Background The global KEYNOTE-671 (clinicaltrials.gov, NCT03425643) study demonstrated significantly improved survival with perioperative pembrolizumab plus neoadjuvant chemotherapy versus neoadjuvant chemotherapy alone in early-stage non–small-cell lung cancer (NSCLC). We present findings from Japanese participants from KEYNOTE-671. Methods Eligible participants (≥18 years) with previously untreated stage II, IIIA, or IIIB (N2) NSCLC were randomized 1:1 to neoadjuvant pembrolizumab 200 mg or placebo plus cisplatin-based chemotherapy every 3 weeks for ≤4 cycles followed by surgery and adjuvant pembrolizumab or placebo for ≤13 cycles (⁓9 months). Primary endpoints were event-free survival (EFS) and overall survival (OS). Results Among 82 participants enrolled in Japan, 39 were randomized to pembrolizumab and 43 to placebo. Median time from randomization to database cutoff (August 19, 2024) was 52.7 (range, 32.7‒74.9) months. The 48-month EFS rates (95% CIs) were 60.3% (42.8%‒74.0%) and 39.2% (24.8%‒53.4%), respectively, and the EFS HR was 0.54 (95% CI, 0.29‒1.02). For OS, 48-month rates (95% CIs) were 79.5% (63.1%‒89.2%) and 68.9% (52.4%‒80.7%), and the OS HR was 0.76 (95% CI, 0.33‒1.78). Grade ≥3 treatment-related AEs occurred in 23 participants (59%) treated with pembrolizumab and 20 participants (47%) with placebo; there were no deaths due to treatment-related AEs. Conclusions Perioperative pembrolizumab plus neoadjuvant chemotherapy improved efficacy versus neoadjuvant chemotherapy alone and had manageable safety in Japanese participants enrolled in KEYNOTE-671, supporting the use of perioperative pembrolizumab in Japanese patients with early-stage NSCLC. (ClinicalTrials.gov, NCT03425643)

OBJECTIVES:Perioperative pembrolizumab plus neoadjuvant chemotherapy significantly improved outcomes versus neoadjuvant chemotherapy alone in early-stage, resectable, non-small-cell lung cancer (NSCLC) in the phase 3 KEYNOTE-671 study. We report outcomes in participants with baseline clinical stage II disease. METHODS:Participants with untreated, resectable, stage II-IIIB (N2) NSCLC were randomized 1:1 to receive pembrolizumab 200 mg or placebo every 3 weeks plus chemotherapy for 4 cycles, followed by surgery and adjuvant pembrolizumab or placebo for 13 cycles (∼9 months). Exploratory analyses were performed in participants with clinical stage II disease. RESULTS:Of 797 randomized participants, 239 had stage II disease (pembrolizumab plus chemotherapy, n = 118; chemotherapy only, n = 121). Median study follow-up at data cutoff (August 19, 2024) was 49.9 (range, 32.2-75.3) months. Among participants who underwent surgery, 94/99 (94.9%) had R0 resections in the pembrolizumab arm and 89/103 (86.4%) in the neoadjuvant chemotherapy only arm. Event-free survival (hazard ratio [HR], 0.50; 95% CI, 0.34-0.74), overall survival (HR, 0.69; 95% CI, 0.43-1.11), major pathological response (difference, 25.7%; 95% CI, 15.3-35.9), and pathological complete response (difference, 21.3%; 95% CI, 13.2-30.2) were improved in the pembrolizumab arm. Grade 3-4 treatment-related adverse events (AEs) occurred in 50.0% of participants treated with pembrolizumab plus chemotherapy and 40.5% with chemotherapy; no treatment-related AEs led to death. CONCLUSIONS:In participants with stage II NSCLC, perioperative pembrolizumab improved efficacy outcomes with manageable safety versus neoadjuvant chemotherapy alone, consistent with the overall KEYNOTE-671 population. These results support the use of this regimen in patients with stage II disease. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03425643, registered/first posted on February 7, 2018 (https://www.clinicaltrials.gov/study/NCT03425643).

