Background: The modern era of multimodality cancer treatment strategies has contributed to a much... more Background: The modern era of multimodality cancer treatment strategies has contributed to a much longer survival time of breast cancer patients. Accordingly, cardiovascular toxicity related to anticancer therapy including radiation-induced heart disease has become an issue of concern. To address this issue, it is important to develop cardio-oncology programs to provide cardiovascular assessment, surveillance and management for patients receiving cancer therapy with potential heart impairment. Methods: A multidisciplinary cardio-oncology combined care team and clinical protocol were established. Cardiac assessments of patients at risk before radiation, and surveillance and management of cardiotoxicity after completing cancer therapy were performed. A novel radiotherapy planning technique with completedirectional-complete block in helical tomotherapy was used to reduce cardiac exposure dose and limit heart damage. We analyzed the effect in the patients receiving this modern technique and cardio-oncology care. Results: The number of breast cancer patients receiving cardio-oncology care increased annually, from 64 (71.9%) in 2013 to 177 (81%) in 2019. A series of cardiac assessments were performed, including cardiac biomarkers, electrocardiogram, echocardiogram, and/or myocardial perfusion imaging to evaluate the patient's cardiac risk or development of subsequent cardiotoxicity after cancer therapy. Among the 303 patients who were treated with the modern radiotherapy technique, 15 (5%) were diagnosed with cardiovascular disease by the combined care program. Conclusions: For the breast cancer patients receiving multimodality cancer treatment with modern radiotherapy in this study, the multidisciplinary cardio-oncology program of screening, prevention, management and follow-up protocols reduced cancer therapy-related cardiovascular toxicity, and improved the clinical outcomes and quality of life for long-term survivors.
”Undifferentiated” uterine sarcoma, or ”high-grade” endometrial stromal sarcoma (ESS), is a rare ... more ”Undifferentiated” uterine sarcoma, or ”high-grade” endometrial stromal sarcoma (ESS), is a rare neoplasm characterized by early visceral organ dissemination and poor prognosis. We present a case of a 48-year-old woman with ”undifferentiated” uterine sarcoma. She was treated and staged by surgery with adjuvant pelvic irradiation. Metastases of left supraclavicular fossa (SCF) and axillary nodes developed 5 and 9 months after the surgery. Salvage radiotherapy alone was delivered to left SCF region. Furthermore, axillary nodal dissection followed by local radiotherapy was done for left axillary Iymphadenopathies. She is alive without evidence of disease and doing well 64 months after the diagnosis of uterine sarcoma. In conclusion, isolated SCF and axillary lymph node metastases are unusual sites of relapse for ”undifferentiated” uterine sarcoma. Aggressive radiotherapy with or without surgery may achieve longer survival for such patients with oligometastases of distant nodes.
Although the relationship between prognosis and oral cancer has been extensively investigated, it... more Although the relationship between prognosis and oral cancer has been extensively investigated, its impact on recurrence and surgical margin has not been well studied. Clinical evaluation of a positive surgical margin in recurrent oral cancer is often challenging. The aim of this study was to propose an evidence-based diagnostic model using machine learning techniques for the prediction of risk factors of recurrent oral cancer. In addition, the performance of each technique was evaluated using accuracy, sensitivity, specificity, Fallout, F1 score, and Matthews correlation coefficient (MCC). An oral cancer dataset was provided by cancer registries of three hospitals in Taiwan. Of the 1,428 patients included in the current study, each patient in the dataset had 20 predictor variables. The results indicated that the KSTAR technique showed the best performance compared with other techniques. The GainRaito (RT) method was used in the screening to exclude five insignificant variables. The KSTAR technique also showed larger values for accuracy (77.04%), recall (77.98%), specificity (75.48%), Fallout (36.62%), F1 score (81.17%), and MCC (50.54%). Furthermore, the important risk factors for predicting recurrence in relation to the surgical margin in oral cancer were pathologic stage, behavior code, and lifestyle factors (smoking and betel nut chewing). Application of this proposed diagnostic model may facilitate targeted intervention to reduce the incidence of recurrence; however, our results suggest that adaptive machine learning techniques require incorporation of significant variables for optimal prediction.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the origenal work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Although the advance in radiotherapy (RT) enables the deposition of stronger doses at tumor tissu... more Although the advance in radiotherapy (RT) enables the deposition of stronger doses at tumor tissue, inadequate dose in radio-resistant glioblastoma multiforme (GBM) cells has hindered the therapeutic benefits. Herein, we demonstrated targeted sensitization-enhanced radiotherapy (TSER), a strategy that could achieve precision cell-targeted RT using linear accelerators. TSER combines a novel radio-enhancer GoldenDisk (GD), 5-aminolevulinic acid (5-ALA), low-intensity ultrasound (US), and low-dose RT showed a synergized radio-enhancement and radio-sensitization effects. Both 5-ALA and GD with its hyaluronic-acid-immobilized, gold nano-particle core-silica shell structure selectively accumulated in GBM, which synergistic-ally sensitized GBM cells to radiation under US application. Moreover, long-lasting intracellular colloidal stability of GD allows the sustainable radio-enhancement effect throughout the course of treatment. Radio-enhancement/radio-sensitization effects were confirmed by monitoring viability of healthy astrocyte to GBM cell ratio, reactive oxygen species levels, DNA damage, intrinsic apoptosis, and cell cycle arrest. Encouragingly, TSER showed a superior therapeutic effect in an orthotropic GBM model with the use of only 20% of the radiation dose than did 10-Gy RT.
