Antibody-platinum(IV)prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma

Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.

Long-term outcomes of a phase Ⅱ randomized controlled trial comparing intensity-modulated radiotherapy with or without weekly cisplatin for the treatment of locally recurrent nasopharyngeal carcinoma

Background:Salvage treatment for locally recurrent nasopharyngeal carcinoma(NPC) is complicated and relatively limited.Radiotherapy,combined with effective concomitant chemotherapy,may improve clinical treatment outcomes.We conducted a phase Ⅱ randomized controlled trial to evaluate the efficacy of intensity-modulated radiotherapy with concomitant weekly cisplatin on locally recurrent NPC.Methods:Between April 2002 and January 2008,69 patients diagnosed with non-metastatic locally recurrent NPC were randomly assigned to either concomitant chemoradiotherapy group(n = 34) or radiotherapy alone group(n = 35).All patients received intensity-modulated radiotherapy.The radiotherapy dose for both groups was 60 Gy in 27 fractions for 37 days(range 23-53 days).The concomitant chemotherapy schedule was cisplatin 30 mg/m^2 by intravenous infusion weekly during radiotherapy.Results:The median follow-up period of all patients was 35 months(range 2-112 months).Between concomitant chemoradiotherapy and radiotherapy groups,there was only significant difference in the 3-year and 5-year overall survival(OS) rates(68.7%vs.42.2%,P = 0.016 and 41.8%vs.27.5%,P = 0.049,respectively).Subgroup analysis showed that concomitant chemoradiotherapy significantly improved the 5-year OS rate especially for patients in stage rT3-4(33.0%vs.13.2%,P = 0.009),stages Ⅲ-Ⅳ(34.3%vs.13.2%,P = 0.006),recurrence interval >30 months(49.0%vs.20.6%,P = 0.017),and tumor volume >26 cm^3(37.6%vs.0%,P = 0.006).Conclusion:Compared with radiotherapy alone,concomitant chemoradiotherapy can improve OS of the patients with locally recurrent NPC,especially those with advanced T category(rT3-4) and stage(lll-IV) diseases,recurrence intervals >30 months,and tumor volume >26 cm^3.

Dosimetry Comparison between Volumetric Modulated Arc Therapy with RapidArc and Fixed Field Dynamic IMRT for Local-Regionally Advanced Nasopharyngeal Carcinoma

Objective: A dosimetric study was performed to evaluate the performance of volumetric modulated arc radiotherapy with RapidArc on locally advanced nasopharyngeal carcinoma (NPC). Methods: The CT scan data sets of 20 patients of locally advanced NPC were selected randomly. The plans were managed using volumetric modulated arc with RapidArc and fixed nine-field coplanar dynamic intensity-modulated radiotherapy (IMRT) for these patients. The dosimetry of the planning target volumes (PTV), the organs at risk (OARs) and the healthy tissue were evaluated. The dose prescription was set to 70 Gy to the primary tumor and 60 Gy to the clinical target volumes (CTV) in 33 fractions. Each fraction applied daily, five fractions per week. The monitor unit (MU) values and the delivery time were scored to evaluate the expected treatment efficiency. Results: Both techniques had reached clinical treatment’s requirement. The mean dose (Dmean), maximum dose (Dmax) and minimum dose (Dmin) in RapidArc and fixed field IMRT for PTV were 68.4±0.6 Gy, 74.8±0.9 Gy and 56.8±1.1 Gy; and 67.6±0.6 Gy, 73.8±0.4 Gy and 57.5±0.6 Gy (P<0.05), respectively. Homogeneity index was 78.85±1.29 in RapidArc and 80.34±0.54 (P<0.05) in IMRT. The conformity index (CI: 95%) was 0.78±0.01 for both techniques (P>0.05). Compared to IMRT, RapidArc allowed a reduction of Dmean to the brain stem, mandible and optic nerves of 14.1% (P<0.05), 5.6% (P<0.05) and 12.2% (P<0.05), respectively. For the healthy tissue and the whole absorbed dose, Dmean of RapidArc was reduced by 3.6% (P<0.05), and 3.7% (P<0.05), respectively. The Dmean to the parotids, the spinal cord and the lens had no statistical difference among them. The mean MU values of RapidArc and IMRT were 550 and 1,379. The mean treatment time of RapidArc and IMRT was 165 s and 447 s. Compared to IMRT, the delivery time and the MU values of RapidArc were reduced by 63% and 60%, respectively. Conclusion: For locally advanced NPC, both RapidArc and IMRT reached the clinic requirement. The target volume coverage was similar for the different techniques. The RapidArc technique showed some improvements in OARs and other tissue sparing while using reduced MUs and delivery time.

