bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of response assessed by RECIST and WHO criteria to neoadjuvant chemotherapy in locally advanced gastric cancer patients
Authors: Park S. R. , Lee J. S. , Kim Y. W. , Choi I. J. , Ryu K. W. , Lee J. H. , Lee J. Y. , Park Y. L. , Park S. Y. , Park Y. I. , Kim N. K. 
Published: August 2020

e15647 Background: In metastatic gastric cancer, the response to chemotherapy is assessed by RECIST or WHO criteria according to the change of tumor size. There are no data, however, on the usefulness of those criteria in evaluating tumor response in the setting of neoadjuvant chemotherapy. The aim of this study was to evaluate the relationship between tumor response to neoadjuvant chemotherapy-as assessed by RECIST and WHO criteria-and clinical outcome in locally advanced gastric cancer (LAGC) patients. Methods: This study recruited LAGC patients who, from January 2003 through November 2005, entered the neoadjuvant arm of prospective randomized phase II trials comparing neoadjuvant chemotherapy to adjuvant chemotherapy. LAGC was defined as stage III or IV (M0) disease based on computed tomography (CT) according to the Japanese Classification of Gastric Carcinoma. Patients with measurable lesions received 3 cycles of neoadjuvant chemotherapy consisting of docetaxel (36 mg/m2) and cisplatin (40 mg/m2) on days 1 and 8 every 3 weeks, followed by surgery. Results: After chemotherapy, 40 (95%) patients underwent surgery and the remaining 2 patients showed new distant metastasis on CT scan. Thirty-five (83%) patients had curative R0 resection. Twenty-eight (67%) patients had a clinical response to neoadjuvant chemotherapy according to RECIST/WHO criteria. Although R0 resection rate (93% vs 64%, P = 0.03), median relapse-free survival (RFS) (43.2 vs 7.5 months, P = 0.14), and overall survival (OS) (not reached vs 27.0 months, P = 0.10) were better in responders than non-responders, they did not differ significantly in the subgroup that subsequently underwent surgery. When we redefined the decrease in tumor size judged as a response by RECIST (≥60% rather than ≥30%) and WHO (≥75% rather than ≥50%) criteria, response correlated significantly with both RFS (P = 0.03) and OS (P = 0.02). Conclusions: In the neoadjuvant setting, which frequently involves smaller measurable lesions than the metastatic setting, larger changes in tumor size than those specified by RECIST and WHO criteria are needed to predict postoperative outcome. No significant financial relationships to disclose.
Incidence of therapy-related leukemia following chemoradiotherapy for esophageal cancer
Authors: Tsujimura H. , Mimura N. , Ise M. , Sakai C. , Shimada H. , Nagata M. , Kumagai K. 
Published: August 2020

e15663 Background: The combination of chemotherapy and concurrent radiotherapy (CRT) has recognized as a curative alternative for several stage of esophageal cancer. On the other hands, a sufficiently long survival time has increased treatment-related late toxicities. However, the frequency and the pathogenesis of secondary malignancies that is the most serious late-onset complication are still unclear. Methods: From July 2000 to March 2008, 348 patients with esophageal squamous cell carcinoma underwent CRT. All patients received chemotherapy consisting with nedaplatin (80 mg/m2, div day1) and fluorouracil (700 mg/m2, ci day 1–5) and concurrent long T field irradiation (2 Gy daily, up to 30 Gy). A hundred patients received a single course as the neoadjuvant setting. Two cycles of CRT as the definitive or palliative setting were administered in 248 patients. Median and average follow-up durations are 8 and 21 months (1 to 92), respectively. Results: Four patients, who achieved CR after CRT, developed leukemia. Case1, 60-yo-male, developed overt acute myeloid leukemia (AML) from myelodysplastic syndrome 48 months after CRT. Cytogenetic analysis showed complicated abnormalities including deletion 5q. Case2, 64-yo-male, developed AML M0 with t(9;22)(q34;q11) 44 months after CRT. Case3, 72-yo-male, developed Burkitt leukemia with t(8;14)(q24;q32) 19 months after CRT. Case4, 65-yo-male, developed myeloid crisis of chronic myelogenous leukemia with complicated abnormalities including t(9;22)(q34;q11) 48 months after CRT. Case 1 and 3 had localized disease and received single course of neoadjuvant CRT. Case 2 and 4 had advance disease and received 2 courses of CRT. All patients eventually died of leukemia. Conclusions: Since platinum and fluorouracil have shown relatively low chance of secondary neoplasm, our data demonstrates that the concurrent radiotherapy which involves massive bone marrow tissue may increase the risk of leukomogenesis. To this end, atypical cytogenetic abnormalities seen in the present cases give a new insight into the biology of therapy-related leukemia. Notably, this is the first report presenting the incidence of secondary leukemia by nedaplatin. No significant financial relationships to disclose.
