Publications by authors named "Takashi Mizowaki"

262 Publications

Chemoradiotherapy for fistula-related perianal squamous cell carcinoma with Crohn's disease.

Int Cancer Conf J 2021 Oct 30;10(4):305-311. Epub 2021 Jun 30.

Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507 Japan.

The reports of chemoradiotherapy for anal squamous cell carcinoma with Crohn's disease are few. Severe toxicity related to radiotherapy is concerned in patients with inflammatory bowel disease. We report a case of chemoradiotherapy for locally advanced fistula-related perianal squamous cell carcinoma in a patient with long-standing Crohn's disease which was controlled by a maintenance therapy. The patient completed standard chemoradiotherapy using intensity-modulated radiotherapy without severe toxicity, and achieved complete remission. Standard chemoradiotherapy using intensity-modulated radiotherapy may be feasible and effective treatment for this population when Crohn's disease is controlled.
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http://dx.doi.org/10.1007/s13691-021-00497-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421484PMC
October 2021

Long-term outcomes of an esophagus-preserving chemoradiotherapy strategy for patients with endoscopically unresectable stage I thoracic esophageal squamous cell carcinoma.

Clin Transl Radiat Oncol 2021 Sep 11;30:88-94. Epub 2021 Aug 11.

Department of Radiology, Tenri Hospital, Tenri, Nara, Japan.

Background And Purpose: To assess the long-term outcomes of a multimodal approach for maximum esophagus preservation in operable patients with endoscopically unresectable stage I thoracic esophageal squamous cell carcinoma (ESCC).

Materials And Methods: The medical records of patients with stage I thoracic ESCC treated with our protocol between 1992 and 2005 were retrospectively reviewed. Our protocol consisted of neoadjuvant concurrent chemoradiotherapy, followed by either additional definitive chemoradiotherapy for good responders (CRT group) or surgery for moderate or poor responders (CRT-S group) after an interim appraisal.

Results: A total of 51 patients were analysed. The median age of the patients was 67 years. The median follow-up period was 124.8 months. After the interim assessment, 49 and 2 cases were assigned to the CRT and CRT-S groups, respectively. In the intent-to-treat analyses, overall survival (OS), disease-free survival (DFS), cumulative incidence for death from esophageal cancer, and that for loss of esophageal function were 78.9%, 53.5%, 10.5%, and 20.4% at 5 years, and 55.2%, 27.8%, 18.2%, and 22.9% at 10 years, respectively. Grade 3 late toxicities occurred with the following incidences: esophageal stenosis in 1 case, esophageal ulcer in 1 case, and pericardial effusion in 2 cases. No grade 4 or higher toxicities were observed.

Conclusion: Long-term survival and esophagus preservation outcomes were favorable, with acceptable toxicities. Our results suggest that CCRT is an alternative treatment for majority of operable patients with endoscopically unresectable stage I thoracic ESCC in combination with salvage therapy.
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http://dx.doi.org/10.1016/j.ctro.2021.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367761PMC
September 2021

Photoneutron-induced damage reduction for cardiac implantable electronic devices using neutron-shielding sheets in high-energy X-ray radiotherapy: A phantom study.

Phys Med 2021 Aug 6;89:151-159. Epub 2021 Aug 6.

Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.

Purpose: To evaluate damage reduction in cardiac implantable electronic devices (CIEDs) caused by photoneutrons in high-energy X-ray radiotherapy using a neutron-shielding sheet (NSS).

Methods: The NSS consists of a bolus with a thickness of 1 or 2 cm (Bls1 or Bls2) as a moderator and several absorbers (20%, 50%, or 80% BC silicone sheet [BC20, BC50, or BC80] or a 40% LiF silicone sheet [LiF40]). First, a linear accelerator (LINAC) with a water-equivalent phantom was modeled in the simulation and measured experimentally. Several NSSs were placed on the phantom, a Eu:LiCaAlF scintillator was placed between the phantom and the NSS, and X-rays were irradiated. The relative counts (Cr = counts when placing the NSS or Bls2) were compared between the experiment and simulation. Second, CIED damage was evaluated in the simulation. The relative damage (Dr = damage when placing or not placing the NSS) was compared among all the NSSs. In addition, the γ-ray and leaking X-ray dose from BC was measured using a dosimetric film. After determining the optimal NSS combination, Dr value analysis was performed by changing the length of one side and the thickness.

Results: The Cr values of the simulation and experiment agreed within a 30% percentage difference, except for Bare or LiF40-only. The Dr value was reduced by 43% when Bls2 + BC80 was applied. The photon dose was less than 5 cGy/1500 MU. The Dr values were smaller for the smaller lengths of one side of BC80 and decreased as the M-layer thickness increased.

Conclusions: The CIED damage induced by photoneutrons generated by a LINAC was effectively reduced by applying the optimal NSS.
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http://dx.doi.org/10.1016/j.ejmp.2021.07.036DOI Listing
August 2021

Ostial common carotid artery occlusion and balloon-mounted stenting: Implication of embolic protection device in tandem lesion.

Radiol Case Rep 2021 Sep 22;16(9):2783-2786. Epub 2021 Jul 22.

Department of Neurosurgery, Shinsuma General Hospital, 3-1-14 Kinugake-cho, Suma-ku, Kobe, Hyogo, 654-0048, Japan.

Ostial common carotid artery (CCA) stenosis is rare, compared to extracranial internal carotid artery bifurcation lesions. In cases of a tandem lesion, the proximal lesion usually involves the extracranial internal carotid artery, and the ostial CCA is rarely implicated. A 69-year-old woman who underwent 3 months of antiplatelet therapy for asymptomatic, right ostial, severely calcified CCA stenosis presented with sudden onset left hemiparesis. Radiographic examination revealed an ostial CCA-intracranial artery tandem lesion. After intracranial revascularization using a clot retrieval stent, we performed the endovascular treatment with a balloon-mounted stent using an embolic protection device. This procedure may be superior to others because it is possible to achieve early intracranial revascularization and prevent distal embolism during the complete treatment of proximal lesions.
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http://dx.doi.org/10.1016/j.radcr.2021.06.071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326589PMC
September 2021

Highly hypofractionated intensity-modulated radiation therapy for nonmetastatic prostate cancer with a simultaneous integrated boost to intraprostatic lesions: a planning study.

Jpn J Radiol 2021 Aug 5. Epub 2021 Aug 5.

Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Purpose: The purpose of this planning study was to develop an acceptable technique for highly hypofractionated intensity-modulated radiation therapy using simultaneous integrated boost technique (SIB-hHF-RT) for nonmetastatic National Comprehensive Cancer Network high-risk prostate cancer.

