Radiation Necrosis in Pediatric Patients with Brain Tumors Treated with Proton Radiotherapy.

BACKGROUND AND PURPOSE: Proton radiotherapy has been increasingly utilized to treat pediatric brain tumors, however, limited information exists regarding radiation necrosis among these patients. Our aim was to evaluate the incidence, timing, clinical significance, risk factors, and imaging patterns of radiation necrosis in pediatric patients with brain tumors treated with proton radiation therapy. MATERIALS AND METHODS: A retrospective study was performed on 60 consecutive pediatric patients with primary brain tumors treated with proton radiation therapy. Radiation necrosis was assessed by examining serial MRIs and clinical records to determine the incidence, timing, risk factors, imaging patterns, and clinical significance associated with the development of radiation necrosis in these patients. Radiation necrosis was defined as areas of new enhancement within an anatomic region with previous exposure to proton beam therapy with subsequent decrease on follow-up imaging without changes in chemotherapy. RESULTS: Thirty-one percent of patients developed radiation necrosis with a median time to development of 5.0 months (range, 3-11 months). Risk factors included multiple chemotherapy agents (>3 cytotoxic agents) and atypical teratoid rhabdoid tumor pathology (P = .03 and P = .03, respectively). The most common imaging patterns were small (median, 0.9 cm) and multifocal (63% of patients) areas of parenchymal enhancement remote from the surgical site. The median time to complete resolution on imaging was 5.3 months (range, 3-12 months). Among patients with imaging findings of radiation necrosis, 25% demonstrated severe symptoms with medical intervention indicated. CONCLUSIONS: Pediatric patients with brain tumors treated with proton radiation therapy demonstrate a high incidence of radiation necrosis and a short time to development of necrosis. Multiple small areas of necrosis are frequently identified on imaging. Exposure to multiple chemotherapy agents was a significant risk factor associated with radiation necrosis in these patients.

Radiation dose response in patients with favorable localized prostate cancer (Stage T1-T2, biopsy Gleason < or = 6, and pretreatment prostate-specific antigen < or = 10).

PURPOSE: To study the radiation dose response as determined by biochemical relapse-free survival in patients with favorable localized prostate cancers, i.e., Stage T1-T2, biopsy Gleason score (bGS) < or = 6, and pretreatment prostate-specific antigen (iPSA) < or = 10 ng/mL. METHODS AND MATERIALS: A total of 292 patients with favorable localized prostate cancer were treated with radiotherapy alone between 1986 and 1999. The median age was 69 years. Sixteen percent of cases (n = 46) were African-American. The distribution by clinical T stage was as follows: T1/T2A, 243 (83%); and T2B/T2C, 49 (17%). The distribution by iPSA was as follows: < or = 4 ng/mL, 49 (17%); and > 4 ng/mL, 243 (83%). The mean iPSA level was 6.2 (median, 6.4). The distribution by bGS was as follows: or = 5 in 89 cases (30%) and 6 in 203 cases (70%). The median radiation dose was 70.0 Gy (range, 63.0-78.0 Gy). Doses of < or = 70.0 Gy were delivered in 175 cases, 70.2-72.0 Gy in 24 cases, 74 Gy in 30 cases, and 78 Gy in 63 cases. For patients receiving < 72 Gy, the median dose was 68 Gy, vs. 78 Gy for patients receiving > or = 72 Gy. A conformal technique was used in 129 (44%) of cases. The median follow-up was 43 months (range, 3-153). RESULTS: For the entire cohort, the projected 5- and 8-year biochemical relapse-free survival (bRFS) rates were both 81%. For patients receiving > or = 72 Gy, the 5- and 8-year bRFS rates were both 95% vs. only 77% for patients receiving < 72 Gy, p = 0.010. For patients receiving 74 Gy, the 4-year bRFS rate was 94% vs. 96% for patients receiving 78 Gy, p = 0.90. A multivariate analysis for factors affecting bRFS rates using Cox proportional hazards was performed for all cases using the following variables: age (continuous variable), race (black vs. white), iPSA (continuous variable), bGS (< or = 5 vs. 6), Stage (T1-2A vs. T2B-C), radiation dose (continuous variable), and radiation technique (conformal vs. standard). From the multivariate analysis, only iPSA (p = 0.017, chi(2) = 5.7), and radiation dose (p = 0.021, chi(2) = 5.3) were independent predictors of outcome. Age (p = 0.94), race (p = 0.89), stage (p = 0.45), biopsy GS (p = 0.40), and radiation technique (p = 0.45) were not. CONCLUSION: There is a clear radiation dose response in patients with favorable localized prostate cancers (i.e., Stage T1-T2, biopsy Gleason score < or = 6, and iPSA < or = 10 ng/mL). At least 74 Gy should be delivered to the prostate and periprostatic tissues. With our cohort of patients, longer follow-up will be needed to assess the importance of doses exceeding 74 Gy.

