bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of brachytherapy on local recurrence after sublobar resection: Results from ACOSOG Z4032 (Alliance), a phase III randomized trial for high-risk operable non-small cell lung cancer (NSCLC).
Authors: Fernando Hiran Chrishantha , Landreneau Rodney Jerome , Mandrekar Sumithra J. , Nichols Francis C , Hillman Shauna L , Heron Dwight Earl , Meyers Bryan F , DiPetrillo Thomas A. , Jones David Randolph , Starnes Sandra Lynne , Tan Angelina D. , Daly Benedict , Putnam Joe B. ,   Alliance for Clinical Trials
Published: March 2020

7502 Background: Prior studies suggest that adjuvant brachytherapy reduces local recurrence (LR) after sublobar resection (SR) for NSCLC. A multicenter randomized study was undertaken in patients (pts) with stage I NSCLC ≤3cm comparing SR to SR with brachytherapy (SRB). Methods: High-risk operable patients with NSCLC were randomized to SR or SRB. Brachytherapy involved placement of I125 seeds incorporated into Vicryl sutures or into Vicryl mesh placed over the staple line. Wedge or segmental resection was allowed. The primary endpoint was time to local recurrence (LR) defined as recurrence within the primary tumor lobe at the staple line (local progression), away from the staple line or within hilar nodes. The trial was designed to have 90% power to detect a hazard ratio (HR) of 0.315 in favor of the SRB arm using a one-sided α of 0.05 with a sample size of 100 eligible pts per arm. Follow-up CT scans were obtained serially for 36 months. Results: 224 pts were randomized; 213 (109 SR,104 SRB) were eligible. Median (range) age was 71 (49-87) yrs; 94 (44%) were male. No differences were found in baseline characteristics. Adverse events, previously reported, were not different between arms. Median (range) follow-up was 4.06 (0.04, 5.0) yrs. There was no difference between arms in time to LR (HR = 0.87; 5% CI: 0.41, 1.86, p=0.72) or to LR or death (LRD) (HR = 0.81, 95% CI: 0.50, 1.32, p=0.40). There was no difference between arms in pattern of LR (table). In subgroups of pts with potentially compromised surgical margin (margin < 1cm; margin:tumor ratio <1; positive staple line cytology) SRB did not reduce LR or LRD at 3-yrs. Overall 3-yr survival was similar for SR (71%) and SRB (72%) (p=0.81). Conclusions: LR remains a concern after sublobar resection. However, local progression at the staple line was low. This trial demonstrated that adjuvant brachytherapy does not impact oncologic outcomes. Clinical trial information: NCT00107172. [Table: see text]
Result of phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small cell lung cancer.
Authors: Sun Yan , Cheng Ying , Hao Xuezhi , Wang Jie , Hu Chengping , Han Baohui , Liu Xiaoqing , Zhang Li , Wan Huiping , Xia Zhongjun , Liu Yunpeng , Li Wei , Hou Mei , Zhang Helong , Xiu Qingyu , Zhu Yunzhong , Feng Jifeng , Qin Shukui 
Published: March 2020

7507 Background: Etoposide combined with cisplatin (EP) has been the first-line chemotherapy regimen for small cell lung cancer (SCLC) for >20 years; however, a more effective regimen has been recommended by many clinical oncologists. Thus, we here present our preliminary results of a phase III clinical trial of the novel drug amrubicin in combination with cisplatin (AP) in comparison to EP in patients with previously untreated extensive SCLC (ED-SCLC). Methods: A total of 299 previously untreated ED-SCLC patients were randomized (ratio, 1:1) into two treatment groups: (1) the AP group (n = 149): 4–6 cycles of amrubicin (40 mg/m2/day on days 1–3) and cisplatin (60 mg/m2/day on day 1) and (2) the EP group (n = 150): 4–6 cycles of etoposide (100 mg/m2/day on days 1–3) and cisplatin (80 mg/m2/day on day 1 every 21 days). Patients were evaluated for therapy response and electrocardiography results every 2 cycles. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), overall response rate (ORR), and general safety. Results: Baseline characteristics were similar among the two groups. For AP and EP groups, the median OS was 11.79 and 10.28 months, the median PFS was 7.13 and 6.37 months, and ORR was 69.8% and 57.3%, respectively. The most frequent adverse events (≥grade 3) in AP and EP groups were bone marrow failure (23.5% and 21.3%, respectively), neutropenia (54.4% and 44.0%, respectively), and leukopenia (34.9% and 19.3%, respectively). Conclusions: Our phase III trial demonstrated that for previously untreated ED-SCLC patients, AP therapy was not inferior to EP therapy in terms of OS and offered predictable and manageable toxicities. Clinical trial information: NCT00660504.
