Abstract
Wide tumour excision is currently the standard approach to surgical treatment of solid cancers including carcinomas of the lower genital tract. This strategy is based on the premise that tumours exhibit isotropic growth potential. We reviewed and analysed local tumour spreading patterns in 518 patients with cancer of the uterine cervix who underwent surgical tumour resection. Based on data obtained from pathological examination of the surgical specimen, we applied computational modelling techniques to simulate local tumour spread in order to identify parameters influencing preferred infiltration patterns and used area-proportional Euler diagrams to detect and confirm ordered patterns of tumour spread. Some anatomical structures, e.g. tissues of the urinary bladder, were significantly more likely to be infiltrated than other structures, e.g. the ureter and the rectum. Computational models assuming isotropic growth could not explain these infiltration patterns. Introducing ontogenetic distance of a tissue relative to the uterine cervix as a parameter led to accurate predictions of the clinically observed infiltration likelihoods. The clinical data indicates that successive infiltration likelihoods of ontogenetically distant tissues are nearly perfect subsets of ontogenetically closer tissues. The prevailing assumption of isotropic tumour extension has significant shortcomings in the case of cervical cancer. Rather, cervical cancer spread seems to follow ontogenetically defined trajectories.
Highlights
Wide tumour excision is currently the standard approach to surgical treatment of solid cancers including carcinomas of the lower genital tract
The surgeon is faced with the following central questions: (I) Which tissues are at risk for both visible or occult tumour infiltration and need to be removed? (II) Which tissues can be safely spared, minimizing treatment-related morbidity? (III) Which locally advanced tumours can still be submitted to surgical treatment? Conventionally, the answer to these questions has been based on two assumptions: First, that local tumour growth is unpredictable and can occur in any direction, and second, that a microscopically invisible tumour front precedes the identifiable tumour margin
These dogmas of local tumour growth are reflected in the surgical treatment strategy of wide excision
Summary
Wide tumour excision is currently the standard approach to surgical treatment of solid cancers including carcinomas of the lower genital tract This strategy is based on the premise that tumours exhibit isotropic growth potential. The goal of surgery should be to minimize loco-regional recurrence rates without increasing operative morbidity unnecessarily To accomplish these objectives, the surgeon is faced with the following central questions: (I) Which tissues are at risk for both visible or occult tumour infiltration and need to be removed? The corresponding null-hypothesis would predict that the observed tumour infiltration patterns could be explained by physical distance alone, which is a function of metric distance and physical tissue type (i.e. adipose tissue or muscle) In this investigation, we use data derived from detailed pathology reports of patients who underwent surgical treatment for cervical cancer at our institution. The assumption of predictable and ordered rather than stochastic tumour growth patterns could form the basis of a roadmap for local tumour growth which might help surgeons or radiotherapists identify tissues at high risk for tumour infiltration
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