bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac changes on MRI and SPECT after definitive radiotherapy in patients with lung cancer
Authors: Lind P. A. , Larsson T. , Lideståhl A. , Thoren L. , Ågren-Cronqvist A. , Nygren A. T. , Brodin O. 
Published: March 2020

17059 Background: To determine if lung cancer irradiation (RT) induces myocardial damage. Methods: Patients undergoing definitive RT with > 10% incidental cardiac RT (>30 Gy) were evaluated pre-RT and at 2 and 6 mos post-RT FUs. They underwent gadolinium enhanced cardiac MRI and rest-SPECT. The mean cardiac (MCD) and left ventricular (MLVD) doses were calculated on the dose planning CT. Data on confounding factors, e.g. diabetes, smoking, and levels of TGF-B, plasma glucose/fats were collected. The MRIs were analyzed for reductions in stroke volume (SV), ejection fraction (EF), left ventricular mass (LVM), and for visual signs of myocardial fibrosis/damage. The severity of SPECT-changes were analyzed with the semiquantitative summed rest score (SRS)-method (16-segments) and the extent was further quantified with the Bull’s-eye-view technique as volume-% (cutoff level for 1.5 SD below the mean). The Wilcoxon Matched Pairs test was used to study changes in repeated measurements. To test variable relation the Pearson’s Correlation Coefficient was calculated. Results: Presently, 13/30 patients are evaluated after their first FU. There was a limited decrease in LVM at first FU compared to pre-RT (median change: −6 g; P = 0.02), but no changes in SV or EF. The correlation coefficient for MCD (range: 2–32 Gy) (MLVD: 1–36 Gy) and MRI-reductions in SV, EF, and LVM at 2 mos were −0.46 (−0.27), −0.22 (−0.1), −0.30 (−0.12), respectively (P-values > 0.05). On rest-SPECT, a clinically significant SRS-increase was evident in one patient (SRS: +13; extent of defect 19%) at 2 mos. A new, extra cardial mass was, however, evident in this patient which would cause attenuation. No myocardial fibrosis/damage was detected on visual inspection of the MRIs. There was no increase in S-troponin levels at the first FU. Conclusions: At this stage of our study, no cardiac changes were evident following lung RT. This contrasts against studies in breast cancer RT were SPECT-defects corresponding to the tangential beams have been reported. RT-induced chest wall damage could in our series explain new SPECT-defects in one patient, who had no structural changes on MRI. Our entire cohort should be evaluated after both planned post-RT FUs before definitive conclusions can be drawn concerning cardiac damage and lung cancer RT. No significant financial relationships to disclose.
A phase II trial of thalidomide (T), irinotecan (I) and gemcitabine (G) in chemonaive patients with advanced non-small cell lung cancer (NSCLC)
Authors: Jazieh A. R. , Komrokji R. , Patil S. , Flora D. , Knapp M. , Gupta A. 
Published: March 2020

17068 Background: Chemotherapy with platinum based doublets provides only a modest benefit in advanced NSCLC with a median overall survival (OS) of 8 months and 1-year survival rate of 33% (Schiller JH et al, N Engl J Med 2002). We performed a phase II study to determine the efficacy of thalidomide, an immunomodulatory agent with antiangiogenic activity, in combination with chemotherapy in patients with advanced NSCLC. Methods: Chemonaive patients with stage IIIB/IV NSCLC with ECOG PS≤ 2 and adequate organ function were treated with G (1000 mg/m2) and I (100 mg/m2) IV on days 1 and 8 of a 21 day cycle. Patients also received T (200 mg orally with escalation as tolerated to a maximum of 400 mg daily). Therapeutic anticoagulation with coumadin was given to the last 11 patients. Results: Twenty four patients were enrolled: median age 57 years (41–76); M:F=17:7; ECOG PS 0/1/2=13/7/3; stage IV: IIIB= 21:3 and CNS involvement: 6. Two pts died before treatment, 1 was ineligible and 1 was lost to follow up. The remaining 20 pts received a median of 4 treatment cycles (range 1–6). The regimen was generally well tolerated and the most common grade 3–4 toxicities encountered were: diarrhea (4); pneumonia (3) and thromboembolic events (3). There were no thromboembolic events after anticoagulation was initiated. Two patients (10%) experienced partial response, 14 (70%) experienced stable disease, 1 had progressive disease. Three patients (15%) were not evaluable for response due to early withdrawal. The median OS was 10.8 months (range 0.6–37+) and 1-year and 2-year survival rates were 37% and 16%, respectively. The median time to progression was 3.6 months (range 0.2–11+). Conclusions: The combination of thalidomide and chemotherapy is reasonably well tolerated and active in advanced NSCLC as evidenced by good OS and 1- and 2-year survival rates. The addition of thalidomide to a non-platinum based regimen appears to compare favorably to the results of the traditional platinum based doublets. [Table: see text]
Clinical efficacy and immunogenicity of the optimized cryptic peptide TERT572Y vaccine (Vx-001) in patients with advanced non-small cell lung cancer (NSCLC)
Authors: Kosmatopoulos K. , Bolonaki E. , Aggouraki D. , Nikoloudi E. , Kanellou P. , Papadimitraki E. , Kotsakis A. , Mavroudis D. , Georgoulias V. 
Published: March 2020

