Jesper Carl

Axillary sampling and the risk of erroneous staging of breast cancer. An analysis of 960 consecutive patients

Axillary nodal status was analysed in 960 consecutive cases of primary invasive breast cancer operated in two Danish hospitals. After stratification according to the number of nodes removed, the rate of node positivity in each subgroup was calculated. We found that the probability of finding at least one metastatic node increased continuously up to about 10 removed nodes. In lymph node negative patients, who did not receive any adjuvant treatment, there was a significant association between the recurrence-free survival and the number of nodes removed, provided that less than 8-10 nodes had been collected. The percentage of node positivity in each subgroup seemed to level off above 10 nodes at about 64%, suggesting that this represents the true rate of node positivity at the time of primary surgery. We conclude that about 10 axillary nodes should be removed in order to minimize the risk of erroneous classification of the axilla.

Assessment of ileal function by abdominal counting of the retention of a gamma emitting bile acid analogue.

In eight patients without gastrointestinal complaints and 30 patients with various gastrointestinal disorders ileal bile acid conservation was assessed by oral administration of 75Se 23-selena-25-homocholic acid (SeHCAT) followed by abdominal gamma counting (SeHCAT-test). The results of the test correlated fairly well with the clinical features and with the [1-14C]-cholylglycine breath test including faecal 14C measurements (breath test). Of the two bile acid absorption tests the new is perhaps the more sensitive and is the one most easily performed.

Skin damage probabilities using fixation materials in high-energy photon beams

INTRODUCTION Patient fixation, such as thermoplastic masks, carbon-fibre support plates and polystyrene bead vacuum cradles, is used to reproduce patient positioning in radiotherapy. Consequently low-density materials may be introduced in high-energy photon beams. The aim of the this study was to measure the increase in skin dose when low-density materials are present and calculate the radiobiological consequences in terms of probabilities of early and late skin damage. METHOD An experimental thin-windowed plane-parallel ion chamber was used. Skin doses were measured using various overlaying low-density fixation materials. A fixed geometry of a 10x10 cm field, a SSD=100 cm and photon energies of 4, 6 and 10 MV on Varian Clinac 2100C accelerators were used for all measurements. Radiobiological consequences of introducing these materials into the high-energy photon beams were evaluated in terms of early and late damage of the skin based on the measured surface doses and the LQ-model. RESULTS The experimental ion chamber gave results consistent with other studies. A relationship between skin dose and material thickness in mg/cm(2) was established and used to calculate skin doses in scenarios assuming radiotherapy treatment with opposed fields. CONCLUSION Conventional radiotherapy may apply mid-point doses up to 60-66 Gy in daily 2-Gy fractions opposed fields. Using thermoplastic fixation and high-energy photons as low as 4 MV do increase the dose to the skin considerably. However, using thermoplastic materials with thickness less than 100 mg/cm(2) skin doses are comparable with those produced by variation in source to skin distance, field size or blocking trays within clinical treatment set-ups. The use of polystyrene cradles and carbon-fibre materials with thickness less than 100 mg/cm(2) should be avoided at 4 MV at doses above 54-60 Gy.

Prognostic factors of local control after radiotherapy in T1 glottic and supraglottic carcinoma of the larynx

This study presents a retrospective analysis of a consecutive series of 161 patients treated with curatively intended radiotherapy for T1 supraglottic or glottic carcinoma from 1972 to 1990 at the Department of Oncology, Aalborg County Hospital, Denmark. All patients received radiotherapy given with 4-MV X-rays on lateral opposed fields. Intended dose was 60 Gy in 30 fractions. Multivariate analysis of recorded clinical parameters was applied to identify possible prognostic factors of local control. Tumor size, differentiation grade and sex were identified as significant independent prognostic parameters of local control. Five-year local control was 58% and 78% for supraglottic and glottic tumors, respectively. Applying salvage surgery the ultimate control rates were 82% and 97% for supraglottic and glottic tumors, respectively. Evaluation of treatment response 3-6 weeks following accomplishment of radiotherapy demonstrated that remaining tumor at the time of evaluation was an indicator of failure in local control.