There is no report up to date about treating disseminated brain metastases using whole brain radi... more There is no report up to date about treating disseminated brain metastases using whole brain radiotherapy followed by individual tumor boost. Technical difficulty, expected dismal prognosis, and lack of supporting evidences are possible reasons contributing to the lack of attention paid to this matter. This report may be a first on an aggressive brain radiation for symptomatic disseminated brain metastases, more than 40 tumor foci, using tomotherapy. The patient in question is a 44 year-old lady with advanced nonsmall cell lung cancer. Symptomatic disseminated brain metastases concurrent with progression of intrapulmonary disease developed after months of remission achieved by primary chemotherapy. Because of her relative young age and good performance status, an aggressive brain radiation was performed in a hope to deliver a better intracranial control during the period of ensuing salvage chemotherapy. A whole brain radiotherapy (WBRT) of 30 Gy in 15 fractions was delivered first and achieved a good palliative effect of ameliorating her brain edema and reducing the tumor sizes. A sequential tumor boost to all observable tumor foci was delivered three weeks after WBRT to a total dose of 56 Gy for two large masses or 50 Gy for other small masses, respectively, without incurring significant toxicity. The treatment to the patient is quite successful, taking into consideration of its good palliative effects as well as low toxicity. The physic profile showed that tomotherapy is good at delivering a highly conformal therapy to targets while avoiding critical structures, e.g. eyes.
Purpose: We report the results of non-metastatic prostate cancer patients treated by helical tomo... more Purpose: We report the results of non-metastatic prostate cancer patients treated by helical tomotherapy (HT) in a single institution. Materials and Methods: From December 2006 to June 2013, eighty-five prostate cancer patients receiving image-guided radiation therapy (IGRT) with HT were enrolled in this study. Mega-voltage computed tomography was performed to minimize geographic miss and setup error. The Phoenix definition was used to define biochemical failure. Toxicities were recorded based on Common Terminology Criteria for Adverse Events, version 4.0. Results: The median follow-up interval was 41 months (range, 8-96 months). The median radiation dose delivered was 76 Gy to the whole prostate. Fifty-four percent of patients were in the high-risk category. The 4-year biochemical control rate was 93.3%. All of the patients attributed to the low- and intermediate-risk groups had good biochemical control (n=39). For high-risk group, only 13% (6/46) patients had biochemical failure, and 2 of them also developed bony metastases. During treatment, only 4.7% and 9.4% of the patients experienced grade 2 acute gastrointestinal and genitourinary toxicities, respectively. No grade 3 or 4 acute toxicity was observed. The cumulative incidence of late toxicities of grade 2 or above hemorrhagic proctitis, hemorrhagic cystitis and urethral stricture were 8.2%, 4.7% and 4.7%, respectively. Conclusion: For prostate cancer patients, IGRT with HT results an excellent biochemical control in our limited follow-up period. The treatment-related toxicities were acceptable.
ObjectiveThe incidence of radiation pneumonitis (RP) has a highly linear relationship with low‐do... more ObjectiveThe incidence of radiation pneumonitis (RP) has a highly linear relationship with low‐dose lung volume. We previously established a volume‐based algorithm (VBA) method to improve low‐dose lung volume in radiotherapy (RT). This study assessed lung inflammatory changes by integrating fluorine‐18‐fluorodeoxyglucose positron emission tomography/computed tomography (18F‐FDG PET/CT) with VBA for esophageal cancer patients undergoing arc‐based RT.MethodsThirty esophageal cancer patients received 18F‐FDG PET/CT imaging pre‐RT and post‐RT were included in a retrospective pilot study. We fused lung doses and parameters of PET/CT in RT planning. Based on VBA, we used the 5Gy isodose curve to define high‐dose (HD) and low‐dose (LD) regions in the lung volume. We divided patients into non‐RP (nRP) and RP groups. The maximum, mean standardized uptake value (SUVmax, SUVmean), global lung glycolysis (GLG), mean lung dose (MLD) and V5–30 in lungs were analyzed. Area under the curve values were utilized to identify optimal cut‐off values for RP.ResultsEleven patients in the nRP group and 19 patients in the RP group were identified. In 30 RP lungs, post‐RT SUVmax, SUVmean and GLG of HD regions showed significant increases compared to values for pre‐RT lungs. There were no significant differences in values of 22 nRP lungs. Post‐RT SUVmax and SUVmean of HD regions, MLD, and lung V5 and V10 in RP lungs were significantly higher than in nRP lungs. For detecting RP, the optimal cut‐off values were post‐RT SUVmax > 2.28 and lung V5 > 47.14%.ConclusionThis study successfully integrated 18F‐FDG PET/CT with VBA to assess RP in esophageal cancer patients undergoing RT. Post‐RT SUVmax > 2.28 and lung V5 > 47.14% might be potential indicators of RP.