17069 Background: BTERT572Y, an optimized cryptic peptide homologous to TERT induces efficient antitumoral T cell cytotoxic immunity but not autoreactivity in vivo in HLA-A*0201 transgenic mice and healthy blood donors and prostate cancer patients (J. Clin. Invest., 2004, 113,425). Moreover, it was well tolerated and effective in eliciting specific T cell immunity in patients (pts) with advanced malignancies (ASCO 2005, abstr 2579). Methods: We evaluated its clinical efficacy, safety and immunogenicity in 13 HLA-A*0201 pts with advanced, stage IIIb (7 pts) and stage IV (6 pts), NSCLC. Three pts were in stable (SD) and ten pts in progressive (PD) disease following prior therapy. The vaccination protocol consisted of two subcutaneous injections of optimized TERT572Y peptide followed by four injections of native TERT572 peptide. Both peptides were emulsified in Montanide ISA51. Results: Eight pts completed the entire vaccination program, 4 discontinued due to PD and 1 is ongoing. The median follow up is 6.5 months (range 2.0–29.9). Three of 10 (30%) pts with prior PD developed SD for 6+, 7+ and 9 months. Overall clinical response was SD in 6 and PD in 7 pts. Median TTP was 8.1 months (range 3.7–9.1) for stage IIIb and 2.3 (range 2–6.9) for stage IV pts. Minimal grade I/II primarily skin toxicity was observed. ELISPot-detected TERT572 specific CD8+ cells were demonstrated in all 7 pts tested. Conclusions: TERT572Y peptide vaccine is well tolerated and effective in eliciting a specific T cell immunity. The disease stabilization observed in 30% of pts with previously progressive disease is very encouraging and deserves further evaluation. [Table: see text]
Feasibility report of stereotactic body radiotherapy with tomotherapy for early stage medically inoperable lung cancer using extreme hypofractionation
Authors: Hodge C. W. , Khuntia D. , Tome W. A. , Jaradat H. , Mehta M. P. 
Published: March 2020

17097 Background: This is a report on the technical feasibility, dosimetric aspects, and daily image-guidance capability with megavoltage computed tomography (MvCT) imaging of stereotactic body radiotherapy (SBRT) using tomotherapy for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). Methods: Treatment planning was performed using 4D PET-CT in a BodyFix device. A pilot group of 4 patients with <5 cm T1/2, N0 tumors, was treated using IMRT (tomotherapy), utilizing daily image guidance with MvCT. Patients received 60 Gy within 10 days, delivered in five 12Gy fractions. The primary endpoint of this study was evaluation of acute and sub-acute treatment related toxicities. The secondary endpoint was radiographic evaluation for objective tumor response. Results: All 20 fractions were successfully delivered. MvCT provided excellent tumor visualization for daily image guidance. No significant tumor regression was observed in any patient during the 2 weeks of therapy, using volumetric contouring on MvCT images. The relevant dosimetric aspects, measured as median normalized total dose (NTD) were as follows: tumor = 116.5 Gy10; whole lung = 6.8 Gy3. Maximum fraction-size equivalent dose (FED) demonstrated median values as follows: esophagus = 4.04 Gy3; spinal cord = 6.53 Gy3. All patients are alive at a median follow-up of 6 months, with no grade 2 or higher acute pulmonary toxicities. Early radiographic follow-up demonstrates all 4 patients experienced a partial response. The mean tumor regression is 79% (range 64–85%). Conclusions: 4D PET-CT permits precise target delineation. In this, the first reported clinical experience, IMRT delivery of SBRT using tomotherapy is feasible, safe and free of major acute toxicities. The conformality which is obtained by helical delivery of the therapeutic dose makes it well-suited for dose escalation through extreme hypofractionation, with extremely low mean NTD to normal tissue. The ability to obtain on-treatment megavoltage CT scans to confirm tumor localization is a substantial advantage. Further studies and longer follow-up are warranted to evaluate the efficacy of this treatment modality. [Table: see text]
A phase I trial of ABT-751 and carboplatin (C) in patients (pts) with previously treated non-small cell lung cancer (NSCLC)
Authors: Dragnev K. H. , Rigas J. R. , Disalvo W. M. , Simeone S. A. , Hagey A. E. , Gordon G. B. , Dmitrovsky E. 
Published: March 2020

