Prognostic factors and failure patterns in non-metastatic nasopharyngeal carcinoma after intensity-modulated radiotherapy

Background: The prognostic values of staging parameters require continual re?assessment amid changes in diag?nostic and therapeutic methods. This study aimed to identify the prognostic factors and failure patterns of non?meta?static nasopharyngeal carcinoma(NPC) in the intensity?modulated radiotherapy(IMRT) era.Methods: We reviewed the data from 749 patients with newly diagnosed, biopsy?proven, non?metastatic NPC in our cancer center(South China, an NPC endemic area) between January 2003 and December 2007. All patients under?went magnetic resonance imaging(MRI) before receiving IMRT. The actuarial survival rates were estimated using the Kaplan–Meier method, and survival curves were compared using the log?rank test. Multivariate analyses with the Cox proportional hazards model were used to test for the independent prognostic factors by backward eliminating insigniicant explanatory variables.Results: The 5?year occurrence rates of local failure, regional failure, locoregional failure, and distant failure were 5.4, 3.0, 7.4, and 17.4%, respectively. The 5?year survival rates were as follows: local relapse?free survival, 94.6%; nodal relapse?free survival, 97.0%; distant metastasis?free survival, 82.6%; disease?free survival, 75.1%; and overall survival, 82.0%. Multivariate Cox regression analysis revealed that orbit involvement was the only signiicant prognostic fac?tor for local failure(P = 0.011). Parapharyngeal tumor extension, retropharyngeal lymph node involvement, and the laterality, longest diameter, and Ho's location of the cervical lymph nodes were signiicant prognostic factors for both distant failure and disease failure(all P < 0.05). Intracranial extension had signiicant prognostic value for distant failure(P = 0.040).Conclusions: The key failure pattern for NPC was distant metastasis in the IMRT era. With changes in diagnostic and therapeutic technologies as well as treatment modalities, the signiicant prognostic parameters for local control have also been altered substantially.

Significant value of 18F-FDG-PET/CT in diagnosing small cervical lymph node metastases in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy

Background: Little is known about the nature of metaistasis to small cervical lymph nodes(SCLNS) in the patients with nasopharyngeal carcinoma(NPC)examined by using 18-fluoro-2-deoxy-glucose(^(18)F-FDG) positron emission tomography/computed tomography(PET/CT).The present study aimed to evaluate the diagnostic values of PET/CT in identifying metastasis in SCLNs in NPC patients.Methods: Magnetic resonance images(MRI) and PET/CT scans for 470 patients with newly diagnosed, non-distant metastatic NPC were analyzed. Metastatic rates of SCLNs were defined by the positive number of SCLNs on PET/CT scans and total number of SCLNs on MRI scans. Receiver operating characteristic curve was applied to compare PET/CT-determined stage with MRI-determined stage.Results: In total, 2082 SCLNs were identified, with 808(38.8%) ≥ 5 and < 6 mm in diameter(group A), 526(25.3%)≥ 6 and < 7 mm in diameter(group B),374(18.0%)≥ 7 and < 8 mm in diameter(group C), 237(11.4%) ≥8 and<9 mm in diameter(group D),and 137(6.5%) ≥ 9 and <10 mm in diameter(group E).The overall metastatic rates examined by using PET/CT for groups A, B,C,D, and E were 3.5%, 8.0%, 31.3%, 60.0%, and 83.9%, respectively(P< 0.001). In level IV/Vb, the metastatic rate for nodes ≥ 8 mm was 84.6%. PET/CT examination resulted in modification of N category and overall stage for 135(28.7%) and 46(9.8%) patients, respectively. The areas under curve of MRIdetermined and PET/CT-determined overall stage were 0.659 and 0.704 for predicting overall survival, 0.661 and 0.711 for predicting distant metastasis-free survival, and 0.636 and 0.663 for predicting disease-free survival.Conclusions: PET/CT was more effective than MRI in identifying metastatic SCLNs, and the radiologic diagnostic criteria for metastatic lymph nodes in level IV/Vb should be re-defined.

