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08 July 2024, Volume 51 Issue 7 Previous Issue    Next Issue

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50th Anniversary of Founding · Proton Therapy

Debates and reflection on modern proton radiotherapy and photon radiotherapy Yu Cedric, Ren Lei, Lu Xiaoguang 2024, 51 (7):  411-416.  doi: 10.3760/cma.j.cn371439-20240619-00068 Abstract ( 94 )   HTML ( 23 )   PDF (2104KB) ( 76 )   Save The debate on the merits of proton radiotherapy and photon radiotherapy has lasted for more than 20 years， mainly reflected in the comparison of dose distribution and clinical outcomes. Because dosimetric advantages do not always translate to better clinical outcomes， several phase Ⅲ comparative clinical studies are being conducted in Western countries. However， it is highly questionable that these studies will bring great value to the advancement of radiation therapy or settle the debate. This is because the effectiveness of the treatment depends not only on the type of radiation， but also on the technology used. Therefore， the focus of the research should not be which type of radiation is superior， but how to avoid its disadvantages while taking full advantage of the dose characteristics of each type of radiation. Both proton therapy and photon therapy will play an important role in cancer treatment in the future， and limited resources should be applied to maximize the effectiveness of each. With the rapid development of radiotherapy technology and systemic therapies including immunotherapy， reducing treatment fractions in the form of stereotactic radiosurgery and stereotactic body radiotherapy （SRS/SBRT） will be the inevitable trend. The need for dose focusing will drive photon therapy toward 4π radiotherapy using more non-coplanar fields， while higher geometric accuracy requirements will cause wide adoption of artificial intelligence-based online adaptive radiotherapy. Figures and Tables | References | Related Articles | Metrics

Breakthroughs and challenges： clinical application and progress of proton and heavy ion radiotherapy for malignant tumors Kong Lin, Lu Jiade 2024, 51 (7):  417-423.  doi: 10.3760/cma.j.cn371439-20240621-00069 Abstract ( 87 )   HTML ( 13 )   PDF (811KB) ( 70 )   Save Particle beam radiation therapy （PBRT）， using proton and heavy ion （mainly carbon ion in clinical practice） beams， provides precise cancer treatment by targeting tumor sites while sparing healthy tissues， by leveraging the Bragg peak for superior dose distribution. Proton beams have a relative-biological-effectiveness （RBE） of 1.1， which is slightly higher than that of photon beams. And carbon ions have an RBE of 2-3 due to their high linear energy transfer， thus being more advantageous for radioresistant and hypoxic tumors. Treatment strategies include single-beam and mixed-beam approaches， the latter of which combines the advantages of different particles and is an important direction of cancer treatment research. PBRT faces challenges such as managing moving targets and dose uncertainties， requiring advanced techniques like respiratory gating and adaptive planning. Additionally， the scarcity of randomized clinical trials （RCTs） limits PBRT's clinical validation. Existing RCTs， such as those from MD Anderson， indicate the benefits， as well as the need for further studies to confirm PBRT's long-term efficacy and safety. Future research should compare PBRT to photon therapy and explore the therapeutic benefit of combining PBRT with systemic therapies like immunotherapy. Reviewing the clinical practice and research of PBRT， and further discussing its cost-effectiveness in tumor treatment， can provide readers with a comprehensive understanding and promote the development and application of PBRT in cancer treatment. References | Related Articles | Metrics

