Goals of work No blood marker available to date is useful for distinguishing infection-related from neoplasm-related fever. We evaluated the expression of the peripheral blood phagocyte CD11b/CD18 adhesion molecule complex for this purpose. Materials and methods Neutrophil and monocyte CD11b/CD18 expression was assessed in two cohorts of patients with advanced solid cancer ( n = 120) and in healthy controls ( n = 63). The cancer series included 89 patients with verified infection, 23 without infection, and eight with neoplastic fever. CD11b/CD18 expression was measured using flow cytometry, and serum C-reactive protein (CRP) concentration was determined with immunoturbidimetric assay. Results Cancer patients with infection had higher blood neutrophil and monocyte CD11b/CD18 expression levels than patients with neoplastic fever, those with advanced cancer without infection, or healthy controls ( p < 0.01 for all analyses). High CD11b/CD18 values were measured exclusively in individuals diagnosed with infection. Receiver-operating characteristic area under the curve (AUC) for neutrophil and monocyte CD11b/CD18 expression for the discrimination of infection from neoplastic fever was 0.80 (95% CI, 0.70 to 0.88), which was superior ( p = 0.039 and p = 0.049, respectively) to serum CRP on admission (AUC 0.51, 0.40 to 0.62). Conclusions Peripheral blood phagocytic cell CD11b/CD18 expression is useful for making a differential diagnosis between infection and neoplasm-related fever in cancer patients.

This article summarizes the current status of 1H MRS in detecting and quantifying a boron neutron capture therapy (BNCT) boron carrier, L-p-boronophenylalanine-fructose (BPA-F) in vivo in the Finnish BNCT project. The applicability of 1H MRS to detect BPA-F is evaluated and discussed in a typical situation with a blood containing resection cavity within the gross tumour volume (GTV). 1H MRS is not an ideal method to study BPA concentration in GTV with blood in recent resection cavity. For an optimal identification of BPA signals in the in vivo 1H MR spectrum, both pre- and post-infusion 1H MRS should be performed. The post-infusion spectroscopy studies should be scheduled either prior to or, less optimally, immediately after the BNCT. The pre-BNCT MRS is necessary in order to utilise the MRS results in the actual dose planning.

For treatment of superficially located tumors, such as head and neck cancers that invade the skin, the tumor dose may remain low on the skin when such tumors are treated with epithermal neutrons in boron neutron capture therapy (BNCT). The goal of this study was to examine the effects of bolus material for BNCT of superficial tumors, to verify the calculated 55Mn(n,γ) and the 197Au(n,γ) activation reaction rates and the neutron and the gamma doses in a phantom irradiated with a bolus, to measure the neutron activation of the bolus materials after irradiation, and according to depth dose distribution, to estimate when it is advantageous to use a bolus in BNCT. The present data show that both paraffin and water gel can be used as a bolus material for BNCT. However, we recommend paraffin for clinical use, since it is durable and can be easily shaped. A 5mm paraffin bolus increases the surface dose approximately 50%, and its use may be advantageous for treatment of superficial tumors where the planning target volume (PTV) reaches to 6cm or less in tissue depth.

Improvements have been made at the FiR 1 BNCT facility to ease the positioning of the patient with a tumor in the head and neck region into a lateral neutron beam. Shoulder recesses were constructed horizontally on both sides of the beam aperture. When shoulder recesses are not needed, they are filled with neutron attenuating filling blocks. MCNP simulations using an anthropomorphic human model BOMAB phantom showed that the main contribution to the increase in the effective dose to the patient's body due to the shoulder recesses was from the neutron dose of the arm. In a position when one arm is inside the shoulder recess, the maximal effective dose of the patient was estimated to be 0.7Sv/h. Dose measurements using the twin ionization chamber technique showed that the neutron dose increased on the sides as predicted by the MCNP model but there was no noticeable change in the gamma doses. When making the recesses into the lithium containing neutron shield material tritium contamination was confined using an underpressurized glove box and machine tools with local exhaust. The shoulder recesses give space for more flexible patient positioning and can be considered as a significant improvement of the Finnish BNCT facility.

