Evaluation of the availability of single-position treatment with a rotating gantry and the validity of deformable image registration dose assessment for pancreatic cancer carbon-ion radiotherapy.

BACKGROUND: This study aimed to evaluate the clinical acceptability of rotational gantry-based single-position carbon-ion radiotherapy (CIRT) to reduce the gastrointestinal (GI) dose in pancreatic cancer. We also evaluated the usefulness of the deformable image registration (DIR)-based dosimetry method for CIRT. MATERIAL AND METHODS: Fifteen patients with pancreatic cancer were analyzed. The treatment plans were developed for four beam angles in the supine (SP plan) and prone (PR plan) positions. In the case of using multiple positions, the treatment plan was created with two angles for each of the supine and prone position (SP + PR plan). Dose evaluation for multiple positions was performed in two ways: by directly adding the values of the DVH parameters for each position treatment plan (DVH sum), and by calculating the DVH parameters from the accumulative dose distribution created using DIR (DIR sum). The D2cc and D6cc of the stomach and duodenum were recorded for each treatment plan and dosimetry method and compared. RESULTS: There were no significant differences among any of the treatment planning and dosimetry methods (p > 0.05). The DVH parameters for the stomach and duodenum were higher in the PR plan and SP plan, respectively, and DVH sum tended to be between the SP and PR plans. DVH sum and DIR sum, DVH sum tended to be higher for D2cc and DIR sum tended to be higher for D6cc. CONCLUSION: There were no significant differences in the GI dose, which suggests that treatment with a simple workflow performed in one position should be clinically acceptable. In CIRT, DIR-based dosimetry should be carefully considered because of the potential for increased uncertainty due to the steep dose distributions.

Development of a Semi-Dry Method for Measuring Drug Permeation into Skin Using an Electric Facial Care Device and Iontophoresis.

INTRODUCTION: Percutaneous drug delivery systems are attractive not only as a therapeutic strategy but also for cosmetic treatment. Iontophoresis is a well-recognized method for promoting transdermal absorption of ionized compounds. Franz cells are generally used to estimate drug permeation of skin by iontophoresis. However, methods using Franz cells are less versatile; for instance, the method is unsuited for use with a portable electric facial care device having a working probe of a certain size and weight. In this study, we constructed a semi-dry apparatus for use with an electric facial care device. METHODS: The apparatus has a multilayer structure consisting of mouse skin and 3 filter papers, modeled after the Franz cell. The skin permeation of the drug edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) was then measured using this apparatus. RESULTS: Edaravone permeation depended on working time, drug concentration, and ionization ratio of edaravone when iontophoresis was carried out with an electric facial care device. Furthermore, glycyrrhizic acid, α-tocopheryl phosphate, retinoic acid, and ascorbyl palmitate, which are recognized as functional cosmetic materials, also permeated the skin by applying iontophoresis with the device. CONCLUSION: These results suggest that the developed measuring apparatus is applicable for use with a portable electric facial care device and that iontophoresis using a portable electric facial care device is potentially useful in the cosmetic field.

Large volume was associated with increased risk of acute non-hematologic adverse events in the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer: preliminary results of prospective phase I/II clinical trial.

