Esophageal cancer is one of the most difficult cancers to treat since it is often at an advanced stage at the time of symptom presentation.For locally advanced esophageal cancer,treatment options include multidiscipli...Esophageal cancer is one of the most difficult cancers to treat since it is often at an advanced stage at the time of symptom presentation.For locally advanced esophageal cancer,treatment options include multidisciplinary treatment such as surgery or definitive chemoradiotherapy.Surgery has a high local control rate because it involves excision of the cancer along with the surrounding organs;however,it is still highly invasive,although advances in surgery have reduced the burden on patients.On the other hand,chemoradiotherapy may also be applicable in cases in which surgery is inoperable owing to complications or distant lymph node metastasis.However,chemoradiotherapy using X-ray irradiation can cause late toxicities,including those to the heart.Proton beam therapy is widely used to treat esophageal cancer because of its characteristics,and some comparisons between proton beam therapy and X-ray therapy or surgery have recently been reported.This review discusses the role of proton beam therapy in esophageal cancer in comparison to X-ray therapy and surgery.展开更多
Background:Few studies compared the effectiveness of the 3-monthly goserelin 10.8-mg and the monthly 3.6-mg depot in inducing ovarian function suppression for premenopausal patients with hormone receptor positive(HR+)...Background:Few studies compared the effectiveness of the 3-monthly goserelin 10.8-mg and the monthly 3.6-mg depot in inducing ovarian function suppression for premenopausal patients with hormone receptor positive(HR+)breast cancer.We conducted a large-scale real-world study(RWS)in China to validate the non-inferiority of goserelin 10.8-mg to the 3.6-mg depot.Methods:This multicenter,retrospective-prospective,non-inferiority study compared goserelin 10.8-mg with 3.6-mg in suppressing estradiol(E2)levels in premenopausal and perimenopausal patients with HR+breast cancer.Eligible patients were identified,and their demographic and clinical data were obtained from hospital medical records.The observation period was 28 weeks.Propensity score matching(PSM)ensured baseline comparability.The primary endpoint was the proportion of patients with E2 suppression to postmenopausal level at Week 12±4.Difference in proportions and 95%CI was calculated by Newcombe-Wilson score method.The non-inferiority margin was-10%.Subgroup and sensitivity analyses assessed result robustness.Results:From 1st January,2015 to 15th December,2023,15,629 patients from 16 hospitals nationwide were screened,with 1,060 eligible patients included in the full analysis set(3.6-mg group:678;10.8-mg group:382).Post-PSM,the primary endpoint was analyzed in 590 patients(295 in each group).At Week 12±4,the proportion of patients with E2 suppression was 99.1%(95%CI:96.9%-99.8%)for goserelin 10.8-mg and 95.3%(95%CI:91.0%-97.6%)for goserelin 3.6-mg.The difference was 3.8%(95%CI:0.6%-8.1%)with the lower limit of 95%CI greater than the non-inferiority margin.All subgroup analyses,including those based on age(≤45 or>45 years)and previous chemotherapy(yes/no),and all sensitivity analyses on the primary endpoint were consistent with the main analysis.展开更多
Radiochromic film for spot-scanning QA provides high spatial resolution and efficiency gains from one-shot irradiation for multiple depths. However, calibration can be a tedious procedure which may limit widespread us...Radiochromic film for spot-scanning QA provides high spatial resolution and efficiency gains from one-shot irradiation for multiple depths. However, calibration can be a tedious procedure which may limit widespread use. Moreover, since there may be an energy dependence, which manifests as a depth dependence, this may require additional measurements for each patient. We present a one-scan protocol to simplify the procedure. A calibration using an EBT3 film, exposed by a 6-level step-wedge plan on a Proteus®PLUS proton system (IBA, Belgium), was performed at depths of 18, 20, 24 cm using Plastic Water®(CIRS, Norfolk, VA). The calibration doses ranged from 65 - 250 cGy (RBE) (relative biological effectiveness) for proton energies of 170 - 200 MeV. A clinical prostate + nodes plan was used for validation. The planar doses at selected depths were measured with EBT3 films and analyzed using one-scan protocol (one-scan digitization of QA film and at least one film exposed to a known dose). The gamma passing rates, dose-difference maps, and profiles of 2D planar doses measured with EBT3 film and IBA MatriXX-PT, versus the RayStation TPS calculations were analyzed and compared. The EBT3 film measurement results matched well with the TPS calculation data with an average passing rate of ~95% for 2%/2 mm and slightly lower passing rates were obtained from an ion chamber array detector. We were able to demonstrate that the use of a proton step-wedge provided clinically acceptable results and minimized variations between film-scanner orientation, inter-scan, and scanning conditions. Furthermore, for relative dosimetry (calibration is not done at the time of experiment), it could be derived from no more than two films exposed to known doses (one could be zero) for rescaling the master calibration curve at each depth. The sensitivity of the calibration to depth variations has been explored. One-scan protocol results appear to be comparable to that of the ion chamber array detector. The use of a proton step-wedge for calibration of EBT3 film potentially increases efficiency in patient-specific QA of proton beams.展开更多