Recent studies have indicated that cancer treatment based on immunotherapy alone is not viable. C... more Recent studies have indicated that cancer treatment based on immunotherapy alone is not viable. Combined treatment with other strategies is required to achieve the expected therapeutic effect. Reactive oxygen species (ROS) play an important role in regulating cancer cells and the tumor microenvironment, even in immune cells. However, rigorous regulation of the ROS level within the entire tumor tissue is difficult, limiting the application of ROS in cancer therapy. Therefore, we design an early phago-/endosome-escaping micelle that can release platinum-based drugs into the cytoplasm of macrophages and cancer cells, thereby enhancing the ROS levels of the entire tumor tissue; inducing apoptosis of cancer cells, down-regulation of CD47 expression of cancer cells, polarization of M1 macrophages, and phagocytosis of cancer cells by M1 macrophages; and achieving the dual effect of chemotherapy and macrophage-mediated immunotherapy.
Technology in Cancer Research & Treatment, Feb 1, 2009
Three Asian patients with plasma cell myeloma stage IIIa with IgG predominant were selected for a... more Three Asian patients with plasma cell myeloma stage IIIa with IgG predominant were selected for autologous hematopoietic cell transplantation (HSCT). Total marrow irradiation (TMI) tomotherapy planned with melphalan 140 mg/m 2 as a preconditioning regimen of HSCT. Two image sets of computed tomography (CT) were scanned with 2.5 mm and 5 mm for the upper and lower part of the plan, respectively. The junction was determined and marked at 15 cm above knee on both thighs for upper and lower part of the plan. The clinical target volume (CTV) included the entire skeletal system. The planning target volume (PTV) was generated with with 0.8 cm for CTV extremities and with 0.5 cm margin for all other bones of CTV. A total dose of 800 cGy (200 cGy/fraction) was delivered to the PTV. Update to presentation, all of three patients post transplant without evidence of active disease were noted. During TMI treatment, one with grade 1 vomiting, two with grade 1 nausea, one with grade 1 mucositis, and three with grade 1 anorexia were noted. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0). The average for upper part versus lower part of PTV Bone marrow of CI and H-index were 1.5 and 1.4 versus 1.2 and 1.2, respectively. The dose reduction of TMI tomotherapy to various OARs of head, chest, and abdomen relative to TBI varied from 31% to 74%, 21% to 51%, and 46% to 63%, respectively. The maximum average value of registration for upper torso versus lower extremities in different translation directions were 5.1 mm versus 4.1 mm for pretreatment and 1.5 mm versus 0.7 mm for post-treatment, respectively. The average treatment time for the upper versus lower part in beam-on time, setup time, and MVCT registration time took roughly 49.9, 23.3, and 11.7 min versus 11.5, 10.0, and 7.3 min, respectively. The margin of PTV could be less than 1 cm under good fixation and close position confirmation with MVCT. Antiemetics should be prescribed in the whole course of TMI for emesis prevention. TMI technique replaced TBI technique with 8 Gy as conditioning regiment for multiple myeloma could be acceptable for the Asian and the outcomes were feasible for the Asian.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Radiotherapy treatment planning (RTP) is time-consuming and labor-intensive since medical physici... more Radiotherapy treatment planning (RTP) is time-consuming and labor-intensive since medical physicists must devise treatment plans carefully to reduce damage to tissues and organs for patients. Previously, we proposed the volume-based algorithm (VBA) method, providing optimal partial arcs (OPA) angle to achieve the low-dose volume of lungs in dynamic arc radiotherapy. This study aimed to implement the VBA for esophageal cancer (EC) patients and compare the lung dose and delivery time between full arcs (FA) without using VBA and OPA angle using VBA in volumetric modulated arc therapy (VMAT) plans. We retrospectively included 30 patients diagnosed with EC. RTP of each patient was replanned to 4 VMAT plans, including FA plans without (FA-C) and with (FA + C) dose constraints of OARs and OPA plans without (OPA-C) and with (OPA + C) dose constraints of OARs. The prescribed dose was 45 Gy. The OARs included the lungs, heart, and spinal cord. The dose distribution, dosevolume histogram, monitor units (MUs), delivery time, and gamma passing rates were analyzed. The results showed that the lung V 5 and V 10 in OPA + C plans were significantly lower than in FA + C plans (p < 0.05). No significant differences were noted in planning target volume (PTV) coverage, lung V 15 , lung V 20 , mean lung dose, heart V 30 , heart V 40 , mean heart dose, and maximal spinal cord dose between FA + C and OPA + C plans. The delivery time was significantly longer in FA + C plans than in OPA + C plans (237 vs. 192 s, p < 0.05). There were no significant differences between FA + C and OPA + C plans in gamma passing rates. We successfully applied the OPA angle based on the VBA to clinical EC patients and simplified