Citations

Abstract Exercise-induced hypoxia is an index of the severity of interstitial lung disease. We hypothesized that desaturation during a 6-minute walk test would predict mortality for patients with usual interstitial pneumonia (n = 83) and nonspecific interstitial pneumonia (n = 22). Consecutive patients with biopsy-proven disease performed a 6-minute walk test between January 1996 and December 2001. Desaturation was defined as a fall in oxygen saturation to 88% or less during the 6-minute walk test. Desaturation was common (44 of 83 usual interstitial pneumonia and 8 of 22 nonspecific interstitial pneumonia; chi square, p = 0.39). Patients with usual interstitial pneumonia or nonspecific interstitial pneumonia who desaturated had a significantly higher mortality than patients who did not desaturate (respective log-rank tests, p = 0.0018, p = 0.0089). In patients with usual interstitial pneumonia, the presence of desaturation was associated with an increased hazard of death (hazard ratio, 4.2; 95% confidence interval, 1.40, 12.56; p = 0.01) after adjusting for age, sex, smoking, baseline diffusion capacity for carbon monoxide, FVC, and resting saturation. We conclude that knowledge of desaturation during a 6-minute walk test adds prognostic information for patients with usual interstitial pneumonia and nonspecific interstitial pneumonia.

Purpose: The North Central Cancer Treatment Group performed a phase III trial to determine whether chemotherapy plus either bid radiation therapy (RT) or daily (qd) RT resulted in a better outcome for patients with stage III non–small-cell lung cancer (NSCLC). No difference in survival was identified between the two arms. This secondary analysis was performed to examine the relationship between patient age and outcome. Patients and Methods: Two hundred forty-six patients were randomized to receive etoposide plus cisplatin and either RT qd or split-course RT bid. This retrospective study compared the outcomes of patients aged ≥70 years (“elderly patients”) with those of younger individuals. Of the 244 assessable patients, 63 (26%) were elderly, and 181 (74%) were younger individuals. Results: The 2-year and 5-year survival rates were 39% and 18%, respectively, in patients younger than 70 years, compared with 36% and 13%, respectively, in elderly patients (P = .4). Grade 4+ toxicity occurred in 62% of patients younger than 70 years compared with 81% of elderly patients (P = .007). Grade 4+ hematologic toxicity occurred in 56% of patients younger than 70 years, compared with 78% of elderly patients (P = .003). Grade 4+ pneumonitis occurred in 1% of those younger than 70 years, compared with 6% of elderly patients (P = .02). Conclusion: Toxicity, especially myelosuppression and pneumonitis, was more pronounced in the elderly patients receiving combined-modality therapy for locally advanced NSCLC. Despite increased toxicity, elderly patients have survival rates equivalent to younger individuals. Therefore, fit, elderly patients with locally advanced NSCLC should be encouraged to receive combined-modality therapy, preferably on clinical trials with cautious, judicious monitoring. Future studies should explore ways to decrease toxicity of therapy in elderly patients.

Purpose: To determine if increasing the dose of paclitaxel increases the probability of clinical response, progression-free survival, or overall survival in women who have persistent or recurrent ovarian cancer, and whether doubling the dose of prophylactic filgrastim accompanying the higher paclitaxel dose decreases the frequency of neutropenic fever. Patients and Methods: Consenting patients with persistent, recurrent, or progressing ovarian cancer, despite first-line platinum therapy (but no prior taxane), were randomly assigned to paclitaxel 135 mg/m2, 175 mg/m2, or 250 mg/m2 over 24 hours every 3 weeks. Patients receiving paclitaxel 250 mg/m2 were also randomly assigned to 5 or 10 μg/kg of filgrastim per day subcutaneously. Results: Accession to the paclitaxel 135-mg/m2 arm was closed early. Among the 271 patients on the other regimens with measurable disease, partial and complete response on paclitaxel 250 mg/m2 (36%) was significantly higher than on 175 mg/m2 (27%, P = .027). This difference was more evident among patients who never responded to prior platinum. However, progression-free and overall survival results were similar. The median durations of overall survival were 13.1 and 12.3 months for paclitaxel 175 mg/m2 and 250 mg/m2, respectively. Thrombocytopenia, neuropathy, and myalgia were greater with paclitaxel 250 mg/m2 (P < .05). The incidence of neutropenic fever after the first cycle of paclitaxel 250 mg/m2 was 19% and 18% on the 5-μg/kg and 10-μg/kg filgrastim dose, respectively (22% for paclitaxel 175 mg/m2 without filgrastim). Conclusion: Paclitaxel exhibits a dose effect with regard to response rate, but there is more toxicity and no survival benefit to justify paclitaxel 250 mg/m2 plus filgrastim. Doubling the filgrastim dose from 5 to 10 μg/kg did not reduce the probability of neutropenic fever after high-dose paclitaxel.