S-1 monotherapy for the treatment of elderly patients with advanced gastric cancer
Authors: Lim J. , Kim J. , Yi H. , Kim H. , Lee M. , Kim C. 
Published: August 2020

e15671 Background: Elderly patients have often been excluded from clinical trials and only limited data are available regarding treatment of these patients. The efficacy of S-1 chemotherapy for elderly patients with advanced gastric cancer (AGC) is not well investigated. The aim of this study is to evaluate the efficacy and safety of S-1 monotherapy in elderly patients with AGC to whom conventional chemotherapy is difficult to deliver. Methods: From January 1, 2007 to August 31, 2008, a total of seventeen patients older than 70 were given S1 monotherapy. They received S-1 at a dose of 40mg/m2 BID either every 3 weeks (2 weeks on, 1 week off) or every 6 weeks (4 weeks on, 2 weeks off). Response was assessed according to RECIST criteria. Results: The patients consisted of 11 men and 6 women whose median age was 77 years (range: 71–83) with their performance status in 1 to 2. Five patients had recurrent AGC and the other 12 patients metastatic AGC at the time of diagnosis. Total 89 cycles of S-1 chemotherapy were given (median 4 cycles, range 2–12). Fifteen patients were evaluable for response because of early death in 2 patients. Response rate was 17.6% (95% Condifence Interval, 0 to 35.7); Complete remission in 0, partial remission in 3 (17.6%) and stable disease in 5 patients (29.4%). At a median follow up of 9.7 months (range: 8–11.4), median progression free survival was 5.1 months (range: 3.5–6.7) and overall survival was 9.5 months (range: 5.6–15.5). Most of the adverse effects of S1 monotherapy did not extend beyond grade 3. Grade 3 or 4 non- hematologic toxicities were not frequent and were easily manageable except in two, one of whom died of neutropenic sepsis and the other who died of subdural hemorrhage in grade 4 thrombocytopenia. Conclusions: S1 chemotherapy showed modest efficacy in elderly patients with AGC. The hematologic toxicity should be cautiously monitored in these elderly patients to avoid fatal events. Further studies are warranted for optimal management of elderly patients with metastatic or recurrent AGC. No significant financial relationships to disclose.
Prevalence of depression, sleep-related disturbances, and anxiety and their effect on quality of life in patients with adenocarcinoma of the pancreas
Authors: Brown D. , Boyd A. , Henrickson C. , Hampton J. , Almani F. , Ben-Josef E. , Zalupski M. , Simeone D. , Taylor J. , Armitage R. , Riba M. 