BACKGROUND Locoregional recurrence of breast cancer is challenging for clinicians,due to the various former treatments patients have undergone.However,treatment of the recurrence with systemic therapy and subsequent r...BACKGROUND Locoregional recurrence of breast cancer is challenging for clinicians,due to the various former treatments patients have undergone.However,treatment of the recurrence with systemic therapy and subsequent reirradiation of chest wall is accompanied by increased toxicities,particularly radiation-induced cardiovascular disease.Reirradiation by proton beam therapy(PBT)enables superior preservation of adjacent organs at risk as well as concurrent dose escalation for delivery to the gross tumor.This technology is expected to improve the overall outcome of recurrent breast cancer.CASE SUMMARY A 47-year-old female presented with an extensive locoregional recurrence at 10 yr after primary treatment of a luminal A breast cancer.Because of tumor progression despite having undergone bilateral ovarectomy and systemic therapy,the patient was treated with PBT BE total dose of 64.40 Gy to each gross tumor and 56.00 Gy to the upper mediastinal and retrosternal lymphatics including the entire sternum in 28 fractions.Follow-up computed tomography showed a partial remission,without evidence of newly emerging metastasis.At 19 mo after the PBT,the patient developed a radiation-induced pericardial disease and pleural effusions with clinical burden of dyspnea,which were successfully treated by drainage and corticosteroid.Cytological analysis of the puncture fluid showed no malignancy,and the subsequent computed tomography scan indicated stable disease as well as significantly decreased pericardial and pleural effusions.The patient remains free of progression to date.CONCLUSION PBT was a safe and effective method of reirradiation for locoregionally recurrent breast cancer in our patient.展开更多
Presented here is the clinical course of a 63-yearold patient with a central, large and unresectable hepatocellular carcinoma(HCC) with liver metastases and tumor invasion of the portal and hepatic veins. After the tu...Presented here is the clinical course of a 63-yearold patient with a central, large and unresectable hepatocellular carcinoma(HCC) with liver metastases and tumor invasion of the portal and hepatic veins. After the tumor had been diagnosed, the patient was immediately treated with proton beam therapy(PBT), at a total dose of 60 Gy(relative biological effectiveness) in 20 fractions administered within 4 wk. To manage the respiratory movements, at the Rinecker Proton Therapy Center, apneic oxygenation was given daily, under general anesthesia. The patient tolerated both the PBT and general anesthesia very well, and did now show any signs of acute or late toxicity. The treatment was followed by constant reductions in the tumor marker alpha-fetoprotein and the cholestatic parameters gamma-glutamyltransferase and alkaline phosphatase. The patient commenced an adjuvant treatment with sorafenib, given at 6-wk intervals, after the PBT. Follow-up with regular magnetic resonance imaging has continued for 40 mo so far, demonstrating remarkable shrinkage of the HCC(maximal diameter dropping from approximately 13 cm to 2 cm). To date, the patient remains free of tumor recurrence. PBT served as a safe and effective treatment method for an unresectable HCC with vascular invasion.展开更多
BACKGROUND Sinonasal malignancies are rare but demanding due to complex anatomy,usually late diagnosis,and inconsistent therapy strategy based on multimodality approaches.Squamous cell carcinoma(SCC)is the most common...BACKGROUND Sinonasal malignancies are rare but demanding due to complex anatomy,usually late diagnosis,and inconsistent therapy strategy based on multimodality approaches.Squamous cell carcinoma(SCC)is the most common histology,with poorer prognosis.In the setting of orbital invasion,an orbital exenteration may be required.However,in case of primary rejection of disfiguring surgery or unresectable disease,proton beam therapy(PBT)should be largely considered,allowing for better sparing of neighboring critical structures and improved outcomes by dose escalation.CASE SUMMARY A 62-year-old male presented with a recurrent SCC in the nasal septum abutting frontal skull base and bilateral orbits at 7 mo after primary partial nasal amputation.Because of refusal of face-deforming surgery and considerable adverse effects of conventional radiotherapy,the patient underwent a PBT by hyperfractionated accelerated scheme,resulting in complete response and moderate toxicities.After 2 years,a nasal reconstruction was implemented with satisfactory appearance and recurrence-freedom to date.Another patient with an initially extended sinonasal SCC,invading right orbit and facial soft tissue,declined an orbital exenteration and was treated with a normofractionated PBT to the gross tumor and elective cervical lymphatics.The follow-up showed a continuous tumor remission with reasonable late toxicities,such as cataract and telangiectasia on the right.Despite T4a stage and disapproval of concurrent chemotherapy owing to individual choice,both patients still achieved outstanding treatment outcomes with PBT alone.CONCLUSION PBT enabled orbit preservation and excellent tumor control without severe adverse effects on both presented patients with locally advanced sinonasal SCC.展开更多
Background: To evaluate the robustness of head and neck treatment using proton pencil beam scanning (PBS) technique with respect to range uncertainty (RU) and setup errors (SE), and to establish a robust PBS planning ...Background: To evaluate the robustness of head and neck treatment using proton pencil beam scanning (PBS) technique with respect to range uncertainty (RU) and setup errors (SE), and to establish a robust PBS planning strategy for future treatment. Methods and Materials: Ten consecutive patients were planned with a novel proton field geometry (combination of two posterior oblique fields and one anterior field with gradient dose match) using single-field uniform dose (SFUD) planning technique and the proton plans were dosimetrically compared to two coplanar arc VMAT plans. Robustness of the plans, with respect to range uncertainties (RU = ± 3% for proton) and setup errors (SE = 2.25 mm for proton and VMAT), in terms of deviations to target coverage (CTV D98%) and OAR doses (max/mean), were evaluated and compared for each patient under worst case scenarios. Results: Dosimetrically, PBS plans provided better sparing to larynx (p = 0.005), oral cavity (p < 0.001) and contralateral parotid (p = 0.004) when compared to VMAT. CTV D98% variations were higher from SE than from RU for proton plans (-1.1% ± 1.3 % vs -0.4% ± 0.7% for nodal CTV and -1.4% ± 1.2 vs -0.4% ± 0.5% % for boost CTV). Overall, the magnitudes of variation of CTV D98% to combined SE and RU were found to be similar to the impact of the SE on the VMAT plans (-1.6% ± 1.9% vs -1.7% ± 1.4% for nodal CTV and -1.9% ± 1.6% vs -1.3% ± 1.5% for boost CTV). Compared to VMAT, a larger range of relative dose deviations were found for OARs in proton plans, but safe doses were maintained for cord (41.8 ± 3.6 Gy for PBS and 41.7 ± 3.9 Gy for VMAT) and brainstem (35.2 ± 8.4 Gy for PBS and 36.2 ± 5.1 Gy for VMAT) in worst case scenarios. Conclusions: Compared to VMAT, proton plans containing three SFUD fields with superior-inferior gradient dose matching had improved sparing to larynx, contralateral parotid and oral cavity, while providing similar robustness of target coverage. Evaluation of OAR dose robustness showed higher sensitivities to uncertainties for proton plans, but safe dose levels were maintained for cord and brainstem.展开更多