Materials And Methods: We created SIB-hHF-RT plans for 14 nonmetastatic prostate cancer patients with MRI-detectable intraprostatic lesions (IPLs) and without intestines locating close to the seminal vesicle and prostate. We prescribed 57 Gy for IPLs and 54 Gy for the remainder of planning target volume (PTV) in 15 fractions. The IPLs were contoured based on magnetic resonance imaging, and PTV was generated by adding 6-8-mm margins to the clinical target volume. For the dose-volume constraints of organs at risk (OARs), the same constraints as 54 Gy plans were used so as not to increase the toxicity.

Results: All created plans fulfilled the dose-volume constraints of all targets and OARs. The median estimated beam-on time was 108.5 s. For patient-specific quality assurance, the global gamma passing rates (3%/2 mm) with 10% dose threshold criteria were greater than 93% in all cases and greater than 95% in 11 cases.

Conclusion: SIB-hHF-RT plans were developed that fulfill the acceptable dose-volume constraints and pass patient-specific quality assurance. We believe these plans can be applied to selected patients with nonmetastatic prostate cancer.
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http://dx.doi.org/10.1007/s11604-021-01186-6DOI Listing
August 2021

Long-term safety of high-dose whole pelvic IMRT for high-risk localized prostate cancer through 10-year follow-up.

Int J Clin Oncol 2021 Aug 2. Epub 2021 Aug 2.

Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto-shi, Kyoto, 606-8507, Japan.

Background: The aim of this study was to evaluate the long-term efficacy and safety of whole pelvic intensity-modulated radiation therapy with a simultaneous-integrated boost (WP-SIB-IMRT) for locally advanced prostate cancer (LAPCa).

Methods: All patients with cT3-4N0M0 prostate cancer treated with WP-SIB-IMRT between February 2006 and September 2009 at our institution were analyzed retrospectively. The prescribed dose was 78 Gy to the prostate and 58.5 Gy to the prophylactic pelvic lymph nodal area in 39 fractions delivered using the simultaneous-integrated boost technique. All patients received short-term neoadjuvant androgen-deprivation therapy alone (median 8.3 months). Propensity-score matching (PSM) analysis was performed to evaluate the additional benefit of prophylactic whole pelvic radiation therapy (WPRT), using the cohort of 203 LAPCa patients treated with prostate-only IMRT (PO-IMRT).

Results: In total, 47 consecutive patients were analyzed. The median estimated risk of pelvic lymph node involvement was 57.5%. The median follow-up period was 10.5 years. The 10 year prostate cancer-specific survival and biochemical failure (BF) rates were 92.2 and 54.8%, respectively. The 10 year cumulative incidence rates of ≥ grade 2 late genitourinary and gastrointestinal toxicities were 21.6 and 17.2%, respectively. From a total of 250 patients, PSM analysis identified 76 patients with similar characteristics, and no significant difference in BF rates was observed between WP-SIB-IMRT and PO-IMRT cohorts (p = 0.261).

Conclusions: WP-SIB-IMRT for LAPCa was safe over long-term observation, although no clear benefit of WPRT was observed among our small and highly selected cohort. Regarding the additional efficacy of WPRT, further investigations are needed.
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http://dx.doi.org/10.1007/s10147-021-02002-xDOI Listing
August 2021

Interfractional target changes in brain metastases during 13-fraction stereotactic radiotherapy.

Radiat Oncol 2021 Jul 28;16(1):140. Epub 2021 Jul 28.

Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

Background: The risk for radiation necrosis is lower in fractionated stereotactic radiotherapy (SRT) than in conventional radiotherapy, and 13-fraction SRT is our method of choice for the treatment of brain metastases ≥ around 2 cm or patients who are expected to have a good prognosis. As 13-fraction SRT lasts for at least 17 days, adaptive radiotherapy based on contrast-enhanced mid-treatment magnetic resonance imaging (MRI) is often necessary for patients undergoing 13-fraction SRT. In this study, we retrospectively analyzed interfractional target changes in patients with brain metastases treated with 13-fraction SRT.

Methods: Our analyses included data from 23 patients and 27 metastatic brain lesions treated with 13-fraction SRT with dynamic conformal arc therapy. The peripheral dose prescribed to the planning target volume (PTV) was 39-44.2 Gy in 13-fractions. The gross tumor volume (GTV) of the initial SRT plan (initial GTV), initial PTV, and modified GTV based on the mid-treatment MRI scan (mid-treatment GTV) were assessed.

Results: The median initial GTV was 3.8 cm and the median time from SRT initiation to the mid-treatment MRI scan was 6 days. Compared to the initial GTV, the mid-treatment GTV increased by more than 20% in five lesions and decreased by more than 20% in five lesions. Interfractional GTV volume changes of more than 20% were not significantly associated with primary disease or the presence of cystic components/necrosis. The mid-treatment GTV did not overlap perfectly with the initial PTV in more than half of the lesions.

Conclusions: Compared to the initial GTV, the mid-treatment GTV changed by more than 20% in almost one-third of lesions treated with 13-fraction SRT. As SRT usually generates a steep dose gradient as well as increasing the maximum dose of PTV compared to conventional radiotherapy, assessment of the volume and locational target changes and adaptive radiotherapy should be considered as the number of fractions increases.
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http://dx.doi.org/10.1186/s13014-021-01869-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317405PMC
July 2021

Development of in-house fully residual deep convolutional neural network-based segmentation software for the male pelvic CT.

Radiat Oncol 2021 Jul 22;16(1):135. Epub 2021 Jul 22.

Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Background: This study aimed to (1) develop a fully residual deep convolutional neural network (CNN)-based segmentation software for computed tomography image segmentation of the male pelvic region and (2) demonstrate its efficiency in the male pelvic region.

Methods: A total of 470 prostate cancer patients who had undergone intensity-modulated radiotherapy or volumetric-modulated arc therapy were enrolled. Our model was based on FusionNet, a fully residual deep CNN developed to semantically segment biological images. To develop the CNN-based segmentation software, 450 patients were randomly selected and separated into the training, validation and testing groups (270, 90, and 90 patients, respectively). In Experiment 1, to determine the optimal model, we first assessed the segmentation accuracy according to the size of the training dataset (90, 180, and 270 patients). In Experiment 2, the effect of varying the number of training labels on segmentation accuracy was evaluated. After determining the optimal model, in Experiment 3, the developed software was used on the remaining 20 datasets to assess the segmentation accuracy. The volumetric dice similarity coefficient (DSC) and the 95th-percentile Hausdorff distance (95%HD) were calculated to evaluate the segmentation accuracy for each organ in Experiment 3.

