Assessing prospective and retrospective metacognitive accuracy following traumatic brain injury remotely across cognitive domains.

The ability to monitor one's behaviour is frequently impaired following TBI, impacting on patients' rehabilitation. Inaccuracies in judgement or self-reflection of one's performance provides a useful marker of metacognition. However, metacognition is rarely measured during routine neuropsychology assessments and how it varies across cognitive domains is unclear. A cohort of participants consisting of 111 TBI patients [mean age = 45.32(14.15), female = 29] and 84 controls [mean age = 31.51(12.27), female = 43] was studied. Participants completed cognitive assessments via a bespoke digital platform on their smartphones. Included in the assessment were a prospective evaluation of memory and attention, and retrospective confidence judgements of task performance. Metacognitive accuracy was calculated from the difference between confidence judgement of task performance and actual performance. Prospective judgment of attention and memory was correlated with task performance in these domains for controls but not patients. TBI patients had lower task performance in processing speed, executive functioning and working memory compared to controls, maintaining high confidence, resulting in overestimation of cognitive performance compared to controls. Additional judgments of task performance complement neuropsychological assessments with little additional time-cost. These results have important theoretical and practical implications for evaluation of metacognitive impairment in TBI patients and neurorehabilitation.

A single-arm, multicenter, phase II trial of osimertinib in patients with epidermal growth factor receptor exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations.

BACKGROUND: For patients with stage IV non-small-cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions and exon 21 L858R mutations, osimertinib is the standard of care. Investigating the activity and safety of osimertinib in patients with EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations is of clinical interest. PATIENTS AND METHODS: Patients with stage IV non-small-cell lung cancer with confirmed EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations were eligible. Patients were required to have measurable disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. Patients were required to be EGFR tyrosine kinase inhibitor-naive. The primary objective was objective response rate, and secondary objectives were progression-free survival, safety, and overall survival. The study used a two-stage design with a plan to enroll 17 patients in the first stage, and the study was terminated after the first stage due to slow accrual. RESULTS: Between May 2018 and March 2020, 17 patients were enrolled and received study therapy. The median age of patients was 70 years (interquartile range 62-76), the majority were female (n = 11), had a performance status of 1 (n = 10), and five patients had brain metastases at baseline. The objective response rate was 47% [95% confidence interval (CI) 23% to 72%], and the radiographic responses observed were partial response (n = 8), stable disease (n = 8), and progressive disease (n = 1). The median progression-free survival was 10.5 months (95% CI 5.0-15.2 months), and the median OS was 13.8 months (95% CI 7.3-29.2 months). The median duration on treatment was 6.1 months (range 3.6-11.9 months), and the most common adverse events (regardless of attribution) were diarrhea, fatigue, anorexia, weight loss, and dyspnea. CONCLUSIONS: This trial suggests osimertinib has activity in patients with these uncommon EGFR mutations.

Differentially expressed genes in the rat cochlear nucleus.

The cochlear nucleus is the first central pathway involved in the processing of peripheral auditory activity. The anterior ventral cochlear nucleus (AVCN), posterior ventral cochlear nucleus (PVCN) and dorsal cochlear nucleus (DCN) each contain predominant populations of neurons that have been well characterized regarding their morphological and electrophysiological properties. Little is known, however, of the underlying genetic factors that contribute to these properties and the initial steps in auditory processing. Serial analysis of gene expression (SAGE), supported by microarray experiments, was performed on each subdivision of the rat cochlear nucleus to identify genes that may sub-serve specialized roles in the central auditory system. Pair-wise comparisons between SAGE libraries from the AVCN, PVCN and DCN were correlated with microarray experiments to identify individual transcripts with significant differential expression. Twelve highly correlated genes were identified representing cytoskeletal, vesicular, metabolic and g-protein regulating proteins. Among these were Rgs4 which showed higher expression in the DCN, Sst and Cyp11b1 with very high expression in the AVCN and Calb2 with preferential expression in the PVCN. The differential expression of these genes was validated with real-time reverse transcriptase-polymerase chain reaction. These experiments provide a basis for understanding normal auditory processing on a molecular level and a template for investigating changes that may occur in the cochlear nucleus with hearing loss, the generation and percept of tinnitus, and central auditory processing disorders.

