Locoregional radiotherapy in patients with distant metastases of nasopharyngeal carcinoma at diagnosis

Chen, Ming Yuan; Jiang, Rou; Guo, Ling; Zou, Xiong; Liu, Qing; Sun, Rui; Qiu, Fang; Xia, Zhong Jun; Huang, Hui Qiang; Zhang, Li; Hong, Ming; Qiang, Hai; Qian, Chao Nan

doi:10.5732/cjc.013.10148

Cited by 111 publications

(112 citation statements)

References 30 publications

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“…However, it is noteworthy that no patient achieved complete remission of the primary tumor after systemic chemotherapy, which underlines the limitation of chemotherapy in eradicating the primary bulky disease. Furthermore, consistent with several previous reports [9,11], increasing the number of cycles of chemotherapy did not seem to improve patients' survival in our cohort. No significant survival benefit was observed for the patients receiving at least four cycles of chemotherapy versus those receiving \4 cycles, raising the possibility of acquired chemoresistance with the increase of chemotherapy cycles.…”

Section: Discussionsupporting

confidence: 93%

“…Investigators of another retrospective review of 234 patients reported that locoregional radiotherapy significantly extended patients' overall survival when combined with chemotherapy versus chemotherapy alone (3yOS 48.3 vs. 12.4 %, P = 0.001), and the survival benefit was particularly prominent for patients who achieved CR or PR of metastatic lesions after systemic chemotherapy [10]. Similar results were also obtained in a third study which retrospectively evaluated the impact of different treatment strategies on patients' survival [11]. Statistical analysis showed that patients' mortality risk in the group undergoing systemic chemotherapy alone was 130 % higher than that of the group undergoing both systemic chemotherapy and locoregional radiotherapy (P \ 0.001).…”

Section: Discussionsupporting

confidence: 57%

“…Recently, several retrospective studies demonstrated a survival benefit with the addition of locoregional definitive radiotherapy to systemic chemotherapy in patients with initially metastatic NPC [9][10][11]. However, in these studies, there were different combinations with respect to the timing of chemotherapy in relation to radiotherapy (i.e., induction, concurrent, adjuvant or other combination), which may have differential impact on treatment outcome.…”

Section: Introductionmentioning

confidence: 95%

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Systemic chemotherapy followed by locoregional definitive intensity-modulated radiation therapy yields prolonged survival in nasopharyngeal carcinoma patients with distant metastasis at initial diagnosis

Dong

et al. 2015

Med Oncol

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Chemotherapy is the current mainstay of treatment for patients with newly diagnosed metastatic nasopharyngeal carcinoma (NPC), whereas the role of locoregional radiotherapy remains to be defined. In this study, we retrospectively evaluated the outcome of systemic chemotherapy followed by locoregional definitive intensity-modulated radiation therapy (IMRT) as first-line treatment for these patients. Forty-one patients with pathologically confirmed NPC with distant metastasis at initial diagnosis seen between March 2005 and February 2014 were included. All the patients were treated with platinum-based systemic chemotherapy followed by definitive IMRT to the primary head and neck region with or without concurrent chemotherapy. In addition, local treatment to metastatic lesions was given in 19 patients. With a median follow-up time of 25 months, 24 patients had died, and the estimated median overall survival time was 31.2 months. The 1-, 2-, 3- and 5-year estimated OS rates were 89.9, 67.4, 41.1 and 22.5%, respectively. Prognostic analyses showed that serum lactate dehydrogenase level (P = 0.021) and number of metastatic sites (single vs. multiple; P = 0.016) were significant prognostic factors. Five patients are still alive without evidence of disease after 52 to >101 months. All of them had a single metastatic lesion and received local treatment to metastatic sites. These results suggest that the use of definitive IMRT to treat the locoregional tumor in combination with systemic chemotherapy may prolong survival in patients with newly diagnosed metastatic NPC, making curability a possible consideration in selected patients with single metastasis. Further prospective clinical trials are warranted.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 95%

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Systemic chemotherapy followed by locoregional definitive intensity-modulated radiation therapy yields prolonged survival in nasopharyngeal carcinoma patients with distant metastasis at initial diagnosis

Dong

et al. 2015

Med Oncol

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“…1 NPC has the highest rate of metastasis among head and neck cancers, and distant metastasis is the main cause of treatment failure. 2 NPC is consistently correlated with EBV infection; the expression of neo-viral antigens in tumor cells induces numerous immune cells, referred to as tumor-infiltrating leukocytes, which are attracted to tumor tissues. 3,4 Most studies of the mechanisms of cancer-related inflammation have focused on cancer initiation; in fact, inflammatory mediators and cells are also involved in the migration, invasion and metastasis of malignant cells.…”

Section: Cox-2 Promotes Metastasis In Nasopharyngeal Carcinoma By Medmentioning

confidence: 99%

COX-2 promotes metastasis in nasopharyngeal carcinoma by mediating interactions between cancer cells and myeloid-derived suppressor cells