Results: In Experiment 1, the median DSC for the prostate were 0.61 for dataset 1 (90 patients), 0.86 for dataset 2 (180 patients), and 0.86 for dataset 3 (270 patients), respectively. The median DSCs for all the organs increased significantly when the number of training cases increased from 90 to 180 but did not improve upon further increase from 180 to 270. The number of labels applied during training had a little effect on the DSCs in Experiment 2. The optimal model was built by 270 patients and four organs. In Experiment 3, the median of the DSC and the 95%HD values were 0.82 and 3.23 mm for prostate; 0.71 and 3.82 mm for seminal vesicles; 0.89 and 2.65 mm for the rectum; 0.95 and 4.18 mm for the bladder, respectively.

Conclusions: We have developed a CNN-based segmentation software for the male pelvic region and demonstrated that the CNN-based segmentation software is efficient for the male pelvic region.
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http://dx.doi.org/10.1186/s13014-021-01867-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299691PMC
July 2021

Definitive radiotherapy for secondary esophageal cancer after allogeneic hematopoietic stem cell transplantation.

Int Cancer Conf J 2021 Jul 20;10(3):201-206. Epub 2021 Mar 20.

Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507 Japan.

The reports for secondary esophageal cancer treated by radiotherapy or chemoradiotherapy is few, however they potentially yield a cure for esophageal cancer. We report a case of definitive radiotherapy for a patient with secondary locally advanced unresectable esophageal cancer after hematopoietic stem cell transplantation for acute myeloid leukemia. Definitive radiotherapy for the current patient was completed with acceptable toxicity despite the poor general condition with long-term chronic graft-versus-host disease. Radiotherapy may be the definitive treatment for this population unfit for concurrent chemotherapy or surgery.
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http://dx.doi.org/10.1007/s13691-021-00479-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206320PMC
July 2021

Efficacy of local salvage therapy for recurrent uterine cervical cancer after definitive radiotherapy.

Int J Clin Oncol 2021 Oct 24;26(10):1968-1976. Epub 2021 Jun 24.

Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

Background: The prognosis of patients with recurrence of uterine cervical cancer after definitive radiotherapy and the efficacy of local salvage therapy for recurrence were evaluated.

Methods: We retrospectively reviewed 110 patients who were treated with definitive radiotherapy/chemoradiotherapy for uterine cervical cancer between 2008 and 2017 at our institution. Local salvage therapy was defined as any surgery or radiotherapy described in the medical record as intended for local control or cure.

Results: We identified 25 patients who developed recurrence after definitive radiotherapy/chemoradiotherapy. The median follow-up time post-recurrence was 18.9 months. Thirteen patients (52%) reported recurrence in the isolated extra-pelvic lymph node (EPLN). The 2-year overall survival after first recurrence (OSr) for patients with isolated EPLN recurrence was 83.1%, compared to that of 31.2% for patients with other patterns of recurrence (p < 0.001). The 2-year OSr for patients who underwent local salvage therapy was 75.2%, whereas that for patients who did not undergo therapy was 41.6% (p = 0.04). Among patients who had recurrence in the isolated EPLN and received local salvage therapy, 20% of the patients reported recurrence in visceral and/or bone metastases after local salvage therapy, and 50% of the patients experienced another EPLN recurrence, which was salvaged with repeating local therapy.

Conclusions: Patients with uterine cervical cancer with isolated EPLN recurrence had favorable prognoses. The indications of local salvage therapy should be considered, especially for patients with isolated EPLN recurrence.
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http://dx.doi.org/10.1007/s10147-021-01974-0DOI Listing
October 2021

Reducing variability among treatment machines using knowledge-based planning for head and neck, pancreatic, and rectal cancer.

J Appl Clin Med Phys 2021 Jul 20;22(7):245-254. Epub 2021 Jun 20.

Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Purpose: This study aimed to assess dosimetric indices of RapidPlan model-based plans for different energies (6, 8, 10, and 15 MV; 6- and 10-MV flattening filter-free), multileaf collimator (MLC) types (Millennium 120, High Definition 120, dual-layer MLC), and disease sites (head and neck, pancreatic, and rectal cancer) and compare these parameters with those of clinical plans.

Methods: RapidPlan models in the Eclipse version 15.6 were used with the data of 28, 42, and 20 patients with head and neck, pancreatic, and rectal cancer, respectively. RapidPlan models of head and neck, pancreatic, and rectal cancer were created for TrueBeam STx (High Definition 120) with 6 MV, TrueBeam STx with 10-MV flattening filter-free, and Clinac iX (Millennium 120) with 15 MV, respectively. The models were used to create volumetric-modulated arc therapy plans for a 10-patient test dataset using all energy and MLC types at all disease sites. The Holm test was used to compare multiple dosimetric indices in different treatment machines and energy types.

Results: The dosimetric indices for planning target volume and organs at risk in RapidPlan model-based plans were comparable to those in the clinical plan. Furthermore, no dose difference was observed among the RapidPlan models. The variability among RapidPlan models was consistent regardless of the treatment machines, MLC types, and energy.

Conclusions: Dosimetric indices of RapidPlan model-based plans appear to be comparable to the ones based on clinical plans regardless of energies, MLC types, and disease sites. The results suggest that the RapidPlan model can generate treatment plans independent of the type of treatment machine.
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http://dx.doi.org/10.1002/acm2.13316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292706PMC
July 2021

Novel metastatic burden-stratified risk model in de novo metastatic hormone-sensitive prostate cancer.

Cancer Sci 2021 Sep 10;112(9):3616-3626. Epub 2021 Jul 10.

Department of Urology, Kagoshima University, Kagoshima, Japan.

The metastatic burden is a critical factor for decision-making in the treatment of metastatic hormone-sensitive prostate cancer (HSPC). This study aimed to develop and validate a novel risk model for survival in patients with de novo low- and high-burden metastatic HSPC. The retrospective observational study included men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We created a risk model for overall survival (OS) in the discovery cohort (n = 1449) stratified by the metastatic burden (low vs high) and validated its predictive ability in a separate cohort (n = 951). Based on multivariate analyses, lower hemoglobin levels, higher Gleason grades, and higher clinical T-stage were associated with poor OS in low-burden disease. Meanwhile, lower hemoglobin levels, higher Gleason grade group, liver metastasis, and higher extent of disease scores in bone were associated with poor OS in patients with high-burden disease. In the discovery and validation cohorts, the risk model using the aforementioned parameters exhibited excellent discriminatory ability for progression-free survival and OS. The predictive ability of this risk model was superior to that of previous risk models. Our novel metastatic burden-stratified risk model exhibited excellent predictive ability for OS, and it is expected to have several clinical uses, such as precise prognostic estimation.
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http://dx.doi.org/10.1111/cas.15038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409413PMC
September 2021

Radiation recall myositis caused by pazopanib in a patient with refractory osteosarcoma.

