1.Factors influencing of lymphopenia in prostate cancer patients during radiotherapy
Yifei LI ; Xianshu GAO ; Hongzhen LI ; Shangbin QIN ; Xin QI ; Mingwei MA ; Yun BAI ; Xueying REN ; Jiayan CHEN ; Feng LYU ; Xiaoying LI
Chinese Journal of Radiation Oncology 2025;34(4):347-354
Objective:To analyze the incidence and influencing factors of lymphopenia in prostate cancer patients undergoing pelvic radiotherapy.Methods:A retrospective analysis was conducted on 123 prostate cancer patients treated at the Department of Radiation Oncology, Peking University First Hospital, from November 2011 to May 2015. Radiotherapy was administered using conventional fractionated intensity-modulated radiotherapy. Blood routine, including absolute lymphocyte count (ALC), was performed on patients before radiotherapy, weekly during radiotherapy, and at the end of radiotherapy. Severe lymphopenia was defined as an ALC <500 cells/μl. Based on whether the minimum ALC during radiotherapy was lower than 500 cells/μl, the entire cohort and 55 patients (excluding those with undelineated pelvic bone marrow due to radiotherapy planning system issues) with delineated pelvic bone marrow (divided into pelvic bone marrow, iliac bone marrow, and lower pelvic bone marrow) were stratified into a severe lymphopenia group (33 cases and 16 cases, respectively) and a mild lymphopenia group (90 cases and 39 cases, respectively). Differences in clinical factors and dosimetric parameters were compared between the groups using the chi-square test (or Fisher's exact test), t-test, and Wilcoxon rank-sum test. Univariate and multivariate logistic regression analyses were performed to identify the clinical and dosimetric factors influencing severe lymphopenia. Results:All 123 prostate cancer patients experienced lymphopenia during radiotherapy, with a median minimum ALC of 0.6×10 9/L [range: (0.2-2.3)×10 9/L]. Severe lymphopenia occurred in 26.8% (33 cases) of patients. Univariate analysis of the entire cohort showed that pre-radiotherapy baseline ALC, initial neutrophil-to-lymphocyte ratio, prostate-specific antigen value, Gleason score, and pelvic radiotherapy were promoting factors for severe lymphopenia ( P<0.05). Multivariate analysis identified pre-radiotherapy baseline ALC ( OR=0.217, 95% CI: 0.072-0.650, P=0.006) and pelvic radiotherapy ( OR=23.852, 95% CI: 2.834-200.787, P=0.004) as promoting factors for severe lymphopenia. In patients with delineated pelvic bone marrow, univariate analysis showed that pelvic bone marrow V 30 Gy and V 40 Gy, iliac bone marrow V 30 Gy and V 40 Gy, lower pelvic bone marrow V 30 Gy and V 40 Gy were promoting factors for severe lymphopenia during treatment ( P<0.05). Conclusions:Lymphopenia is common in prostate cancer patients undergoing radiotherapy, with a high incidence of severe lymphopenia. Pre-radiotherapy baseline ALC, as well as pelvic, iliac, and lower pelvic bone marrow V 30 Gy and V 40 Gy, are promoting factors for severe lymphopenia during radiotherapy.
