bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiological data of cancer of the only cancer center of the western Black Sea region of Turkey
Authors: Engin H. , Ozdamar S. , Gun B. , Bahadir B. , Kertis G. , Numanoglu G. , Ustundag Y. , Kuzey G. 
Published: March 2020

16041 Background: 600 patients diagnosed as having cancer between years 2000–2005 at Zonguldak Karaelmas University were evaluated. Methods: All information pertaining to patient characteristics were retrieved from files of the Pathology and Medical Oncology Departments. Results: 383 (63,83%) were male and 217 (36,17%) were female. The most common malignancies among males are; prostate cancer 21,40 %, stomach cancer 14,62%, tumors of the bronchi and the lungs 12,10%, colorectal cancers 10,70%, skin tumors (non-melanoma 8,90%, melanoma 1,30%), malignancies of the lymphatic and hematopoietic system 7,83%, bladder cancer 6,52%, metastasis of unknown origin 3,40%, laryngeal cancer 2,61%, tumors of the hepatobiliary system 2,61%, brain tumors 2,00%, tumors of the bone and soft tissues 1,82%, tumors of the oral cavity and pharynx 1,31%, esophagus cancers 1,04%, thyroid cancers 1,04%, testicular cancers 0,52%, renal tumors 0,26%, tumors of the small intestine 0,26%. The most common malignancies among females are: breast cancer 22,11%, skin tumors (non-melanoma 15,60%, melanoma 0,92%), colorectal cancers 12,37%, stomach cancers 8,29%, malignancies of the lymphatic and hematopoietic system 5,99%, endometrial cancers 5,52%, ovarian cancers 3,22%, thyroid cancers 5,06%, metastatic tumors of unknown origin 4,14%, brain tumors 3,22%, tumors of the hepatobiliary system 2,76%, tumors of the bronchi and the lungs 2,30%, tumors of the bones and soft tissues 2,30%, esophagus cancers 1,38%, tumors of the oral cavity and pharynx 0.92%, tumors of the cervix uteri, vulva and vagina 0,50%, renal tumors 0,46% and tumors of the small intestine 0,46%. Conclusions: Although Turkish Health Department data demonstrates that the tumors of the bronchi and the lungs are the most common malignancies in the general Turkish population, prostate cancer was found to be the most common malignancy among our patient population. Additionally, colorectal tumors were also found to be more prevalent in our patient population than in the general Turkish population. Breast cancer was the most common malignancy among female patients in our patient population, as it is in general. While stomach and colorectal tumors among women were more prevalent than in the general population, gynecological tumors were rare. No significant financial relationships to disclose.
Predictors of autologous stem cell transplant related mortality in older adults
Authors: Klepin H. D. , Harish V. , Lovato J. , Keung Y. , Owen J. , Hurd D. 
Published: March 2020

16509 Background: Autologous stem cell transplantation (ASCT) is increasingly performed in older adults. Predictors of transplant related mortality (TRM) are not well established in this population. Our objective was to identify characteristics associated with TRM in older adults treated with ASCT. Methods: A retrospective chart review was conducted to identify all patients ≥ 60 years of age treated with ASCT at our institution between July 1990 and July 2005. We used logistic regression to investigate the effect of baseline characteristics and of transplant complications on TRM. Results: 143 patients met eligibility criteria of whom 139 were evaluable for the 100 day mortality outcome. The median age was 64.5 (range 60–76.6) years, 34% were female. Primary diagnoses included non-Hodgkin’s lymphoma (55%), multiple myeloma (29%), acute myelogenous leukemia (8%), breast cancer (5%), and Hodgkin’s lymphoma (3%). 100 day TRM was 7.9%. The mean time to engraftment (absolute neutrophil count >1000) was 12.2 ± 5.5 days. Complications included bacteremia (26.3%), cardiac events (myocardial infarction, congestive heart failure or arrhythmia) (11.5%), renal failure (7.4%), and respiratory failure (6.7%). Multivariate analysis including age, sex, diagnosis, number of comorbidities, number of medications, congestive heart failure, coronary artery disease, diabetes mellitus, hemoglobin, and creatinine at the time of transplant did not identify any baseline predictors of 100 day TRM (p > .05 for all). Development of renal failure or respiratory failure during transplantation was associated with increased TRM with an odds ratio of 11.2 (CI 2.5, 49.2) and 13.6 (CI 3.0, 62.2) respectively. Peritransplant cardiac events or bacteremia were not associated with increased TRM. Conclusions: Development of renal failure or respiratory failure is associated with increased TRM in this study. However, age and baseline comorbidities are not predictive of TRM. Future prospective studies should incorporate specific measures of functional and cognitive status which may be more reflective of decreased physiologic reserve in older adults being considered for ASCT. No significant financial relationships to disclose.