Pediatr Blood Cancer 2021 Sep 14;68(9):e29147. Epub 2021 Jun 14.

Department of Radiation Oncology and Image-Applied Therapy, Kyoto University, Kyoto, Japan.

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http://dx.doi.org/10.1002/pbc.29147DOI Listing
September 2021

Pharmacological inhibition of sodium-calcium exchange activates NADPH oxidase and induces infection-independent NETotic cell death.

Redox Biol 2021 07 26;43:101983. Epub 2021 Apr 26.

Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan.

In addition to its function of innate immunity against invading pathogens, neutrophil extracellular traps (NETs) promote thrombosis, autoimmune disease, and cancer metastasis; therefore, unnecessary exposure to the triggers of infection-independent NET generation should be avoided. We herein show that inhibition of forward-mode Na/Ca exchange by amiloride analogs, 5-(N-ethyl-N-isopropyl)amiloride (EIPA) and 5-(N-Methyl-N-isobutyl)amiloride (MIA), triggers NETotic cell death independently of infectious stimuli. Isolated human neutrophils treated with EIPA and MIA undergo NETotic cell death by an increase of intracellular Ca following activation of NADPH oxidase and the resultant upregulation of intracellular ROS. EIPA- and MIA-mediated intracellular Ca increase is attributed to the competitive binding of EIPA and MIA against Na to Na/Ca exchanger 1 (NCX1). These results demonstrate a new mechanism of infection-independent NET generation and implicate NCX1 as a physiologic regulator of intracellular calcium balance and NETotic cell death.
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http://dx.doi.org/10.1016/j.redox.2021.101983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105669PMC
July 2021

Long-term clinical outcomes of external beam radiation therapy for oligometastatic prostate cancer: A combination of prostate-targeted treatment and metastasis-directed therapy.

Int J Urol 2021 Jul 2;28(7):749-755. Epub 2021 Apr 2.

Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Objective: To assess the efficacy of combination of prostate-targeted treatment and metastasis-directed therapy for oligometastatic prostate cancer.

Methods: We retrospectively evaluated the clinical outcomes of synchronously diagnosed oligometastatic prostate cancer patients treated with external beam radiation therapy for the prostate and all metastatic lesions (≤3 lesions) at Kyoto University Hospital between January 2004 and April 2019. The prescribed dose was basically ≥70 Gy for the prostate with or without whole pelvic irradiation, and ≥45 Gy for the metastatic lesions. Clinical outcomes were compared with a contemporary cohort of 55 synchronous oligometastatic prostate cancer patients treated with the standard of care.

Results: In total, 16 consecutive patients with synchronous oligometastatic prostate cancer were analyzed. The median follow-up period was 7.4 years. The 8-year overall survival, prostate cancer-specific survival, biochemical failure-free, clinical failure-free and castration-resistant prostate cancer-free rates were 64.8%, 71.3%, 38.5%, 47.3% and 67.3%, respectively. No grade 3 or higher radiation-induced late toxicities occurred. Patients with prostate-targeted treatment plus metastasis-directed therapy had a significantly higher castration-resistant prostate cancer-free rate than those without prostate-targeted treatment plus metastasis-directed therapy (P = 0.00741).

Conclusions: Prostate-targeted treatment plus metastasis-directed therapy through external beam radiation therapy can result in favorable long-term disease-free and survival outcomes with acceptable morbidities among synchronous oligometastatic prostate cancer patients. Therefore, this approach may represent a promising treatment strategy for this population. Further investigation is required.
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http://dx.doi.org/10.1111/iju.14567DOI Listing
July 2021

Quantitative autoradiography in boron neutron capture therapy considering the particle ranges in the samples.

Phys Med 2021 Feb 12;82:306-320. Epub 2021 Mar 12.

Particle Radiation Oncology Research Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University, Osaka, Japan. Electronic address:

Purpose: Boron neutron capture therapy is a cellular-scale particle therapy exploiting boron neutron capture reactions in boron compounds distributed in tumour cells. Its therapeutic effect depends on both the accumulation of boron in tumour cells and the neutron fluence. Autoradiography is used to visualise the micro-distribution of boron compounds.

Methods: Here, we present an equation for the relationship between boron concentration and pit density on the solid-state nuclear track detector, taking into consideration the particle ranges in the samples. This equation is validated using liver-tissue sections and boron standard solutions. Moreover, we present a simple co-localisation system for pit and tissue-section images that requires no special equipment.

Results: The equation reproduces the experimentally observed trends between boron concentration and pit density. This equation provides a theoretical explanation for the widely used calibration curve between pit density and boron concentration; it also provides a method to correct for differences of tissue-section thickness in quantitative autoradiography.

Conclusions: Using the equation together with this co-localisation system could improve micro-scale quantitative estimation in tissue sections.
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http://dx.doi.org/10.1016/j.ejmp.2021.02.012DOI Listing
February 2021

Incidence and Risk Factors of Symptomatic Radiation Pneumonitis in Non-Small-Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy and Consolidation Durvalumab.

Clin Lung Cancer 2021 Sep 4;22(5):401-410. Epub 2021 Feb 4.

Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Introduction: Data on the risk factors for symptomatic radiation pneumonitis (RP) in non-small-cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) and consolidation durvalumab are limited; we aimed to investigate these risk factors.

Materials And Methods: This multicenter retrospective study, conducted at 15 institutions in Japan, included patients who were ≥20 years of age; who started definitive CCRT for NSCLC between July 1, 2018, and July 31, 2019; and who then received durvalumab. The primary endpoint was grade 2 or worse (grade 2+) RP.

Results: In the 146 patients analyzed, the median follow-up period was 16 months. A majority of the patients had stage III disease (86%), received radiation doses of 60 to 66 Gy equivalent in 2-Gy fractions (93%) and carboplatin and paclitaxel/nab-paclitaxel (77%), and underwent elective nodal irradiation (71%) and 3-dimensional conformal radiotherapy (75%). RP grade 2 was observed in 44 patients (30%); grade 3, in four patients (3%); grade 4, in one patient (1%); and grade 5, in one patient (1%). In the multivariable analysis, lung V20 was a significant risk factor, whereas age, sex, smoking history, irradiation technique, and chemotherapy regimen were not. The 12-month grade 2+ RP incidence was 34.4% (95% confidence interval [CI], 26.7%-42.1%); the values were 50.0% (95% CI, 34.7%-63.5%) and 27.1% (95% CI, 18.8%-36.2%) in those with lung V20 ≥ 26% and < 26%, respectively (P = .007).