Purpose: The recommended value for the relative biological effectiveness (RBE) of proton beams is currently assumed to be 1.1. However, there is increasing evidence that RBE increases towards the end of proton beam ra...Purpose: The recommended value for the relative biological effectiveness (RBE) of proton beams is currently assumed to be 1.1. However, there is increasing evidence that RBE increases towards the end of proton beam range that may increase the biological effect of proton beam in the distal regions of the dose deposition. Methods: A computational approach is presented for estimating the biological effect of the proton beam. It includes a method for calculating the dose averaged linear energy transfer (LET) along the measured Bragg peak and published LET to RBE conversion routine. To validate the proposed method, we have performed Monte Carlo simulations of the pristine Bragg peak at various beam energies and compared the analysis with the simulated results. A good agreement within 5% is observed between the LET analysis of the modeled Bragg peaks and Monte Carlo simulations. Results: Applying the method to the set of Bragg peaks measured at a proton therapy facility we have estimated LET and RBE values along each Bragg peak. Combining the individual RBE-weighted Bragg peaks with known energy modulation weights we have calculated the RBE-weighted dose in the modulated proton beam. The proposed computational method provides a tool for calculating dose averaged LET along the measured Bragg peak. Conclusions: Combined with a model to convert LET into RBE, this method enables calculation of RBE-weighted dose both in pristine Bragg peak and in modulated beam in proton therapy.展开更多
<strong>Background:</strong><span style="font-family:;" "=""><span style="font-family:Verdana;"> Hepatocellular carcinoma (HCC) is more likely to occur in pat...<strong>Background:</strong><span style="font-family:;" "=""><span style="font-family:Verdana;"> Hepatocellular carcinoma (HCC) is more likely to occur in patients with a history of Fontan surgery, possibly due to long-term liver congestion. Proton beam therapy (PBT) may be effective for HCC that develops after Fontan surgery. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> Six lesions in 5 patients (3 females, 2 males) received PBT. The median age of the patients was 33 (range 21 - 42) years, and the median age at the time of the Fontan procedure was 6 (5 - 13) years. Four patients had multiple HCC at the time of PBT. The median tumor size was 57 (22 - 80) mm and 4 patients were classified as Child-Pugh B. Two patients received transcatheter arterial chemoembolization before PBT. The schedule of PBT was 66 Gy (RBE) in 10 fractions for 2 lesions, 72.6 Gy (RBE) in 22 fractions for 2 lesions, and 74 GyE (RBE) in 37 fractions for 2 lesions. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> The median follow-up period was 31 (10 - 46) months, and the numbers of survivors, deaths from primary diseases, and deaths from other diseases were 3, 1, and 1, respectively. There were no local recurrences, one intrahepatic metastasis, one lung metastasis, and one intrathoracic metastasis. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Although experiences on </span></span><span style="font-family:Verdana;">a </span><span style="font-family:Verdana;">small number of patients cannot conclude things, we believe that PBT can be a reasonable choice of radical treatment for HCC occurring after </span><span style="font-family:Verdana;">the </span><span style="font-family:Verdana;">Fontan procedure.</span>展开更多
Purpose: The experimental verification of the Acuros XB (AXB) algorithm was conducted in a heterogeneous rectangular slab phantom, and compared to the Anisotropic Analytical Algorithm (AAA). The dosimetric impact of t...Purpose: The experimental verification of the Acuros XB (AXB) algorithm was conducted in a heterogeneous rectangular slab phantom, and compared to the Anisotropic Analytical Algorithm (AAA). The dosimetric impact of the AXB for stereotactic body radiation therapy (SBRT) and RapidArc planning for 16 non-small-cell lung cancer (NSCLC) patients was assessed due to the dose recalculation from the AAA to the AXB. Methods: The calculated central axis percentage depth doses (PDD) in a heterogeneous slab phantom for an open field size of 3 ×3 cm2 were compared against the PDD measured by an ionization chamber. For 16 NSCLC patients, the dose-volume parameters from the treatment plans calculated by the AXB and the AAA were compared using identical jaw settings, leaf positions, and monitor units (MUs). Results: The results from the heterogeneous slab phantom study showed that the AXB was more accurate than the AAA;however, the dose underestimation by the AXB (up to ?3.9%) and AAA (up to ?13.5%) was observed. For a planning target volume (PTV) in the NSCLC patients, in comparison to the AAA, the AXB predicted lower mean and minimum doses by average 0.3% and 4.3% respectively, but a higher maximum dose by average 2.3%. The averaged maximum doses to the heart and spinal cord predicted by the AXB were lower by 1.3% and 2.6% respectively;whereas the doses to the lungs predicted by the AXB were higher by up to 0.5% compared to the AAA. The percentage of ipsilateral lung volume receiving at least 20 and 5 Gy (V20 and V5 respectively) were higher in the AXB plans than in the AAA plans by average 1.1% and 2.8% respectively. The AXB plans produced higher target heterogeneity by average 4.5% and lower plan conformity by average 5.8% compared to the AAA plans. Using the AXB, the PTV coverage (95% of the PTV covered by the 100% of the prescribed dose) was reduced by average 8.2% than using the AAA. The AXB plans required about 2.3% increment in the number of MUs in order to achieve the same PTV coverage as in the AAA plans. Conclusion: The AXB is more accurate to use for the dose calculations in SBRT lung plans created with a RapidArc technique;however, one should also note the reduced PTV coverage due to the dose recalculation from the AAA to the AXB.展开更多
