bluuebunny/crossref_metadata_2025_split huggingface dataset:
CyberKnife high-dose fractionated stereotactic radiosurgery with tumor tracking: An effective non-surgical treatment alternative for single small peripheral lung tumors
Authors: Malik S. M. , Erickson K. , Collins S. , Reichner C. , Jamis-Dow C. , Banovac F. , Anderson E. D. , Smith F. P. , Hwang J. , Collins B. T. 
Published: March 2020

18125 Background: We report preliminary outcomes using CyberKnife radiosurgery with tumor tracking to treat small (<4 cm) peripheral inoperable stage I lung cancers and single pulmonary metastases. Methods: Enrollment of eligible pts began in July 2004. Prior conventional thoracic irradiation and the incorporation of systemic therapy were permitted. Fiducials (3–5) were placed near tumors under CT guidance. Pts received 45–60 Gy in 3 equal 1–2 hour fractions delivered over a 5–9 day period. Results: The median follow-up period of survivors was 12 months (range = 3–24 months). A total of 24 lesions were treated, 15 clinical stage I lung cancers and 9 single lung metastases. Four patients had prior conventional thoracic radiation (17%) and 6 patients received systemic therapy in conjunction with radiosurgery (25%). Two received systemic doses of platinum based doublet chemotherapy, 3 received gefitinib and 1 received sunitinib. Pneumothorax was a complication of fiducial placement in 7 pts, requiring tube thoracostomy in 4. All pts completed treatment with few acute side effects. No unexpected additional toxicities were noted with systemic therapy except for one pt who developed Grade III radiation pneumonitis while receiving gefitinib. A second pt with Grade III radiation pneumonitis had prior extensive conventional thoracic radiation. All tumors responded to treatment at 3 months as seen by a decrease in gross tumor volume. At 12 months 14 CT scans were evaluable. Four lesions responded completely (33%), 2 exhibited a partial response and the remaining 8 were obscured by radiation fibrosis corresponding to the high-dose irradiated volume (57%). Local progression was seen in only 2 single lung metastases at 10 and 12 months. There have been no regional lymph node failures. Four patients have died, 1 of progressive metastatic disease and 3 of comorbid illnesses. Conclusion: CyberKnife high-dose fractionated stereotactic radiosurgery with tumor tracking is an effective well-tolerated treatment option for small peripheral lung tumors, both primary and metastatic. The integration of systemic therapy appears feasible but needs to be further evaluated in clinical trials. No significant financial relationships to disclose.
Palliative radiotherapy versus palliative chemoradiotherapy in treatment of NSCLC stage IIIA and IIIB: Phase II randomized trial
Authors: Nawrocki S. , Krzakowski M. , Wasilewska-Teńluk E. , Kowalski D. 
Published: March 2020

18128 Background: The optimal treatment for stage IIIA/IIIB NSCLC patients who do not qualify for radical treatment has not been identified. Different palliative radiotherapy regimens and chemotherapy are used but have not been compared. We decided to combine short chemotherapy and radiotherapy (CT-RT) in order to improve therapeutic index of radiotherapy (RT). Methods: Eligibility criteria: Locally advanced, inoperable patients (pts) in IIIA (N2 positive) -IIIB clinical stage with tumor larger than 8 cm in longest diameter or/and FEV1 smaller than 40%, PS: 0–2 (ECOG), non-eligible for radical CT-RT. Treatment: RT arm - 3-D radiotherapy, 30 Gy/3 Gy, 2 weeks. CT-RT arm - two cycles of CT (cisplatin: 80 mg/m2; d 1, 22; vinorelbine: 25 mg/m2 iv; d 1,8,22,29) followed by RT as in Arm 1 with concurrent third cycle of CT (cisplatin 80 mg/m2, d 43; vinorelbine 25 mg/m2 iv., d 