Increased Pneumocystis carinii recovery from the upper lobes in Pneumocystis pneumonia. The effect of aerosol pentamidine prophylaxis.

STUDY OBJECTIVE: To determine the relative distribution of Pneumocystis carinii in the lungs of patients with P carinii pneumonia and to see the effect of aerosol pentamidine prophylaxis on this distribution. DESIGN: A prospective study of all human immunodeficiency virus-infected patients with pulmonary symptoms over a nine-month period. Patients were followed up for at least six weeks after bronchoscopy. SETTING: Inpatient and outpatient service at one referral center. PATIENTS: Human immunodeficiency virus-infected patients with pulmonary symptoms were referred for evaluation. Those patients subsequently found to have P carinii pneumonia were studied. INTERVENTION: Bronchoalveolar lavage was performed in the middle lobe (or lingula) and the apical segment of the same lung. MEASUREMENTS AND RESULTS: The aspirated fluids were kept separate and modified Wright-Giemsa-stained cytocentrifuge-prepared slides were made from each area, and the number of P carinii clusters per 500 nucleated cells was counted. Fifty patients were studied: 27 receiving pentamidine prophylaxis and 23 receiving no aerosol therapy. There was no significant difference in the amount of fluid retrieved by lavage from the middle or upper lobe for either group. Both groups had significantly lower numbers of P carinii clusters per 500 cells in the middle lobe (receiving pentamidine: 10 +/- 15.8 [SD]; not receiving pentamidine: 15 +/- 12.3) than in the upper lobe (receiving pentamidine: 22 +/- 19.8; not receiving pentamidine: 24 +/- 21.5; p < 0.02). In six patients, there were no P carinii organisms seen in the middle lobe lavage specimen. CONCLUSION: Pneumocystis carinii has a preference for the upper lobes which may be apparent even in patients not receiving aerosol pentamidine. In addition, yield for P carinii may be increased by performing lavage in the apical segment.

Prevalence of digital clubbing in bronchogenic carcinoma by a new digital index.

OBJECTIVE: Clubbing can be a paraneoplastic manifestation of bronchogenic carcinoma. We assessed a new digital index of clubbing and used it to determine the prevalence of clubbing for different cell types of lung cancer. METHODS: Clubbing was assessed by measurement of the thickness of both the base of the nailbed (distal phalangeal depth--DPD) and the distal interphalangeal depth (IPD) of the index finger in a control group compared to patient groups with either chronic obstructive lung disease, or lung cancer. RESULTS: Of the 55 normal subjects, no patient had a DPD/IPD ratio of more than 1.05 on either hand, while 11% of the patients with COPD had a ratio of more than one. For the cancer patients, 33% had a ratio greater than one, with 30 of 109 (37%) having a ratio > 1.05 (chi(2) = 17.6, p < 0.0001). There was no difference in the prevalence of clubbing between the 33 squamous cell patients, the 43 adenocarcinoma patients, and the 33 small cell lung carcinoma patients included. CONCLUSIONS: Measurement of the interphalangeal and distal phalangeal distance demonstrated that one-third of patients with lung cancer had evidence of clubbing. The type of bronchogenic carcinoma did not appear to affect the proportion of patients with clubbing.

SU-E-T-295: Factors Affecting Accuracy in Proton Therapy.

PURPOSE: To examine the various processes involved and to assess their effects on the accuracy in proton therapy. METHODS: Proton therapy involved several processes: (1) Beam commissioning. (2) CT scan of patient. (3) Contouring. (4) Treatment planning. (5) Output factor measurements for each field. (6) Patient setup verification with image guidance. (7) Dose delivery. (8) Neutron dose and proton RBE at the distal edge. Within each step, there are several sub-processes that each may contribute to the uncertainty in the treatment. By analyzing each of the subprocesseswithin each process, based on measurements or published data, we estimated a % uncertainty to each sub-process and/or a distance uncertainty (in millimeter) on the proton range. A total uncertainty in proton therapy is estimated. RESULTS: The uncertainties assessed for the various processes are : (1) ±1.5%; (4) ±3.0%, and 1-3mm; (5) ±2.0%; (6) ±2 mm; (7) ±2.0%, ±2mm. The uncertainties in (2) CT, (3) contouring and neutron dose in (8) strongly depend on the location and type of the tumor. On the other hand, the proton RBE at the distal edge in (9) is still debatable and may affect the dose uncertainty from 0-20% depending on which value we want to accept. Thus the overall uncertainty in proton therapy is at least ±4.5% and ±4 mm (by adding the various uncertainties in quadrature), without consideration of processes (2), (3) and (8), and the RBE effect. CONCLUSIONS: Due to the complexity in proton therapy and the various factors that may affect the accuracy in proton therapy, it is far more complicated to assess the accuracy in proton therapy. Our preliminary study showed that the accuracy in proton therapy is at least ± 4.5% in dose delivered to a tumor with an uncertainty of ±4mm to the distal edge of the SOBP.

