bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I trial of concurrent chemoradiotherapy (cCRT) with the conventional administration of docetaxel (D) and cisplatin (P) for dry-stage III non-small cell lung cancer (NSCLC) (JCOG9901DI)
Authors: Hida N. , Tsujimura S. , Fujii T. , Naoki K. , Kunikane H. , Okamoto H. , Shimizu T. , Watanabe K. 
Published: August 2020

7549 Background: In cCRT for locally advanced NSCLC, full dose chemotherapy with a new agent plus a platinum doublet is considered to have unacceptable toxicities. Consequently, weekly or split chemotherapy doses are often used. However, cCRT plus conventional regimens are expected to enhance systemic effects. This phase I trial aimed to establish the MTD of cCRT plus conventional administration of DP (conv-DP). Methods: Unresectable stage III NSCLC patients (pts) (<70 years) with ECOG performance status 0–1 and adequate organ function were eligible. Pts received 60 Gy in 30 fractions by once daily radiotherapy. Concurrent P (day1; 60 mg/m2 at levels 1–3, 80 mg/m2 at level 4) and D (day1; 30 mg/m2 at level 1, 40 mg/m2 at level 2, 50 mg/m2 at levels 3–4) were given every 4 weeks for at least 2, and up to 4 courses. DLT was defined as either Gr3/4 febrile neutropenia, Gr4 neutropenia lasting ≥ 4 days, Gr4 thrombocytopenia, Gr2 pneumonitis or any Gr3 non-hematological toxicities except for nausea, vomiting and alopecia. Results: Eighteen pts were enrolled from 06/1999 to 05/2006: 6 pts at levels 2 and 4, 3 pts at levels 1 and 4; 13 males; median age 60 years (range 43–70); stage IIIA/IIIB 5/13; histology Ad/Sq/Large 9/7/2. DLTs were observed for 3 pts at level 2 (D40/P60): Gr4 pneumonitis at level 3(D50/P60), Gr3 cerebral infarction and Gr3 atrial fibrillation. Although 3 cases were added at these levels, tolerability for each level was cleared, as DLTs occurred for ≤ 2 pts among 6. MTD was not detected, even at the highest dose (D50/P80). However, dose escalation was stopped, as D60/P80 was the recommended dose for chemotherapy alone in Japan. Radiotherapy (60 Gy) was completed for 15 pts. Seventeen pts received more than 2 courses of chemotherapy. No Gr3/4 esophagitis or severe hematologic toxicities were observed. Objective response rate was 89% and 1-yr survival rate was 55%. Conclusions: The recommended dose in this regimen was D50/P80, which was near the full dose for conv-DP. Based on these promising results, we are planning a phase II trial to evaluate the efficacy and toxicity of this cCRT with conv-DP therapy. No significant financial relationships to disclose.
A phase I/II trial of perioperative paclitaxel (P), carboplatin (C), and erlotinib (E) with concurrent accelerated hyperfractionated radiation (HFRT) followed by maintenance E for stage III non-small cell lung cancer (NSCLC)
Authors: Pennell N. A. , Videtic G. M. , Murthy S. , Mason D. , Rice T. W. , Mazzone P. , Samsa J. , Rich T. , Shapiro M. , Mekhail T. 
