of efficacy between RFA and MWC were not found. No significant financial relationships to disclose.
Phase III intermittent MAB vs continuous MAB
Authors: Calais Da Silva F. M. , Calais Da Silva F. , Bono A. , Brausi M. , Whelan P. , Queimadelos A. , Portillo J. , Portillo J. , Kirkali Z. , Robertson C. 
Published: March 2020

4513 Background: Patients with locally advanced or metastatic prostate cancer cannot be cured with any of the therapeutic tools available today. Methods: After an initial induction treatment of three months, with CPA 200 mg for two week’s and then monthly depot injections of LHRH analogue (decaptyl) plus 200 mg of CPA daily in 766 patients with locally advanced or metastatic prostate cancer, 626 patients whose PSA decreased below 4 or to 80% below their initial value, were randomised to intermittent or continuous therapy. Results: Among the 314 patients on Intermittent therapy, 50% have been off therapy for at least 52 weeks following the initial LHRH therapy, 29% have been off therapy for over 36 months. For the 197 patients whose PSA went down to ≤ 2 ng/ml, the median time off therapy was 74 weeks. When these patients returned to therapy they had a median of 14 weeks of treatment, followed by a second period off therapy, median 70 weeks. Patients with PSA < 2 ng/ml have spent a median of 82% of their time receiving no therapy.After a median follow up of 51 months, 321 patients have died: 162 in the Intermittent arm compared to 159 in the Continuous arm (HR = 1.03 [95% confidence interval 0.83, 1.28; p = 0.79]). Estimated survival at 5 years was 53.8% in the Intermittent Group and 51.0% in the Continuous Group.Subjective or Objective progression was noted in 224 patients, 113 on the intermittent arm and 111 on the continuous arm with a hazard ratio of 1.09 (95% CI 0.84, 1.42), p=0.52. The main differences in quality of life between the two arms of the study were confined to sexual function.Sexual activity was significantly greater (p<0.01) in the intermittent arm with 41% of men reporting sexual activity at 9 months, 40% at 15 months and 35% at 21 months.The most commonly reported side effects were hot flushes, were more frequently among those on Continuous Therapy, 30% of continuous patients compared to 20% of intermittent patients, p < 0.01. Conclusions: There is no evidence that Intermittent therapy leads to a significantly elevated hazard of dying (p = 0.79) or to a greater subjective or objective progression (p = 0.52) and with less impact on quality of live and less medication, patients with PSA < 2 ng/ml on randomisation have spent a median of 82% of their time receiving no therapy. We think that intermittent therapy is an option to use in regular clinic. No significant financial relationships to disclose.
Medical Research Council trial of 2 versus 5 CT scans in the surveillance of patients with stage I non-seminomatous germ cell tumours of the testis
Authors: Mead G. M. , Rustin G. J. , Stenning S. P. , Vasey P. , Aass N. , Huddart R. , Sokal M. , Kirk S. 
Published: March 2020

4519 Background: Surveillance is a standard management approach for stage 1 non seminomatous germ cell tumours (NSGCT), yet there is no agreement on the number of CT scans that are required to detect relapses. A randomised trial of 2 versus 5 CT scans was performed to determine whether the number of scans influenced the prognostic group (J Clin Oncol 15:594–603, 1997) at relapse. Methods: Patients with clinical stage 1 NSGCT opting for surveillance were randomised to chest and abdominal CT scans at either 3 and 12 or 3, 6, 9, 12, and 24 months, with all other investigations (clinical exams, markers, chest X-rays) carried out at equal frequency in the two arms. 3/5 patients were allocated to the 2 scan schedule. 400 patients were required to exclude a 3% increase in the proportion of patients relapsing with IGCCCG intermediate or poor prognosis disease with 90% power at the 5% significance level (1-sided). Results: 247 patients were allocated to 2 CT scans and 167 to 5 CT scans. With a median follow up of 40 months 37 (15%) relapses have occurred in the 2 scan arm and 33 (20%) in the 5 scan arm. No patients were poor prognosis at relapse but 2 (0.8%) of those relapsing in the 2 scan arm were intermediate prognosis compared to 1 (0.6%) in the 5 scan arm a difference of 0.2% (90% CI −1.2%, +1.6%). The mean diameter of abdominal mass at relapse was 2.1 cm in the two scan arm and 2.2 cm in the five scan arm. After chemotherapy a residual mass was present in 35% in the 2 scan and 36% in the 5 scan arm. No deaths have been reported. Conclusions: This study can exclude with 95% probability an increase in the proportion of patients relapsing with intermediate or poor prognosis disease of more than 1.6% if they have 2 rather than 5 CT scans as part of their surveillance protocol. CT scans at 3 and 12 months after orchidectomy should be considered as the new standard and will be associated with a reduction in radiation exposure. No significant financial relationships to disclose.
[18F]-FDG-PET in germ cell tumors following chemotherapy: Results of the German multicenter trial
Authors: De Wit M. , Hartmann M. , Brenner W. , Weiβbach L. , Amthauer H. , Franzius C. , Kliesch S. , Krege S. , Heicappell R. , Bares R. , Bokemeyer C. 
Published: March 2020