BACKGROUND Neoantigens are immunogenic molecules arising from patient-specific tumor mutations. Intismeran autogene (intismeran; formerly V940, mRNA-4157), an mRNA-based individualized neoantigen therapy (INT) encoding ≤34 neoantigens unique to each patient’s tumor, is designed to promote an antitumor immune response. In early-phase studies, adjuvant intismeran plus pembrolizumab showed antitumor activity with solid tumors. Standard-of-care therapy for non‒small-cell lung cancer (NSCLC) tumors ≥4 cm includes platinum-based chemotherapy and pembrolizumab given after (adjuvant) or both before and after (perioperative) surgical resection. We describe study designs for the INTerpath-002 and INTerpath-009 studies evaluating the addition of intismeran to adjuvant pembrolizumab-based therapy in stage II‒IIIB (N2) NSCLC. METHODS INTerpath-002 and INTerpath-009 are randomized, double-blind, phase 3 trials. Eligible participants for INTerpath-002 have completely resected, margin-negative, stage II‒IIIB (N2) NSCLC (American Joint Committee on Cancer 8th edition) and have received 1‒4 cycles of adjuvant platinum-based chemotherapy. Eligible participants for INTerpath-009 have resectable stage II‒IIIB (N2) NSCLC and have received ≤4 cycles of neoadjuvant pembrolizumab plus chemotherapy every 3 weeks. Participants with tumors that do not achieve a pathologic complete response, per pathological examination of the resected tumor specimen, and have R0‒R1 resection are eligible for randomized treatment. In both studies, participants are randomized 1:1 to receive pembrolizumab intravenously every 6 weeks plus either intismeran intramuscularly every 3 weeks or placebo. The primary endpoint in both studies is disease-free survival per investigator. RESULTS Recruitment is ongoing for both studies. CONCLUSIONS Results from these studies will provide insight into the potential role of INT in NSCLC.

Patients (pts) with non-small-cell lung cancer (NSCLC) who do not achieve pathologic complete response (pCR) after neoadjuvant chemoimmunotherapy and surgery have a worse prognosis than those who achieve pCR, and escalation of therapy for improved outcomes may be warranted. Pembrolizumab (pembro) is approved in several countries as monotherapy for the adjuvant treatment of pts with NSCLC following neoadjuvant pembro plus platinum-based chemotherapy (chemo) and resection. V940 (mRNA-4157) is a novel, mRNA-based, individualized neoantigen therapy that encodes up to 34 neoantigens specific to each pt’s unique tumor mutanome and is encapsulated in a lipid nanoparticle that is administered intramuscularly (IM). Preliminary antitumor activity for V940 as monotherapy and in combination with pembro was shown in the phase 1 KEYNOTE-603 study in solid tumors, including NSCLC, and in KEYNOTE-942 in melanoma. The INTerpath-009 study (NCT06623422) evaluates adjuvant pembro with and without V940 in pts with resected stage II-IIIB (N2) NSCLC that did not achieve pCR after neoadjuvant pembro plus chemo. This phase 3, multicenter, double-blind study is enrolling pts ≥18 years old with histologically-confirmed stage II-IIIB (N2) squamous (sq) or nonsquamous (nonsq) NSCLC (AJCC v8) with no tumor-activating EGFR and no known ALK alterations. Eligible pts are able to undergo protocol therapy, including surgery, and have ECOG PS 0 or 1. Pts eligible for randomization must have resected (R0 or R1) tumors that did not achieve pCR after ≤4 cycles of neoadjuvant pembro plus chemo, and surgical tumor sample available for biomarker analysis and next-generation sequencing. Pts who received neoadjuvant pembro plus chemo prior to enrollment are eligible provided other eligibility criteria are met. Approximately 680 pts will be randomized 1:1 to V940 1 mg IM or placebo Q3W for 9 doses, both in combination with pembro (400 mg IV Q6W for 7 cycles). Treatment will continue until PD, pt withdrawal, unacceptable toxicity, or an additional malignancy requiring treatment. Randomization will be stratified by histology (sq vs nonsq), PD-L1 expression (TPS <1% vs ≥1%), disease stage (II vs III), and geographic location (North America/Western Europe/Australia vs rest of world). Tumor imaging will occur at baseline and every 12 wk until wk 48, every 24 wk through year 3, and every 48 wk thereafter from randomization until distant recurrence, death, withdrawal of consent, or end of study. The primary endpoint is disease-free survival (DFS) per investigator assessment. Secondary endpoints include OS, distant metastasis-free survival, DFS after next-line therapy, lung cancer-specific survival, patient-reported outcomes, and safety. The first pt was screened on October 21, 2024, and recruitment is ongoing. Tina Cascone, Nir Peled, Alona Zer, David Chism, Danko Martincic, Laureen S. Ojalvo, Joydeep Banerjee, Zheng Wang, Steven M. Keller, Jonathan D. Spicer. Phase 3 INTerpath-009 study: Individualized neoantigen therapy V940 (mRNA-4157) plus pembrolizumab for resected stage II-IIIB (N2) NSCLC with incomplete pathological response to neoadjuvant immunochemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT251.