Prognostic value and predictive threshold of tumor volume for patients with locally advanced nasopharyngeal carcinoma receiving intensity-modulated radiotherapy

Background: Gross target volume of primary tumor(GTV?P) is very important for the prognosis prediction of patients with nasopharyngeal carcinoma(NPC), but it is unknown whether the same is true for locally advanced NPC patients treated with intensity?modulated radiotherapy(IMRT). This study aimed to clarify the prognostic value of tumor volume for patient with locally advanced NPC receiving IMRT and to ind a suitable cut?of value of GTV?P for prognosis prediction.Methods: Clinical data of 358 patients with locally advanced NPC who received IMRT were reviewed. Receiver oper?ating characteristic(ROC) curves were used to identify the cut?of values of GTV?P for the prediction of diferent end?points [overall survival(OS), local relapse?free survival(LRFS), distant metastasis?free survival(DMFS), and disease?free survival(DFS)] and to test the prognostic value of GTV?P when compared with that of the American Joint Committee on Cancer T staging system.Results: The 358 patients with locally advanced NPC were divided into two groups by the cut?of value of GTV?P as determined using ROC curves: 219(61.2%) patients with GTV?P ≤46.4 mL and 139(38.8%) with GTV?P >46.4 mL. The 3?year OS, LRFS, DMFS, and DFS rates were all higher in patients with GTV?P ≤46.4 mL than in those with GTV?P > 46.4 mL(all P < 0.05). Multivariate analysis indicated that GTV?P >46.4 mL was an independent unfavorable prognostic factor for patient survival. The ROC curve veriied that the predictive ability of GTV?P was superior to that of T category(P < 0.001). The cut?of values of GTV?P for the prediction of OS, LRFS, DMFS, and DFS were 46.4, 57.9, 75.4 and 46.4 mL, respectively.Conclusion: In patients with locally advanced NPC, GTV?P >46.4 mL is an independent unfavorable prognostic indi?cator for survival after IMRT, with a prognostic value superior to that of T category.

A model to predict the risk of lethal nasopharyngeal necrosis after re-irradiation with intensity-modulated radiotherapy in nasopharyngeal carcinoma patients

Background:For patients with nasopharyngeal carcinoma(NPC) who undergo re-irradiation with intensity-modulated radiotherapy(IMRT),lethal nasopharyngeal necrosis(LNN) is a severe late adverse event.The purpose of this study was to identify risk factors for LNN and develop a model to predict LNN after radical re-irradiation with IMRT in patients with recurrent NPC.Methods:Patients who underwent radical re-irradiation with IMRT for locally recurrent NPC between March 2001 and December 2011 and who had no evidence of distant metastasis were included in this study.Clinical characteristics,including recurrent carcinoma conditions and dosimetric features,were evaluated as candidate risk factors for LNN.Logistic regression analysis was used to identify independent risk factors and construct the predictive scoring model.Results:Among 228 patients enrolled in this study,204 were at risk of developing LNN based on risk analysis.Of the 204 patients treated,31(15.2%) developed LNN.Logistic regression analysis showed that female sex(P = 0.008),necrosis before re-irradiation(P = 0.008),accumulated total prescription dose to the gross tumor volume(GTV) ≥ 145.5 Gy(P = 0.043),and recurrent tumor volume >25.38 cm3(P = 0.009) were independent risk factors for LNN.A model to predict LNN was then constructed that included these four independent risk factors.Conclusions:A model that includes sex,necrosis before re-irradiation,accumulated total prescription dose to GTV,and recurrent tumor volume can effectively predict the risk of developing LNN in NPC patients who undergo radical re-irradiation with IMRT.

Clinical treatment considerationsin the intensity-modulated radiotherapy era for patients with NO-category nasopharyngeal carcinoma and enlarged neck lymph nodes