Published: August 2020

e15678 Purpose: To evaluate the prevalence of depression, sleep related disturbances and anxiety and their effect on quality of life in patients with recently diagnosed adenocarcinoma of the pancreas who present to a multidisciplinary pancreatic cancer clinic. Methods: Cross-sectional and longitudinal psychosocial distress was assessed utilizing Personal Health Questionnaire 9 (PHQ9) to screen for depression and monitor symptoms during the course of care, the Penn State Worry Questionnaire (PSWQ) for generalized anxiety, and the Sleep Problems Questionnaire 4 (SPQ4)/ University of Michigan Sleep Questionnaire to monitor sleep symptoms. Patients were evaluated at their intake consultation and at subsequent follow up visits. Results: 24 patients (pts; mean age 66 years, 48% females) consented to participate during the 6 month pilot study with longitudinal follow up for 13. The PHQ9 scores on presentation revealed mild to moderate depressive symptoms in 54% (13 pts) of pts and moderately severe depressive symptoms in only 8% (2 pts). A minority (2 pts, 8%) had PSWQ scores characteristic of an anxiety disorder, while 33% (8 pts) had moderate anxiety scores. Only 3 pts (12.5%) scores revealed a clear sleep problem; 10 pts, (41.67%) had no sleep problem and 10 pts had a potential sleep problem. Due to the limited follow up, a statistical difference in scores over time was not observed. Conclusions: Our results indicate that mild to moderate depressive symptoms, anxiety and potential sleep problems are common in patients referred to a multidisciplinary pancreatic cancer clinic. Moderately severe depressive symptoms, severe anxiety and clear sleep problems are not as prevalent as is generally believed. To better characterize the relationship of depression (and potential causes) with pancreatic cancer, additional prospective longitudinal studies are needed. No significant financial relationships to disclose.
HER-2/Neu overepression in gastric cancer
Authors: Vergara R. , Torrazza I. , Castillo Fernandez O. 
Published: August 2020

e15679 Background: Gastric cancer is one of the most frequent causes of cancer-related deaths in the world.Overexpression of human epidermal growth factor receptor 2 (HER-2) has been shown to be a significant negative prognostic variable, with estimates ranging from 6- 35%. This is the first study done in our country regarding HER-2 overexpresion in gastric cancer. Methods: 90 cases with histologic diagnosis of gastric cancer were reviewed, in the period between October 2007 and July 2008. Formalin-fixed paraffin- embedded gastric cancer specimens were tested for HER-2 status using Herceptest (Dako). They were analyzed with HER-2 scores for gastric cancer. Other parameters evaluated were: demographic, clinical, histological characteristics, and treatment administrared. Results: The average age of our patients was 60.3 ± 15.8 years, with similar gender distribution. The more frequent symptoms of presentation were loss of weight (68.9%) and dyspepsia (58.9%). The most frequent anatomical location was the antrum (32%). HER-2 overexpression was 5.6% (four cases of intestinal type and one case of diffuse type). 63.3% of the patients presented with clinical stage IV, which is associated with worse survival (p< 0.001). 40% of the patients underwent complete surgical excision of the neoplasia, from which 44% received adjuvant chemotherapy and radiotherapy. 52.2% of the patients had already died when developing this study. Conclusions: The majority of our patients presented with advange stage at the time of diagnosis, HER-2 overexpression was 5.6%. There was no statistical significance when comparing it with the histological type, nor survival (p= 0.086). No significant financial relationships to disclose.
Treatment outcome and survival for patients (pts) with sarcomatoid-variant metastatic renal cell carcinoma (RCC): Memorial Sloan-Kettering Cancer Center (MSKCC) experience
Authors: Molina A. M. , Tickoo S. K. , Ishill N. , Trinos M. J. , Schwartz L. H. , Russo P. , Feldman D. R. , Patil S. , Motzer R. J. 
