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.

Prognostic scoring system for locoregional control among the patients with nasopharyngeal carcinoma treated by intensity-modulated radiotherapy

The prognostic value of T category for locoregional control in patients with nasopharyngeal carcinoma(NPC)has decreased with the extensive use of intensity-modulated radiotherapy(IMRT).We aimed to develop a prognostic scoring system(PSS)that incorporated tumor extension and clinical characteristics for locoregional control in NPC patients treated with IMRT.The magnetic resonance imaging scans and medical records of 717 patients with nonmetastatic NPC treated with IMRT at Sun Yat-sen University Cancer Center between January 2003 and January 2008 were reviewed.Age,pathologic classification,primary tumor extension,primary gross tumor volume(GTV-p),T and N categories,and baseline lactate dehydrogenase(LDH)level were analyzed.Hierarchical cluster analysis as well as univariate and multivariate analyses were used to develop the PSS.Independent prognostic factors for locoregional relapse included N2–3 stage,GTV-p≥26.8 mL,and involvement of one or more structures within cluster3.We calculated a risk score derived from the regression coefficient of each factor and classified patients into four groups:low risk(score 0),intermediate risk(score>0 and≤1),high risk(score>1 and≤2),and extremely high risk(score>2).The 5-year locoregional control rates for these groups were 97.4%,93.6%,85.2%,and 78.6%,respectively(P<0.001).We have developed a PSS that can help identify NPC patients who are at high risk for locoregional relapse and can guide individualized treatments for NPC patients.

Neoadjuvant chemotherapy plus intensity-modulated radiotherapy versus concurrent chemoradiotherapy plus adjuvant chemotherapy for the treatment of locoregionally advanced nasopharyngeal carcinoma:a retrospective controlled study

Background:In the era of intensity-modulated radiotherapy(IMRT),the role of neoadjuvant chemotherapy(NAC)for locoregionally advanced nasopharyngeal carcinoma(NPC)is under-evaluated.The aim of this study was to compare the efficacy of NAC plus IMRT and concurrent chemoradiotherapy(CCRT)plus adjuvant chemotherapy(AC)on locoregionally advanced NPC.Methods:Between January 2004 and December 2008,240 cases of locoregionally advanced NPC confirmed by pathologic assessment in Sun Yat-sen University Cancer Center were reviewed.Of the 240 patients,117 received NAC followed by IMRT,and 123 were treated with CCRT plus AC.The NAC+IMRT group received a regimen that included cisplatin and 5-fluorouracil(5-FU).The CCRT+AC group received cisplatin concurrently with radiotherapy,and subsequently received adjuvant cisplatin and 5-FU.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.Results:The 5-year overall survival(OS),locoregional relapse-free survival(LRRFS),distant metastasis-free survival(DMFS),and disease-free survival(DFS)were 78.0,87.9,79.0,and 69.8%,respectively,for the NAC+IMRT group and78.7,84.8,76.2,and 65.6%,respectively,for the CCRT+AC group.There were no significant differences in survival between the two groups.In multivariate analysis,age(<50 years vs.>50 years)and overall stage(Ⅲvs.Ⅳ)were found to be independent predictors for OS and DFS;furthermore,the overall stage was a significant prognostic factor for DMFS.Compared with the CCRT+AC protocol,the NAC+IMRT protocol significantly reduced the occurrence rates of grade 3-4 nausea-vomiting(6.5 vs.1.5%,P=0.023)and leukopenia(9.7 vs.0.8%,P=0.006).Conclusions:The treatment outcomes of the NAC+IMRT and CCRT+AC groups were similar.Distant metastasis remained the predominant mode of treatment failure.

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.

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.

Intensified intensity-modulated radiotherapy in anal cancer with prevalent HPV p16 positivity