MRI target delineation may reduce long-term toxicity after prostate radiotherapy

Abstract Background and purpose. Aiming for minimal toxicity after radical prostate cancer (PC) radiotherapy (RT), magnetic resonance imaging (MRI) target delineation could be a possible benefit knowing that clinical target volumes (CTV) are up to 30% smaller, when CTV delineation on MRI is compared to standard computed tomography (CT). This study compares long-term toxicity using CT or MRI delineation before PC RT. Material and methods. Urinary and rectal toxicity assessments 36 months after image-guided RT (78 Gy) using CTC-AE scores in two groups of PC patients. Peak symptom score values were registered. One group of patients (n = 72) had standard CT target delineation and gold markers as fiducials. Another group of patients (n = 73) had MRI target delineation and a nickel-titanium stent as fiducial. Results. At 36 months no difference in overall survival (92% in both groups, p = 0.29) or in PSA-relapse free survival was found between the groups (MRI = 89% and CT = 94%, p = 0.67). A significantly smaller CTV was found in the MRI group (p = 0.02). Urinary retention and frequency were significantly reduced in the MRI group (p = 0.03 in the matter of both). The overall urinary and rectal toxicity did not differ between the two groups. Conclusion. MRI delineation leads to a significantly reduced CTV. Significantly lower urinary frequency and urinary retention toxicity scores were observed following MRI delineation. The study did not find significant differences in overall urinary or rectal toxicity between the two groups. PSA-relapse survival did not differ between the two groups at 36 months.

FAMILIAL HYPOCALCIURIC HYPERCALCAEMIA II. INTESTINAL CALCIUM ABSORPTION AND VITAMIN D METABOLISM

We compared intestinal calcium absorption, measured by a single isotope technique, and serum concentrations of vitamin D metabolites in ten patients with familial hypocalciuric hypercalcaemia (FHH) and ten age‐ and sex‐matched healthy controls. Our results showed no significant differences in intestinal calcium absorption or in serum concentrations of vitamin D metabolites. There was a significant correlation between serum concentrations of PTH, measured with one of our assays, and 1,25(OH)2D. We conclude that neither increased intestinal calcium absorption nor altered vitamin D metabolism plays a part in the hypercalcaemia of FHH.

A consecutive series of patients with laryngeal carcinoma treated by primary irradiation

In Denmark there is an increasing frequency of laryngeal carcinoma, in particular in women and among these especially in supraglottic tumours. The incidence during the past 20 years has risen from about 40 to 60 cases per million per year. A series of 335 consecutive patients treated with primary radiation is presented. In one-third of all patients the tumour was localized in the supraglottic area; in women in more than half and in men in about one-fourth of the cases. The frequency of primary lymph node metastases in the supraglottic and the glottic tumours was 24% and 2% respectively. A multivariate analysis identified sex and tumour size as independent prognostic parameters of local control. Five-year survival corrected for intercurrent deaths was obtained in 59% of all cases, in 56% of supraglottic and in 92% of glottic tumours. A multivariate analysis defined localization, tumour grade and stage as independent prognostic parameters of survival. Salvage surgery was performed in about 32% of the cases, total laryngectomy in 26%, and partial laryngectomy in 6%. The survival rate among all total laryngectomies was 55%. A tracheostomy during or before radiation treatment prior to total laryngectomy had no influence on complication rate, admission time or recurrence rate. The frequency of pharyngo-cutaneous fistulae in the entire series was 11.5%; after routine use of metronidazol, however, only 5.7%. Radical neck dissection was carried out in 7.8% of the cases, by far most in the supraglottic group, only a few in the glottic carcinomas, in three-fourth in connection with a laryngectomy and in one-fourth without local recurrence in the larynx.

Differences in supratentorial white matter diffusion after radiotherapy - new biomarker of normal brain tissue damage?