2.Efficacy and safety analysis of reduced-field postoperative radiotherapy of upper tract urothelial carcinoma
Xiaoying LI ; Xianshu GAO ; Hongzhen LI ; Shangbin QIN ; Xin QI ; Mingwei MA ; Yun BAI ; Tian CHENG ; Zheng ZHANG ; Qi TANG ; Zihao TAO ; Chunru XU ; Xuesong LI
Chinese Journal of Radiation Oncology 2025;34(12):1215-1222
Objective:To compare the efficacy and safety of extended-field versus reduced-field radiotherapy in upper tract urothelial carcinoma (UTUC) patients after radical operation.Methods:A retrospective analysis was conducted on the data of 210 UTUC patients who underwent full-length nephrectomy and received postoperative adjuvant radiotherapy in Peking University First Hospital from January 2013 to November 2023, and follow-up continued until June 2024. According to the target area of postoperative radiotherapy, patients were divided into the extended-field radiotherapy group (127 cases) and the reduced-field radiotherapy group (83 cases). The overall survival (OS), distant metastasis free survival (DMFS), local recurrence free survival (LRFS) and adverse reactions were compared. In the same period, 114 patients with recurrent abdominal and pelvic lymph nodes who did not receive adjuvant therapy after surgery for UTUC in our center were prospectively collected, and the coverage of the reduced-field target area was analyzed. Chi square test was used to compare the clinical characteristics, Kaplan-Meier method was used to analyze survival outcomes, log-rank test was used to compare the survival rate, and Cox multivariate regression analysis was performed on the influencing factors of survival.Results:The median follow-up was 24.5 (range: 3-74) months. There were no significant differences between the extended-field and reduced-field radiotherapy groups in terms of 2-year LRFS (93.3% vs. 98.1%, P=0.156), 2-year DMFS (84.8% vs. 91.2%, P=0.176), and 2-year OS (90.4% vs. 90.7%, P=0.707). The most common toxicities of adjuvant radiotherapy were nausea and leukopenia, with significantly higher grade 1-2 incidence in the extended-field group compared to the reduced-field group ( P<0.05). According to the analysis of patients with retroperitoneal lymph node recurrence after surgery, the reduced-field target designed according to the location of the primary tumor can cover more than 90% of the postoperative metastatic lymph node area Multivariate analysis revealed that variant histology ( HR=2.180,95% CI: 1.021-4.658, P=0.044) was an independent predictor of worse DMFS, while variant histology ( HR=3.825,95% CI: 1.514-9.662, P=0.005) and T 3-4 stage ( HR=4.452,95% CI: 1.025-19.339, P=0.046) were independent predictors of poorer OS. Conclusions:Compared with extended-field radiotherapy, reduced-field radiotherapy designed based on primary tumor location significantly reduced treatment-related toxicities without compromising postoperative therapeutic efficacy, and the reduced-field can cover more than 90% of local recurrent lesions.
3.Impact of Postoperative Reduction Quality on Biomechanics of the Femoral Head Following Internal Fixation of Femoral Neck Fractures
Shixiong ZHANG ; Jianxiong MA ; Bin LU ; Ying WANG ; Aixian TIAN ; Lei SUN ; Zhe HAN ; Jiahui CHEN ; Jing DAI ; Haohao BAI ; Hongzhen JIN ; Jie ZHAO ; Pengfei LI ; Xinlong MA
Journal of Medical Biomechanics 2025;40(5):1144-1149
Objective To investigate the effect of postoperative reduction quality in femoral neck fracture internal fixation on mechanical properties of the femoral head from the perspective of trabecular bone biomechanics.Methods From patients who underwent hip replacement surgery for femoral neck fractures,a total of 26 femoral head slice specimens were obtained.The central axis of the primary compressive trabeculae was defined as the 0° group,with the intersection point of the primary compressive trabeculae and the femoral calcar serving as the center.By rotating the specimens to simulate different reduction angles,the cut femoral head slice specimens were randomly divided into five groups:-10°,-5°,0°,5°,and 10°,representing femoral heads with varying reduction qualities.The specimens were subjected to single compression load tests and fatigue load tests.The load was set from 70 N to 1 400 N,at a frequency of 1 Hz,with 10 000 cycles.Axial stiffness,displacement,and the number of collapse cycles were measured,to compare the biomechanical properties of femoral head specimens under different reduction qualities.Results There were differences in the axial stiffness,displacement,and number of collapse cycles among the femoral head specimens in different groups.Under 800 N load,the axial stiffness of 0° group was significantly greater than that of±10° groups(P<0.05).The axial stiffness of 0° group was also greater than that of the±5° groups,but the differences were not statistically significant(P>0.05).The axial stiffness of±5° groups was greater than that of±10° groups(P<0.05).0° group had a lower displacement than±5° groups and±10° groups.However,the differences in displacement between 0° group and±5° groups were not statistically significant(P>0.05),while the differences between the 0° group and±10° groups were statistically significant(P<0.05).The differences in displacement between±5° groups and±10° groups were also statistically significant(P<0.05).0° group had a significantly higher number of collapse cycles than±10° groups(P<0.05).The number of collapse cycles in 0° group was also higher than that in±5° groups,but the differences were not statistically significant(P>0.05).The number of collapse cycles in±5° groups was significantly higher than that±10° groups(P<0.05).Conclusions The quality of reduction after internal fixation of femoral neck fractures significantly affects the biomechanical properties of the femoral head.This study provides a scientific basis for optimizing treatment and postoperative management,aiming to improve clinical outcomes and patients' quality of life.
