Outcomes And Prognostic Factors Of Hypofractionated Radiotherapy In Treatment Of Organ Metastases

Part ⅠOutcomes and prognostic factors of hypofractionated radiotherapy in treatment of organ metastasesPurpose:This retrospective study was conducted to analyze the clinical results,prognostic factors of hypofractionated radiotherapy in the treatment of organ metastases,and construct the prognostic model.Materials and Methods:Organ metastatic patients treated by hypofractionated radiotherapy in our hospital were analyzed,including lung,liver and adrenal metastases.Based on different site of metastases,suitable positioning method and radiation technology were applied.Target was delineated according to two imaging examinations.Radiation dose was delivered according to site of lesions and actual dose distributions.Kaplan-Meier method was used to calculate treated-metastases control(TMC),local recurrence-free survival(LRFS),progression-free survival(PFS)and overall survival(OS).Long-rank test and Cox model were used to perform univariate and multivariate analysis,respectively.A statistically significant difference was considered when p<0.05.Results:262 organ metastatic patients treated by hypofractionated radiotherapy in our hospital were enrolled.Median age was 58 years,and median KPS was 80.The primary tumor included lung cancer(95 patients,pts),colorectal cancer(55 pts),head and neck cancer(31 pts),and breast cancer(31 pts).1-y,2-y,3-y,4-y and 5-y LRFS was 95.3%,90.5%,89.1%,87.9%and 87.9%,respectively.Median survival time was 35.5 months,1-y,2-y,3-y,4-y and 5-y OS was 87.7%,67.4%,48.0%,40.6%and 35.2%,respectively.Median PFS was 9.7 months,1-y,2-y,3-y,4-y and 5-y PFS was 45.5%,26.8%,21.3%,15.0%and 15.0%,respectively.BED10≥100 Gy was a significant factor for TMC(p=0.041).Uncontrolled primary and new extracranial metastases were significant factors for LRFS.Disease-free interval from primary tumor to distant metastases(DFI),radiation frequency to extracranial metastases,metastases to lung-only,uncontrolled primary,new extracranial metastases and intracranial metastases were factors for OS.While metastases to lung-only,uncontrolled primary,new extracranial metastases and intracranial metastases were factors for PFS.Group with 0-1 factors had better OS and PFS than ≥2 factors.Conclusions:Hypofractionated radiotherapy in the treatment of organ metastases had satisfying TMC,LRFS,PFS and OS.Patients with≥2 factors had worse clinical outcome.Part ⅡOutcomes of hypofractionated radiotherapy in treatment of lung,liver and adrenal metastasesPurpose:Based on results from part I,patients with different organ metastases had different clinical outcomes.This retrospective study was conducted to analyze the clinical results of hypofractionated radiotherapy in the treatment of lung,liver and adrenal metastases,respectively,and provide detailed data about localizing,target and dose regimens.Materials and Methods:Lung,liver and adrenal metastatic patients treated by hypofractionated radiotherapy in our hospital were analyzed.(1)lung:Internal target volume(ITV)was delineated on 4-dimensional CT simulation images with or without PET-CT scan,and expanded by 3 mm to create planning target volume(PTV).Dose regimens included 60 Gy in 8 to 15 fractions.(2)Liver:GTV(gross tumor volume)was delineated on enhanced CT scan with or without MRI scan,and expanded to generate PTV.Dose regimens included 45 Gy in 3 fractions,and 60 Gy in 10 to 15 fractions.(3)adrenal:ITV was delineated on 4-dimensional CT simulation images with or without PET-CT scan,and expanded by 3 mm to create PTV.Dose regimens included 60 Gy in 12 to 20 fractions.Image guided radiotherapy was applied for accuracy daily.Kaplan-Meier method was used to calculate local recurrence-free survival(LRFS),progression-free survival(PFS)and overall survival(OS).Results:(1)193 patients with 317 lung metastases were enrolled.Median volume of GTV and PTV was 5.0 cm3(0.2-142.3 cm3)and 12.0 cm3(1.0-200.0 cm3),respectively.Median dose of PTV and BED was 60 Gy(45-70 Gy)and 96 Gy(60-150 Gy),respectively.1-year LRFS was 95.7%.1-y,3-y OS and PFS were 90.1%,60.8%and 54.3%,30.3%,respectively.(2)45 patients with 52 liver metastases were enrolled.Median volume of GTV and PTV was 10.1 cm3(0.3-175.2 cm3)and 29.8 cm3(5.0-209.6 cm3),respectively.Median dose of PTV and BED was 60 Gy(40-60 Gy)and 90 Gy(60-132 Gy),respectively.1-year LRFS was 94.0%.1-y and 3-y OS were 91.1%and 17.0%,1-y PFS was 26.7%.(3)35 patients with 42 adrenal metastases were enrolled.Median volume of GTV and PTV was 23.2 cm3(3.5-97.8 cm3)and 38.3 cm3(10.2-135.6 cm3),respectively.Median dose of PTV and BED was 60 Gy(40-66.3 Gy)and 84 Gy(56-110 Gy),respectively.1-year LRFS was 92.7%.1-y,3-y OS and PFS were 76.9%,26.5%and 25.1%,14.4%,respectively.Radiation dose to normal organs were acceptable,and no sever adverse events or treatment-related death were observed.Conclusions:Hypofractionated radiotherapy in the treatment of lung,liver and adrenal metastases had satisfying clinical results,without sever toxicities or treatment-related death,and could be applied in clinical practice safely.Part ⅢPrognostic value of different metastatic spectrum in metastatic patients treated by hypofractionated radiotherapyPurpose:Based on the diversity of metastatic spectrum in this cohort study,the aim of this part was to explore the prognostic value of different metastatic spectrum in metastatic patients treated by hypofractionated radiotherapy.This factor was put into previous prognostic model in part Ⅰ to readjust and reassess prognostic factors.Materials and Methods:According to different metastatic spectrum,patients were divided into four groups.