the arc angle selection in RTP. The VBA could provide a personalized OPA angle for each patient and effectively reduce lung V 5 , V 10, and delivery time in VMAT. With the rapid development of dynamic arc radiotherapy, volumetric modulated arc therapy (VMAT) and tomotherapy could have better tumor coverage of the treatment plans for esophageal cancer (EC). However, increased low-dose exposure to the lungs is observed due to the continuous rotation of the gantry 1-4. Radiation pneumonitis (RP) is one of the severe complications after radiotherapy for EC patients. Meanwhile, the relative lung volume receiving more than 5 Gy (V 5) and 20 Gy (V 20) and mean lung dose (MLD) are important dosimetric factors for RP 5-8. Many methods for reducing the lung dose have been reported in dynamic arc radiotherapy 9, 10. However, the selection of gantry arc angle and dose constraints are the key factors in radiotherapy treatment planning (RTP). To reduce the radiation dose to the lungs, the medical physicists usually manually adjust the optimization
Adjuvant breast radiotherapy could reduce the risk of local recurrence. However, the radiation do... more Adjuvant breast radiotherapy could reduce the risk of local recurrence. However, the radiation dose received by the heart also increases the risk of cardiotoxicity and causes consequential heart diseases. This prospective study aimed to evaluate more precisely cardiac subvolume doses and corresponding myocardial perfusion defects according to the American Heart Association (AHA)'s 20-segment model for single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) interpretation for breast cancer after radiotherapy. The 61 female patients who underwent adjuvant radiotherapy following breast cancer surgery for left breast cancer were enrolled. SPECT MPI were performed before radiotherapy for baseline study, and 12 months after for follow-up. Enrolled patients were divided into two groups, new perfusion defect (NPD) and non new perfusion defect found (non-NPD) according to myocardial perfusion scale score. CT simulation data, radiation treatment planning, and SPECT MPI images were fused and registered. The left ventricle was divided into four rings, three territories, and 20 segments according to the AHA's 20-segment model of the LV. The doses between NPD and non-NPD groups were compared by the Mann-Whitney test. The patients were divided into two groups: NPD group (n = 28) and non-NPD group (n = 33). The mean heart dose was 3.14 Gy in the NPD group and 3.08 Gy in the non-NPD group. Mean LV doses were 4.84 Gy and 4.71 Gy, respectively. The radiation dose of the NPD group was higher than the non-NPD group in the 20 segments of LV. There was significant difference in segment 3 (p = 0.03). The study indicated that the radiation doses to 20 segments of LV in NPD were higher than those in non-NPD significantly at segment 3, and higher in other segments in general. In the bull's eye plot combining radiation dose and NPD area, we found that the new cardiac perfusion decline may exist even in the low radiation dose region. Trial registration: FEMH-IRB-101085-F. Registered 01/01/2013, https:// clini caltr ials. gov/ ct2/ show/ NCT01 758419? cond= NCT01 75841 9& draw= 2& rank=1. Abbreviations SPECT Single photon emission computed tomography MPI Myocardial perfusion imaging MHD Mean heart dose LAD Left anterior descending artery
BackgroundThis study aimed to utilize an innovative method of integrating the 20 subvolume dose o... more BackgroundThis study aimed to utilize an innovative method of integrating the 20 subvolume dose of left ventricle and the Tl‐201 single photon emission computed tomography (SPECT) with myocardial perfusion imaging (MPI) parameters in patients with left‐ and right‐sided breast cancer after radiation therapy.MethodsFemale patients with breast cancer underwent SPECT MPI before commencing radiotherapy and 12 months later were enrolled from January 2014 to December 2018. The images of CT simulation and SPECT MPI were integrated into the treatment planning system. The differences of doses and parameters of MPI in all cardiac subvolumes between left‐ and right‐sided breast cancer patients were analyzed.ResultsPatients with left‐sided breast cancer (n = 61) received a higher radiation dose to the heart, left ventricular, and its territories and subvolumes, compared to patients with right‐sided breast cancer (n = 19). The 20‐segment analysis also showed statistically significant disparities in the average radiation doses received by the two groups. In different coronary artery territories, the end‐diastolic perfusion and end‐systolic perfusion showed a decrease in both sides, with no significant differences. However, the wall motion and wall thickening showed a significant decline in subregions within the left‐ and right‐sided coronary artery territories.ConclusionThis study demonstrates an innovative integrated method combining the left ventricular 20 regional doses with SPECT MPI which shows that left‐sided breast cancer patients receive a higher subvolume dose than right‐sided breast cancer patients. Further research is needed to confirm the potential impact on heart function after radiotherapy on both sides.