Three-arm randomized phase II study of cisplatin and etoposide (CE) versus CE with either vismodegib (V) or cixutumumab (Cx) for patients with extensive stage-small cell lung cancer (ES-SCLC) (ECOG 1508).
Authors: Belani Chandra Prakash , Dahlberg Suzanne Eleanor , Rudin Charles M. , Fleisher Martin , Chen Helen X. , Takebe Naoko , Ramalingam Suresh S , Schiller Joan H. 
Published: March 2020

7508 Background: Targeted inhibition of the Hedgehog (HH) pathway by V & Insulin-like Growth Factor type-1 Receptor (IGF-1R) by Cx enhances efficacy of chemotherapy, and also demonstrates activity against the tumor cell fraction responsible for disease recurrence in SCLC. Methods: Patients (Pts) with newly diagnosed ES-SCLC with measurable disease, ECOG PS 0-1 were randomized to receive (four 21-day cycles) CE alone [(C 75 mg/m2 D1 & E 100 mg/m2 D1-3) Arm A] or in combination with either V [(150 mg/day PO) Arm B] or Cx [(6mg/kg weekly IV) Arm C]. Pts with responsive or stable disease on Arms B & C were continued on V or Cx respectively until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), stratified on gender. Circulating tumor cells (CTCs) were isolated/enumerated by Veridex Cell Search Platform at baseline, after 1or 2 cycles of chemotherapy, at completion of 4 cycles & 3 months (m). thereafter for correlation with efficacy parameters. The study was designed to detect a PFS HR of 0.58 with 90% power & an overall one-sided type I error rate of 0.10 for each of the comparisons of the V and Cx arms to CE alone. Results: 155 eligible pts were treated; 136 have died & 149 have experienced a PFS event. Pt. demographics & disease characteristics are well-balanced between the three arms except higher rate of PS 0 on Arm B (p=0.03). The median PFS on Arms A, B & C are 4.7, 4.4 & 4.6 m, the median OS 9.1, 9.8 & 10.1 m, & the RR are 43%, 52% & 49% respectively. None of the comparisons of these outcomes are statistically significant. PFS HR for V+CE vs. CE: 1.32, p=0.21, and for Cx+CE vs. CE: 1.12, p=0.58. The median OS among those with low CTC count (≤100 per 7.5ml) at baseline is 10.7 m vs. 7.2 m for those with high CTC count [HR1.70, p=0.01]. Toxicities in all three arms are as expected with the combination of CE alone. Conclusions: There is no significant improvement in PFS or OS with the addition of either V or Cx to CE vs.CE alone in pts with ED-SCLC. Low baseline CTC count is associated with improved OS, suggesting its role as a prognostic biomarker in SCLC. Clinical trial information: NCT00887159.
Multitrial evaluation of progression-free survival (PFS) as a surrogate endpoint for overall survival (OS) in previously untreated extensive-stage small cell lung cancer (ES-SCLC): An Alliance-led analysis.