Published: August 2020

7557 Background: Concurrent chemoradiotherapy (CRT) is standard treatment for stage III NSCLC, although the management of resectable patients (pts) remains controversial. We report an open-label phase I/II trial of the epidermal growth factor receptor inhibitor E added to perioperative CRT for resectable stage III NSCLC pts, followed by maintenance (m) E. Methods: Eligible pts had stage IIIA/B NSCLC, PS 0–1, and were resectable as determined by a thoracic surgeon. Pts received weekly P (50 mg/m2), and C (AUC 2) with daily oral E for 28 days concurrent with twice daily thoracic radiation (1.5 Gy/fraction) to 30 Gy, followed by restaging. Non-progressors underwent resection followed by the same CRT regimen and 2 years of mE (150mg). The primary endpoint of the phase I portion was the maximum tolerated dose (MTD) of E given with CRT; and for the phase II was safety and tolerability. Secondary endpoints were pathologic complete response (pCR) rate, pathologic downstaging of mediastinal nodes, progression free survival (PFS), and overall survival (OS). Results: 9 pts were enrolled in the phase I trial. The MTD of E was150mg, which was the phase II dose used. 25 pts were treated in the phase II component: median age 60, 92% stage IIIA, 64% female, 72% PS 0, 64% adenocarcinoma, and 16% never smokers. The median duration of mE was 5.5 months, with the most common reason for discontinuation being pt preference. There was no grade 4 toxicity. Grade 3 toxicity seen in >5% of pts: rash (12%), diarrhea (9%), nausea (9%), and encephalopathy (6%). The most common toxicities during mE: grade 1/2 diarrhea (72%), rash (61%), fatigue (56%), nausea (22%), and dry eyes (17%).1 pt (4%) had a pCR after neoadjuvant CRT, and 46% were downstaged to pN0–1 at surgery. At a median follow-up of 36.5 mos the median PFS is 41.8 mos (95% CI 9.3-not yet reached). The median OS has not been reached. 3 year survival is 69%. Pts downstaged to pN0–1 vs those with persistent pN2–3 had a median PFS of 41.8 vs 18.1 mos (p=0.11). Conclusions: Perioperative P, C, and E given concurrently with HFRT was well tolerated and showed promising efficacy, while compliance was poor with maintenance E. [Table: see text]
Comparative use of perioperative chemotherapy (CT) in non-small cell lung cancer (NSCLC) between 2004 and 2007
Authors: Le Naour B. , Mauguen A. , Fabre D. , Pignon J. , Planchard D. , Soria J. , Dartevelle P. , Besse B. 
Published: August 2020

7564 Background: Adjuvant (ADJ) platinum-based CT has become a new standard of care for patients (pts) with resected stage II and III NSCLC, and is discussed in selected stage IB pts. Impact of positive randomized trials which showed significant survival improvement (first published in 2004) on the use of ADJ CT has been poorly studied to date. Methods: A retrospective study of consecutive pts with NSCLC who underwent curative surgery during the first half of year 2004 and 2007 in the surgical center Marie Lannelongue (France) was conducted. Logistic regression models were employed to identify cofactors associated with the use of ADJ CT (excluding stage IV). Odds ratio (OR) > 1 corresponds to a more frequent use than in reference group. Results: A total of 240 pts (116 in 2004, 124 in 2007) underwent curative surgery for NSCLC (11% IA; 30% IB; 27% II; 27% III; 5% IV). Among all pts, 12 % received neoADJ CT (less in 2007, 8% vs 16% p=.04), 35% ADJ (4% both). Reasons for not receiving ADJ CT included stage I (34%), death (11%), comorbidities (10%), poor performance status (10%), advanced age (8%), post-operative complications (7%), patient refusal (3%). More ADJ CT was prescribed in 2007 (41% vs 30% in 2004, p=.009). Overall, 45% of pts with stage II-III received ADJ CT in 2004 versus 69% did so in 2007. In multivariate analysis (194 pts), ADJ CT was associated with the year of inclusion (OR=2.67 p=.009), stage (stage II, OR=6.77, stage III, OR=16.85; p<.0001), serious medical history (OR=.41 p=.01) and salvage surgery (OR=.26 p=.03). Cisplatin was the preferred platinum compound in 76% of neoADJ regimens (mostly cisplatin-docetaxel), and 70% of ADJ CT (mostly cisplatin-vinorelbine). Conclusions: The presentation and publication of “positive” ADJ CT trials had significantly increased prescription of ADJ CT in pts with stage II-III NSCLC. Nevertheless 31% of the stage II-III did not received CT mostly because of comorbidities, highlighting the need of a personalized CT. No significant financial relationships to disclose.