Treatment outcomes for different subgroups of nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy

Although many studies have investigated intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC),sample sizes in the reported studies are usually small and different in outcomes in different T and N subgroups are seldom analyzed.Herein,we evaluated the outcomes of NPC patients treated with IMRT and further explored treatment strategy to improve such outcome.We collected clinical data of 865 NPC patients treated with IMRT alone or in combination with chemotherapy,and classified all cases into the following prognostic categories according to different TNM stages:early stage group (T1-2N0-1M0),advanced local disease group (T3-4N0-1M0),advanced nodal disease group (T1-2N2-3M0),and advanced locoregional disease group (T3-4N2-3M0).The 5-year overall survival (OS),local relapse-free survival (LRFS),and distant metastases-free survival (DMFS) were 83.0%,90.4%,and 84.0%,respectively.The early disease group had the lowest treatment failure rate,with a 5-year OS of 95.6%.The advanced local disease group and advanced nodal disease group had similar failure pattern and treatment outcomes as well as similar hazard ratios for death (4.230 and 4.625,respectively).The advanced locoregional disease group had the highest incidence of relapse and death,with a 5-year DMFS and OS of 62.3% and 62.2%,respectively,and a hazard ratio for death of 10.402.Comparing with IMRT alone,IMRT in combination with chemotherapy provided no significant benefit to locoregionally advanced NPC.Our results suggest that the decision of treatment strategy for NPC patients should consider combinations of T and N stages,and that IMRT alone for early stage NPC patients can produce satisfactory results.However,for advanced local,nodal,and locoregional disease groups,a combination of chemotherapy and radiotherapy is recommended.

Volumetric modulation arc radiotherapy with flattening filter-free beams compared with conventional beams for nasopharyngeal carcinoma:a feasibility study

There is increasing interest in the clinical use of flattening filter-free(FFF) beams.In this study,we aimed to investigate the dosimetric characteristics of volumetric modulated arc radiotherapy(VMAT) with FFF beams for nasopharyngeal carcinoma(NPC).Ten NPC patients were randomly selected to undergo a RapidArc plan with either FFF beams(RA-FFF) or conventional beams(RA-C).The doses to the planning target volumes(PTVs),organs at risk(OARs),and normal tissues were compared.The technical delivery parameters for RapidArc plans were also assessed to compare the characteristics of FFF and conventional beams.Both techniques delivered adequate doses to PTVs.For PTVs,RA-C delivered lower maximum and mean doses and improved conformity and homogeneity compared with RA-FFF.Both techniques provided similar maximum doses to the optic nerves and lenses.For the brain stem,spinal cord,larynx,parotid glands,oral cavity,and skin,RA-FFF showed significant dose increases compared to RA-C.The dose to normal tissue was lower in RA-FFF.The monitor units(MUs) were(536 ± 46) MU for RA-FFF and(501± 25) MU for RA-C.The treatment duration did not significantly differbetween plans.Although both treatment plans could meet clinical needs,RA-C is dosimetrically superior to RA-FFF for NPC radiotherapy.