Conclusion: The incidence of grade 2+ RP was relatively high in this multicenter real-world study, and its risk increased remarkably at elevated lung V20. Our findings can aid in RP risk prediction and the safe radiotherapy treatment planning.
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http://dx.doi.org/10.1016/j.cllc.2021.01.017DOI Listing
September 2021

Appropriate margin for planning target volume for breast radiotherapy during deep inspiration breath-hold by variance component analysis.

Radiat Oncol 2021 Mar 6;16(1):49. Epub 2021 Mar 6.

Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Kyoto, 606-8507, Japan.

Background: This study aimed to quantify errors by using a cine electronic portal imaging device (cine EPID) during deep inspiration breath-hold (DIBH) for left-sided breast cancer and to estimate the planning target volume (PTV) by variance component analysis.

Methods: This study included 25 consecutive left-sided breast cancer patients treated with whole-breast irradiation (WBI) using DIBH. Breath-holding was performed while monitoring abdominal anterior-posterior (AP) motion using the Real-time Position Management (RPM) system. Cine EPID was used to evaluate the chest wall displacements in patients. Cine EPID images of the patients (309,609 frames) were analyzed to detect the edges of the chest wall using a Canny filter. The errors that occurred during DIBH included differences between the chest wall position detected by digitally reconstructed radiographs and that of all cine EPID images. The inter-patient, inter-fraction, and intra-fractional standard deviations (SDs) in the DIBH were calculated, and the PTV margin was estimated by variance component analysis.

Results: The median patient age was 55 (35-79) years, and the mean irradiation time was 20.4 ± 1.7 s. The abdominal AP motion was 1.36 ± 0.94 (0.14-5.28) mm. The overall mean of the errors was 0.30 mm (95% confidence interval: - 0.05-0.65). The inter-patient, inter-fraction, and intra-fractional SDs in the DIBH were 0.82 mm, 1.19 mm, and 1.63 mm, respectively, and the PTV margin was calculated as 3.59 mm.

Conclusions: Errors during DIBH for breast radiotherapy were monitored using EPID images and appropriate PTV margins were estimated by variance component analysis.
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http://dx.doi.org/10.1186/s13014-021-01777-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937254PMC
March 2021

Multi-institutional dose-segmented dosiomic analysis for predicting radiation pneumonitis after lung stereotactic body radiation therapy.

Med Phys 2021 Apr 2;48(4):1781-1791. Epub 2021 Mar 2.

Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Purpose: To predict radiation pneumonitis (RP) grade 2 or worse after lung stereotactic body radiation therapy (SBRT) using dose-based radiomic (dosiomic) features.

Methods: This multi-institutional study included 247 early-stage nonsmall cell lung cancer patients who underwent SBRT with a prescribed dose of 48-70 Gy at an isocenter between June 2009 and March 2016. Ten dose-volume indices (DVIs) were used, including the mean lung dose, internal target volume size, and percentage of entire lung excluding the internal target volume receiving greater than x Gy (x = 5, 10, 15, 20, 25, 30, 35, and 40). A total of 6,808 dose-segmented dosiomic features, such as shape, first order, and texture features, were extracted from the dose distribution. Patients were randomly partitioned into two groups: model training (70%) and test datasets (30%) over 100 times. Dosiomic features were converted to z-scores (standardized values) with a mean of zero and a standard deviation (SD) of one to put different variables on the same scale. The feature dimension was reduced using the following methods: interfeature correlation based on Spearman's correlation coefficients and feature importance based on a light gradient boosting machine (LightGBM) feature selection function. Three different models were developed using LightGBM as follows: (a) a model with ten DVIs (DVI model), (b) a model with the selected dosiomic features (dosiomic model), and (c) a model with ten DVIs and selected dosiomic features (hybrid model). Suitable hyperparameters were determined by searching the largest average area under the curve (AUC) value in the receiver operating characteristic curve (ROC-AUC) via stratified fivefold cross-validation. Each of the final three models with the closest the ROC-AUC value to the average ROC-AUC value was applied to the test datasets. The classification performance was evaluated by calculating the ROC-AUC, AUC in the precision-recall curve (PR-AUC), accuracy, precision, recall, and f1-score. The entire process was repeated 100 times with randomization, and 100 individual models were developed for each of the three models. Then the mean value and SD for the 100 random iterations were calculated for each performance metric.

Results: Thirty-seven (15.0%) patients developed RP after SBRT. The ROC-AUC and PR-AUC values in the DVI, dosiomic, and hybrid models were 0.660 ± 0.054 and 0.272 ± 0.052, 0.837 ± 0.054 and 0.510 ± 0.115, and 0.846 ± 0.049 and 0.531 ± 0.116, respectively. For each performance metric, the dosiomic and hybrid models outperformed the DVI models (P < 0.05). Texture-based dosiomic feature was confirmed as an effective indicator for predicting RP.

Conclusions: Our dose-segmented dosiomic approach improved the prediction of the incidence of RP after SBRT.
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http://dx.doi.org/10.1002/mp.14769DOI Listing
April 2021

Short diameter may be a useful simple indicator of the tumor response in skull base meningiomas after conventionally fractionated stereotactic radiotherapy.

Eur Radiol 2021 Aug 10;31(8):6367-6373. Epub 2021 Feb 10.

Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

Objectives: The purpose of this study was to assess the radiological change patterns in skull base meningiomas after conventionally fractionated stereotactic radiotherapy (CFSRT) to determine a simple and valid method to assess the tumor response.

Materials And Methods: Forty-one patients with a benign skull base meningioma treated by CFSRT from March 2007 to August 2015 were retrospectively evaluated. We measured tumor volume (TV), long-axis diameter (LD), and short-axis diameter (SD) on both pre-treatment images and follow-up images of 1, 3, and 5 years after CFSRT, respectively. The paired t test was used to detect differences in the LD and SD change rates. Spearman's correlation coefficients were calculated to evaluate relationships between the TV and the diameters changes.

Results: The number of available follow-up MRIs that was performed at 1, 3, and 5 years after the CFSRT was 41 (100%), 34 (83%), and 23 (56%), respectively. The change rates of SD were significantly higher than those of LD at every time point and more strongly correlated with the change rates of tumor volume at 3 and 5 years after CFSRT.

Conclusions: SD may be useful as a simple indicator of the tumor response for skull base meningioma after CFSRT.

Key Points: • The change rate in short-axis diameter is a useful and simple indicator of the response of skull base meningioma to conventionally fractionated stereotactic radiotherapy. • Conventionally fractionated stereotactic radiotherapy for skull base meningioma achieved excellent 5-year local control.
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http://dx.doi.org/10.1007/s00330-021-07707-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270820PMC
August 2021

Evaluation of intrafractional head motion for intracranial stereotactic radiosurgery with a thermoplastic frameless mask and ceiling-floor-mounted image guidance device.

