Comparison of homogenization with the GentleMacs Dissociator vs conventional methods for routine tissue processing.

Tissue specimens are valuable materials for microbiological diagnosis. The method of tissue processing can have a significant effect on sensitivity. This study aimed to compare different biopsy processing methods in terms of efficacy and standardization. Pork tissue artificially inoculated with Staphylococcus aureus and Escherichia coli, and samples of infected human tissue were processed by different methods before culture, and the results compared. Bacterial recovery from artificially inoculated pork tissue was significantly higher by homogenization with GentleMacs Dissociator than with sonication. No significant difference was observed between the GentleMacs Dissociator and manual treatment with a scalpel and vortexing. The microbial yield from homogenized human tissues was significantly higher after homogenization with GentleMacs Dissociator than with the conventional method. Homogenization with the GentleMacs Dissociator retrieves bacteria from tissue effectively. Tissue homogenization with the Dissociator is easy and fast to perform and allows for a high degree of standardization.

Accuracy of a rapid intrapartum group B Streptococcus test: A new immunochromatographic assay.

OBJECTIVES: To decrease the incidence of early-onset group B streptococcal (GBS) disease, a culture-based screening of all pregnant women at 35-37 weeks is recommended. This gold standard test requires 24-72hours culture. This delay precludes its use for intrapartum screening. This study assesses a new immunoassay, the DIMA test, for identifying GBS-positive patients in the labor ward. MATERIALS AND METHODS: This was a prospective observational study of 195 pregnant women presenting with full-term labor at a single site in France between June and August 2012. We assessed the diagnostic accuracy of intrapartum DIMA testing as compared to intrapartum GBS culture and prenatal screening at 35-38 weeks. RESULTS: The DIMA test sensitivity and specificity were 57.1% and 83.2%, respectively, as compared to 42.9% and 97% for prenatal culture screening. CONCLUSION: The DIMA test assay is a rapid and inexpensive test for the detection of maternal GBS colonization in the labor ward. Its sensitivity is higher than antepartum culture but its specificity is lower. Its performance was inferior to that reported for rapid polymerase chain reaction assays.

Targeting colorectal cancer-associated bacteria: A new area of research for personalized treatments.

Most cases of colorectal cancer (CRC) are sporadic, and numerous studies have suggested that gut microbiota may play a crucial role in CRC development. Escherichia coli is a member of the gut microbiota frequently associated with colorectal tumors. CRC-associated E. coli strains frequently harbor the pks genomic island. This genomic island is responsible for the synthesis of colibactin genotoxin, which increases tumor numbers in CRC mouse models. We recently showed that targeting ClbP, a key enzyme involved in colibactin synthesis, blocks the deleterious effect of this toxin in vitro and leads to a significant decrease in tumor numbers in vivo. Altogether, our results suggest that the personalized treatment of CRC should also take into consideration the bacteria associated with the tumor in order to limit their deleterious effects.

[Position Paper: Significance of the Forced Vital Capacity in Idiopathic Pulmonary Fibrosis]. / Positionspapier zur Bedeutung der forcierten Vitalkapazität für Patienten mit idiopathischer Lungenfibrose (IPF).

Spirometry is a highly standardized method which allows to measure the forced vital capacity (FVC) with high precision and reproducibility. In patients with IPF FVC is directly linked to the disease process which is characterized by scaring of alveoli and shrinkage of the lungs. Consequently, there is ample evidence form clinical studies that the decline of FVC over time is consistently associated with mortality in IPF. As for the first time effective drugs for the treatment of IPF are available it becomes obvious that in studies which could demonstrate that the drug reduces FVC decline, a numerical effect on mortality was also observed, while in one study where a significant effect on FVC decline was missed, there was also no change in mortality. Based on these studies FVC decline is a validated surrogate of mortality in IPF. It is concluded that FVC decline is not only accepted as an endpoint of clinical treatment trials in IPF but is also valid as a patient related outcome parameter which should be considered for the assessment of the efficacy of an IPF drug.

[Pulmonary neuroendocrine neoplasms]. / Neuroendokrine Neoplasien der Lunge.