OBJECTIVE: This is the preliminary results of a multi-center prospective clinical trial evaluating the feasibility of the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer. METHODS: Patients with FIGO stage IB2, IIA2, IIB, IIIA, IIIB and IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by MRI were eligible. Protocol therapy consisted of 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of hybrid of intracavitary and interstitial and pelvic radiotherapy with central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase I part was that the rate of grade ≥ 3 acute non-hematologic adverse events related to hybrid of intracavitary and interstitial would be <10%. RESULTS: Between October 2015 and October 2019, 74 patients underwent primary registration, with 52 patients eventually proceeding to the secondary registration. The median pretreatment tumor width was 5.7 cm, and FIGO Stages were IB2 10, IIA2 2, IIB 20 and IIIB 20, respectively. The median high-risk clinical target volume D90 was 72.0 Gy (54.8-86.6 Gy, EQD2), rectum D2cc was 53.7 Gy (29.3-80.3 Gy) and bladder D2cc was 69.8 Gy (38.9-84.8 Gy). The rate of grade ≥ 3 non-hematologic adverse events related to hybrid of intracavitary and interstitial was 1.9% (1/52), and 17.3% (9/52) of patients experienced non-hematologic adverse events related to hybrid of intracavitary and interstitial of any grade. In multivariate analysis, high-risk clinical target volume ≥ 35 ml was associated with an increased risk of any grade of acute non-hematologic adverse events related to hybrid of intracavitary and interstitial (P = 0.036). CONCLUSION: The feasibility and reproducibility of hybrid of intracavitary and interstitial were demonstrated from a multi-center prospective clinical trial.

Implementation rate and effects of multidisciplinary team meetings on decision making about radiotherapy: an observational study at a single Japanese institution.

BACKGROUND: Cancer treatment requires a multidisciplinary approach. Therefore, multidisciplinary team meetings (MDTMs) have been widely used to determine the direction of treatment. However, no standard provisions exist for conducting MDTMs, and recommendations discussed in MDTMs are sometimes not implemented. ​This study analyzed the indications for radiotherapy discussed and recommended at MDTMs, identified the rate of radiotherapy recommendations for patients that were not implemented, and clarified the reasons at a single academic center in Japan. METHODS: This was a cross-sectional study that analyzed the minutes and electronic medical records of cases discussed at MDTMs held between April 2012-March 2017 at Yamagata University Hospital. We categorized how radiotherapy was initially presented at MDTMs, determined the rate of radiotherapy recommendations made through MDTMs, analyzed whether treatment recommendations were subsequently implemented, and examined the causes of non-implementation. We performed a statistical analysis to assess some clinical factors (sex, age, number of multidisciplinary team meetings, and classification of planned treatment) associated with the non-implementation of radiotherapy recommendations from MDTMs. RESULTS: A total of 1813 cases were discussed at MDTMs, of which 71% (1293 cases) were presented with treatment plans, including radiotherapy. Further, 66% (1205 cases) were recommended for radiotherapy through the MDTMs. Recommendations from MDTMs were not implemented in 7% (142 cases). The most typical reason for non-implementation was the clinician's opinion (30%), followed by patient preferences (27%) and disease progression (20%). Change in cancer stage and improvement in symptoms were 12% and 4%, respectively. These ratios were similar each year. We could not find the factors associated with the non-implementation of radiotherapy recommendations from MDTMs. CONCLUSIONS: MDTMs had a significant effect on the recommendation of radiotherapy for each patient with a tumor. The primary reason for the non-implementation of decisions made at MDTMs was the opinion of clinicians and the patient's preference. These results were similar to previous studies. We need to establish a monitoring system where patients themselves can decide the treatments based on their choices while using the recommendations from MDTMs.

Maximum tumor diameter and renal function can predict the declining surface dose rate after 177Lu-Dotatate: preliminary results of single institution in Japan.