Abstract Idiopathic interstitial pneumonias are a diverse group of lung diseases with varied prognoses. We hypothesized that changes in physiologic and radiographic parameters would predict survival. We retrospectively examined 80 patients with usual interstitial pneumonia and 29 patients with nonspecific interstitial pneumonia. Baseline characteristics were examined together with 6-month change in forced vital capacity, diffusing capacity for carbon monoxide, and ground glass infiltrate and fibrosis on high resolution computed tomography. Patients with usual interstitial pneumonia were more likely to have a statistically significant or marginally significant decline in lung volume, diffusing capacity for carbon monoxide, and an increase in ground glass infiltrates (p ⩽ 0.08) compared with patients with nonspecific interstitial pneumonia. For patients with usual interstitial pneumonia, change in forced vital capacity was the best physiologic predictor of mortality (p = 0.05). In a multivariate Cox proportional hazards model controlling for histopathologic diagnosis, gender, smoking history, baseline forced vital capacity, and 6-month change in forced vital capacity, a decrease in forced vital capacity remained an independent risk factor for mortality (decrease &gt; 10%; hazard ratio 2.47; 95% confidence interval 1.29, 4.73; p = 0.006). We conclude that a 6-month change in forced vital capacity gives additional prognostic information to baseline features for patients with idiopathic interstitial pneumonia.

Abstract A histologic feature of usual interstitial pneumonia is the presence of fibroblastic foci. As some patients with usual interstitial pneumonia and an underlying collagen vascular disease have a better prognosis, we hypothesized that they would have fewer fibroblastic foci. Pathologists reviewed surgical lung biopsies from 108 patients with usual interstitial pneumonia (nine with collagen vascular disease) and assigned a score (absent 0, mild 1, moderate 2, and marked 3) for fibroblastic foci. Patients with idiopathic usual interstitial pneumonia had a higher median profusion of fibroblastic foci (1.75 vs. 1.0, p = 0.003). Baseline characteristics were similar, although patients with a collagen vascular disease were younger, had a shorter duration of symptoms, and had a higher percentage of predicted total lung capacity. Profusion of fibroblastic foci was the most discriminative feature for separating idiopathic from collagen vascular disease–associated usual interstitial pneumonia (odds ratio 8.31; 95% confidence interval, 1.98, 59.42; p = 0.002 for a one-unit increase in fibroblastic foci score). No deaths were noted in the collagen vascular disease–associated usual interstitial pneumonia group; 52 deaths occurred in the idiopathic usual interstitial pneumonia group (log rank; p = 0.005). We conclude that patients with collagen vascular disease–associated usual interstitial pneumonia have fewer fibroblastic foci and improved survival.

AbstractLight chain–associated amyloidosis (AL) is a plasma cell dyscrasia in which the secreted monoclonal immunoglobulin (Ig) light chains form amyloid fibrils. There is considerable heterogeneity in clinical presentation, and prognosis of the disease relates to the severity of organ dysfunction induced by amyloid deposits. The mechanisms by which the amyloid fibrils are deposited as well as the predilection for specific organ sites have not been clearly elucidated. This study characterizes the repertoire of immunoglobulin light chain variable genes used by the clonal B cell in AL amyloid patients, and the association of light chain variable region (VL) genes with clinical presentation and outcome is assessed in 58 (32 λ and 26 κ) patients. A preferential use of VL germ-line genes was noted for both AL κ and λ patients. There was a significant correlation between the use of the Vλ VI germ-line donor, 6a, and renal involvement as well as the Vλ III gene, 3r, with soft-tissue AL. The use of a biased VL gene repertoire also correlated with clinical outcome, revealing important trends for predicting prognosis. The use of Vλ II germ-line genes was associated with cardiac amyloidosis and affected survival adversely. The presence of multiple myeloma also correlated with a poor prognosis. The presence of renal disease, on the other hand, was associated with improved survival. Therefore, identification of the clonal VL gene in AL has important implications in determining clinical outcome.

