Intensity-modulated particle therapy(IMPT)with carbon ions is comparatively susceptible to various uncertainties caused by breathing motion,including range,setup,and target positioning uncertainties.To determine relat...Intensity-modulated particle therapy(IMPT)with carbon ions is comparatively susceptible to various uncertainties caused by breathing motion,including range,setup,and target positioning uncertainties.To determine relative biological effectiveness-weighted dose(RWD)distributions that are resilient to these uncertainties,the reference phase-based four-dimensional(4D)robust optimization(RP-4DRO)and each phase-based 4D robust optimization(EP-4DRO)method in carbon-ion IMPT treatment planning were evaluated and compared.Based on RWD distributions,4DRO methods were compared with 4D conventional optimization using planning target volume(PTV)margins(PTV-based optimization)to assess the effectiveness of the robust optimization methods.Carbon-ion IMPT treatment planning was conducted in a cohort of five lung cancer patients.The results indicated that the EP-4DRO method provided better robustness(P=0.080)and improved plan quality(P=0.225)for the clinical target volume(CTV)in the individual respiratory phase when compared with the PTV-based optimization.Compared with the PTV-based optimization,the RP-4DRO method ensured the robustness(P=0.022)of the dose distributions in the reference breathing phase,albeit with a slight sacrifice of the target coverage(P=0.450).Both 4DRO methods successfully maintained the doses delivered to the organs at risk(OARs)below tolerable levels,which were lower than the doses in the PTV-based optimization(P<0.05).Furthermore,the RP-4DRO method exhibited significantly superior performance when compared with the EP-4DRO method in enhancing overall OAR sparing in either the individual respiratory phase or reference respiratory phase(P<0.05).In general,both 4DRO methods outperformed the PTV-based optimization in terms of OAR sparing and robustness.展开更多
Hepatic epithelioid hemangioendothelioma(HEH)is a rare neoplasm of vascular origin with variable malignant potential.Because most patients with this condition have multiple bilobar lesions,liver transplantation is the...Hepatic epithelioid hemangioendothelioma(HEH)is a rare neoplasm of vascular origin with variable malignant potential.Because most patients with this condition have multiple bilobar lesions,liver transplantation is the standard treatment,and hepatectomy is much less frequently indicated.We describe a case of a 35-yearold woman with unresectable multiple bilobar HEH successfully treated by combination treatment with hepatectomy and carbon-ion radiotherapy.This case is very meaningful since it demonstrated the effectiveness of carbon-ion radiotherapy for HEH and the possibility of expanding the curative treatment options for multiple bilobar hepatic tumors.展开更多
BACKGROUND Although the bystander effect and abscopal effect are familiar in medicine,they are relatively rare in clinical practice.Herein,we report the case of a patient who demonstrated an obvious bystander effect a...BACKGROUND Although the bystander effect and abscopal effect are familiar in medicine,they are relatively rare in clinical practice.Herein,we report the case of a patient who demonstrated an obvious bystander effect and abscopal effect response following carbon-ion irradiation for recurrent thymic carcinoma.CASE SUMMARY A 44-year-old female presented with shortness of breath.Eleven years prior,she was diagnosed with athymic tumor located in the anterosuperior mediastinum.She underwent extensive tumor resection,and the postoperative pathologic diagnosis was thymic carcinoma.She was administered 50 Gy/25 Fx of postoperative radiation.In 2019,she was diagnosed with a recurrence of thymic carcinoma,with multiple recurrent nodules and masses in the left thoracic chest and peritoneal cavity,the largest of which was in the diaphragm pleura proximal to the pericardium,with a size of 6.7 cm×5.3 cm×4.8 cm.She received carbonion radiotherapy.After carbon-ion radiotherapy treatment,the treated masses and the untreated masses were observed to have noticeably shrunk on the day of carbon-ion radiotherapy completion and on follow-up imaging.We followed the CARE Guidelines for consensus-based clinical case reporting guideline development and completed the CARE Checklist of information to report this case.CONCLUSION This report is the first of obvious abscopal and bystander effects following carbonion irradiation in a human patient,and further research is needed to better elucidate the mechanisms of bystander and abscopal effects.展开更多