Pemetrexed in combination with cisplatin or carboplatin as adjuvant chemotherapy in early-stage NSCLC
Authors: Schmid-Bindert G. , Chemaissani A. , Fischer J. R. , Schütte W. , Mazières J. , Viñolas N. , Wolf M. , Thareau Vaury A. , Leschinger M. , Reck M. 
Published: August 2020

7565 Background: Platinum based chemotherapy after complete resection of stage I-IIIa non-small cell lung cancer (NSCLC) has improved 5-yr survival by 4–15%. Pemetrexed (P) in combination with cisplatin (C) or carboplatin (Carb) has shown to be effective and safe in first-line Tx of advanced NSCLC, thus being a promising option in the adjuvant setting. Methods: Multicenter, open phase 2 in pts with resected stage Ib/II NSCLC. Pts were randomized to P (500 mg/m2)+C (75mg/m2) or P (500 mg/m2)+Carb (AUC5) d1 q3 wks, for 4 cycles; adequate organ function and ECOG PS 0–1 required. Primary endpoint was feasibility of the regimen defined as compliance to 4 Tx cycles with ≥ 95% of planned dose without ≥ Grade 3 toxicities (tox) at 30 d after last infusion. A regimen was deemed feasible if the rate (feasible pts/total pts) was >60%. Results: Please see Table for results. Conclusions: According to the strict definitions in this protocol neither regimen was feasible. The reason was poor compliance with at least one of the components that defined feasibility, but dose intensity and % pts completing cycle 4 was notably high, compared to other adjuvant trials. P+C was the more favourable regimen concerning feasibility and tolerability. In terms of tolerability pemetrexed could be combined with either platinum compound. [Table: see text] [Table: see text]
Predictive role of 18F-FDG-PET/CT 1 month before and after hypofractionated stereotactic body radiation therapy for stage I non-small cell lung cancer
Authors: Song S. , Ryu J. , Lee S. , Ahn S. , Kim J. , Lee J. , Park C. , Choi E. 
Published: August 2020

7569 Background: To know the predictive role of 18F-FDG-PET/CT 1month before and after stereotactic body radiation therapy (SBRT) to stage I non-small cell lung cancer (NSCLC). Methods: Between 2004 and 2007, 20 patients received SBRT with 48 Gy for 4 consecutive days and checked two times of FDG- PET/CT and chest CT with contrast-enhancement at 1 month before and after SBRT. Change of maximal SUV (SUVmax) on FDG-PET/CT and the longest tumor diameter on chest CT before and after SBRT was measured. Patients only with high FDG uptake, SUVmax 3.0 or above, on FDG-PET/CT before SBRT and tumor diameter below 5 cm were analyzed in this study. Change of tumor diameter was classified to PR (partial response), SD (stable disease), and DP (disease progression) as RECIST criteria and change of SUVmax was described as % change. Chest CT was checked at every 3 or 6 months during follow-up. Results: Mean time intervals from SBRT to FDG-PET/CT and chest CT were 32 and 30 days respectively. Mean longest tumor diameter was changed from 2.59 cm (1.36–3.93) to 2.17 cm (1.18–3.41), and its reduction rate was -16.2%. By RECIST criteria, 4 patients showed PR, 15 patients showed SD, and other 1 patient showed DP. Mean decrease rate of SUVmax on FDG-PET/CT was -52.1% and its mean value was changed from 7.1 (3.2–13.1) to 3.4 (0.3–9.8). Median follow-up time was 16 months. Local tumor progression developed in 2 (10%) patients and time to progression was 3.4, 6.1 months. Tumor responses on post-SBRT chest CT were PR in 1 and SD in the other 1 patient, and SUVmax changes were -31.9%, -25.5% in each. Most of patients showing no response, SD or DP, didn't recur after SBRT, and so chest CT at 1 month could not predict actuarial tumor response. On the contrary to chest CT, no patients showing SUVmax decreases over 40% experienced tumor progression after SBRT. High decrease rate of SUVmax over 40% decrease on FDG-PET/CT 1 month after SBRT could warrant good actuarial local tumor control earlier. Conclusions: Change of SUVmax on FDG-PET/CT 1 month before and after SBRT could predict actuarial local tumor control of stage I NSCLC earlier and 1 month after SBRT was adequate timing for the earlier evaluation of tumor response. No significant financial relationships to disclose.