BACKGROUND:The phase 3 KEYNOTE-671 study (NCT03425643) demonstrated significantly improved event-free survival (EFS) and overall survival with neoadjuvant pembrolizumab plus chemotherapy followed by surgery and adjuvant pembrolizumab vs neoadjuvant chemotherapy and surgery for early-stage non-small cell lung cancer (NSCLC). We describe participant characteristics, surgical outcomes, and EFS in surgically relevant subgroups. METHODS:Participants with untreated, resectable, stage II-IIIB (N2) NSCLC were randomized 1:1 to neoadjuvant pembrolizumab 200 mg or placebo plus cisplatin-based chemotherapy every 3 weeks for 4 cycles, then surgery and adjuvant pembrolizumab or placebo for 13 cycles. Surgery was performed ≤20 weeks after first neoadjuvant dose (if 4 cycles of neoadjuvant therapy) or 4-8 weeks after last neoadjuvant dose (1-3 cycles); surgery beyond this was considered surgical delay. Adjuvant therapy began 4-12 weeks after surgery. EFS was assessed in the surgical population. RESULTS:Of 397 participants randomized to pembrolizumab and 400 to placebo, 325 (82.1%) and 317 (79.4%), respectively, underwent surgery. At data cutoff (July 10, 2023), 4.9% (pembrolizumab) and 7.6% (placebo) of participants experienced surgical delay; 38.9% and 28.4%, respectively, experienced nodal downstaging; 78.8% and 75.1% underwent lobectomy; and 92.0% and 84.2% had R0 resections. Pembrolizumab improved EFS irrespective of disease stage, nodal status, and type of surgery vs chemotherapy. Eight participants (pembrolizumab, n = 6; placebo, n = 2) died ≤30 days after surgery from surgery-related adverse events. CONCLUSIONS:Neoadjuvant pembrolizumab did not adversely affect surgical outcomes, was associated with numerically higher R0 resections, and improved EFS vs neoadjuvant chemotherapy in surgically relevant subgroups in early-stage NSCLC.

8012 Background: Neoadjuvant pembrolizumab + cisplatin-based chemotherapy (neoadj pembro + chemo), resection, and adjuvant (adj) pembro (pembro arm; n=397) significantly improved EFS, OS, pCR, and mPR and had an expected safety profile versus neoadj placebo (pbo) + chemo, resection, and adj pbo (pbo arm; n=400) in patients (pts) with resectable stage II, IIIA, or IIIB (N2) NSCLC. We present prespecified pt-reported outcome (PRO) endpoints from KEYNOTE-671. Methods: Pts completed EORTC QLQ-C30 and QLQ-LC13 questionnaires at baseline (BL), the last scheduled presurgery visit, adj cycles 1-4, 7, 10, and 13, and each post treatment visit. A constrained longitudinal data analysis model was used to estimate least squares mean (LSM) score changes from BL to neoadj wk 11 and adj wk 10 (latest time of ≥60% completion and ≥80% compliance) in QLQ-C30 global health status (GHS)/QoL, physical functioning (PF), role functioning (RF), and dyspnea and QLC-LC13 cough and chest pain in all treated pts who completed ≥1 PRO assessment. Data are from interim analysis 2 (10 Jul 2023 cutoff). Results: Across arms, questionnaire completion was ≥87% at neoadj wk 11 and ≥62% at adj wk 10; compliance was ≥87% and ≥92%, respectively. There were no differences in LSM change from BL in the neoadj or adj phase for any PRO score (Table). Conclusions: Adding perioperative pembro maintained HRQoL in both the neoadj and adj settings versus neoadj chemo and surgery alone in pts with resectable early-stage NSCLC. Together with the significant efficacy improvements and absence of new safety signals, HRQoL data support the perioperative pembro regimen as a new standard of care. Clinical trial information: NCT03425643 . [Table: see text]

