Hypofractionated and intensity-modulated radiotherapy combined with systemic therapy in metastatic hepatocellular carcinoma:A case report

BACKGROUND Liver cancer treatment is characterized by multidisciplinary participation and coexistence of multiple treatment methods.Hypofractionated and intensity-modulated radiotherapy is a new precise radiotherapy technique applied to the treatment of systemic malignant tumors.There is a lack of understanding of hypofractionated and intensity-modulated radiotherapy combined with systemic therapy in metastatic hepatocellular carcinoma(HCC).CASE SUMMARY We report a case of metastatic HCC treated with hypofractionated and intensity-modulated radiotherapy combined with systemic therapy.A 41-year-old man was diagnosed with metastatic HCC(T3N1M1 stage IVB).Because it was found to be in the late stage of cancer and had already metastasized,it was impossible to undergo surgical treatment.In addition to aggressive comprehensive treatment for the primary lesion,local treatment for metastatic cancer can improve the patient's survival potential.Hypofractionated and intensity-modulated radiotherapy can provide a larger single treatment dose within a shorter overall treatment time,and improve the local control rate of the tumor.Follow-up examination demonstrated that the tumor and metastatic lesions had shrunk after therapy.The treatment has showed good efficacy.The patient survived for 18 months without disease progression and stable disease persisted for>38 months.CONCLUSION Targeted therapy and immunotherapy followed by hypofractionated and intensity-modulated radiotherapy are also effective for advanced metastatic HCC.

Simultaneous integrated dose reduction intensity-modulated radiotherapy effectively reduces cardiac toxicity in limited-stage small cell lung cancer

Objective:To assess the clinical outcomes and toxicities of once daily(QD)simultaneous dose reduction intensity-modulated radiotherapy(SDR-IMRT-QD;SDR-QD)versus conventional QD IMRT(C-QD)and twice daily(BID)IMRT in patients with limited-stage small cell lung cancer(LS-SCLC).Methods:After propensity score matching(PSM),a retrospective analysis involving 300 patients with LS-SCLC treated using SDR-QD,C-QD,or BID was performed from January 1,2014 to December 31,2019.The prescribed irradiation dose in the SDR-QD cohort was 60 Gy/PGTV and 54 Gy/PTV QD.The radiation dose was 60 Gy for both PGTV and PTV QD in the C-QD cohort.The radiation dose was 45 Gy for both PGTV and PTV in the BID cohort.Toxicities,short-term effects,and survival outcomes were recorded.A meta-analysis on the protective effects of pharmaceuticals for cardiac toxicities induced by anti-tumor therapy was performed.Results:The median overall survival time(MST)in the 3 cohorts were 32.7 months(SDR-QD),26.3 months(C-QD),and 33.6 months(BID);the differences between groups were statistically significant.Lower toxicities and doses to organs-at-risk(OARs)occurred in the SDR-QD and BID cohorts.Further,the cardiac dose dosimetric parameter Vheart40 was negatively associated with survival(r=-0.35,P=0.007).A Vheart40 value of 16.5%was recommended as a cut-off point,which yielded 54.7%sensitivity and 85.7%specificity for predicting negative survival outcomes.The meta-analysis indicated that pharmaceuticals significantly reduced the cardiac toxicities induced by chemotherapy,but not radiotherapy.Conclusions:SDR-QD was shown to have similar toxicities and survival compared with BID,but fewer toxicities and better survival than C-QD.In addition,cardiac dose exposure was negatively associated with survival.Thus,16.5%of the cardiac dosimetric parameter Vheart40 is recommended as the cut-off point,and a Vheart40>16.5%predicts poor survival.

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 consequences of tumor volume changes after kilovoltage cone-beam computed tomography for non-operative lung cancer during adaptive intensity-modulated radiotherapy or fractionated stereotactic radiotherapy