Background:Nasopharyngeal carcinoma(NPC) shows a high proportion of lymph node metastasis,and treatment guidelines have been developed for positive nodes.However,no irradiation guidelines have been proposed for patients with enlarged neck lymph nodes(ENLNs) that do not meet the radiological criteria of 10 mm in diameter for positive lymph nodes.This study aimed to determine the prognostic value and radiation dose for ENLNs in NO-category NPC patients treated with intensity-modulated radiotherapy(IMRT).Methods:We reviewed the medical data of 251 patients with non-metastatic,NO-category NPC treated with IMRT.Receiver operating characteristic curves were used to calculate the cut-off value of the ENLN diameter for the prediction of disease failure.The biological equivalent dose(BED) for ENLNs was calculated.Patient survival was compared between the small and large ENLN groups.Independent prognostic factors were identified using the Cox proportional hazards model.Results:The estimated 4-year regional relapse-free survival rate was higher in patients with ENLNs ≥5.5 mm than in those with ENLNs <5.5 mm(100%vs.98.8%,P=0.049),whereas disease-free,overall,and distant metastasis-free survival rates were similar between the two groups.After adjusting for various factors,ENLN diameter was not identified as an independent prognostic factor(P > 0.05 for all survival rates).In the subgroup analysis,patients receiving BED ≥72 Gy had a similar prognosis as patients receiving BED <72 Gy in both the small and large ENLN groups.The multivariate analysis also confirmed that BED≥72 Gy was not associated with significantly improved prognosis in patients with NO-category NPC.Conclusions:A BED of 72 Gy to ENLNs is considerably sufficient to provide a clinical benefit to patients with NO-category NPC.Prospective studies are warranted to validate the findings in the present study.

Signal intensity changes of dentate nucleus on plain MR T1WI innasopharyngeal carcinoma patients after radiotherapy andmultiple injections of gadolinium-base contrast agent

Objective To observe changes of plain MR T1WI signal intensity of dentate nucleus in nasopharyngeal carcinoma patients after radiotherapy and multiple times of intravenous injection of gadolinium-based contrast agent(GBCA).Methods Fifty patients with pathologically confirmed nasopharyngeal carcinoma and received intensity-modulated radiotherapy were retrospectively enrolled as the nasopharyngeal carcinoma group,and 50 patients with other malignant tumors and without history of brain radiotherapy were retrospectively enrolled as the control group.All patients received yearly GBCA enhanced MR examinations for the nasopharynx or the head.T1WI signal intensities of the dentate nucleus and the pons on same plane were measured based on images in the year of confirmed diagnosis(recorded as the first year)and in the second to the fifth years.T1WI signal intensity ratio of year i(ranging from 1 to 5)was calculated with values of dentate nucleus divided by values of the pons(ΔSI i),while the percentage of relative changes of year j(ranging from 2 to 5)was calculated withΔSI j compared toΔSI 1(Rchange j).The values of these two parameters were compared,and the correlation ofΔSI and GBCA injection year-time was evaluated within each group.Results No significant difference of gender,age norΔSI 1 was found between groups(all P>0.05).The second to the fifth yearΔSI and Rchange in nasopharyngeal carcinoma group were all higher than those in control group(all P<0.05).Within both groups,ΔSI was positively correlated with GBCA injection year-time(both P<0.05).Conclusion Patients with nasopharyngeal carcinoma who underwent radiotherapy and multiple times of intravenous injection of GBCA tended to be found with gradually worsening GBCA deposition in dentate nucleus,for which radiotherapy might be a risk factor.

Selective partial salivary glands sparing during intensity-modulated radiation therapy for nasopharyngeal carcinoma

Objective This study evaluated the dosimetric consequences of selective partial salivary gland sparing during intensity-modulated radiotherapy(IMRT) for patients with nasopharyngeal carcinoma(NPC).Methods Ten patients with NPC were enrolled in the study.Two IMRT plans were produced for each patient:conventional(control) and partial salivary glands-sparing(treatment),with dose constraints to the entire parotid glands or partial salivary glands(including the parotid and submandibular glands,delineated with the adjacent distance of at least 0.5 cm between the glands and PTV,the planning target volume) in planning,respectively.Dosimetric parameters were compared between the two plans,including the V_(110%),V_(100%),V_(95%)(the volume covered by more than 110%,100%,or 95% of the prescribed dose),Dmin(the minimum dose) of PTV,homogeneity index(HI),conformity index(CI),and the mean dose and percentage of the volume receiving 30 Gy or more(V_(30)) for the parotid glands and submandibular glands.Results Treatment plans had significantly lower mean doses and V_(30) to both the entire parotid glands and partial parotid glands than those in control plans.The mean doses to the partial submandibular glands were also significantly lower in treatment plans than in control plans.The PTV coverage was comparable between the two plans,as indicated by V_(100%),V_(95%),Dmin,CI,and HI.The doses to critical structures,including brainstem and spinal cord,were slightly but not significantly higher in treatment plans than in control plans.Conclusion A selective partial salivary gland-sparing approach reduces the doses to parotid and submandibular glands during IMRT,which may decrease the risk of post-radiation xerostomia while not compromising target dose coverage in patients with NPC.