Value of FDG-PET/CT findings revised using an anthropomorphic body phantom for the evaluation of tumor malignancy grade in small-sized lung adenocarcinomas: A multicenter study
Authors: Nakayama H. , Kato Y. , Tsuboi M. , Okumura S. , Daisaki H. , Uehara H. , Adachi S. , Yoshimura M. , Okada M. 
Published: August 2020

7573 Background: The malignant behavior of small lung adenocarinomas (AD), which have been detected with increasing frequency recently, has not yet been clearly evaluated, and an understanding of this biological characteristic is vital for selecting the appropriate therapeutic strategy. We examined the malignancy grade of small lung ADs using FDG-PET/CT (PET), in addition to high-resolution CT (HRCT) and pathologic evaluation in a multicenter setting. Methods: A total of 204 patients with cT1N0M0 AD underwent PET and HRCT, followed by complete resection with lymph node dissection. The associations between components of bronchioloalveolar carcinoma (BAC) on pathologic examination and maximum standardized uptake value (maxSUV) on PET, ground-glass opacity (GGO) ratio and tumor disappearance rate (TDR) on HRCT were examined, and these findings were analyzed in relation to pathologic features and surgical outcomes. To reduce the errors in PET machines used for this analysis, maxSUV data were adjusted using an anthropomorphic body phantom of the NEMA standards (corrected maxSUV). Results: Examination of tumor aggressiveness based on the presence of lymphatic, vascular and pleural invasion, and of nodal metastasis, showed that maxSUV, BAC ratio, TDR, and GGO ratio, in the order, can reflect the malignancy grade. MaxSUV and BAC ratio were also valuable prognostic predictors of the disease-free survival. There were no significant differences in the values between maxSUV and corrected maxSUV. Although BAC ratio was significantly associated with maxSUV, GGO ratio and TDR (all p<0.0001), the degree of association with maxSUV (R2=0.2533) was weaker than that with GGO (R2=0.5843) ratio or TDR (R2=0.5123). Conclusions: A higher maxSUV reflects an aggressive malignant behavior of cT1N0M0 ADs, independently of BAC component. Assessment by PET in addition to HRCT is useful for selection of the appropriate treatment strategy for small lung AD. [Table: see text] No significant financial relationships to disclose.
The impact of length of hospitalization following surgical resection of stage I non-small cell lung cancer on long-term survival
Authors: Kilic A. , Schuchert M. J. , Landreneau J. R. , Landreneau J. P. , Oostdyk A. , Wilson D. O. , Luketich J. D. , Landreneau R. J. 
Published: August 2020

7584 Background: The aim of this study was to evaluate the impact of length of hospital stay (LOS) following surgical resection of stage I non-small cell lung cancer (NSCLC) on long-term survival. Methods: We reviewed the records of patients undergoing surgical resection for stage I NSCLC at our institution between 1990–2003. Patients not surviving hospitalization related to their surgery were excluded from analysis. Multivariate analysis was utilized to evaluate the impact of age, gender, tumor histology, tumor stage, LOS, and type of operation (lobar or sublobar) on long-term (>5 year) survival. As a secondary analysis, Kaplan-Meier survival curves of patients stratified according to LOS were compared using the log-rank test. Two-tailed p-values less than 0.05 were considered statistically significant. Results: A total of 730 patients underwent lobectomy (n=518) or sublobar resection during the study time period. There were 18 (2.5%) operative or in-hospital mortalities. Median LOS was 6 (range 1–81) and 7 (range 1–46) days in the lobar and sublobar cohorts, respectively. Patients with a longer hospital stay (≥14 days) had significantly worse 5- and 10-year overall survival rates as compared to those with a shorter hospitalization (lobectomy: 5-year- 60.3% vs 33.8%; 10-year-27.3% vs 8.4%; p<0.001; sublobar: 5-year-44.3% vs 11.7%; 10-year-9.9% vs 0%; p=0.006). There were 171 patients with extended clinical follow-up who had survived at least 5 years (mean follow-up = 88.1 ± 2.0 months). Multivariate analysis demonstrated that LOS predicted long-term survival independent of patient age, gender, tumor histology, tumor stage, and type of operation (p=0.013). Conclusions: LOS following surgical resection of stage I NSCLC is an independent predictor of long-term survival. These survival differences related to hospital stay may be related to underlying medical co-morbidities important to the decision making regarding therapy of patients with otherwise resectable stage I lung cancer. Prospective assessment of medical co-morbidities may be an important initiative for future treatment planning of early stage lung cancer patients. No significant financial relationships to disclose.