43, 50). Study design: Phase II, two-center, randomized study, stratification IIIA vs. IIIB, PS 0–1 vs. 2, treating center (Warsaw vs. Olsztyn). Two-stage design, a and β errors = 0,1; p1 minus p0 = 0,20. Planned sample size - 46 pts/arm. Primary endpoint: response rate (RECIST). Secondary end-points: overall survival (OS), toxicity, progression free survival (PFS). Results: During 2 years 104 pts randomized, 98 eligible for toxicity and survival/progression analysis, 82 for response assessment. Demographics: median age - 65 (45–78), IIIA/IIIB: 27/71 pts. PS 0–1/2: 72/26. Well balanced between arms. Response rate: RT arm- 26%, CT-RT arm- 46%, median OS for RT arm - 195 days, CT-RT arm 2 - 385 days, log-rank test p=0,047, median PFS for RT arm - 140 days, CT-RT arm - 172 days, log-rank test p=0,16. Toxicity: deaths - 2 in RT arm, 2 in CT-RT arm; hematological G3–4 - 0 in RT arm, Arm CT- RT: anemia - 2, thrombocytopenia - 6, neutropenia - 11, esophagitis - 2. Other G3–4: RT arm -3, CT-RT arm -1. Conclusions: Palliative radiotherapy (30Gy) with chemotherapy postponed to progression is a suboptimal treatment for patients with locally advanced NSCLC. 2 cycles of cisplatin/vinorelbine plus RT concomitantly with 3 cycle increases clinical response rate and significantly prolongs survival at the cost of acceptable toxicity in palliative setting. No significant financial relationships to disclose.
Combination chemotherapy with irinotecan and cisplatin in elderly patients (≥65 years) with extensive-disease small-cell lung cancer
Authors: Lee G. , Kim K. , Cho Y. , Kim H. , Hwang I. , Kim H. , Kang J. , Jang J. , Lee J. 
Published: March 2020

18135 Background: Combination chemotherapy with irinotecan and cisplatin is one of the standard treatments for patients with small-cell lung cancer (SCLC). In elderly patients, however, its efficacy and toxicity has not been well documented. In this Phase II study, we assessed the efficacy and toxicity of combination chemotherapy with irinotecan and cisplatin and examined whether advanced age compromises it in elderly patients with previously untreated extensive-disease small-cell lung cancer (ED-SCLC). Methods: In this study, 43 previously untreated elderly patients (65 years or older) with ED-SCLC were given combination chemotherapy consisting of irinotecan 60mg/m2 on days 1, 8 and 15 and cisplatin 60mg/m2 on days 1. The treatment was repeated every four weeks until patients completed the maximum six cycles. Results: Patients consisted of 34 men and 9 women, whose median age was 70 years (range 65 - 81 years). A complete response and a partial response were observed in 23.3% (10/43) and 58.1% (25/43), respectively. The overall response rate was 81.4% (95% C.I; 69.7 - 93.0%). The overall median survival was 10.3 months (range 7.8 - 12.7 months). The 1-year and 2- year survival rates were 31.8% and 3.4%, respectively. The median progression-free survival was 8.32 months (range 6.8 - 9.8 months). Major toxicities included neutropenia (grade 3 to 4, 55.9%), leukopenia (grade 3 to 4, 46.5%), infection (grade 3 to 4, 37.3%) and diarrhea (grade 3 to 4, 30.3%). Incidence of febrile neutropenia was significantly higher in patients with ECOG performance status 2 compared with ECOG performance 1 (70.7% vs. 5.2%; p < 0.001). There were two treatment related deaths in patients ECOG performance status 2. Conclusions: Our results indicate that combination chemotherapy with irinotecan and cisplatin is an effective treatment for elderly patients with ED-SCLC. However, physicians should be aware of the mortality and morbidity due to myelosuppression following this treatment in elderly ED-SCLC patients with ECOG performance status 2. No significant financial relationships to disclose.