The volumetric modulated arc therapy(VMAT)technique,in the form of RapidArc,is widely used to treat prostate cancer.The full-single arc(f-SA)technique in RapidArc planning for prostate cancer treatment provides effici...The volumetric modulated arc therapy(VMAT)technique,in the form of RapidArc,is widely used to treat prostate cancer.The full-single arc(f-SA)technique in RapidArc planning for prostate cancer treatment provides efficient treatment,but it also delivers a higher radiation dose to the rectum.This study aimed to compare the dosimetric results from the new partial-single arc(p-SA)technique with those from the f-SA technique in RapidArc planning for prostate cancer treatment.In this study,10 patients with lowrisk prostate cancer were selected.For each patient,two sets of RapidArc plans(f-SA and p-SA)were created in the Eclipse treatment planning system.The f-SA plan was created using one full arc,and the p-SA plan was created using planning parameters identical to those of the f-SA plan but with anterior and posterior avoidance sectors.Various dosimetric parameters of the f-SA and p-SA plans were evaluated and compared for the same target coverage and identical plan optimization parameters.The f-SA and p-SA plans showed an average difference of±1%for the doses to the planning target volume(PTV),and there were no clear differences in dose homogeneity or plan conformity.In comparison to the f-SA technique,the p-SA technique reduced the doses to the rectum by approximately 6.1%to 21.2%,to the bladder by approximately 10.3%to 29.5%,and to the penile bulb by approximately 2.2%.In contrast,the dose to the femoral heads,the integral dose,and the number of monitor units were higher in the p-SA plans by approximately 34.4%,7.7%,and 9.2%,respectively.In conclusion,it is feasible to use the p-SA technique for RapidArc planning for prostate cancer treatment.For the same PTV coverage and identical plan optimization parameters,the p-SA technique is better in sparing the rectum and bladder without compromising plan conformity or target homogeneity when compared to the f-SA technique.展开更多
Objective:Concurrent chemoradiotherapy using cisplatin was thought to be standard treatment for squamous cell carcinoma of cervix,but it had not been effective for adenocarcinoma.Concurrent chemoradiotherapy using iri...Objective:Concurrent chemoradiotherapy using cisplatin was thought to be standard treatment for squamous cell carcinoma of cervix,but it had not been effective for adenocarcinoma.Concurrent chemoradiotherapy using irinotecan hydrochloride(CPT-11)had been effective for colorectal cancer,thus,we chose CPT-11 as a candidate for gynecologic adenocarcinoma.To evaluate the maximum tolerated dose(MTD)of weekly CPT-11 with external pelvic radiotherapy,a phase 1/2 study was conducted according to modified Fibonacci method.Methods:Eligible patients were advanced uterine cancer with measurable diseases[performance score(PS):0-2].Study period was from August 1 st,2002 to December 31 st,2008.The starting dose level(DL)of CPT-11 was 30 mg/m2(DL1)given weekly for 4 weeks.Subsequently,dose escalation was scheduled in 10 mg/m2 increments to 60 mg/m^2(DL4).The fixed radiotherapy consisted of whole pelvic 1.8 Gy/d,once a day in weekday for five weeks and it amounted to 45 Gy(25 fractions)in total.Results:Seventeen patients were enrolled.As for toxicities,one(1/17:5.9%)grade(G)4 neutropenia lasting 7 days had been seen in DL4.G2 diarrhea was identified in 35.3%(6/17)of the patients,and 11.8%(2/17)G3 diarrhea was observed in DL3 and DL4.Thus,the MTD of CPT-11 was defined as dose of 60 mg/m^2.The recommended dose was decided as 50 mg/m^2.The response rate was 88.2%[9 complete response(CR),3 partial response(PR),3 stable disease(SD),2 not evaluable(NE)].Disease control rate at 1 month after treatment completion was 100%but distant metastases were found in 24%(4/17)in longer outcome.Conclusions:MTD was 60 mg/m^2 and recommended dose was set as 50 mg/m2.This concurrent chemoradiation using weekly CPT-11 was feasible at 50 mg/m^2,and it might be effective even in adenocarcinoma of the uterus.展开更多
The influence of initial placement of molecular or ion substance is investigated on the diffusion fluxes across the cell membrane. The diffusion fluxes and recovery curves are obtained by considering both the singlesp...The influence of initial placement of molecular or ion substance is investigated on the diffusion fluxes across the cell membrane. The diffusion fluxes and recovery curves are obtained by considering both the singlespot and double-spot concentrations inside the cell membrane. The results show that the additional concentration inside the membrane reduces the net fluxes at the cell interior as well as the exterior. In addition, it is found that the change in diffusion flux at the two outer walls of the membrane by the two-spot concentrations in the cell membrane is weaker than that of the single-spot concentration at the center. The variation of the influence of initial locations of the molecular concentrations inside the cell membrane on the diffusion fluxes is also discussed. This result can be applied to the diffusion process in avascular collagenous tissues.展开更多
We proposed the use of a hybrid deformable image registration approach that combines compact-support radial basis functions (CSRBF) spline registration with intensity-based image registration. The proposed method firs...We proposed the use of a hybrid deformable image registration approach that combines compact-support radial basis functions (CSRBF) spline registration with intensity-based image registration. The proposed method first uses the pre-viously developed image intensity-based method to achieve voxel-by-voxel correspondences over the entire image re-gion. Next, for those areas of inaccurate registration, a sparse set of landmark correspondences was defined for local deformable image registration using a multi-step CSRBF approach. This hybrid registration takes advantage of both intensity-based method for automatic processing of entire images and the CSRBF spline method for fine adjustment over specific regions. The goal of using this hybrid registration is to locally control the quality of registration results in specific regions of interest with minimal human intervention. The major applications of this approach in radiation ther-apy are for the corrections of registration failures caused by various imaging artifacts resulting in, low image contrast, and non-correspondence situations where an object may not be imaged in both target and source images. Both synthetic and real patient data have been used to evaluate this hybrid method. We used contours mapping to validate the accuracy of this method on real patient image. Our studies demonstrated that this hybrid method could improve overall registra-tion accuracy with moderate overhead. In addition, we have also shown that the multi-step CSRBF registration proved to be more effective in handling large deformations while maintaining the smoothness of the transformation than origi-nal CSRBF.展开更多