Assessment of the safety and efficacy of percutaneous cryoablation for lung tumors
Authors: Yamauchi Y. , Izumi Y. , Tsukada N. , Asakura K. , Inoue M. , Yashiro H. , Nakatsuka S. , Kawamura M. 
Published: August 2020

7592 Background: Percutaneous cryoablation using high resolution fluoroscopic CT guidance under local anesthesia offers a potential tool for local control of lung tumors in combination with systemic treatments. In this study, we retrospectively analyzed the safety, and efficacy of percutaneous cryoablation for lung tumors (PCLT). Methods: This study was approved by the institutional review board. From October 2002, PCLT was performed in patients who either did not oncologically fulfill the indications for resection, or refused resection. CT scan was examined every 3 months after PCLT. >20% increase in the treated lesion size was diagnosed as local failure. Survival analysis was done by Kaplan-Meier. Results: There were 147 patients (95 male, 52 female, mean age 60, 20 primary lung cancer, metastases; 29 of lung cancer, 35 of colorectal cancer, 63 of other sites). 251 sessions were done for 462 tumors. Mean tumor diameter was 18.3mm. PCLT was well tolerated in most patients. In 1 case, broncho-thoracic fistula occurred in the treated region which lead to empyema. Other complications were pneumothorax (153 sessions, 61%, chest tube required in 23 sessions), pleural effusion (160 sessions, 64%), and transient hemoptysis (82 sessions, 33%). Overall one- and two-year local control rates were 81.0% and 59.1%, respectively. Overall one- and two-year survival rates were 80.0% and 54.5%, respectively. In the 1–20 mm sized (n=362) vs. over 21mm sized (n=100) lesions, the local control rates at one year were 84% vs. 56% (p=0.0007), and at two years were 63% vs. 35% (p=0.017), respectively. There were no differences in local control between primary and metastatic tumors, carcinomas and sarcomas. Survival of patients whose lesions were limited to 1–20mm (n=89) was prolonged vs. those who had at least one over 21mm lesion (n=58) (p=0.01). However, one, and two-year survival rates did not differ significantly between these groups (one-year; 85.5% vs. 71.7% (p=0.07), two-year; 60.7% vs. 46.5% (p=0.16)). Conclusions: PCLT was minimally invasive and safe. 1–20mm tumors were good candidates. Contribution of PCLT to survival was not clear in this mixed patient population. To improve local control in over 20 mm tumors, we are computer simulating freezing kinetics to optimize the number and the positioning of the probes. No significant financial relationships to disclose.
SATURN: A double-blind, randomized, phase III study of maintenance erlotinib versus placebo following nonprogression with first-line platinum-based chemotherapy in patients with advanced NSCLC
Authors: Cappuzzo F. , Ciuleanu T. , Stelmakh L. , Cicenas S. , Szczesna A. , Juhasz E. , Esteban Gonzalez E. , Molinier O. , Klingelschmitt G. , Giaccone G. 