AIM: To investigate the toxicity and response of intensity-modulated radiotherapy schedule intensified with a simultaneous integrated boost in anal canal cancer.METHODS: From March 2009 to March 2014, we retrospectively analyzed 41 consecutive patients treated with intensity-modulated radiotherapy(IMRT) and concurrent chemotherapy for anal canal squamous cell carcinoma at our center. Radiotherapy was delivered via simultaneous integrated boost(SIB) technique by helical tomotherapy, and doses were adapted to two clinical target volumes according to the tumor-nodemetastasis(TNM) stage: 50.6 Gy and 41.4 Gy in 23 fractions in T1N0, 52.8 Gy and 43.2 Gy in 24 fractionsin T2N0, and 55 Gy and 45 Gy in 25 fractions in all patients with N positive and/or ≥ T3, respectively, to planning target volumes 1 and 2. The most common chemotherapy regimen was 5-fluorouracil and mitomycin-based. Human papilloma virus(HPV) p16 expression was performed by immunohistochemistry and evaluated in the majority of patients. Acute and late toxicity was scored according to CTCAe v 3.0 and RTOG scales.RESULTS: The median follow-up was 30 mo(range:12-71). Median age was 63 years(range 32-84). The stage of disease was: stage Ⅰ in 2 patients, stage Ⅱin 13 patients, stage ⅢA in 12 patients, and stage ⅢB in 14 patients, respectively. Two patients were known to be HIV positive(4.9%). HPV p16 expression status was positive in 29/34(85.3%) patients. The 4-year progression-free survival and overall survival in HPVpositive patients were 78% and 92%, respectively.Acute grade 3 skin and gastrointestinal toxicities were reported in 5% and 7.3% of patients, respectively;patients' compliance to the treatment was good due to a low occurrence of severe acute toxicity, although treatment interruptions due to toxicity were required in 7.3% of patients. At 6 mo from end of treatment,36/40(90%) patients obtained complete response;during follow-up, 5(13.8%) patients presented with disease progression(local or systemic).CONCLUSION: In our experience, intensified SIBIMRT with chemotherapy is very feasible in clinical practice, with excellent results in terms of overall survival and local control.

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.

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.

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.

Comparison of Dosiology between Three Dimensional Conformal and Intensity-modulated Radiotherapies (5 and 7 fields) in Gastric Cancer Post-surgery

The purpose of this study was to compare the dose distribution of intensity-modulated ra- diotherapy （IMRT） in 7 and 5 fields as well as 3-D conformal radiotherapy （3D-CRT） plans for gastric cancer using dosimetric analysis. In 15 patients with gastric cancer after D1 resection, dosimetric pa- rameters for IMRT （7 and 5 fields） and 3D-CRT were calculated with a total dose of 45 Gy （1.8 Gy/day） These parameters included the conformal index （CI）, homogeneity index （HI）, maximum dose spot for the planned target volume （PTV）, dose-volume histogram （DVH） and dose distribution in the organs at risk （OAR）, mean dose （Dmean）, maximal dose （Dmax） in the spinal cord, percentage of the normal liver volume receiving more than 30 Gy （V30） and percentage of the normal kidney volume receiving more than 20 Gy （V20）. IMRT （7 and 5 fields） and 3D-CRT achieved the PTV coverage. However, IMRT presented significantly higher CI and HI values and lower maximum dose spot distribution than 3D-CRT （P=0.001）. For dose distribution of OAR, IMRT had a significantly lower Dmean and Dmax in spinal cord than 3D-CRT （P=-0.009）. There was no obvious difference in V30 of liver and V20 of kidney between IMRT and 3D-CRT, but 5-field IMRT showed lower Dmean in the normal liver than other two plans （P=0.001）. IMRT revealed favorable tumor coverage as compared to 3D-CRT and IMRT plans. Specifically, 5-field IMRT plan was superior to 3D-CRT in protecting the spinal cord and liver, but this superiority was not observed in the kidney. Further studies are needed to compare differences among the three approaches.

Dosimetric study comparing intensity modulated and conformal pelvic radiotherapy boost plans in locally advanced cancer cervix in NCI-Cairo

Objective:This study was to compare 5 field conformal technique to the intensity modulated radiotherapy (IMRT) 8 fields technique in boosting locally advanced cancer cervix cases after external beam radiotherapy with respect to target volume coverage and dose to normal tissues. Methods:We conducted a single institutional comparative dosimetric analysis of 10 patients with cancer cervix who was presented to radiotherapy department in National Cancer Institute, Cairo in period between June 2012 to September 2012 and received a CRT boost in the place of planned brachytherapy after large field pelvic radiotherapy (PRT) with concurrent chemotherapy were retrospectively identified. All tumors were situated in the low central pelvis. Two plans were done for every patient; one using the 8 fields IMRT and the second one using 5 fields' 3DCRT the two techniques were then compared using dose volume histogram (DVH) analysis for the PTV, bladder, rectum and both femoral heads. Results:Comparing different DVHs, it was found that the planning target volume (PTV) was adequately covered in both plans while it was demonstrates that the 8 fields IMRT technique carried less doses reaching OARs (rectum, bladder, both femoral heads). Conclusion:From the present study, it is concluded that IMRT technique spared more efficiently OARs than CRT technique but both techniques covered the PTV adequately so whenever possible IMRT technique should be used.