Long-term Therapeutic Outcome and Prognostic Factors of Patients with Nasopharyngeal Carcinoma Receiving Intensity-modulated Radiotherapy: An Analysis of 608 Patients from Low-endemic Regions of China

Objective To evaluate the long-term outcome and prognostic factors of patients with nasopharyngeal carcinoma(NPC)from low-endemic regions of China who received definitive intensity-modulated radiation therapy(IMRT).Methods The clinical data from 608 patients with newly-diagnosed non-metastatic NPC who have received initial treatment at our cancer center from January,2008 to December,2013 were retrospectively reviewed.All patients received definitive IMRT,and 87.7%received platinum-based chemotherapy.Results The median follow-up duration was 51 months(follow-up rate,98.5%;range,10–106 months)for the entire cohort.The 5-year overall survival rate was 79.7%.The 5-year local relapse-free survival rate,regional relapse-free survival rate,distant metastasis-free survival rate and progression-free survival rate were 92.4%,93.3%,79.2%and 74.3%,respectively.A total of 153 patients had experienced treatment failure,with distant metastasis as the primary cause in 77.1%(118/153).Patients with T4 or N3 diseases had a significantly poorer prognosis than other subcategories.Stage T4 and N3 were closely associated with distant metastasis,with the metastatic rate of 29.3%and 45.5%,respectively.Conclusion IMRT provides patients with non-metastatic NPC with satisfactory long-term survival.Both T stage and N stage are important prognostic factors for NPC patients.Patients with T4 or N3 diseases have significantly increased distant metastatic rates and poor survival time.

Local definitive intensity-modulated radiation therapy recommended for patients initially diagnosed with nasopharyngeal carcinoma with distant metastasis after an effective systemic chemotherapy

Objective The aim of the study was to propose a hypothesis that local definitive intensity-modulated radiation therapy(IMRT) should be recommended for initially diagnosed metastatic nasopharyngeal carcinoma(NPC) and demonstrate its feasibility.Methods Recently published papers on local definitive radiotherapy for initially diagnosed metastatic NPC were reviewed to propose a hypothesis.Results Several studies revealed the survival benefits of adding local definitive radiotherapy to the systemic chemotherapy in patients initially diagnosed with metastatic NPC.Conclusion We suggested that local definitive IMRT should be recommended in patients initially diagnosed with NPC with distant metastasis after an effective systemic chemotherapy, which may possibly prolong their survival time and potentially treat the disease.

A Survey of Researches on Synergy and Toxicity Abatement of Traditional Chinese Medicine in Radiotherapy of Nasopharyngeal Carcinoma

Even though radiotherapy is a therapy of first choice in the treatment of nasopharyngeal carcinoma, its radiotoxicity is often difficult to bear for patients in addition to the unsatisfactory effect in some patients. Therefore, an important problem in the treatment of nasopharyngeal carcinoma is to abate radiotherapeutic toxicity and improve its effect. Some progresses in promoting the effect of radiotherapy and abating its toxicity have been made through application of traditional Chinese medicine (TCM) which is briefly reviewed as follows.

A dosimetric comparative study between conformal and intensity modulated radiation therapy in the treatment of primary nasopharyngeal carcinomas: the Egyptian experience

Objective: The study is a comparative study, the aim of which is to compare 3D conformal radiation therapy (3D-CRT) and intensity modulated radiation therapy (IMRT) in treating nasopharyngeal carcinomas; dosimetrically evaluating and comparing both techniques as regard target coverage and doses to organs at risk (OAR). Methods: Twenty patients with nasopharyngeal carcinoma were treated by 3D-CRT technique and another 20 patients were treated by IMRT. A dosimetric comparison was done by performing two plans for the same patient using Eclipse planning system (version 8.6). Results: IMRT had a better tumor coverage and conformity index compared to 3D-CRT plans (P value of 0.001 and 0.004), respectively. As for the dose homogeneity it was also better in the IMRT plans and the reason for this was attributed to the dose inhomogeneity at the photon/electron junction in the 3D-CRT plans (P value 0.032). Also, doses received by the risk structures, particularly parotids, was significantly less in the IMRT plans than those of 3D-CRT (P value 0.001). Conclusion: IMRT technique was clearly able to increase the dose delivery to the target volume, improve conformity and homogeneity index and spare the parotid glands in comparison to 3D-CRT technique.