In order to see whether carbon ion (C-ion) beams have a biological advantage over X-rays, studies were designed to examine the effects of C-ion beams on radiosensitivity in X-ray resistant cells. Clinically relevant X...In order to see whether carbon ion (C-ion) beams have a biological advantage over X-rays, studies were designed to examine the effects of C-ion beams on radiosensitivity in X-ray resistant cells. Clinically relevant X-ray resistant SAS-R cells derived from human tongue cancer SAS cells were used. The cells were exposed to X-rays or Spread-Out Bragg peak (SOBP) beam C-ions. Cell survival was measured using a modified high-density survival assay. Cell survival signaling and cell death signaling were analyzed using flow cytometry. The cells were labeled with putative cancer stem cell markers such as CD44 and CD326. SAS-R cells were 1.6 times more radioresistant than SAS cells after exposure to X-rays. Cell survival was similar in each cell line after exposure to C-ion beams. SAS-R cells displayed enhanced cell survival signaling when compared to SAS cells under normal conditions. On the other hand, the phosphorylation of AKT-related proteins decreased and polycaspase activities were enhanced when cells were irradiated with C-ion beams in both cell lines. More CD44 and CD326 positive cells were seen in SAS-R cells than in SAS cells. Moreover, the marker positive cell numbers significantly decreased after exposure to C-ion beams when compared to X-rays at iso-survival doses in SAS-R cells. C-ion beams efficiently induced cell killing in X-ray resistant cells which displayed activated cell survival signaling and contained more numerous cancer stem-like cells.展开更多
The hematological effects of space radiation contribute to the compromised immune defense in astronauts observed in the space environment as well as upon landing[1]. The complications associated with the hematopoietic...The hematological effects of space radiation contribute to the compromised immune defense in astronauts observed in the space environment as well as upon landing[1]. The complications associated with the hematopoietic syndrome include infection and internal hemorrhage. The decrease in peripheral blood cell counts after radiation serves not only as a marker for the severity of the exposure, but also as a marker for treatment and prognosis[2]. In the present research, we investigated the effects of whole-body heavy-ion (80 MeV/u carbon-ion) radiation and conventional X-ray (6 MV) radiation on peripheral blood cell counts in mice model. Time effects were determined to compare the effects of the different types of radiation.展开更多
Background: After deinitive chemoradiotherapy for non-metastatic nasopharyngeal carcinoma(NPC), more than 10% of patients will experience a local recurrence. Salvage treatments present signiicant challenges for locall...Background: After deinitive chemoradiotherapy for non-metastatic nasopharyngeal carcinoma(NPC), more than 10% of patients will experience a local recurrence. Salvage treatments present signiicant challenges for locally recurrent NPC. Surgery, stereotactic ablative body radiotherapy, and brachytherapy have been used to treat locally recurrent NPC. However, only patients with small-volume tumors can beneit from these treatments. Re-irradiation with X-ray—based intensity-modulated radiotherapy(IMXT) has been more widely used for salvage treatment of locally recurrent NPC with a large tumor burden, but over-irradiation to the surrounding normal tissues has been shown to cause frequent and severe toxicities. Furthermore, locally recurrent NPC represents a clinical entity that is more radioresistant than its primary counterpart. Due to the inherent physical advantages of heavy-particle therapy, precise dose delivery to the target volume(s), without exposing the surrounding organs at risk to extra doses, is highly feasible with carbon-ion radiotherapy(CIRT). In addition, CIRT is a high linear energy transfer(LET) radiation and provides an increased relative biological efectiveness compared with photon and proton radiotherapy. Our prior work showed that CIRT alone to 57.5 Gy E(gray equivalent), at 2.5 Gy E per daily fraction, was well tolerated in patients who were previously treated for NPC with a deinitive dose of IMXT. The short-term response rates at 3–6 months were also acceptable. However, no patients were treated with concurrent chemotherapy. Whether the addition of concurrent chemotherapy to CIRT can beneit locally recurrent NPC patients over CIRT alone has never been addressed. It