Simultaneous Integrated Boost Intensity Modulated Radiotherapy In Nasal NK/T-cell Lymphoma And Study Of ¹⁸F-FDG PET/CT For Aids The Stage And Response Assessment

Part One Value of Radiotherapy in Early Stage Extranodal NK/T-cellLymphomaObjective:The aim of this study was to analyze the value of radiotherapy in early stage extranodal NK/T-cell lymphoma and the clinical characteristics,treatment,survival and their prognostic factors for the all patients.Methods:A total of 99 patients with pathologically confirmed extranodal NK/T cell lymphoma in the Fourth Hospital of Hebei Medical University from January 2010 to December 2015.Mean age was 45.5years（range,6-76 years）;male:female ratio was 2.1:1.Of all patients,56（56.6%）patients had B symptoms.Seven patients received radiotherapy alone,29 patients received chemotherapy alone,and 63 patients received concurrent chemoradiotherapy.Median radiation dose was 52Gy（34-60）.There were 73 patients with L-asparaginase or pegaspargase and 19 not.Median chemotherapy were 6cycles（1-12 cycles）.Results:1.The median overall survival（OS）was 59.9 months for all patients.The median local control（LC）was 73.5 months.The 1-,2-and 5-year OS was76.8%,68.8%and 61.4%,respectively.The 1-,2-and 5-year LC was 84.5%,81.6%and 78.3%,respectively.2.The patients who received radiotherapy alone and concurrent chemoradiotherapy had significantly longer survival than those who received chemotherapy alone.The 5-year OS was 66.0%and 47.3%（χ²=4.782,P=0.029）,respectively.The 5-year LC was 85.8%and 58.7%（χ²=5.949,P=0.015）,respectively.3.The patients with primary tumor invasion（PTI）or not,the 5-year OS was 71.5%and 55.5%（χ²=4.950,P=0.026）,the 5-year LC was 81.5%and72.0%（χ²=0.983,P=0.321）.4.The patients with Ann Arbor stage I and II,the 5-year OS was 68.9%and 35.7%（χ²=11.329,P=0.001）.the 5-year LC was 81.5%and 47.9%（χ²=4.425,P=0.035）.5.The complete response（CR）was observed in 62.6%.The 5-year OS was 84.1%in patients with CR and 27.6%in no-CR（χ²=31.566,P=0.000）,The 5-year LC was 92.2%and 52.4%（χ²=18.417,P=0.000）.6.Multivariate Cox-regression analysis for OS showed that Ann Arbor stage and lactate dehydrogenase（LDH）were independent prognostic factors.The LDH was independent prognostic factor for LC.7.The nomogram-revised risk index（NRI）model is validated as a robust useful tool to identify various discrete risk patients with different outcomes.The 5-year OS was 74.9%,67.0%,42.3%and 33.3%in the low,intermediate-low,intermediate-high,high groups（χ²=14.668,P=0.002）.Summaries:Most patients with early stage extranodal NK/T cell lymphoma who received radiotherapy alone and chemoradiotherapy had significantly favorable prognosis than those who received chemotherapy alone.The patients with primary tumor invasion had poor prognosis and the CR of treatment had favorable prognosis.Multivariate Cox-regression analysis for OS showed that Ann Arbor stage and LDH were independent prognostic factors.The LDH was an independent prognostic factor for LC.The NRI significantly improved prognostication with respect to the capability of discrimination and the effectiveness of clinical decision-making,and was particularly useful in early-stage patients.Part Two The Preliminary Outcome with Simultaneous IntegratedBoost Intensity Modulated Radiotherapy in Confined Nasal Extranodal NK/T-cell LymphomaObjective:The study aimed to retrospectively analyze the prognosis of patients with stage IE nasal natural killer/T-cell lymphoma（ENKTL）with dose reduction to clinical target volume（CTV）by using simultaneous integrated boost intensity-modulated radiotherapy（SIB-IMRT）.Methods:The data of patients with the newly diagnosed stage IE nasal ENKTL treated with radiotherapy alone or combination chemoradiotherapy in the Fourth Hospital of Hebei Medical University from January 2011 to June2016 were reviewed retrospectively.A total of 44 patients with pathologically confirmed nasal natural killer/T-cell lymphoma were reviewed retrospectively.The prescribed dose was 45Gy/25 fractions for extended