OuYang

et al. 2015

OncoImmunology

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Keywords: COX-2, myeloid-derived suppressor cells, nasopharyngeal carcinomaAbbreviations: ARG-1, arginase 1; COX-2, cyclooxygenase-2; DFS, disease-free survival; EMT, epithelial-mesenchymal transition; GM-CSF, granulocyte-monocyte-colony stimulating factor; iNOS, inducible nitric oxide synthase; LNMMA, L-NG-monomethylarginine; MDSCs, myeloid-derived suppressor cells; NAC, N-acetylcysteine; NOHA, N-hydroxy-nor-L-arginine; NOX2, NADPH oxidase; NPC, nasopharyngeal carcinoma; ROS, reactive oxygen species; siRNA, small interfering RNA; TCF4, T-cell factor 4; TGF, transforming growth factor b; T-MDSCs, tumor-induced MDSCs; VEGF, vascular endothelial growth factorThe expansion of myeloid-derived suppressor cells (MDSCs) is a common feature of cancer, but its biological roles and molecular mechanism remain unclear. Here, we investigated a molecular link between MDSC expansion and tumor cell metastasis in nasopharyngeal carcinoma (NPC). We demonstrated that MDSCs expanded and were positively correlated with the elevated tumor COX-2 expression and serum IL-6 levels in NPC patients. Importantly, COX-2 and MDSCs were poor predictors of patient disease-free survival (DFS). Knocking down tumor COX-2 expression hampered functional TW03-mediated-MDSC cell (T-MDSC) induction with IL-6 blocking. We identified that T-MDSCs promoted NPC cell migration and invasion by triggering the epithelial-mesenchymal transition (EMT) on cell-to-cell contact, and TMDSCs enhanced tumor experimental lung metastasis in vivo. Interestingly, the contact between T-MDSCs and NPC cells enhanced tumor COX-2 expression, which subsequently activated the b-catenin/TCF4 pathway, resulting in EMT of the cancer cells. Blocking transforming growth factor b (TGFb) or inducible nitric oxide synthase (iNOS) significantly abolished the T-MDSC-induced upregulation of COX-2 and EMT scores in NPC cells, whereas the administration of TGFb or L-arginine supplements upregulated COX-2 expression and EMT scores in NPC cells. These findings reveal that COX-2 is a key factor mediating the interaction between MDSCs and tumor cells, suggesting that the inhibition of COX-2 or MDSCs has the potential to suppress NPC metastasis.

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“…Secondly, neoadjuvant chemotherapy based on cisplatin could improve local control and survival rate in radiotherapy of locally advanced NPC (Xu et al, 2012;Du et al, 2013;Kong et al, 2014). The radiotherapy of nasopharynx, neck and/ or bone metastases to treat the NPC patients with distant metastases could prolong complete response time and increase the survival rate after systematic chemotherapy (Chen et al, 2013;Agnese et al, 2014). Thirdly, NPC was sensitive to chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Selective Radiotherapy after Distant Metastasis of Nasopharyngeal Carcinoma Treated with Dose-Dense Cisplatin plus Fluorouracil

Bu¹,

Cheng²,

Gao³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Purpose: To investigate the efficacy and safety of selective radiotherapy after distant metastasis of nasopharyngeal carcinoma (NPC) treated with dose-dense cisplatin plus fluorouracil. Materials and Methods: Eligible patients were randomly assigned to a study group treated with dose-dense cisplatin plus fluorouracil following selective radiotherapy and a control group receiving traditional cisplatin plus fluorouracil following selective radiotherapy according to a 1:1 distribution using a digital random table method. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate, relapse or progression rate in the radiation field and treatment toxicity. Results: Of 52 patients in the study group, 20 cases underwent radiotherapy., while in the control group of 51 patients, 16 underwent radiotherapy. The median PFS, median OS, survival rates in 1, 2 and 3 years in study and control group were 20.9 vs 12.7months, 28.3 vs 18.8months, 85.2%vs 65.9%, 62.2% vs 18.3%, and 36.6%vs 5.2% (p values of 0.00, 0.00, 0.04, 0.00 and 0.00, respectively). Subgroup analysis showed that the median OS and survival rates of 1, 2, 3 years for patients undergoing radiotherapy in the study group better than that in control group( 43.2vs24.1 months, 94.1% vs 86.7%, 82.4% vs 43.3%, 64.7% vs 17.3%, (p=0.00, 0.57, 0.04 and 0.01, respectively). The complete response rate, objective response rate after chemotherapy and three months after radiotherapy, relapse or progression rate in radiation field in study group and in control group were 19.2% vs 3.9%, 86.5% vs 56.9%, 85% vs 50%, 95% vs 81.3% and 41.3% vs 66.7% (p =0.03, 0.00, 0.03,0.30, 0.01 respectively). The grade 3-4 acute adverse reactions in the study group were significantly higher than in the control group (53.8% vs 9.8%, p=0.00). Conclusions: The survival of patients benefits from selective radiotherapy after distant metastasis of NPC treated with dose-dense cisplatin plus fluorouracil.

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Locoregional radiotherapy in patients with distant metastases of nasopharyngeal carcinoma at diagnosis

Cited by 111 publications

References 30 publications

Systemic chemotherapy followed by locoregional definitive intensity-modulated radiation therapy yields prolonged survival in nasopharyngeal carcinoma patients with distant metastasis at initial diagnosis

Systemic chemotherapy followed by locoregional definitive intensity-modulated radiation therapy yields prolonged survival in nasopharyngeal carcinoma patients with distant metastasis at initial diagnosis

COX-2 promotes metastasis in nasopharyngeal carcinoma by mediating interactions between cancer cells and myeloid-derived suppressor cells

Selective Radiotherapy after Distant Metastasis of Nasopharyngeal Carcinoma Treated with Dose-Dense Cisplatin plus Fluorouracil

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