Radiotherapy with neoadjuvant chemotherapy versus concurrent chemoradiotherapy for ascending-type nasopharyngeal carcinoma:a retrospective comparison of toxicity and prognosis

Background:In the era of intensity?modulated radiotherapy(IMRT),the role of neoadjuvant chemotherapy(NACT)in treating ascending?type nasopharyngeal carcinoma(NPC)is under?evaluated.This study was to compare the efficacy of NACT followed by IMRT(NACT+RT)with the efficacy of concurrent chemoradiotherapy(CCRT)on ascending?type NPC.Methods:Clinical data of 214 patients with ascending?type NPC treated with NACT+RT or CCRT between Decem?ber 2009 and July 2011 were analyzed.Of the 214 patients,98 were treated with NACT followed by IMRT,and 116 were treated with CCRT.The survival rates were assessed using Kaplan–Meier analysis,and the survival curves were compared using a log?rank test.Results:The 4?year overall survival,locoregional failure?free survival,distant failure?free survival,and failure?free sur?vival rates were not significantly different between the two groups(all P>0.05).However,patients in the CCRT group exhibited more severe acute adverse events than did patients in the NACT+RT group during radiotherapy,includ?ing leukopenia(30.2%vs.15.3%,P=0.016),neutropenia(25.9%vs.11.2%,P=0.011),and mucositis(57.8%vs.40.8%,P=0.028).After radiotherapy,patients in the CCRT group exhibited significantly higher rates of xerostomia(21.6%vs.Conclusions:The treatment outcomes of the NACT+RT and CCRT groups were similar;however,CCRT led to higher rates of acute and late toxicities.NACT+RT may therefore be a better treatment strategy for ascending?type NPC.

Effects of dosimetric inadequacy on local control and toxicities in the patients with T4 nasopharyngeal carcinoma extending into the intracranial space and treated with intensity.modulated radiotherapy plus chemotherapy

Background:To 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.Methods:We prospectively enrolled patients who had non-metastaticT4 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(D_(min)) 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.Results:In 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 D_(min) 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.Conclusions:With 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.

Dosimetric study of five-field intensity-modulated radiotherapy compared with conventional three-dimensional conformal radiotherapy for rectal cancer

Objective： The aim of the study was to compare the difference of dose distribution in clinical target volume and organ at risk （OAR） between five-field intensity-modulated radiotherapy （IMRT） and conventional three-dimensional conformal radiotherapy （3DCRT） in the radiotherapy of rectal cancer. Methods： Fifteen patients with rectal cancer treated with radio- therapy （RT） were retrospectively analyzed. Among the patients, seven received RT preoperatively and 8 postoperatively. The target volume and the OARs such as the small bowel, bladder and femoral heads were contoured for each patient. 3DCRT-plan and IMRT-plan were performed for each patient respectively, with the prescribed dose covering at least 95% of the planning target volume （PTV）. The conformity index （CI） and homogeneity index （HI） were used for evaluation of the dose distribution in the target volume, and the Dx% （the lowest dose to the x% volume of the OARs that received the highest dose of irradiation） and the mean dose were used for evaluation of the dose to OARs. Paired-T test was used for companson of the difference between the two plans. Results： In the IMRT-plan and 3DCRT-plan, the CI were 0.94 and 0.87 （P = 0.000） and the HI were 1.13 and 1.17, respectively （P = 0.001）. For small bowel, the D30%, D50% and the mean dose were 19.67 Gy, 15.13 Gy and 18.81 Gy in the IMRT-plan and 25.20 Gy, 22.20 Gy and 22.89 Gy in the 3DCRT-plan, respectively （P 〈 0.001 for all pairs of parameters）. For bladder, the D30%, D50%, and the mean dose were 24.80 Gy, 34.20 Gy and 28.70 Gy in the IMRT- plan, and 35.07 Gy, 44.67 Gy and 35.68 Gy in the 3DCRT-plan, respectively （P 〈 0.001 for all pairs of parameters）. For femoral heads, the D5% in the IMRT-plan and 3DCRT-plan were 40.6 Gy and 40.47 Gy, respectively （P = 0.936）, and the mean dose were 30.14 Gy and 25.57 Gy, respectively （P = 0.001）. Conclusion： Five-field IMRT-plan is better than 3DCRT-plan in the conformity and the dose homogeneity within target volume and also better in sparing the small bowel and bladder.