(1)De-novo oligo-metastases:metastases were diagnosed with primary cancer at the same time,involved 1-3 organs,1-5 metastatic lesions.(2)Oligo-recurrence:new metastases to distant orans after radical treatment to the primary cancer,involved 1-3 organs,1-5 metastatic lesions.(3)Oligo-progression:after systemic therapy,most lesions were well-controlled,with the remained 1-5 uncontrolled lesions.(4)poly-metastases:poly-metastatic patients,not satisfied with three metastatic spectrum above.Kaplan-Meier method was used to calculate progression-free survival(PFS)and overall survival(OS).Long-rank test and Cox model were used to perform univariate and multivariate analysis,respectively.A statistically significant difference was considered when p<0.05.Results:Patients in the de-novo oligo-metastases,oligo-recurrence,oligo-progression,and poly-metastases group were 19 patients(pts),110 pts,97 pts and 36 pts,respectively.Median survival time were 41.0 months,77.9 months,28.5 months and 12.8 months,respectively.Median PFS were 6.9 months,19.3 months,6.3 months and 3.5 months,respectively.Patients in the poly-metastatic group had significant worst OS and PFS compared with other three groups.Patients in oligo-recurrence group had better outcomes than oligo-progression group.There was no significant difference between oligo-recurrence group with de-novo oligo-metastatic group.In subgroup analysis of lung cancer,breast cancer,colorectal cancer and head and neck cancer,metastatic spectrum was still significant factor for OS and PFS,regardless of primary tumor type.The differences in four metastatic spectrums were not affected by other prognostic factors for OS and PFS,metastatic spectrum was kept in the prognostic model.Conclusions:Patients in the de-novo oligo-metastases,oligo-recurrence,oligo-progression,and poly-metastases group had significant different clinical outcomes after hypofractionated radiotherapy.De-novo oligo-metastases and oligo-recurrence had best prognosis,followed by oligo-progression.Poly-metastases group had worst results.Metastatic spectrum was significant factor when putting into Cox model.The classification of four metastatic spectrum can be applied in the selection of patients,treatment strategies and prognostic evaluation.Part Ⅳ Failure patterns after hypofractionated radiotherapy in treatment of organ metastasesPurpose:This study was conducted to analyze failure patterns after hypofractionated radiotherapy in treatment of organ metastases,treatment methods and treatment results after failureMaterials and Methods:Patients were enrolled with clear failure pattern,including local failure in the treated lesions,progression of primary cancer,new extracranial metastases and intracranial progression.Patients without any progression and patients with unknown failure were removed.Time and site of failure,treatment strategies including systemic therapies such as chemotherapy,target therapy and immunotherapy and local treatment such as surgery,radiofrequency ablation therapy and radiotherapy,were all recorded.The primary end point was survival time after failure,defined as time from first failure after hypofractionated radiotherapy to death or end of follow-up.Kaplan-Meier method was used to calculate survival time after failure.Long-rank test and Cox model were used to perform univariate and multivariate analysis,respectively.A statistically significant difference was considered when p<0.05.Results:215 patients with clear failure patterns were enrolled finally.Number of patients with failure was 30,53,50,27,19 and 36,in the first 1 year,1-2 year,2-3 year,3-4 year,4-5 year and 5 years later.134 patients(pts)(61.9%)failed in the first 3 year after hypofractionated radiotherapy,while 179 pts(83.3%)failed in the first 5 year.Failure patterns included new extracranial metastases(194 pts),intracranial progression(53 pts),progression of primary cancer(39 pts)and local failure in the treated lesions(23 pts).Median time to new extracranial metastases was 12.6 months.Radiotherapy after failure could improve survival time from 15.8 months to 27.1 months(p=0.006).8 pts received immunotherapy after failure,but the survival time had no significant differences compared with no immunotherapy group.There were no significant correlations between chemotherapy,target therapy,surgery or radiofrequency ablation therapy with survival time after failure.Conclusions:New extracranial metastasis was the most common failure pattern after hypofractionated radiotherapy,followed by intracranial progression.Radiotherapy after failure could improve survival time after failure.Further larger sample studies were needed to explore the role of immunotherapy,chemotherapy,target therapy and other treatment strategies.