Phase I clinical/pharmacokinetic and pharmacodynamic trial of the c-raf-1 antisense oligonucleotide ISIS 5132 (CGP 69846A).

PURPOSE: Raf-1 is a protein kinase that plays a broad role in oncogenic signaling and acts as a downstream effector of Ras in the mitogen-activated protein kinase pathway. The present study was designed to determine the maximum-tolerated dose (MTD), toxicity profile, pharmacokinetics, and antitumor activity of the c-raf-1 antisense oligodeoxynucleotide ISIS 5132 (CGP 69846A; ISIS Pharmaceuticals Inc, Carlsbad, CA). The effect of ISIS 5132 on c-raf-1 gene expression in peripheral-blood mononuclear cells (PBMCs) of treated patients was studied using a reverse transcriptase polymerase chain reaction assay. PATIENTS AND METHODS: Patients with refractory malignancies received ISIS 5132 as a 2-hour intravenous infusion three times weekly for 3 consecutive weeks. Pharmacokinetic sampling was performed during the first cycle in all patients; PBMCs for c-raf-1 mRNA analysis were collected at baseline and on days 3, 5, 8, and 15 of cycle 1 and on day 1 of each cycle thereafter. RESULTS: Thirty-one patients received ISIS 5132 at one of nine dose levels ranging from 0.5 mg/kg to 6.0 mg/kg. Clinical toxicities included fever and fatigue, but these were not dose limiting. A clinically defined MTD was not reached. The harmonic mean half-life of ISIS 5132 was 59.8 minutes (range, 35.5 to 107.3 minutes). The area under the concentration-time curve increased linearly with dose, and mean plasma clearance was 1.86 mL/kg/min (range, 1.21 to 2.41 mL/kg/min). Two patients experienced prolonged stable disease lasting more than 7 months, which was associated with persistent reduction in c-raf-1 expression in PBMCs. Significant decreases in c-raf-1 expression were identified at time points after the baseline value (P <.05) at doses >/= 2.5 mg/kg. CONCLUSION: ISIS 5132 is well tolerated at doses up to 6.0 mg/kg when administered as a thrice weekly 2-hour infusion for 3 consecutive weeks. The pharmacokinetic behavior of the drug is reproducible, and suppression of target gene expression is observed in circulating PBMCs.

First hints in non-small cell lung cancer (NSCLC).

All-trans retinoic acid was evaluated in metastatic measurable non-small cell lung cancer. All-trans retinoic acid was given at 175 mg/m2 orally on a daily basis. Twenty-eight patients (median age 58, 16 males, 12 women) had an ECOG performance status of 0 (26 patients) and 1 (two patients). Sixteen of the 28 had no weight loss. Eleven had between 5 and 10% and only one had greater than 10% weight loss at time of entry. Toxicities included cutaneous (cheletis 25/28), fatigue (10/28), myalgias/anthralgias (9/28), and headache (17/28). Alterations in triglycerides and hepatic transaminases were noted in a majority of patients. Two partial responses occurred in patients with adenocarcinoma. Both responses were 7 months in duration. Activity of all-trans retinoic acid in metastatic non-small cell lung cancer is minimal, but due to its low toxicity profile it should be tested in setting with other agents.

Identification of the cap binding domain of human recombinant eukaryotic protein synthesis initiation factor 4E using a photoaffinity analogue.

Binding of eIF-4E to the 5' m7G cap structure of eukaryotic mRNA signals the initiation of protein synthesis. In order to investigate the molecular basis for this recognition, photoaffinity labeling with [gamma-32P]8-N3GTP was used in binding site studies of human recombinant cap binding protein eIF-4E. Competitive inhibition of this cap analogue by m7GTP and capped mRNA indicated probe specificity for interaction at the protein binding site. Saturation of the binding site with [gamma-32P]8-N3GTP further demonstrated the selectivity of photoinsertion. Aluminum (III)-chelate chromatography and reverse-phase HPLC were used to isolate the binding site peptide resulting from digestion of photolabeled eIF-4E with modified trypsin. Amino acid sequencing identified the binding domain as the region containing the sequence Trp 113-Arg 122.Lys 119 was not identified in sequencing analysis nor was it cleaved by trypsin. These results indicate that Lys 119 is the residue directly modified by photoinsertion of [gamma-32P]8-N3GTP. A detailed understanding of eIF-4E.m7G mRNA cap interactions may lead the way to regulating this essential protein-RNA interaction for specific mRNA in vivo.

