Variation of vascular density within and between tumors of the uterine cervix and its predictive value for radiotherapy

Révész, Láśzló; Siracká, E; Siracký, J; Delides, G; Pavlaki, K.

doi:10.1016/0360-3016(89)90274-5

Cited by 42 publications

(5 citation statements)

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“…Although numerous other methods have been developed to try and identify hypoxia in human tumors ( 25 , 76 , 77 ), not all have been used to demonstrate the relationship between hypoxia and radiation response. The earliest attempts to do the latter were based on indirect approaches ( 78 ), and involved estimates of tumor vascularization, using such endpoints as intercapillary distance, vascular density and the distance from tumor cells to the nearest blood vessel ( 79 – 81 ). All showed that patients with less well vascularized tumors, and presumably more hypoxic, had a poorer outcome to radiation therapy.…”

Section: Significance Of the Tumor Microenvironment For Cancermentioning

confidence: 99%

Pathophysiological Basis for the Formation of the Tumor Microenvironment

2016

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Poor microenvironmental conditions are a characteristic feature of solid tumors. Such conditions occur because the tumor vascular supply, which develops from the normal host vasculature by the process of angiogenesis, is generally inadequate in meeting the oxygen and nutrient demands of the growing tumor mass. Regions of low oxygenation (hypoxia) is believed to be the most critical deficiency, since it has been well documented to play a significant role in influencing the response to conventional radiation and chemotherapy treatments, as well as influencing malignant progression in terms of aggressive growth and recurrence of the primary tumor and its metastatic spread. As a result, significant emphasis has been placed on finding clinically applicable approaches to identify those tumors that contain hypoxia and realistic methods to target this hypoxia. However, most studies consider hypoxia as a single entity, yet we now know that it is multifactorial. Furthermore, hypoxia is often associated with other microenvironmental parameters, such as elevated interstitial fluid pressure, glycolysis, low pH, and reduced bioenergetic status, and these can also influence the effects of hypoxia. Here, we review the various aspects of hypoxia, but also discuss the role of the other microenvironmental parameters associated with hypoxia.

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Section: Significance Of the Tumor Microenvironment For Cancermentioning

confidence: 99%

Pathophysiological Basis for the Formation of the Tumor Microenvironment

2016

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“…Since tissue oxygenation strongly depends on the efficiency of the vascular network, several methods have been developed that focus on measuring parameters like intercapillary distance (Kolstad, 1968;Awwad et al, 1986), vascular density (Delides et al, 1988;Révész et al, 1989;Hoper and Jahn, 1995;Plasswilm et al, 1999) and the distance from tumor cells to the nearest vessel (Lauk et al, 1989). A way to get a more direct measure of oxygenation is to digitize a microscopic tissue photograph and calculate the corresponding oxygen distribution by solving the diffusion equation for the acquired vascular geometry (Secomb et al, 1993).…”

Section: The Radiation Response Of Hypoxic Cells and Tumorsmentioning

confidence: 99%

Accurate description of heterogeneous tumors for biologically optimized radiation therapy

Nilsson

2005

Medical Physics

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In this thesis, a model of tissue oxygenation is presented, that takes into account the heterogeneous nature of tumor vasculature. Even though the model is rather simple, the resulting oxygen distributions agree very well with clinically observed oxygen distributions for most tumors and healthy normal tissues. The model shows that the vascular density may not describe the oxygenation of a tissue sufficiently well, unless the heterogeneity of the vascular system is taken into account. Based on the oxygen distributions from the tissue model, the associated radiation response at low and high doses can be determined.The radiation response of heterogeneous tumors should preferably be described by two clonogen compartments, one resistant and one sensitive, dominating the response at high and low radiation doses, respectively. Furthermore, each compartment should be characterized by the effective radiation resistance and the effective clonogen number. The resistant-sensitive model of radiation response has been analyzed in great detail. It accurately describes the response of severely heterogeneous tumors, both at low and high doses and LET values. The effective response parameters are given as integrals, averaged over the whole spectrum of radiation resistance. The parameters can also be determined from clinically established dose-response relations.The main properties of the dose-response relation for a generally heterogeneous tumor is described in some detail. The normalized dose-response gradient has been generalized to take heterogeneities in both dose delivery and radiation response into account. This quantity is important for accurate treatment plan optimization using intensity modulated radiation therapy for individual patients.

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“…The endpoints included measurements of intercapillary distance (Kolstad 1968;Awwad et al 1986), vascular density (Delides et al 1988;Révész et al 1989;Streffer et al 1989) and the distance from tumour cells to the nearest blood vessel (Lauk et al 1989). Positive correlations were found between the degree of vascularisation and outcome to radiation therapy in carcinoma of the cervix (Kolstad 1968;Awwad et al 1986), nasopharyngeal tumours (Delides et al 1988) and rectal carcinomas (Streffer et al 1989), consistent with better vascularised tumours being less hypoxic.…”

Section: Vasculature-based Parametersmentioning

confidence: 81%

Clinical Imaging of Hypoxia

et al. 2013

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This is an exciting time in Oncology! The tremendous progress in our understanding of genetic and epigenetic alterations that drive the oncogenic process has provided a number of new opportunities for the development of more effective and less toxic anticancer therapies. More importantly, the emphasis that researchers have placed on the cross-talk between cancer cells and the host is finally paying off, with novel therapeutic strategies boosting the patient's immune system generating transformational results in diseases that were difficult to treat with available therapies. The interaction between cancer cells and immune cells takes place in the context of a tumor microenvironment that is profoundly impacted by many factors. This book emphasizes the role of a universal adaptive mechanism, i.e., adaptation to changes in oxygen levels, as a fundamental biological variable of the tumor microenvironment. The inevitable imbalance between oxygen demand and supply caused by a dysfunctional and inefficient tumor vasculature is a hallmark of human cancers. The unprecedented progress in elucidating the molecular mechanisms underlying tumor hypoxia has fueled enthusiasm and efforts in better understanding the biological implications and exploiting potential therapeutic opportunities. This book attempts to capture this wealth of information in a coherent and comprehensive collection of contributions by world renowned scientists and investigators, involved in basic, translational and clinical research. The goal of this book is to provide a framework to generate novel hypotheses and opportunities that can ultimately be translated to the clinic to benefit cancer patients. Despite the unquestionable progress in the development of novel cancer therapies, achieving cures in metastatic disease remains an elusive and sought-after goal. Only a comprehensive and systematic approach that takes into account all of the components that ultimately embody the "oncogenic paradigm" will allow to overcome this challenging disease.It has been a privilege for me to have an opportunity to work with such a talented group of scientists and investigators and I would like to thank all of them for their outstanding contributions to this book. I also would like to thank all of the patients who participate in clinical trials and contribute to the progress in the development of novel and more effective cancer therapies. Lastly, I would like to thank my family; without them I would have never been able to do what I love.

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Variation of vascular density within and between tumors of the uterine cervix and its predictive value for radiotherapy

Cited by 42 publications

References 5 publications

Pathophysiological Basis for the Formation of the Tumor Microenvironment

Pathophysiological Basis for the Formation of the Tumor Microenvironment

Accurate description of heterogeneous tumors for biologically optimized radiation therapy

Clinical Imaging of Hypoxia

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