Phase I/II study of oral TS-1 and gemcitabine in elderly patients with advanced non-small cell lung cancer (NSCLC): Thoracic Oncology Research Group 0502
Authors: Seto T. , Yamanaka T. , Eguchi K. , Okamoto H. , Shibuya M. , Ogura T. , Shinkai T. , Takiguchi Y. , Masuda N. , Ichinose Y. , Watanabe K. 
Published: March 2020

18137 Background: Optimal treatment for elderly patients with NSCLC has been under active investigation. This study evaluated the safety and initial efficacy of a novel combination regimen of oral fluoropyrimidine TS-1 plus gemcitabine (GEM) for elderly patients (pts) with advanced NSCLC. Methods: A phase I/II trial in 11 centers examined TS-1 and GEM in pts with age = 70, stage IIIB/IV previously untreated NSCLC. The starting dose was 60 mg/m2day (day 1–14) for TS-1 and 800 mg/m2 for GEM (day 8, 15). GEM was increased to 1,000 mg/m2 at dose level 2 and TS-1 was increased to 80 mg/mg2/day at dose level 3. Phase II portion of the study assessed the efficacy and tolerability of the combination regimen at the dose determined in the phase I portion. The primary endpoint was objective response rate. Results: Twenty two pts were enrolled in the phase I portion: 6 pts on dose level 1, 10 on dose level 2 and 6 on dose level 3. Median age of this group was 75 yrs (range 70–85). Dose limiting toxicities included Gr. 4 neutropenia (2 pts) and Gr.3 skin toxicity (4 pts). The recommended dose (RD) was TS-1 60 mg/day and GEM 1,000 mg/m2, with which 20 pts were subsequently treated in the phase II portion. The median age of 30 pts treated with the RD was 76 yrs (range 70–85). Grade (Gr) 3/4 toxicities include neutropenia (12 pts; 7 with Gr 4), thrombocytopenia (4 pts; 0 with Gr 4), skin toxicity (8 pts), thrombus (1 pt) and peumonitis (2 pts). Nine patients (30%, 95% confidence interval [CI] = 14 to 46%) had partial responses and 16 (53%, 95% CI = 35 to 71%) had stable disease. Conclusions: Encouraging antitumor activity and safety of TS-1 plus gemcitabine support further development of this combination therapy for elderly patients with advanced NSCLC. No significant financial relationships to disclose.
Phase I study of bortezomib plus cetuximab in patients with tumors expressing epidermal growth factor receptor (EGFR)
Authors: Dudek A. , Gada P. , Mulamalla K. , Shehadeh N. 
Published: March 2020

18143 Background: Bortezomib is a proteasome inhibitor that augments EGFR inhibitor activity (Cancer Research 2007; 67:(2),1–8). Cetuximab is a chimeric mouse-human antibody against EGFR that has been found to induce tumor responses in patients with colon cancer and head and neck cancer. The purpose of this study was to establish a maximum tolerated dose (MTD) for the combination of bortezomib plus cetuximab in patients with EGFR-expressing epithelial tumors. Methods: A 21-day treatment cycle was given with a maximum of six cycles per patient. Bortezomib was administered intravenously on days 1 and 8 via dose escalation, beginning with a minimum dose of 1.3 mg/m2 and increasing in one-tenth increments to 2.0 mg/m2 for a total of eight dose levels. Cetuximab was delivered with an initial dose of 400mg/m2 on day 1 cycle 1, with subsequent doses of 250mg/ m2 on days 1, 8 and 15. Results: Twenty patients (13 male and 7 female) with an ECOG PS <2 were enrolled in this study from November 2005 to December 2006. The median age was 59.5 (range: 41- 68), and the median number of prior chemotherapy regimens was 5 (range 1–7). Primary tumor sites included lung (9), head and neck (4), kidney (3), pancreas (2), bladder (1), and ovary (1). A total of 54 cycles of chemotherapy were administered; the median number of cycles per patient was 2.5 (range 1–6). Thirteen patients discontinued therapy because of disease progression. Two patients completed all six cycles of therapy. One dose-limiting toxicity (DLT) was seen at dose level 4 (bortezomib 1.6 mg/m2), which included grade 3 nausea, vomiting and dysphagia based on evaluation using CTCAE (version 3.0). Level 4 was expanded to enroll 3 additional patients, and no further grade 3 or 4 toxicities were observed. Grade 3/4 non- hematological toxicities were observed in 14 patients after their first cycle of therapy. Nine patients had delay in treatment. Conclusions: MTD for bortezomib plus cetuximab was not achieved at dose levels 1–6. This combination therapy has shown limited clinical activity in our extensively pretreated group of patients with solid tumors. Complete results for all dose levels, including dose levels 7–8, will be reported at the 2007 meeting of the American Society of Clinical Oncology. [Table: see text]
Toxicity of g-csf given for neutropenia during chest radiotherapy in limited-stage small cell lung cancer (SCLC)
Authors: Karcznmarczyk A. , Nawrocki S. 