Currently available treatments that can alter lung inflammation have failed to significantly alter mortality of acute lung injury (ALI). Peroxiredoxin 6 PLA 2 inhibitory peptide-2 (PIP-2) targets the liberation of reactive O 2 species (ROS) that is associated with adverse cell signaling events, thereby decreasing the tissue oxidative injury that occurs early in the ALI syndrome. We propose that treatment with PIP-2 may be effective in preventing progression of early disease into its later stages with irreversible lung damage and relatively high mortality.

Background At the first interim analysis of the KEYNOTE-671 trial, adding perioperative pembrolizumab to neoadjuvant chemotherapy significantly improved event-free survival in participants with early-stage non-small-cell lung cancer (NSCLC). We report overall survival and health-related quality of life outcomes from the second interim analysis. Methods KEYNOTE-671 was a global phase 3 trial done at 189 medical centres. Eligible participants (aged >= 18 years) with resectable stage II, IIIA, or IIIB (N2) NSCLC were randomly assigned (1:1) to four cycles of neoadjuvant pembrolizumab (200 mg administered intravenously every 3 weeks) plus cisplatin-based chemotherapy followed by surgery and 13 cycles of adjuvant pembrolizumab (200 mg administered intravenously every 3 weeks) or to four cycles of neoadjuvant placebo (administered intravenously every 3 weeks) plus cisplatin-based chemotherapy followed by surgery and 13 cycles of adjuvant placebo (administered intravenously every 3 weeks). Randomisation was done centrally using an interactive response technology system and was stratified by disease stage, PD-L1 expression, histology, and geographical region in blocks of four. Participants, investigators, and sponsor personnel were masked to treatment assignments; local pharmacists were unmasked to support treatment preparation. The dual primary endpoints were overall survival and event-free survival evaluated in the intention-to-treat population. This study is registered at ClinicalTrials.gov, NCT03425643, and is ongoing but closed to enrolment. Findings Between May 11, 2018, and Dec 15, 2021, 797 participants were randomly assigned to the pembrolizumab group (n=397) or the placebo group (n=400). Median study follow-up at the second interim analysis was 366 months (IQR 276-478). 36-month overall survival estimates were 71% (95% CI 66-76) in the pembrolizumab group and 64% (58-69) in the placebo group (hazard ratio 072 [95% CI 056-093]; one-sided p=00052; threshold, one-sided p=00054). Median event-free survival was 472 months (95% CI 329 to not reached) in the pembrolizumab group and 183 months (148-221) in the placebo group (hazard ratio 059 [95% CI 048-072]). In the as-treated population, grade 3-5 treatment-related adverse events occurred in 179 (45%) of 396 participants in the pembrolizumab group and in 151 (38%) of 399 participants in the placebo group. Treatment-related adverse events led to death in four (1%) participants in the pembrolizumab group and three (1%) participants in the placebo group. Interpretation The significant overall survival benefit of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab compared with neoadjuvant chemotherapy alone coupled with a manageable safety profile support the use of perioperative pembrolizumab in patients with resectable, early-stage NSCLC.