Dosimetric analysis of tomotherapy-based intensity-modulated radiotherapy with and without bone marrow sparing for the treatment of cervical cancer

Objective The aim of the study was to compare tomotherapy-based bone marrow-sparing intensity-mod- ulated radiotherapy （BMS-IMRT） with intensity-modulated radiotherapy （IMRT） without entering the pelvic bone marrow as a planning constraint in the treatment of cervical cancer after hysterectomy. Methods BMS-IMRT and IMRT plans were designed for a cohort of nine patients. The prescribed dose was 45 Gy in 1.8 Gy daily fractions, and 95% of the planned target volume received this dose. The doses were computed using a commercially available treatment planning system with the convolution/superposition algorithm. Plans were compared according to dose-volume histogram analysis in terms of planning target volume homogeneity and conformity indices （HI and CI） as well as organ at risk dose and volume parameters. Results BMS-IMRT had advantages over IMRT in terms of CI, but was equivalent to the latter in H1. V5, V10, V20, V30, and V40 of pelvic bone marrow in BMS-IMRT decreased by 0.06%, 17.33%, 22.19%, 13.85%, and 16.46%, respectively, compared with IMRT. Except for V30 of the small bowel and V30 and V40 of the bladder, no statistically significant differences were found between BMS-IMRT and IMRT in the small bowel, bladder, and rectum. Conclusion For cervical cancer patients receiving tomotherapy-based radiotherapy after hysterectomy, BMS-IMRT reduced pelvic bone marrow volume receiving low-dose radiation, and it may be conducive to preventing acute hematologic toxicity.

Comparison of efficacy between two boost treatments in residual tumor of nasopharyngeal carcinoma after radical radiotherapy

Objective： To compare the efficacy between stereotactic radiotherapy （SRT） and intracavitary brachytherapy （brachytherapy） in residual tumor of nasopharyngeal carcinoma （NPC） after treating with conventional external beam radiotherapy. Methods： 60 patients with residual tumor of NPC after radical external beam radiotherapy （range 68 to 72 Gy） were randomized into SRT group （27 patients） and brachytherapy group （33 patients）. Patients in SRT group received boost treatment of 10-20 Gy, 2-3 fractions, once every other day; patients in brachytherapy group were treated with boost 10-20 Gy, 5 Gy per fraction, twice a week. Results： Efficacy in the near future： in SRT group, the complete recession （CR）, partial recession （PR） and no change （NC） rates were 77.8% （21/27）, 18.5% （5/27）, 3.7% （1/27）, respectively and the efficacy rate was 96.3% （CR ＋ PR）; in brachytherapy group： the CR, PR and NC rates were 75.8% （25/33）, 18.2% （6/33）, 6.1% （2/33）, respectively and the efficacy rate was 93.9% （CR ＋ PR）. The efficacy rates of the above two groups were compared （x^2 = 0.032, P 〉 0.05）. Long term efficacy： in SRT group, 1-year and 3-year survival rates were 96.3%, 66.5% respectively and the median live time was 48 months; in brachytherapy group： 1-year and 3-year survival rates were 93.9%, 60.2% respectively and the median live time was 46 months. The survival rates of two groups were compared （x^2 = 0.172, P 〉 0.05）. Conclusion： Both boost techniques of SRT and brachytherapy had elevated efficacy in patients with residual tumor of NPC and there was no obvious difference between the efficacy of the near and long term in SRT and brachytherapy group.

