bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results of the IFCT 0002 phase III study comparing a preoperative and a perioperative chemotherapy (CT) with two different CT regimens in resectable non-small cell lung cancer (NSCLC)
Authors: Westeel V. , Milleron B. , Quoix E. , Breton J. L. , Braun D. , Puyraveau M. , Bigay-Game L. , Pujol J. L. , Morin F. , Depierre A. 
Published: August 2020

7530 Background: Association of surgery and CT is standard for early-stage NSCLC. Meta-analyses showed comparable efficacy of adjuvant and neoadjuvant CT. The primary objective was to compare survival between two different CT strategies: all before surgery (PRE) versus perioperative (PERI). Methods: Between 2001 and 2005, 528 patients with a stage IA-II resectable NSCLC were randomized to 4 parallel arms (A: 2 GP + 2 GP in responders, then surgery, B:2 GP - surgery + 2 GP in responders, C: 2 TC + 2 TC in responders then surgery, D: 2 TC - surgery + 2 TC in responders; GP: Gemcitabine 1250 mg/m2/d1, 8 and cisplatin 75 mg/m2/d1 q3 wk; TC: Paclitaxel 200 mg/m2/d1 and carboplatin AUC 6, q3 wk). Results: 501 patients were operated on, 96.2% in the preoperative CT arms (PRE: A+C) and 95.8% in the perioperative CT arms (PERI: B+D). Ninety- day postoperative mortality was 4.9% and 4.2%, respectively. Pathological complete response was not significantly influenced by the number of preoperative cycles (PRE:8.6%, PERI:6.4%). In an intent-to-treat analysis, 3-yr survival was 67.8% and 68.6%, respectively (p=0.96). In responders, despite a dramatic difference in CT compliance (90.4% and 75.2% having received the 4 cycles, respectively, p=0.001), 3-yr survival was 75.1% and 79.5%, respectively (p=0.82). Survival did not differ with the CT regimen (GP versus TC, p=0.84). Three-yr survival increased from 68.1% in the PRE arms to 77.2% in the PERI arms in squamous cell carcinomas (SCC), and decreased from 67.7% to 61.6% in non SCC, respectively (Cox model interaction, p=0.35). Three-yr survival was 74.6% in the GP arms and 70.7% in the TC arms, in SCC, and was 64.2% and 65.4%, in non SCC, respectively (interaction, p=0.51). There was no interaction between CT strategy and stage. In stage II patients, 3-yr survival was 59.1% but 76.5% in responders, comparable to that of all stage I patients (72.9%). Conclusions: Despite an increased compliance of the all preoperative chemotherapy strategy, no difference was observed between the PRE and PERI arms. There might be an advantage for perioperative CT and for gemcitabine-based in SCC and for preoperative CT and for taxane-based in non SCC. No significant financial relationships to disclose.
Cetuximab in combination with concurrent chemoradiotherapy (CRT) in locally advanced non-small cell lung carcinoma (NSCLC): A feasibility study
Authors: van den Heuvel M. M. , Belderbos J. , Dalesio O. , van der Pol M. , Uitterhoeve L. , van de Vaart P. , Verheij M. , van Zandwijk N. 
Published: August 2020

7540 Background: Despite modest benefits from CRT regimens in patients with locally advanced NSCLC, more efficacious treatment options are needed. Cetuximab, a monoclonal antibody that selectively binds to the epidermal growth factor receptor, has demonstrated activity in patients with metastatic NSCLC. This trial was initiated to assess the feasibility of combining cetuximab with concurrent CRT. Methods: Patients with non-operable locally advanced NSCLC received cetuximab (400 mg/m2 on day 1, 250 mg/m2 q1w from weeks 2–6) in combination with cisplatin (6 mg/m2 q1d from weeks 2–6), and RT (66 Gy in 24 fractions from weeks 2–6). Results: Between April and July 2008, 12 consecutive, eligible patients entered the study. The mean age was 61 years (range: 43–77) and 50% were male. Baseline NSCLC staging was: IIb (1 patient), IIIa (5 patients), and IIIb (6 patients). Treatment was generally well tolerated. Acne-like rash and radiation esophagitis were the most common side effects (grade ≤3 according to CTCAE v 3.0) (see table). No unexpected toxicities were observed. Early-response monitoring using PET-CT scans was performed 4 weeks after the last fraction of RT in 10/12 patients. A metabolic response was seen in 50% (complete: 3 patients; partial: 2 patients) of patients. One patient showed progressive disease. Conclusions: Cetuximab added to CRT in patients with NSCLC was generally well tolerated and produced promising early clinical responses. A randomized phase II study comparing CRT with CRT and cetuximab is ongoing. [Table: see text] [Table: see text]
Radiotherapy (RT) dose escalation study with concurrent cisplatin and S-1 in patients with inoperable stage III non-small cell lung cancer (NSCLC)
Authors: Harada H. , Nishio M. , Murakami H. , Ohyanagi F. , Kozuka T. , Ishikura S. , Horiike A. , Morota M. , Nishimura T. , Yamamoto N. 
Published: August 2020