involved-field site and 50-55Gy/25 fractions for primary tumor site by using SIB-IMRT Mean age was 43.5years（range,21-71 years）;male:female ratio was 1.8:1.Of all patients,22（50%）patients had B symptoms,4 patients received radiotherapy alone,and 40 patients received concurrent chemoradiotherapy.There were 36patients with L-asparaginase or pegaspargase.Median chemotherapy were 6cycles（2-8 cycles）.Results:1.The median follow-up time for the 44 patients was 64 months（range,12-107 months）.The median OS,1-year,5-year,and 8-year OS rates were 72months,95.5%,81.2%,and 81.2%,respectively.The median PFS,1-year,5-year,and 8-year PFS rates were 68 months,88.6%,78.8%,and 78.8%,respectively.And the median LC time,1-year,5-year,and 8-year LC rates were 65 months,95.5%,93.0%,and 93.0%,respectively.2.The response was evaluated at the end of whole treatment.The complete response（CR）and non-CR were observed in 37 patients and 7patients,respectively.The 5-year OS rates were 88.5%in CR patients and42.9%in non-CR patients（P=0.005;HR=0.133,95%confidence interval0.033-0.534）.And the 5-year PFS rates were 85.6%in CR patients and 42.9%in non-CR patients（P=0.007;HR=0.165,95%confidence interval0.044-0.617）.3.Non-hematologic toxicities related to radiation included mucositis,dermatitis and dry nose cavity and usually were grade 1 or 2.There was only one patient with grade 3 mucositis.Hematologic toxicities including leukopenia,neutropenia,anemia and thrombocytopenia occurred in 2 patients.No treatment was interrupted duo to severe adverse events during the radiotherapy,and no radiation-related deaths occurred.No severe late toxicities were observed in all patients.4.Six patients experienced treatment failure during the follow-up period.The median failure time was 10 months（range,6-45months）after treatment.Three patients with chemoradiotherapy developed local recurrence which all occurred in the 50-55Gy volume.Two patients had local failure in the pre-chemotherapy tumor location and one patient had local failure in the marginal region of pre-chemotherapy tumor location.No patient developed regional failure.Three patient developed systemic failures.There were 6.8%（3/44）,0 and 6.8%（3/44）respectively with local failure,regional failure and systemic failures.Summaries:The study showed that appropriate dose reduction to CTV was feasible and conferred a promising outcome in stage IE nasal ENKTL.The protocol of 50Gy to GTV and 45Gy to CTV in 25 fractions could be well realized concurrently by SIB-IMRT and was well tolerated.Part Three Study of¹⁸F-FDG PET/CT for aids the stage andresponse assessmentObjective:The aim of this study was to explore the relationship between pretreatment PET/CT for aids the stage,the interim and the end of treatment¹⁸F-FDG PET/CT parameters for response assessment.Methods:The data of extranodal nasal-type NK/T cell lymphoma patients in the Fourth Hospital of Hebei Medical University from January2014 to May 2021 were reviewed retrospectively.Pretreatment ¹⁸F-FDG PET/CT scans of the 39 patients had been obtained before treatment.The interim and the end of treatment ¹⁸F-FDG PET/CT scans of the 58 patients had been obtained for the assess treatment effectiveness.Of the 43 patients with the interim of treatment and 15 patients with the end of treatment ¹⁸F-FDG PET/CT scans had the complete metabolism parameters.Results:1.Pretreatment PET/CT scans of the 39 patients had been obtained were reviewed retrospectively.We evaluated the role of ¹⁸F-FDG PET/CT for determining disease staging by comparing its results to those of conventional staging methods in patients with nasal-type NK/T-cell lymphoma.Of the 11patients（11/39）for whom there was a discrepancy between the stage findings of their ¹⁸F-FDG PET/CT scans and conventional staging methods.The remain 28 patients had the same stage findings.