P-type ZnO is crucial for the realization of ZnO-based homojunction ultraviolet optoelectronic devices. The problem associated with the preparation of stable p-type ZnO with high hole density still hinders device appl...P-type ZnO is crucial for the realization of ZnO-based homojunction ultraviolet optoelectronic devices. The problem associated with the preparation of stable p-type ZnO with high hole density still hinders device applications. In this paper,we introduce an alternative route to stabilizing N in the oxidation process, the thermal stability of p-ZnO is significantly improved. Finally, we discuss the limitations of the alternative doping method and provide some prospective outlook of the method.展开更多
文摘Esophageal cancer is one of the most difficult cancers to treat since it is often at an advanced stage at the time of symptom presentation.For locally advanced esophageal cancer,treatment options include multidisciplinary treatment such as surgery or definitive chemoradiotherapy.Surgery has a high local control rate because it involves excision of the cancer along with the surrounding organs;however,it is still highly invasive,although advances in surgery have reduced the burden on patients.On the other hand,chemoradiotherapy may also be applicable in cases in which surgery is inoperable owing to complications or distant lymph node metastasis.However,chemoradiotherapy using X-ray irradiation can cause late toxicities,including those to the heart.Proton beam therapy is widely used to treat esophageal cancer because of its characteristics,and some comparisons between proton beam therapy and X-ray therapy or surgery have recently been reported.This review discusses the role of proton beam therapy in esophageal cancer in comparison to X-ray therapy and surgery.
文摘Background:Few studies compared the effectiveness of the 3-monthly goserelin 10.8-mg and the monthly 3.6-mg depot in inducing ovarian function suppression for premenopausal patients with hormone receptor positive(HR+)breast cancer.We conducted a large-scale real-world study(RWS)in China to validate the non-inferiority of goserelin 10.8-mg to the 3.6-mg depot.Methods:This multicenter,retrospective-prospective,non-inferiority study compared goserelin 10.8-mg with 3.6-mg in suppressing estradiol(E2)levels in premenopausal and perimenopausal patients with HR+breast cancer.Eligible patients were identified,and their demographic and clinical data were obtained from hospital medical records.The observation period was 28 weeks.Propensity score matching(PSM)ensured baseline comparability.The primary endpoint was the proportion of patients with E2 suppression to postmenopausal level at Week 12±4.Difference in proportions and 95%CI was calculated by Newcombe-Wilson score method.The non-inferiority margin was-10%.Subgroup and sensitivity analyses assessed result robustness.Results:From 1st January,2015 to 15th December,2023,15,629 patients from 16 hospitals nationwide were screened,with 1,060 eligible patients included in the full analysis set(3.6-mg group:678;10.8-mg group:382).Post-PSM,the primary endpoint was analyzed in 590 patients(295 in each group).At Week 12±4,the proportion of patients with E2 suppression was 99.1%(95%CI:96.9%-99.8%)for goserelin 10.8-mg and 95.3%(95%CI:91.0%-97.6%)for goserelin 3.6-mg.The difference was 3.8%(95%CI:0.6%-8.1%)with the lower limit of 95%CI greater than the non-inferiority margin.All subgroup analyses,including those based on age(≤45 or>45 years)and previous chemotherapy(yes/no),and all sensitivity analyses on the primary endpoint were consistent with the main analysis.
文摘Radiochromic film for spot-scanning QA provides high spatial resolution and efficiency gains from one-shot irradiation for multiple depths. However, calibration can be a tedious procedure which may limit widespread use. Moreover, since there may be an energy dependence, which manifests as a depth dependence, this may require additional measurements for each patient. We present a one-scan protocol to simplify the procedure. A calibration using an EBT3 film, exposed by a 6-level step-wedge plan on a Proteus®PLUS proton system (IBA, Belgium), was performed at depths of 18, 20, 24 cm using Plastic Water®(CIRS, Norfolk, VA). The calibration doses ranged from 65 - 250 cGy (RBE) (relative biological effectiveness) for proton energies of 170 - 200 MeV. A clinical prostate + nodes plan was used for validation. The planar doses at selected depths were measured with EBT3 films and analyzed using one-scan protocol (one-scan digitization of QA film and at least one film exposed to a known dose). The gamma passing rates, dose-difference maps, and profiles of 2D planar doses measured with EBT3 film and IBA MatriXX-PT, versus the RayStation TPS calculations were analyzed and compared. The EBT3 film measurement results matched well with the TPS calculation data with an average passing rate of ~95% for 2%/2 mm and slightly lower passing rates were obtained from an ion chamber array detector. We were able to demonstrate that the use of a proton step-wedge provided clinically acceptable results and minimized variations between film-scanner orientation, inter-scan, and scanning conditions. Furthermore, for relative dosimetry (calibration is not done at the time of experiment), it could be derived from no more than two films exposed to known doses (one could be zero) for rescaling the master calibration curve at each depth. The sensitivity of the calibration to depth variations has been explored. One-scan protocol results appear to be comparable to that of the ion chamber array detector. The use of a proton step-wedge for calibration of EBT3 film potentially increases efficiency in patient-specific QA of proton beams.