Decreased surfactant protein A in patients with bacterial pneumonia.

Abnormalities have been previously noted in the lipid content of the lavage fluid of patients with bacterial pneumonia. In order to determine if these changes were also seen in surfactant apoproteins, we studied levels of surfactant protein A (SP-A) in patients with bacterial pneumonia. Patients without human immunodeficiency virus who were being evaluated for pulmonary infiltrates underwent bronchoscopy with bronchoalveolar lavage (BAL). Twenty-two patients with pneumonia, 12 caused by gram-positive organisms (Gm+ PNEU) and 10 caused by gram-negative organisms (Gm- PNEU), were compared with 10 patients with idiopathic pulmonary fibrosis (IPF) and 11 control subjects (CON). The percentage of neutrophils in the BAL was significantly higher in the patients with IPF and the pneumonia groups than in the control group (CON: mean, 1; range, 0 to 3. IPF: mean, 26; range, 13 to 42). Gm+ PNEU: mean, 33; range, 8 to 99. Gm- PNEU: mean, 64; range, 10 to 92; p < 0.0001). The amount of SP-A in the BAL fluid was similar for the CON and the IPF groups (CON: mean, 15; range, 5.75 to 26.5 micrograms/ml BAL. IPF: mean, 18.4; range, 6.49 to 45.64 micrograms/ml), whereas both pneumonia groups had significantly less SP-A (Gm- PNEU: mean, 5.54; range, 0.58 to 12.7. G+ PNEU: mean, 1.93; range, 0.47 to 6.74; p < 0.001). There was significantly less SP-A in the Gm+ PNEU group than in the Gm- PNEU group (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Release of tumor necrosis factor by alveolar macrophages of patients with sarcoidosis.

Tumor necrosis factor (TNF) is a monokine released by macrophages and is important in the inflammatory response. We compared the spontaneous release of TNF by alveolar macrophages (AMs) from patients with symptomatic pulmonary sarcoidosis, some of whom were receiving corticosteroid therapy, with AMs from control smokers. TNF was released from AMs of sarcoidosis patients at significantly higher levels than was released by control AM subjects (sarcoids, 15 U/ml [0 to 1140 U (median [range]]); controls, all less than 5 U/ml, p less than 0.01). By using a specific polyclonal antibody, the detected TNF was found to be TNF-alpha. Among the sarcoidosis patients, the amount of TNF released was significantly lower for those patients given treatment with corticosteroids (5 U/ml [0 to 15 U/ml]) compared with untreated persons (50 U/ml [0 to 1140 U/ml], p less than 0.05). In vitro studies demonstrated that incubation of peripheral blood monocytes or AMs with dexamethasone for 42 hours suppressed subsequent release of TNF. We conclude that AMs from sarcoidosis patients often spontaneously release TNF and this release is suppressed by prolonged corticosteroid therapy.

Isolation of functionally active pleural macrophages.

Pleural fluid provides an easily accessible source of tissue macrophages (MACS). We established a method for retrieval and isolation of these cells. Thirty thoracenteses were performed on patients with the clinical diagnosis of congestive heart failure or malignancy. Within 4 hr of thoracentesis, the specimen was placed on a Ficoll-Hypaque gradient, centrifuged, and the mononuclear cells were isolated. Assessment for total cell count, cell viability, and percentage of cells which were MACS as determined by nonspecific esterase staining was recorded. Pleural MACS were separated by glass adherence. In 24 cases, sufficient cells were available to measure the release of hydrogen peroxide spontaneously and with phorbol myristate acetate (PMA) stimulation. Nine of 24 specimens had spontaneous hydrogen peroxide release. In all cases, stimulation of pleural MACS resulted in a significant increase in the amount of hydrogen peroxide released. We report a simple method for retrieving viable and functionally active pleural macrophages.