4.Impact of Postoperative Reduction Quality on Biomechanics of the Femoral Head Following Internal Fixation of Femoral Neck Fractures
Shixiong ZHANG ; Jianxiong MA ; Bin LU ; Ying WANG ; Aixian TIAN ; Lei SUN ; Zhe HAN ; Jiahui CHEN ; Jing DAI ; Haohao BAI ; Hongzhen JIN ; Jie ZHAO ; Pengfei LI ; Xinlong MA
Journal of Medical Biomechanics 2025;40(5):1144-1149
Objective To investigate the effect of postoperative reduction quality in femoral neck fracture internal fixation on mechanical properties of the femoral head from the perspective of trabecular bone biomechanics.Methods From patients who underwent hip replacement surgery for femoral neck fractures,a total of 26 femoral head slice specimens were obtained.The central axis of the primary compressive trabeculae was defined as the 0° group,with the intersection point of the primary compressive trabeculae and the femoral calcar serving as the center.By rotating the specimens to simulate different reduction angles,the cut femoral head slice specimens were randomly divided into five groups:-10°,-5°,0°,5°,and 10°,representing femoral heads with varying reduction qualities.The specimens were subjected to single compression load tests and fatigue load tests.The load was set from 70 N to 1 400 N,at a frequency of 1 Hz,with 10 000 cycles.Axial stiffness,displacement,and the number of collapse cycles were measured,to compare the biomechanical properties of femoral head specimens under different reduction qualities.Results There were differences in the axial stiffness,displacement,and number of collapse cycles among the femoral head specimens in different groups.Under 800 N load,the axial stiffness of 0° group was significantly greater than that of±10° groups(P<0.05).The axial stiffness of 0° group was also greater than that of the±5° groups,but the differences were not statistically significant(P>0.05).The axial stiffness of±5° groups was greater than that of±10° groups(P<0.05).0° group had a lower displacement than±5° groups and±10° groups.However,the differences in displacement between 0° group and±5° groups were not statistically significant(P>0.05),while the differences between the 0° group and±10° groups were statistically significant(P<0.05).The differences in displacement between±5° groups and±10° groups were also statistically significant(P<0.05).0° group had a significantly higher number of collapse cycles than±10° groups(P<0.05).The number of collapse cycles in 0° group was also higher than that in±5° groups,but the differences were not statistically significant(P>0.05).The number of collapse cycles in±5° groups was significantly higher than that±10° groups(P<0.05).Conclusions The quality of reduction after internal fixation of femoral neck fractures significantly affects the biomechanical properties of the femoral head.This study provides a scientific basis for optimizing treatment and postoperative management,aiming to improve clinical outcomes and patients' quality of life.
5.Factors influencing of lymphopenia in prostate cancer patients during radiotherapy
Yifei LI ; Xianshu GAO ; Hongzhen LI ; Shangbin QIN ; Xin QI ; Mingwei MA ; Yun BAI ; Xueying REN ; Jiayan CHEN ; Feng LYU ; Xiaoying LI
Chinese Journal of Radiation Oncology 2025;34(4):347-354
Objective:To analyze the incidence and influencing factors of lymphopenia in prostate cancer patients undergoing pelvic radiotherapy.Methods:A retrospective analysis was conducted on 123 prostate cancer patients treated at the Department of Radiation Oncology, Peking University First Hospital, from November 2011 to May 2015. Radiotherapy was administered using conventional fractionated intensity-modulated radiotherapy. Blood routine, including absolute lymphocyte count (ALC), was performed on patients before radiotherapy, weekly during radiotherapy, and at the end of radiotherapy. Severe lymphopenia was defined as an ALC <500 cells/μl. Based on whether the minimum ALC during radiotherapy was lower than 500 cells/μl, the entire cohort and 55 patients (excluding those with undelineated pelvic bone marrow due to radiotherapy planning system issues) with delineated pelvic bone marrow (divided into pelvic bone marrow, iliac bone marrow, and lower pelvic bone marrow) were stratified into a severe lymphopenia group (33 cases and 16 cases, respectively) and a mild lymphopenia group (90 cases and 39 cases, respectively). Differences in clinical factors and dosimetric parameters were compared between the groups using the