is possible that the beneits of high-LET CIRT may make radiosensitizing chemotherapy unnecessary. We therefore implemented a phase I/II clinical trial to address these questions and present our methodology and results.Methods and design: The maximal tolerated dose(MTD) of re-treatment using raster-scanning CIRT plus concurrent cisplatin will be determined in the phase I, dose-escalating stage of this study. CIRT dose escalation from 52.5 to 65 Gy E(2.5 Gy E × 21–26 fractions) will be delivered, with the primary endpoints being acute and subacute toxicities. Eicacy in terms of overall survival(OS) and local progression-free survival of patients after concurrent chemotherapy plus CIRT at the determined MTD will then be studied in the phase II stage of the trial. We hypothesize that CIRT plus chemotherapy can improve the 2-year OS rate from the historical 50% to at least 70%.Conclusions: Re-treatment of locally recurrent NPC using photon radiation techniques, including IMXT, provides moderate eicacy but causes potentially severe toxicities. Improved outcomes in terms of eicacy and toxicity proile are expected with CIRT plus chemotherapy. However, the MTD of CIRT used concurrently with cisplatin-based chemotherapy for locally recurrent NPC remains to be determined. In addition, whether the addition of chemotherapy to CIRT is needed remains unknown. These questions will be evaluated in the dose-escalating phase I and randomized phase II trials.展开更多
This study investigated the impact of simulated microgravity on acute injury induced by low doses of carbon ions in male reproductive organs of mice,and determined alterations in spermatogenic function and expression ...This study investigated the impact of simulated microgravity on acute injury induced by low doses of carbon ions in male reproductive organs of mice,and determined alterations in spermatogenic function and expression levels of apoptotic factors in mice following exposure to acute irradiation after 7 days of simulated microgravity.The results demonstrated that significant reductions in spermatozoa,primary spermatocytes and spermatogonia,and increased globular cells in seminiferous tubule and pro-apoptotic proteins were observed in the group exposed to over0.4 Gy irradiation.Collectively,the data suggest that lesions inflicted by simulated microgravity are not markedly modified by lower doses of irradiation(0.2 Gy)in mouse testis compared to the control group.However,testicular impairments were markedly evident in the group exposed to higher doses of carbon ions plus simulated microgravity,which may be due at least in part to elevated apoptosis initiated by the mitochondrial apoptosis pathway in germ cells.展开更多
The bystander effects induced by medium from human hepatoma SMMC-7721 and adenocarcinoma F56 cells irradiated with carbon ions were investigated. It was found that the survival fraction (SF) of the irradiated cells de...The bystander effects induced by medium from human hepatoma SMMC-7721 and adenocarcinoma F56 cells irradiated with carbon ions were investigated. It was found that the survival fraction (SF) of the irradiated cells decreased exponentially along with the increased dose. SMMC-7721 cells were more radiosensitive than F56 cells. The plating efficiency (PE) of the non-irradiated cells treated with irradiated conditioned medium (ICM) was obvi-ously lower than the PE of control cells for SMMC-7721 cells but not for F56 cells. Moreover, the reduced PE and SF by ICM treatment were more significant for 1Gy irradiation than for 6Gy irradiation on SMMC-7721 cells. These results suggest that the irradiated cells can secrete factor(s) into medium that is cytotoxic to bystander non-irradiated cells. The bystander effects are dependent on cell genotype presented at the time of irradiation and radiation dose. This makes impact on the precise estimation of the effects of radiation and tumor radiotherapy.展开更多
本文以管状和盘状两种天然硅藻土作为初始原料,制备了一系列硅藻土衍生硅碳负极材料,并采用X射线衍射仪(XRD)、拉曼光谱(Raman)、扫描电子显微镜(SEM)、透射电子显微镜(TEM)、X-射线光电子能谱(XPS)等测试手段系统表征了所制备样品的晶...本文以管状和盘状两种天然硅藻土作为初始原料,制备了一系列硅藻土衍生硅碳负极材料,并采用X射线衍射仪(XRD)、拉曼光谱(Raman)、扫描电子显微镜(SEM)、透射电子显微镜(TEM)、X-射线光电子能谱(XPS)等测试手段系统表征了所制备样品的晶体结构、微观形貌及化学组成.将制备的硅藻土衍生硅碳负极材料作为活性物质组装为锂离子电池,对比了管状和盘状两种形貌对其储锂性能的影响,并详细考察了沥青衍生碳包覆层的加入量对硅碳负极材料比容量及循环稳定性的影响.测试结果表明,样品管DE-1∶3和管DE-1∶6在0.2 A g^(-1)较低电流密度下均具有较好的容量保持率,循环500次之后比容量分别可保持443 mAh g^(-1)和414 mAh g^(-1),而样品管DE-1∶6则在0.5 A g^(-1)较大电流密度下具有更好的结构稳定性.展开更多
基金supported by National Key Research and Development Program of China(No.2022YFC2401503)National Natural Science Foundation of China(Nos.11875299,61631001,U1532264,and 12005271).
