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Combined vascular endothelial growth factor-targeted therapy and radiotherapy for rectal cancer: theory and clinical practice.

ABSTRACT: Despite the routine use of adjuvant and neoadjuvant chemoradiotherapy, patients with advanced rectal tumors experience significant rates of treatment failure and disease recurrence. Resistance to radiation is a particular problem. Adding a vascular endothelial growth factor (VEGF)-targeted therapy may improve outcomes in these patients. Epidemiologic studies have shown that tumor expression of VEGF predicts disease recurrence and lower overall survival in patients treated with radiation. In tumor xenograft models in mice, VEGF-targeted agents increase the response to radiation, with a greater probability of tumor control and a greater delay in tumor growth. In addition to killing cancer cells indirectly by damaging tumor blood vessels (antivascular effect), VEGF-targeted therapy may sensitize tumors to radiation through two mechanisms: by normalizing the tumor vasculature, leading to greater tumor oxygenation, and thereby increasing the cytotoxicity of radiation to cancer cells, and by increasing the radiosensitivity of tumor-associated endothelial cells. In addition, anti-VEGF agents may inhibit the regrowth of tumors after radiation by decreasing the number of circulating endothelial cells and endothelial progenitor cells. A phase I dose-escalation study has shown the safety of bevacizumab at a dose of 5 mg/kg in combination with 5-fluorouracil and radiation in patients with rectal carcinoma, and has provided evidence of both vascular normalization and antivascular mechanisms. Phase II evaluation of bevacizumab in this setting is under way.

SUBMITTER: Willett CG

PROVIDER: S-EPMC2686124 | biostudies-other | 2006 Oct

REPOSITORIES: biostudies-other

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Combined vascular endothelial growth factor-targeted therapy and radiotherapy for rectal cancer: theory and clinical practice.

Willett Christopher G CG Kozin Sergey V SV Duda Dan G DG di Tomaso Emmanuelle E Kozak Kevin R KR Boucher Yves Y Jain Rakesh K RK

Seminars in oncology 20061001 5 Suppl 10

Despite the routine use of adjuvant and neoadjuvant chemoradiotherapy, patients with advanced rectal tumors experience significant rates of treatment failure and disease recurrence. Resistance to radiation is a particular problem. Adding a vascular endothelial growth factor (VEGF)-targeted therapy may improve outcomes in these patients. Epidemiologic studies have shown that tumor expression of VEGF predicts disease recurrence and lower overall survival in patients treated with radiation. In tumo ...[more]

PMID: 17145523

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Project description:IntroductionWith the introduction of tyrosine kinase inhibitors and systemic antibodies, including immune checkpoint inhibitors, the survival of advanced-stage cancer patients has improved for many tumor types. These patients are increasingly referred for radiotherapy, but it is unclear whether radiotherapy combined with these drugs is safe. No international guidelines exist on whether or how to combine these drugs with radiotherapy. Therefore, we investigated the current clinical practice in the Netherlands regarding hypofractionated radiotherapy in patients using targeted drugs and immunotherapy.Materials and methodsWe sent a survey to all 21 Dutch radiotherapy institutes. Dedicated radiation oncologists, medical oncologists and pulmonologists were asked to fill out the survey. The questions explored their familiarity with the combination of targeted drugs and immunotherapy with radiotherapy, the encountered clinical difficulties and factors influencing treatment decisions.ResultsThe survey was filled out by 54 respondents from 19 different institutes. The median annual number of patients per radiation oncologist referred for radiotherapy when using targeted drugs or immunotherapy was 10 and 15, respectively. Despite this high number, only 11% of the radiation oncologists stated that they had sufficient information (resources) for adequate treatment decision making. Among all physicians, 44% stated that there was insufficient knowledge within their institute regarding this topic. Only 17% stated that there was a multidisciplinary protocol available. The application of radiotherapy treatment adaptations (technique, dose, fractionation, field size) varied widely. Generally, there seemed to be no consensus regarding the expected toxicity of combined drug-radiotherapy treatments and the expected risk of tumor flare upon temporary drug discontinuation.ConclusionThere is no consensus amongst involved medical specialties on expected toxicity. Consequently, it is necessary to perform clinical studies examining the safety of combined drug-radiotherapy treatments, to add radiotherapy to phase I-III clinical trials for new drugs and to incorporate outcomes into multidisciplinary, evidence-based guidelines.

Project description:BackgroundDespite the rich proximity and vascularization to the pelvic organs, metastatic lesions to the penis are incredibly uncommon. Most primary tumors are genitourinary cancers, and rectal origins are rare. Only 56 cases of metastatic penile tumors have been reported since 1870. Several palliative or curative methods, such as chemotherapy, total penectomy, and radiotherapy, have been applied to treat this condition in previous cases; however, the patient prognosis is poor. Immunotherapy is a beneficial treatment approach for multiple cancers, and recent investigations have shown that it may be beneficial for patients with advanced penile cancer.Case descriptionHerein, we report the case of a 59-year-old Chinese man who had metastatic adenocarcinoma in the penile tissue 3 years after rectal cancer resection. The patient presented with penile pain and dysuria for 6 months when he was 54 years old, and Immunohistochemical staining showed that the origin was the rectum after total penectomy. The patient received surgery, chemotherapy, radiotherapy, targeted therapy and immunotherapy positively and still survived for a further 4 years and 6 months following penectomy despite the late metastasis of rectal cancer. There are two major changes and progress after penectomy, all of which have undergone surgical treatment during continuous treatment and follow-up, the patient completed right inguinal lymphadenectomy when his right regional nodes metastasis was found 23 months after penectomy. While the patient suffered from radiation injury after 47 months after penectomy, which led to radiation necrosis and hip soft tissue infection, and the patient tended to lay prone instead of lying on the back because of the hip pain. The patient ultimately died of multiple organ failure.ConclusionsAll of the previously reported cases of penile metastasis from rectal cancer since 1870 have been reviewed. Yet, the metastatic prognosis remains poor regardless of the treatment options, except for lesions where metastasis is only limited to the penis. We found that the patient may derive more benefit from strategic therapies including surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy.

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Combined vascular endothelial growth factor-targeted therapy and radiotherapy for rectal cancer: theory and clinical practice.

Publications

Combined vascular endothelial growth factor-targeted therapy and radiotherapy for rectal cancer: theory and clinical practice.

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