4521 Background: The aim of this study was to evaluate the viability of residual masses following chemotherapy in patients (pts) with germ cell cancer (GCT) using FDG-PET. Methods: Pts with diagnosis of GCT at primary diagnosis or at relapse were included if residual masses (> 1 cm) were present following chemotherapy. 140 pts, 27 with primary extragonadal GCT, aged 15.7–59.2 (mean age: 32.7 years) treated in 18 centers were examined with concurrent FDG-PET and CT. FDG-PET was performed in fasting state. Images were reconstructed by filtered back projection. All PET-scanners were calibrated using the same phantom. The presented data are based on visual scan analysis. All pts underwent surgery for residual masses. Thus, all results were validated by histology. Results: Histology of the primary tumor included 20 seminoma and 109 NSGCT, while 11 pts had no primary histology. 88 pts (63%) had no persistent GCT. 120 pts (86%) demonstrated residual masses in retroperitoneal lymph nodes; in 56 pts (40%) residual masses were localized in the thorax and in 8 pts elsewhere (multiples possible). 40 pts (29%) presented active residual carcinoma and 54 (39%) presented residual teratoma (combination possible) following chemotherapy. Correct classification of the residual mass by FDG-PET was achieved in 79 of 140 (56%), while CT scans were correct in 58 of 140 pts (42%). 46 of 89 patients with a positive FDG-PET turned out to have viable tumor while in 36 out of 52 patients with a negative scan no lymph node metastases were found. FDG-PET turned out to show a sensitivity of 73% and specificity of 44%. Positive and negative predictive value (PPV, NPV) were 48% and 69% and accuracy 56%, respectively. In NSGCT 58 pts had no active tumor and 28 were true negative with FDG-PET resulting in a specificity of 47% and a NPV of 67%. 36 patients were true positive with a PPV of 54% and a sensitivity of 72%. Conclusion: FDG-PET for GCT following chemotherapy has a higher accuracy than CT, but sensitiviy is still too low to avoid subsequent resections in patients with NSGCT. [Table: see text] No significant financial relationships to disclose.
Efficacy and safety of sunitinib malate (SU11248) in bevacizumab-refractory metastatic renal cell carcinoma (mRCC)
Authors: Rini B. I. , George D. J. , Michaelson M. D. , Rosenberg J. E. , Bukowski R. M. , Sosman J. A. , Stadler W. M. , Margolin K. , Hutson T. E. , Baum C. M. 
Published: March 2020