Novel tyrosine kinase inhibitor therapy (NTKI) prior to allogeneic stem cell transplantation (ASCT) in patients (pts) with chronic myeloid leukemia (CML): No evidence for increased transplant-related toxicity
Authors: De Lima M. J. , Jabbour E. , Cortes J. E. , Kantarjian H. , Giralt S. , Andersson B. S. , Champlin R. E. 
Published: March 2020

16515 Background: Patients undergoing ASCT for CML are increasingly likely to have received a NTKI after failing imatinib mesylate. It is unknown whether the use of these NTKIs prior to ASCT increases transplant-related toxicity. Methods: We retrospectively analyzed the outcome of 8 patients with CML (1 chronic, 4 accelerated, and 3 in blastic) who received dasatinib (n = 2) or AMN-107 (n = 6) prior to ASCT. Results: The median time on treatment was 85 days, and the median time from the end of NTKI therapy to HSCT was 37 days. Preparative regimen was ablative in 5 patients and non-ablative in 3. All patients engrafted within 13 days. There was no significant early transplant-related toxicity. Five patients achieved a molecular response after a median follow-up of 8 months; three complete and two major (Q-PCR < 0.05%). Three patients relapsed within 3 months. Two patients died of disease progression, and extensive GVHD, respectively. Conclusions: Previous treatment with NTKI did not increase transplant-related toxicity in this preliminary experience. Further follow-up and larger number of patients will be necessary to confirm these observations. No significant financial relationships to disclose.
A randomized, phase II trial comparing sequential paclitaxel/cisplatin/gemcitabine/vinorelbine/ (PCGV) with cisplatin/gemcitabine/vinorelbine/ (CGV) in patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: De Castro J. , Belda-Iniesta C. , Casado Saenz E. , Feliu J. , Sereno M. , Chacon J. , Martin G. , Madroñal C. , Jara C. , Torrego J. , Gonzalez-Baron M. 