17098 Background: NSCLC is the leading cause of cancer mortality for men and women in the United States. More effective treatments are needed to prolong survival and improve quality of life. Platin-containing chemotherapy doublets are commonly used in NSCLC treatment. ABT-751 is a novel oral anti-microtubule agent targeting the colchicine binding site. As single agent, it was well-tolerated and showed a preliminary signal of activity in previously treated NSCLC. In vivo studies demonstrated additive activity between ABT-751 and cisplatin in a NSCLC xenograft model. Methods: A phase I trial of ABT-751 and C was conducted in pts with advanced previously treated NSCLC. Primary objective - maximum tolerated dose (MTD). Secondary objectives - toxicities, efficacy, and surrogate markers of response (cell cycle changes and cyclin D1 expression) in buccal swabs from pts at the phase II dose. Six dose levels - 1: ABT-751 100mg bid, C AUC 4.5; 2: ABT-751 125 mg bid, C AUC 4.5; 3: ABT-751 125 mg bid, C AUC 6; 4: ABT-751 150 mg bid, C AUC 6; 5: ABT-751 175 mg bid, C AUC 6; 6: ABT-751 200 mg bid, C AUC 6. ABT-751 was taken orally twice a day for 14 days in a 21 day cycle, C was administered intravenously on day 4 during cycle 1 and on day 1 on subsequent cycles. Rapid dose escalation was used for the first 3 dose levels followed by cohorts of at least 3 patients for the remaining dose levels. Results: Eight pts were enrolled, all stage IV NSCLC, 4 women, median age 62 (47–73), all KPS 80, 6 had one and 2 had 2 prior therapies. A median of 3.5 (1–4) cycles was administered. Dose-limiting toxiticies of grade 3 fatigue and grade 4 thrombocytopenia and neutropenia were observed in 2/5 patients on dose level 4. Common grade 2 toxicites were constipation and peripheral sensory neuropathy (levels 2–4). MTD was dose level 3. Seven pts were evaluable for response, 2 had partial responses (levels 2 and 4, both had one prior therapy), 4 had stable disease, 1 had disease progression. Median time to progression was 18.7 weeks (6–24+). Pharmacokinetic analyses and buccal swabs are being performed. Conclusions: The recommended phase II doses are ABT-751 125 mg twice daily for 14 days and carboplatin AUC 6 on a 21-day cycle. This regimen is well tolerated and shows preliminary evidence of activity for previously treated NSCLC. [Table: see text]
Evaluation of the role of FDG-PET imaging in malignant pleural mesothelioma (MPM)
Authors: Power D. G. , Farrelly C. T. , McDermott R. A. , O’Byrne K. J. 
Published: March 2020

17113 Background: MPM is a rapidly progressive malignancy with a median survival of 6 to 9 months. Studies in non-small cell lung cancer, gastrointestinal stromal tumours, and breast cancer suggest that Positron Emission Tomography (PET) scanning may predict the clinical outcome of chemotherapy at an early stage of treatment. The role of PET in predicting and monitoring response to treatment in MPM is unclear. In this study we assessed if baseline and early interval PET scanning could be of benefit in MPM, correlating the results with standard Computerised Tomography (CT) assessment using the modified Response Evaluation Criteria In Solid Tumours (RECIST) of Byrne and Nowak. Methods: 10 patients with histologically proven MPM proceeded to baseline PET and CT scanning prior to chemotherapy. In 8 patients a second PET scan was performed within three weeks of commencing treatment. The following PET derived parameters were calculated: Standard Uptake Value (SUV)maximum, SUVaverage, PETvolume, and Total Lesion Glycolysis (TLG). Baseline SUVmaximum and early PET response was compared with CT response and survival. Results: Baseline SUVmaximum predicted subsequent CT response in the 10 patients studied. Four out of 5 patients with baseline SUVmaximum of <15 showed a subsequent partial response on CT, whilst the 5th patient had resolution of a pleural effusion. All 5 patients with baseline SUVmaximum of >15 had stable or progressive disease on CT. In contrast change in early SUVmaximum from baseline to 3 weeks did not predict subsequent CT response (Kappa value 0.07) in the 8 patients evaluated. Change in PET volume and TLG correlated with subsequent CT response (Kappa value= 0.80 for both). Only 1 patient with a partial response on % PETvolume and %TLG has died 14 months after commencing treatment. The other 3 patients are alive at 17+, 19+ and 20+ months. The 4 patients with stable or progressive disease using these parameters were deceased at 5, 6, 10, and 12 months respectively. Conclusion: PET may be useful in predicting and evaluating response to treatment in MPM. Furthermore, the results suggest that PET response may be a useful prognostic tool in this disease. It is important to use the appropriate PET derived parameters. Further study with a larger patient population is warranted. No significant financial relationships to disclose.
Influence of histological type, smoking history and chemotherapy after 1st line on treatment outcome in advanced non-small cell lung cancer
Authors: Yamamoto N. , Itaya T. , Takahashi T. , Asai G. , Ebisawa M. 
Published: March 2020