4522 Background: Sunitinib malate (SU11248) is an oral, multitargeted tyrosine kinase inhibitor of the vascular endothelial growth factor receptor (VEGFR) family, platelet-derived growth factor receptor (PDGFR) and other related receptors. It has demonstrated anti-tumor activity in cytokine-refractory mRCC patients (pts). The activity of sunitinib in pts refractory to VEGF binding agents such as bevacizumab, however, has not been evaluated. It was hypothesized that tumor resistance to bevacizumab may be driven, in part, through pathways sensitive to inhibition by sunitinib. A phase II study evaluating the activity of sunitinib in bevacizumab-refractory mRCC was thus conducted. Methods: Pts with mRCC who demonstrated RECIST-defined disease progression within 3 months after bevacizumab-based therapy were treated with sunitinib (50 mg daily, 4 weeks of a 6-week cycle). Additional eligibility included measurable disease, clear cell histology, ≤ 2 prior systemic regimens, prior nephrectomy, performance status 0 or 1 and adequate organ function. The primary endpoint was objective response by RECIST criteria. A single-stage design was employed to test the null hypothesis that the true response rate is ≤ 5% versus the alternative hypothesis that the true response rate is ≥ 15%. Results: Accrual of 60 patients has been completed. Baseline characteristics include a median age of 59 years; 92% of pts had ≥ 2 metastatic sites and 23% had prior radiotherapy. Thirty-two of 60 pts enrolled are evaluable for response; 28 pts are too early for assessment. Twenty-six pts (81%) demonstrated some degree of tumor shrinkage, including, 4 pts (13%; 95% CI 4%, 29%) demonstrating an objective partial response. The most common treatment-related adverse events (AEs) included fatigue, diarrhea, dysgeusia, and nausea. Serious treatment-related AEs included fatigue, diarrhea, nausea and one fatal cerebral hemorrhage; 3 pts withdrew due to an AE. Conclusions: Sunitinib has substantial antitumor activity in bevacizumab-refractory mRCC pts, suggesting that sunitinib may inhibit signaling pathways involved in bevacizumab resistance. The precise mechanisms of response to sunitinib in bevacizumab-refractory tumors will require additional studies. [Table: see text]
Sorafenib plus interferon-α2b (IFN) as first-line therapy for advanced renal cell carcinoma (RCC): SWOG 0412
Authors: Ryan C. W. , Goldman B. H. , Lara P. N. , Beer T. M. , Drabkin H. A. , Crawford E. 
Published: March 2020

4525 Background: Sorafenib is a RAF and multiple receptor tyrosine kinase inhibitor active in RCC. IFN has modest activity in RCC and has immunologic, anti-angiogenic, and anti-proliferative effects. Sorafenib and IFN may simultaneously target anti-angiogenic and MAP kinase pathways, providing the basis for this phase II combination study. Methods: Eligible patients (pts) had metastatic or unresectable RCC with a clear cell component, no prior systemic therapy, performance status 0–1, measurable disease. Treatment: IFN 10 x 106 IU s.c. 3x/week and sorafenib 400 mg p.o. BID. Response assessment was performed q8 weeks. This was a single-stage trial with a planned sample size of 55. Primary endpoint was RECIST response rate. Results: Of 67 registered pts, 58 are eligible & evaluable. Pt characteristics: median age 61 years (42–84), male:female (40:18), prior nephrectomy 86%. MSKCC prognostic categories (42 pts) were good:intermediate:poor (28%:67%:5%). With a median follow-up of 6.5 months, 79% (46/58) of pts are alive, 41% (24/58) remain on treatment. Assessment of progression-free survival is premature. Overall response rate (53 pts) is 19% (95% CI: 9%, 32%) with CR 2% and PR 17% (9% confirmed, 8% unconfirmed). Toxicities affecting >50% of subjects were: fatigue, anorexia, diarrhea, nausea, rigors/chills, fever, anemia, leukopenia. Most common Grade 3+ toxicities were fatigue (24%), leukopenia (10%), anorexia (6%), diarrhea (6%), hyponatremia (6%). All pts experienced some toxicity, with 36 (62%) experiencing at least one Grade 3+ toxicity. Hand-foot syndrome, a common side effect of sorafenib, was seen in only 10% of pts. Conclusions: The overall response rate of 19% for the combination of sorafenib and IFN in advanced RCC is greater than expected with either IFN or sorafenib alone. Toxicity is typical of IFN and notable for minimal hand-foot syndrome. Further studies with this combination are warranted. [Table: see text]
Phase II trial of sorafenib plus interferon-alpha 2b (IFN-α2b) as first- or second-line therapy in patients (pts) with metastatic renal cell cancer (RCC)
Authors: Gollob J. , Richmond T. , Jones J. , Rathmell W. K. , Grigson G. , Watkins C. , Peterson B. , Wright J. 
Published: March 2020