Published: August 2020

e16017 Background: Sarcomatoid-variant represents a spindle cell phenotype of RCC that can be present in any subtype, usually showing aggressive biological behavior. MSKCC experience was studied to provide data on outcome and survival to systemic therapy for metastatic, sarcomatoid-variant RCC. Methods: Clinical features, treatment outcome and survival were reviewed in 63 pts with sarcomatoid-variant metastatic RCC from a database of 650 pts treated at MSKCC with systemic therapy (cytokines, anti-angiogenesis targeted therapy and chemotherapy). Response to therapy, progression-free survival (PFS), and overall survival (OS) was determined for pts based on their first treatment at MSKCC. The percentage of sarcomatoid component in the tumors was assessed. Results: Histology subtypes with sarcomatoid-variant among the 63 pts included 46 clear cell, 5 papillary, 5 chromophobe, 1 collecting duct, and 6 unclassified. 60 pts had prior nephrectomy. MSKCC risk group distribution was 37% good risk, 59% intermediate risk, and 5% poor risk. 34 pts received targeted therapy (29 sunitinib, 3 sorafenib, 2 temsirolimus), 20 pts received cytokine therapy (19 interferon, 1 interleukin) and 9 received other therapies. 5/63 pts achieved an objective response: 1/19 to interferon and 4/29 to sunitinib. In 63 pts, median PFS was 3 months (95% CI 2–4) and median OS was 10 months (95% CI 8–14). Differences in PFS were observed based on therapy (sunitinib vs. all other) and histology (clear cell vs. non-clear cell). The median PFS for sunitinib therapy was 4.4 months (95% CI 2.2–6.7) versus 2 months (95% CI 1.7–2.7) for all other therapies (p = 0.02); and 3 months (95% CI 2.3–4.5) for clear cell versus 1.6 months (95% CI 1.0–2.1) for non-clear cell histology (p = 0.007). In a subset (n = 31) with available specimen, the median % sarcomatoid content was 20% (range 2%-100%). No difference in PFS or OS was observed according to % sarcomatoid content. Conclusions: Metastatic sarcomatoid-variant RCC is associated with a poor prognosis. Sunitinib resulted in a modest response rate and longer PFS versus other therapies. Studies to assess outcome, characterize tumor biology, and develop novel treatment strategies are warranted. [Table: see text]
Outcome of patients (pts) with metastatic renal cell carcinoma (mRCC) treated with systemic therapy without cytoreductive nephrectomy (CN)
Authors: Richey S. L. , Culp S. H. , Wood C. G. , Corn P. G. , Jonasch E. , Tannir N. M. 
Published: August 2020

e16035 Background: Targeted therapies (TT) have replaced cytokines in the management of pts with mRCC. CN has been incorporated in the management of pts with mRCC but many pts are not suitable candidates for CN. The median overall survival (OS) time of pts treated with interferon alfa (IFN-α) without CN was 7.8 months (mos) [Flanigan et al. Journal of Urology 2004]. The median OS time for pts with mRCC treated with TT sequentially without CN is unknown. Methods: We retrospectively reviewed the medical records of pts with mRCC who did not undergo CN and who received one or more TT (bevacizumab, sorafenib, sunitinib, or temsirolimus) sequentially for at least one month with or without chemotherapy (gemcitabine + capecitabine or 5-FU). We calculated OS time from date of diagnosis until date of death or last follow up. We excluded pts who had embolization, radiofrequency ablation or cryotherapy of the primary tumor. Results: We identified 88 pts between Jan 2002 and Dec 2007. Median follow-up time is 9.7 mos (range: 1.2–49.2). Median OS time for all pts is 10.7 mos (95% CI: 7.6–15.4). 55 pts (62.5%) had clear-cell and 33 (37.5%) had non-clear cell histology, with median OS times of 15.1 mos (95% CI: 9.6–17.7) and 7.4 mos (95% CI: 4.4–13.0), respectively. ECOG performance status (PS) at time of diagnosis was correlated with OS (HR 1.54; 95% CI: 1.16–2.05; p<0.01). Pts with PS 0, 1, 2, and 3 had median OS times of 22.8 mos (95% CI: 5.7,*), 16.5 mos (95% CI: 8.1–24.7), 7.6 mos (95% CI: 5.7–11.9), and 7.1 mos (95% CI: 3.3–9.6), respectively. Pts with clinical evidence of lymph node (LN) involvement had worse outcome,with median OS time of 7.6 mos (95% CI: 5.6–9.8) versus 17.2 mos (95% CI: 9.8–35.5) for pts without clinical evidence of LN involvement. Conclusions: In this analysis, median OS time for pts with mRCC treated in the modern era with TT without CN is superior to historical experience with IFN- α.Compromised PS, LN involvement, and non-clear cell histology were associated with worse outcome. This data is useful in the design of randomized trials investigating the role of CN in mRCC. [Table: see text]
Cardiovascular events (CVEs) associated with tyrosine kinase inhibitor (TKI) therapy in patients with metastatic renal cell carcinoma (mRCC) at a regional cancer center
Authors: McGhie J. , Mackenzie M. J. , Winquist E. , Ernst S. , Sax L. , O'Brien P. 
