Laurence Goethals

Respiration-induced movement of the upper abdominal organs: a pitfall for the three-dimensional conformal radiation treatment of pancreatic cancer.

Respiration-induced movement of the upper abdominal organs (pancreas, liver and kidneys) was assessed in 12 subjects using dynamic magnetic resonance imaging. The movement of each organ in the cranio-caudal, the lateral and the anterior-posterior direction was deduced from the movement of the center of gravity on two-dimensional images. This center of gravity was computed from the volume delineated on sequential 8-mm slices of both sagittal and coronal dynamic series. The largest movements were noticed in the cranio-caudal direction for pancreas and liver (23.7+/-15.9 mm and 24.4+/-16.4 mm). The kidneys showed smaller movements in the cranio-caudal direction (left kidney 16.9+/-6.7 mm and right kidney 16.1+/-7.9 mm). The movements of the different organs in the anterior-posterior and lateral directions were less pronounced. It is of the greatest importance to be aware of these movements in the planning of a conformal radiation treatment for pancreatic cancer.

A new approach to the validation of tissue microarrays

Although tissue microarrays (TMA) have been widely used for a number of years, it is still not clear how many core biopsies should be taken to determine a reliable value for percentage positivity or how much heterogeneity in marker expression influences this number. The first aim of this study was to validate the human visual semi‐quantitative scoring system for positive staining of tumour tissue with the exact values determined from computer‐generated images. The second aim was to determine the minimum number of core biopsies needed to estimate percentage positivity reliably when the immunohistochemical staining pattern is heterogeneous and scored in a non‐binary way. Tissue sections from ten colorectal cancer specimens were stained for carbonic anhydrase IX (CA IX). The staining patterns were digitized and 400 artificial computer‐generated images were generated to test the accuracy of the human scoring system. To determine the minimal number of core biopsies needed to account for tumour heterogeneity, 50 (artificial) core biopsies per section were taken from the tumoural region of the ten digitally recorded full tissue sections. Based on the semi‐quantitative scores from the 50 core biopsies per section, 2500 × n (n = 1–10 core biopsies) experimental core biopsies were then generated and scores recorded. After comparison with field‐by‐field analysis from the tumoural region of the whole tissue section, the number of core biopsies that need to be taken to minimize the influence of heterogeneity could be determined. In conclusion, visual scoring accurately estimated the percentage positivity and the percentage tumour present in a section, as judged by comparison with the artificial images. The exact number of core biopsies that has to be examined to determine tumour marker positivity using TMAs is affected by the degree of heterogeneity in the expression pattern of the protein, but for most purposes at least four is recommended. Copyright

Molecular and clinico-pathological markers in rectal cancer: a tissue micro-array study.

AimsThe aims of the study were to study the effect of pre-operative treatment on the expression of tumour-related proteins and to correlate the expression of these proteins with response and survival of patients with advanced rectal cancer.Materials and methodsTissue micro-arrays from pre- and post-treatment biopsies of 99 patients with rectal cancer treated with pre-operative (chemo)radiotherapy were stained for epidermal growth factor receptor (EGFR), carbonic anhydrase IX, Ki67, vascular endothelial growth factor, cyclo-oxygenase 2 (COX-2) and cleaved cytokeratin 18 (c-CK18). Also, fibro-inflammatory alterations after treatment were evaluated.ResultsPre-operative (chemo)radiotherapy caused fibro-inflammatory changes, a downregulation of proliferation (Ki67) and EGFR and an upregulation of apoptosis (cleaved CK18). Patients with a good regression during pre-operative treatment showed less proliferating and apoptotic cells in the resection specimen. Multivariate analysis showed that T downstaging, fibro-inflammatory changes in the resection specimen and COX-2 expression in the biopsy correlated with overall survival.ConclusionsPre-operative treatment has an effect on proliferation, apoptosis, inflammation and EGFR expression. The classical clinical parameters as well as fibro-inflammatory changes and COX-2 expression seem most valuable as predictors for survival.

Morphological features and molecular markers in rectal cancer from 95 patients included in the European Organisation for Research and Treatment of Cancer 22921 trial: prognostic value and effects of preoperative radio (chemo) therapy.

In this study, the prognostic and/or predictive value of different proteins (cyclo-oxygenase 2 (COX-2), Ki67 and cleaved cytokeratin (CK) 18) and fibro-inflammatory changes which might be of importance for the response to treatment were evaluated using tissue micro arrays. Samples were obtained from a subset of 95 patients included in the European Organisation for Research and Treatment of Cancer 22921 clinical trial, which randomised patients with rectal cancer to one of four arms treated with preoperative radiotherapy with or without pre- and/or postoperative chemotherapy. From our results, we can conclude that the addition of preoperative chemotherapy to radiotherapy led to significantly less COX-2 upregulation, less proliferation and more inflammation, as was seen in the resection specimen as well as less invasion and metastasis. For COX-2, Ki67 or cleaved CK18, no predictive or prognostic value could be identified. However, the fibro-inflammatory reaction after preoperative radiochemotherapy correlated with T-downstaging and seems to be an important factor for response.

Case report of cold-weather-induced radiation recall dermatitis after chemoradiotherapy with cisplatin

BackgroundThe radiation recall reaction (RRR) is an inflammatory reaction that occurs in previously irradiated areas. The phenomenon is probably due to an idiosyncratic hypersensitivity reaction, in which a second agent can recall the inflammatory reaction.Case reportThis case report documents a cold-weather-induced radiation recall dermatitis (RRD). We observed a severe RRD in a patient after chemoradiotherapy treatment with cisplatin for a nasopharyngeal carcinoma, precipitated by cold temperatures, which developed 9xa0days after completion of therapy. In the medical literature, RRD following extreme cold temperatures seems to be a peculiar event.ConclusionUntil further information on the interaction is available, future studies on combined chemotherapy with cisplatin should be carefully monitored and any side effects clearly documented. This case suggests that environmental conditions may play a contributing role in the development of RRD. This case also implies that neither fraction size nor total radiation dose is a determining factor in the development of the dermatologic reaction.ZusammenfassungHintergrundDie „Radiation-Recall-Reaktion“ (RRR) ist eine Entzündungsreaktion, die in zuvor bestrahlten Bereichen auftritt. Das Phänomen wird wahrscheinlich durch eine spezifische Überempfindlichkeitsreaktion verursacht, bei der ein zweites Agens die Entzündungsreaktion hervorruft.FallberichtDieser Fallbericht beschreibt eine kaltwetterinduzierte RR-Hautentzündung. Wir beobachteten bei dem Patienten nach einer Radiochemotherapie mit Cisplatin aufgrund eines Nasopharynxkarzinoms eine heftige RR-Dermatitis (RRD) aufgrund kalter Temperaturen, die sich 9xa0Tage nach Therapiebeendigung entwickelte. In der medizinischen Literatur scheint eine RRD infolge extrem kalter Temperaturen ein besonderes Ereignis.SchlussfolgerungBis weitere Informationen zu der Interaktion verfügbar sind, sollten zukünftige Studien zur Kombinationstherapie mit Cisplatin sorgfältig überwacht und Nebenwirkungen eindeutig dokumentiert werden. Dieser Fall deutet darauf hin, dass Umgebungsbedingungen zur Entwicklung der RRD beitragen können. Dieser Fall impliziert auch, dass weder Fraktionsgröße, noch Strahlendosis bestimmende Faktoren bei der Entwicklung der dermatologischen Reaktion sind.