Lipid metabolism of hepatocellular carcinoma impacts targeted therapy and immunotherapy

Hepatocellular carcinoma(HCC)is a common malignant tumor that affecting many people's lives globally.The common risk factors for HCC include being overweight and obese.The liver is the center of lipid metabolism,synthesizing most cholesterol and fatty acids.Abnormal lipid metabolism is a significant feature of metabolic reprogramming in HCC and affects the prognosis of HCC patients by regulating inflammatory responses and changing the immune microenvironment.Targeted therapy and immunotherapy are being explored as the primary treatment strategies for HCC patients with unresectable tumors.Here,we detail the specific changes of lipid metabolism in HCC and its impact on both these therapies for HCC.HCC treatment strategies aimed at targeting lipid metabolism and how to integrate them with targeted therapy or immunotherapy rationally are also presented.

Role of autophagy in tumorigenesis,metastasis,targeted therapy and drug resistance of hepatocellular carcinoma

Autophagy is a "self-degradative" process and is involved in the maintenance of cellular homeostasis and the control of cellular components by facilitating the clearance or turnover of long-lived or misfolded proteins, protein aggregates, and damaged organelles. Autophagy plays a dual role in cancer, including in tumor progression and tumor promotion, suggesting that autophagy acts as a double-edged sword in cancer cells. Liver cancer is one of the greatest leading causes of cancer death worldwide due to its high recurrence rate and poor prognosis. Especially in China, liver cancer has become one of the most common cancers due to the high infection rate of hepatitis virus. In primary liver cancer, hepatocellular carcinoma (HCC) is the most common type. Considering the perniciousness and complexity of HCC, it is essential to elucidate the function of autophagy in HCC. In this review, we summarize the physiological function of autophagy in cancer, analyze the role of autophagy in tumorigenesis and metastasis, discuss the therapeutic strategies targeting autophagy and the mechanisms of drug-resistance in HCC, and provide potential methods to circumvent resistance and combined anticancer strategies for HCC patients.

Hepatic cancer stem cells and drug resistance: Relevance in targeted therapies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have indicated an association between drug resistance and the existence of the cancer stem cells (CSCs) as tumor initiating cells. The CSCs are resistant to conventional chemotherapies and might be related to the mechanisms of the ATP Binding Cassette (ABC) transporters and alterations in the CSCs signaling pathways. Therefore, to contribute to the development of new HCC treatments, further information on the characterization of CSCs, the modulation of the ABC transporters expression and function and the signaling pathway involved in the self renewal, initiation and maintenance of the cancer are required. The combination of transporters modulators/inhibitors with molecular targeted therapies may be a potent strategy to block the tumoral progression. This review summarizes the association of CSCs, drug resistance, ABC transporters activities and changes in signaling pathways as a guide for future molecular therapy for HCC.

T cells expressing a LMP1-specific chimeric antigen receptor mediate antitumor effects against LMP1-positive nasopharyngeal carcinoma cells in vitro and in vivo

T cells modified with chimeric antigen receptor are an attractive strategy to treat Epstein-Barr virus（EBV） associated malignancies.The EBV latent membrane protein 1（LMP1） is a 66-KD integral membrane protein encoded by EBV that consists of transmembrane-spanning loops.Previously,we have identified a functional signal chain variable fragment（scFv） that specifically recognizes LMP1 through phage library screening.Here,we constructed a LMP1 specific chimeric antigen receptor containing anti-LMP1 scFv,the CD28 signalling domain,and the CD3ζchain（HELA/CAR）.We tested its functional ability to target LMP1 positive nasopharyngeal carcinoma cells.HELA/CAR cells were efficiently generated using lentivirus vector encoding the LMP1-specific chimeric antigen receptor to infect activated human CD3＋ T cells.The HELA/CAR T cells displayed LMP1 specific cytolytic action and produced IFN-γ and IL-2 in response to nasopharyngeal carcinoma cells overexpressing LMP1.To demonstrate in vivo anti-tumor activity,we tested the HELA/CAR T cells in a xenograft model using an LMP1 overexpressing tumor.Intratumoral injection of anti-LMP1 HELA/CAR-T cells significantly reduced tumor growth in vivo.These results show that targeting LMP1 using HELA/CAR cells could represent an alternative therapeutic approach for patients with EBV-positive cancers.