Published: March 2020

17008 Background: New effective therapies are needed to improve the outcome of patients with advanced NSCLC. In this regard, new approaches such as cisplatin-based triplets have been explored with promising results but high toxicity. Furthermore, sequential chemotherapy schedules with taxanes followed by cisplatin-based regimens or viceversa could improve activity. A phase II study showed that sequential chemotherapy with weekly paclitaxel followed by CGV was highly active. Methods: A multicenter, randomized phase II trial of PCGV vs CGV in advanced NSCLC patients was conducted. Primary end-point: time to progression and survival. Eligible pts had unresectable, histologically confirmed NSCLC; no prior chemotherapy; PS 0–2; measurable disease. Pts received: Arm A (PCGV): P 150 mg /m2/week × 6, followed 2 weeks later by C 100 mg/m2 on day 1, gemcitabine 1,000 mg/m2 on days 1 and 14, and vinorelbine 25 mg/m2 on days 1 and 14 (CGV), every 28 days for a maximum of six courses. Arm B (CGV): C 100 mg/m2 on day 1, gemcitabine 1,000 mg/m2 on days 1 and 14, and vinorelbine 25 mg/m2 on days 1 and 14 (CGV), every 28 days for a maximum of six courses. Results: 106 Pts were included. Pts baseline characteristics (A/B: 52/54): male 82/79%; median age 60/59 (range 38–75 years); PS 0: 30/33%; 1 63/60%; 2: 7/7%; % squamous carcinoma:44/42%.WHO grade 3–4 toxicities for P were: neutropenia 18%; anemia 10%; thrombocytopenia 2%, peripheral neuropathy 18%. Grade 3–4 toxicities for CGV after P were: neutropenia 31%,nausea-vomiting 20%,thrombocytopenia 7%,anemia 5%,peripheral neuropathy 21%. WHO grade 3–4 toxicities for arm B were: neutropenia 35%,nausea-vomiting 19%, anemia 12%, thrombocytopenia 11% and peripheral neuropathy 15%. After therapy with arm A, 44% achieved a partial response, 15% had stabilization and 41% progressed. Arm B response rate were as follows: partial response 33%, stable disease 24% and progressive disease 43%. Median time to progression was (A/B) 7/6 months (log rank test, p 0.13) and median survival was (A/B): 11/10 months (log rank test, p 0.5). Conclusions: In spite of high response rate in TCGV arm, no survival benefit was detected in advanced NSCLC patients. No significant financial relationships to disclose.
Phase I study of two different schedules of bortezomib (BORT) and pemetrexed (PEM) in advanced solid tumors
Authors: Metzger A. S. , Lara P. , Lau D. , Mack P. , Gumerlock P. , Gandara D. , Davies A. M. 
Published: March 2020

17051 Background: BORT(PS-341) is a small molecule proteasome inhibitor while PEM, a multi-targeted antifolate, inhibits multiple enzymes involved in purine/pyrimidine formation. Both are approved anti-cancer agents. We examined the safety and tolerability of two different schedules of BORT and PEM in patients with advanced solid tumors. Methods: Two dose escalation trials (Arm A and Arm B) were conducted simultaneously. PEM was given every 21 days in both arms (500–600 mg/m2 IV). Arm A: BORT was given D1,4,8 &11 (0.7–1.3 mg/m2). Arm B: BORT was given D1 & 8 (1.0–1.6 mg/m2). All patients received vitamin B12, folic acid and decadron. Dose limiting toxicity (DLT) was defined as: grade (GR) 4 platelets (plts) (≤25K); GR 3 plts (25K-49,999K) with bleeding, requirement for transfusion, or lasting > 7 days; febrile neutropenia; GR3 ANC (ANC ≤1.0 × 109) with documented infection, or any ≥ GR3 non-heme toxicity. Results: 18 patients have been treated on 3 of the 4 planned dose levels. Tumor types included lung (12), prostate (2), breast (1), thymus (1), head & neck (1) and adenoid cystic carcinoma (1). Pt. characteristics: Median age 65 years; Sex M/F = 7/11; Performance Status ≤1/2 = 18/0. There have been no DLTs in either arm (Dose level 3-Arm A: PEM 500 mg/m2, BORT 1.3 mg/m2; Arm B:PEM 500 mg/m2, BORT 1.6 mg/m2). Most common GR3/4 toxicities were: neutropenia 27% and lymphopenia 11%. Of 17 evaluable patients: 1 had partial response, 11 had stable disease, 5 had progressive disease. Mean number of cycles: 4. Arm A had more doses held during the first cycle than Arm B (6 doses held vs. 1 dose held). Accrual to the final dose level in both arms is ongoing. Conclusions: 1) PEM in combination with BORT is feasible and tolerable. 2) Thus far, there are no differences in toxicity between the arms. 3) A randomized, multi-institutional phase II study will examine the efficacy of these two schedules in patients with NSCLC. No significant financial relationships to disclose.
Multicenter, randomized trial comparing a combined gemcitabine and cisplatin 3-week regimen with a 4-week regimen in non-small cell lung cancer (NSCLC) patients
Authors: Liao M. , Zhu Y. , Li L. , Wan H. , Yu S. , Hall B. J. , Wang L. 