Three-Dimensional Conformal and Intensity Modulated Dynamic Radiotherapy in Juvenile Nasopharyngeal Angiofibroma

Objective: Juvenile Nasopharyngeal Angiofibroma (JNA) is a benign neoplasm with a high vascularity component, greater craniofacial involvement in adolescent patients, and aggressive local behaviour. In unresectable patients, radiotherapy is a therapeutic option for local control. Our aim in this study was to analyze the clinical benefit and local control provided by two modalities of radiotherapy: the Three-Dimensional Conformal (3DC) technique and volumetric modulated arc therapy (VMAT), applied to pediatric patients with JNA considered unresectable and non-recurrent. Methods: In retrospective study, the information was recorded from pediatric patients with a diagnosis of non-recurrent and unresectable JNA treated with radiotherapy at the Oncology Hospital of the National Medical Center SXXI of Mexico City, from March 2010 to March 2021. Radiotherapy management and its association with clinical outcomes of tumour control, and symptoms were assessed. In addition, an evaluation of acute and chronic toxicity was performed. Results: It was found that the median age was 14 years. 9 patients (37.5%) underwent 3DC and 15 (62.5%) VMAT. In terms of local control, and progression-free survival, we did not find significant difference between radiotherapy modalities (p ≤ 0.57). Acute toxicity for both modalities presented statistical differences for radio epithelitis (p = 0.03). Only Grade I and II radiation-induced acute toxicity was observed. Regarding chronic toxicity, statistical significance was observed for craniofacial hypoplasia, in relation to its absence in the VMAT group (p = 0.001). Conclusion: The VMAT presents improvements in dosimetry parameters that improve patient toxicity. In both techniques adequate tumour control was observed, however, the rarity of the disease is a limitation to establish the most appropriate therapeutic technique.

Technical and Dosimetric Study of Four Facio-cervical Fields Conformal Radiotherapy for Nasopharyngeal Carcinoma

Objective： The aim of this study is to establish the methods of four facio-cervical fields＇ conformal radiotherapy （4F-CRT） for nasopharyngeal carcinoma （NPC）, and to optimize the methods for clinical practice. Methods and Materials： 40 patients with untreated NPC of T1-T4 （1997AJCC Staging System） were rolled into this study. Conventional and four ratio-cervical fields conform plans were designed for each patient using Pinnacle 8.0 three-dimension treatment planning system （3D-TPS）： 1） Improved plan, four ratio-cervical fields＇conform plans, anterior, posterior ratio-cervical and 2 lateral opposing facio-eervical fields; 2） Conventional plan, two lateral opposing facio-cervical fields only with the same dose delivered to the target in each plan, close volume histograms （DVHs） of the targets and normal organs, brain stem, spinal cord, parotid glands, and temporal mandibular joints （TMJs） were compared and the dose distribution were evaluated. Results： 1） The dose distribution of the improved plan could meet the requirements for the target volume. 2） There was not any significant difference in the dose of spinal cord between the two plans. The mean doses of Dmax for brain stem in conventional plan were much lower than those in the improved plan, though both were within safety limits. 3） Compared with the conventional plans, the improved plan significantly decreased the hotspot areas in the target volume and had better parotid glands and temporal mandibular joints sparing effect. Conclusion： Compared with the conventional plan, the improved plan provides satisfactory dose coverage to the tumor volume and better sparing of the parotid gland, TMJs and other normal tissues in external beam radiotherapy of NPC.

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.