Abstract Introduction. Therapy-induced injury to normal brain tissue is a concern in the treatment of all types of brain tumours. The purpose of this study was to investigate if magnetic resonance diffusion tensor imaging (DTI) could serve as a potential biomarker for the assessment of radiation-induced long-term white matter injury. Material and methods. DTI- and T1-weighted images of the brain were obtained in 19 former radiotherapy patients [nine men and 10 women diagnosed with astrocytoma (4), pituitary adenoma (6), meningioma (8) and craniopharyngioma (1), average age 57.8 (range 35–71) years]. Average time from radiotherapy to DTI scan was 4.6 (range 2.0–7.1) years. NordicICE software (NIC) was used to calculate apparent diffusion coefficient maps (ADC-maps). The co-registration between T1 images and ADC-maps were done using the auto function in NIC. The co-registration between the T1 images and the patient dose plans were done using the auto function in the treatment planning system Eclipse from Varian. Regions of interest were drawn on the T1-weighted images in NIC based on isocurves from Eclipse. Data was analysed by t-test. Estimates are given with 95% CI. Results. A mean ADC difference of 4.6(0.3;8.9)× 10−5 mm2/s, p = 0.03 was found between paired white matter structures with a mean dose difference of 31.4 Gy. Comparing the ADC-values of the areas with highest dose from the paired data (dose > 33 Gy) with normal white matter (dose < 5 Gy) resulted in a mean dose difference of 44.1 Gy and a mean ADC difference of 7.87(3.15;12.60)× 10−5 mm2/s, p = 0.003. Following results were obtained when looking at differences between white matter mean ADC in average dose levels from 5 to 55 Gy in steps of 10 Gy with normal white matter mean ADC: 5 Gy; 1.91(−1.76;5.58)× 10−5 mm2/s, p = 0.29; 15 Gy; 5.81(1.53;10.11)× 10−5 mm2/s, p = 0.01; 25 Gy; 5.80(2.43;9.18)× 10−5 mm2/s, p = 0.002; 35 Gy; 5.93(2.89;8.97)× 10−5 mm2/s, p = 0.0007; 45 Gy; 4.32(−0.24;8.89)× 10−5 mm2/s, p = 0.06; 55 Gy; −4.04(−14.96;6.89)× 10−5 mm2/s, p = 0.39. Conclusion. The results indicate that the structural integrity of white matter, assessed by ADC-values based on DTI, undergoes changes after radiation therapy starting as early as total dose levels between 5 and 15 Gy.

Modelling of serial carcinoembryonic antigen changes in colorectal cancer

Carcinoembryonic antigen (CEA) is a tumour marker mainly used for detection of recurrent colorectal cancer. CEA series in 295 patients, who had a macroscopic radical resection of a primary colorectal cancer were studied. A kinetic model was fitted to CEA series of individual patients. Applying the kinetic model recurrences were identified with a sensitivity of 70-80% and specificity of 80-90%. Simulations were performed in order to find the optimal sampling strategy for CEA during follow-up. Simulations showed that CEA determinations at a few weeks interval between would be optimal for early detection of recurrences.

MEGAVOLTAGE IMAGE-BASED DYNAMIC MULTILEAF COLLIMATOR TRACKING OF A NITI STENT IN PORCINE LUNGS ON A LINEAR ACCELERATOR

PURPOSE To investigate the accuracy and potential limitations of MV image-based dynamic multileaf collimator (DMLC) tracking in a porcine model on a linear accelerator. METHODS AND MATERIALS A thermo-expandable NiTi stent designed for kilovoltage (kV) X-ray visualization of lung lesions was inserted into the bronchia of three anaesthetized Göttingen minipigs. A four-dimensional computed tomography scan was used for planning a five-field conformal treatment with circular multileaf collimator (MLC) apertures. A 22.5 Gy single fraction treatment was delivered to the pigs. The peak-to-peak stent motion was 3 to 8 mm, with breathing periods of 1.2 to 4 s. Before treatment, X-ray images were used for image-guided setup based on the stent. During treatment delivery, continuous megavoltage (MV) portal images were acquired at 7.5 Hz. The stent was segmented in the images and used for continuous adaptation of the MLC aperture. Offline, the tracking error in beams eye view of the treatment beam was calculated for each MV image as the difference between the MLC aperture center and the segmented stent position. The standard deviations of the systematic error Σ and the random error σ were determined and compared with the would-be errors for a nontracking treatment with pretreatment image-guided setup. RESULTS Reliable stent segmentation was obtained for 11 of 15 fields. Segmentation failures occurred when image contrast was dominated by overlapping anatomical structures (ribs, diaphragm) rather than by the stent, which was designed for kV rather than MV X-ray visibility. For the 11 fields with reliable segmentation, Σ was 0.5 mm/0.4 mm in the two imager directions, whereas σ was 0.5 mm/1.1 mm. Without tracking, Σ and σ would have been 1.7 mm/1.4 mm and 0.8 mm/1.4 mm, respectively. CONCLUSION For the first time, in vivo DMLC tracking has been demonstrated on a linear accelerator showing the potential for improved targeting accuracy. The study mimicked the envisioned patient workflow of future patient treatments. Clinical implementation of MV image-based tracking would require markers designed for MV visibility.