Published: August 2020

e16040 Background: Recent studies suggest the incidence of CVEs associated with TKIs has been underestimated. Phase III trials have reported low incidences of heart failure, cardiac ischemia and hypertension. A recent observational study reported that one third of patients taking sunitinib or sorafenib experienced a cardiovascular event often without symptoms. We assessed the incidence of CVEs in mRCC patients who received TKIs at our centre. Methods: Eligible mRCC patients were identified from a mRCC database between January 2006 and November 2008. Data was retrospectively extracted including age, sex, diagnosis, histology, past cardiac history, cardiac risk factors, number and type of TKI regimens, and CVEs. A CVE was defined as unexplained death, acute coronary syndrome (ACS), heart failure, or arrhythmia requiring intervention. We also identified any new or exacerbated cases of hypertension after the start of TKI therapy, as a CVE. Results: Eighty-five eligible patients were identified. Average age was 61 years (range, 23–78), 72% were male and 80% were clear cell in origin. A total of 31 CVEs occurred in 28 patients (33%). These events occurred at a median of 5 weeks of TKI therapy (range, 1 - 64 weeks). There were 8 cases of ACS, 2 of heart failure, 2 of arrhythmia, and 3 unknown causes of death. Only 2 of these particular CVEs were associated with new or increased hypertension. There were 16 cases of hypertension alone. Those who had CVEs had a higher mean number of cardiac risk factors. They were also more likely to have an echocardiogram during treatment, and less likely to receive sorafenib following sunitinib. Conclusions: Our study suggests a lower rate of CVEs than recent studies, but the true rate may be underestimated, as routine cardiac studies were not performed in all patients. Rational surveillance strategies for patients receiving TKI therapies should be developed. Prospective trials should address predictive and prognostic factors for CVEs. [Table: see text] [Table: see text]
Vaccination with survivin and PSMA-derived peptides for controlling biochemical recurrence in prostate cancer: A pilot study
Authors: Valdagni R. , Marrari A. , Squarcina P. , Villa S. , Filipazzi P. , Salvioni R. , Rancati T. , Asioli M. , Parmiani G. , Rivoltini L. 