THREE-DIMENSIONAL CONFORMAL RADIATION THERAPY FOR LOCALLY RECURRENT NASOPHARYNGEAL CARCINOMA

Objective: To investigate the safety and effectiveness of three-dimensional conformal radiation therapy (3-D CRT) for locally recurrent nasopharyngeal carcinoma (NPC). Methods: From April 1998 to March 2000, 34 patients who had undergone previous external beam radiation therapy were retreated with 3-D CRT for locally recurrent NPC (33 poorly differentiated squamous cell carcinomas, 1 adenoma). The patients were re-staged according to Huaqing staging system with the following distribution: T1N0M0 in 5 cases, T2N0M0 in 11 cases, T3N0M0 in 12 cases, T4N0M0 in 6 cases. The maximal dimension of the gross tumor volume (GTV) ranged from 1.0 cm to 5.0 cm (median: 2.9 cm). CT simulation and 3-D planning were used to ensure full and conformal coverage of the planning target volume (PTV) by treated volume, while minimizing the absorbed dose of the adjacent normal tissue. 5–7 static conformal coplanar or noncoplanar portals were delivered for each fraction irradiation. The total dose delivered ranged from 65–70 Gy, with 2.5 Gy per fractionation, one fractionation per day, 5 days a week. Median follow-up time from 3-D CRT was 25 months (range: 12–36 months). Results: Over the follow-up period, local recurrence was observed in 3 patients, regional failure in 3, distant metastasis in 3, and six patients died; 88.2% (30/34) of the patient maintained local control, 82.4% (28/34) survived, and 76.5% (26/34) survived with no evidence of tumor. Acute complications were minor and few. The overall incidence of late complication was 20.6% (7/34), and severe complication was 14.7% (5/34), after re-irradiation with 3-D CRT. Conclusion: 3-D CRT is safety and effectiveness for most of the patients with locally recurrent NPC. Our preliminary results indicate a high local control rate and a low complication rate. The long-term curative effect and sequelae await further study.

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.

Minimally invasive surgery alone compared with intensity-modulated radiotherapy for primary stage I nasopharyngeal carcinoma

Background:The National Comprehensive Cancer Network guidelines recommend intensity-modulated radiotherapy(IMRT)as the primary curative treatment for newly diagnosed nasopharyngeal carcinoma(NPC),but the radiation-related complications and relatively high medical costs remain a consequential burden for the patients.Endoscopic nasopharyngectomy(ENPG)was successfully applied in recurrent NPC with radiation free and relatively low medical costs.In this study,we examined whether ENPG could be an effective treatment for localized stage I NPC.Methods:Ten newly diagnosed localized stage I NPC patients voluntarily received ENPG alone from June 2007 to September 2017 in Sun Yat-sen University Cancer Center.Simultaneously,the data of 329 stage I NPC patients treated with IMRT were collected and used as a reference cohort.The survival outcomes,quality of life(QOL),and medical costs between two groups were compared.Results:After a median follow-up of 59.0 months(95%CI 53.4-64.6),no death,locoregional recurrence,or distant metastasis was observed in the 10 patients treated with ENPG.The 5-year overall survival,local relapse-free survival,regional relapse-free survival,and distant metastasis-free survival among the ENPG-treated patients was similar to that among the IMRT-treated patients(100%vs.99.1%,100%vs.97.7%,100%vs.99.0%,100%vs.97.4%,respectively,P>0.05).In addition,compared with IMRT,ENPG was associated with decreased total medical costs($4090.42±1502.65 vs.$12620.88±4242.65,P<0.001)and improved QOL scores including dry mouth(3.3±10.5 vs.34.4±25.8,P<0.001)and sticky saliva(3.3±10.5 vs.32.6±23.3,P<0.001).Conclusions:ENPG alone was associated with promising long-term survival outcomes,low medical costs,and satisfactory QOL and might therefore be an alternative strategy for treating newly diagnosed localized stage I NPC patients who refused radiotherapy.However,the application of ENPG should be prudent,and prospective clinical tri-als were needed to further verify the results.

