G. Storme

Patterns of axillary lymph node metastasis in breast cancer

The pattern of axillary lymph node involvement was analyzed in a review of 377 cases of T1–4 breast cancers. Clinical judgment of the axillary status proved to be wrong in approximately one-third of the cases. In univariate analysis, a strong correlation (P < .01) between the number of involved nodes, tumor size, and blood vessel invasion was found. Other features of the primary tumor (lymphatic invasion, degree of differentiation, presence of necrotic areas) were related to a lesser degree (P < .05). While others (age, site) were not at all significant. However, the number of nodes resected proved to be the most important determinant of all (P = .003). Also, the simple distinction between node-negative and node-positive cases is strongly dependent on the extent of axillary dissection (P = .009). In multivariate analysis, only the number of resected nodes and T stage showed a good relationship with the number of positive nodes. Skip metastases above levels 1 and 2 were seen in only 2% of the cases. A clear influence of the number of invaded nodes on survival could be demonstrated. These findings are discussed, especially as concerns the technique, prognostic significance, and therapeutic usefulness of axillary dissection.

An overview of volumetric imaging technologies and their quality assurance for IGRT

Image-guided radiation therapy (IGRT) aims at frequent imaging in the treatment room during a course of radiotherapy, with decisions made on the basis of this information. The concept is not new, but recent developments and clinical implementations of IGRT drastically improved the quality of radiotherapy and broadened its possibilities as well as its indications. In general IGRT solutions can be classified in planar imaging, volumetric imaging using ionising radiation (kV- and MV- based CT) or non-radiographic techniques. This review will focus on volumetric imaging techniques applying ionising radiation with some comments on Quality Assurance (QA) specific for clinical implementation. By far the most important advantage of volumetric IGRT solutions is the ability to visualize soft tissue prior to treatment and defining the spatial relationship between target and organs at risk. A major challenge is imaging during treatment delivery. As some of these IGRT systems consist of peripheral equipment and others present fully integrated solutions, the QA requirements will differ considerably. It should be noted for instance that some systems correct for mechanical instabilities in the image reconstruction process whereas others aim at optimal mechanical stability, and the coincidence of imaging and treatment isocentre needs special attention. Some of the solutions that will be covered in detail are: (a) A dedicated CT-scanner inside the treatment room. (b) Peripheral systems mounted to the gantry of the treatment machine to acquire cone beam volumetric CT data (CBCT). Both kV-based solutions and MV-based solutions using EPIDs will be covered. (c) Integrated systems designed for both IGRT and treatment delivery. This overview will explain some of the technical features and clinical implementations of these technologies as well as providing an insight in the limitations and QA procedures required for each specific solution.

High-performance liquid chromatographic determination of vinca-alkaloids in plasma and urine.

A liquid chromatographic method is described for separating and determining vinblastine, vincristine and vindesine in plasma and urine. The drugs are extracted from the biological material using an ion-pair extraction, with sodium octylsulphate as counter-ion at pH 3. The extracts are injected on a reversed-phase system with a cyano column as stationary phase and a mobile phase composed of acetonitrile-phosphate buffer, pH 3 (65:35, vol. %). Stability studies are carried out for stock solutions of the drugs in water at different temperatures and pH values. The stability of these compounds in plasma is also investigated in the presence of an antioxidant. The method is applied to determine drug levels of vindesine and vinblastine in preliminary pharmacokinetic studies, using vincristine as the internal standard.

Phase II study of helical tomotherapy for oligometastatic colorectal cancer

BACKGROUND To evaluate the efficacy and toxicity of helical tomotherapy in the treatment of oligometastatic colorectal cancer (CRC) patients who were not amenable for metastasectomy and/or (further) systemic treatment. PATIENTS AND METHODS CRC patients with five or less metastases were enrolled. No limitations concerning dimension or localization of the metastases were imposed. Patients were treated with intensity-modulated and image-guided radiotherapy using helical tomotherapy, delivering a total dose of 40 Gy in fractions of 4 Gy. Positron emission tomography-computed tomography (PET-CT) was carried out at baseline and 3 months after the initiation of radiotherapy to evaluate the metabolic response rate according to PET Response Criteria in Solid Tumors (PERCIST) version 1.0. Side-effects were scored using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTC AE) version 3.0. RESULTS Twenty-three patients were enrolled. A total of 52 metastases were treated. One patient (4%) experienced grade 3 vomiting; two patients (9%) grade 2 diarrhea and dysphagia, respectively. Twenty-two patients were evaluated by post-treatment PET-CT. Five (23%) and seven patients (32%) achieved a complete and partial metabolic response, respectively, resulting in an overall metabolic response rate of 55%. The actuarial 1-year local control, progression-free survival, and overall survival were 54%, 25% and 86%, respectively. CONCLUSION The use of helical tomotherapy in oligometastatic CRC patients resulted in a promising metabolic response rate of 55%.

Prognostic factors in locoregional non - small cell lung cancer treated with radiotherapy

By means of a retrospective study an evaluation was made of prognostic factors on survival in patients with inoperable locoregional non-small cell lung cancer. The study was performed on a group of 239 patients with a median age of 69 years, 225 men, and 14 women. Patients were treated with external radiotherapy without (184) or with (55) chemotherapy. They received either continuous-course radiotherapy (5,500 cGy in 27–28 fractions and 5.5 weeks) or split-course radiotherapy (1 series of 3,000 cGy, 2 series of respectively 3,000 cGy and 2,500 cGy, or 3 series of, respectively 3,000 cGy, 2,500 cGy, and 2,000 cGy; each series in 10 fractions and 2 weeks, separated by a 4-week interval). Univariate analysis was done by life-table analysis and log-rank test, multivariate analysis by the Cox Proportional Hazards model. The overall survival at 1, 2, and 3 years was 36%, 11%, and 4%. Survival was not significantly influenced by localization of the tumor, grading, distance to the carina, growth pattern, diameter, partial or total atelectasis, lymph node invasion or stage. No significant difference in survival was found between patients who received only radiotherapy and those treated with a combination of radiotherapy and chemotherapy. Univariate analysis showed significant better survival in patients with squamous cell epithelioma, patients without pleural effusion, patients younger than 75 years and patients receiving higher radiation doses. Multivariate analysis showed dose of radiation (P < .001) and pleural effusion (P = .03) to be independent prognostic factors.