Authors: Foster Nathan R. , Renfro Lindsay A. , Schild Steven E. , Redman Mary Weber , Wang Xiaofei F. , Dahlberg Suzanne Eleanor , Ding Keyue , Bradbury Penelope Ann , Ramalingam Suresh S. , Gandara David R. , Vokes Everett E. , Adjei Alex A. , Mandrekar Sumithra J. 
Published: March 2020

7510 Background: We previously demonstrated that PFS may be a candidate surrogate endpoint for OS in ES-SCLC using data from 3 randomized trials (Foster, Cancer 2011). Here, we sought to formally assess the patient- and trial-level surrogacy of PFS using data from 9 additional randomized phase II and III trials conducted by the NCI-funded cancer cooperative groups since 1986. Methods: Individual patient data from all 12 trials (3178 patients: 9 phase III and 3 phase II) were pooled. OS was the primary endpoint in all phase III trials; 3 phase III and 1 phase II trial were positive per protocol. Patient-level surrogacy (Kendall’s tau) was assessed using the Clayton copula bivariate survival model. Trial-level surrogacy was assessed via association of the log hazard ratios on OS and PFS across trials, including: weighted (by trial size) least squares regression of Cox model effects (R² WLS) and weighted (by trial size) correlation of the copula effects (R² Copula). One trial had 4 treatment arms thus 14 total two-arm comparisons were made. Results: With a median follow-up of 41.8 months in the 106 patients still alive, the median OS and PFS across trials were 9.7 months (95% CI: 9.5, 9.9) and 5.7 months (95% CI: 5.5, 5.8), respectively. There were 3120 PFS events in total (2564 disease progressions and 556 deaths without progression). The median time from progression to death was 4.1 months (95% CI: 3.9, 4.3). PFS showed modest association with OS at the patient-level (tau= 0.56) and at the trial-level (R² WLS = 0.58; R² Copula (standard error) = 0.55 (0.29)). The 95% CIs for the predicted HR for OS given observed HR on PFS under a weighted leave-one-out prediction always included the observed HR for OS; however such intervals were wide, suggesting uncertainty on the practical use of PFS as a surrogate for OS in this setting. Conclusions: PFS failed to demonstrate surrogacy for OS in ES-SCLC based on this large pooled analysis. Given that the difference in the median PFS and OS is less than 6 months, we recommend using OS as the primary endpoint in phase III trials of previously untreated ES-SCLC.
Surgery for early non-small cell lung cancer with preoperative erlotinib (SELECT): A correlative biomarker study.
Authors: Sacher Adrian G. , Lara-Guerra Humberto , Waddell Thomas K. , Kim Lucia , Chen Zhuo , Salvarrey Alexandra , Darling Gail , Yasufuku Kazuhiro , Keshavjee Shaf , de Perrot Marc , Shepherd Frances A. , Liu Geoffrey , Tsao Ming Sound , Leighl Natasha B. 
Published: March 2020

7516 Background: Erlotinib has demonstrated major activity in EGFR mutation positive NSCLC, but may also benefit those with wild-type tumours. We conducted a single-arm trial of pre-operative erlotinib in early stage NSCLC to assess radiologic and functional response as well as correlation with known and investigational biomarkers. Methods: Patients with clinical stage IA-IIB NSCLC received erlotinib 150 mg daily for 4 weeks followed by surgical resection. Tumor response was assessed using pre- and post-treatment CT and PET imaging. Pharmacodynamic changes were assessed through comparison of pre- and post-treatment tumour samples (including Sequenom MassARRAY analysis) and measurement of circulating markers/ligands for EGFR activation (TGF-α, amphiregulin, epiregulin, EGFR SNP, EGFR ECD). Secondary endpoints included pathological response, toxicity and progression-free survival. Results: Twenty-five patients were enrolled; 22 received erlotinib treatment with a median follow up of 4.4 years (range 2.2 to 6.4 years). Histology was predominantly adenocarcinoma (14) with smaller numbers of squamous carcinoma (7) and large cell carcinoma (1). PET response (25% SUV reduction) was observed in 2 patients (9%), both with confirmed squamous carcinoma histology. All patients met criteria for stable disease by RECIST and several experienced minor radiographic regression with histologic findings of fibrosis/necrosis, including 2 with squamous histology. The presence of an EGFR exon 19 deletion was detected in one adenocarcinoma case; the patient experienced a minor radiographic response to treatment. Genotyping, functional protein assays and ligand analysis are ongoing. Conclusions: Erlotinib appears to demonstrate some activity in patients with squamous histology. While EGFR mutations have been infrequently demonstrated in squamous NSCLC, the potential exists for other biomarkers predictive of benefit. Clinical trial information: NCT00462995.