The pulmonary neuroendocrine neoplasms originate from the enterochromaffin cells which are diffusely distributed in the body. The incidence of these tumors has increased significantly in recent decades due to the available diagnostics. They make up about 1-2% of all lung tumors and 20-30% of all neuroendocrine neoplasms. The current WHO classification from 2004 divides them into typical carcinoids (TC), atypical carcinoids (AC), large cell neuroendocrine carcinomas (LCNEC) and small cell carcinomas (SCLC). The major neuroendocrine biomarkers are chromogranin A, synaptophysin and CD56. TC have a low mitotic rate of <2 mitoses/2mm(2) (10 HPF), whereas the mitotic rate of the AC is 2-10 mitoses/2 mm(2) (10 HPF). The Ki-67 staining is helpful to distinguish typical and atypical carcinoids from the highly malignant LCNEC and SCLC. Clinically, the patient presents usually with cough, hemoptysis or bronchial obstruction. The occurrence of a carcinoid or Cushing's syndrome and a tumor-associated acromegaly are rare. Surgical resection with radical lymph node dissection is the treatment of choice for achieving long-term survival. Endoscopic resection of the endobronchial tumor growth is a good alternative for inoperable endobronchially localized tumors. Peptide receptor radionuclide therapy (PRRT) is a promising treatment option for patients with metastatic or unresectable pulmonary neuroendocrine tumors. New targeted therapies using angiogenesis inhibitors, mTOR inhibitors, and tyrosine kinase inhibitors are being tested for their effectiveness in many previous studies. Typical carcinoid tumors metastasize less frequently than AC, the 5-year survival rate of patients with TC being over 90%. Patients with AC have a 5-year survival rate between 35% and 87%. The highly malignant LCNEC and SCLC, on the other hand, have a 5-year survival rate between 15% and 57%, and <5% respectively. The increasing number of therapeutic options and diagnostic procedures requires a multidisciplinary approach and decision-making in multidisciplinary tumor conferences to ensure a personalized treatment approach. Therefore patients with a neuroendocrine neoplasm of the lung should be treated in specialized centers.

[Parotid involvement in Churg-Strauss syndrome]. / Atteinte parotidienne et syndrome de Churg-Strauss.

INTRODUCTION: Churg-Strauss syndrome is a rare systemic vascularitis. This disease causes eosinophilic tissue infiltration. The most frequent manifestations are cortico-dependent asthma, mono- or polyneuropathy, paranasal sinus polyposis, and digestive and renal dysfunction. Salivary glands are very rarely involved. OBSERVATION: We describe a case of CSS in a patient presenting with bilateral parotid swelling. The morphological study of salivary glands revealed an unusual thickening of the salivary duct walls. DISCUSSION: Salivary gland involvement in Churg and Strauss syndrome can be difficult to demonstrate histologically; it does not usually present in the clinical foreground of the disease, and can be a source of misdiagnosis. The biopsy should be performed in the symptomatic gland, away from any previous corticoid treatment.

[50 years WATL (Scientific Working Group for the Therapy of Lung Diseases)]. / 50 Jahre WATL (Wissenschaftliche Arbeitsgemeinschaft für die Therapie von Lungenkrankheiten e.V.).

On the occasion of the 50th anniversary of the Scientific Working Group for the Therapy of Lung Diseases (WATL) the history is described from its foundation to the present situation. Research topics during this long period are specified and the studies are briefly outlined. In the beginning, WATL was engaged mainly in studies on tuberculosis, later on, the spectrum of WATL was broadened considerably to diseases like sarcoidosis, pulmonary Langerhans' cell histiocytosis, pulmonary emphysema due to α1-antitrypsin deficiency, chronic obstructive bronchitis and bronchial asthma as well as nontuberculous mycobacterioses. Finally, realising that the methodological capabilities of WATL were not sufficient to conduct large trials in classical lung diseases considering current requirements, WATL has begun to acquire competence in rare lung diseases such as lymphangioleiomyomatosis and alveolar proteinosis. In addition, WATL is dedicated to educative aims by organising conferences on topics which are not part of main stream respiratory medicine.

[German guideline for diagnosis and management of idiopathic pulmonary fibrosis]. / S2K-Leitlinie zur Diagnostik und Therapie der idiopathischen Lungenfibrose.