Trends of the use of proton beam radiation therapy in patients with central nervous system tumors： analysis of National Cancer Database (2004-2021） Saber Amin, Chi Lin 2024, 51 (7):  424-431.  doi: 10.3760/cma.j.cn371439-20240624-00070 Abstract ( 50 )   HTML ( 11 )   PDF (3492KB) ( 55 )   Save Objective To evaluate trends in the use of proton beam radiation therapy (PBT） in patients with central nervous system (CNS） tumors in the United States and the factors associated with such use. Methods The National Cancer Database was queried for CNS tumors patients between 2004 and 2021 to explore the time trend in the use of PBT by histology type， age at diagnosis， insurance， median household income level， education level， and hospital type. Multivariable logistic regression analysis was used to report the association of various factors with the use of PBT. Results Of all the 192 696 CNS patients， 5 901 （3.1%） received PBT， among whom 4 109 （69.6%） were ≥18 years of age. The use of PBT in CNS tumors increased from only 1.0% in 2004 to 11.4% in 2021. In patients who received PBT， embryonal tumor was the most common pediatric tumor while astrocytoma was most common adult tumor. Multivariable logistic regression analysis revealed that patients with glioblastoma， ependymoma， medulloblastoma， germinoma were more likely to received PBT compared to astrocytoma. Age<18 years， no-comorbidity， private insurance， higher household income level and being diagnosed in recent years were also positively associated with the use of PBT. Conclusion The patients with younger age， no-comorbidity， higher household income， private insurance， diagnosed in recent years and certain tumor histologists are more likely to receive PBT in the United States. The use of PBT increased from 1.0% in 2004 to 11.4% in 2021. However， there is still a distinguished gap between the number of patients who should receive PBT and the number of patients who received PBT. Figures and Tables | References | Related Articles | Metrics

Expert Editorial

Current situation and countermeasure of overdiagnosis and overtreatment of pulmonary ground-glass nodule Liang Xinyu, Wei Zhigang, Ye Xin 2024, 51 (7):  432-440.  doi: 10.3760/cma.j.cn371439-20240509-00071 Abstract ( 84 )   HTML ( 22 )   PDF (879KB) ( 83 )   Save Lung cancer has emerged as one of the most prevalent malignant diseases globally， characterized by the highest incidence and mortality rates. Thus， early detection， diagnosis， and treatment play crucial roles in reducing the mortality associated with lung cancer. Research has revealed that low-dose computed tomography （LDCT） screening significantly reduces the mortality rate of lung cancer among high-risk populations. Nevertheless， the expansion of LDCT screening initiatives has led to an increased detection of asymptomatic pulmonary ground-glass nodule （GGN）. This heightened detection rate may result in overdiagnosis， overtreatment， inappropriate utilization of medical resources， and heightened anxiety amongst patients. References | Related Articles | Metrics

Original Articles

Dosimetric study of intensity-modulated radiotherapy and volumetric intensity modulated arc therapy based on the inner edge tangent field for radiotherapy after breast-conserving surgery of left-sided breast cancer Zhao Biao, Pu Qin, Yuan Meifang, Ma Lishuang, Li Han, Yang Yi, Sun Chaoxi 2024, 51 (7):  441-447.  doi: 10.3760/cma.j.cn371439-20231204-00072 Abstract ( 64 )   HTML ( 14 )   PDF (1304KB) ( 54 )   Save Objective To explore the dosimetry difference between intensity-modulated radiotherapy （IMRT） and volumetric intensity modulated arc therapy （VMAT） based on the inner edge tangent field （IETF） after left-sided breast conserving surgery. Methods The localization CT and target organ at risk （OAR） data of 35 patients with left-sided breast cancer treated with IMRT after breast conserving surgery at Department of Radiotherapy in Yunnan Cancer Hospital from June 2022 to June 2023 were selected. The IETF-IMRT and the IETF-VMAT plans were designed for the same patient based on IETF， the dosimetry differences of target areas and OAR， as well as the planned execution time were compared between the two groups. Results Dosimetry of target areas： for IETF-IMRT and IETF-VMAT， the D98% of the planning target volume were （47.92±0.51） and （48.21±0.33） Gy， respectively， while the D50% were （52.04±0.22） and （51.91±0.26） Gy， respectively， and the D2% were （53.93±0.36） and （53.62±0.41） Gy， respectively， the conformity index were 0.84±0.03 and 0.87±0.02， respectively， while the homogeneity index were 0.12±0.01 and 0.10±0.01， respectively， with statistically significant differences （t=-3.87， P<0.001； t=3.53， P=0.001； t=5.30， P<0.001； t=-13.60， P<0.001； t=6.24， P<0.001）. Dosimetry of OAR： for IETF-IMRT and IETF-VMAT， the left lung V5 were （31.91±6.28）% and （33.99±6.31）%， respectively， and the V20 were （11.71±2.06）% and （9.73±2.12）%， respectively， with statistically significant differences （t=-4.18， P<0.001； t=12.40， P<0.001）. The right lung V5 were （0.11±0.08）% and （7.13±3.12）%， respectively， and the Dmean were （1.05±0.12） and （2.71±0.27） Gy， respectively， with statistically significant differences （t=-33.62， P<0.001； t=-13.30， P<0.001）. The spinal cord D2% were （1.08±0.11） and （4.83±1.40） Gy， respectively， with a statistically significant difference （t=-15.99， P<0.001）. The left lung Dmean were （7.45±1.08） and （7.37±1.03） Gy， the heart Dmean were （4.21±0.96） and （4.41±0.48） Gy， and the right-sided breast Dmean were （3.74±1.52） and （3.48±1.11） Gy， respectively， with no statistically significant difference （t=1.16， P=0.253； t=-1.76， P=0.088； t=1.41， P=0.169）. Planned execution time： the execution time of IETF-IMRT and IETF-VMAT was （10.73±1.21） and （2.18±0.17） min， respectively， with a statistically significant difference （t=44.71， P<0.001）. Conclusion Both IETF-IMRT and IETF-VMAT can meet clinical requirements， however the two techniques have their own characteristics. IETF-VMAT has better conformity and homogeneity of target region. The planned OAR dosimetry in both plans are significantly lower than the dose limit of postoperative radiotherapy for breast cancer， among which the left lung V5， the right lung V5， Dmean and spinal cord D2% of IETF-IMRT are slightly lower， the left lung V20 of IETF-VMAT is slightly lower. IETF-VMAT significantly reduces the planned execution time compared with IETF-IMRT， thus can greatly reduce the dose deviation caused by patient position change， and significantly improve patients experience and comfort of radiotherapy. Taken together， IETF-VMAT has advantages over IETF-IMRT in radiotherapy after breast conserving surgery of left-sided breast cancer. Figures and Tables | References | Related Articles | Metrics