Phys Med 2021 Jan 20;81:245-252. Epub 2021 Jan 20.

Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.

Purpose: To evaluate intrafractional head motion (IFM) in patients who underwent intracranial stereotactic radiosurgery with the ExacTrac X-ray system (ETX) and a frameless mask.

Methods: A total of 143 patients who completed a pre-treatment examination for IFM were eligible for this study. The frameless mask type B R408 (Klarity Medical & Equipment Co., Ltd., Guangzhou, China), which covers the back of the head, and the entire face, was used for patient immobilization. After the initial 6D correction and first X-ray verification (IFM), X-ray verification was performed every 3 min for a duration of 15 min. The IFM (2 ≤ p ≤ 6) was calculated as the positional difference from IFM. In addition, the inter-phase IFM (IP-IFM) and IFM were calculated. The IP-IFM was defined as |IFM - IFM|, and IFM as the difference between the values after all patients were asked to move their heads intentionally with the frameless mask on.

Results: Both translational IFM and IP-IFM exceeded 1 mm for a single patient, whereas, for all patients, the translational IFM values were kept to within 1 mm in all directions. The proportions of the rotational IFM, IP-IFM, and IFM values within 0.5° were greater than 94.4%, 98.6%, and 90.2% for all of the rotational axes, respectively.

Conclusions: A frameless mask achieved highly accurate patient positioning in combination with ETX and a 6°-of-freedom robotic couch; however, a deviation over 1 mm and 0.5° was observed with low frequency. Therefore, X-ray verification and correction are required during treatment.
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http://dx.doi.org/10.1016/j.ejmp.2020.12.019DOI Listing
January 2021

Evaluation of Optimal Post-Injection Timing of Hypoxic Imaging with F-Fluoromisonidazole-PET/CT.

Mol Imaging Biol 2021 08 21;23(4):597-603. Epub 2021 Jan 21.

Department of Radiation Oncology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan.

Purpose: Positron emission tomography (PET)/computed tomography (CT) using F-fluoromisonidazole (FMISO) has been used as an imaging tool for tumour hypoxia. However, it remains unclear whether they are useful when scanning is performed earlier, e.g. at 2-h post-injection with a high sensitivity PET scanner. This study aimed to investigate the relationship between quantitative values in F-fluoromisonidazole (F-FMISO)-PET obtained at 2- and 4-h post-injection in patients with head and neck cancer.

Procedures: We enrolled 20 patients with untreated locally advanced head and neck cancer who underwent F-FMISO-PET/CT scan between August 2015 and March 2018 at our institute. Image acquisition was performed 2 h and 4 h after F-FMISO administration using a combined PET/CT scanner. The SUVmax, SUVmean, SUVpeak, tumour-to-blood ratio (TBR), tumour-to-muscle ratio (TMR), metabolic tumour volume (MTV), and total lesion hypoxia (TLH) were measured in the region of interest of the primary tumour. We evaluated the between-image Spearman's rank correlation coefficients and percentage differences in the quantitative values. The locations of the maximum uptake pixel were identified in both scans, and the distance between them was measured.

Results: The mean (SD) SUVmax at 2 h and 4 h was 2.2(0.7) and 2.4(0.8), respectively. The Spearman's rank correlation coefficients (ρ) and mean (SD) of the percentage differences of the measures were as follows: SUVmax (0.97; 7.0 [5.1]%), SUVmean (0.97; 5.2 [5.8]%), SUVpeak (0.94; 5.3 [4.7]%), TBR (0.96; 14.2 [9.8]%), TMR (0.96; 14.7 [8.4]%), MTV (0.98; 39.9 [41.3]%), and TLH (0.98; 40.1 [43.4]%). There were significant between-scan correlations in all quantitative values. The mean (SD) distance between the two maximum uptake pixels was 7.3 (5.3) mm.

Conclusions: We observed a high correlation between the quantitative values at 2 h and 4 h. When using a combined high-quality PET/CT, the total examination time for FMISO-PET can be shortened by skipping the 4-h scan.
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http://dx.doi.org/10.1007/s11307-021-01580-6DOI Listing
August 2021

Quantification and correction of the scattered X-rays from a megavoltage photon beam to a linac-mounted kilovoltage imaging subsystem.

BJR Open 2020 11;2(1):20190048. Epub 2020 Dec 11.

Department of Radiation Oncology and Image-applied Therapy, Kyoto University Hospital, Kyoto 606-8507, Japan.

Objective: To quantify and correct megavoltage (MV) scattered X-rays (MV-scatter) on an image acquired using a linac-mounted kilovoltage (kV) imaging subsystem.

Methods And Materials: A linac-mounted flat-panel detector (FPD) was used to acquire an image containing MV-scatter by activating the FPD only during MV beam irradiation. 6-, 10-, and 15 MV with a flattening-filter (FF; 6X-FF, 10X-FF, 15X-FF), and 6- and 10 MV without an FF (6X-FFF, 10X-FFF) were used. The maps were acquired by changing one of the irradiation parameters while the others remained fixed. The mean pixel values of the MV-scatter were normalized to the 6X-FF reference condition (MV-scatter value). An MV-scatter database was constructed using these values. An MV-scatter correction experiment with one full arc image acquisition and two square field sizes (FSs) was conducted. Measurement- and estimation-based corrections were performed using the database. The image contrast was calculated at each angle.

Results: The MV-scatter increased with a larger FS and dose rate. The MV-scatter value factor varied substantially depending on the FPD position or collimator rotation. The median relative error ranges of the contrast for the image without, and with the measurement- and estimation-based correction were -10.9 to -2.9, and -1.5 to 4.8 and -7.4 to 2.6, respectively, for an FS of 10.0 × 10.0 cm.

Conclusions: The MV-scatter was strongly dependent on the FS, dose rate, and FPD position. The MV-scatter correction improved the image contrast.

Advances In Knowledge: The MV-scatters on the TrueBeam linac kV imaging subsystem were quantified with various MV beam parameters, and strongly depended on the fieldsize, dose rate, and flat panel detector position. The MV-scatter correction using the constructed database improved the image quality.
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http://dx.doi.org/10.1259/bjro.20190048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731796PMC
December 2020

Actual delivered dose calculation on intra-irradiation cone-beam computed tomography images: a phantom study.

Phys Med Biol 2021 01 14;66(1):015007. Epub 2021 Jan 14.

Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.