Roles of conventional and complementary therapies in recurrent hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the fifth most common type of cancer and the fourth leading cause of cancer-related deaths in the world.HCC has a reported recurrence rate of 70%-80%after 5 years of follow-up.Controlling tumor recurrence is the most critical factor associated with HCC mortality.Conventional salvage therapies for recurrent HCC include re-hepatectomy or liver transplantation,transcatheter arterial chemoembolization,Y-90,target therapy,and immunotherapy;however,these conventional treatment modalities have yet to achieve consistently favorable outcomes.Meanwhile,previous studies have demonstrated that conventional therapies in combination with traditional Chinese medicine(TCM),acupuncture,moxibustion or dietary supplements could notably benefit patients with HCC recurrence by strengthening and augmenting the overall management strategy.However,systemic reviews related to the interactions between complementary therapies and conventional therapy in recurrent HCC are limited.In this review,we discuss the molecular mechanisms underlying the functions of complementary therapies for recurrent HCC,which include augmenting the local control to improve the congestion status of primary tumors and reducing multicentric tumor occurrence via inducing autophagy,apoptosis or cell cycle arrest.TCM and its derivatives may play important roles in helping to control HCC recurrence by inhibiting epithelial-mesenchymal transition,migration,invasion,and metastasis,inhibiting cancer stem cells,and ameliorating drug resistance.

Hepatocellular carcinoma and multidrug resistance: Past, present and new challenges for therapy improvement

Hepatocellular carcinoma(HCC) is the most frequent form of liver cancer and the third most common cause of cancer-related death in the world. The main risk factor worldwide for this type of malignancy is chronic hepatitis caused by hepatitis B virus and hepatitis C virus infections. Advances in early detection and treatmenthave improved life expectancy of patients with HCC. However, this disorder remains as a disease with poor prognosis. In fact, epidemiological studies have revealed that there is an 8-mo median survival rate in patients, approximately 20% of whom survive one year while only 5% remain alive after three years. Additionally, HCC is particularly difficult to treat because of its high recurrence rate, and its resistance to conventional chemotherapy is due, among other mechanisms, to several members of the ATP-Binding Cassette protein family involved in drug transport being overexpressed. Fortunately, there is evidence that these patients may benefit from alternative molecular-targeted therapies. This manuscript intends to provide further insight into the etiology and molecular mechanisms related to HCC development and the latest therapeutic approaches to treat this malignancy. The development of effective delivery systems of antitumor drugs able to target the liver parenchyma is also assessed. Finally, the prospects in the development of more efficient drug therapies to overcome multidrug resistance are also examined.

Treatment results and prognostic analysis of 1093 primary nasopharyngeal carcinoma: the experience of a single institution of Guangzhou in the beginning of the 21st century

Objective： To analyze the treatment results of primary nasopharyngeal carcinoma （NPC） treated in our institution in the beginning of the 21st century to identify key failures and late effects for refining future treatments. Methods： 1093 patients with primary NPC treated during December 2001 and June 2003 were retrospectively analyzed. The distribution according to the AJCC/UICC （2002 edition） staging system was stage Ⅰ in 5.8%, stage Ⅱ 40.2%, stage Ⅲ 32.7% and stage Ⅳa-b 21.3%. Four different ERT techniques were used： fluoroscopy simulation conventional radiotherapy （CR） in 74.3% of patients, computer tomography simulation conventional radiotherapy （CT-sim CR） 14.2%, three-dimensional conformal radiotherapy （3D-CRT） 6.3%, intensity modulated radiotherapy （IMRT） 5.2%. In the whole series, 46.7% of patients had additional treatment with chemotherapy. Results： The 4-year local failure-free rate （LFFR）, nodal failure-free rate, distant metastasis-free rate, progression-free survival and overall survival （OS） was 89.6%, 96.1%, 85.9%, 73.0% and 82.4%, respectively. The stage was the most important prognostic factor. The 4-year OS and LFFR of patients treated by CR, CT-sim CR, 3D-CRT and IMRT was 80.2%, 89.8%, 89.8%, 92.4% and 87.7%, 96.4%, 91.0%, 96.5%, respectively. The morbidity and degree of xerostomia and trismus were lower in the patients treated by 3D-CRT and IMRT than by CR and CT-sim CR. Conclusion： Treatment results of primary NPC in our institution have been substantially improved. Distant metastasis is the main failure. The CT simulation and conformal radiotherapy can enhance the OS and LFFR, and conformal radiotherapy can reduce the morbidity and degree of late effects.