Objective The aim of this study was to investigate tumor volume changes with kilovoltage cone-beam computed tomography （kV-CBCT） and their dosimetric consequences for non-operative lung cancer during intensity-modulated radiotherapy （IMRT） or fractionated stereotactic radiotherapy. Methods Eighteen patients with non-operative lung cancer who received IMRT consisting of 1.8-2.2 Gy/fraction and five fractions per week or stereotactic radiotherapy with 5-8 Gy/fraction and three fractions a week were studied, kV-CBCT was performed once per week during IMRT and at every fraction during stereotactic radiotherapy. The gross tumor volume （GTV） was contoured on the kV-CBCT images, and adaptive treatment plans were created using merged kV-CBCT and primary planning computed tomogra- phy image sets. Tumor volume changes and dosimetric parameters, including the minimum dose to 95% （D95） or 1% （D1） of the planning target volume （PTV）, mean lung dose （MLD）, and volume of lung tissue that received more than 5 （Vs）, 10 （Vl0）, 20 （V20）, and 30 （V30） Gy were retrospectively analyzed. Results The average maximum change in GTV observed during IMRT or fractionated stereotactic radio- therapy was -25.85% （range, -13.09% --56.76%）. The D95 and Dr of PTV for the adaptive treatment plans in all patients were not significantly different from those for the initial or former adaptive treatment plans. In patients with tumor volume changes of 〉20% in the third or fourth week of treatment during IMRT, adap- tive treatment plans offered clinically meaningful decreases in MLD and V5, V10, V20, and V30; however, in patients with tumor volume changes of 〈 20% in the third or fourth week of treatment as well as in patients with stereotactic radiotherapy, there were no significant or clinically meaningful decreases in the dosimetric parameters. Conclusion Adaptive treatment planning for decreasing tumor volume during IMRT may be beneficial for patients who experience tumor volume changes of 〉20% in the third or fourth week of treatment.

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.

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.

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.

Bone marrow-sparing intensity-modulated radiotherapy for postoperative treatment of cervical cancer

Objective： The aim of this study was to compare bone marrow-sparing intensity-modulated radiotherapy （IMRT） with IMRT without entering pelvic bone marrow as a planning constraint in the treatment of cervical cancer after hysterectomy. Methods： For a cohort of 10 patients, bone marrow-sparing IMRT and routine IMRT planning were designed. The prescribed dose was 45 Gy/1.8 Gy/25f, 95% of the planning target volume received this dose. Doses were computed with a commercially available treatment planning system （TPS） using convolution/superimposition （CS） algorithm. Plans were compared according to dose-volume histogram （DVH） analysis in terms of planning target volume （PTV） homogeneity and conformity indices （HI and CI） as well as organs at risk （OARs） dose and volume parameters. Results： Bone marrow-sparing IMRT had an vantages over routine IMRT in terms of CI, but inferior to the latter for HI. Compared with routine IMRT, V5, Vl0, V20, V30, V40 of pelvic bone marrow of bone marrow-sparing IMRT reduced by 1.81%, 8.61%, 31.81%, 29.50%, 28.29%, respectively. No statistically significant differences were observed between bone marrow-sparing IMRT and routine IMRT in terms of small bowel, bladder and rectum. Conclusion： For patients with cervical cancer after hysterectomy, bone marrowsparing IMRT reduced the pelvic bone marrow volume irradiated at all dose levels and might be conducive to preventing the occurrence of acute bone marrow toxicity.

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.

Observation of Intensity-Modulated Radiotherapy with Different Fractionated Doses Used in 58 Cases with Astrocytoma

OBJECTIVE To analyze the therapeutic effects and side effects of intensity-modulated radiotherapy （IMRT） with different fractionated doses in treating astrocytoma.METHODS During a period from October 2001 to December 2006, 58 patients with astrocytoma were treated using IMRT. Based on the World Health Organization （WHO） classification, 32 of the 58 cases were grade-Ⅱ, 20 grade-Ⅲ and 6 grade-IV （glioblastoma multiforme, GBM）. Thirty-two of the 58 patients （3 with grade IV, 11 with grade Ⅲ, and the other 18 with grade II who were over 40 years） were treated with hyperfractionated IMRT （Hyper Fr IMRT）, and the other 26 patients were treated with standard fractionated IMRT （St Fr IMRT）.RESULTS The 1-, 3- and 5-year overall survival （OS） rates were respectively 86%, 52%, and 45%, and the 1-, 3- and 5-year progression-free survival （PFS） rates were respectively 77%, 38%, and 25%. Using an analytical hierarchy process it was shown that concerning the patients with grade II astrocytoma classified based on WHO grading, the therapeutic effect was much better in the group of Hyper Fr IMRT than in the St Fr IMRT group. There was no statistical significance of the differences in the OS and PFS rates between the 2 groups （P = 0.049 and P = 0.006）. The OS and PFS rates of the patients with grade-III astrocytoma were both higher in the group with Hyper Fr IMRT than in the St Fr IMRT group. However, there was no statistical significance of the differences between the 2 groups. Advanced RTOG grade-Ⅲ（radiation therapy oncology group, RTOG） neurotoxicity occurred only in 1 of the cases.CONCLUSION Compared with the St Fr IMRT, the Hyper Fr IMRT may help to prolong the survival of patients with astrocytoma.