Blinded assessment of radiological changes after stereotactic ablative radiotherapy (SABR) for early-stage lung cancer: Local recurrences versus fibrosis.
Authors: Senan Suresh , Huang Kitty , Senthi Sashendra , Spoelstra Femke , Warner Andrew , Slotman Ben J. , Palma David 
Published: March 2020

7520 Background: Stereotactic ablative radiotherapy (SABR) is a guideline-recommended treatment for unfit patients with early-stage lung cancer. The 5-year local recurrence rates are approximately 10% but fibrotic changes are common during follow-up, leading to difficulty with timely detection and salvage therapies. Previously reported high-risk features (HRFs) on computed tomography (CT) are 1) enlarging opacity at the primary site; 2) sequential enlarging opacity; 3) enlarging opacity after 12 months; 4) bulging margin; 5) loss of linear margin and 6) loss of air bronchograms. We performed a blinded assessment of CT imaging of patients with and without local recurrences. Methods: Patients treated with SABR for early stage lung cancer between 2003 and 2012, who developed pathology-proven local recurrence (n=12), were matched 1:2 to patients without recurrences (n=24), based on baseline factors. The median age at diagnosis was 68 years and median post-SABR imaging follow-up was 24 months (range 6 to 67 months). Patients were well-matched in the recurrence and non-recurrence groups. A total of 153 CT scans were available. Serial CT images were assessed by 3 radiation oncologists blinded to outcomes, viewing anonymized images projected onto a large screen. Results: All established HRFs were significantly associated with local recurrence (p<0.01), and one additional HRF was identified: cranio-caudal growth (p<0.001). The best individual predictor of local recurrence was opacity enlargement after 12 months(100% sensitivity, 83% specificity, p<0.001). The odds of recurrence increased 4-fold for each additional HRF detected in an individual patient. The presence of ≥3 HRFs in an individual patient was highly sensitive and specific for recurrence (both >90%). The HRFs enlarging opacity and cranio-caudal growth were each detected ≥3 months prior to the actual diagnosis of local recurrence in 42% of patients. Conclusions: Local recurrences following SABR can be accurately predicted by the presence of HRF’s on post-treatment CT scans. This approach may reduce unnecessary diagnostic procedures, and ensure earlier use of salvage therapies.
Factors impacting oncologic outcomes after sublobar pulmonary resection: Results from ACOSOG Z4032 (Alliance), a randomized trial for high-risk operable non-small cell lung cancer (NSCLC).