文摘Intensity-modulated particle therapy(IMPT)with carbon ions is comparatively susceptible to various uncertainties caused by breathing motion,including range,setup,and target positioning uncertainties.To determine relative biological effectiveness-weighted dose(RWD)distributions that are resilient to these uncertainties,the reference phase-based four-dimensional(4D)robust optimization(RP-4DRO)and each phase-based 4D robust optimization(EP-4DRO)method in carbon-ion IMPT treatment planning were evaluated and compared.Based on RWD distributions,4DRO methods were compared with 4D conventional optimization using planning target volume(PTV)margins(PTV-based optimization)to assess the effectiveness of the robust optimization methods.Carbon-ion IMPT treatment planning was conducted in a cohort of five lung cancer patients.The results indicated that the EP-4DRO method provided better robustness(P=0.080)and improved plan quality(P=0.225)for the clinical target volume(CTV)in the individual respiratory phase when compared with the PTV-based optimization.Compared with the PTV-based optimization,the RP-4DRO method ensured the robustness(P=0.022)of the dose distributions in the reference breathing phase,albeit with a slight sacrifice of the target coverage(P=0.450).Both 4DRO methods successfully maintained the doses delivered to the organs at risk(OARs)below tolerable levels,which were lower than the doses in the PTV-based optimization(P<0.05).Furthermore,the RP-4DRO method exhibited significantly superior performance when compared with the EP-4DRO method in enhancing overall OAR sparing in either the individual respiratory phase or reference respiratory phase(P<0.05).In general,both 4DRO methods outperformed the PTV-based optimization in terms of OAR sparing and robustness.
文摘Hepatic epithelioid hemangioendothelioma(HEH)is a rare neoplasm of vascular origin with variable malignant potential.Because most patients with this condition have multiple bilobar lesions,liver transplantation is the standard treatment,and hepatectomy is much less frequently indicated.We describe a case of a 35-yearold woman with unresectable multiple bilobar HEH successfully treated by combination treatment with hepatectomy and carbon-ion radiotherapy.This case is very meaningful since it demonstrated the effectiveness of carbon-ion radiotherapy for HEH and the possibility of expanding the curative treatment options for multiple bilobar hepatic tumors.
基金Supported by Key R&D Plan of Science and Technology Program of Gansu Province,China,No.19YF3FH001.
文摘BACKGROUND Although the bystander effect and abscopal effect are familiar in medicine,they are relatively rare in clinical practice.Herein,we report the case of a patient who demonstrated an obvious bystander effect and abscopal effect response following carbon-ion irradiation for recurrent thymic carcinoma.CASE SUMMARY A 44-year-old female presented with shortness of breath.Eleven years prior,she was diagnosed with athymic tumor located in the anterosuperior mediastinum.She underwent extensive tumor resection,and the postoperative pathologic diagnosis was thymic carcinoma.She was administered 50 Gy/25 Fx of postoperative radiation.In 2019,she was diagnosed with a recurrence of thymic carcinoma,with multiple recurrent nodules and masses in the left thoracic chest and peritoneal cavity,the largest of which was in the diaphragm pleura proximal to the pericardium,with a size of 6.7 cm×5.3 cm×4.8 cm.She received carbonion radiotherapy.After carbon-ion radiotherapy treatment,the treated masses and the untreated masses were observed to have noticeably shrunk on the day of carbon-ion radiotherapy completion and on follow-up imaging.We followed the CARE Guidelines for consensus-based clinical case reporting guideline development and completed the CARE Checklist of information to report this case.CONCLUSION This report is the first of obvious abscopal and bystander effects following carbonion irradiation in a human patient,and further research is needed to better elucidate the mechanisms of bystander and abscopal effects.