Biogenesis of liver delta-aminolevulinate synthase. The role of cAMP in the induction.

In primary cultures of chick embryo hepatocytes pulse labeled with [35S]methionine, immunochemical analyses indicated that adenosine 3':5'-cyclic monophosphate (cAMP) did not affect either the rate of production or the maturation of delta-aminolevulinate synthase (ALA synthase). In addition, allylisopropylacetamide caused a slight drop in intracellular cAMP while testosterone caused the levels of cAMP to rise to 260% of the basal levels measured in hepatocytes in culture. Thus the results of this study did not indicate a direct short-term role for cAMP in the regulation of production of ALA synthase.

A phase II trial of docetaxel (Taxotere) in hormone-refractory prostate cancer: correlation of antitumor effect to phosphorylation of Bcl-2.

Twenty-one patients with hormone refractory prostate cancer were enrolled to receive single-agent docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) 75 mg/m2 intravenously every 21 days. Six patients consented to biopsies of the prostate tumor before and following the first cycle of chemotherapy and 11 patients underwent periodic blood collection for isolation of the mononuclear cell fraction. The toxicities of treatment were moderate but included eight episodes of grade III and two episodes of grade IV nonhematologic toxicity as well as seven episodes of grade III and 11 episodes of grade IV hematologic toxicity (primarily neutropenia, including four episodes of febrile neutropenia). An objective response of more than 50% reduction in prostate-specific antigen was observed in seven patients (38%) and more than half of the patients with symptomatic disease at the initiation of therapy had improvements on treatment. Radiographic or scintigraphic evidence of tumor regression was observed in six patients. Nine patients experienced a prolonged period of stable disease on treatment (median, six cycles). Tumor specimens are currently being analyzed for bcl-2 expression and phosphorylation. The current series confirms the substantial single-agent activity of docetaxel in hormone refractory prostate cancer and may help to further elucidate its mechanism of action at the molecular level.

The role of oral etoposide in non-small cell lung cancer.

Oral etoposide has been tested alone and in combination in a number of tumour types since the late 1980s because of its mild toxicity, high response rates, ease of administration, and comparatively low cost. Encouraging early results with protracted oral etoposide therapy in small cell lung cancer have not been borne out in non-small cell lung cancer (NSCLC), particularly in the advanced-disease setting. However, in stage IV NSCLC, oral etoposide does appear to be as compatible with most of the newer agents as it has been with platinum compounds; these combinations continue to be explored, although they have not penetrated into standard usage. In stage III NSCLC, large combined-modality studies are ongoing. Other investigations examining protracted administration in combination with radiation 'sensitisers' are planned. It is possible that by exploiting the 'radiosensitising effect' of prolonged low dose oral etoposide, combined with that of other proven radiosensitisers such as paclitaxel, gemcitabine, and topotecan, we may identify a niche for oral etoposide in the future.

New chemotherapy agents in the treatment of advanced non-small cell lung cancer: an update including data from the Seventh World Conference on Lung Cancer.

Over the past two decades, modest gains have been made in chemotherapy for non-small cell lung cancer with the addition of cisplatin-based regimens to the therapeutic armamentarium. Over the last decade, several new agents with significant activity have reached the level of Phase II and III testing. This list of new drugs includes: navelbine, the taxanes--taxol and taxotere, gemcitabine, edatrexate and the camptothecins--irinotecan and topotecan. During this period, oral etoposide and epirubicin were re-investigated and biological agents such as the retinoids, interferons and interleukins were also explored as alternatives to traditional chemotherapy. As these new drug investigations proceeded, basic scientists made important discoveries which are now beginning to be applied to therapy. The future promises to combine these active new drugs with therapies directed against targets unique to non-small cell lung cancer cells.

Spread of the Spanish multi-resistant serotype 23F clone of Streptococcus pneumoniae to Seoul, Korea.