Background and purposeTo investigate the salivary gland function following intensity modulated radiotherapy (IMRT) for head and neck cancer.Patients and methodsSeventeen patients with oropharyngeal (n=11) or nasopharyngeal (n=6) carcinoma located adjacent to the major salivary glands were treated with IMRT with an emphasis to spare the salivary glands from high-dose irradiation and to reduce the risk of postirradiation xerostomy. Three patients had stage 2, 4 stage III, and 10 stage IVA cancer. The total basal and stimulated saliva flow rates were measured before the treatment, and 6 and 12 months after radiotherapy.ResultsThe median basal saliva flow rate measured before radiation treatment was 0.13mL/min, and at 6 and 12 months after the completion of IMRT 0.04mL/min and 0.07mL/min, respectively. The corresponding median stimulated saliva flow rates were 0.49mL/min, 0.33mL/min, and 0.45mL, respectively. The D50 for an impaired stimulated parotid gland saliva flow rate was 25.5Gy. Only two (12%) patients developed grade 3 and none grade 4 xerostomia during a median follow-up of 24 months (range, 12–40 months). No patients had locoregional cancer recurrence following IMRT.ConclusionsThe results suggest that much of the salivary gland function can be maintained with IMRT without jeopadizing the local control rate in the treatment of locally advanced oropharynx or nasopharynx carcinoma.

Breast cancer patients with c-erbB-2-positive tumours seem to benefit from anthracycline-based adjuvant chemotherapy. The predictive value of c-erbB-2 for taxane sensitivity is not yet clear. The purpose of this study was to assess whether c-erbB-2 expression is associated with clinical sensitivity to docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). A total of 283 patients with metastatic breast cancer were initially enrolled in a randomised multicentre trial comparing docetaxel with sequential MF in advanced breast cancer. Paraffin-embedded blocks of the primary tumour were available for 131 patients (46%). c-erbB-2 status was determined by immunohistochemistry using a polyclonal antibody to the c-erbB-2 protein. C-erbB-2 expression was scored in a semi-quantitative fashion using a 0 to 3+ scale. Staining scores 2+ or greater were considered positive. Response evaluation was performed according to World Health Organization (WHO) recommendations. Overall 54 (42%) patients had c-erbB-2-positive tumours. There was no association between treatment outcome and c-erbB-2 overexpression. The overall response rates (RR) (n=128) among c-erbB-2-negative and -positive patients were 35 and 44%, respectively (P=0.359). In the MF arm (n=62), the RR was somewhat higher in the c-erbB-2 overexpressors (33% versus 18%, P=0.18). In the docetaxel arm the RRs were very similar, regardless of the c-erbB-2 expression (53% versus 53%). While several studies have suggested a prognostic and putative predictive significance of c-erbB-2 overexpression in early breast cancer, the significance of c-erbB-2 expression as a predictive factor for response to various cytotoxic treatments in advanced breast cancer is still controversial. In this study, c-erbB-2 expression could not predict response to either MF or T. Thus, tumours over-expressing c-erbB-2 are not uniformly more sensitive to taxanes and c-erbB-2 expression cannot yet be applied clinically as a predictive factor for response in advanced breast cancer.

Rituximab (IDEC-C2B8, Mabthera®, Rituxan®), a chimeric monoclonal antibody against the B-cell specific CD20-antigen, has been demonstrated to be effective in the treatment of non-Hodgkin's B-cell lymphoma (B-NHL). Previous in vitro studies have shown that direct complement-dependent cytotoxicity (CDC), ADCC and apoptosis are important in the rituxi-mab-induced killing of lymphoma cells. It is, however, unknown whether rituximab penetrates the blood-brain barrier. Therefore, we studied rituximab levels and complement (C) activation in blood and cerebrospinal fluid (CSF) following intravenous rituximab therapy in a patient with relapsing non-Hodgkin's lymphoma with central nervous system (CNS) involvement. Longitudinal samples from blood and CSF were taken at 13 time-points during the treatment period. The results show that the C cascade becomes activated in blood during the first mAb infusion (C3a-desArg concentration rose from 55 to 138 μg/ml during the first 2 hours). After the first infusion the proportions of lymphocytes positive for the CD 19- and CD20-antigens in the peripheral blood were reduced from 41% and 35%, respectively, to a level of 2% (for both). In CSF the rituximab concentration increased after successive infusions, but remained below 0.55 μg/ml (compared to a Cmax of 400 μg/ml in peripheral blood). Although a minor and delayed C activation response was seen in the CSF the treatment did not clear CD20-positive cells away from the CNS. Thus, it appears that an intact blood-brain barrier restricts the entry of rituximab into the CNS. Possible options to circumvent this would be dose escalation or intrathecal rituximab treatment.