Levels of serum HMGB2 and HMGB3 and clinical significance in non-small cell lung cancer patients Liu Hao, Jin Ermei, Ding Hongjuan, Jin Lei 2024, 51 (7):  448-452.  doi: 10.3760/cma.j.cn371439-20231110-00073 Abstract ( 58 )   HTML ( 26 )   PDF (1010KB) ( 39 )   Save Objective To investigate the levels of serum high mobility group box （HMGB） 2 and HMGB3 and clinical significance in patients with non-small cell lung cancer （NSCLC）. Methods A total of 137 NSCLC patients admitted to the First Affiliated Hospital of Xi'an Medical University from January 2020 to January 2022 were selected as the NSCLC group， and another 90 cases who underwent healthy medical checkups during the same period were selected as the healthy group. Serum HMGB2 and HMGB3 levels were compared between the two groups. The relationship between serum HMGB2 and HMGB3 levels and the clinical and pathological characteristics of NSCLC patients was analyzed. NSCLC patients were divided into a good prognosis group （n=86） and a poor prognosis group （n=51） according to the prognosis， and the clinical data of the two groups were compared. Multivariate logistic regression was used to analyze the influencing factors of the prognosis of NSCLC patients. Receiver operator characteristic （ROC） curve was used to analyze the predictive value of serum HMGB2 and HMGB3 on the prognosis of NSCLC patients. Results Serum HMGB2 [（6.35±1.66） ng/ml vs. （2.58±0.76） ng/ml， t=20.19， P<0.001] and HMGB3 [（2.48±0.56） ng/ml vs. （1.09±0.13） ng/ml， t=23.13， P<0.001] levels in NSCLC group were higher than those in healthy group. Serum HMGB2 and HMGB3 levels of NSCLC patients with a history of smoking （t=2.80， P=0.006； t=5.04， P<0.001）， lymph node metastasis （t=3.53， P=0.001； t=4.02， P<0.001）， and TNM stage Ⅲ-Ⅳ （t=2.58， P=0.011； t=3.82， P<0.001） were significantly higher than those of patients with no history of smoking， no lymph node metastasis， and TNM stage Ⅰ-Ⅱ. The serum levels of HMGB2 [（7.80±1.83） ng/ml vs. （5.49±1.56） ng/ml， t=7.85， P<0.001] and HMGB3 [（2.91±0.78） ng/ml vs. （2.23±0.43） ng/ml， t=6.58， P<0.001）] in the poor prognosis group were higher than those in the good prognosis group， and the proportion of patients with lymph node metastasis （χ2=4.81， P=0.028）， history of smoking （χ2=11.67， P=0.001）， and TNM stage Ⅲ-Ⅳ （χ2=6.18， P=0.013） was significantly higher than that in the good prognosis group. Multivariate logistic regression analysis showed that lymph node metastasis （OR=1.96， 95%CI： 1.14-3.36， P=0.015）， smoking history （OR=2.02， 95%CI： 1.33-3.06， P=0.001）， TNM stage （OR=2.28， 95%CI： 1.35-3.86， P=0.002）， HMGB2 （OR=2.01， 95%CI： 1.40-2.91， P<0.001）， and HMGB3 （OR=1.99， 95%CI： 1.25-3.15， P=0.003） levels were independent influencing factors of prognosis of NSCLC patients. ROC curve analysis showed that the area under the curve （AUC） of serum HMGB2 and HMGB3 alone and in combination to predict the prognosis of NSCLC patients were 0.833， 0.862 and 0.922， respectively， and the AUC predicted by the combination was significantly higher than that predicted by serum HMGB2 （Z=2.44， P=0.015） and HMGB3 （Z=2.54， P=0.011） alone. Conclusion Serum HMGB2 and HMGB3 levels are up-regulated in NSCLC patients and are closely associated with poor prognosis， and the combined detection of the two has certain predictive efficacy for prognosis of NSCLC patients. Figures and Tables | References | Related Articles | Metrics