Multi-resistant serotype 23F pneumococcal strains from an outbreak in a day-care centre in South Africa and strains from sporadic cases in Korea were analysed for their relatedness, by means of arbitrarily-primed PCR (AP-PCR), repetitive extragenic palindromic PCR (rep-PCR) and penicillin-binding protein (PBP) gene profiles. The South African strains previously shown to be identical to the 23F Spanish clone had identical AP-PCR and rep-PCR patterns to 13 Korean isolates. PBP gene analysis of strains from this cluster showed identical fingerprints, suggesting clonality. Isolates, identical genotypically to the 23F clone appeared to have acquired the type 19F and 14 capsular serotypes, respectively, a result that suggests horizontal transfer of capsular biosynthetic genes. These same techniques revealed three serotype 9V isolates not closely related to the 23F clone but which harbour PBP genes identical to the 23F clone. The data presented suggests that a clone of S. pneumoniae serotype 23F related to isolates from Spain and South Africa has become disseminated in Korea.

Preliminary report on reduction of esophagitis by amifostine in patients with non-small-cell lung cancer treated with chemoradiotherapy.

Esophagitis is a major toxicity of chemoradiotherapy for lung cancer. Twenty-four patients with non-small-cell lung cancer received induction chemotherapy (paclitaxel/carboplatin) followed by concurrent thoracic irradiation (RT) and weekly paclitaxel. Acute esophagitis was scored weekly. Since a high rate of grade 3 esophagitis was noted in the initial group of 12 patients, amifostine (AMI) 500 mg intravenously twice weekly was added to the regimen in the subsequent 12 patients. Esophagitis Index (EI) was calculated as an area under the curve reflecting esophagitis grade over time. Median number of AMI doses was 12 per patient. AMI was well tolerated. Two patients were not evaluable for esophagitis. The incidence of grade 3 esophagitis was 18% in the initial 11 patients versus 9% in the AMI-treated patients (P = not significant). Mean EI was numerically lower in the AMI-treated patients than in the initial group (5.1 vs. 11.6, P = 0.14). The product of RT dose and length of esophagus in the RT field was larger in the AMI group (934 vs. 761, P = 0.035). Median survival time for all patients was 12.4 months. Esophagitis Index, a novel measure of the severity and duration of acute esophagitis, may be reduced in lung cancer patients receiving twice-weekly AMI with thoracic RT and paclitaxel. Twice weekly AMI did not eliminate grade 3 esophagitis; therefore, dose escalation of AMI is planned. The effect of AMI was not due to the shorter irradiated esophageal length. A phase III randomized trial is now open to assess AMI's effect on esophagitis.

Small-cell lung cancer: a perspective on the past and a preview of the future.

Despite advances in the treatment of small-cell lung cancer during the 1970s, with the use of combination chemotherapy, and in the 1980s, with the combination of etoposide and cisplatin plus concurrent radiation therapy, treatment success seems to have reached a plateau in the current decade. Research should now be directed into three areas: (1) strategies to prevent the development of second cancers, one of the major causes of death in people "cured" of their first primary cancer; (2) introduction of new agents such as paclitaxel (Taxol) and other newer chemotherapeutic drugs into clinical trials, particularly in conjunction with radiation therapy in limited disease; and (3) development of new therapeutic approaches, such as the modulation of drug resistance, molecular biology interventions, and monoclonal antibody therapy, strategies that are based on increased understanding of small-cell lung cancer biology. Although it is doubtful that any single strategy will be curative, selective approaches that exploit new research findings in conjunction with moderately effective, more conventional treatments might allow us to raise remission and survival rates significantly.

Evaluation of surgical approaches to endoscopic auditory brainstem implantation.

OBJECTIVES: This study investigates the use of endoscopy for the placement of an auditory brainstem implant by translabyrinthine, retrosigmoid (suboccipital), and middle cranial fossa approaches. STUDY DESIGN: Cadaver dissection and endoscope-assisted placement of the auditory brainstem implant. METHODS: Translabyrinthine, retrosigmoid, and middle cranial fossa dissections were performed bilaterally in five cadaveric heads. An auditory brainstem implant was placed within the lateral recess of the fourth ventricle under endoscopic visualization. The implantation was performed with all approaches and documented by digital image capture followed by production of dye-sublimation photographic prints. RESULTS: The lateral recess was visualized with the endoscope in all three approaches to the brainstem. The 30 degrees endoscope provided the best visualization by translabyrinthine and retrosigmoid dissection and was essential for the middle cranial fossa approach. Refinement of implant position was readily achieved, as even the deepest portion of the recess could be seen with all three approaches. CONCLUSIONS: This study finds that endoscopy provides superior visualization of the lateral recess of the fourth ventricle than the operating microscope with all approaches. The retrosigmoid approach is recommended, as it provides the best view of the implantation site and the easiest angle for placement of the prosthesis. The use of the endoscope may allow for a smaller craniotomy than with conventional microscopic techniques, depending on tumor size. The translabyrinthine approach provides a good view of the lateral recess but had no advantage over other approaches. The middle cranial fossa approach is only possible with angled endoscopes; however, it is technically the most difficult and places the facial nerve at greatest risk.