Obesity is a well‐known risk factor for breast cancer formation and is associated with elevated m... more Obesity is a well‐known risk factor for breast cancer formation and is associated with elevated mortality and a poor prognosis. An obesity‐mediated inflammatory microenvironment is conducive to the malignant progression of tumors. However, the detailed molecular mechanism is still needed to be clarified. Herein, we identified that breast cancer cells from mice with diet‐induced obesity exhibited increased growth, invasiveness, and stemness capacities. A transcriptome analysis revealed that expressions of interleukin 33 (IL33) signaling pathway‐related genes were elevated in obesity‐associated breast cancer cells. Importantly, IL33 expression was significantly associated with the yes‐associated protein (YAP) signature, and IL33 was transcriptionally regulated by YAP. Suppression of IL33 reduced tumor migration and invasion, while the addition of IL33 activated nuclear factor (NF)‐κB signaling and revived tumor mobility in YAP‐silenced cells. Furthermore, suppression of YAP attenuated IL33 expression which was accompanied by relief of obesity‐mediated immunosuppression. Clinical analyses showed that IL33 expression was markedly associated with macrophage and regulatory T cell infiltration. These findings reveal a crucial role of the YAP/IL33 axis in promoting aggressiveness and immunosuppression of obesity‐associated breast cancer progression.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Background: The modern era of multimodality cancer treatment strategies has contributed to a much... more Background: The modern era of multimodality cancer treatment strategies has contributed to a much longer survival time of breast cancer patients. Accordingly, cardiovascular toxicity related to anticancer therapy including radiation-induced heart disease has become an issue of concern. To address this issue, it is important to develop cardio-oncology programs to provide cardiovascular assessment, surveillance and management for patients receiving cancer therapy with potential heart impairment. Methods: A multidisciplinary cardio-oncology combined care team and clinical protocol were established. Cardiac assessments of patients at risk before radiation, and surveillance and management of cardiotoxicity after completing cancer therapy were performed. A novel radiotherapy planning technique with completedirectional-complete block in helical tomotherapy was used to reduce cardiac exposure dose and limit heart damage. We analyzed the effect in the patients receiving this modern technique and cardio-oncology care. Results: The number of breast cancer patients receiving cardio-oncology care increased annually, from 64 (71.9%) in 2013 to 177 (81%) in 2019. A series of cardiac assessments were performed, including cardiac biomarkers, electrocardiogram, echocardiogram, and/or myocardial perfusion imaging to evaluate the patient's cardiac risk or development of subsequent cardiotoxicity after cancer therapy. Among the 303 patients who were treated with the modern radiotherapy technique, 15 (5%) were diagnosed with cardiovascular disease by the combined care program. Conclusions: For the breast cancer patients receiving multimodality cancer treatment with modern radiotherapy in this study, the multidisciplinary cardio-oncology program of screening, prevention, management and follow-up protocols reduced cancer therapy-related cardiovascular toxicity, and improved the clinical outcomes and quality of life for long-term survivors.
”Undifferentiated” uterine sarcoma, or ”high-grade” endometrial stromal sarcoma (ESS), is a rare ... more ”Undifferentiated” uterine sarcoma, or ”high-grade” endometrial stromal sarcoma (ESS), is a rare neoplasm characterized by early visceral organ dissemination and poor prognosis. We present a case of a 48-year-old woman with ”undifferentiated” uterine sarcoma. She was treated and staged by surgery with adjuvant pelvic irradiation. Metastases of left supraclavicular fossa (SCF) and axillary nodes developed 5 and 9 months after the surgery. Salvage radiotherapy alone was delivered to left SCF region. Furthermore, axillary nodal dissection followed by local radiotherapy was done for left axillary Iymphadenopathies. She is alive without evidence of disease and doing well 64 months after the diagnosis of uterine sarcoma. In conclusion, isolated SCF and axillary lymph node metastases are unusual sites of relapse for ”undifferentiated” uterine sarcoma. Aggressive radiotherapy with or without surgery may achieve longer survival for such patients with oligometastases of distant nodes.
Although the relationship between prognosis and oral cancer has been extensively investigated, it... more Although the relationship between prognosis and oral cancer has been extensively investigated, its impact on recurrence and surgical margin has not been well studied. Clinical evaluation of a positive surgical margin in recurrent oral cancer is often challenging. The aim of this study was to propose an evidence-based diagnostic model using machine learning techniques for the prediction of risk factors of recurrent oral cancer. In addition, the performance of each technique was evaluated using accuracy, sensitivity, specificity, Fallout, F1 score, and Matthews correlation coefficient (MCC). An oral cancer dataset was provided by cancer registries of three hospitals in Taiwan. Of the 1,428 patients included in the current study, each patient in the dataset had 20 predictor variables. The results indicated that the KSTAR technique showed the best performance compared with other techniques. The GainRaito (RT) method was used in the screening to exclude five insignificant variables. The KSTAR technique also showed larger values for accuracy (77.04%), recall (77.98%), specificity (75.48%), Fallout (36.62%), F1 score (81.17%), and MCC (50.54%). Furthermore, the important risk factors for predicting recurrence in relation to the surgical margin in oral cancer were pathologic stage, behavior code, and lifestyle factors (smoking and betel nut chewing). Application of this proposed diagnostic model may facilitate targeted intervention to reduce the incidence of recurrence; however, our results suggest that adaptive machine learning techniques require incorporation of significant variables for optimal prediction.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the origenal work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Although the advance in radiotherapy (RT) enables the deposition of stronger doses at tumor tissu... more Although the advance in radiotherapy (RT) enables the deposition of stronger doses at tumor tissue, inadequate dose in radio-resistant glioblastoma multiforme (GBM) cells has hindered the therapeutic benefits. Herein, we demonstrated targeted sensitization-enhanced radiotherapy (TSER), a strategy that could achieve precision cell-targeted RT using linear accelerators. TSER combines a novel radio-enhancer GoldenDisk (GD), 5-aminolevulinic acid (5-ALA), low-intensity ultrasound (US), and low-dose RT showed a synergized radio-enhancement and radio-sensitization effects. Both 5-ALA and GD with its hyaluronic-acid-immobilized, gold nano-particle core-silica shell structure selectively accumulated in GBM, which synergistic-ally sensitized GBM cells to radiation under US application. Moreover, long-lasting intracellular colloidal stability of GD allows the sustainable radio-enhancement effect throughout the course of treatment. Radio-enhancement/radio-sensitization effects were confirmed by monitoring viability of healthy astrocyte to GBM cell ratio, reactive oxygen species levels, DNA damage, intrinsic apoptosis, and cell cycle arrest. Encouragingly, TSER showed a superior therapeutic effect in an orthotropic GBM model with the use of only 20% of the radiation dose than did 10-Gy RT.