Idiopathic pulmonary fibrosis is a fatal lung disease with a variable and unpredictable natural history and limited treatment options. Since publication of the ATS-ERS statement on IPF in the year 2000 diagnostic standards have improved and a considerable number of randomized controlled treatment trials have been published necessitating a revision. In the years 2006 - 2010 an international panel of IPF experts produced an evidence-based guideline on diagnosis and treatment of IPF, which was published in 2011. In order to implement this evidence-based guideline into the German Health System a group of German IPF experts translated and commented the international guideline, also including new publications in the field. A consensus conference was held in Bochum on December 3rd 2011 under the protectorate of the "Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin (DGP)" and supervised by the "Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften" (AWMF). Most recommendations of the international guideline were found to be appropriate for the german situation. Based on recent clinical studies "weak negative" treatment recommendations for pirfenidone and anticoagulation were changed into "weak positive" for pirfenidone and "strong negative" for anticoagulation. Based on negative results from the PANTHER-trial the recommendation for the combination therapy of prednisone plus azathiorpine plus N-acetlycsteine was also changed into strong negative für patients with definite IPF. This document summarizes essential parts of the international IPF guideline and the comments and recommendations of the German IPF consensus conference.

[Expert dialogue: neuroendocrine tumours of the lungs and gastroenteropancreatic system]. / Expertendialog: Neuroendokrine Tumore der Lunge und des gastroenteropankreatischen Systems.

BACKGROUND: Neuroendocrine tumours of the lung exhibit an increasing incidence and prevalence. However, data on the diagnosis of and therapy for these tumours are sparse compared to neuroendocrine tumours of the gastroenteropancreatic system. METHODS: The present article reflects a dialogue between experts on neuroendocrine tumors of the lung and the gastroenteropancreatic system held on February 25th and 26th in Weimar, Germany. RESULTS: Many similarities exist between neuroendocrine tumours of the lung and the gastroenteropancreatic system but there are also significant differences. Similarities exist mainly concerning pathology, diagnosis and therapy. Differences exist regarding the systemic therapy and the significantly lower incidence of paraneoplastic syndromes. Somatostatin receptor PET/CT with gallium-68 labelled somatostatin analogues and peptide receptor radiotherapy are innovative methods for the diagnosis of and therapy for neuroendocrine tumours of the lung. The first treatment option remains complete resection of the tumour. Small molecules like everolimus (Afinitor®) have been tested in clinical trials and have been shown to prolong progression-free survival. CONCLUSIONS: Additional studies are necessary and efforts should be undertaken to establish a registry to increase data on methods suitable for he diagnosis of and therapy for neuroendocrine tumours of the lung.

[Medial proximal tibia donor site: contribution to alveolar cleft repair in children]. / Le prélèvement tibial médioproximal : intérêt dans l'alvéoloplastie secondaire chez l'enfant.

INTRODUCTION: Cancellous bone is the best material for alveolar cleft repair (or secondary alveolar cleft repair). It is usually harvested from the iliac bone but morbidity of this donor site is high. Among the other possible donor sites the tibial harvesting procedure seems safe with lower morbidity. The authors assessed the medio-proximal tibial harvesting procedure on a consecutive series of 55 children having undergone secondary alveoloplasty. PATIENTS AND METHOD: An individual questionnaire was used to assess retrospectively the intensity and duration of postoperative pain, functional impotence, possible late complications, and scar length. Postoperative tibial in frontal and profile radiographs were used to assess corticotomy diameter, the distance between corticotomy and growth plate, and local complications. RESULTS: The mean patient age was nine years. No complications were reported. Sixty nine percent of patients complained of postoperative pain with an average intensity of four out of 10 for a period of 17 days. Sixty five percent of patients complained of discomfort in walking for an average of 12 days. The average scar length was 10 mm. Two patients (3.6%) presented with sequels two years after surgery, residual scar pain for one, and painless ectopic tibial ossification next to the sampling site for the other. DISCUSSION: The medio-proximal tibial site bone harvesting morbidity is low. The surgical procedure is easy, rapid, and safe. The amount of cancellous bone collected is sufficient for two simultaneous alveolar defect grafts. This site seems especially well adapted for secondary alveoloplasty in children.

Treatment of advanced emphysema with emphysematous lung sealant (AeriSeal®).