文摘In order to see whether carbon ion (C-ion) beams have a biological advantage over X-rays, studies were designed to examine the effects of C-ion beams on radiosensitivity in X-ray resistant cells. Clinically relevant X-ray resistant SAS-R cells derived from human tongue cancer SAS cells were used. The cells were exposed to X-rays or Spread-Out Bragg peak (SOBP) beam C-ions. Cell survival was measured using a modified high-density survival assay. Cell survival signaling and cell death signaling were analyzed using flow cytometry. The cells were labeled with putative cancer stem cell markers such as CD44 and CD326. SAS-R cells were 1.6 times more radioresistant than SAS cells after exposure to X-rays. Cell survival was similar in each cell line after exposure to C-ion beams. SAS-R cells displayed enhanced cell survival signaling when compared to SAS cells under normal conditions. On the other hand, the phosphorylation of AKT-related proteins decreased and polycaspase activities were enhanced when cells were irradiated with C-ion beams in both cell lines. More CD44 and CD326 positive cells were seen in SAS-R cells than in SAS cells. Moreover, the marker positive cell numbers significantly decreased after exposure to C-ion beams when compared to X-rays at iso-survival doses in SAS-R cells. C-ion beams efficiently induced cell killing in X-ray resistant cells which displayed activated cell survival signaling and contained more numerous cancer stem-like cells.
文摘The hematological effects of space radiation contribute to the compromised immune defense in astronauts observed in the space environment as well as upon landing[1]. The complications associated with the hematopoietic syndrome include infection and internal hemorrhage. The decrease in peripheral blood cell counts after radiation serves not only as a marker for the severity of the exposure, but also as a marker for treatment and prognosis[2]. In the present research, we investigated the effects of whole-body heavy-ion (80 MeV/u carbon-ion) radiation and conventional X-ray (6 MV) radiation on peripheral blood cell counts in mice model. Time effects were determined to compare the effects of the different types of radiation.
基金Shanghai Hospital Development Center(Joint Breakthrough Project for New Frontier Technologies.Project No.SHDC 12015118)Science and Technology Commission of Shanghai Municipality(Project No.15411950102&15411950106)Natural Science Foundation of Shanghai(Project No.14ZR1407100)
文摘Background: After deinitive chemoradiotherapy for non-metastatic nasopharyngeal carcinoma(NPC), more than 10% of patients will experience a local recurrence. Salvage treatments present signiicant challenges for locally recurrent NPC. Surgery, stereotactic ablative body radiotherapy, and brachytherapy have been used to treat locally recurrent NPC. However, only patients with small-volume tumors can beneit from these treatments. Re-irradiation with X-ray—based intensity-modulated radiotherapy(IMXT) has been more widely used for salvage treatment of locally recurrent NPC with a large tumor burden, but over-irradiation to the surrounding normal tissues has been shown to cause frequent and severe toxicities. Furthermore, locally recurrent NPC represents a clinical entity that is more radioresistant than its primary counterpart. Due to the inherent physical advantages of heavy-particle therapy, precise dose delivery to the target volume(s), without exposing the surrounding organs at risk to extra doses, is highly feasible with carbon-ion radiotherapy(CIRT). In addition, CIRT is a high linear energy transfer(LET) radiation and provides an increased relative biological efectiveness compared with photon and proton radiotherapy. Our prior work showed that CIRT alone to 57.5 Gy E(gray equivalent), at 2.5 Gy E per daily fraction, was well tolerated in patients who were previously treated for NPC with a deinitive dose of IMXT. The short-term response rates at 3–6 months were also acceptable. However, no patients were treated with concurrent chemotherapy. Whether the addition of concurrent chemotherapy to CIRT can beneit locally recurrent NPC patients over CIRT alone has never been addressed. It is possible that the beneits of high-LET CIRT may make radiosensitizing chemotherapy unnecessary. We therefore implemented a phase I/II clinical trial to address these questions and present our methodology and results.Methods and design: The maximal tolerated dose(MTD) of re-treatment using raster-scanning CIRT plus concurrent cisplatin will be determined in the phase I, dose-escalating stage of this study. CIRT dose escalation from 52.5 to 65 Gy E(2.5 Gy E × 21–26 fractions) will be delivered, with the primary endpoints being acute and subacute toxicities. Eicacy in terms of overall survival(OS) and local progression-free survival of patients after concurrent chemotherapy plus CIRT at the determined MTD will then be studied in the phase II stage of the trial. We hypothesize that CIRT plus chemotherapy can improve the 2-year OS rate from the historical 50% to at least 70%.Conclusions: Re-treatment of locally recurrent NPC using photon radiation techniques, including IMXT, provides moderate eicacy but causes potentially severe toxicities. Improved outcomes in terms of eicacy and toxicity proile are expected with CIRT plus chemotherapy. However, the MTD of CIRT used concurrently with cisplatin-based chemotherapy for locally recurrent NPC remains to be determined. In addition, whether the addition of chemotherapy to CIRT is needed remains unknown. These questions will be evaluated in the dose-escalating phase I and randomized phase II trials.