Risk factors and predictive model construction of brain metastases in patients with limited-stage SCLC undergoing preventive brain radiotherapy after remission Yu Hongxin, Bai Yan, Gong Yuan, Wang Jianzhuang, Fan Zhigang 2024, 51 (7):  453-457.  doi: 10.3760/cma.j.cn371439-20230715-00074 Abstract ( 57 )   HTML ( 24 )   PDF (1024KB) ( 38 )   Save Objective To investigate the risk factors of brain metastases in patients with limited-stage small cell lung cancer （SCLC） undergoing preventive brain radiotherapy after remission and to construct prediction model. Methods A total of 231 patients with limited-stage SCLC who received chemoradiotherapy and achieved remission in 3201 Hospital from January 2015 to January 2023 were selected as the study objects. Logistic regression was used to analyze the influencing factors on the occurrence of brain metastases after remission in patients with limited-stage SCLC who received preventive brain radiotherapy. Binary logistic regression was used to construct a prediction model. Receiver operator characteristic （ROC） curve was used to evaluate the diagnostic efficacy of each indicator and the prediction model on the occurrence of brain metastases in patients. Results The median follow-up time of the whole group was 73 months， and 42 cases of brain metastases occurred， with an incidence rate of 18.18%. There were statistically significant differences in the incidence of brain metastases among patients with different T stage （Z=-4.97， P<0.001）， clinical stage （Z=-8.17， P<0.001）， and time from initial treatment to thoracic radiotherapy （χ2=21.38， P<0.001）. Multivariate analysis showed that T stage （stage T3： OR=6.29， 95%CI： 1.58-25.06， P=0.009； stage T4： OR=12.91， 95%CI： 3.74-44.57， P<0.001）， clinical stage （stageⅡ， OR=8.75， 95%CI： 2.89-26.51， P<0.001； stage Ⅲ， OR=18.43， 95%CI： 7.24-46.92， P<0.001）， and time from initial treatment to thoracic radiotherapy （OR=0.25， 95%CI： 0.11-0.56， P=0.001） were independent influencing factors on the occurrence of brain metastases after remission in patients with limited-stage SCLC who received preventive brain radiotherapy. The diagnostic prediction model based on the above indicators was logit（P）=-19.91+1.84× stage T3 +2.56× stage T4+2.17× stage Ⅱ+2.91× stage Ⅲ-1.38× time from initial treatment to thoracic radiotherapy. ROC curve analysis showed that the area under the curve of T stage， clinical stage， time from initial treatment to thoracic radiotherapy， and the diagnostic prediction model for predicting the occurrence of brain metastasis after remission in patients with limited-stage SCLC who received preventive brain radiotherapy were 0.728， 0.660， 0.687， and 0.846， respectively， and the area under the curve of the diagnostic prediction model was significantly larger than those of the other indicators （all P<0.05）. Conclusion T stage， clinical stage and the time from initial treatment to thoracic radiotherapy are all influential factors for the occurrence of brain metastases after remission in patients with limited-stage SCLC who received preventive brain radiotherapy. The diagnostic prediction model based on the above indicators can help to guide clinicians to accurately screen patients at high risk of brain metastases in the early stage. Figures and Tables | References | Related Articles | Metrics

