Major Late Toxicities After Conformal Radiotherapy for Nasopharyngeal Carcinoma—Patient- and Treatment-Related Risk Factors

Lee, Anne W.M.; Ng, Wai Tong; Hung, Wai Man; Choi, Cheuk-Wai; Tung, Raymond; Ling, YH; Cheng, Peter T.C.; Yau, Tsz‐Kok; Chang, Amy; Leung, S.; Lee, Michael C. H.; Bentzen, Søren M.

doi:10.1016/j.ijrobp.2008.05.023

Cited by 94 publications

(87 citation statements)

References 20 publications

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“…In addition to its ability for rapid growth, NPC has a tendency to invade the adjacent regions and metastasize to the regional lymph nodes and distant organs. Despite the sequela of radiation, radiotherapy remains the standard treatment for NPC (2,3). However, only early stage NPC cases are able to obtain effective results, including good prognosis and function.…”

Section: Introductionmentioning

confidence: 99%

HGF stimulates proliferation through the HGF/c-Met pathway in nasopharyngeal carcinoma cells

et al. 2012

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Abstract. Hepatocyte growth factor (HGF) and its receptor c-Met are important in the development and homeostasis of a variety of human malignancies. However, the role of the HGF/c-Met signaling pathway in nasopharyngeal carcinoma (NPC) has not been clearly elucidated. This study examined the effect of HGF/c-Met on proliferation and migration in several NPC cell lines. RT-PCR was used to detect the HGF gene in CNE-1, CNE-2, HK-1, HONE-1 and SUNE-1 NPC cells. However, HGF gene expression was not detected in any of these cells. Using immunoblotting analysis, the Met25 protein was identified in HONE-1, HK-1 and CNE-1 cells. Results from fluorescence-activated cell sorting (FACS) analysis revealed that anti-Met25 mAb specifically bound Met-expressing HONE-1, HK-1 and CNE-1 cells. It was further demonstrated that exogenous HGF was able to stimulate the proliferation of HONE-1 and HK-1 cells and the healing of scrape wounds in HONE-1 NPC cells. Our results reveal the potential therapeutic applications of combination therapy with antibodies targeting HGF in NPC patients. IntroductionNasopharyngeal carcinoma (NPC) is one of the most common types of cancer in South East Asia, and remains a cause of high morbidity in Southern China (1). In addition to its ability for rapid growth, NPC has a tendency to invade the adjacent regions and metastasize to the regional lymph nodes and distant organs. Despite the sequela of radiation, radiotherapy remains the standard treatment for NPC (2,3). However, only early stage NPC cases are able to obtain effective results, including good prognosis and function. The combination of radiotherapy and chemotherapy is crucial in the therapy of locoregional advanced cases of NPC (4). Although over 95% of biopsies belong to the WHO type Ⅱ or Ⅲ classification, which are sensitive to radiotherapy and chemotherapy, there are many treatment-failure cases (5). Thus, there is a requirement for new therapeutic targets and a better understanding of the mechanisms involved in the metastasis of NPC.The Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), are overexpressed and/or activated in a variety of human malignancies. The hepatocyte growth factor/ scatter factor (HGF/SF) and its receptor Met are important in the development, homeostasis, tumorigenesis, angiogenesis, invasion and metastasis of human malignancies (6). However, the mechanisms of the HGF/c-Met signaling pathway that contribute to the invasiveness of malignancies remain unknown. The Met receptor is frequently overexpressed in NPC patients, and high expression is associated with short patient survival (7). The availability of the Met receptor has been shown to modify NPC cell response to HGF. This finding enhanced our understanding of the mechanisms of signaling transduction in the HGF-induced progression of NPC. However, the role of the HGF/c-Met signaling pathway in NPC has not been clearly elucidated. In this study, we detected the effect of HGF/c-Met on proliferation and migration in several NPC cell lines. Our r...

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Section: Introductionmentioning

confidence: 99%

HGF stimulates proliferation through the HGF/c-Met pathway in nasopharyngeal carcinoma cells

et al. 2012

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“…It has previously been reported in retrospective series with incidences ranging from 1% to 9%, the hypoglossal nerve being the most frequently affected (1,10,11,13,(16)(17)(18). This finding illustrates that meticulous evaluation can reveal much higher morbidity rates than generally reported.…”

Section: Discussionmentioning

confidence: 53%

“…This is much higher than in most retrospective studies reporting incidences of 15% to 21% (11)(12)(13). Most frequently observed were severe xerostomia and severe mucosal toxicity including nasopharyngeal crust formation.…”