PURPOSE: This study aimed to develop a user-friendly prediction formula for dose rate adjustment after initial 177Lu-Dotatate therapy from a prospective observational study of patients. MATERIALS AND METHODS: This study included consenting patients in a prospective observational study who underwent their first treatment in four cycles of 177Lu-Dotatate treatment at our hospital between January 2022 and February 2024. All patients received 7.4 GBq of 177Lu-Dotatate. The prediction formula was derived from the regression analysis of tumor-related factors and renal function. Creatinine clearance was estimated using the Cockcroft-Gault equation in this study for renal function. RESULTS: Among the 13 patients (seven males, six females, median age: 59 years), logarithmically transformed total tumor volume (cc) and maximum tumor diameter (mm) of primary tumors or metastases showed strong correlations (p < 0.001, R2 = 0.897). As such, the maximum tumor diameter was used as the tumor parameter in the prediction formula. Additionally, maximum tumor diameter and creatinine clearance showed strong (p < 0.001, R2 = 0.768) and moderate (p = 0.013, R2 = 445) correlations, respectively, with the ratio of the dose rate 5.5-h post-administration to the dose rate immediately post-administration (%) at 1 m from the body surface. The resulting formula, 51.4 + 0.360 × maximum tumor diameter (mm) - 0.212 × creatinine clearance (ml/min), demonstrated an extremely strong correlation (p < 0.001, R2 = 0.937). CONCLUSION: The present study showed that the maximum tumor diameter and renal function affected the declining the dose rate of patients surface after 177Lu-Dotatate, which can inform post-administration dose rate management and potentially facilitate outpatient treatment in Japan.

Influence of a multidisciplinary cancer board on treatment decisions.

BACKGROUND: To clarify how a multidisciplinary cancer board (CB) influences treatment decisions. METHODS: From March 2010 to June 2011, a total of 475 cases were discussed at our CB and the minutes of the board were reviewed for this study. RESULTS: Of the 475 patients, minor changes in treatment methods were made in 42 patients (9 %) and major changes were made in 28 patients (6 %). Further diagnostic procedures, further publication surveys and reconfirmation of patient's wishes were recommended in 80 patients (17 %). In the 392 patients for whom treatment was recommended, the CB's recommendation was realized in 349 patients (89 %) and was not realized in 20 (5 %) patients. CONCLUSIONS: It is obvious that a CB has a great influence on cancer treatment decisions, but the effectiveness of the CB in our hospital should be verified in the future by analyzing treatment outcomes.

A phase I trial of S-1 with concurrent radiotherapy in patients with locally recurrent rectal cancer.

BACKGROUND: The purpose of this phase I trial of S-1 chemotherapy in combination with pelvic radiotherapy for locally recurrent rectal cancer was to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose-limiting toxicity (DLT) of S-1. METHODS: We enrolled 9 patients between April 2005 and March 2009. Radiotherapy (total dose, 60 Gy in 30 fractions) was given to the gross local recurrent tumor and pelvic nodal metastases using three-dimensional radiotherapy planning. We administered oral S-1 twice a day on days 1-14 and 22-35 during radiotherapy. The dose of S-1 was initially 60 mg/m(2)/day and was increased to determine the MTD and RD for this regimen. RESULTS: DLT appeared at dose level 2 (70 mg/m(2)/day) in 2 patients, who experienced grade 3 enterocolitis and consequently required suspension of S-1 administration for longer than 2 weeks. Hematological toxicity was mild and reversible. At the initial evaluation, complete regression and partial regression were seen in 1 patient (11%) and 2 patients (22%), respectively. CONCLUSION: This phase I trial of S-1 chemotherapy with pelvic radiotherapy for locally recurrent rectal cancer revealed that the MTD for S-1 was 70 mg/m(2)/day and the RD was 60 mg/m(2)/day.

Phase I/II prospective clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer.

OBJECTIVE: The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial. METHODS: Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%. RESULTS: Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9-52.9 months), the 2- PPFS was 80.7% (90% confidence interval [CI]=69.7%-88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met. CONCLUSION: The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses.

MRI Grading Scale Predicts Ambulatory Function After Radiotherapy for Metastatic Spinal Cord Compression: A Prospective Single-Institution Observational Study.