Determination of vinca alkaloids in mouse tissues by high-performance liquid chromatography

A high-performance liquid chromatographic method is described for the determination of vinblastine in various normal mouse tissues, such as lung, heart, liver, kidney and muscles, and in implanted MO4 tumours. Vincristine was used as the internal standard. Freshly obtained mouse tissue or tumour tissue was frozen at -20 degrees C and then lyophilized. After lyophilisation, the dry tissues were pulverized and homogeneously mixed, and an aliquot was suspended in 0.1 M hydrochloric acid. The drugs of interest were then isolated from this suspension using ion-pair extraction at pH 3 with octylsulphate as counter-ion. The obtained extracts were analysed on a reversed-phase system with a cyanopropyl stationary phase. The detection limit was 1 ng/l in plasma and 10 ng/g in tissue. The extraction recoveries of vincristine and vinblastine were between 45 and 67%, and there were no interferences from blank components. Preliminary pharmacokinetic data for different mouse tissues and tumour implanted in muscle tissue are presented.

Attachment of mouse fibrosarcoma cells to precultured fragments of embryonic chick heart

SummaryTo study the early steps of invasion in vitro, spheroidal aggregates of invasive mouse fibrosarcoma cells (MO4) were confronted with precultured fragments of embryonic chick heart. The confronting tissues attached to one another within 45 min of incubation at 37° C. Photo- and electron microscopy indicate that attachment is brought about by extensions from MO4 cells penetrating between the peripheral fibroblastic cells of the heart fragment. Formation of such extensions appears to be triggered by immediate contact of the MO4 cells with the heart tissue. Attachment did not occur at 4° C, and the rate of attachment at 37° C was lowered by KCN, indicating an active cellular process depending on ATP energy. Cytochalasin B also lowered the rate of attachment, whereas cycloheximide had no significant effect. The latter measurements and the ultrastructure of the extensions suggested that bundling of microfilaments was involved in the attachment. Nocodazole at doses which prevented assembly of cytoplasmic microtubules, like 5-fluorouracil and ionizing radiation at doses which inhibited the growth of the MO4 aggregates but left the cytoplasmic microtubular complex intact, hardly influenced the rate of attachment. These experiments indicated that attachment resulted from random motility, contrary to further steps of invasion which were shown to depend on directional migration.

Relations of image quality in on-line portal images and individual patient parameters for pelvic field radiotherapy

AbstractWe have previously demonstrated that on-line portal imaging (OPI) can detect and correct significant errors in field set-up. Such errors occurred very frequently when irradiating the pelvic region and were typically detected after 10% of the field dose was delivered. The image quality on pelvic fields was, however, disappointing. The aims of the present study involving 566 pelvic fields on 13 patients were: 1.To study the machine- and patient-related factors influencing image quality.2.To study the factors related to machine, patient and patient set-up, influencing the errors of field set-up.3.To develop a method for predicting the camera settings. The OPI device consisted of a fluorescent screen scanned by a video camera. An image quality score on a scale 0–5 was given for 546/566 fields. In a univariate analysis, open field subtraction adversely affected the score (P < 0.001). The image score of anterior fields was significantly better than that of posterior fields (P < 0.001). Multivariate stepwise logistic regression showed that, in addition to anterior or posterior field (P < 0.001) and subtraction (P = 0.003), gender (P = 0.02) was also a significant predictor of image score. Errors requiring field adjustments were detected on 289/530 (54.5%) evaluable fields or 229/278 (82.4%) evaluable patient set-ups. Multivariate logistic regression showed that the probability of performing an adjustment was significantly related to gender (P < 0.001), image quality (P = 0.001) and AP-PA diameter (P = 0.04). The magnitude of adjustments made in the lateral direction correlated significantly (P < 0.0001) with patient bulk. The camera kV level with gain held constant showed an exponential dependency on dose rate at the image detector plate and can thus be predicted by treatment planning.

High-performance liquid chromatographic determination of navelbine in MO4 mouse fibrosarcoma cells and biological fluids

A high-performance liquid chromatographic method is described for separating and determining navelbine and possible metabolites in plasma, cell culture medium and MO4 cells. Navelbine is extracted from these fluids by ion-pair extraction with sodium octylsulphate as the counter-ion at pH 3. The system uses a cyano column as the stationary phase and a mobile phase of acetonitrile-0.12 M phosphate buffer (pH 3) (60:40, v/v). Application of the method to a study of the pharmacokinetic behaviour of navelbine in MO4 mouse fibrosarcoma cells is reported.

NF-κB inhibition impairs the radioresponse of hypoxic EMT-6 tumour cells through downregulation of inducible nitric oxide synthase

Hypoxic EMT-6 tumour cells displayed a high level of inducible nitric oxide synthase (iNOS) and an increased radiosensitivity after a 16 h exposure to lipopolysaccharide, a known activator of nuclear factor-κB (NF-κB). Both iNOS activation and radioresponse were impaired by the NF-κB inhibitors phenylarsine oxide and lactacystin. Contrasting to other studies, our data show that inhibition of NF-κB may impair the radioresponse of tumour cells through downregulation of iNOS.