7542 Background: Standard treatment for inoperable stage III NSCLC is concurrent chemoradiotherapy using 3-D conformal RT to a total dose of 60 Gy, but the outcome is still dismal with median survival time (MST) of 16 months and 5-year survival of 15%. We conducted a phase II trial using cisplatin, S-1 and concurrent RT of 60 Gy (J Clin Oncol 2008;26:a7556). MST (33months) was encouraging, however, local failure rate with this trial remained still high. The purpose of this study was to establish the recommended dose (RD) of RT with concurrent cisplatin and S-1. Methods: The eligibility criteria were: histologically or cytologically proven NSCLC, 20–75 years old, performance status 0–1, without any prior chemotherapy or RT. Patients were treated with cisplatin (60 mg/m2 on day 1) and S-1 (orally at 40 mg/m2/dose b.i.d., on days 1–14) repeated every 4 weeks for 4 cycles and RT was started on day 1. Radiation dose was escalated from 66 Gy in 33 fractions (Arm 1) to 70 Gy in 35 fractions (Arm 2), then 74 Gy in 37 fractions (Arm 3). The dose was to be escalated if DLTs were observed in 2 or less patients. The target volume of RT included primary tumor and metastatic node only and elective nodal irradiation was not performed. Dose constraints to the organs at risk were: the lung, V20 < 30%; the esophagus, mean dose < 34 Gy and V55 < 30%; the spinal cord, max dose < 50 Gy. Results: Six patients in each arm were enrolled. Two patients in Arm 1 experienced DLTs: one patient developed grade 3 febrile neutropenia, grade 3 mucositis in oral cavity and grade 3 diarrhea and one patient developed grade 3 febrile neutropenia. One patient in Arm 3 has not been completed evaluation yet. Otherwise no DLT was observed. Conclusions: The radiation dose of 74 Gy in 37 fractions with concurrent cisplatin and S-1 seemed to be tolerable and was judged to be the RD. This study is still open to accrue another six patients to confirm the safety of the RD. No significant financial relationships to disclose.
Survival of patients (pts) treated with high-dose radiotherapy (RT) and concurrent chemotherapy for unresectable non-small cell lung cancer (NSCLC)
Authors: Schild S. , Graham D. , Hillman S. , Vora S. , Yolanda G. , Molina J. , Shahidi H. , Kugler J. , Adjei A. 
Published: August 2020

7544 Background: NCCTG N0028 was a trial that determined the MTD of RT that could be given with carboplatin & paclitaxel was 74 Gy/34 fractions. This secondary analysis was performed to determine the survival of pts treated on this trial. Methods: Eligible pts had medically or surgically unresectable NSCLC, PS=0–1, weight loss <10% in the prior 3 months(mo), no prior therapy, adequate laboratory & pulmonary functions. Included were 25 pts with clinical stages I (4pts), II (1 pt), IIIa (12 pts), & IIIb (8 pts). Treatment included: weekly I.V. paclitaxel (50mg/m2) & carboplatin (AUC=2) during RT. The RT included 2 Gy daily to an initial dose of 70 Gy. The total dose was increased in 4 Gy increments until the MTD was determined. RT was delivered with 3-D treatment planning but no elective nodal RT. Three pts received 70 Gy, 18 pts received 74 Gy, & 4 pts received 78Gy. Results: Pts were followed until death or from 10–67 mo (median: 28mo) in those alive at last evaluation. The median survival (MS) of the entire cohort was 42mo. The 5 stages I-II pts had a MS of 53 mo & the 20 stage III pts had MS of 42mo. Conclusions: Standard dose RT is unable to sterilize disease in the majority of pts with unresectable NSCLC. While the addition of chemotherapy has significantly improved survival of these pts, the MS is generally 15–24 mo. These preliminary results suggest higher than standard doses of RT may improve disease control & prolong survival. A phase III trial comparing standard-dose RT(60Gy) to high-dose RT (74Gy) is open and should more definitively address the issue of RT dose with concurrent chemotherapy for unresectable NSCLC. Future technological improvements in imaging & targeting will provide methods to safely administer even greater RT doses which will likely further improve disease control. No significant financial relationships to disclose.
Phase I study of concurrent high-dose three-dimensional conformal radiotherapy (3D-CRT) without elective nodal irradiation with chemotherapy using cisplatin and vinorelbine for unresectable stage III non-small cell lung cancer (NSCLC)
Authors: Sekine I. , Sumi M. , Ito Y. , Nokihara H. , Yamamoto N. , Kunitoh H. , Ohe Y. , Tamura T. 
Published: August 2020