INTRODUCTION: Although magnetic resonance imaging (MRI) is an important modality for the diagnosis of metastatic spinal cord compression (MSCC), there are only a few reports on MSCC findings and symptoms after radiotherapy. We aimed to reveal the factors related to ambulatory function after treatment, including the MRI findings, in a prospective observational study. METHODS: Patients with suspected MSCC who were treated with radiotherapy were included in this study. Orthopedic surgeons evaluated the neurological function according to the Frankel grade. All patients underwent spinal MRI, and the degree of spinal cord compression was assessed by a radiologist and a radiation oncologist using an MRI grading scale. One month after treatment, orthopedic surgeons reassessed the Frankel grade. Twenty-three patients who were evaluated 1 month after radiotherapy were included in the analysis. RESULTS: Before radiotherapy, 17 patients were ambulatory and six were unable to walk. Furthermore, 13 patients were diagnosed with grade 3 compression on MRI (spinal cord compression with no cerebrospinal fluid seen on axial T2-weighted imaging). Patients with grade 3 MSCC were significantly more likely to be non-ambulatory at 1 month. CONCLUSIONS: The MRI grading scale for MSCC may be a prognostic factor for ambulatory function after radiotherapy. MRI findings could aid in determining the indication for radiotherapy.

Prediction of the minimum spacer thickness required for definitive radiotherapy with carbon ions and photons for pelvic tumors: an in silico planning study using virtual spacers.

We aimed to predict the minimum distance between a tumor and the gastrointestinal (GI) tract that can satisfy the dose constraint by creating simulation plans with carbon-ion (C-ion) radiotherapy (RT) and photon RT for each case assuming insertion of virtual spacers of various thicknesses. We enrolled 55 patients with a pelvic tumor adjacent to the GI tract. Virtual spacers were defined as the overlap volume between the GI tract and the volume expanded 7-17 mm from the gross tumor volume (GTV). Simulation plans (70 Gy in 35 fractions for at least 95% of the planning target volume [PTV]) were created with the lowest possible dose to the GI tract under conditions that meet the dose constraints of the PTV. We defined the minimum thickness of virtual spacers meeting D2 cc of the GI tract <50 Gy as 'MTS'. Multiple regression was used with explanatory variables to develop a model to predict MTS. We discovered that MTSs were at most 9 mm and 13 mm for C-ion RT and photon RT plans, respectively. The volume of overlap between the GI tract and a virtual spacer of 14 mm in thickness (OV14)-PTV was found to be the most important explanatory variable in the MTS prediction equation for both C-ion and photon RT plans. Multiple R2 values for the regression model were 0.571 and 0.347 for C-ion RT and photon RT plans, respectively. In conclusion, regression equations were developed to predict MTS in C-ion RT and photon RT.

Intervention efficacy for eliminating patient misidentification using step-by-step problem-solving procedures to improve patient safety.

This study aimed to evaluate the efficacy of interventions to reduce patient misidentification incidents classified as level 2 and over (adverse events occurred for patients) with the step-by-step problem-solving method. All incidents related to patient misidentification were selected, and relevant information was collected from the original electronic incident reports. We then conducted an eight-step problem-solving process with the aim of reducing patient misclassification and improving patient safety. Step 1: the number of misidentification-related incident reports and the percentage of these reports in the total incident reports increased each year. Step 2: the most frequent misidentification type was sample collection tubes, followed by drug administration and hospital meals. Step 3: we set a target of an 20% decrease in patient misidentification cases classified as level 2 or over compared with the previous year, and established this as a hospital priority. Step 4: we found that discrepancies in patient identification procedures were the most important causes of misidentification. Step 5: we standardized the patient identification process to achieve an 10% reduction in misidentification. Step 6: we disseminated instructional videos to all staff members. Step 7: we confirmed there was an 18% reduction in level 2 and over patient misidentification compared with the previous year. Step 8: we intend to make additional effort to decrease misidentification of patients by a further 10%. Level 2 and over patient misidentification can be reduced by a patient identification policy using a step-by-step problem-solving procedure. This study aimed to evaluate the efficacy of interventions to reduce patient misidentification incidents with step-by-step problem-solving method. Continued seamless efforts to eliminate patient misidentification are mandatory for this activity.

In silico comparison of the dosimetric impacts of a greater omentum spacer for abdominal and pelvic tumors in carbon-ion, proton and photon radiotherapy.