Authors: Kent Michael S , Landreneau Rodney Jerome , Mandrekar Sumithra J. , Nichols Francis C , DiPetrillo Thomas A. , Meyers Bryan F , Heron Dwight Earl , Putnam Joe B. , Jones David R , Starnes Sandra Lynne , Daly Benedict , Tan Angelina D. , Fernando Hiran Chrishantha ,   Alliance for Clinical Trials
Published: March 2020

7524 Background: A multicenter study (Z4032) compared sublobar resection (SR) to sublobar resection with brachytherapy (SRB) for stage I NSCLC. Local recurrence (LR) and overall survival (OS) rates at 3-years (3-yr) were similar between arms (see abstract 113613). This analysis combines arms, and evaluates the effect of factors previously reported to impact oncological outcomes after SR. Methods: 213 patients (pts) were evaluable for analysis. LR was defined as recurrence at the staple line (local progression), same lobe away from the staple line, or within hilar nodes. Factors assessed for impact on 3-yr outcomes were: resection type (wedge/segmentectomy), margin size (<1cm /≥1cm), margin:tumor ratio (<1/ ≥1), tumor size (≤2cm/>2cm) and staple line cytology (+/-). Results: LR occurred in 27/213 (12.6%) pts and included local progression in 12/213 (5.6%). OS rate at 3-yr was 152/213 (71.4%). Trends favored the use of segmentectomy, margin:tumor ratio≥1, tumor size ≤2cm and negative staple line cytology; no factor reached statistical significance at 3-yr. The only factor significantly (p=0.02) associated with decreased 3-yr LR was margin size ≥1cm (8.3%) compared to margin<1cm (19.3%). Conclusions: SR is a good option for high-risk pts with NSCLC. The 3-yr OS rate of 71.4% and local progression rate of 5.6% are useful benchmarks to compare to other therapies. A resection margin of at least 1 cm is desirable. Clinical trial information: NCT00107172. [Table: see text]
A phase I study of cediranib (NSC #732208) in combination with cisplatin and pemetrexed in chemonaive patients with malignant pleural mesothelioma (SWOG S0905).
Authors: Tsao Anne S. , Moon James , Wistuba Ignacio Ivan , Vogelzang Nicholas J. , Kalemkerian Gregory Peter , Redman Mary Weber , Gandara David R. ,   Southwest Oncology Group
Published: March 2020

7527 Background: The VEGF/VEGFR and PDGF/PDGFR pathways are potential therapeutic targets in mesothelioma. Cediranib, a VEGFR/PDGFR inhibitor, showed anti-tumor activity in a salvage monotherapy study S0509. Methods: S0905 combined cediranib (2 dose cohorts 30 mg and 20 mg daily) with cisplatin and pemetrexed for 6 cycles followed by maintenance cediranib in unresectable chemo-naïve MPM patients. Results: A total of 20 patients (7 to cohort 1 - 30 mg, 13 to cohort 2 - 20 mg) were enrolled. In first cohort, 2 patients reported grade 3 DLTs of diarrhea and fatigue. Cohort 2 DLTs included 2 patients with grade 3 hyponatremia/dehydration and mucositis. For all cycles, 12 patients reported Grade 3 AEs, the most common being diarrhea (4), dehydration (3), fatigue (3) and neutropenia (3). Two grade 4 thrombocytopenia were reported with 1 treatment-related death (cohort 2) due to pneumonia/sepsis. Based on the toxicity profile, a decision was made to proceed with cediranib 20 mg daily for the remaining phase I/II trial. Two radiographic response measurements were utilized (RECIST 1.1, modified RECIST). 18/20 patients were evaluable for response by RECIST 1.1 (7 - 30 mg cohort, 11 - 20 mg cohort). The RECIST 1.1 RR was 22% (95% CI: 6% - 48%) and median PFS was 14 months (95% CI: 8 – 17). Two patients had inadequate assessments and are classified as non-responders. There were 19 patients measurable by modified RECIST with RR 53% (95% CI: 29%-76%) and median PFS 10 months (7-13). For all patients, the median OS was 16 months (95% CI: 11-19). One patient in the 30 mg cohort remains on trial after 25 cycles of therapy; 2 patients at the 20 mg cohort remain on trial on cycles 19 and 15 of therapy. Conclusions: Cisplatin-pemetrexed-cediranib shows significant clinical activity and acceptable toxicity with cediranib 20 mg/day. The randomized phase II portion of the trial is ongoing. Clinical trial information: NCT01064648. [Table: see text]
Carboplatin versus cisplatin-based adjuvant chemotherapy in elderly patients with stages IB, II, and IIIA non-small cell lung cancer in the community setting.