Abstract Background With advances in antiretroviral therapy, life-expectancy for people living with HIV (PLWH) has increased. Many HIV specialists function as primary care providers for PLWH and are often the front-line of defense when it comes to preventative healthcare. The Infectious Disease Practice (IDP) at University Hospital in Newark, NJ serves as a medical home and primary care site for many PLWH. The clinic incorporates preventative healthcare measures into providing whole patient care as well as focusing on HIV specific care. Here, we present data from multiple quality assessment projects at our clinic assessing preventative health measures in PLWH. Methods Following IRB NHS determination, data was collected from an EPIC database of PLWH seen at IDP. Guidelines for Primary Care by Infectious Disease Society of America, the Advisory Committee on Immunization Practices, JNC8, and the US Department of Health and Human Services were reviewed. Results Bone mineral density (BMD) screening was ordered for 59% and completed in 39% of PLWH who met guideline criteria compared to national average of 7.4% Among PLWH with Diabetes mellitus (DM), 62% achieved A1C goals, 65% achieved blood pressure goals and 67% achieved LDL-c goals. National averages for achieving A1C, blood pressure, and LDL-C goals in people with DM were 51%, 70%, and 66% respectively in 2018. Hypertension pharmacologic therapy was initiated, and blood pressure controlled to systolic blood pressure < 150 diastolic blood pressure < 90 in 72% of PLWH compared to national average of 65% Among PLWH, 64% received at least one dose of PCV13, 60% received at least one dose of PPSV23, and 38% were fully up to date compared with national average 23% in PLWH in 2018 receiving at least one dose of either vaccine. Conclusion Clinicians practicing in HIV clinics should be up to date on age-appropriate screenings and vaccinations. The IDP has matched or outperformed national standards in several aspects of preventative healthcare for PLWH including DM, hypertension, vaccinations, and BMD screening. Infectious disease specialists who provide care for PLWH are in a unique, trusted position to deliver preventative healthcare and should have expertise in primary care to optimize patient centered care. Disclosures Eli S. Goshorn, MD, Genmark Diagnostics Inc: Advisor/Consultant

Supplementary Figure 1 from Targeting Protein Translation in Human Non–Small Cell Lung Cancer via Combined MEK and Mammalian Target of Rapamycin Suppression

Supplementary Figure 3 from Targeting Protein Translation in Human Non–Small Cell Lung Cancer via Combined MEK and Mammalian Target of Rapamycin Suppression

Supplementary Figures S1 & S2 from Enhancement of the Therapeutic Efficacy of Taxol by the Mitogen-Activated Protein Kinase Kinase Inhibitor CI-1040 in Nude Mice Bearing Human Heterotransplants

1Department of Emergency Medicine, Rutgers New Jersey Medical School 2Department of Family Medicine, Rutgers New Jersey Medical School Presentations: This material in part was presented at STFM’s Annual Spring Conference on Medical Education at Austin, Texas on 2 March 2018 at 10:30am. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.ajmqonline.com). Corresponding Author:, Christine Ramdin, PhD, Department of Emergency Medicine and Department of Family Medicine, Rutgers New Jersey Medical School, 185 South Orange Avenue, E-610, Newark, NJ 07103., Email: [email protected]

Supplementary Figures S1-S4; Supplementary Tables S1-S2.

BACKGROUND:Among patients with resectable early-stage non-small-cell lung cancer (NSCLC), a perioperative approach that includes both neoadjuvant and adjuvant immune checkpoint inhibition may provide benefit beyond either approach alone. METHODS:We conducted a randomized, double-blind, phase 3 trial to evaluate perioperative pembrolizumab in patients with early-stage NSCLC. Participants with resectable stage II, IIIA, or IIIB (N2 stage) NSCLC were assigned in a 1:1 ratio to receive neoadjuvant pembrolizumab (200 mg) or placebo once every 3 weeks, each of which was given with cisplatin-based chemotherapy for 4 cycles, followed by surgery and adjuvant pembrolizumab (200 mg) or placebo once every 3 weeks for up to 13 cycles. The dual primary end points were event-free survival (the time from randomization to the first occurrence of local progression that precluded the planned surgery, unresectable tumor, progression or recurrence, or death) and overall survival. Secondary end points included major pathological response, pathological complete response, and safety. RESULTS:A total of 397 participants were assigned to the pembrolizumab group, and 400 to the placebo group. At the prespecified first interim analysis, the median follow-up was 25.2 months. Event-free survival at 24 months was 62.4% in the pembrolizumab group and 40.6% in the placebo group (hazard ratio for progression, recurrence, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.72; P<0.001). The estimated 24-month overall survival was 80.9% in the pembrolizumab group and 77.6% in the placebo group (P = 0.02, which did not meet the significance criterion). A major pathological response occurred in 30.2% of the participants in the pembrolizumab group and in 11.0% of those in the placebo group (difference, 19.2 percentage points; 95% CI, 13.9 to 24.7; P<0.0001; threshold, P = 0.0001), and a pathological complete response occurred in 18.1% and 4.0%, respectively (difference, 14.2 percentage points; 95% CI, 10.1 to 18.7; P<0.0001; threshold, P = 0.0001). Across all treatment phases, 44.9% of the participants in the pembrolizumab group and 37.3% of those in the placebo group had treatment-related adverse events of grade 3 or higher, including 1.0% and 0.8%, respectively, who had grade 5 events. CONCLUSIONS:Among patients with resectable, early-stage NSCLC, neoadjuvant pembrolizumab plus chemotherapy followed by resection and adjuvant pembrolizumab significantly improved event-free survival, major pathological response, and pathological complete response as compared with neoadjuvant chemotherapy alone followed by surgery. Overall survival did not differ significantly between the groups in this analysis. (Funded by Merck Sharp and Dohme; KEYNOTE-671 ClinicalTrials.gov number, NCT03425643.).