17118 Background: Primary endpoint of clinical trials of 1st line chemotherapy in advanced non-small cell lung cancer (NSCLC) is usually used over all survival. However, we know that 2nd line chemotherapy is prolonged survival time. Especially, Asian ethnicity, non-smokier and adenocarcinoma (Ad) were possible to be associated with survival in EGFR TKI such as gefitinib. Thus, we undertook this analysis to identify the prognostic factors of the progression free survival (PFS) and overall survival (OS) and to examine the effect of chemotherapy after 1st line in advanced NSCLC patients. Methods: We selected the patients who were received 1st line chemotherapy in the Shizuoka Cancer Center between October, 2002 and September 2005 and fullfilled following criteria: 1. stage IIIB or IV NSCLC, 2. no prior therapy for lung cancer, 3. chemotherapy regimen was CBDCA AUC 6 + Paclitaxel 200 mg/m2, 4. PS 0 or 1. Univariate and multivariate analyses were performed on possible porgnostic factors such as gender, PS, smoking history, histology (adenocarcinoma or other), and stage. Results: A total of 98 patients (35 females, median age 61 years [range 340–78], 74 adenocarcinomas, 73 smokers, 56 PS 0) fullfilled above selection criteria. 71 (78%) in these patients received 2nd line chemothrapy (gefitinib 44%, erlotinib 4%, and docetaxel 48%). Median-PFS and MST was 4.9 months(m) and 16.1m. PFS was not significant difference in smoking history (M-PFS: smoker 5.0m, non-smoker 4.4m) and histlogical type (Ad 4.9m, others 4.7m). However, OS was significant diference in each factor(2 yr survival rate: smoker 61%, non-smoker 17%, p = .0001, Ad 39%, others 8%, P = .0001). Multivariate analysis in 71 patients received 2nd line chemotheraoy revealed that treatment of EGFR TKI was only independent predictors of OS. Conclusions: OS of non-smoker or adenocarcinoma patients was very excellent. the usage of EGFR TKI was associate with prolongation of these OS. No significant financial relationships to disclose.
The use of statins and the effect on survival in patients with small cell lung cancer
Authors: Hanbali A. S. , Urbaez Duran E. , Wang D. , Jankowski M. , Syed A. , Farhan S. , Chapman R. 
Published: March 2020

17121 Background: Hypercholesterolemia is one of the most common morbidities in United States. Statins have been proven as effective cholesterol-lowering agents and have been widely used in this country. They have been reported reducing the incidence and risk of various cancer types. However, the impact of using statins on the survival of patients with diagnosed small cell lung cancer is unknown. Methods: A retrospective study involved a cohort of 282 patients with diagnosed small cell lung cancer. Patients were identified from the Tumor Registry at Henry Ford Health System between January 1995 and December 2002. Electronic medical records of these patients were reviewed. Statistical analyses were performed and stratified for statin users versus non statin users. Results: Out of 282 patients, there were 73 patients with hypercholesterolemia, 37 of them were statin users at the time of their small cell lung cancer diagnosis. Average age was 65 (range 34–87) years for non statin users and 69 (range 52–85) years for statin users. Median survival of 282 subjects was 7.37 months. After stratifying for statin use, the median survival of statin users was 8.66 months while the median survival of non statin users was 7.17 months (p = 0.29). Conclusion: Though slightly prolonged median survival in statin-users was observed, no survival benefit is demonstrated from this patient population. Factors that may have contributed to this result will be further discussed. With the trend of an increase in median survival among statin users, whenever possible, continuation of statins as co-morbidity management may still benefit patients with small cell lung cancer, during their receiving standard anti-tumor therapies. No significant financial relationships to disclose.
A preclinical survey on the efficacy of NSC-290205 in combination with doxorubicin (ADR) in Lewis lung carcinoma (LLC)
Authors: Papageorgiou A. , Stergiou E. , Boukovinas I. , Geromichalos G. , Stergiou I. 
Published: March 2020