Authors: Gu Fei , Wisnivesky Juan P. , Mhango Grace , Strauss Gary M. 
Published: March 2020

7533 Background: It remains controversial whether completely resected elderly NSCLC patients should receive adjuvant chemotherapy (ACT) and with what treatment regimen. We previously reported from a SEER-Medicare analysis of cases diagnosed up to 2005, that carbo-ACT is given much more frequently than cis-ACT and both are associated with improved overall survival (OS). Since randomized ACT trials were published around 2005, an update is necessary to reflect more recent practice patterns. Methods: We identified 16,420 patients >65 years in the SEER-Medicare database with resected stage IB-IIIA NSCLC, diagnosed between 1992 and 2007. Among these patients, 1,803 (11%) received platinum-ACT. Propensity score methods and Cox regression analyses were used to assess survival outcomes, as well as to compare carbo- versus cis-based therapy, while controlling for potential confounders. Results: Among those receiving platinum-based ACT, of whom 83% received carbo, there was a significant OS survival advantage compared to those receiving no ACT (TABLE). Carbo-ACT is associated with similar OS as compared to cis-ACT. The carbo/paclitaxel doublet was the most commonly used regimen, given to 52%. Chemotherapy-related toxicities requiring hospitalization were comparable between carbo- and cis-ACT groups, except for significantly less dehydration and anemia among those receiving carbo-ACT. Conclusions: In community practice reflected in this SEER-Medicare study, a minority of completely resected stage IB-IIIA NSCLC received platinum-based ACT that is associated with improved OS. Carbo-ACT was given in a 5:1 ratio compared to cis-ACT, had comparable OS advantage, and a somewhat more favorable toxicity profile. [Table: see text]
Test performance of PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumors.
Authors: Pattenden Holly , Beddow Emma , Dusmet Michael , Nicholson Andrew G , Swetha Iyer , Marchbank Adrian , Greenwood Amy , West Douglas , Ariyaratnam Priyadharshanan , Loubani Mahmoud , Granato Felice , Kirk Alan , Lim Eric Kian Saik ,   UK Thoracic Surgery Collaborative
Published: March 2020

7544 Background: PET-CT is a standard investigation to stage the mediastinum in non-small cell lung cancer when radical management is planned. The clinical utility of PET-CT in carcinoid tumours is uncertain as its test performance at identifying mediastinal lymph node disease in these tumours is as yet undefined with such tumours being rare and FDG avidity often variable or low. We sought to determine the test performance of PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumours. Methods: We collated retrospective data from 5 institutions for a consecutive series of patients who underwent thoracic surgery for carcinoid tumours and had preoperative PET-CT staging prior to surgery (with lymph nodal dissection). PET-CT results were compared against the reference standard of pathologic results obtained from lymph node dissection, and test performance reported using sensitivity and specificity. Results: From November 1999 to May 2012, a total of 153 patients with a preoperative PET-CT scan from 5 institutions underwent surgery for a carcinoid tumour. The mean age of the patients was 60 (SD 16) and 67 were male (44%). The pathologic sub-type was typical carcinoid in 138 patients (90%) and atypical carcinoid in 15 patients (10%). The mean SUV uptake in the primary tumour was 4.9 (SD 5). Results from lymph node dissection were obtained in 125 patients and the sensitivity and specificity of PET-CT to identify mediastinal lymph node disease was 40% (95% CI 5-85%) and 93% (93-99%) respectively. Conclusions: In this largest cohort study to date, our results suggest that PET-CT has a poor sensitivity but good specificity for mediastinal lymph node metastases for pulmonary carcinoid tumours. Therefore lymph node metastases cannot accurately be ruled out in carcinoid tumours with a negative PET-CT. If treatment decisions are based on the N2 status, invasive mediastinal staging should be undertaken in carcinoid tumours.