7546 Background: The optimal dose of radiotherapy remains unclear in concurrent chemoradiotherapy for unresectable stage III NSCLC. Methods: Eligible patients (unresectable stage III NSCLC, age ≥ 20 years, PS 0–1, V20 ≤ 30%) received cisplatin (80mg/m2 day 1) and vinorelbine (20mg/m2 days 1 and 8) repeated every 4 weeks for 3–4 cycles. The dose of 3D-CRT was 66 Gy in 33 fractions, 72 Gy in 36 fractions, and 78 Gy in 39 fractions at levels 1–3, respectively. The dose-limiting toxicity (DLT), defined as grade ≥3 esophagitis, pneumonitis, myelitis, dermatitis and heart injury, and early stop of protocol treatment, was evaluated in 6–12 patients at each level. Results: Of the 17, 16 and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled into levels 1–3, respectively, of the study. A total of 26 patients were excluded because of V20 > 30% (n=10), overdose to the esophagus (n=8) and brachial plexus (n=2), comorbidity (n=3), or patient refusal (n=3). There were 26 men and 5 women with a median (range) age of 60 (41–75) years. Of these, 23 (74%) had adenocarcinoma and 20 (65%) had stage IIIA disease. The full planned dose of radiotherapy could be administered in all the patients, and more than 80% of the patients received 3–4 cycles of chemotherapy. Grade 3–4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, grade 3 esophagitis and grade 3 pulmonary toxicity were noted in one, two and one patients, respectively. DLT was noted in 17% of the patients at each level. Two (6%) complete and 27 (87%) partial responses were obtained. In a preliminary survival analysis, the median progression-free and overall survivals were determined to be 15.0 months and 37.6 months, respectively. Conclusions: At the level of 78Gy, only 25% of the patients assessed for eligibility were actually eligible. Toxicity was relatively mild up to 78 Gy in this highly selective patient group. Thus, we determined that the recommended dose of 3D-CRT administered concurrently with cisplatin and vinorelbine chemotherapy was 72Gy. [Table: see text]
The serial effects of multimodality therapy for stage III non-small cell carcinoma on lung function
Authors: Mazzone P. J. , Videtic G. , Murthy S. , Mason D. , Rice T. , Pennell N. , Rich T. , Machuzak M. , Mekhail T. 
Published: August 2020

7551 Purpose: To describe the effects of multimodality treatment on lung function in patients with stage III non-small cell carcinoma of the lung (NSCLC) Methods: Pulmonary function tests (PFTs) were reviewed for 32 patients with stage III NSCLC who were enrolled in a multimodality protocol that included neoadjuvant (NAd) combined chemoradiotherapy (taxol 50 mg/m2, carboplatin AUC 2 weekly X 3, radiation (XRT) 1.8 Gy BID to 30 Gy + erlotinib 150 mg/d for 28 days, followed by resection (R) and adjuvant (Ad) chemoradiotherapy (same as induction) followed by erlotinib 150mg/d maintenance (M) for 2 years. Changes in PFTs were analyzed at multiple time points (baseline to after NAd, after NAd to after R, after R to after Ad) and for the overall effect of treatment (baseline to the end of treatment). Results: The table below shows changes in percent predicted pulmonary function test values at each step in the treatment course. + signifies an increase and - a decrease. P indicates pneumonectomy and L lobectomy. Numbers in parentheses are the number of patients with complete testing at that time point. Conclusions: Neoadjuvant combined chemoradiotherapy has a small effect on lung function testing. The combined effect of multimodality therapy for stage III lung cancer that includes surgical resection leads to larger declines in lung function than have been reported historically for resection alone. [Table: see text] [Table: see text]
Analysis of four sorts of clinical factors associated with radiation-induced lung injury in patients with NSCLC after 3D-CRT
Authors: Zhang Y. , Liang C. , Li J. , Tian S. , Yu J. 
Published: August 2020