The Effect of Treatment Position on Rectal and Bladder Dose-Volume Histograms for Prostate Radiotherapy Planned with 3-Dimensional Conformal Radiotherapy, Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy

Purpose: To compare target coverage and organ at risk (OAR) sparing in the supine and prone positions with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) in low- and high-risk prostate radiotherapy cases. Materials and Methods: Using magnetic resonance images of five healthy volunteers, six treatment plans (supine 3DCRT, prone 3DCRT, supine IMRT, prone IMRT, supine VMAT and prone VMAT) were generated. Planning target volume 1 (PTV1) was defined as the prostate gland plus the seminal vesicles with adequate margins in a high-risk setting, while PTV2 was defined as prostate only with margins in a low-risk setting. The mean dose for both PTV1 and PTV2 was set at 78 Gy. Plans generated by each of the 3 techniques were compared between the supine and prone positions using dose-volume histograms (DVHs). Results: For PTV1, prone 3DCRT provided a significantly higher D98% than did supine 3DCRT, and its homogeneity index (HI) was significantly better. IMRT and VMAT values did not differ significantly between the prone and supine positions. For PTV2, no values differed significantly between the supine and prone positions under any treatment plan. With respect to OAR, the rectal D mean, D2%, V50, and V60 values of PTV1 were statistically higher in supine 3DCRT than in prone 3DCRT, while there were no significant differences in rectal values between the supine and prone positions with IMRT or VMAT. The rectal Dmean, V50, V60, V70, and V75 values of prone 3DCRT were significantly higher than those of supine IMRT or supine VMAT. There were no significant differences in any values for the rectum and bladder for PTV2. Conclusion: Although prone 3DCRT was found to be superior to supine 3DCRT in terms of rectal sparing in high-risk prostate cancer, IMRT and VMAT techniques could possibly cover this disadvantage.

Effect of intensity-modulated radiotherapy combined with local hyperthermia on Mortalin expression in advanced liver cancer lesions and its relationship with cell proliferation and EMT

Objective:To investigate the effect of intensity-modulated radiotherapy combined with local hyperthermia on Mortalin expression in advanced liver cancer lesions and its relationship with cell proliferation and EMT.Methods: A total of 82 patients with advanced liver cancer who were treated in this hospital between February 2016 and September 2017 were chosen as the research subjects, and the therapeutic regimens were reviewed and used to divide these patients into the control group (n=43) who received intensity-modulated radiotherapy and the combined treatment group (n=39) who received intensity-modulated radiotherapy combined with local hyperthermia. Abdominal puncture was done after treatment to obtain liver cancer tissue samples, and the differences in Mortalin gene, cell proliferation gene and EMT gene expression in tissues were compared.Results: After treatment, Mortalin mRNA expression in liver cancer tissues of combined treatment group was lower than that of control group;Fbxw7 mRNA expression in liver cancer tissues was higher than that of control group whereas NCX1, PRMT5 and XBP1S mRNA expression were lower than those of control group;Twist, ZEB-1, ZEB-2, Snail and HOXB7 mRNA expression in liver cancer tissues were lower than those of control group. Pearson test showed that the Mortalin gene expression in liver cancer tissues was directly correlated with cell proliferation genes and EMT genes.Conclusion:Intensity-modulated radiotherapy combined with local hyperthermia can effectively reduce Mortalin gene expression, and further optimize patients'condition by inhibiting hepatic cell proliferation, EMT activity and other pathways.

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.

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.

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.

The impact of artificial intelligence-assisted intensity-modulated radiotherapy plan optimization on the radiation doses received by the rectum and bladder as well as radiation-induced injuries in patients with locally advanced cervical cancer

This study aimed to investigate the impact of artificial intelligence-assisted intensity-modulated radiotherapy(IMRT)plan optimization on the radiation doses received by the rectum and bladder as well as radiation-induced injuries in patients with locally advanced cervical cancer.A total of 100 patients with locally advanced cervical cancer were enrolled and divided into a conventional IMRT group and an artificial intelligence-assisted IMRT group.The results showed that in terms of the radiation doses to the rectum and bladder,all dosimetric parameters(such as mean dose,maximum dose,and volume-dose parameters,etc.)in the artificial intelligence-assisted group were significantly lower than those in the conventional group(p<0.05).Regarding radiation-induced injuries,the incidences and severities of both acute and late radiation-induced proctitis and cystitis in the artificial intelligence-assisted group were lower than those in the conventional group(p<0.05).These findings suggest that artificial intelligence-assisted IMRT plan optimization can effectively reduce the radiation doses to the rectum and bladder and decrease radiation-induced injuries in patients with locally advanced cervical cancer,which is expected to provide a more precise and safer treatment strategy for radiotherapy of locally advanced cervical cancer.However,this study has limitations such as a limited sample size and being a single-center study.Future research with multi-center,large-sample,and more in-depth investigations is needed.