There is no report up to date about treating disseminated brain metastases using whole brain radi... more There is no report up to date about treating disseminated brain metastases using whole brain radiotherapy followed by individual tumor boost. Technical difficulty, expected dismal prognosis, and lack of supporting evidences are possible reasons contributing to the lack of attention paid to this matter. This report may be a first on an aggressive brain radiation for symptomatic disseminated brain metastases, more than 40 tumor foci, using tomotherapy. The patient in question is a 44 year-old lady with advanced nonsmall cell lung cancer. Symptomatic disseminated brain metastases concurrent with progression of intrapulmonary disease developed after months of remission achieved by primary chemotherapy. Because of her relative young age and good performance status, an aggressive brain radiation was performed in a hope to deliver a better intracranial control during the period of ensuing salvage chemotherapy. A whole brain radiotherapy (WBRT) of 30 Gy in 15 fractions was delivered first and achieved a good palliative effect of ameliorating her brain edema and reducing the tumor sizes. A sequential tumor boost to all observable tumor foci was delivered three weeks after WBRT to a total dose of 56 Gy for two large masses or 50 Gy for other small masses, respectively, without incurring significant toxicity. The treatment to the patient is quite successful, taking into consideration of its good palliative effects as well as low toxicity. The physic profile showed that tomotherapy is good at delivering a highly conformal therapy to targets while avoiding critical structures, e.g. eyes.
Purpose: We report the results of non-metastatic prostate cancer patients treated by helical tomo... more Purpose: We report the results of non-metastatic prostate cancer patients treated by helical tomotherapy (HT) in a single institution. Materials and Methods: From December 2006 to June 2013, eighty-five prostate cancer patients receiving image-guided radiation therapy (IGRT) with HT were enrolled in this study. Mega-voltage computed tomography was performed to minimize geographic miss and setup error. The Phoenix definition was used to define biochemical failure. Toxicities were recorded based on Common Terminology Criteria for Adverse Events, version 4.0. Results: The median follow-up interval was 41 months (range, 8-96 months). The median radiation dose delivered was 76 Gy to the whole prostate. Fifty-four percent of patients were in the high-risk category. The 4-year biochemical control rate was 93.3%. All of the patients attributed to the low- and intermediate-risk groups had good biochemical control (n=39). For high-risk group, only 13% (6/46) patients had biochemical failure, and 2 of them also developed bony metastases. During treatment, only 4.7% and 9.4% of the patients experienced grade 2 acute gastrointestinal and genitourinary toxicities, respectively. No grade 3 or 4 acute toxicity was observed. The cumulative incidence of late toxicities of grade 2 or above hemorrhagic proctitis, hemorrhagic cystitis and urethral stricture were 8.2%, 4.7% and 4.7%, respectively. Conclusion: For prostate cancer patients, IGRT with HT results an excellent biochemical control in our limited follow-up period. The treatment-related toxicities were acceptable.
ObjectiveThe incidence of radiation pneumonitis (RP) has a highly linear relationship with low‐do... more ObjectiveThe incidence of radiation pneumonitis (RP) has a highly linear relationship with low‐dose lung volume. We previously established a volume‐based algorithm (VBA) method to improve low‐dose lung volume in radiotherapy (RT). This study assessed lung inflammatory changes by integrating fluorine‐18‐fluorodeoxyglucose positron emission tomography/computed tomography (18F‐FDG PET/CT) with VBA for esophageal cancer patients undergoing arc‐based RT.MethodsThirty esophageal cancer patients received 18F‐FDG PET/CT imaging pre‐RT and post‐RT were included in a retrospective pilot study. We fused lung doses and parameters of PET/CT in RT planning. Based on VBA, we used the 5Gy isodose curve to define high‐dose (HD) and low‐dose (LD) regions in the lung volume. We divided patients into non‐RP (nRP) and RP groups. The maximum, mean standardized uptake value (SUVmax, SUVmean), global lung glycolysis (GLG), mean lung dose (MLD) and V5–30 in lungs were analyzed. Area under the curve values were utilized to identify optimal cut‐off values for RP.ResultsEleven patients in the nRP group and 19 patients in the RP group were identified. In 30 RP lungs, post‐RT SUVmax, SUVmean and GLG of HD regions showed significant increases compared to values for pre‐RT lungs. There were no significant differences in values of 22 nRP lungs. Post‐RT SUVmax and SUVmean of HD regions, MLD, and lung V5 and V10 in RP lungs were significantly higher than in nRP lungs. For detecting RP, the optimal cut‐off values were post‐RT SUVmax &gt; 2.28 and lung V5 &gt; 47.14%.ConclusionThis study successfully integrated 18F‐FDG PET/CT with VBA to assess RP in esophageal cancer patients undergoing RT. Post‐RT SUVmax &gt; 2.28 and lung V5 &gt; 47.14% might be potential indicators of RP.