chi-square test (or Fisher's exact test), t-test, and Wilcoxon rank-sum test. Univariate and multivariate logistic regression analyses were performed to identify the clinical and dosimetric factors influencing severe lymphopenia. Results:All 123 prostate cancer patients experienced lymphopenia during radiotherapy, with a median minimum ALC of 0.6×10 9/L [range: (0.2-2.3)×10 9/L]. Severe lymphopenia occurred in 26.8% (33 cases) of patients. Univariate analysis of the entire cohort showed that pre-radiotherapy baseline ALC, initial neutrophil-to-lymphocyte ratio, prostate-specific antigen value, Gleason score, and pelvic radiotherapy were promoting factors for severe lymphopenia ( P<0.05). Multivariate analysis identified pre-radiotherapy baseline ALC ( OR=0.217, 95% CI: 0.072-0.650, P=0.006) and pelvic radiotherapy ( OR=23.852, 95% CI: 2.834-200.787, P=0.004) as promoting factors for severe lymphopenia. In patients with delineated pelvic bone marrow, univariate analysis showed that pelvic bone marrow V 30 Gy and V 40 Gy, iliac bone marrow V 30 Gy and V 40 Gy, lower pelvic bone marrow V 30 Gy and V 40 Gy were promoting factors for severe lymphopenia during treatment ( P<0.05). Conclusions:Lymphopenia is common in prostate cancer patients undergoing radiotherapy, with a high incidence of severe lymphopenia. Pre-radiotherapy baseline ALC, as well as pelvic, iliac, and lower pelvic bone marrow V 30 Gy and V 40 Gy, are promoting factors for severe lymphopenia during radiotherapy.
6.Efficacy and safety analysis of reduced-field postoperative radiotherapy of upper tract urothelial carcinoma
Xiaoying LI ; Xianshu GAO ; Hongzhen LI ; Shangbin QIN ; Xin QI ; Mingwei MA ; Yun BAI ; Tian CHENG ; Zheng ZHANG ; Qi TANG ; Zihao TAO ; Chunru XU ; Xuesong LI
Chinese Journal of Radiation Oncology 2025;34(12):1215-1222
Objective:To compare the efficacy and safety of extended-field versus reduced-field radiotherapy in upper tract urothelial carcinoma (UTUC) patients after radical operation.Methods:A retrospective analysis was conducted on the data of 210 UTUC patients who underwent full-length nephrectomy and received postoperative adjuvant radiotherapy in Peking University First Hospital from January 2013 to November 2023, and follow-up continued until June 2024. According to the target area of postoperative radiotherapy, patients were divided into the extended-field radiotherapy group (127 cases) and the reduced-field radiotherapy group (83 cases). The overall survival (OS), distant metastasis free survival (DMFS), local recurrence free survival (LRFS) and adverse reactions were compared. In the same period, 114 patients with recurrent abdominal and pelvic lymph nodes who did not receive adjuvant therapy after surgery for UTUC in our center were prospectively collected, and the coverage of the reduced-field target area was analyzed. Chi square test was used to compare the clinical characteristics, Kaplan-Meier method was used to analyze survival outcomes, log-rank test was used to compare the survival rate, and Cox multivariate regression analysis was performed on the influencing factors of survival.Results:The median follow-up was 24.5 (range: 3-74) months. There were no significant differences between the extended-field and reduced-field radiotherapy groups in terms of 2-year LRFS (93.3% vs. 98.1%, P=0.156), 2-year DMFS (84.8% vs. 91.2%, P=0.176), and 2-year OS (90.4% vs. 90.7%, P=0.707). The most common toxicities of adjuvant radiotherapy were nausea and leukopenia, with significantly higher grade 1-2 incidence in the extended-field group compared to the reduced-field group ( P<0.05). According to the analysis of patients with retroperitoneal lymph node recurrence after surgery, the reduced-field target designed according to the location of the primary tumor can cover more than 90% of the postoperative metastatic lymph node area Multivariate analysis revealed that variant histology ( HR=2.180,95% CI: 1.021-4.658, P=0.044) was an independent predictor of worse DMFS, while variant histology ( HR=3.825,95% CI: 1.514-9.662, P=0.005) and T 3-4 stage ( HR=4.452,95% CI: 1.025-19.339, P=0.046) were independent predictors of poorer OS. Conclusions:Compared with extended-field radiotherapy, reduced-field radiotherapy designed based on primary tumor location significantly reduced treatment-related toxicities without compromising postoperative therapeutic efficacy, and the reduced-field can cover more than 90% of local recurrent lesions.