The impact of intensity modulated radiotherapy on the skin dose for deep seated tumors

Objective: The purpose of this study was to investigate the impact of intensity modulated radiotherapy (IMRT) on surface doses for brain, abdomen and pelvis deep located tumors treated with 6 MV photon and to evaluate the skin dose calculation accuracy of the XIO 4.04 treatment planning system. Methods: More investigations for the influences of IMRT on skin doses would increase its applications for many treatment sites. Measuring skin doses in real treatment situations would reduce the uncertainty of skin dose prediction. In this work a pediatric human phantom was covered by a layer of 1 mm bolus at three treatment sites and thermoluminescent dosimeter (TLD) chips were inserted into the bolus at each treatment site before CT scan. Two different treatment plans [three-dimensional conformal radiation therapy (3DCRT) and IMRT] for each treatment sites were performed on XIO 4.04 treatment planning system using superposition algorism. Results: The results showed that the surface doses for 3DCRT were higher than the surface doses in IMRT by 1.6%, 2.5% and 3.2% for brain, abdomen and pelvis sites respectively. There was good agreement between measured and calculated surface doses, where the calculated surface dose was 15.5% for brain tumor calculated with 3DCRT whereas the measured surface dose was 12.1%. For abdomen site the calculated surface dose for IMRT treatment plan was 16.5% whereas the measured surface dose was 12.6%. Conclusion: The skin dose in IMRT for deep seated tumors is lower than that in 3DCRT which is another advantage for the IMRT. The TLD readings showed that the difference between the calculated and measured point dose is negligible. The superposition calculation algorism of the XIO 4.04 treatment planning system modeled the superficial dose well.

Intensity-modulated Radiotherapy for Sinonasal Teratocarcinosarcoma

Surgical excision and postoperative radiotherapy are widely accepted therapeutic modalities for sinonasal teratocarcinosarcoma （SNTCS）. Previous studies have shown that intensity-modulated radiation therapy （IMRT） is safe and effective for the treatment of some sinonasal malignancies. We hypothesize that use of IMRT for SNTCS may result in clinical benefits. We report here two cases of SNTCS that were treated by IMRT. One patient was given extensive IMRT involving elective neck irradiation. Follow-up examinations revealed no recurrence and metastasis 3.5 years after IMRT. Another patient simultaneously suffered from multiple systematical diseases and was administered involved-field radiotherapy. He was found to have a marginal recurrence during the follow up and eventually died 8 months after disease diagnosis. It was suggested in this study that appropriate use of IMRT for the treatment of SNTCS may achieve excellent local control.

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.

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.

Dosimetric Improvements Utilising Intensity Modulated Radiation Therapy for Patients with Glioblastoma Multiforme

Aims: The EORTC-NCI study investigating the addition of temozolomide trial to standard radiation therapy has demonstrated improved duration of survival in patients with Glioblastoma multiforme (GBM). With longer survival duration, there is the potential for latent RT morbidity, not previously seen in historical patients. This study evaluates the potential dosimetric advantages of utilising IMRT over 3D-conformal RT in such patients. Methods: 10 consecutive patients with GBM formally screened for a clinical study over a two-month period were planned and treated with IMRT utilising daily on-board imaging (OBI). The EORTC protocol dosimetric criteria and constraints were used in target delineation and planning. For each patient, a 3DCRT plan was also produced. Endpoints for dosimetric evaluation analysed related to tumour dose: mean PTV60 dose (mPTV60Dose), Conformity Index (CI);and normal tissue dose: mean normal brain dose (mBrainDose) and V40 Brain (Brainv40). IGRT endpoints were the median isocentre shifts required in 3 axes measured in one direction. The variation between the IMRT and 3DCRT dosimetric endpoints was examined using Wilcoxon analysis. Results: The 10 patients had tumours located in temporal (3), parietal (3), occipital (2) and callosal (2) regions. The median PTV and normal brain volumes were 308.1 cm3 and 1077.5 cm3 respectively. The IMRT dosimetry was significantly improved in all endpoints specifically CI (p = 0.002), mPTV60Dose (p = 0.004), mBrainDose (p = 0.002) and Brainv40 (p = 0.019). OBI directed isocentre measurements in the patient group were available for 230 treatments. The median shifts (and 95% C.I.s) were 0.1 cm vertical (0.1 - 0.2), 0.1 cm longitudinal (0.1 - 0.2) and 0.2 cm lateral (0.2 - 0.2). At a minimum follow-up of 2 years’ post diagnosis, the median survival of the group is 18.0 months (95% CI: 13.4 - 22.6 months). Conclusion: IMRT for GBM produces significant dosimetric advantages in relation to planning target volume and normal tissue dose compared with 3D conformal plans. The data also confirm the accuracy of IMRT technique for CNS with IGRT delivery utilising OBI demonstrating minimal deviation from planned to treated isocentre.

