Re-Treatment After Full-Course Radiotherapy: Is It a Viable Option?

Stewart, Fiona

doi:10.1080/028418699432545

Cited by 56 publications

(42 citation statements)

References 49 publications

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“…Primary tumors recurring after unsuccessful radiation therapy commonly show aggressive growth, have exceptionally poor oxygen supply, are resistant to treatment, and may have elevated metastatic propensity (3)(4)(5). The treatment of patients with postirradiation local recurrences, therefore, represents a difficult and challenging problem (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

The Tumor Bed Effect: Increased Metastatic Dissemination from Hypoxia-Induced Up-regulation of Metastasis-Promoting Gene Products

et al. 2005

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Cancer patients with recurrent local disease after radiation therapy have increased probability of developing regional and distant metastases. The mechanisms behind this observation were studied in the present work by using D-12 and R-18 human melanoma xenografts growing in preirradiated beds in BALB/c-nu/nu mice as preclinical models of recurrent primary tumors in humans. D-12 tumors metastasize to the lungs, whereas R-18 tumors develop lymph node metastases. Based on earlier studies, we hypothesized that metastasis was governed primarily by the proangiogenic factor interleukin-8 (IL-8) in D-12 tumors and by the invasive growth-promoting receptor urokinase-type plasminogen activator receptor (uPAR) in R-18 tumors. Pimonidazole was used as a hypoxia marker, and hypoxia, microvascular hotspots, and the expression of IL-8 and uPAR were studied by immunohistochemistry. The metastatic frequency was significantly higher in tumors in preirradiated beds than in control tumors in unirradiated beds, and it increased with the preirradiation dose. D-12 tumors showed increased fraction of hypoxic cells, increased fraction of IL-8-positive cells, and increased density of microvascular hotspots in preirradiated beds, and R-18 tumors showed increased fraction of hypoxic cells and increased fraction of uPAR-positive cells in preirradiated beds. Strong correlations were found between these parameters and metastatic frequency. IL-8 was up-regulated in hypoxic regions of D-12 tumors, and uPAR was up-regulated in hypoxic regions of R-18 tumors. Daily treatment with anti-IL-8 antibody (D-12) or anti-uPAR antibody (R-18) suppressed metastasis significantly. Our preclinical study suggests that primary tumors recurring after inadequate radiation therapy may show increased metastatic propensity because of increased fraction of hypoxic cells and hypoxia-induced up-regulation of metastasis-promoting gene products. Two possible mechanisms were identified: hypoxia may enhance metastasis by inducing neoangiogenesis facilitating hematogenous spread and by promoting invasive growth facilitating lymphogenous spread. The aggressive behavior of postirradiation local recurrences suggests that they should be subjected to curative treatment as early as possible to prevent further metastatic dissemination. Moreover, the possibility that patients with a high probability of developing local recurrences after radiation therapy may benefit from postirradiation treatment with antiangiogenic and/or anti-invasive agents merits clinical investigation. (Cancer Res 2005; 65(6): 2387-96)

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Section: Introductionmentioning

confidence: 99%

The Tumor Bed Effect: Increased Metastatic Dissemination from Hypoxia-Induced Up-regulation of Metastasis-Promoting Gene Products

et al. 2005

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“…In the majority, surgical salvage is either not feasible or carries a high risk of complications (Watson and Ridge, 1998). Similarly, further radiotherapy is often impossible as surrounding tissues will already have received the maximum tolerable dose of ionising radiation (De Crevoisier et al, 1998;Stewart, 1999). Only a very small portion of these patients are long-term survivors.…”

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confidence: 99%

Interstitial photodynamic therapy as salvage treatment for recurrent head and neck cancer

et al. 2004

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Interstitial photodynamic therapy (IPDT) is a technique for applying photodynamic therapy (PDT) to internal tumours using light delivered via fibres inserted percutaneously. This phase I -II study assessed the safety and efficacy of IPDT for patients with persistent or recurrent head and neck cancer unsuitable for further treatment with surgery, radiotherapy or chemotherapy, recruited for 'last hope' salvage treatment. Patients were sensitised with 0.15 mg kg À1 mTHPC (meso-tetrahydroxyphenyl chlorin) 4 days prior to light delivery from fibres inserted directly into the target tumour (20 J per site at 652 nm) under image guidance. In all, 45 patients were treated. Nine achieved a complete response. Five are alive and free of disease 10 -60 months later. Symptomatic relief (mainly for bleeding, pain or tumour debulking) was achieved in a further 24. The median survival (Kaplan -Meier) was 16 months for the 33 responders, but only 2 months for the 12 nonresponders. The only serious complication was a carotid blow out 2 weeks after PDT. No loss of function was detected in nerves encased by treated tumours. Interstitial photodynamic therapy provides worthwhile palliation with few complications and occasional long-term survivors for otherwise untreatable advanced head and neck cancers. It is a treatment option worth adding to those available to integrated head and neck oncology teams.

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“…34,35 She studied the link between functional damage and vascular mediated inflammatory and thrombotic changes. 36 One of her big interests is photodynamic therapy in oncology.…”

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confidence: 99%

The contribution of women to radiobiology: Marie Curie and beyond

Gasińska

2016

Reports of Practical Oncology & Radiotherapy

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Radiobiology Ionizing radiationTumor radiobiology a b s t r a c t Marie Sklodowska-Curie, an extraordinary woman, a Polish scientist who lived and worked in France, led to the development of nuclear energy and the treatment of cancer. She was the laureate of two Nobel Prizes, the first woman in Europe who obtained the degree of Doctor of Science and opened the way for women to enter fields which had been previously reserved for men only. As a result of her determination and her love of freedom, she has become an icon for many female scientists active in radiation sciences. In 1911, Marie Sklodowska-Curie was awarded her second Nobel Prize for the discovery of radium. Her pioneering work demonstrated that radiation is a powerful tool with a wide range of potential applications, which include a range of diagnostic and therapeutic medical procedures. Marie Curie has left a great deal to the world. Her work led to the development http://dx

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Re-Treatment After Full-Course Radiotherapy: Is It a Viable Option?

Cited by 56 publications

References 49 publications

The Tumor Bed Effect: Increased Metastatic Dissemination from Hypoxia-Induced Up-regulation of Metastasis-Promoting Gene Products

The Tumor Bed Effect: Increased Metastatic Dissemination from Hypoxia-Induced Up-regulation of Metastasis-Promoting Gene Products

Interstitial photodynamic therapy as salvage treatment for recurrent head and neck cancer

The contribution of women to radiobiology: Marie Curie and beyond

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