4538 Background: Sorafenib is a VEGFR/PDGFR-β/Raf inhibitor that improves PFS in metastatic RCC with a RR of 2%. IFN-α improves OS in RCC with a RR of ≈10%. Methods: Based on the activity of sorafenib and IFN-α in RCC, a phase II combination trial was undertaken. Pts with RCC of any histology were eligible if they had received ≤1 prior treatment (excluding IFN-α). Treatment consisted of 8-wk cycles of sorafenib 400 mg po bid + IFN-α2b 10 MU sc tiw. Cycles were repeated until disease progression with 2-wk breaks between cycles permitted. This single-stage trial has a planned n = 40; primary objectives are RR and tolerability. Results: From November 2004-December 2005, 31 pts were enrolled. Pt characteristics included: median age 47, M/F: 23/8, PS 0/1: 25/6, clear cell/papillary: 24/3, no prior Rx/prior high-dose IL-2: 17/12, prior Nx: 26. Toxicities (n = 27) were mostly grade 1/2: fatigue (78%), anorexia (74%), rash (70%; 11% grade 3), diarrhea (67%), weight loss (63%), hypophosphatemia (59%; 33% grade 3), nausea (56%), neutropenia (48%; 19% grade 3), alopecia (44%), and oral mucositis (26%). Dose reductions of both agents for toxicity occurred in 58% of pts. The most common reasons for dose reduction were grade 3 rash or neutropenia and grade 2 fatigue or anorexia. Among 24 pts evaluable for response, the RR by RECIST criteria was 42% (38% PR, 4% CR). An additional 46% had stable disease for at least 1 cycle, including 8% with ≥20% regression. Responses were seen in lungs, pleura, kidney, liver, pancreas, and nodes. Three of the 10 responses occurred in patients who had failed prior high-dose IL-2. Conclusions: Sorafenib + IFN-α2b is a well-tolerated outpatient regimen with substantial antitumor activity in both untreated and IL-2-resistant metastatic RCC. Further investigation of this regimen in RCC is warranted. [Table: see text]
Hormonal status and the quality of life of testicular cancer survivors
Authors: Wiechno P. J. , Sadowska M. A. , Kubiak K. S. , Demkow T. , Kaminska J. 
Published: March 2020

4548 Background: Testicular cancer is a highly curable neoplasm and treated patients may potentially survive many decades. The aim of the study was to assess the rate of hormonal abnormalities among testicular cancer survivors and the effect of these changes on patients’ quality of life. Methods: Men with complete remission of testicular cancer lasting over 2 years were eligible. Patients completed State-Trait Anxiety Inventory (STAI), Hospital Anxiety and Depression Scale (HADS), Beck’s Depression Inventory (BDI), International Index of Erectile Dysfunction (IIEF), Sexual Functioning Questionnaire (SFQ) and rated their physical and psychological well-being, quality of life and relationship with partners. Levels of the following hormons were determined: testosterone, estradiol, thyreotropin, folicule stimulating hormone (FSH), luteinizing hormone (LH) and prolactin. Relations between hormone levels and questionaires results were analysed. Results: A total of 326 men were tested from November 2004 till December 2005. Median age was 37 years (range: 18–72). Median disease free survival was 59 months (range: 19–291). Only 24% of patients had all tested hormones within normal ranges. The most common of endocrine abnormalities were gonadotropins over normal (LH - 55% and FSH - 49% of cases) and lowered testosterone (15%). Percentage of patients with abnormal anxiety levels was 27% (STAI) and 28% (HADS), depression rate was 15% (BDI) and 18% (HADS), 40% of patients had erectile disfunction. Hormone levels and scores of the used scales corelated strongly with patients’ age, then a linear regression analysis was performed to exclude the influence of age factor. It was shown that higher depression levels in BDI are found amongst patients with elevated LH (p = 0.010) or FSH (p = 0.017). Men with higher than normal FSH were more anxious in STAI (p = 0.026). Patients with overnormal LH shown more sexual problems in SFQ (p = 0.030). Abnormal gonadotropins levels corelated with a deteriorated physical well-being (p = 0.028). Men with abnormal estradiol were more prone to erectile disfunction (p = 0.009). Conclusions: Hormonal abnormalities are frequent among testicular cancer survivors and have negative impact on the patients’ physical and psychological well-being as well as on their sexual functioning. No significant financial relationships to disclose.