BACKGROUND: This report summarizes initial tests of an emphysematous lung synthetic polymer sealant (ELS) designed to reduce lung volume in patients with advanced emphysema. OBJECTIVES: The primary study objective was to define a therapeutic strategy to optimize treatment safety and effectiveness. METHODS: ELS therapy was administered bronchoscopically to 25 patients with heterogeneous emphysema in an open-label, noncontrolled study at 6 centers in Germany. Treatment was performed initially at 2-4 subsegments. After 12 weeks, patients were eligible for repeat therapy to a total of 6 sites. Safety and efficacy were assessed after 6 months. Responses were evaluated in terms of changes from baseline in lung physiology, functional capacity, and health-related quality of life. Follow-up is available for 21 of 25 patients. RESULTS: Treatment was well tolerated. There were no treatment-related deaths (i.e., within 90 days of treatment), and an acceptable short- and long-term safety profile. Physiological and clinical benefits were observed at 24 weeks. Efficacy responses were better among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III patients [n = 14; change in residual volume/total lung capacity (ΔRV/TLC) = -7.4 ± 10.3%; Δ forced expiratory volume in 1 s (ΔFEV(1)) = +15.9 ± 22.6%; change in forced vital capacity (ΔFVC) = +24.1 ± 22.7%; change in carbon monoxide lung diffusion capacity (ΔDLCO) = +19.3 ± 34.8%; change in 6-min walk test (Δ6MWD) = +28.7 ± 59.6 m; change in Medical Research Council Dyspnea (ΔMRCD) score = -1.0 ± 1.04 units; change in St. George's Respiratory Questionnaire (ΔSGRQ) score = -9.9 ± 15.3 units] than for GOLD stage IV patients (n = 7; ΔRV/TLC = -0.5 ± 6.4%; ΔFEV(1) = +2.3 ± 12.3%; ΔFVC = +2.6 ± 21.1%; ΔDLCO = -2.8 ± 17.2%; Δ6MWD = +28.3 ± 58.4 m; ΔMRCD = 0.3 ± 0.81 units; ΔSGRQ = -6.7 ± 7.0 units). CONCLUSIONS: ELS therapy shows promise for treating patients with advanced heterogeneous emphysema. Additional studies to assess responses in a larger cohort with a longer follow-up are warranted.

[Analysis of a severe septic transfusion reaction with standard platelet concentrate]. / Analyse d'un incident bactérien grave transmis par transfusion d'un concentré plaquettaire.

We recently observed a near fatal case of transfusion-transmitted infection with standard platelet concentrate. Streptococcus dysgalactiae subspecies equisimilis was isolated both from donor, residual component container and cultures of the patient's blood. This should question the usefulness of systematic bacterial detection in platelet concentrates, however a lethal accident has occurred recently which escaped bacterial detection. This observation calls for implementation of pathogen inactivation procedures for platelets concentrates.

[Should presumptive meningoencephalitis treatment in adults be active against Mycoplasma pneumoniae?]. / Le traitement de première intention d'une méningoencéphalite de l'adulte doit-il tenir compte de Mycoplasma pneumoniae?

INTRODUCTION: Meningoencephalitis is the most common central nervous system complication caused by Mycoplasma pneumoniae. Its frequency is probably underestimated. OBJECTIVE: The study's aim was to determine the retrospectively incidence of M. pneumoniae meningoencephalitis among other cases of encephalitis diagnosed in infectiology, neurology and ICU at the Clermont-Ferrand University hospital in 2004 and 2005. DESIGN: A case of meningoencephalitis was defined by encephalopathy (altered level of consciousness and/or change in personality), with one or more of the following symptoms: fever, seizure, focal neurological findings, meningitis, electroencephalography or neuroimaging findings consistent with encephalitis. Tumor and hematoma diagnosed by scan were excluded. M. pneumoniae was considered as a possible cause when patients had positive serological test (IgM Elisa) and/or positive PCR results for the CSF. RESULTS: Four (8.3%) patients among 48 cases of encephalitis could have been caused by M. pneumoniae. All except one convulsed initially. Pneumopathy was found in two patients. All received a specific treatment later. Antibiotics seemed to influence evolution in only two patients. These 4 cases appeared during an epidemic between November 2004 and August 2005: 48 hospitalized adults had positive serological test for M. pneumoniae in 2005 and 15 in 2004, whereas the number of tests was the same in 2004 and in 2005. CONCLUSIONS: M. pneumoniae should be investigated as a cause of meningoencephalitis if initial tests are negative, if patients have respiratory symptoms and in case of epidemic. Presumptive treatment of meningoencephalitis should include an antibiotic active against M. pneumoniae.

Pseudomonas aeruginosa and Pseudomonas putida outbreak associated with contaminated water outlets in an oncohaematology paediatric unit.