Bacterial colonization of endotracheal tubes in intubated neonates.

OBJECTIVE: To obtain in vivo bacterial colonization profiles on endotracheal tubes at different sites in the neonatal airway in an attempt to better characterize one potential element of chondritis. DESIGN: A case series in which cultures were obtained from calculated segments of 33 endotracheal tubes immediately following extubation. This allowed for sampling at specific levels of the airway corresponding to the trachea, the subglottis, and the oropharynx. Data collected included gender, race, duration of intubation, use of antibiotic therapy, comorbidities, gestational age at birth and extubation, crown-rump length, weight, radiographic distance from tube tip to carina, and culture results. SETTING: Newborn intensive care unit at a tertiary care medical center. PATIENTS: Twenty-nine neonates intubated for longer than 24 hours (range, 24 hours to 15 days). MAIN OUTCOME MEASURES: Bacterial and fungal cultures obtained from 3 endotracheal tube segments for each extubation. RESULTS: A statistically significant difference (P < .05) was found in colonization rates between patients intubated for less than 4 days and those intubated for longer periods. No significant difference was noted in bacterial profile between the 3 sites. CONCLUSIONS: Data demonstrate that bacterial colonization of an indwelling object in the neonatal airway increases with the duration of intubation. Furthermore, 4 days seems to represent a critical period in the formation of such colonization (possibly in the form of a biofilm). These bacteria may contribute to the chondritis known to precede the development of subglottic stenosis. Further studies are indicated to suggest ways to interrupt this process and reduce the incidence of airway injury.

Lymphatic malformation: predictive factors for recurrence.

OBJECTIVE: Although lymphatic malformations are often found to be well circumscribed when surgery is undertaken in early childhood, complete surgical excision can be difficult when the lesion is infiltrative. This study retrospectively evaluates these patients in an attempt to identify prognostic factors that may predict recurrence. STUDY DESIGN AND SETTING: A retrospective chart review was conducted covering the years 1991 to 1998. Seventeen patients were identified having undergone 32 surgical resections of tumors described as lymphatic malformations. Data abstracted from the charts included the site of the lesion, surgical and histologic assessment of encapsulation, and status at follow-up examination. RESULTS: Six of 17 patients developed a recurrence after surgery. Correlation between recurrence and histologic or operative impressions of encapsulation was significant by chi(2) analysis (P<0.01). CONCLUSION: On the basis of the findings of this case series, lymphatic malformations that are found to be nonencapsulated and infiltrative by intraoperative or histologic assessment are more likely to recur.

Cochlear implantation for auditory rehabilitation in Camurati-Engelmann disease.

Camurati-Engelmann disease (progressive hereditary diaphyseal dysplasia) is a rare sclerotic bone disease involving the diaphyses of the long bones, skull base, and clavicles. Progressive sclerosis of cranial nerve foramina has been implicated in cranial nerve deficits. including facial nerve palsy, vestibular disturbances, and hearing loss. Two patients with Camurati-Engelmann disease and concomitant sensorineural hearing loss are presented. Both patients were evaluated for cochlear implantation. One patient was successfully implanted after preoperative imaging revealed no involvement of the internal auditory canals. The porous nature of the affected bone, however. necessitated the inactivation of 1 electrode to prevent facial nerve stimulation. A second patient was rejected as a potential implant recipient due, in part, to narrow internal auditory canals and rapidly progressive disease. The otologic manifestations of Camurati-Engelmann disease are reviewed, and issues related to cochlear implantation in this rare disease are discussed.

Rapid resolution of fetal goiter associated with maternal Grave's disease: a case report.