7.The experimental study of X-ray diagnosis of closed reduction rotational displacement of femoral neck fractures
Xinlong MA ; Jianxiong MA ; Bin LU ; Fei LI ; Haohao BAI ; Ying WANG ; Aixian TIAN ; Lei SUN ; Yan WANG ; Benchao DONG ; Hongzhen JIN ; Yan LI ; Jiahui CHEN
Chinese Journal of Orthopaedics 2024;44(2):105-113
Objective:To explore the optimal index of rotational displacement of femoral neck fractures by modeling the axial rotational displacement of femoral neck fractures after reduction and based on X-ray projections.Methods:Six dry human femur specimens, comprising 2 males and 4 females, were utilized in the study. Design and manufacture a proximal femur ortholateral and oblique X-ray casting jigs and mounts. The femoral neck fracture was modeled on the femoral specimen, with Pauwells 30°, 50°, and 70° models (2 each) made according to Pauwells typing. The fractures were manually repositioned with residual anterior 20°, 40° and 60° axial rotational displacements. Each fracture model was projected at different angles (pedicled 40°, pedicled 20°, vertical 0°, cephalad 20°, and cephalad 40°), and the trabecular angle and Garden's alignment index of the model were measured to observe the imaging characteristics of the fracture line on the medial oblique and lateral oblique radiographs.Results:In the presence of a 20° and 40° anterior rotational displacement following reduction of a femoral neck fracture, the trabecular angle in the rotationally displaced group was not significantly different from that of the anatomically repositioned group in various projection positions. However, when a residual rotational displacement of 60° was present, the trabeculae appeared blurred at most projection angles in the Pauwells 30° and 50° models, failing to measure trabecular angles. In the Pauwells 70° fracture model, the trabecular angle in the rotational displacement group was significantly different from that in the anatomical reduction group. In anteroposterior radiographs, when the anterior rotation displacement was 60° in the Pauwells 70° group, Garden's contralateral index showed an unsatisfactory restoration (150°, 142°), whereas all rotationally displaced models in the Pauwells 30° and Pauwells 50° groups had a Garden's contralateral index of >155°, which achieved an acceptable restoration. In lateral radiographs, all rotational displacement models with Garden's alignment index>180° failed to achieve acceptable repositioning, and the larger the Pauwells angle the greater the Garden's alignment index at the same rotational displacement. In the internal oblique position with a bias towards the foot side, the image showed partial overlap between the femoral head and the shaft, making it difficult to assess the quality of the reduction. Conversely, when projected cephalad, the femoral neck appeared longer, particularly at a projection angle of 40° cephalad, allowing for clear observation of the fracture line and the anatomy of the proximal femur. The trabeculae were not well visualized in the external oblique position.Conclusion:There are limitations in applying the trabecular angle to assess the axial rotational displacement of the femoral head after reduction of femoral neck fractures. The Pauwells 70° with residual rotational anterior displacement of 60° was the only way to detect axial rotational displacement of the femoral head on anteroposterior radiographs Garden's alignment index. For the determination of axial rotational displacement of the femoral head, the Garden's alignment index on lateral radiographs provides higher reliability.
8.Research progress on mechanisms of mutual regulation between the muscular system and the skeletal system in the elderly
Yan WANG ; Jianxiong MA ; Benchao DONG ; Aixian TIAN ; Yan LI ; Lei SUN ; Hongzhen JIN ; Bin LU ; Ying WANG ; Haohao BAI ; Xinlong MA
Chinese Journal of Geriatrics 2024;43(1):82-85
Examining mechanisms involved in the mutual regulation between the muscular system and the skeletal system, elucidating the key issues responsible for loss of muscle and bone mass and strength, and thus halting the progression of these conditions are critical measures for reducing fractures caused by falls and subsequent disability and mortality.At present, most studies have treated the muscular system and the skeletal system separately, often ignoring the mutual regulation and connections between them.This article reviews the current research progress on the mechanisms of interaction between the two systems, aiming to provide a basis for the prevention, diagnosis and treatment of disuse-related diseases in the elderly population.