基金Supported by Rinecker Proton Therapy Center,Munich,Germany
文摘BACKGROUND Locoregional recurrence of breast cancer is challenging for clinicians,due to the various former treatments patients have undergone.However,treatment of the recurrence with systemic therapy and subsequent reirradiation of chest wall is accompanied by increased toxicities,particularly radiation-induced cardiovascular disease.Reirradiation by proton beam therapy(PBT)enables superior preservation of adjacent organs at risk as well as concurrent dose escalation for delivery to the gross tumor.This technology is expected to improve the overall outcome of recurrent breast cancer.CASE SUMMARY A 47-year-old female presented with an extensive locoregional recurrence at 10 yr after primary treatment of a luminal A breast cancer.Because of tumor progression despite having undergone bilateral ovarectomy and systemic therapy,the patient was treated with PBT BE total dose of 64.40 Gy to each gross tumor and 56.00 Gy to the upper mediastinal and retrosternal lymphatics including the entire sternum in 28 fractions.Follow-up computed tomography showed a partial remission,without evidence of newly emerging metastasis.At 19 mo after the PBT,the patient developed a radiation-induced pericardial disease and pleural effusions with clinical burden of dyspnea,which were successfully treated by drainage and corticosteroid.Cytological analysis of the puncture fluid showed no malignancy,and the subsequent computed tomography scan indicated stable disease as well as significantly decreased pericardial and pleural effusions.The patient remains free of progression to date.CONCLUSION PBT was a safe and effective method of reirradiation for locoregionally recurrent breast cancer in our patient.
基金Supported by Rinecker Proton Therapy Center(RPTC),Munich,Germany
文摘Presented here is the clinical course of a 63-yearold patient with a central, large and unresectable hepatocellular carcinoma(HCC) with liver metastases and tumor invasion of the portal and hepatic veins. After the tumor had been diagnosed, the patient was immediately treated with proton beam therapy(PBT), at a total dose of 60 Gy(relative biological effectiveness) in 20 fractions administered within 4 wk. To manage the respiratory movements, at the Rinecker Proton Therapy Center, apneic oxygenation was given daily, under general anesthesia. The patient tolerated both the PBT and general anesthesia very well, and did now show any signs of acute or late toxicity. The treatment was followed by constant reductions in the tumor marker alpha-fetoprotein and the cholestatic parameters gamma-glutamyltransferase and alkaline phosphatase. The patient commenced an adjuvant treatment with sorafenib, given at 6-wk intervals, after the PBT. Follow-up with regular magnetic resonance imaging has continued for 40 mo so far, demonstrating remarkable shrinkage of the HCC(maximal diameter dropping from approximately 13 cm to 2 cm). To date, the patient remains free of tumor recurrence. PBT served as a safe and effective treatment method for an unresectable HCC with vascular invasion.
文摘BACKGROUND Sinonasal malignancies are rare but demanding due to complex anatomy,usually late diagnosis,and inconsistent therapy strategy based on multimodality approaches.Squamous cell carcinoma(SCC)is the most common histology,with poorer prognosis.In the setting of orbital invasion,an orbital exenteration may be required.However,in case of primary rejection of disfiguring surgery or unresectable disease,proton beam therapy(PBT)should be largely considered,allowing for better sparing of neighboring critical structures and improved outcomes by dose escalation.CASE SUMMARY A 62-year-old male presented with a recurrent SCC in the nasal septum abutting frontal skull base and bilateral orbits at 7 mo after primary partial nasal amputation.Because of refusal of face-deforming surgery and considerable adverse effects of conventional radiotherapy,the patient underwent a PBT by hyperfractionated accelerated scheme,resulting in complete response and moderate toxicities.After 2 years,a nasal reconstruction was implemented with satisfactory appearance and recurrence-freedom to date.Another patient with an initially extended sinonasal SCC,invading right orbit and facial soft tissue,declined an orbital exenteration and was treated with a normofractionated PBT to the gross tumor and elective cervical lymphatics.The follow-up showed a continuous tumor remission with reasonable late toxicities,such as cataract and telangiectasia on the right.Despite T4a stage and disapproval of concurrent chemotherapy owing to individual choice,both patients still achieved outstanding treatment outcomes with PBT alone.CONCLUSION PBT enabled orbit preservation and excellent tumor control without severe adverse effects on both presented patients with locally advanced sinonasal SCC.
文摘Background: To evaluate the robustness of head and neck treatment using proton pencil beam scanning (PBS) technique with respect to range uncertainty (RU) and setup errors (SE), and to establish a robust PBS planning strategy for future treatment. Methods and Materials: Ten consecutive patients were planned with a novel proton field geometry (combination of two posterior oblique fields and one anterior field with gradient dose match) using single-field uniform dose (SFUD) planning technique and the proton plans were dosimetrically compared to two coplanar arc VMAT plans. Robustness of the plans, with respect to range uncertainties (RU = ± 3% for proton) and setup errors (SE = 2.25 mm for proton and VMAT), in terms of deviations to target coverage (CTV D98%) and OAR doses (max/mean), were evaluated and compared for each patient under worst case scenarios. Results: Dosimetrically, PBS plans provided better sparing to larynx (p = 0.005), oral cavity (p < 0.001) and contralateral parotid (p = 0.004) when compared to VMAT. CTV D98% variations were higher from SE than from RU for proton plans (-1.1% ± 1.3 % vs -0.4% ± 0.7% for nodal CTV and -1.4% ± 1.2 vs -0.4% ± 0.5% % for boost CTV). Overall, the magnitudes of variation of CTV D98% to combined SE and RU were found to be similar to the impact of the SE on the VMAT plans (-1.6% ± 1.9% vs -1.7% ± 1.4% for nodal CTV and -1.9% ± 1.6% vs -1.3% ± 1.5% for boost CTV). Compared to VMAT, a larger range of relative dose deviations were found for OARs in proton plans, but safe doses were maintained for cord (41.8 ± 3.6 Gy for PBS and 41.7 ± 3.9 Gy for VMAT) and brainstem (35.2 ± 8.4 Gy for PBS and 36.2 ± 5.1 Gy for VMAT) in worst case scenarios. Conclusions: Compared to VMAT, proton plans containing three SFUD fields with superior-inferior gradient dose matching had improved sparing to larynx, contralateral parotid and oral cavity, while providing similar robustness of target coverage. Evaluation of OAR dose robustness showed higher sensitivities to uncertainties for proton plans, but safe dose levels were maintained for cord and brainstem.