The incidence of abnormal fetal thyroid function with maternal Grave's disease is about 2-12%. The development of larger fetal goiters can complicate labor and precipitate life-threatening airway obstruction at delivery. A case is presented of a large stable goiter confirmed by sonography, which unexpectedly resolved by the time of parturition. A 3 x 6 cm fetal goiter was detected at 34 weeks gestation in a mother treated with propylthiouracil for Grave's disease. A repeat sonogram at 36 weeks showed no change in goiter size. Umbilical blood sampling showed the fetus to be markedly hyperthyroid. Planned Cesarean section took place 11 days after the final sonogram. A multi-disciplinary operative team was present including the Otolaryngology service with equipment for emergency intubation, bronchoscopy and tracheotomy. Upon delivery, the infant had no evidence of goiter and no airway compromise. Fetal goiter is a rare entity, and recent advances in the field of maternal-fetal medicine have enabled intra-uterine diagnosis and treatment of such conditions. A review of published case reports demonstrates two trends in treated fetuses: preterm progressive resolution of the goiter, or delivery with gross evidence of goiter. This reported case is unique, as a persistent goiter resolved completely in less than 2 weeks. Otolaryngologic response to and management of potential congenital airway compromise is discussed.

A cost-effectiveness analysis of the high risk register and auditory brainstem response.

OBJECTIVE: To evaluate an infant hearing screening program utilizing the high risk register (HRR) and auditory brainstem response (ABR). DESIGN: A cost-effectiveness analysis of the screening program employing a retrospective cohort identified by chart review. The analysis was performed on a hypothetical cohort of 100,000 births and the results compared with a base model derived from literature review. SETTING: Mount Sinai Hospital, New York City, an urban, tertiary care institution. PATIENTS: All infants born between November 1990 and October 1993, approximately 16,500. Cost-effectiveness analysis focused on test results of 420 infants failing the HRR and 381 who subsequently received ABR. RESULTS: Analysis of the Mount Sinai Hospital (MSH) protocol showed it to be less cost-effective than other similar programs. The cost per hearing loss was far more at MSH than that found elsewhere. Further, the MSH program was ineffective in detecting infants with congenital hearing loss--identifying only one case between 1990 and 1993. Analysis of high risk criteria finds a low incidence of family history of hearing loss in the Mount Sinai cohort while other studies find a very high incidence. CONCLUSIONS: It appears that the poor performance of the MSH protocol is due to low specificity and sensitivity of the HRR. This generates a costly and ineffective program as follow-up exams focus on ruling-out false-positives rather than correctly identifying true hearing losses. Further evaluation is needed to determine whether changes in the application of the HRR or utilization of newer, low-cost tests such as otoacoustic emissions (OAE) may be effective in universal infant hearing screening.

A multicenter phase II study of cetuximab in combination with chest radiotherapy and consolidation chemotherapy in patients with stage III non-small cell lung cancer.

BACKGROUND: Cetuximab has demonstrated improved efficacy in combination with chemotherapy and radiotherapy. We evaluated the integration of cetuximab in the combined modality treatment of stage III non-small cell lung cancer (NSCLC). METHODS: Patients with surgically unresectable stage IIIA or IIIB NSCLC were treated with chest radiotherapy, 73.5 Gy (with lung and tissue heterogeneity corrections) in 35 fractions/7 weeks, once daily (63 Gy without heterogeneity corrections). Cetuximab was given weekly during radiotherapy and continued during consolidation therapy with carboplatin and paclitaxel up to a maximum of 26 weekly doses. The primary endpoint was overall survival. Baseline tumor tissue was analyzed for EGFR by fluorescence in situ hybridization (FISH). RESULTS: Forty patients were enrolled in this phase II study. The median overall survival was 19.4 months and the median progression-free survival 9.3 months. The best overall response rate in 31 evaluable patients was 67%. No grade 3 or 4 esophagitis was observed. Three patients experienced grade 3 rash; 16 patients (69%) developed grade 3/4 neutropenia during consolidation therapy. One patient died of pneumonitis, possibly related to cetuximab. EGFR gene copy number on baseline tumor tissues, analyzed by FISH, was not predictive of efficacy outcomes. CONCLUSIONS: The addition of cetuximab to chest radiotherapy and consolidation chemotherapy was tolerated well and had modest efficacy in stage III NSCLC. Taken together with the lower incidence of esophagitis, our results support evaluation of targeted agents instead of chemotherapy with concurrent radiotherapy in this setting.