1-year postactivation results for sequentially implanted bilateral cochlear implant users.

OBJECTIVE: Evaluate speech recognition in quiet and in noise for a group of 12 children, all of whom underwent sequential bilateral cochlear implantation at various ages (range, 1 yr, 8 mo to 9 yr, 6 mo at time of second implant). STUDY DESIGN: Retrospective. SETTING: Outpatient cochlear implant clinic. PATIENTS: Children who underwent sequential bilateral cochlear implantation. INTERVENTION: Rehabilitative. MAIN OUTCOME MEASURES: Speech recognition in quiet was evaluated for each ear separately using single-word speech recognition assessments (Multisyllabic Lexical Neighborhood Test and Early Speech Perception Test) via recorded presentation. Speech recognition in noise was assessed for each ear separately and in the bilateral condition by obtaining a spondee recognition threshold in the presence of speech-weighted noise presented at 45 dB hearing level. The primary outcome measure for speech recognition in noise assessment was the signal-to-noise ratio for 50% performance, which was calculated by determining the difference between the presentation level of the noise and the presentation level at which the speech recognition threshold was obtained. The results of these assessments were contrasted between children receiving their second cochlear implant before 4 years of age and children receiving their second cochlear implant after 4 years of age. RESULTS: A statistically significant difference for speech recognition scores in quiet was obtained between the early-implanted ear and the late-implanted ears for children receiving their second cochlear implant after 4 years of age. There was not a statistically significant difference in speech recognition scores in quiet between the early-implanted and late-implanted ears of children receiving their second cochlear before 4 years of age. Both groups of children possessed better speech recognition scores in noise (statistically significant at an alpha = 0.05) in the bilateral condition relative to either unilateral condition. However, there was not a statistically significant relationship between speech recognition performance in noise and the duration of deafness of the later implanted ear. CONCLUSION: Bilateral cochlear implantation allowed for better speech recognition in noise relative to unilateral performance for a group of 12 children who underwent sequential bilateral cochlear implantation at various ages. There was not a statistically significant relationship between speech recognition in noise benefit, which was defined as the difference in performance between the first implanted ear and the bilateral condition and the age at which the second implant was received. Children receiving bilateral cochlear implants younger than 4 years of age achieved better speech recognition in quiet performance for the later implanted ear as compared with children receiving their second cochlear implant after 4 year of age.

Post-chemotherapy gross tumor volume is predictive of survival in patients with stage III non-small cell lung cancer treated with combined modality therapy.

PURPOSE: To evaluate the influence of clinical covariates, particularly pre-chemotherapy gross tumor volume (GTV), post-chemotherapy GTV, on overall survival in the treatment of stage III non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: We retrospectively analyzed 102 patients who were enrolled on three consecutive clinical trials, which employed the treatment paradigm of two cycles of induction chemotherapy followed by thoracic radiation therapy. The pre-chemotherapy GTV, post-chemotherapy GTV, change in GTV, histology, disease stage, performance status, age, race, treatment with concurrent chemoradiotherapy versus radiotherapy alone were evaluated to determine their impact on overall survival. The log10 of the GTV was used to normalize the data and thereby reduce the impact of exceptionally large values. RESULTS: Both the log10 of the post-chemotherapy GTV and Eastern Cooperative Oncology Group (ECOG) performance status covariates were highly prognostic for overall survival (p = 0.006 and p = 0.008, respectively). Disease stage (at diagnosis) was also significant (p = 0.048). The log10 pre-chemotherapy GTV covariate was borderline significant (p = 0.067). The strongest prognostic model was the two-covariate model, which contained the log10 post-chemotherapy GTV and ECOG performance status covariates, (model chi2 of 18.67, with p = 0.001 for each covariate). CONCLUSIONS: The log10 post-chemotherapy GTV has significant prognostic survival value when the strategy of induction chemotherapy is employed in the treatment on stage III NSCLC. ECOG performance status and stage were also significant prognostic factors for survival.

A phase I/II trial of weekly docetaxel and gefitinib in elderly patients with stage IIIB/IV non-small cell lung cancer.