7552 Background: There are different clinical factors associated with radiation-induced lung injury in patients with non-small cell lung cancer (NSCLC) after three-dimensional conformal radiation therapy (3D-CRT) that have been studied, whereas their value are not same. According to their source, the factors can be sorted to four types. Methods: 119 NSCLC patients treated with 3D-CRT during 2003–2005 were retrospectively reviewed. They were divided into two arms according to whether grade >2 radiation- induced lung injury named by RTOG 3.0 were observed. The clinical parameters related to radiation-induced lung injury were divided into four sorts: general state of health and systematic sickness (gender, age, KPS, COPD, heart disease, diabetes), tumor-related factors (location, stage, volume), radiotherapy-related factors (dose, fraction per day, target margin, dosimetric parameters), other treatment factors (chemotherapy timing and agents). Univariate and multivariate analyses of the relation between clinical parameters and radiation pneumonitis were performed. Results: Occurrence of grade >2 radiation-induced lung injury was observed in 17/119 patients. In univariate analyses, GTV (p=0.009), ipsilateral mean lung dose (MLD)(p=0.017), ipsilateral lung V20 (p=0.036)and total lung MLD (p=0.034) were associated with radiation-induced lung injury. In multivariate analysis, ipsilateral lung MLD was the only independent factor associated with radiation-induced lung injury (p=0.019). A significant correlation was also observed between the three volumetric parameters (p≤0.001). Conclusions: Ipsilateral lung MLD was the only independent factor associated with grade >2 radiation-induced lung injury in our study, so that it should be included as a dose constraint factor for 3D-CRT of NSCLC. No significant financial relationships to disclose.
Operative outcomes using bevacizumab, docetaxel, and cisplatin as induction therapy in patients with operable lung cancer
Authors: Finley D. J. , Shen R. , Rizvi N. A. , Rusch V. W. , Kris M. G. 
Published: August 2020

7559 Background: Induction chemotherapy in patients with operable non-small cell lung cancer (NSCLC) is better tolerated than adjuvant chemotherapy. Bevacizumab improves survival in patients with advanced NSCLC; however its impact as an induction agent in patients undergoing lung resection is unknown. Here, we evaluated surgical outcomes in patients undergoing resection for NSCLC after induction therapy with bevacizumab (Bev), docetaxel (D) and cisplatin (C). Methods: Patients with stage IB-IIIA NSCLC, who could undergo resection with curative intent, were eligible for this phase II trial. None had squamous histology, large central tumors, or recent hemoptysis. All patients received up to 4 cycles of D 75 mg/m2 and C 75 mg/m2 and also received 3 cycles of Bev 15 mg/kg, followed by surgery. Two age and stage matched controls who received induction chemotherapy were selected per study patient. Fisher's exact tests compared pathologic stage, gender, and smoking history. Conditional logistic regression explored the association between clinical variables and outcomes in study versus control patients. Results: 30 patients received Bev-DC. Gender, smoking history, operative time, blood loss, and overall 30-day morbidity was similar between study and control patients. The 30 patients who received Bev-DC preoperatively had 12 complications vs 23 in the 60 controls. In the Bev-DC group there were 7 grade 3/4 complications (abscess (1), empyema (1), bronchopleural fistula (2), sigmoid volvulus (1), anastomotic dehiscence (1), GI bleed (1)) as compared to 2 in the control group (p=0.004). There were no deaths in the Bev-DC group and 2 among the controls. After controlling for age, gender and stage, patients in the study group had a trend towards increase incidence of overall complications (OR=3.89 (95%CI: 0.61–24.77) p=0.151). Conclusions: Although rates of 30-day morbidity were comparable, patients receiving Bev-DC induction had a higher incidence of grade 3/4 complications. There was no 30-day mortality among the patients receiving Bev-DC. Based on this interim analysis, patients receiving Bev-DC in the preoperative setting merit close monitoring. [Table: see text]
A multicenter, phase III study of carboplatin/paclitaxel versus oral uracil-tegafur as the adjuvant chemotherapy in resected non-small cell lung cancer (NSCLC): Planned interim analyses
Authors: Toyooka S. , Hotta K. , Nakamura H. , Nakata M. , Tada H. , Yamashita M. , Watanabe N. , Sakamoto J. , Aoe M. , Date H. 
Published: August 2020