PURPOSE: The purpose of this study was to compare carbon-ion (C-ion), proton and photon radiotherapy (RT) plans with regard to dose reduction of the gastrointestinal (GI) tract by using a greater omentum spacer (GO spacer). METHODS: We retrospectively retrieved data for ten patients who received the GO spacer as surgical spacer placement for abdominal and pelvic tumors. Simulation plans were created on pre-spacer Computed Tomography (CT) and post-spacer CT for C-ion RT, proton RT and photon RT to compare the dose of the GI tract. The plans were normalized so that at least 95% of the planning target volume (PTV) received 70 Gy (relative biological effectiveness equivalent) delivered in 35 fractions. All plans were created with the lowest possible dose to the GI tract under conditions that meet the dose constraints for the PTV and spinal cord (maximum dose < 45 Gy). The part of the GI tract to be evaluated was defined as that most adjacent to the PTV. C-ion RT plans and proton RT plans were calculated by a spot scanning technique, and photon RT plans were calculated employing by fixed-field intensity-modulated radiation therapy. RESULTS: D2 cc and V10-70 of the GI tract were significantly lower on post-spacer plans than on pre-spacer plans for all three RT modalities. Regarding post-spacer plans, D2 cc of the GI tract was significantly lower on C-ion RT plans and proton RT plans than on photon RT plans (C-ion vs photon p = 0.001, proton vs photon p = 0.002). However, there was no significant difference between C-ion RT plans and proton RT plans for D2 cc of the GI tract (C-ion vs proton p = 0.992). In the photon RT plan for one patient, D2 cc of the GI tract did not meet < 50 Gy. CONCLUSIONS: The GO spacer shows a significant dose reduction effect on the GI tract.

The Role of Cancer Boards in the Treatment Decisions Regarding Chemotherapy.

Objective The influence of cancer boards with respect to the treatment decisions regarding chemotherapy remains to be elucidated. In the present study, we investigated the cases that presented at our institutional cancer boards, to assess the effect of cancer boards on the treatment decisions regarding chemotherapy. Methods Data from the cancer boards at Yamagata University Hospital, Yamagata, Japan, were collected. Along with data from the clinical records, the details of the discussions and the chosen plan of treatment of the cancer boards were analyzed. Results From February 2010 to February 2014, 1,541 cases were discussed at our cancer boards. Of these, 811 cases (52.6%) involved discussions about chemotherapy. Of those 811 cases, recommendations were made to alter the treatment plans for 189 cases (23.3%). The reasons for discouraging chemotherapy varied; however, 29/45 (64.4%) cases involved discouragement for the following reasons: old age, a comorbid condition, the physical (performance) status, or insufficient evidence to administer chemotherapy. Eighty-six patients were referred to the medical oncology department through the cancer boards. Conclusion Our results showed that cancer boards have a great influence on the treatment decisions regarding chemotherapy and the prompt referral of cases to medical oncologists as necessary. In terms of future research, we will evaluate the effect of cancer boards on the prognosis and outcomes of cases using the institutional cancer registry.

Modified simultaneous integrated boost radiotherapy for unresectable locally advanced breast cancer: preliminary results of a prospective clinical trial.