鼻咽癌放化疗治疗患者外周血PD-1及免疫指标水平的变化及其临床意义

目的探讨鼻咽癌放化疗治疗患者外周血程序性死亡受体1(PD-1)及免疫指标水平的变化及其临床意义。方法回顾性选取2020年1月至2023年江苏省肿瘤医院收治的90例鼻咽癌患者,所有患者均经病理确诊并接受放化疗治疗,采集其血液样本之后采用流式细胞术对不同时间段(治疗前、新辅助化疗后、放疗后)外周血淋巴细胞亚群比例、外周血PD-1、CD8^(+)CD28^(+)细胞比例的水平变化予以动态监测并比较。结果鼻咽癌患者新辅助化疗后CD3^(+)、CD4^(+)细胞比例、CD4^(+)/CD8^(+)比值分别为(72.28±8.37)%、(39.27±8.58)%、1.58±0.67,均明显高于治疗前,CD3-CD16^(+)CD56^(+)、CD19^(+)细胞比例分别为(18.27±8.38)%、(7.87±4.08)%,均明显低于治疗前,差异均有统计学意义(P<0.05);新辅助化疗后与治疗前的CD8^(+)细胞比例比较,差异无统计学意义(P>0.05)。鼻咽癌患者新辅助化疗之后CD8^(+)CD28^(+)细胞比例为(10.68±3.87)%,明显高于治疗前,差异有统计学意义(P<0.05);新辅助化疗后与治疗前的外周血PD-1水平比较,差异无统计学意义(P>0.05)。放疗后与治疗前的CD3^(+)细胞比例比较,差异无统计学意义(P>0.05);鼻咽癌患者放疗后CD4^(+)细胞比例、CD4^(+)/CD8^(+)比值、CD19^(+)细胞比例分别为(26.68±6.09)%、0.88±0.29、(3.69±2.36)%,均明显低于治疗前,CD8^(+)、CD3-CD16^(+)CD56^(+)细胞比例分别为(31.03±8.08)%、(27.39±10.26)%,均明显高于治疗前,差异均有统计学意义(P<0.05)。鼻咽癌患者放疗后CD8^(+)CD28^(+)细胞比例为(7.08±2.57)%,明显低于治疗前,外周血PD-1水平为(13.38±6.27)%,明显高于治疗前,差异均有统计学意义(P<0.05)。结论新辅助化疗之后鼻咽癌患者外周血T细胞亚群比值处于持续上调趋势,而放疗完成后处于下降趋势,表明鼻咽癌患者于放疗完成后免疫功能受损;放疗完成后鼻咽癌患者T细胞PD-1表达水平明显上调,提示PD-1抑制剂最佳使用时间可能为放化疗完成时,抗PD-1维持治疗可发挥持久、高效的抗肿瘤作用。

长链非编码RNA-ROR介导上皮-间质转化对鼻咽癌细胞放疗抵抗作用的体外研究

目的 探讨lncRNA-ROR介导上皮-间质转化在鼻咽癌细胞放疗抵抗中的作用。方法 将鼻咽癌细胞CNE2分为空白组、阴性对照组、lncRNA-ROR沉默组,进行相应的处理。将CNE2细胞分为空白组、放疗组、放疗+阴性对照组、放疗+lncRNA-ROR过表达组(放疗处理为6 Gy射线照射24 h),进行相应的处理。用CCK-8法检测CNE2增殖能力,通过细胞划痕实验和Transwell 细胞迁移实验检测细胞迁移能力,用流式细胞术检测细胞凋亡的情况,用蛋白印迹法检测凋亡相关蛋白和上皮-间质转化相关蛋白的表达。结果 与空白组、阴性对照组相比,抑制lncRNA-ROR表达48、72 h后鼻咽癌细胞CNE2的增殖能力均减弱(均P<0.05)。抑制lncRNA-ROR表达后鼻咽癌细胞CNE2的迁移率低于阴性对照组(P<0.05),而放疗+lncRNA-ROR过表达组CNE2细胞的迁移能力高于放疗组与放疗+阴性对照组(均P<0.05)。与放疗组、放疗+阴性对照组相比,放疗+lncRNA-ROR过表达组CNE2细胞的凋亡率均降低(均P<0.05)。抑制lncRNA-ROR后,活化的caspase 3、caspase 9蛋白表达均较空白组和阴性对照组升高(均P<0.05);而放疗+lncRNA-ROR过表达组活化的caspase 3、caspase 9蛋白表达均较放疗组和放疗+阴性对照组下降(均P<0.05)。抑制lncRNA-ROR可导致上皮标志蛋白(E-钙黏蛋白、β-联蛋白)表达升高,间质标志蛋白(N-钙黏蛋白、波形蛋白)表达下降(均P<0.05);而与放疗组和放疗+阴性对照组相比,放疗+lncRNA-ROR过表达组CNE2细胞的上皮标志蛋白表达下降、间质标志蛋白表达升高(均P<0.05)。结论 lncRNA-ROR可通过调控鼻咽癌细胞增殖、迁移、凋亡及上皮-间质转化影响其放疗抵抗,是逆转鼻咽癌细胞放疗抵抗的潜在靶点。