17131 Background: NSC-290205 (A) is a hybrid synthetic antitumor ester, which combines a D-lactam derivative of androsterone and nitrogen mustard. Studies on modified steroidal esters of carboxylic derivatives of N,N-bis(2-chloroethyl)aniline, have shown that they exhibit reduced toxicity and increased antitumor activity and specificity. In this study we investigated the antitumor activity of compound A in combination with ADR (AHOP) in comparison with standard CHOP regimen. Methods: C57Bl mice were used for the antitumor evaluation of AHOP/CHOP. Experiments were initiated by implanting the tumor. LLC cells (purchased by NCI, Bethesda, USA) were implanted intramuscularly into the right hind leg as a suspension of 7 × 106 cells in 0.1 ml. The antitumor activity was assessed from the inhibition of tumor growth by volume in cm3 and the oncostatic parameter T/C % according to the protocol of experimental evaluation of antitumor drugs of the NCI, USA. Treatments were given as a single dose (D) on day 1, intermitted dose (D/2 × 3) on days 1, 5, 9 or consecutive dose (D/4 × 9) on days 1 through 9. Results: Treatment with A or cyclophosphamide produced almost equal borderline activity. Moreover, both CHOP and AHOP regimens showed significant and comparable antitumor effect (p < 0.05 by the Wilkoxon test). AHOP caused the maximum effect inhibiting the tumor growth by 67.7% and T/C values of 270%. CHOP was less effective producing 54.8% tumor inhibition and T/C values of 238%. Conclusions: It is very likely that the D-lactamic steroid (androstan) alkylator for A, containing the -NHCO group, combined with ADR, which intercalates between base-pairs, is the explanation for higher activity of AHOP vs. CHOP. This significant effect of NSC-290205 with the anthracycline adriamycin on LLC adds to NSC-290205 advantage for further clinical development. No significant financial relationships to disclose.
Phase II trial of oxaliplatin and gemcitabine in patients with malignant pleural or peritoneal mesothelioma
Authors: Boyar M. S. , Hesdorffer M. , Taub R. N. 
Published: March 2020

17133 Background: A prior phase II trial of oxaliplatin and gemcitabine in malignant pleural mesothelioma reported activity with a 40% partial response rate and stable disease in 24% of 25 previously untreated patients (Schutte W. et al., Clin Lung Cancer 2003;4:294). This trial was designed to further evaluate the efficacy of oxaliplatin and gemcitabine in patients with malignant pleural or peritoneal mesothelioma. Methods: Patients with histologically-confirmed malignant pleural or peritoneal mesothelioma not amenable to curative surgical treatment are eligible for enrollment on this single-institution phase II trial. One prior chemotherapy regimen is allowed, including pemetrexed with a platinum compound or gemcitabine. Presence of at least one radiologically-measurable lesion that has not been previously irradiated is required. Gemcitabine 1000 mg/m2 IV over 90 minutes is administered followed by oxaliplatin 100 mg/m2 IV over 2 hours on day 1 of a 14-day cycle. Treatment is continued for at least 6 cycles unless unacceptable toxicity or disease progression occurs. The primary outcome is to evaluate efficacy as measured by tumor response rate. The sequential two-stage design allows for enrollment of a total of 29 patients if 3 of 18 patients enrolled in the first stage have at least a partial response. Results: Ten eligible patients have been enrolled thus far and 6 are evaluable for response. Sites of disease include pleural (3) and peritoneal (3), and histologic subtypes are epithelioid (5) and sarcomatoid (1). Four patients had received prior chemotherapy. A total of 42 cycles have been given with a median of 8 cycles per patient. There are no partial or complete responses. Four patients have had stable disease for at least 4 months. Two patients with stable disease had received prior pemetrexed/gemcitabine or pemetrexed/cisplatin. Frequently observed toxicities include grade II fatigue, neuropathy and upper gastrointestinal dysmotility. Conclusion: This regimen of gemcitabine and oxaliplatin may provide disease stabilization in a subset of patients with malignant pleural and peritoneal mesothelioma, including those who have received prior chemotherapy. The regimen is well-tolerated. This study remains open to accrual. No significant financial relationships to disclose.