BACKGROUND: Phase III trials in elderly patients with advanced (stage IIIB/IV) non-small cell lung cancer (NSCLC) reveal treatment with single agent chemotherapy improves survival. The role of double agent therapy in this patient population is an area of investigation. METHODS: A phase I/II trial was performed in elderly patients (age>or=70 years) with stage IIIB/IV disease and Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Patients were treated with gefitinib 250 mg daily. Patients received docetaxel on a treatment schedule of days 1, 8, 15 of an every 28 days schedule. The phase I portion of the trial consisted of dose escalation docetaxel from 30 to 36 mg/m2 using a three patient cohort design. The trial design contained continuous monitoring for excessive toxicity with pre-selected toxicity boundaries. RESULTS: Twenty-six patients were evaluable for efficacy and toxicity analysis. The median age was 75.5 years. The majority of the patients had stage IV disease (85%), ECOG functional status of 0-1 (81%), were male (65%), and current or former smokers (88%). Eleven patients experienced National Cancer Institute Common Toxicity Criteria grades 3-5 non-hematologic toxicity during the first cycle. The toxicity was determined to be unexpected, and the trial was discontinued. Overall response rate (complete+partial responses) was 31%, and the median survival was 6.5 months (95% confidence interval (CI) (3.6-9.0)), and estimated 1-year survival rate was 27% (95% CI (13-55%)). CONCLUSIONS: The combination of weekly docetaxel and gefitinib had activity; however, unexpected toxicity was observed in the elderly patient population.

Carboplatin-based chemotherapy in patients with advanced non-small cell lung cancer and a poor performance status.

BACKGROUND: Poor performance status patients with advanced non-small cell lung cancer (NSCLC) have frequently been excluded from clinical trials due to the perception that they would have excessive treatment-related toxicity and a limited life expectancy. METHODS: A retrospective review of two multicenter trials centered at the University of North Carolina of patients who were treated with platinum-based chemotherapy for advanced NSCLC was conducted. Patients were divided into two subgroups based on Karnofsky performance status (KPS). Patients with a KPS = 70 were considered to have poor performance status, while patients with a KPS > or =80 were considered to have good performance status. RESULTS: Of the 387 patients, 19% (n = 73) had a poor performance status. The response rate (complete and partial responses) was similar between the two sub-groups (26% versus 28%); however, there was a difference in survival (p = 0.0004, log-rank test) between the groups. The median survival and 1-year survival rate for the poor performance status patients was 4.9 months and 21%, while the good performance status patients had a median survival of 8.4 months and a 1-year survival rate of 31%. The rate of National Cancer Institute (NCI) Common Toxicity Criteria (CTC) toxicities was similar between the two groups (p = 0.33). The percentage of patients receiving <4 cycles of therapy in the poor and good performance status was 55 and 39%, respectively (p = 0.012). CONCLUSIONS: Patients with poor performance status treated with platinum based chemotherapy have a similar rate of toxicity compared to good performance status patients. Their overall survival was lower despite a similar response to chemotherapy.

Induction and concurrent chemotherapy with high-dose thoracic conformal radiation therapy in unresectable stage IIIA and IIIB non-small-cell lung cancer: a dose-escalation phase I trial.

PURPOSE: Local control rates at conventional radiotherapy doses (60 to 66 Gy) are poor in stage III non-small-cell lung cancer (NSCLC). Dose escalation using three-dimensional thoracic conformal radiation therapy (TCRT) is one strategy to improve local control and perhaps survival. PATIENTS AND METHODS: Stage III NSCLC patients with a good performance status (PS) were treated with induction chemotherapy (carboplatin area under the curve [AUC] 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) followed by concurrent chemotherapy (carboplatin AUC 2 and paclitaxel 45 mg/m(2) weekly for 7 to 8 weeks) beginning on day 43. Pre- and postchemotherapy computed tomography scans defined the initial clinical target volume (CTV(I)) and boost clinical target volume (CTV(B)), respectively. The CTV(I) received 40 to 50 Gy; the CTV(B) received escalating doses of TCRT from 78 Gy to 82, 86, and 90 Gy. The primary objective was to escalate the TCRT dose from 78 to 90 Gy or to the maximum-tolerated dose. RESULTS: Twenty-nine patients were enrolled (25 assessable patients; median age, 59 years; 62% male; 45% stage IIIA; 38% PS 0; and 38% > or = 5% weight loss). Induction CIP was well tolerated (with filgrastim support) and active (partial response rate, 46.2%; stable disease, 53.8%; and early progression, 0%). The TCRT dose was escalated from 78 to 90 Gy without dose-limiting toxicity. The primary acute toxicity was esophagitis (16%, all grade 3). Late toxicity consisted of grade 2 esophageal stricture (n = 3), bronchial stenosis (n = 2), and fatal hemoptysis (n = 2). The overall response rate was 60%, with a median survival time and 1-year survival probability of 24 months and 0.73 (95% CI, 0.55 to 0.89), respectively. CONCLUSION Escalation of the TCRT dose from 78 to 90 Gy in the context of induction and concurrent chemotherapy was accomplished safely in stage III NSCLC patients.