Reviews

Tumor-infiltrating immune cells from a single-cell perspective Du Qilian, Hu Qinyong 2024, 51 (7):  458-463.  doi: 10.3760/cma.j.cn371439-20231130-00075 Abstract ( 66 )   HTML ( 8 )   PDF (840KB) ( 37 )   Save Immune microenvironment is closely related to the treatment and prognosis of tumors. Tumor-infiltrating immune cells exhibit significant heterogeneity in different stages of tumors. Single-cell RNA sequencing （scRNA-seq） is widely used in the study of various tumor microenvironment to analyze the biological behavior， mechanisms， and relationship between cells and the body at the single-cell level. The results showed that using scRNA-seq can deeply understand the immune characteristics of tumor-infiltrating immune cells. References | Related Articles | Metrics

Progress in the study of redifferentiation therapy for radioactive iodine-refractory differentiated thyroid carcinoma Liu Jing, Zhang Jun 2024, 51 (7):  464-467.  doi: 10.3760/cma.j.cn371439-20231008-00076 Abstract ( 54 )   HTML ( 8 )   PDF (806KB) ( 25 )   Save The overall prognosis of differentiated thyroid cancer is good， but a small number of patients will still develop local recurrence and distant metastasis， and lose iodine uptaking ability in the initial or treatment process， becoming radioactive iodine-refractory differentiated thyroid carcinoma （RAIR-DTC）， with a poor prognosis. Treatment options for RAIR-DTC patients are limited with poor results， and restoration of iodine uptaking capacity in RAIR-DTC through pharmacological promotion of redifferentiation is one of the important strategies for treatment. References | Related Articles | Metrics

Advances in clinical molecular diagnosis and treatment of pulmonary large cell neuroendocrine carcinoma Han Yi, Zhang Tongmei, Qi Fei, Zhang Yong 2024, 51 (7):  468-473.  doi: 10.3760/cma.j.cn371439-20231130-00077 Abstract ( 76 )   HTML ( 14 )   PDF (822KB) ( 32 )   Save Pulmonary large cell neuroendocrine carcinoma （LCNEC） is a rare type of malignant neuroendocrine tumor with poor prognosis， with the median overall survival being around one year in advanced diseases. The prognosis of patients with non-small cell lung cancer has been greatly improved with the application of molecular detecting techniques， targeted therapy and immunotherapy. However， little progress has been made in the diagnosis and treatment of LCNEC with no unified standard of diagnosis and treatment protocol. The clinical molecular diagnosis and treatment of LCNEC is of great significance. Exploring the research progress related to the diagnosis and treatment of LCNEC can provide reference for improving the existing clinical diagnosis and treatment difficulties of LCNEC. References | Related Articles | Metrics

Advances in the study of EVI1 in acute myeloid leukemia Wu Shiwei, Pei Kangjia, Zhang Dongxing, Qin Zhanyu, Guo Shuxia 2024, 51 (7):  474-477.  doi: 10.3760/cma.j.cn371439-20231218-00078 Abstract ( 69 )   HTML ( 12 )   PDF (778KB) ( 33 )   Save Acute myeloid leukemia （AML） is a common malignant disease of the hematological system， with high EVI1 expression accounting for 8%-10% of adult AML. Studies have shown that high EVI1 expression plays an important role in the treatment and prognosis of AML. In recent years， researchers have continuously revealed the structure and role of EVI1， but its mechanism of mediating AML has not been fully clarified. Therefore， systematically exploring the role of EVI1 in AML may provide a useful reference for the precise treatment of AML patients with high EVI1 expression. References | Related Articles | Metrics