Published: March 2020

18148 Background: There are concerns that use of white blood cell growth factors during radiotherapy, especially chest radiotherapy may lead to severe thrombocytopenia. Bunn P reported (J Clin Oncol 1995) that use of gm-csf during radical CT-RT of limited- stage SCLC is associated with life-threatening thrombocytopenia and did not reduce significantly neutropenia. On the other hand the prolongation of CT-RT total time in limited-stage SCLC has negative impact on survival. We have evaluated the safety of g-scf administration given for neutropenia (ANC<500/mm3) in limited-stage SCLC. Methods: 32 patients, 19 men, 13 women (median age 58,5 range 49–71, PS (WHO) = 0 or 1 - 30 patients, PS=2 - 2 patients. Chemotherapy during RT: cisplatin 60 mg/m2 d 1, etoposide 120 mg/m2 d 1–3, every 3 weeks. RT: 54 Gy/2 Gy/5 days a week together with 3rd and 4th CT cycle to gross tumor, ipsilateral hilar and bilateral lymph nodes planned in 3-D planning system, 6 MV photons. G-csf given for 3 to 10 days (median - 6 d) once (22 patients) or twice during RT-CT (10 patients) for G4 (CTC) neutropenia or febrile neutropenia, 30 mln u/d for 19 patients, 48 mln u/d for 13 patients. Toxicity was recorded (CTC v.2.0) Hematology tests done every 7 days during RT and every 7 days after RT till resolution of thrombocytopenia. No breaks in RT due to neutropenia, break if thrombocytopenia G3/G4. Results: G3-G4 thrombocytopenia was observed in 15 out of 32 patients during or after RT. In 2 patients platelet’s transfusions were given, in 1 patient haemoptysis was observed, no toxic deaths were noticed. Febrile neutropenia in 10 out of 32 patients. No breaks in RT in 20 out of 32 patients. 1 to 3 days’ breaks in 7 patients, 4 to 6 days breaks in 2 patients, longer breaks in 3 patients. Mean platelet count before RT - 221,000/mm3, after RT in 3 following weeks: 135,000/mm3, 149,000/mm3, 137,000/mm3. In 21 out of 32 patients clinical response (CR or PR) was observed after CT-RT. Thrombocytopenia was not associated (p>0,1) with age, PS or radiotherapy dose, associated with number of chemotherapy cycles (p=0.07). Conclusions: Use of g-csf during CT-RT in SCLC seems to be safe, regarding thrombocytpenia. G-csf given in lower doses for shorter times than in P. Bunn’s paper may be safer. Randomized study with g-csf in limited- stage SCLC is justified. No significant financial relationships to disclose.
Elevated serum level of sialylated glycoprotein KL-6 predicts a poor prognosis in patients with non-small cell lung cancer treated with gefitinib
Authors: Fujiwara Y. , Kiura K. , Toyooka S. , Hotta K. , Tabata M. , Takigawa N. , Soh J. , Kato K. , Date H. , Tanimoto M. 