This paper describes an outbreak of Pseudomonas aeruginosa and Pseudomonas putida that occurred in an oncohaematology paediatric unit between January and April 2005. Eight children had nosocomial infections due to P. aeruginosa (N=5) or P. putida (N=3), which were recovered from central venous catheter blood cultures (N=4), the catheter exit site alone (N=2), or the catheter exit site and the catheter tip (N=2). Subsequent investigation showed that contaminated water outlets represented the possible source of spread. Studies of nursing and environmental cleaning practices revealed two modes of catheter contamination. A reduction in the size of the catheter dressing at the exit site gave less protective cover during showers, and a detergent-disinfectant diluted with tap water had contaminated perfusion bottles. Repetitive intergenic consensus polymerase chain reaction indicated two discrete patterns for P. aeruginosa and one for P. putida. The water network was chlorinated, and disposable seven-day filters were fitted on all taps and showers. Due to the deleterious effects of chlorination on the water network and the cost of the weekly filter change, a water loop producing microbiologically controlled water was installed. In addition, the concentration of the detergent-disinfectant was increased and refillable sprayers were replaced with ready-to-use detergent-disinfectant solution for high-risk areas. Following these measures, no Pseudomonas spp. have since been isolated in clinical or environmental samples from the ward.

2,9-Dimethyl-beta-carbolinium, a neurotoxin occurring in human brain, is a potent inducer of apoptosis as 1-methyl-4-phenylpyridinium.

The causes of neurodegeneration are not well understood. However, the role of environmental and endogenous toxins is receiving much attention. In this study, we compared the synthetic neurotoxin 1-methyl-4-phenyl-pyridinium with beta-carbolines occurring in human brain. Methylation of both nitrogens is necessary to convert a beta-carboline into a potent inhibitor of mitochondrial complex I. The respective beta-carboline, 2,9-dimethyl-beta-carbolinium ion is neurotoxic in rats. To investigate the underlying mechanisms, we incubated mouse neuroblastoma 2A cells with 2,9-dimethyl-beta-carbolinium ion, and compared the findings with effects of norharman, the precursor beta-carboline of methylated derivatives, and with 1-methyl-4-phenyl-pyridinium. 2,9-Dimethyl-beta-carbolinium ion caused a significant increase of reactive oxygen species (higher efficiency than 1-methyl-4-phenyl-pyridinium) and of mitochondrial membrane potential within the first minutes. After 60 min, the membrane potential dissipated. Concomitantly, the levels of glutathione increased in 2,9-dimethyl-beta-carbolinium ion but not in 1-methyl-4-phenyl-pyridinium treated cells. After 24 h effector caspases 3 and 7 were activated and the number of apoptotic cells increased as revealed by fluorescence-activated cell sorting cytometry. When incubated longer (48 h), cells underwent late apoptosis/secondary necrosis as shown by fluorescence-activated cell sorting analysis and confirmed qualitatively by an electron microscopy study. The effects of 2,9-dimethyl-beta-carbolinium ion on apoptotic changes were similar to those induced by 1-methyl-4-phenyl-pyridinium(,) while norharman showed only a weak potency at the very high doses. To investigate whether 2,9-dimethyl-beta-carbolinium ion is neurotoxic under in vivo conditions and whether only dopaminergic neurones are affected we conducted a dose-response study. Three weeks after injection of 2,9-dimethyl-beta-carbolinium ion in the substantia nigra we found a dose-dependent decrease of dopamine and its metabolites in the striatum of rats. The levels of 5-hydroxytryptamine were diminished although the decrease was less. The levels of noradrenaline increased after some doses. The findings strongly suggest an important role of endogenous beta-carbolines in neurodegeneration with apoptosis as the predominant mechanism.

[Correlation of histologic results with PET findings for tumor regression and survival in locally advanced non-small cell lung cancer after neoadjuvant treatment]. / Korrelation histologischer und nuklearmedizinischer Befunde der Tumorregression in behandelten bösartigen Lungentumoren.