9.Stress Distributions Affected by Different Filling Blocks in Medial Opening Wedge High Tibial Osteotomy
Chengshuang YU ; Jianxiong MA ; Bin LU ; Ying WANG ; Haohao BAI ; Hongzhen JIN ; Xinlong MA
Journal of Medical Biomechanics 2023;38(1):E084-E089
Objective To analyze the influence from material and size of the filling block on stress distributions of the tibial osteotomy model. Methods The filling blocks with three different materials (iliac bone, cancellous bone and polyetheretherketone (PEEK)) and five different sizes were established and implanted to the tibial osteotomy models, respectively. The mechanical loads were applied on the model, the stress distribution and edge displacement of the model were analyzed. Results For three kinds of materials, the stress at proximal end of the tibia and the plate, as well as edge displacement in the model implanted with filling block by iliac bone material were lower than those of the cancellous bone and PEEK, but the filling block by iliac bone material had the highest stress. When the filling blocks with different sizes were implanted in osteotomy space, the stress distribution on each part of the tibial osteotomy and edge displacement were different. Especially when the width of the filling block was reduced from 30 mm to 10 mm, the peak stress of the proximal tibia, steel plate and filling block was increased by 49. 3% , 92. 7% and 54. 4% on average. Conclusions Different filling block parameters will affect the stress distribution in different parts of the tibial osteotomy. The research results provide the theoretical basis for parameter selection of the tibial osteotomy filling block in clinic.
10.Partial stereotactic ablative boost radiotherapy in bulky non-small cell lung cancer: a dosimetric comparison between proton and photon
Yun BAI ; Xianshu GAO ; Mingwei MA ; Zhilei ZHAO ; Peilin LIU ; Xi CAO ; Shangbin QIN ; Siwei LIU ; Yan GAO ; Xueying REN ; Hongzhen LI ; Min ZHANG ; Xiaomei LI ; Feng LYU ; Xiaoying LI ; Xin QI ; Jiayan CHEN ; Mu XIE
Chinese Journal of Radiation Oncology 2022;31(8):710-715
Objective:Partial stereotactic ablative boost radiotherapy(P-SABR)is a method to deliver SABR boost to the gross tumor boost volume(GTVb), followed by conventionally fractionated radiotherapy to the whole tumor area(GTV). GTVb is the max volume receiving SABR while ensuring the critical organ-at-risk(OAR)falloff to 3 GyE/f. We investigated the potential advantage of proton therapy in treating bulky non-small cell lung cancer(the tumor length greater than 8 cm).Methods:Nine patients with bulky NSCLC treated with photon P-SABR in our institute were selected. For the treatment planning of proton therapy, the GTVb target area was gradually outwardly expanded based on the photon GTVb target area until the dose to critical OARs reached 3 GyE/f. The GTV and CTV areas remained the same as photon plan. A proton intensity-modulated radiation treatment plan(proton-IMPT), a photon intensity-modulated radiation treatment plan(photon-IMRT)and a photon volumetric modulated arc therapy(photon-VMAT)were created for each patient, respectively. The dosimetric parameters of different treatment plans were compared.Results:The volume ratio of GTVb-photon and GTVb-proton to GTV was(25.4±13.4)% and(69.7±30.0)%,respectively( P<0.001). In photon-IMRT, photon-VMAT, and proton-IMPT plan groups, the mean dose of CTV was(76.1±4.9)Gy, (78.2±3.6)Gy, and(84.7±4.9)Gy, respectively; the ratio of tumor volume with Biologic Effective Dose(BED)≥ 90 Gy to GTV volume was(70.7±21.7)%, (76.8±22.1)%,and(97.9±4.0)%,respectively. The actual dose and BED to the tumor area of the proton-IMPT plan group were significantly higher than those of the photon plan group(both P<0.05). Besides, the OARs dose was significantly decreased in the proton-IMPT group, with(49.2±22.0)%, (56.8±19.0)% and(16.1±6.3)% of the whole lung V5 for photon-IMRT, photon-VMAT and proton-IMPT, respectively(all P<0.001). Conclusions:Larger GTV boost target volume, higher BED and reduced OARs dose can be achieved in proton plans compared with photon plans. Proton P-SABR is expected to further improve the local control rate of bulky NSCLC with fewer adverse effects.

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