Published: March 2020

18162 Background: The Factors affecting survival after gefitinib treatment in patients with non-small cell lung cancer (NSCLC) remain to be fully elucidated, although epidermal growth factor receptor (EGFR) mutation is a substantial prognostic factor. KL-6 has been studied as a useful indicator for interstitial lung diseases, however, it was first discovered as a pulmonary adenocarcinoma-related antigen. The aim of this study was to investigate the prognostic value of the serum KL-6 levels in advanced NSCLC patients treated with gefitinib and thus determine its association with the EGFR mutation status. Methods: Between September 2002 and September 2005, 41 patients with NSCLC were treated with gefitinib after having their serum KL-6 levels measured at Okayama University Hospital. EGFR mutations were analyzed by direct sequence methods. Results: The serum KL-6 levels ranged from 199 to 9080 U/ml (median, 550 U/ml), and 54% of 41 patients showed a level higher than the cut-off level of 500 U/ml. The median progression-free survival (PFS) time and the median overall survival (OS) time were 4.7 months and 13.9 months, respectively. Multivariate analyses revealed that the elevated KL-6 level was an independent adverse prognostic factor for PFS (hazard ratio: 2.278, p = 0.040) as well as OS (hazard ratio: 4.858, p = 0.002) in NSCLC patients treated with gefitinib. The EGFR mutation status was analyzed in 22 patients (54%). Among those with wild-type EGFR, the patients with high serum KL-6 levels also had a worse survival than those within normal serum KL-6 levels (6.5 months versus 13.3 months, p = 0.0194). Conclusions: Our data suggest that NSCLC patients with high serum KL-6 levels tended to have a poor clinical outcome when treated with gefitinib. No significant financial relationships to disclose.
Gefitinib (ZD-1839) with concurrent docetaxel and conformal three-dimensional thoracic radiation followed by consolidative docetaxel/gefitinib for patients with stage III NSCLC: A phase I study
Authors: Blackstock A. , Petty J. , Oaks T. , Porosnicu M. , Clark H. , Lovato J. , Miller A. 
Published: March 2020

18165 Background: The safety of 3-dimensional (3D) conformal thoracic radiation delivered with concurrent gefitinib/docetaxel chemotherapy in patients with inoperable stage III NSCLC has not been evaluated. Methods: Patients with inoperable stage III NSCLC received weekly intravenous (i.v.) docetaxel starting at a dose of 15 mg/m2 escalating to 30 mg/m2 in 5 mg/m2 increments and daily gefitinib (250 mg given orally). Patients recieved concurrent thoracic radiation to a dose of 70 Gy utilizing 3-D techniques. The chemoradiation therapy was followed by 2 cycles of consolidative docetaxel (75 mg/m2) given q 21 days and gefitinib 250 mg p.o. for 1 year or until disease progression. Results: Beginning December 2003, 15 patients have been entered to date to this IRB approved phase I trial to determine the maximum tolerated dose of weekly docetaxel when given concurrent with gefitinib and thoracic radiation. The dose-limiting toxicities (DLT) observed were primarily non-hematologic and occured at dose level 3 (25 mg/m2). One patient experienced grade III esophagitis that resulted in a grade III dehydration, a second patient experienced grade III diarrhea while a third patient suffered a grade V interstitial pneumonitis, believed to be related to the gefinitib. While 14 of 15 patients completed the chemoradiation portion of the study and 2 patients completed all planned therapy, 4 patients progressed during therapy, 3 patients discontinued treatment due to toxicity, and 2 patients refused to continue treatment. The median and 1-year survival thus far is 21 months and 56%, respectively. Conclusions: 70 Gy conformal thoracic radiation and concurrent gefitinib/docetaxel thus far appears feasible but with modest toxicity. The study is currently enrolling patients at the weekly 20 mg/m2 docetaxel dose level concurrent with 250 mg of daily gefitinib. This study was supported in-part by Sanofi-Aventis and Astra Zeneca. No significant financial relationships to disclose.