Role of deubiquitinase JOSD2 in the pathogenesis of esophageal squamous cell carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.

Occipital lymph node metastasis from nasopharyngeal carcinoma:a special case report and literature review

Cervical lymph node metastasis is common in patients with nasopharyngeal carcinoma(NPC),but occipital lymph node metastasis in NPC patients has not yet been reported.In this case report,we describe an NPC patient with occipital lymph node metastasis.The clinical presentation,diagnostic procedure,treatment,and outcome of this case were presented,with a review of the related literature.

COMPARISON OF AMINOLEVULINIC ACID AND ITS METHYL ESTER MEDIATED PHOTOCYTOTOXICITY ON HUMAN NASOPHARYNGEAL CARCINOMA CELLS

Nasopharyngeal carcinoma(NPC)is a prevalent cancer in some areas of southern Asia.To explore the potential of photodynamic therapy(PDT)for the treatment of NPC,a small molecule prodrug 5-aminolevulinic acid(ALA)and its methyl ester(MAL)mediated PDT was studied in vitro.The results showed that human NPC cells were sensitive to both ALA-and MAL-mediated PDT.However,ALA was more effective than MAL,possiblly due to a higher efficiency of ALA on producing endogenous protoporphyrin(PpIX)in NPC cells.Neither ALA nor MAL caused any significant genotoxicity.The ALA-based PDT might be a useful modality in the treatment ofNPC.

Study on the effect of PET/CT-guided nasopharyngeal carcinoma target delineation on the dose received by endangered organs

Objective:To compare the differences of radiation-induced doses between 18F-FDG-PET/CT and CT/MRI-guided target delineation in nasopharyngeal carcinoma in intensity-modulated radiotherapy.Methods:A total of 31 patients with locally advanced nasopharyngeal carcinoma receiving treatment in our hospital from December 2016 to December 2017 were studied in this research,and 18F-FDG-PET/CT and CT/MRI were used to guide the target delineation to develop an intensity-modulated radiotherapy plan(experimental group and control group).The dose differences between GTV and endangered organs in the two groups were compared.Results:Comparison of primary tumor volume:PET/CT was smaller than CT/MRI,and volumes of T3 and T4 were significantly different(P<0.001).Comparison of the two delineation plans,in terms of PGTV in Dmin,Dmean,and D95,the data of experimental group was smaller than that of the control group;in Dmax,the PGTV of the experimental group was larger than that of the control group with P<0.001 considered as a significant difference.In Dmin and Dmax,doses of experimental groups of the spinal cord were lower than those of the control group,showing a significant difference(P=0.022,0.042);In Dmean,there was no difference between the two groups.In Dmax doses of an experimental group of the brainstem and parotid gland were significantly smaller than the control group(P=0.001,0.047)while there was no difference between Dmin and Dmean.There was no difference between the two groups of Dmin,Dmean,and Dmax in the doses received by chiasm and temporal lobe.Conclusion:PET/CT guided target delineation is applied in the simultaneous dose adjustment of intensity-modulated radiation therapy in patients with advanced nasopharyngeal carcinoma.In primary lesion targets shown by MRI/CT,the tumor tissue of PET/CT concentration zone was given a higher dose with relatively smaller average dose and minimum dose in the overall tumor target area.Statistics also showed that the doses received by the spinal cord,brain stem,and parotid gland were reduced with no effect on the optic chiasm and temporal lobe.In the future,more studies should probe into the long-term effects of dose changes on lesion control and endangered organs.