Section: Discussionmentioning

confidence: 60%

External Beam Radiotherapy With Endocavitary Boost for Nasopharyngeal Cancer: Treatment Results and Late Toxicity After Extended Follow-Up

Schinagl¹,

Marres²,

Kappelle³

et al. 2010

International Journal of Radiation Oncology*Biology*Physics

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“…The outcome or complication of brain necrosis is not well known. The necrosis in brain induced by RT for treatment of nasopharyngeal carcinoma were reported several times [3,4,11]. In addition, the necrotic brains after RT were more frequently encountered at considering whole cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Most cases are related with cancer and got therapeutic RT. Nasopharyngeal carcinoma, usually treated with RT, were reported by several late complications, and infrequently reported for brain necrosis [3][4][5]. Thus, for physiatrists, post-radiation brain necrosis is a cause of burdens for disabilities.…”

Section: Introductionmentioning

confidence: 99%

Pontine Necrosis Related with Radiation Therapy, Complicated with Spontaneous Hemorrhage

et al. 2017

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Highlights• Radiation therapy (RT) is frequently used. for treatment of head and neck cancer.• RT might induce vascular injury, such as telangiectasia and endothelial cell injury.• These vascular injuries may result in spontaneous hemorrhage in necrotic brain.• Physicians should be aware of complication, as brain necrosis with hemorrhage. ABSTRACTThe brain necrosis induced by radiation therapy (RT) is an uncommon pathology of brain. A case of spontaneous hemorrhage at necrotic brain is also rare. A 52-year-old man who had nasopharyngeal carcinoma and had been treated with RT, presented with gait disturbance, dizziness, ataxia, dysarthria, and dysphagia. Magnetic resonance imaging (MRI) demonstrated progressed radiation necrosis of pons, and spontaneous hemorrhage at the site of necrosis. The hematoma was diminished by conservative treatment. However, the patient's neurologic symptoms did not recover. Two years later, spontaneous bleeding recurred at necrotic brain. His neurologic symptoms worsened. One year later, his neurologic symptoms were more progressed. He showed severe dysphagia, profound weakness and respiratory failure. This case provides the description of relapsed spontaneous hemorrhage and medullary dysfunction caused by pontine necrosis and progressed post-radiation injury, complicated with hemorrhage, and urges caution in that the necrotic brain tissue may be vulnerable to bleeding. Keywords: Radiation Necrosis; Radiation Therapy; Pontine Hemorrhage INTRODUCTIONThe brain necrosis is an infrequent late complication related with radiation therapy (RT), and usually induces progressive and irreversible process, and requires medical or surgical treatment [1,2]. Most cases are related with cancer and got therapeutic RT. Nasopharyngeal carcinoma, usually treated with RT, were reported by several late complications, and infrequently reported for brain necrosis [3][4][5]. Thus, for physiatrists, post-radiation brain necrosis is a cause of burdens for disabilities.In this case report, we describe a patient with pontine demyelination and necrosis, who had been treated with RT for nasopharyngeal carcinoma. Spontaneous bleeding occurred after necrosis, twice. The recovery of patient was significantly impaired and showed poor Conflict of InterestThe authors have no potential conflicts of interest to disclose. Ha Min CASE REPORTA 52-year-old man was presented with gait disturbance, dizziness, ataxia, dysarthria, and progressed dysphagia in December 2009. The patient had nasopharyngeal carcinoma, stage IV (T4N2M0) involving sphenoid, infratemporal fossa and skull base and was treated with radiation therapy (RT, total dose of irradiation 85GY) and chemotherapy for 2 years ago. After treatment, his cancer was diminished as clinical remission. Magnetic resonance imaging (MRI) showed contrast enhancing lesion with edema (Fig. 1). The lesion was revealed as postradiation brain injury by magnetic resonance (MR) spectroscopy, for differential diagnosis from metastatic cancer (Fig. 1). And then he got steroid therapy f...

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Major Late Toxicities After Conformal Radiotherapy for Nasopharyngeal Carcinoma—Patient- and Treatment-Related Risk Factors

Cited by 94 publications

References 20 publications

HGF stimulates proliferation through the HGF/c-Met pathway in nasopharyngeal carcinoma cells

HGF stimulates proliferation through the HGF/c-Met pathway in nasopharyngeal carcinoma cells

External Beam Radiotherapy With Endocavitary Boost for Nasopharyngeal Cancer: Treatment Results and Late Toxicity After Extended Follow-Up

Pontine Necrosis Related with Radiation Therapy, Complicated with Spontaneous Hemorrhage

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