Published: March 2020

17062 Background: This multicenter, randomized Phase II study (B9E-GH-JHSE) was aimed to compare the efficacy and safety of a gemcitabine-cisplatin combination over a 3-week schedule versus a 4-week schedule as first line treatment for Chinese patients with advanced NSCLC. Methods: Patients (pts) with pathologically or histologically confirmed stage IIIB/IV NSCLC not amenable to curative surgery, and presenting at least one measurable lesion were eligible for this study. Pts were randomized to receive cisplatin (cis) 75 mg/m2 on Day 1 plus either gemcitabine (gem) 1250 mg/m2 on Day 1 and 8 of a 21-day cycle (3-week arm) or gem 1000 mg/m2 on Day 1, 8, and 15 of a 28-day cycle (4-week arm). Patients received up to 6 cycles of treatment during this study. The primary endpoint was WHO objective response rate (ORR) and secondary endpoints included time to progression (TTP), CTC toxicity, and overall survival. Results: Of the 100 pts who were randomized to treatment, there were 51 pts in the 3-week arm: 14 females; mean age 59±8 yrs; 37% stage IIIB, 63% stage IV. In the 4-week arm, there were 49 pts: 24 females; mean age 56 ± 13 yrs; 33% stage IIIB, 67% stage IV. In the 3-week arm the overall response rate (complete response or partial response) was 24%, compared to 27% in the 4-week arm (Odds ratio: 1.17, 95% CI 0.47– 2.9, p = .819). There were no statistically significant differences between the two treatment arms in median overall survival time (3-week: 12.1 mths, 4-week: 13.8 mths; Hazard ratio (HR): 1.19, 95% CI 0.68–2.1, p = .54) and TTP (3-week: 4.9 mths, 4-week: 6.9 mths; HR: 1.33, 95% CI 0.85–2.1, p = .21). The difference in grade 3/4 hematological toxicities did not reach statistical significance (3-week: 37%, 4-week: 57%, p = .07), while grade 3/4 non-hematological toxicities were statistically significantly reduced in the 3-week arm (33% vs. 63%, p = .005). Grade 3/4 study drug related neutropenia (3-week: 27%, 4-week: 51%, p = .02) and thrombocytopenia (3-week: 8%, 4-week: 31%, p = .005) were reduced in the 3-week arm. Conclusions: While all efficacy endpoints were numerically superior in the 4-week arm, the difference was not statistically significant. However, grade 3/4 toxicities were reduced in the 3-week arm. [Table: see text]
Cooperative antitumor activity between the retinoid X receptor (RXR)-selective agonist bexarotene and EGFR-tyrosine kinase inhibitors in preclinical models of NSCLC
Authors: Bissonnette R. P. , Fan B. , Roegner K. , Ng S. , Corpuz M. , Prudente R. , Negro-Vilar A. , Yen W. 