Cone-beam computed tomography (CBCT) images acquired during volumetric modulated arc therapy (VMAT; ii-CBCT) can be used to calculate actual delivered doses (ADDs). However, such ii-CBCT images are degraded by scattered megavoltage x-rays (MV-scatters). We aimed to evaluate the dose calculation accuracy of the MV-scatter uncorrected or corrected ii-CBCT images acquired during VMAT deliveries. For MV-scatter correction on concurrent kilovoltage projections (P ), projections consisting only of MV-scatters (P ) were acquired under the same MV beam parameters and gantry angles and subtracted from P (P ). In addition, the projections by kilovoltage beams were acquired for reference (P ). The corresponding CBCT images were reconstructed using the Feldkamp-Davis-Kress algorithm (CBCT, CBCT, and CBCT as reference). A multi-energy phantom with rods of various relative electron densities (REDs) was used to generate a CBCT-number-to-RED conversion table. First, CBCT was reconstructed. Then, the mean CBCT-numbers within each rod were extracted, and a reference table was generated. Concurrent kilovoltage imaging with various field sizes was also demonstrated, and CBCT and CBCT were reconstructed. The extracted CBCT-numbers of each ii-CBCT image were converted into REDs using the reference table. Next, the absolute differences of RED between the ii-CBCT image and CBCT were calculated. Ten VMAT plans using a 10 MV flattening-filter-free beam were used for concurrent imaging of an anthropomorphic torso phantom. Moreover, an iterative reconstruction algorithm (IRA) was used for CBCT. The plans were recalculated for the corresponding CBCT, CBCT, CBCT, and CBCT with the reference table. Finally, the doses were evaluated using 3D gamma analysis (1%/1 mm). The median difference ranges between CBCT/CBCT and the reference values were -0.58 to -0.10/-0.03 to 0.00. The median gamma pass rates of the doses on CBCT, CBCT, and CBCT to the rate on CBCT were 70.4, 99.5, and 98.2%, respectively. CBCT were comparable with CBCT for calculating the ADD from VMAT.
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http://dx.doi.org/10.1088/1361-6560/abcdebDOI Listing
January 2021

Statistical shape model-based planning organ-at-risk volume: application to pancreatic cancer patients.

Phys Med Biol 2021 01 14;66(1):014001. Epub 2021 Jan 14.

Division of Medical Physics, Department of Information Technology and Medical Engineering, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.

Purpose: To introduce the concept of statistical shape model (SSM)-based planning organ-at-risk volume (sPRV) for pancreatic cancer patients.

Methods: A total of 120 pancreatic cancer patients were enrolled in this study. After correcting inter-patient variations in the centroid position of the planning target volume (PTV), four different SSMs were constructed by registering a deformable template model to an individual model for the stomach and duodenum. The sPRV, which focused on the following different components of the inter-patient variations, was then created: Scenario A: shape, rotational angle, volume, and centroid position; Scenario B: shape, rotational angle, and volume; Scenario C: shape and rotational angle; and Scenario D: shape. The conventional PRV (cPRV) was created by adding an isotropic margin R (3-15 mm) to the mean shape model. The corresponding sPRV was created from the SSM until the volume difference between the cPRV and sPRV was less than 1%. Thereafter, we computed the overlapping volume between the PTV and cPRV (OL) or sPRV (OL) in each patient. OL being larger than OL implies that the local shape variations in the corresponding OAR close to the PTV were large. Therefore, OL/OL was calculated in each patient for each R-value, and the median value of OL/OL was regarded as a surrogate for plan quality for each R-value.

Results: For R = 3 and 5 mm, OL/OL exceeded 1 for the stomach and duodenum in all scenarios, with a maximum OL/OL of 1.21. This indicates that smaller isotropic margins did not sufficiently account for the local shape changes close to the PTV.

Conclusions: Our results indicated that, in contrast to conventional PRV, SSM-based PRVs, which account for local shape changes, would result in better dose sparing for the stomach and duodenum in pancreatic cancer patients.
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http://dx.doi.org/10.1088/1361-6560/abcd1bDOI Listing
January 2021

[Posterior Approach for Cervical Spondylotic Myelopathy in Patients Older than 80 Years of Age].

No Shinkei Geka 2020 Nov;48(11):1013-1019

Department of Neurosurgery, Jikeikai Shinsuma General Hospital.

Objective: We aimed to investigate the characteristics and operative results of elderly patients with cervical spondylotic myelopathy(aged ≧80 years)treated using the posterior approach.

Methods: Between April 2010 and December 2018, 21 patients aged ≧80 years(older group:8 men and 13 women;age range, 80-90 years)who underwent laminoplasty were reviewed and compared with 23 patients aged <80 years(younger group;13 men and 10 women;age range, 42-79 years)who underwent laminoplasty. The following data were obtained from chart reviews:age;sex;cervical canal stenosis level;time to operation;symptoms(e.g., gait disturbance);comorbidities(hypertension, diabetes mellitus, cancer, heart disease, ischemic cerebrovascular disease, and lumbar canal stenosis);antithrombotic drug use;cardiac, pulmonary, and renal functions;operative time;volume of blood loss during the operation;postoperative delirium;and follow-up period. Neurological deficits before and after the surgery were assessed using the neurosurgical cervical spine scale(NCSS). Data were statistically analyzed, and p-values <0.05 were considered statistically significant.

Results: The operative time, symptoms(hypertension), renal function, and preoperative NCSS score were significantly different between the older and younger groups. Meanwhile, most variables showed no significant differences between the groups. Although the preoperative NCSS score was lower in the older group, there was no significant difference in the degree of improvement in the NCSS score after surgery.

Conclusions: The findings of this study suggest that we should not hesitate to perform surgery for cervical spondylotic myelopathy in elderly patients with favorable cardiorespiratory function.
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http://dx.doi.org/10.11477/mf.1436204314DOI Listing
November 2020

Image quality evaluation of intra-irradiation cone-beam computed tomography acquired during one- and two-arc prostate volumetric-modulated arc therapy delivery: A phantom study.

J Appl Clin Med Phys 2020 Dec 16;21(12):231-239. Epub 2020 Nov 16.

Department of Radiation Oncology and Image-applied Therapy, Kyoto University Hospital, Kyoto, Japan.

Purpose: To evaluate (a) the effects of megavoltage (MV)-scatter on concurrent kilovoltage (kV) projections (P ) acquired during rotational delivery, and (b) the image quality of intra-irradiation cone-beam computed tomography (ii-CBCT) images acquired during prostate volumetric-modulated arc therapy (VMAT) delivery.