文摘Purpose: The recommended value for the relative biological effectiveness (RBE) of proton beams is currently assumed to be 1.1. However, there is increasing evidence that RBE increases towards the end of proton beam range that may increase the biological effect of proton beam in the distal regions of the dose deposition. Methods: A computational approach is presented for estimating the biological effect of the proton beam. It includes a method for calculating the dose averaged linear energy transfer (LET) along the measured Bragg peak and published LET to RBE conversion routine. To validate the proposed method, we have performed Monte Carlo simulations of the pristine Bragg peak at various beam energies and compared the analysis with the simulated results. A good agreement within 5% is observed between the LET analysis of the modeled Bragg peaks and Monte Carlo simulations. Results: Applying the method to the set of Bragg peaks measured at a proton therapy facility we have estimated LET and RBE values along each Bragg peak. Combining the individual RBE-weighted Bragg peaks with known energy modulation weights we have calculated the RBE-weighted dose in the modulated proton beam. The proposed computational method provides a tool for calculating dose averaged LET along the measured Bragg peak. Conclusions: Combined with a model to convert LET into RBE, this method enables calculation of RBE-weighted dose both in pristine Bragg peak and in modulated beam in proton therapy.
文摘<strong>Background:</strong><span style="font-family:;" "=""><span style="font-family:Verdana;"> Hepatocellular carcinoma (HCC) is more likely to occur in patients with a history of Fontan surgery, possibly due to long-term liver congestion. Proton beam therapy (PBT) may be effective for HCC that develops after Fontan surgery. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> Six lesions in 5 patients (3 females, 2 males) received PBT. The median age of the patients was 33 (range 21 - 42) years, and the median age at the time of the Fontan procedure was 6 (5 - 13) years. Four patients had multiple HCC at the time of PBT. The median tumor size was 57 (22 - 80) mm and 4 patients were classified as Child-Pugh B. Two patients received transcatheter arterial chemoembolization before PBT. The schedule of PBT was 66 Gy (RBE) in 10 fractions for 2 lesions, 72.6 Gy (RBE) in 22 fractions for 2 lesions, and 74 GyE (RBE) in 37 fractions for 2 lesions. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> The median follow-up period was 31 (10 - 46) months, and the numbers of survivors, deaths from primary diseases, and deaths from other diseases were 3, 1, and 1, respectively. There were no local recurrences, one intrahepatic metastasis, one lung metastasis, and one intrathoracic metastasis. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Although experiences on </span></span><span style="font-family:Verdana;">a </span><span style="font-family:Verdana;">small number of patients cannot conclude things, we believe that PBT can be a reasonable choice of radical treatment for HCC occurring after </span><span style="font-family:Verdana;">the </span><span style="font-family:Verdana;">Fontan procedure.</span>
文摘Purpose: The experimental verification of the Acuros XB (AXB) algorithm was conducted in a heterogeneous rectangular slab phantom, and compared to the Anisotropic Analytical Algorithm (AAA). The dosimetric impact of the AXB for stereotactic body radiation therapy (SBRT) and RapidArc planning for 16 non-small-cell lung cancer (NSCLC) patients was assessed due to the dose recalculation from the AAA to the AXB. Methods: The calculated central axis percentage depth doses (PDD) in a heterogeneous slab phantom for an open field size of 3 ×3 cm2 were compared against the PDD measured by an ionization chamber. For 16 NSCLC patients, the dose-volume parameters from the treatment plans calculated by the AXB and the AAA were compared using identical jaw settings, leaf positions, and monitor units (MUs). Results: The results from the heterogeneous slab phantom study showed that the AXB was more accurate than the AAA;however, the dose underestimation by the AXB (up to ?3.9%) and AAA (up to ?13.5%) was observed. For a planning target volume (PTV) in the NSCLC patients, in comparison to the AAA, the AXB predicted lower mean and minimum doses by average 0.3% and 4.3% respectively, but a higher maximum dose by average 2.3%. The averaged maximum doses to the heart and spinal cord predicted by the AXB were lower by 1.3% and 2.6% respectively;whereas the doses to the lungs predicted by the AXB were higher by up to 0.5% compared to the AAA. The percentage of ipsilateral lung volume receiving at least 20 and 5 Gy (V20 and V5 respectively) were higher in the AXB plans than in the AAA plans by average 1.1% and 2.8% respectively. The AXB plans produced higher target heterogeneity by average 4.5% and lower plan conformity by average 5.8% compared to the AAA plans. Using the AXB, the PTV coverage (95% of the PTV covered by the 100% of the prescribed dose) was reduced by average 8.2% than using the AAA. The AXB plans required about 2.3% increment in the number of MUs in order to achieve the same PTV coverage as in the AAA plans. Conclusion: The AXB is more accurate to use for the dose calculations in SBRT lung plans created with a RapidArc technique;however, one should also note the reduced PTV coverage due to the dose recalculation from the AAA to the AXB.