基金Supported by grants from the National Basic Research Program of China(No.2010CB834202)Knowledge Innovation Projection of Chinese Academy of Science(No.KJCX2-YW-L08)The National Natural Science Foundation of China(No.10835011,No.10675151,No.41161058,No.31060065 and No.10805064)
文摘This study investigated the impact of simulated microgravity on acute injury induced by low doses of carbon ions in male reproductive organs of mice,and determined alterations in spermatogenic function and expression levels of apoptotic factors in mice following exposure to acute irradiation after 7 days of simulated microgravity.The results demonstrated that significant reductions in spermatozoa,primary spermatocytes and spermatogonia,and increased globular cells in seminiferous tubule and pro-apoptotic proteins were observed in the group exposed to over0.4 Gy irradiation.Collectively,the data suggest that lesions inflicted by simulated microgravity are not markedly modified by lower doses of irradiation(0.2 Gy)in mouse testis compared to the control group.However,testicular impairments were markedly evident in the group exposed to higher doses of carbon ions plus simulated microgravity,which may be due at least in part to elevated apoptosis initiated by the mitochondrial apoptosis pathway in germ cells.
基金Supported by the National Natural Science Foundation of China (Grant No.10105012) and the Major Subject of National Natural Science Foundation of China (10335050)
文摘The bystander effects induced by medium from human hepatoma SMMC-7721 and adenocarcinoma F56 cells irradiated with carbon ions were investigated. It was found that the survival fraction (SF) of the irradiated cells decreased exponentially along with the increased dose. SMMC-7721 cells were more radiosensitive than F56 cells. The plating efficiency (PE) of the non-irradiated cells treated with irradiated conditioned medium (ICM) was obvi-ously lower than the PE of control cells for SMMC-7721 cells but not for F56 cells. Moreover, the reduced PE and SF by ICM treatment were more significant for 1Gy irradiation than for 6Gy irradiation on SMMC-7721 cells. These results suggest that the irradiated cells can secrete factor(s) into medium that is cytotoxic to bystander non-irradiated cells. The bystander effects are dependent on cell genotype presented at the time of irradiation and radiation dose. This makes impact on the precise estimation of the effects of radiation and tumor radiotherapy.
文摘本文以管状和盘状两种天然硅藻土作为初始原料,制备了一系列硅藻土衍生硅碳负极材料,并采用X射线衍射仪(XRD)、拉曼光谱(Raman)、扫描电子显微镜(SEM)、透射电子显微镜(TEM)、X-射线光电子能谱(XPS)等测试手段系统表征了所制备样品的晶体结构、微观形貌及化学组成.将制备的硅藻土衍生硅碳负极材料作为活性物质组装为锂离子电池,对比了管状和盘状两种形貌对其储锂性能的影响,并详细考察了沥青衍生碳包覆层的加入量对硅碳负极材料比容量及循环稳定性的影响.测试结果表明,样品管DE-1∶3和管DE-1∶6在0.2 A g^(-1)较低电流密度下均具有较好的容量保持率,循环500次之后比容量分别可保持443 mAh g^(-1)和414 mAh g^(-1),而样品管DE-1∶6则在0.5 A g^(-1)较大电流密度下具有更好的结构稳定性.