¹⁸F-FDG PET/CT scans detected more anatomic regions with malignant tumors than did the conventional staging methods and upstaged for 11 patients.The results of the¹⁸F-FDG PET/CT scans affected treatment planning in 4 patients,because of an increase in the initial stage from stage I/II to IV.2.Pretreatment maximum standardized uptake values（SUVmax）of ¹⁸F FDG PET/CT were recorded.Receiver operating curve（ROC）analysis was used to determine the accuracy of the ideal cut-off value for distinguishing the high SUVmax group from the low SUVmax group.The estimated area under the ROC curve of SUVmax was 0.693（P=0.041）.Various SUVmax cut-off values were used to obtain a reasonable balance of sensitivity and specificity.A value of 9.6 provided sensitivity of 0.824 and specificity of 0.682.The patients were separated into two SUVmax groups such as low（<9.6）and high SUVmax groups（≥9.6）.the low SUVmax group was higher survival compared to those in the high SUVmax group（3-year PFS,73.5%vs.25.7%,P=0.001;3-year OS,67.5%vs.19.8%,P=0.001）.3.The interim of treatment deauville scale（DS）of ¹⁸F-FDG PET/CT were recorded.43 patients had been obtained for the assess treatment effectiveness.The DS 1-3（29 patients）group was higher survival compared to those in the high DS 4-5（14 patients）group（3-year PFS,72.6%vs.28.6%,P=0.000;3-year OS,74.8%vs.29.7%,P=0.053）.15 patients had been obtained for the assess treatment effectiveness in the end of treatment using¹⁸F-FDG PET/CT.The DS 1-3（13 patients）group was higher survival compared to those in the high DS 4-5（2 patients）group（3-year PFS,60.9%vs.0,P=0.062;3-year OS,65.5%vs.0,P=0.009）.4.Of the 43 patients with the interim of treatment ¹⁸F-FDG PET/CT scans had the complete metabolism parameters.4.1 When ORR was used as the endpoint of the study:The SUVmin,SUVmax,SUVmean SUVstd,TLG and MTV were significant difference of effective group（31 patients）and ineffective group（12 patients）.the threshold values of SUVmax,TLG,and MTV were 3.324,12.001 and 5.580cm³,respectively.4.2 When PFS was used as the endpoint of the study:The SUVmax,TLG and MTV were significant difference of progression group（17 patients）and progression-free group（26 patients）.the threshold values of SUVmax,TLG,and MTV were 3.980,12.001 and5.580cm³,respectively.The 3-year PFS rates in the SUVmax<3.980 and SUVmax≥3.980 groups were 70.8%and 36.8%,respectively（χ²=8.128,P=0.004）.The 3-year PFS rates in the TLG<12.001 and TLG≥12.001 groups were 77.9%and 22.1%,respectively（χ²=17.027,P=0.000）.The 3-year PFS rates in the MTV<5.580cm³and MTV≥5.580cm³groups were 75.7%and20.8%,respectively（χ²=16.117,P=0.000）.4.3 When OS was used as the endpoint of the study:The SUVmax,TLG and MTV were not significant difference of dead group（11 patients）and survival group（32 patients）.5.Of the 15 patients with the end of treatment ¹⁸F-FDG PET/CT scans had the complete metabolism parameters.5.1 When PFS was used as the endpoint of the study:The SUVmax,TLG and MTV were not significant difference of progression group（6 patients）and progression-free group（9 patients）.5.2 When OS was used as the endpoint of the study:The TLG and MTV were significant difference of dead group（5 patients）and survival group（10patients）.the threshold values of TLG and MTV were 7.336 and 4.640cm³,respectively.The 3-year OS rate in the TLG<7.336 and TLG≥7.336 groups were 100%and 31.3%,respectively（χ²=3.713,P=0.054）.The 3-year OS rate in the MTV<4.640cm³and MTV≥4.640cm³groups were 80.0%and 25.0%,respectively（χ²=4.767,P=0.029）.Summaries:1.The utility of ¹⁸F-FDG PET/CT could be used as an accurate valuable diagnostic and staging tool for extranodal nasal-type NK/T-cell lymphoma.2.Receiver operating curve of ¹⁸F-FDG PET/CT pretreatment analyses indicated that an SUVmax of 9.6 was the ideal cut-off to distinguish PFS between low and high SUVmax groups.3.The interim and end of treatment ¹⁸F-FDG PET/CT based on DS were significant predictors of PFS and OS.The DS 1-3 had a favorable prognosis compared to the DS 4-5.4.The interim of treatment ¹⁸F-FDG PET/CT metabolism parameters SUVmax,TLG and MTV were predictor factors of ORR,PFS,but not OS.5.The end of treatment ¹⁸F-FDG PET/CT metabolism parameters TLG and MTV were predictor factors of OS.