Published: March 2020

17073 Background: Gefitinib and erlotinib, small molecule inhibitors of the EGFR-tyrosine kinase (EGFR-TKI), can have antitumor activity in patients with advanced NSCLC. However, analysis of clinical samples and in vitro characterization of NSCLC cell lines has revealed EGFR mutations that correlate with the clinical responses. While EGFR-mutant cell lines are hypersensitive to EGFR-TKI-mediated growth inhibition and have a greater tendency to undergo apoptosis in response to EGFR inhibition, wild-type EGFR cell lines undergo growth inhibition only at high concentrations, and are resistant to apoptosis induction. Bexarotene (Targretin) is a RXR modulator with clinical activity enhancing survival in a subset of NSCLC patients. We have shown that bexarotene can suppress the growth of epithelial tumors by modulating the expression and function of the EGFR pathway. This study examined the effect of bexarotene/EGFR-TKI combinations in preclinical models of NSCLC, and evaluated the possible molecular mechanisms for cooperative antitumor activity between these agents. Results: Bexarotene enhanced the activity of gefitinib in most of the cell lines tested, and did so regardless of their EGFR mutation status or intrinsic sensitivity to gefitinib alone. Resistant lines were sensitized by the combination, which decreased gefitinib IC50s to clinically achievable concentrations. Bexarotene increased the pro-apoptotic activity of both gefitinib and erlotinib, an effect which was paralleled by enhanced repression of p-Akt and p-Her2 levels by the combinations. In ex vivo cultures of human NSCLC explant tissue, the addition of bexarotene enhanced the growth inhibitory activity of both gefitinib and erlotinib. Finally, combinations of bexarotene and EGFR-TKI produced growth inhibition of TKI-resistant A427 NSCLC xenograft tumors that was superior to either agent alone. Conclusions: These results indicate that bexarotene can sensitize NSCLC cells which are unresponsive to the effects of EGFR-TKIs, resulting in cooperative growth inhibition and apoptosis induction. Combination therapy using bexarotene in conjunction with EGFR-TKIs may provide a powerful new therapeutic strategy. [Table: see text]
Analysis of neuroendocrine, signal transduction and adhesion proteins in SCLC tissue to predict the tumor response and the rogression free survival (PFS) in limited stage SCLC (SCLC-LS) patients subjected to chemo-radiation therapy
Authors: Benedetti G. , Damiani S. , Cancellieri A. , Magrini E. , Fedele M. , Tamberi S. , Frezza G. , Crino L. 
Published: March 2020

17075 Background: Most of SCLC-LS patients (pts) relapse within 12 months because of chemo and radio resistance. This phenomenon seems related to the induction of morphologically variant cells, which lack the neuroendocrine expression proteins and seem to trigger Akt-dependent inhibition of apoptosis. We analyzed neuroendocrine, signal transduction and adhesion molecules on tumor tissue from pts treated with chemoradiation therapy for SCLC-LS. Methods: We treated twenty-two pts with cisplatin/etoposide and concurrent thoracic irradiation. Paraffin blocks of the tumor obtained from each pt were used in the immunohistochemical analysis (IHA). Sections were stained with antibodies against phospho-Akt (p-Akt), phospho-MAP Kinase (p-MAPK), by a routine IHA method. Sections were stained in parallel with an automated immunostainer with antibodies against chromogranin A (ChrA), Neuron Specific Enolase (NSE), E-cadherin (Cad). Results: A preliminary IHA analysis obtained in ten out of twenty-two pts demonstrated that 9 out of 10 (9/10) tumor were NSE-positive; 6/10 ChrA-positive; 8/10 Cad-positive; 3/10 p-MAPK-positive; 5/10 p-Akt-positive. The correlation with tumor response and progression free survival (PFS) showed that the five patients with prolonged (10–60 months) complete remission (CR) had a p-Akt-positive, on the opposite the pts with short CR (6–18 months ) or partial remission (PR) had a p-Akt-negative staining. The two patient with prolonged and mantained CR (30+ and 60+ months) had a p-Akt-positive and Cad-negative profile. Conclusions: The expression of p-Akt and the absence of E-cadherin seems predict a prolonged CR after chemo-radiation therapy in SCLC-LS pts. Conclusive analysis will be presented at the meeting. No significant financial relationships to disclose.
Induction chemotherapy with paclitaxel and cisplatin followed by concurrent chemoradiation therapy for Stage IIIB non-small cell lung cancer
Authors: Lee G. , Kang K. , Kang J. , Kim H. , Jang J. , Lee J. 