7560 Background: Recent studies have demonstrated that adjuvant chemotherapy provides a survival benefit in patients with resected NSCLC. In Japan, uracil-tegafur has been recognized as a standard adjuvant strategy for resected NSCLC, however, carboplatin based adjuvant chemotherapy has not been fully evaluated for the treatment of NSCLC patients in an adjuvant setting. The present phase III study assessed the efficacy and safety of carboplatin/paclitaxel and oral uracil-tegafur as the first study to compare intravenous and oral drugs in resected stage IB-IIIA NSCLC. Methods: The patients with pathological stage IB-IIIA NSCLC who underwent complete resection were randomized 1:1 to carboplatin (AUC 5) /paclitaxel (175 mg/m2) every 3 week for 4 cycles (A arm) or uracil-tegafur (250 mg/m2) daily for 2 years (B arm). The primary endpoint was overall survival (OS) and secondary endpoints were disease-free survival and toxicity. The accrual of 200 patients per arm is required to demonstrate an improvement of OS (15% increase) in the A arm compared to B arm. Randomization was stratified by histology and tumor stage. An interim analysis was planned to perform on the first 200 patients recruited and data of survival and toxicity were examined in the first 100 patients. Results: Between November 2004 and November 2008, 200 patients from 31 Japanese centers were randomized and the first 100 patients were included for interim analysis. Median age was 69 (range; 50–80) years. Ninety-eight patients had PS of 0–1 and 2 patients had PS of 2. Sixty-seven patients were male and 23 patients were female. Sixty patients had adenocarcinoma, 30 had squamous cell carcinoma, and 10 had other histologies. Disease stage was IB in 53, IIA in 14, IIB in 19, and IIIA in 14 patients. Toxicities observed during adjuvant chemotherapy were well tolerable. There was no toxic death. The median survival time of A and B arms combined was 4.1 year. Monitoring Committees approved to continue the present study. Conclusions: The present phase III trial with carboplatin/paclitaxel or uracil-tegafur is feasible with manageable toxicity. The study is on course to achieve its primary endpoint. [Table: see text]
Randomized phase II trial of the biweekly schedule of adjuvant chemotherapy with carboplatin plus paclitaxel versus carboplatin plus gemcitabine in patients with non-small cell lung cancer (NSCLC)
Authors: Sugio K. , Nagashima A. , Nakanishi R. , Uchiyama A. , Inoue M. , Osaki T. , Yoshimatsu T. , Takenoyama M. , Hanagiri T. , Yasumoto K. 
Published: August 2020

7562 Background: Carboplatin plus paclitaxel and carboplatin plus gemcitabine chemotherapy have shown a good response and an improved survival against advanced NSCLC. This phase II trial assessed the feasibility, safety and efficacy of a bi-weekly schedule for adjuvant chemotherapy. Methods: Patients with completely resected stage IB-IIIB NSCLC were randomized to either carboplatin (AUC3) plus paclitaxel (90mg/m2) (arm A) or carboplatin (AUC3) plus gemcitabine (1000 mg/m2) (arm B), q2w for 8 cycles within 8 weeks after surgery. The main inclusion criteria were no prior chemotherapy or radiotherapy, ECOG PS 0–1, an age of less than 80 years, and an adequate organ function. The primary endpoint was compliance, and secondary endpoints were the disease free survival (DFS) and toxicity. The patients were stratified by gender, histology (adenoca vs. non-adenoca) and disease stage. Results: Between 07/2005 and 06/2007, 76 patients were randomized and 75 were eligible (including 48 males, 27 females; median age 66 years) for intent-to-treat analysis (39 in arm A, 36 in arm B). The histologic types included adenocarcinoma (n=51), squamous cell carcinoma (n=18), large cell carcinoma (n=5), and adenosquamous cell carcinoma (n=1). The pathological stages were IB/IIA/IIB/IIIA/IIIB: 22/10/13/29/1. Twenty-one of 39 pts (54%) in arm A and 25 of 36 pts (69%) in arm B completed 8 cycles, and 59% in arm A and 81% in arm B completed ≥6 cycles. Grade 3/4 hematologic toxicities (%) in arms A/B were respectively; neutropenia 36/53, anemia 0/17, thrombocytopenia 3/0, nausea 3/3. No treatment related deaths were observed. Up to 12/2008, 11 of 39 pts in arm A and 13 of 36 pts in arm B had recurrent disease, but no significant difference was observed. Conclusions: This adjuvant bi- weekly scheduled chemotherapy in both arms resulted in a good compliance and feasible with acceptable levels of toxicity in completely resected NSCLC. No significant financial relationships to disclose.