Intensity modulated radiation therapy with simultaneous integrated boost based dose escalation on neoadjuvant chemoradiation therapy for locally advanced distal esophageal adenocarcinoma

AIM:To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost(IMRT-SIB).METHODS:We retrospectively reviewed the patients who underwent four-dimensional-based IMRT-SIBbased neoadjuvant chemoradiation protocol.During the concurrent chemoradiation therapy,radiation therapy was through IMRT-SIB delivered in 28 consecutive daily fractions with total radiation doses of 56 Gy to tumor and 5040 Gy dose-painted to clinical tumor volume,with a regimen at the discretion of the treating medical oncologist.This was followed by surgical tumor resection.We analyzed pathological completion response(p CR) rates its relationship with overall survival and event-freesurvival.RESULTS:Seventeen patients underwent dose escalation with the IMRT-SIB protocol between 2007 and 2014 and their records were available for analysis.Among the IMRT-SIB-treated patients,the toxicity appeared mild,the most common side effects were grade 1-3 esophagitis(46%) and pneumonitis(11.7%).There were no cardiac events.The Ro resection rate was 94%(n = 16),the p CR rate was 47%(n = 8),and the postoperative morbidity was zero.There was one mediastinal failure found,one patient had local failure at the anastomosis site,and the majority of failures were distant in the lung or bone.The 3-year diseasefree survival and overall survival rates were 41%(n = 7) and 53%(n = 9),respectively.CONCLUSION:The dose escalation through IMRT-SIB in the chemoradiation regimen seems responsible for down-staging the distal esophageal with well-tolerated complications.

Leakage-Penumbra effect in intensity modulated radiation therapy step-and-shoot dose delivery

AIM: To study the leakage-penumbra(LP) effect with a proposed correction method for the step-and-shoot intensity modulated radiation therapy(IMRT).METHODS: Leakage-penumbra dose profiles from 10 randomly selected prostate IMRT plans were studied. The IMRT plans were delivered by a Varian 21 EX linear accelerator equipped with a 120-leaf multileaf collimator(MLC). For each treatment plan created by the Pinnacle3 treatment planning system,a 3-dimensional LP dose distribution generated by 5 coplanar photon beams,starting from 0o with equal separation of 72 o,was investigated. For each photon beam used in the stepand-shoot IMRT plans,the first beam segment was set to have the largest area in the MLC leaf-sequencing,and was equal to the planning target volume(PTV). The overshoot effect(OSE) and the segment positional errors were measured using a solid water phantom with Kodak(TL and X-OMAT V) radiographic films. Film dosimetric analysis and calibration were carried out using a film scanner(Vidar VXR-16). The LP dose profiles were determined by eliminating the OSE and segment positional errors with specific individual irradiations. RESULTS: A non-uniformly distributed leaf LP dose ranging from 3% to 5% of the beam dose was measured in clinical IMRT beams. An overdose at the gap between neighboring segments,represented as dose peaks of up to 10% of the total BP,was measured. The LP effect increased the dose to the PTV and surrounding critical tissues. In addition,the effectdepends on the number of beams and segments for each beam. Segment positional error was less than the maximum tolerance of 1 mm under a dose rate of 600 monitor units per minute in the treatment plans. The OSE varying with the dose rate was observed in all photon beams,and the effect increased from 1 to 1.3 Gy per treatment of the rectal intersection. As the dosimetric impacts from the LP effect and OSE may increase the rectal post-radiation effects,a correction of LP was proposed and demonstrated for the central beam profile for one of the planned beams. CONCLUSION: We concluded that the measured dosimetric impact of the LP dose inaccuracy from photon beam segment in step-and-shoot IMRT can be corrected.

Dose Perturbations of Gold Fiducial Markers in the Prostate Cancer Intensity Modulated Proton Radiation Therapy (IMPT)

The objective of this study is to investigate the dose perturbations introduced by the implanted gold fiducial markers in the prostate cancer intensity modulated proton therapy (IMPT) and the impacts of different plan designs on the pertur-bations. Five proton plans: a single lateral field 3D-modulation (3D-mod) plan, 2 fields laterally opposing 3D-mod plan, 6-, 9-, and 18-field distal edge tracking (DET) plans were designed on the CT images of a prostate patient. The dose distributions were first generated for the plans free of fiducial markers with 78 Gy prescribed to 95% of the PTV. To derive the dose perturbations of the gold fiducial markers, three cylindrical shaped gold fiducial markers (3 mm long and 1 mm in diameter) were artificially inserted into the prostate, and the dose distributions were re-computed. Monte Carlo method was used for dose computation. It was found that the gold fiducial markers perturbed the dose distribu-tions, especially along the beam paths. The markers caused a shadowing effect reducing the doses in the areas beyond the markers. Overall, due to the presence of the fiducial markers, D99% of prostate were reduced by 2.96 Gy, 4.21 Gy, 0.16 Gy, 0.34 Gy, 0.15 Gy for the plans of single field 3D-mod, 2-field parallel opposed 3D-mod, 6-, 9-, and 18-field DET respectively. Our study showed these dose perturbation effects decreased with the increase of number of beam angles. Up to 6 beam angles may be required to reduce the dose perturbations from the gold fiducial markers to a clini- cally acceptable level in IMPT.