Published: March 2020

17090 Background: We conducted a phase II study of Induction chemotherapy with paclitaxel and cisplatin followed by concurrent chemoradiation in patients with stage IIIB non-small-cell lung cancer to evaluate the response and toxicity profiles. Methods: All enrolled patients were scheduled to receive 2 cycles of induction chemotherapy with paclitaxel (175 mg/m2) intravenous infusion on day 1 and cisplatin (75 mg/m2) intravenously on day 1 every 3 weeks. All non-progressing patients were subsequently treated with concurrent chemoradiation. Concurrent chemoradiation included paclitaxel (60 mg/m2) plus cisplatin (25 mg/m2) intravenously for 6 weeks on day 43, 50, 57, 71, 78, and 85 and once-daily thoracic irradiation. Results: Between July 2000 and October 2005, 39 patients diagnosed as stage IIIB non-small cell lung cancer were enrolled in this study. Four patients achieved a complete response (10.3%) and 21 patients achieved a partial response (53.8 %), for an overall response rate of 64.1% [95% C.I. (49.4%–79.2 %)]. The 1, 2, and 3 year overall survival rate of all 39 patients were 66.7%, 40.6%, and 27.4% respectively, with a median survival time of 20 months. The median progression free survival was 10.7 months [95% C.I. (4.5%–16.9%)]. Esophagitis was the principal toxicity. Grade 3 or 4 esophagitis occurred in 18 patients (45%). Conclusions: Induction chemotherapy with paclitaxel and cisplatin followed by concurrent chemoradiation for stage IIIB non-small cell lung cancer seems to be effective treatment. However, Physicians should also be aware of severe esophagitis to require inpatient parenteral nutrition support and pain control. No significant financial relationships to disclose.
K-ras and EGFR mutations in 24 Chinese patients with non-small-cell lung cancer (NSCLC) treated with gefitinib
Authors: Wang Z. , Wu Y. , Zhang G. , Lin J. , Zhou Q. , Xu C. , Guo A. 
Published: March 2020

17109 Background: It was previously reported that K-ras mutations could behave as a resistance marker for response to gefitinib while EGFR mutations make NSCLC more responsive to this medication. And it is known that Asians and Westerners have different responses to gefitinib. Therefore, we are to identify the mutational status of K-ras and EGFR in the group of Chinese patients with NSCLC especially adenocarcinoma treated with gefitinib to find some helpful information. Methods: Genomic DNA was extracted from tumor specimens, including liquid nitrogen frozen tumor, paraffin blocks and fine needle biopsies from 24 patients with advanced NSCLC, who failed at least one platinum-based regimen, treated with gefitinib. Nested polymerase chain reaction products of codons 12, 13, 59, and 61 of K-ras and exon 18 through 21 of EGFR were directly sequenced at least twice. Results: Patients’ age ranges from 24 to 71 years (54.8 ± 10.2). Male/female was 14/10. Thirteen patients were smokers and 11 were non-smokers. Eighteen were adenocarcinomas, 2 were bronchioloalveolar carcinomas, 2 were squamous cell carcinomas and 2 were large cell carcinomas. The disease control (CR+PR+SD) rate was 79.2% (19/24) and the objective response (CR+PR) rate was 50.0% (12/24). No K-ras gene mutation was found in all patients. Fifteen patients (62.5%, 15/24) harbored EGFR mutations, which were delE746-A750 (8), delE746-A751 (1), delE746-A751insA (1), L861Q (1), L858R (5) and A871G (1). Two patients had double mutations (delE746-A750 and L858R). The disease control rate for wild type and mutant EGFR were 66.7% (6/9) and 86.7% (13/15), and the objective response rate were 33.3% (3/9) and 60.0% (9/15). Median time to progress (TTP) for wild type and mutant EGFR were 439 days (SE 249.8) and 367 days (SE 108.8). However, no statistically significant differences were found between these two groups regarding the response rates and TTP. Conclusions: K-ras mutation may occur at a low frequency in Chinese NSCLC groups despite the pathology, status of smoking, gender and EGFR mutations. And the relationship between the response to gefitinib and K-ras mutation might still remain to be determined at least in Chinese NSCLC. And the role of EGFR mutations in prediction of response to gefitinib should be further studied. No significant financial relationships to disclose.