Methods: Experiment (1): P s were acquired with various MV beam parameters using a cylindrical phantom: field size (FS), MV energy (6 or 15 MV), dose rate (DR), and gantry speed. The average pixel values were calculated in a region on each P which were extracted at eight equally spaced gantry angles. Experiment (2): 11 one-arc and seven two-arc 15 MV prostate VMAT plans were used along with a pelvis phantom. One plan was selected from each of arc plans and its MV energy was changed to 6 MV. After P s were acquired, projections consisting of MV-scatter only (P ) were acquired with closing kV blades and subtracted from P (P ). Projections by kV beams only were acquired (P ). The corresponding CBCT images were reconstructed (CBCT , CBCT , and CBCT ). The root-mean-square errors (RMSEs) were calculated in prostate region and 3D gamma analysis was conducted, in which the CBCT-number was used instead of doses between ii-CBCT images and CBCT (30 HU/1 mm).

Results: Experiment (1): The MV-scatters were dependent on the FSs, MV energies, and DRs. Experiment (2): The median RMSEs for CBCT were decreased by 107.5 HU (1-arc) and 42.9 HU (2-arc) compared to those for CBCT . The median GPRs for CBCT were 94.7% (1-arc) and 93.4% (2-arc), while those for CBCT were 61.1% and 79.9%, respectively. GPRs for 6 MV plans were smaller than those for 15 MV plans.

Conclusions: The number of MV-scatters increased with larger FSs and DRs, and smaller MV energy. The MV-scatters were corrected on the CBCT regardless of the number of arcs.
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http://dx.doi.org/10.1002/acm2.13095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769406PMC
December 2020

Hypofractionated intensity-modulated radiotherapy with concurrent chemotherapy for elderly patients with locally advanced pancreatic carcinoma.

Radiat Oncol 2020 Nov 13;15(1):264. Epub 2020 Nov 13.

Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.

Background: It is important to understand how elderly patients with locally advanced pancreatic carcinoma (LAPC) should be treated, since the number of elderly cancer patients will increase. However, the optimal treatment for elderly patients with LAPC remains unclear. The purpose of this study was to evaluate the efficacy and safety of hypofractionated intensity-modulated radiotherapy (IMRT) with concurrent gemcitabine for elderly patients with LAPC.

Methods: We retrospectively analysed the data from LAPC patients aged ≥ 75 years treated with hypofractionated IMRT (48 Gy in 15 fractions) with concurrent weekly gemcitabine at our institution from February 2013 to December 2018. Overall survival (OS), progression-free survival (PFS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), and the pattern of recurrence and toxicity were analysed.

Results: Fifteen patients received treatment during the study period. The median age was 78 years (range 75-86 years), and the Eastern Cooperative Oncology Group (ECOG) performance status (PS) of all patients was 0-1. The median survival time (MST) and median PFS were 20.4 [95% confidence interval (CI) 10.3-36.8] and 13.5 (95% CI 6.4-20.3) months, respectively, and the 1-year OS and PFS rates were 80.0% (95% CI 50-93.1%) and 66.7% (95% CI 37.5-84.6%), respectively. The median LRPFS and median DMFS were 15.6 (95% CI 6.4-36.8) and 14.9 (95% CI 7.0-20.5) months, respectively, and the 1-year LRPFS and DMFS rates were 73.3% (95% CI 43.6-89.1%) and 66.7% (95% CI 37.5-84.6%), respectively. Non-haematologic grade 3 toxicity was observed in three cases, of which only one was induced by radiotherapy, whereas grade 4-5 non-haematologic acute or late toxicities were not observed.

Conclusions: The OS and PFS of elderly patients with LAPC treated using hypofractionated IMRT with concurrent gemcitabine were favourable and without the occurrence of severe toxicity. This treatment strategy is feasible and promising for elderly LAPC patients with good PS.
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http://dx.doi.org/10.1186/s13014-020-01712-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666451PMC
November 2020

Postoperative pancreatic fistulas decrease the survival of pancreatic cancer patients treated with surgery after neoadjuvant chemoradiotherapy: A retrospective analysis.

Surg Oncol 2020 Dec 24;35:527-532. Epub 2020 Oct 24.

Division of Hepatobiliary Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University Hospital, Japan.

Background And Objectives: A postoperative pancreatic fistula (POPF) is a critical complication after surgery for pancreatic cancer. Whether a POPF affects the long-term prognosis of pancreatic cancer cases remains controversial. This study aimed to clarify the effect of a POPF on the long-term prognosis of pancreatic cancer patients, especially after neoadjuvant chemoradiotherapy (NACRT).

Methods: Patients who underwent curative pancreatectomy for pancreatic cancer between January 2012 and June 2019 at Kyoto University Hospital were retrospectively investigated. A fistula ≥ Grade B was considered a POPF.

Results: During the study period, 148 patients underwent upfront surgery (Upfront group), and 52 patients underwent surgery after NACRT (NACRT group). A POPF developed in 16% of patients in the Upfront group and 13% in the NACRT group (p = 0.824). In the Upfront group, development of a POPF did not have a significant effect on recurrence-free survival (p = 0.766) or overall survival (p = 0.863). However, in the NACRT group, development of a POPF significantly decreased recurrence-free survival (HR 5.856, p = 0.002) and overall survival (HR 7.097, p = 0.020) on multivariate analysis.

Conclusions: The development of a POPF decreases the survival of pancreatic cancer patients treated by surgery after NACRT.
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http://dx.doi.org/10.1016/j.suronc.2020.10.010DOI Listing
December 2020

Differential prognostic factors in low- and high-burden de novo metastatic hormone-sensitive prostate cancer patients.

Cancer Sci 2021 Apr 13;112(4):1524-1533. Epub 2021 Feb 13.

Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan.

Metastatic burden is a critical factor for therapy decision-making in metastatic hormone-sensitive prostate cancer. The present study aimed to identify prognostic factors in men with high- or low-metastatic burden treated with primary androgen-deprivation therapy. The study included 2450 men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We investigated the prognostic value of various clinicopathological parameters for progression-free survival (PFS) and overall survival (OS) in patients stratified by low- or high-metastatic burden. Among the 2450 men, 841 (34.3%) and 1609 (65.7%) were classified as having low- and high-metastatic burden, respectively. Median PFS of the low- and high-burden groups were 44.5 and 16.1 months, respectively, and the median OS was 103.2 and 62.7 months, respectively. Percentage of biopsy-positive core, biopsy Gleason grade group, T-stage, and N-stage were identified to be differentially prognostic. M1a was associated with worse PFS than was M1b in the low-burden group, whereas lung metastasis was associated with better PFS and OS than was M1b in the high-burden group. Differential prognostic factors were identified for patients with low- and high-burden metastatic prostate cancer. These results may assist in decision-making to select the optimal therapeutic strategies for patients with different metastatic burdens.
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http://dx.doi.org/10.1111/cas.14722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019198PMC
April 2021
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