Published: August 2020

e16042 Background: A significant percentage of patients (pts) progress after first line treatment of prostate cancer (PCa). We present preliminary results of pilot study using a multiple peptide-based anti-tumor vaccine. Methods: A phase I-II trial of vaccination (vax) with HLA-A*0201-restricted peptides from PSMA and Survivin was carried out in 20 pts with b-failure after surgery or radiotherapy (mean pre-vax PSA: 1.83 ng/ml). Vax consisted of two peptides from PSMA (PSMA4–12 and PSMA711–719) and one from Survivin (SVV96–104/97M) given by 4 fortnightly (priming) and 4 monthly administrations (boosting). To selectively eliminate regulatory T cells (Treg) and possibly enhance immunization, peptides were preceded by low dose cyclophosphamide (CTX, 300 mg/mq, i.v.). Antigen (Ag) and tumor-specific T cell responses were extensively monitored in peripheral blood together with CD4+CD25+Foxp3+ Treg frequency. PSA trend was also registered. Results: Vax was well tolerated. Most pts (19/20) showed a significant increase of SVV96–104/97M-specific T cells (mean 14 in pre-vax vs 170 in post-vax PBMC), while response to PSMA was achieved in about half of the pts and only to PSMA711–719 peptide (mean 12 in pre-vax vs 86 in post-vax PBMC). Increments of HLA-A*0201/SVV96–104/97M or PSMA711–719 multimer+ CD8+ T cells were induced in 50 and 35% pts, respectively. Vax-induced Ag-specific T cells displayed however limited cross-reactivity with HLA-A*0201+ PCa cells. No effect of CTX on Treg frequency was observed. 6 pts had no biochemical response to vax and switched to hormonal therapy, while 14/20 exhibited a significant although transient PSA decrease during vax (11 in the priming phase and 3 in boosting). Conclusions: Peptide vax could rapidly enhance Ag-specific immune responses in most treated pts. However, the reduced ability of vax-induced Ag-specific CD8+ T cells to cross-recognize PCa cells, together with their low frequency in PBMC, could explain why PSA control was achieved only transiently and in strict dependence with vax administration. Anti- tumor vax represent a useful tool for controlling PCa biochemical recurrence in the absence of major side effects, but immunization protocols inducing efficient tumor cell killing still need to be identified. No significant financial relationships to disclose.
Differential protein expression profiling by iTRAQ-2DLC-MS/MS of human bladder cancer EJ138 cells transfected with the metastasis suppressor KiSS-1 gene
Authors: Grau L. , Ruppen I. , Gil M. , Piulats J. M. , Bellmunt J. , Ashman K. , Ecke T. , Sanchez-Carbayo M. 
Published: August 2020

e16043 Background: The use of isobaric tags for relative and absolute quantization (iTRAQ) followed by multidimensional liquid chromatography (LC) and tandem mass spectrometry (MS/MS) analysis is emerging as a powerful methodology for biomarker and drug target discovery. KiSS-1 is a metastasis suppressor gene reported to be involved in the progression of several solid neoplasias. The loss of KiSS-1 expression has been shown to be inversely correlated with increasing tumor stage and poor overall survival in bladder tumors. In order to identify the molecular pathways associated with the metastasis suppressor role of KiSS-1 in bladder cancer, we carried out a proteome discovery analysis using an iTRAQ approach. Methods: Bladder cancer cells (EJ138) were transiently transfected with a vector encompassing the full length KiSS-1 gene. Protein extracts collected after 24h and 48h transfection were fractionated, digested with trypsin and treated with iTRAQ reagents. The labelled peptides were separated through Strong Cation Exchange (SCX) and Reversed Phase LC and analysed by MALDI TOF/TOF MS. Several software packages were utilized for data analysis: ProteinPilot, Protein Center for gene ontology (GO) analysis and Ingenuity Pathway. Results: Comparative analysis among transfected, mock and empty vector exposed cells have identified more than 800 proteins with high confidence (>99%), showing high correlation rates among replicates (>70%). The involvement of the identified proteins in biological networks has served to characterize molecular pathways associated with KiSS-1 expression and to select critical candidates for validation analyses by Western Blot using independent transfected replicates. As part of complementary clinical validation strategies, inmunohistochemical analyses performed in metastatic bladder tumours spotted onto tissue microarrays (n = 175) have revealed the role of KiSS-1, ezrin and filamin in bladder cancer progression. Conclusions: Our proteomic study not only has served to reveal molecular mechanisms associated with the metastasis suppressor role of KiSS-1 in bladder cancer, but also to identify novel potential metastatic biomarkers for patients affected with bladder tumors. No significant financial relationships to disclose.