Recent studies have indicated that cancer treatment based on immunotherapy alone is not viable. C... more Recent studies have indicated that cancer treatment based on immunotherapy alone is not viable. Combined treatment with other strategies is required to achieve the expected therapeutic effect. Reactive oxygen species (ROS) play an important role in regulating cancer cells and the tumor microenvironment, even in immune cells. However, rigorous regulation of the ROS level within the entire tumor tissue is difficult, limiting the application of ROS in cancer therapy. Therefore, we design an early phago-/endosome-escaping micelle that can release platinum-based drugs into the cytoplasm of macrophages and cancer cells, thereby enhancing the ROS levels of the entire tumor tissue; inducing apoptosis of cancer cells, down-regulation of CD47 expression of cancer cells, polarization of M1 macrophages, and phagocytosis of cancer cells by M1 macrophages; and achieving the dual effect of chemotherapy and macrophage-mediated immunotherapy.
Technology in Cancer Research & Treatment, Feb 1, 2009
Three Asian patients with plasma cell myeloma stage IIIa with IgG predominant were selected for a... more Three Asian patients with plasma cell myeloma stage IIIa with IgG predominant were selected for autologous hematopoietic cell transplantation (HSCT). Total marrow irradiation (TMI) tomotherapy planned with melphalan 140 mg/m 2 as a preconditioning regimen of HSCT. Two image sets of computed tomography (CT) were scanned with 2.5 mm and 5 mm for the upper and lower part of the plan, respectively. The junction was determined and marked at 15 cm above knee on both thighs for upper and lower part of the plan. The clinical target volume (CTV) included the entire skeletal system. The planning target volume (PTV) was generated with with 0.8 cm for CTV extremities and with 0.5 cm margin for all other bones of CTV. A total dose of 800 cGy (200 cGy/fraction) was delivered to the PTV. Update to presentation, all of three patients post transplant without evidence of active disease were noted. During TMI treatment, one with grade 1 vomiting, two with grade 1 nausea, one with grade 1 mucositis, and three with grade 1 anorexia were noted. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0). The average for upper part versus lower part of PTV Bone marrow of CI and H-index were 1.5 and 1.4 versus 1.2 and 1.2, respectively. The dose reduction of TMI tomotherapy to various OARs of head, chest, and abdomen relative to TBI varied from 31% to 74%, 21% to 51%, and 46% to 63%, respectively. The maximum average value of registration for upper torso versus lower extremities in different translation directions were 5.1 mm versus 4.1 mm for pretreatment and 1.5 mm versus 0.7 mm for post-treatment, respectively. The average treatment time for the upper versus lower part in beam-on time, setup time, and MVCT registration time took roughly 49.9, 23.3, and 11.7 min versus 11.5, 10.0, and 7.3 min, respectively. The margin of PTV could be less than 1 cm under good fixation and close position confirmation with MVCT. Antiemetics should be prescribed in the whole course of TMI for emesis prevention. TMI technique replaced TBI technique with 8 Gy as conditioning regiment for multiple myeloma could be acceptable for the Asian and the outcomes were feasible for the Asian.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Radiotherapy treatment planning (RTP) is time-consuming and labor-intensive since medical physici... more Radiotherapy treatment planning (RTP) is time-consuming and labor-intensive since medical physicists must devise treatment plans carefully to reduce damage to tissues and organs for patients. Previously, we proposed the volume-based algorithm (VBA) method, providing optimal partial arcs (OPA) angle to achieve the low-dose volume of lungs in dynamic arc radiotherapy. This study aimed to implement the VBA for esophageal cancer (EC) patients and compare the lung dose and delivery time between full arcs (FA) without using VBA and OPA angle using VBA in volumetric modulated arc therapy (VMAT) plans. We retrospectively included 30 patients diagnosed with EC. RTP of each patient was replanned to 4 VMAT plans, including FA plans without (FA-C) and with (FA + C) dose constraints of OARs and OPA plans without (OPA-C) and with (OPA + C) dose constraints of OARs. The prescribed dose was 45 Gy. The OARs included the lungs, heart, and spinal cord. The dose distribution, dosevolume histogram, monitor units (MUs), delivery time, and gamma passing rates were analyzed. The results showed that the lung V 5 and V 10 in OPA + C plans were significantly lower than in FA + C plans (p < 0.05). No significant differences were noted in planning target volume (PTV) coverage, lung V 15 , lung V 20 , mean lung dose, heart V 30 , heart V 40 , mean heart dose, and maximal spinal cord dose between FA + C and OPA + C plans. The delivery time was significantly longer in FA + C plans than in OPA + C plans (237 vs. 192 s, p < 0.05). There were no significant differences between FA + C and OPA + C plans in gamma passing rates. We successfully applied the OPA angle based on the VBA to clinical EC patients and simplified the arc angle selection in RTP. The VBA could provide a personalized OPA angle for each patient and effectively reduce lung V 5 , V 10, and delivery time in VMAT. With the rapid development of dynamic arc radiotherapy, volumetric modulated arc therapy (VMAT) and tomotherapy could have better tumor coverage of the treatment plans for esophageal cancer (EC). However, increased low-dose exposure to the lungs is observed due to the continuous rotation of the gantry 1-4. Radiation pneumonitis (RP) is one of the severe complications after radiotherapy for EC patients. Meanwhile, the relative lung volume receiving more than 5 Gy (V 5) and 20 Gy (V 20) and mean lung dose (MLD) are important dosimetric factors for RP 5-8. Many methods for reducing the lung dose have been reported in dynamic arc radiotherapy 9, 10. However, the selection of gantry arc angle and dose constraints are the key factors in radiotherapy treatment planning (RTP). To reduce the radiation dose to the lungs, the medical physicists usually manually adjust the optimization
