BackgroundAccording to the 7th edition of the American Joint Committee on Cancer (AJCC) staging system, over 50% of patients with nasopharyngeal carcinoma (NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node (GTVnd) and pretreatment serum copy number of Epstein–Barr virus (EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients.MethodsThe medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were analyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood samples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic (ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan–Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model.ResultsThe 5-year distant metastasis-free survival (DMFS) rates for patients with GTVnd > 18.9 vs. ≤ 18.9 mL were 82.2% vs. 93.2% (P < 0.001), and for patients with EBV DNA copy number > 4000 vs. ≤ 4000 copies/mL were 83.5% vs. 93.9% (P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis (both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-, moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1, 87.4, and 73.8%, respectively (P < 0.001). Multivariate analysis confirmed the prognostic value of this model for distant metastatic risk stratification (hazard ratio [HR], 4.17; 95% confidence interval [CI] 2.34–7.59; P < 0.001).ConclusionsGTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.

Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology to promote cancer research and accelerate collaborations. In this article, 10 questions are presented as followed. Question 76. How to develop effective therapeutics for cancer cachexia? Question 77. How can we develop preclinical animal models to recapitulate clinical situations of cancer patients for more effective anti-cancer drug development? Question 78. How can we develop novel effective therapeutics for pancreatic cancer and hepatocellular carcinoma? Question 79. What are the true beneficial mechanisms of antiangiogenic therapy in cancer patients? Question 80. How to approach the complex mechanisms of interplay among various cellular and molecular components in the tumor microenvironment? Question 81. Can tissue oxygenation improve the efficacy of conventional chemotherapy on cancer? Question 82. Can tissue oxygenation improve the efficacy of radiotherapy on digestive system tumors including liver cancer? Question 83. Can we integrate metabolic priming into multimodal management of liver cancer? Question 84. Has the limit of anti-androgen strategy in prostate cancer treatment been reached by the new generation of anti-androgen drugs? Question 85. Can we identify individuals with early-stage cancers via analyzing their clinical and non-clinical information collected from social media, shopping history, and clinical, pathological, and molecular traces?

Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, 9 more questions are presented as followed. Question 67. How could we overcome the resistance of hepatocellular carcinoma against chemotherapeutics? Question 68. Is pursuit of non-covalent small-molecule binders of RAS proteins viable as a strategy of cancer drug discovery? Question 69. In what oligomeric structures do RAS proteins signal? Question 70. How can we achieve non-invasive early detection and diagnosis of lung cancer? Question 71. Does genetic information influence the volatolome enabling diagnosis of lung cancer with genetic mutations via cell headspace or breath analysis? Question 72. Is heavy ion beam radiotherapy effective to kill cancer stem cells? Question 73. Is there any diversity among different types of cancer in terms of sensitivity to heavy ion beam radiotherapy? Question 74. Can targeted alpha-particle therapy augment the effect of carbon ion radiotherapy on malignancies? Question 75. How does chromosomal instability drive tumor progression?

BackgroundTo protect neurological tissues, underdosing occurs in most cases of T4 nasopharyngeal carcinoma (NPC) with intracranial extension. In this study, we aimed to evaluate the effect of dosimetric inadequacy on local control and late neurological toxicities for patients treated with intensity-modulated radiotherapy (IMRT) plus chemotherapy.MethodsWe prospectively enrolled patients who had non-metastatic T4 NPC with intracranial extension treated between January 2009 and November 2013. The prescribed dose was 66.0–70.4 Gy to the primary planning target volume (primary gross tumor volume [GTVp; i.e., the nasopharyngeal tumor] + 5.0 mm). Dose–volume histogram parameters were calculated, including minimum point dose (Dmin) and dose to 95% of the target volume (D95). All patients received chemotherapy with the cisplatin, 5-fluorouracil, and docetaxel regimen. Survivals were estimated using the Kaplan–Meier method and compared using the log-rank test.ResultsIn total, 41 patients were enrolled. The local partial response rate was 87.8% after induction chemotherapy. With a median follow-up of 51 months, 7 patients experienced failure in the nasopharynx; the 3-year local failure-free survival and overall survival rates of the 41 patients were 87.4% and 90.2%, respectively. The actual mean Dmin to the GTVp was 55.2 Gy (range 48.3–67.3 Gy), and D95 was 61.6 Gy (range 52.6–69.0 Gy). All doses received by neurological organs remained well within their dose constraints. No patients developed temporal lobe necrosis or other neurological dysfunctions.ConclusionsWith relative underdosed IMRT plus effective chemotherapy, the patients achieved satisfactory local control with few late toxicities of the central nervous system. Determining the acceptable extent of dosimetric inadequacy requires further exploration.

BackgroundEsophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends.MethodsFrom 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan (CNY; 1 CNY = 0.155 USD) based on the 2011 value and inflated using the year-specific health care consumer price index for China.ResultsA total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27% was observed from 2002 (25,111 CNY) to 2011 (46,124 CNY). The average expenditures were 34,460 CNY for stage I, 39,302 CNY for stage II, 40,353 CNY for stage III, and 37,432 CNY for stage IV diseases (P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy (P < 0.05). Drugs contributed to 45.02% of the overall expenditure.ConclusionsThese conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.

Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, seven more questions are presented as followed. Question 50. When tumor cells spread from primary site to distant sites, are they required to be “trained” or “armed” in the bone marrow niche prior to colonizing soft tissues? Question 51. Are there tipping points during cancer progression which can be identified for manipulation? Question 52. Can we replace molecular biomarkers by network biomarkers? Question 53. Are conventional inhibitors of key cellular processes such as cell proliferation and differentiation more effective than targeted chemotherapeutics that antagonize the downstream cell signaling network via cell-surface receptors such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR) and c-Met, or intracellular receptors such as androgen receptor (AR) and estrogen receptor (ER), by drugs like erlotinib, sunitinib and cabozantinib, or enzalutamide and tomoxifen? Question 54. How can we robustly identify the candidate causal event of somatic genome alteration (SGA) by using computational approach? Question 55. How can we systematically reveal the immune evasion mechanism exploited by each tumor and utilize such information to guide targeted therapy to restore immune sensitivity? Question 56. Can the nasopharyngeal carcinoma (NPC) patients with sarcomatoid carcinoma (SC) subtype benefit from more specific targeted therapy?

Five-year survival rate for patients with all cancers combined, in China, is only 30.9%, which is much lower than those in developed countries. The three main reasons for the low cancer curative rates in China include differences in the spectrum of cancer types, in early detection rates, and in the percentage of cancer patients receiving standardized treatment between China and developed countries. The most important mechanism for improving the curative rate is to improve early detection rates of major cancers in China using novel and affordable technologies that can be operated at home by the patients themselves. This attempt could be helpful in setting up a practical example for other developing countries with limited medical resources and a limited number of healthcare practitioners.

To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology. In this article, 10 more questions are presented as follows. Question 15: Can tumor-induced erythrogenesis provide qualified red blood cells for carrying oxygen to distant organs? Question 16: Can we overcome tumor resistance to platinum-containing antineoplastic drugs by activating the sensitivity factors in the tumor? Question 17: How can a cancer cell stay dormant for years? Question 18: Why do cancer cells use distinct transcriptomic and proteomic programs to reach the same metastatic phenotype? Question 19: Why do some cancers regress spontaneously? Question 20: What are the regulatory mechanisms occurring in donor cells that determine selective sorting of biological content into vesicles and their biological consequences in recipient cells? Are the genetic transfer and exchange of biological messages between cells transient? Is the phenotypic manipulation of recipient cells temporary or prolonged and persistent? If extracellular vesicles possess immune-modulatory potential, how could they be exploited for immune interventions and cancer immunotherapy? Presumably the cargo of extracellular vesicles reflects the cells of their origin and can be used for cancer diagnosis, how could the uniform/stringent capture criteria be met universally for applying EVs in point-of-care diagnostics for cancer patients? Question 21: Can we use self-sampling technologies to monitor the tumor genetic alterations for more precise targeted therapy? Can we cure a heterogeneous tumor by sequentially targeting the driver molecules? Question 22: Can we postpone the onset of non-infection-related cancers? Question 23: How many types of cells can jointly form the tumor vasculature to provide blood supply for tumor progression? Question 24: How tumor cells transmit their epigenetic features to daughter cells and maintain the malignant phenotype?

To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology. In this article, nine more questions are presented as followed. Question 6. Why do nasopharyngeal carcinomas rarely metastasize to the brain? Question 7. Can distant spread of cancer cells be blocked by inhibiting the remodeling of high endothelial venules in the sentinel lymph node? Question 8. What sort of live-imaging techniques can be developed to directly observe the dynamic processes of metastasis? Question 9. How does chronic hepatitis prevent liver metastasis from colorectal cancer? Question 10. How many types of host cells contribute to forming the pre-metastatic niche in the lung favorable for metastasis? Question 11. Why do cancers rarely metastasize to the small bowel? Question 12. Why do glioblastomas rarely metastasize outside the central nervous system? Question 13. Despite increased understanding of the molecular genetic events leading to the development and progression of high-grade gliomas, these tumors are the most therapeutically refractory among all human cancers. What then would be the most effective therapeutic approaches to treat what in essence can be regarded as a whole brain malignancy, since even a surgical resection of greater than 99% of tumor tissues is invariably associated with recurrence? Question 14. The blood–brain barrier (BBB) effectively limits a wide variety of potential therapeutic agents from reaching glioma cells widely dispersed in the brain. What therapeutic approaches can be used to breach the BBB and allow therapeutic agents to seek out and kill these tumor cells?