UNLABELLED: CT cannot provide useful information in a timely manner after neoadjuvant treatment. To evaluate the role of (18)F FDG PET after neoadjuvant chemoradiation for early therapy response and its effect on survival as compared to histopathologic tumor response, findings in 32 patients were analyzed prospectively in an ongoing multicenter trial (LUCAS-MD). INCLUSION CRITERIA: histologically confirmed NSCLC stage IIIA/IIIB. Neoadjuvant treatment: 2-3 cycles with paclitaxel/carboplatin and a block of chemoradiation followed by surgery. Pretherapeutic staging: PET scan in addition to a spiral CT and/or MRI. Second PET scan after completion of neoadjuvant therapy prior to surgery. Documentation of lymph node involvement. Assessment of SUV and the metabolic tumor index for primary tumor and metastatic lymph nodes. Image fusion of PET with CT data followed by molecular radiation treatment planning. Evaluation of histologic regression grade and correlation with PET for primary tumor and each lymph node location. All patients (10/32) with complete response in lymph node metastases detected by PET prior to surgery, had no vital tumor cells (i.e. histologic regression grade/RG III, sensitivity 100%). In primary tumors showing complete response, the RG was IIb or III, in one patient IIa (false negative in PET). False positive findings in PET are due to inflammation (5 patients, histologically confirmed). Univariate analyses: actuarial tumor-specific survival for complete metabolic remission vs. incomplete remission after 24 months: 76 vs. 20% (p=0,0079); for RG III/IIb vs. RG IIa/I after 24 months: 63 vs. 36% (p=0,0123).(18)F FDG PET precedes CT in measuring the tumor response and may predict (long term) therapeutic outcome in stage III NSCLC. Histologic regression grade correlates well with metabolic remission as detected by PET.

Effects of proton and combined proton/photon beam radiation on pulmonary function in patients with resectable but medically inoperable non-small cell lung cancer.

STUDY OBJECTIVES: We evaluated the effects on pulmonary function of irradiating lung cancer with protons alone or protons combined with photons. DESIGN: Prospective phase I/II study. SETTING: University medical center. PATIENTS AND INTERVENTIONS: Ten patients with stage I-II non-small cell lung cancer (NSCLC) and FEV(1) < or = 1.0 L were irradiated with protons to areas of gross disease only, using 51 cobalt gray equivalents (CGE) in 10 fractions (protocol 1). Fifteen patients with stage I-IIIA NSCLC and FEV(1) > 1.0 L received 45-Gy photon irradiation to the primary lung tumor and the mediastinum, plus a 28.8-CGE proton boost to the gross tumor volume (protocol 2). MEASUREMENTS: Pulmonary function was evaluated prior to treatment and 1 month, 3 months, and 6 to 12 months following irradiation. RESULTS: In patients receiving protocol 1, no significant changes in pulmonary function occurred. In patients receiving protocol 2, at 6 to 12 months, the diffusion capacity of the lung for carbon monoxide had declined from 61% of predicted to 45% of predicted (p < 0.05), total lung capacity had declined from 114% of predicted to 95% of predicted (p < 0.05), and residual volume had declined from 160% of predicted to 132% of predicted (p < 0.05). Airway resistance increased from 3.8 to 5.2 cm H(2)O/L/s (p < 0.05). No statistically significant changes occurred in vital capacity, FEV(1), or PaO(2). CONCLUSIONS: Our observations indicate that it is feasible to apply higher-than-conventional doses of radiation at a higher-than-conventional dose per fraction without excess pulmonary toxicity when conformal radiation techniques with protons are used.

Proton-beam radiotherapy for early-stage lung cancer.

STUDY OBJECTIVE: A prospective study was undertaken to assess the efficacy and toxicity of conformal proton-beam radiotherapy for early-stage, medically inoperable non-small cell lung cancer. DESIGN: Eligible patients had clinical stage I to IIIa non-small cell lung cancer and were not candidates for surgical resection for medical reasons or because of patient refusal. Patients with adequate cardiopulmonary function received 45 Gy to the mediastinum and gross tumor volume with photons with a concurrent proton boost to the gross tumor volume of an additional 28.8 cobalt gray equivalents (CGE). Total tumor dose was 73.8 CGE given over 5 weeks. Patients with poor cardiopulmonary function received proton-beam radiotherapy to the gross tumor volume only, with 51 CGE given in 10 fractions over a 2-week period. RESULTS: Thirty-seven patients were treated in the study from July 1994 to March 1998. Clinical staging of patients was as follows: stage I, 27 patients; stage II, 2 patients; and stage IIIa, 8 patients. Eighteen patients received a combination of protons and x rays, while 19 patients received proton-beam radiation only. Follow-up of evaluable patients ranged from 3 to 45 months, with a median of 14 months. Two patients in the proton and photon arm developed pneumonitis that resolved with oral steroids; otherwise, no significant toxicities were encountered. The actuarial disease-free survival at 2 years for the entire group was 63%; for stage I patients, disease-free survival at 2 years was 86%. Local disease control was 87%. CONCLUSION: Preliminary results from this study indicate that proton-beam radiotherapy can be used safely in this group of patients. Disease-free survival and local control appear to be good and compare favorably with published reports utilizing conventional photon irradiation.