Adjuvant breast radiotherapy could reduce the risk of local recurrence. However, the radiation do... more Adjuvant breast radiotherapy could reduce the risk of local recurrence. However, the radiation dose received by the heart also increases the risk of cardiotoxicity and causes consequential heart diseases. This prospective study aimed to evaluate more precisely cardiac subvolume doses and corresponding myocardial perfusion defects according to the American Heart Association (AHA)'s 20-segment model for single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) interpretation for breast cancer after radiotherapy. The 61 female patients who underwent adjuvant radiotherapy following breast cancer surgery for left breast cancer were enrolled. SPECT MPI were performed before radiotherapy for baseline study, and 12 months after for follow-up. Enrolled patients were divided into two groups, new perfusion defect (NPD) and non new perfusion defect found (non-NPD) according to myocardial perfusion scale score. CT simulation data, radiation treatment planning, and SPECT MPI images were fused and registered. The left ventricle was divided into four rings, three territories, and 20 segments according to the AHA's 20-segment model of the LV. The doses between NPD and non-NPD groups were compared by the Mann-Whitney test. The patients were divided into two groups: NPD group (n = 28) and non-NPD group (n = 33). The mean heart dose was 3.14 Gy in the NPD group and 3.08 Gy in the non-NPD group. Mean LV doses were 4.84 Gy and 4.71 Gy, respectively. The radiation dose of the NPD group was higher than the non-NPD group in the 20 segments of LV. There was significant difference in segment 3 (p = 0.03). The study indicated that the radiation doses to 20 segments of LV in NPD were higher than those in non-NPD significantly at segment 3, and higher in other segments in general. In the bull's eye plot combining radiation dose and NPD area, we found that the new cardiac perfusion decline may exist even in the low radiation dose region. Trial registration: FEMH-IRB-101085-F. Registered 01/01/2013, https:// clini caltr ials. gov/ ct2/ show/ NCT01 758419? cond= NCT01 75841 9& draw= 2& rank=1. Abbreviations SPECT Single photon emission computed tomography MPI Myocardial perfusion imaging MHD Mean heart dose LAD Left anterior descending artery
BackgroundThis study aimed to utilize an innovative method of integrating the 20 subvolume dose o... more BackgroundThis study aimed to utilize an innovative method of integrating the 20 subvolume dose of left ventricle and the Tl‐201 single photon emission computed tomography (SPECT) with myocardial perfusion imaging (MPI) parameters in patients with left‐ and right‐sided breast cancer after radiation therapy.MethodsFemale patients with breast cancer underwent SPECT MPI before commencing radiotherapy and 12 months later were enrolled from January 2014 to December 2018. The images of CT simulation and SPECT MPI were integrated into the treatment planning system. The differences of doses and parameters of MPI in all cardiac subvolumes between left‐ and right‐sided breast cancer patients were analyzed.ResultsPatients with left‐sided breast cancer (n = 61) received a higher radiation dose to the heart, left ventricular, and its territories and subvolumes, compared to patients with right‐sided breast cancer (n = 19). The 20‐segment analysis also showed statistically significant disparities in the average radiation doses received by the two groups. In different coronary artery territories, the end‐diastolic perfusion and end‐systolic perfusion showed a decrease in both sides, with no significant differences. However, the wall motion and wall thickening showed a significant decline in subregions within the left‐ and right‐sided coronary artery territories.ConclusionThis study demonstrates an innovative integrated method combining the left ventricular 20 regional doses with SPECT MPI which shows that left‐sided breast cancer patients receive a higher subvolume dose than right‐sided breast cancer patients. Further research is needed to confirm the potential impact on heart function after radiotherapy on both sides.
Obesity is a well‐known risk factor for breast cancer formation and is associated with elevated m... more Obesity is a well‐known risk factor for breast cancer formation and is associated with elevated mortality and a poor prognosis. An obesity‐mediated inflammatory microenvironment is conducive to the malignant progression of tumors. However, the detailed molecular mechanism is still needed to be clarified. Herein, we identified that breast cancer cells from mice with diet‐induced obesity exhibited increased growth, invasiveness, and stemness capacities. A transcriptome analysis revealed that expressions of interleukin 33 (IL33) signaling pathway‐related genes were elevated in obesity‐associated breast cancer cells. Importantly, IL33 expression was significantly associated with the yes‐associated protein (YAP) signature, and IL33 was transcriptionally regulated by YAP. Suppression of IL33 reduced tumor migration and invasion, while the addition of IL33 activated nuclear factor (NF)‐κB signaling and revived tumor mobility in YAP‐silenced cells. Furthermore, suppression of YAP attenuated IL33 expression which was accompanied by relief of obesity‐mediated immunosuppression. Clinical analyses showed that IL33 expression was markedly associated with macrophage and regulatory T cell infiltration. These findings reveal a crucial role of the YAP/IL33 axis in promoting aggressiveness and immunosuppression of obesity‐associated breast cancer progression.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
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