For detecting field carcinogenesis non-invasively, early technical development and case-control testing of exhaled breath condensate microRNAs was performed. In design, human lung tissue microRNA-seq discovery was reconciled with TCGA and published tumor-discriminant microRNAs, yielding a panel of 24 upregulated microRNAs. The airway origin of exhaled microRNAs was topographically "fingerprinted", using paired EBC, upper and lower airway donor sample sets. A clinic-based case-control study (166 NSCLC cases, 185 controls) was interrogated with the microRNA panel by qualitative RT-PCR. Data were analyzed by logistic regression (LR), and by random-forest (RF) models. Feasibility testing of exhaled microRNA detection, including optimized whole EBC extraction, and RT and qualitative PCR method evaluation, was performed. For sensitivity in this low template setting, intercalating dye-based URT-PCR was superior to fluorescent probe-based PCR (TaqMan). In application, adjusted logistic regression models identified exhaled miR-21, 33b, 212 as overall case-control discriminant. RF analysis of combined clinical + microRNA models showed modest added discrimination capacity (1.1-2.5%) beyond clinical models alone: all subjects 1.1% (p = 8.7e-04)); former smokers 2.5% (p = 3.6e-05); early stage 1.2% (p = 9.0e-03), yielding combined ROC AUC ranging from 0.74 to 0.83. We conclude that exhaled microRNAs are qualitatively measureable, reflect in part lower airway signatures; and when further refined/quantitated, can potentially help to improve lung cancer risk assessment.

We performed a retrospective chart review at our adult allergy and immunology clinic to evaluate the quality of care of patients with chronic urticaria. This study was reviewed by the Rutgers IRB Newark Campus and was determined to be a non-human subject study Pro2022000829. Using the International EAACI/GA2LEN/EuroGuiDerm/APAAACI guidelines, eleven recommendations were selected to evaluate the care of patients with chronic urticaria. Then a retrospective chart review was performed at our inner-city academic allergy and immunology clinic. Fifty-patient charts were randomly selected from patients who received care between 01/01/2021 to 12/31/2021 for chronic urticaria. All patients had a diagnosis of chronic urticaria (≥ 6 weeks) and were between the age of 18-80 years old. It was determined whether or not eleven recommendations from the guidelines were followed during the visit. The results revealed that 100% of the patients were prescribed 2nd generation H1-antihistamines for relief, 88% were assessed for associated angioedema, 68% were assessed regarding the characteristics of their rash, 66% were assessed regarding other physical triggers of urticaria, 64% were assessed regarding the duration of individual hives, 52% were assessed for dermatographia, 40% were assessed for post-hive pigmentation, bruising or scarring and systemic symptoms such as joint pain, fatigue or weight loss, and 18% were assessed regarding worsening of hives with NSAIDs. This quality assurance study highlights the strengths and the weaknesses of an adult Allergy and Immunology clinic at an inner-city academic center.

Supplementary Figure S3 from Enhancement of the Therapeutic Efficacy of Taxol by the Mitogen-Activated Protein Kinase Kinase Inhibitor CI-1040 in Nude Mice Bearing Human Heterotransplants

CCR Translation for This Article from Both Gene Amplification and Allelic Loss Occur at 14q13.3 in Lung Cancer