VEGF-D expression in lung adenocarcinoma with or without acquired resistance to gefitinib and normal lung
Authors: Wang Z. , Wu Y. , Zhang G. , Guo A. , Su J. , Chen Z. 
Published: March 2020

18166 Background: VEGF-D is related with pathogenesis and metastasis of lung cancer, however, its relationship with resistance to gefitinib in NSCLC remains unknown. Methods: Lung adenocarcinoma, normal lung tissues adjacent to the carcinoma and adenocarcinoma with acquired resistance to gefitinib including some metastastic lymph nodes were obtained during operation. Relative quantitation of VEGF-D gene expression was performed by SYBR Green real-time PCR with beta actin gene as the endogenous control. VEGF-D expression of each group was analyzed by comparing them qualitatively and quantitatively. The expression ratios were compared by Fisher’s exact test and expression levels were compared by two-related-samples nonparametric test. Results: CVEGF-D expression ratio of lung adenocarcinoma with acquired resistance to gefitinib (16.7%, 1/6) was not different from lung adenocarcinoma (50%, 7/14, P=0.325) but was significantly lower than that of normal lung (93.8%, 15/16, P=0.001). The logarithmically transformed VEGF-D relative expression levels in six lung adenocarcinomas and the matched normal lung tissues, which were 2.214±0.376 and 3.388±0.209, were found to be significantly different from each other by the analysis of Wilcoxon signed ranks test (P=0.028). Conclusions: VEGF-D expression is in a high-level state in normal lung tissues while in low-level or absent in lung adenocarcinoma with or without acquired resistance to gefitinib, suggesting that the role VEGF-D plays in normal lung tissue could be different from in lung adenocarcinoma with or without acquired resistance to gefitinib. No significant financial relationships to disclose.
Intensified treatment might improve survival in small cell lung cancer (SCLC) limited disease (LD). The STING study
Authors: Brodin O. , Wagenius G. 
Published: March 2020

18167 Background: Intensified treatment in SCLC is not used, in spite of 19% improved 2-year survival from high dose or dose densified treatment according to a comprehension of 20 randomised studies. (Annals of Oncology 13:1519, 2002). What would happen if both the doses were increased, one further drug was given and dose density increased? Methods: A standard (ST) and an intensified treatment (INT) schedule were given in a phase II study in which 42 patients were included, 18 of which with LD. Patients up to 75 were included. The ST consisted of 6 courses of carboplatin, 5 AUC and etoposide 100 mg/m2 iv day 1–3 with 3 weeks interval. Thoracic radiotherapy was given 1.5 Gy bid to 45 Gy in patients with LD, starting concommitantly with course two. INT consisted of carboplatin 6 AUC, etoposide 120 mg/m2 and ifosfamide 5,000 mg/m2 course 1 and 3,000 mg/m2 in courses 2–6. Treatment was given with 2 weeks interval, which was possible by the addition of filgrastim. Radiotherapy was given in the same way as in the ST. Results: There was more problems with trombocytopenia and fatigue in the INT arm but not more problems with leucopenia. Two year survival in the ST was 4/11 (37 %) and in the INT 5/7 (72%). We now also have reached 5 year survival and there are 3/11 (27%) survivors in the ST and 4/7 (57%) in the INT. One further patient with limited disease, not included in the study was also treated according to the INT schedule and she has now reached two year survival, thus 6/8 patients treated according to that schedule are 2 year survivors. Concerning extensive disease patients there was 0/13 ST and 2/11 (18%) surviving 2 years and no 5 year survivors. Conclusion: There were too few patients with LD in this study to prove a superiority of INT, however, we consider the results very promising. The INT treatment is possible to give to patients up to 75 years and the toxicity is feasible. INT earns further studies in SCLC. We plan to start a phase III study with the same treatment arms in patients with LD during the spring 2007 and would like to get in contact with other groups that might be interested to participate, who could contact ola.brodinkarolinska.se. No significant financial relationships to disclose.