文摘The volumetric modulated arc therapy(VMAT)technique,in the form of RapidArc,is widely used to treat prostate cancer.The full-single arc(f-SA)technique in RapidArc planning for prostate cancer treatment provides efficient treatment,but it also delivers a higher radiation dose to the rectum.This study aimed to compare the dosimetric results from the new partial-single arc(p-SA)technique with those from the f-SA technique in RapidArc planning for prostate cancer treatment.In this study,10 patients with lowrisk prostate cancer were selected.For each patient,two sets of RapidArc plans(f-SA and p-SA)were created in the Eclipse treatment planning system.The f-SA plan was created using one full arc,and the p-SA plan was created using planning parameters identical to those of the f-SA plan but with anterior and posterior avoidance sectors.Various dosimetric parameters of the f-SA and p-SA plans were evaluated and compared for the same target coverage and identical plan optimization parameters.The f-SA and p-SA plans showed an average difference of±1%for the doses to the planning target volume(PTV),and there were no clear differences in dose homogeneity or plan conformity.In comparison to the f-SA technique,the p-SA technique reduced the doses to the rectum by approximately 6.1%to 21.2%,to the bladder by approximately 10.3%to 29.5%,and to the penile bulb by approximately 2.2%.In contrast,the dose to the femoral heads,the integral dose,and the number of monitor units were higher in the p-SA plans by approximately 34.4%,7.7%,and 9.2%,respectively.In conclusion,it is feasible to use the p-SA technique for RapidArc planning for prostate cancer treatment.For the same PTV coverage and identical plan optimization parameters,the p-SA technique is better in sparing the rectum and bladder without compromising plan conformity or target homogeneity when compared to the f-SA technique.
基金supported by grant of Japanese Foundation for Multidisciplinary Treatment of Cancer(JFMC)for Cancer Research in 2005(26 th)。
文摘Objective:Concurrent chemoradiotherapy using cisplatin was thought to be standard treatment for squamous cell carcinoma of cervix,but it had not been effective for adenocarcinoma.Concurrent chemoradiotherapy using irinotecan hydrochloride(CPT-11)had been effective for colorectal cancer,thus,we chose CPT-11 as a candidate for gynecologic adenocarcinoma.To evaluate the maximum tolerated dose(MTD)of weekly CPT-11 with external pelvic radiotherapy,a phase 1/2 study was conducted according to modified Fibonacci method.Methods:Eligible patients were advanced uterine cancer with measurable diseases[performance score(PS):0-2].Study period was from August 1 st,2002 to December 31 st,2008.The starting dose level(DL)of CPT-11 was 30 mg/m2(DL1)given weekly for 4 weeks.Subsequently,dose escalation was scheduled in 10 mg/m2 increments to 60 mg/m^2(DL4).The fixed radiotherapy consisted of whole pelvic 1.8 Gy/d,once a day in weekday for five weeks and it amounted to 45 Gy(25 fractions)in total.Results:Seventeen patients were enrolled.As for toxicities,one(1/17:5.9%)grade(G)4 neutropenia lasting 7 days had been seen in DL4.G2 diarrhea was identified in 35.3%(6/17)of the patients,and 11.8%(2/17)G3 diarrhea was observed in DL3 and DL4.Thus,the MTD of CPT-11 was defined as dose of 60 mg/m^2.The recommended dose was decided as 50 mg/m^2.The response rate was 88.2%[9 complete response(CR),3 partial response(PR),3 stable disease(SD),2 not evaluable(NE)].Disease control rate at 1 month after treatment completion was 100%but distant metastases were found in 24%(4/17)in longer outcome.Conclusions:MTD was 60 mg/m^2 and recommended dose was set as 50 mg/m2.This concurrent chemoradiation using weekly CPT-11 was feasible at 50 mg/m^2,and it might be effective even in adenocarcinoma of the uterus.
文摘The influence of initial placement of molecular or ion substance is investigated on the diffusion fluxes across the cell membrane. The diffusion fluxes and recovery curves are obtained by considering both the singlespot and double-spot concentrations inside the cell membrane. The results show that the additional concentration inside the membrane reduces the net fluxes at the cell interior as well as the exterior. In addition, it is found that the change in diffusion flux at the two outer walls of the membrane by the two-spot concentrations in the cell membrane is weaker than that of the single-spot concentration at the center. The variation of the influence of initial locations of the molecular concentrations inside the cell membrane on the diffusion fluxes is also discussed. This result can be applied to the diffusion process in avascular collagenous tissues.
文摘We proposed the use of a hybrid deformable image registration approach that combines compact-support radial basis functions (CSRBF) spline registration with intensity-based image registration. The proposed method first uses the pre-viously developed image intensity-based method to achieve voxel-by-voxel correspondences over the entire image re-gion. Next, for those areas of inaccurate registration, a sparse set of landmark correspondences was defined for local deformable image registration using a multi-step CSRBF approach. This hybrid registration takes advantage of both intensity-based method for automatic processing of entire images and the CSRBF spline method for fine adjustment over specific regions. The goal of using this hybrid registration is to locally control the quality of registration results in specific regions of interest with minimal human intervention. The major applications of this approach in radiation ther-apy are for the corrections of registration failures caused by various imaging artifacts resulting in, low image contrast, and non-correspondence situations where an object may not be imaged in both target and source images. Both synthetic and real patient data have been used to evaluate this hybrid method. We used contours mapping to validate the accuracy of this method on real patient image. Our studies demonstrated that this hybrid method could improve overall registra-tion accuracy with moderate overhead. In addition, we have also shown that the multi-step CSRBF registration proved to be more effective in handling large deformations while maintaining the smoothness of the transformation than origi-nal CSRBF.
基金Project supported by the National Natural Science Foundation of China(Grant No.11474076)
文摘P-type ZnO is crucial for the realization of ZnO-based homojunction ultraviolet optoelectronic devices. The problem associated with the preparation of stable p-type ZnO with high hole density still hinders device applications. In this paper,we introduce an alternative route to stabilizing N in the oxidation process, the thermal stability of p-ZnO is significantly improved. Finally, we discuss the limitations of the alternative doping method and provide some prospective outlook of the method.