Purpose: This phase II study was undertaken to define the efficacy and pharmacodynamics of R115777, a farnesyl transferase inhibitor, in the first-line treatment of patients with advanced non–small-cell lung cancer. Patients and Methods: Forty-four patients with measurable stage IIIB (pleural effusion) or stage IV disease received 193 courses of treatment (median, 2.0; range, 1 to 22) with R115777 300 mg administered orally twice daily for 21 of every 28 days. Buccal mucosa samples and peripheral blood mononuclear cells (PBMCs) were collected before and after 8 days of treatment to evaluate inhibition of farnesyl transferase in vivo. Results: No objective complete or partial responses were documented. Seven patients (16%; 95% confidence interval [CI], 8% to 31%) had disease stabilization for greater than 6 months. Median survival was 7.7 months (95% CI, 6.5 to 10.5) and time to progression was 2.7 months (95% CI, 1.9 to 3.1). The most severe toxicity was neutropenia (9% grade 3, 7% grade 4) and the most common toxicities were anemia (50% grade 1 or 2, 5% grade 3) and anorexia (50% grade 1 or 2, 2% grade 3). Mild peripheral neuropathy occurred in 25% of patients. Evidence of farnesyl transferase inhibition was documented in 83% of patients. Conclusion: Single-agent R115777 was well tolerated in patients with advanced NSCLC, but demonstrated minimal clinical activity. Inhibition of farnesylation in vivo was consistently documented. On the basis of promising results of farnesyl transferase inhibitor combinations with standard chemotherapy agents, future studies of this agent in NSCLC should be in combination with systemic chemotherapy.

Purpose: Studies have documented that the majority of consent documents for medical diagnosis and treatment are written at a reading level above that of the majority of the U.S. population. This study hypothesized that use of an easy-to-read consent statement, when compared with a standard consent statement, will result in higher patient comprehension of the clinical treatment protocol, lower patient anxiety, higher patient satisfaction, and higher patient accrual.Methods: A randomized controlled trial was conducted in 44 institutions that were members or affiliates of three cooperative oncology groups. Institutions were randomly assigned to administer either an easy-to-read consent statement or the standard consent statement to patients being recruited to participate in selected cancer treatment trials. Telephone interviews were conducted with a total of 207 patients to assess study outcomes.Results: Patients in the intervention arm demonstrated significantly lower consent anxiety and higher satisfaction compared with patients in the control arm. Patient comprehension and state anxiety were not affected by the intervention. Accrual rates into the parent studies also did not differ significantly between the two study groups.Conclusion: Clinical trial informed consent statements can be modified to be easier to read without omitting critical information. Patient anxiety and satisfaction can be affected by the consent document. The generalizability of these study results is limited by the characteristics of the patient sample. Ninety percent of the sample were white women, and the mean Rapid Estimate of Adult Literacy in Medicine score was approximately 64, indicating a literacy level at or above the ninth grade.

Purpose: Preoperative chemotherapy is the conventional primary treatment in locally advanced breast cancer (LABC). We investigated the safety and efficacy of primary twice-weekly paclitaxel and concurrent radiation (RT) before modified radical mastectomy followed by adjuvant doxorubicin-based chemotherapy. Patients and Methods: Stage IIB (T3N0) to III LABC patients were eligible. Primary chemoradiation consisted of paclitaxel, 30 mg/m2 delivered intravenously for 1 hour twice weekly for a total of 8 to 10 weeks, and concurrent RT (45 Gy at 1.8 Gy/fraction). Modified radical mastectomy was performed at least 2 weeks after completion of chemoradiation or on recovery of skin toxicity. Postoperatively, patients who responded to paclitaxel and RT received four cycles of doxorubicin/paclitaxel, whereas patients who did not respond received doxorubicin/cytoxan. Results: Forty-four patients were accrued. Toxicity from paclitaxel/RT included grade 3 skin desquamation (7%), hypersensitivity (2%), and stomatitis (2%). Postsurgery complications occurred in six patients (14%). The only grade 4 toxicity of postmastectomy chemotherapy was hematologic (10%). Grade 3 toxicities were leukopenia (24%), infection (22%), peripheral neuropathy (17%), arthralgia and pain (17%), stomatitis (12%), fatigue (10%), esophagitis (5%), and nausea (2%). Overall clinical response rate to preoperative paclitaxel and RT was 91%. Thirty-four percent of patients achieved a pathologic response in the mastectomy specimen: 16% pathologic complete responses (clearance of invasive cancer in the breast and axillary contents) and 18% pathologic partial responses (< 10 residual microscopic foci of invasive breast cancer). Conclusion: Twice-weekly paclitaxel with concurrent RT is a feasible and effective primary treatment for LABC. Future studies should compare primary chemoradiation to chemotherapy in LABC.

OBJECTIVEThe goal was to examine the current scope of otolaryngologists’ practices, their geographic distribution, and the roles otolaryngologists and other specialists play in caring for patients with otolaryngic and related conditions of the head and neck.STUDY DESIGNA large national survey and administrative claims databases were examined to develop practice profiles and compile a physician supply for otolaryngology. A focus group of otolaryngologists provided information to model future scenarios.RESULTSThe current and predicted workforce supply and demographics are at a satisfactory level and are decreasing as a proportion of the increasing population. Empiric data analysis supports the diverse nature of an otolaryngologist's practice and the unique role for otolaryngologists that is not shared by many other providers. Together with the focus group results, the study points to areas for which more background and training are warranted.CONCLUSIONSThis study represents a first step in a process to form coherent workforce recommendations for the field of otolaryngology.