Published: August 2020

8001 Background: Erlotinib (E), a small-molecule EGFR TKI, is proven to extend survival versus placebo (P) in 2nd/3rd-line advanced NSCLC. The phase III SATURN study (BO18192) was initiated to evaluate E as maintenance therapy after standard 1st-line platinum-based chemotherapy (CT) in advanced NSCLC. Methods: Patients with no evidence of disease progression after 4 cycles of CT were randomized to receive either E 150 mg/day or P until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) in all patients and the co-primary endpoint was PFS in EGFR immunohistochemistry-positive (IHC+) patients. Results: A total of 1,949 patients entered the CT phase, of whom 889 were randomized to E (n=438) or P (n=451). Median age was 60 years for both arms. Baseline characteristics for E and P arms (%): male/female: 73/27 and 75/25; adenocarcinoma + BAC/squamous-cell/other: 47/38/15 and 44/43/13; stage IIIB/IV: 26/74 and 24/76; Caucasian/Asian/other: 84/14/2 and 83/15/2; ECOG PS 0/1: 31/69 and 32/68; current/former/never smoker: 55/28/18 and 56/27/17. PFS (by investigator assessment; confirmed by independent review) was significantly prolonged with E versus P in all patients (HR 0.71 [95% CI 0.62–0.82]; p<.0001) and in EGFR IHC+ patients (HR 0.69 [95% CI 0.58–0.82]; p<.0001). Subgroup analyses will be reported. Response rate was 12% with E versus 5% with P. Disease control rate (complete response + partial response + stable disease >12 wks) was 40.8% with E versus 27.4% with P (p<.0001). OS data are not yet mature. E was well tolerated: the majority of treatment-related adverse events (AEs) were grade 1/2. AEs reported in ≥10% of all patients were rash (60% with E versus 9% with P) and diarrhea (20% with E versus 5% with P); again, most were grade 1/2. Only 2.3% of patients receiving E had a serious treatment-related AE and 2.8% withdrew due to a treatment-related AE. Conclusions: The SATURN study met its primary and co-primary endpoints with high statistical significance. Erlotinib in the 1st-line maintenance setting is well tolerated, and significantly improves disease control and delays progression versus placebo across patient subgroups. [Table: see text]
Multicenter prospective trial of customized erlotinib for advanced non-small cell lung cancer (NSCLC) patients (p) with epidermal growth factor receptor (EGFR) mutations: Final results of the Spanish Lung Cancer Group (SLCG) trial
Authors: Massuti B. , Morán T. , Porta R. , Queralt C. , Cardenal F. , Mayo C. , Camps C. , Majem M. , Tarón M. , Rosell R. 
Published: August 2020

8023 Background: The purpose of the study was to evaluate the efficacy of erlotinib and the feasibility of screening for EGFR mutations in advanced NSCLC p (chemonaive or relapsed after 2 prior chemotherapy regimens). Methods: Exon 19 deletions and L858R mutations in tumor and paired serum DNA were assessed in one central laboratory, using three different techniques. Results: From April 2005 to December 2008, 2507 p were screened. EGFR mutations were detected in 358 p; 217 were entered on the trial: 158 (72.8%) female; 148 (68.2%) never-smokers; 176 (81.1%) adenocarcinoma; 134 (62.3%) exon 19 deletion, 83 (37.7%) L858R mutation; 112 (51.6%) first-line, 104 (48.4%) second-line. Response in 139/197 evaluable p (70.6%); complete response (CR) in 24 p (12.2%). Odds ratio for response: 3 for p with exon 19 deletion (P=0.001). Time to progression (TTP): 14 months (m). Median survival (MS): 27 m. MS according to response shown in table. Cox model for TTP showed that male gender (hazard ratio [HR], 2.3; P=0.001), L858R mutation (HR, 1.8; P=0.008), and mutated EGFR in serum (HR,1.6; P=0.03) had a negative impact. Conclusions: A multicenter study of customized erlotinib, using a central screening laboratory, is feasible and shows the outstanding benefit to p for selecting erlotinib treatment based on EGFR mutation status. The SLCG has initiated a randomized trial of first-line erlotinib vs chemotherapy. [Table: see text] No significant financial relationships to disclose.