BACKGROUND: The purpose of this study was to evaluate the effect of modified simultaneous integrated boost (SIB) radiotherapy for patients with extensive breast cancer. PATIENTS AND METHODS: Patients with macroscopic tumor and histologically proven adenocarcinoma of the breast were enrolled in the study. Patients were included whether they had or did not have previous surgery, chemotherapy, hormone therapy, or molecular targeted therapy; patients with past history of thoracic radiotherapy were excluded. Under conditions of not exceeding the tolerance dose for normal tissue, irradiation to the tumor was increased to the maximum possible extent using the modified SIB technique. RESULTS: Three breast cancer patients were treated with the modified SIB technique. All patients were diagnosed as T4b (median maximum diameter of the tumor: 16 cm; range, 15.5-22 cm), and all patients exhibited symptoms because of the extremely large tumor. The median total dose to the part of tumor tissue was 128.8 Gy (range, 110-140 Gy). Total dose to normal tissue was < 72 Gy in all patients. Although large tumors were radio-resistant, it was macroscopically confirmed that all tumors eventually disappeared. Although skin defects persisted because of tumor disappearance, there were no Grade ≥ 3 toxicities due to radiotherapy. CONCLUSION: Although much care is required in delivering extremely high doses of radiotherapy to the tumor, modified SIB radiotherapy was shown to be effective against extremely large tumors that could not be controlled using conventional radiotherapy. In future, an increase in the number of study patients and establishment of the technique will be required.

Modified simultaneous integrated boost radiotherapy for large retroperitoneal malignant tumor: A case report.

The current study reports the case of a large retroperitoneal tumor treated with modified simultaneous integrated boost (SIB) radiotherapy. A 45-year-old female presented to the emergency department complaining of left abdominal pain and fever. A computed tomography scan detected a retroperitoneal tumor of 12×16×16 cm, and a biopsy revealed a poorly-differentiated adenocarcinoma. The patient was diagnosed with a large adenocarcinoma originating from the left ureter, with no distant metastasis. Due to the patient's poor physical condition, surgery was not recommended, and the patient was referred to the Department of Radiation Oncology (Yamagata University Hospital, Yamagata, Japan). Modified SIB radiotherapy was administered following the acquisition of written consent from the patient. The total irradiation dose to the center of the tumor and to the surrounding healthy tissue was ∼96 Gy/33 fractions and <60 Gy/33 fractions, respectively. At the end of the radiotherapeutic course, the tumor volume was reduced by ≥80%, and the residual tumor was surgically resected. As a result of the resection, a complete pathological response was confirmed; the patient has been recurrence-free for >3 years with no complications. Modified SIB radiotherapy may be safely administered, with favorable outcomes. Complete recovery can be achieved with this technique, even in a patient with a large radioresistant tumor.

Status of radiotherapy in a multidisciplinary cancer board.

Multidisciplinary cancer boards (CBs) for making cancer treatment decisions have become popular in many countries; however, the status of radiotherapy in CBs and the influence of CBs on radiotherapy decisions have not been studied. To clarify these issues, we reviewed the minutes of our CBs from February 2010 to March 2012, and we classified planned treatments discussed at the CBs into five categories and analyzed decisions concerning radiotherapy in each category. The fraction of cases for which radiotherapy was recommended was 536/757 (71%). These cases included 478 cases (63%) for which radiation therapy was planned and four cases (0.5%) for which radiation therapy was unexpectedly recommended. On the other hand, radiation therapy was canceled in 21 cases (4%) for which radiation therapy had been planned. This study showed that radiotherapy was discussed in many cases at CBs and that CBs have a great influence on decisions concerning radiotherapy.

Modified simultaneous integrated boost radiotherapy for an unresectable huge refractory pelvic tumor diagnosed as a rectal adenocarcinoma.

A clinical trial of radiotherapy with modified simultaneous integrated boost (SIB) technique against huge tumors was conducted. A 58-year-old male patient who had a huge pelvic tumor diagnosed as a rectal adenocarcinoma due to familial adenomatous polyposis was enrolled in this trial. The total dose of 77 Gy (equivalent dose in 2 Gy/fraction) and 64.5 Gy was delivered to the center of the tumor and the surrounding area respectively, and approximately 20% dose escalation was achieved with the modified SIB technique. The tumor with an initial maximum size of 15 cm disappeared 120 d after the start of the radiotherapy. Performance status of the patient improved from 4 to 0. Radiotherapy with modified SIB may be effective for patients with a huge tumor in terms of tumor shrinkage/disappearance, improvement of QOL, and prolongation of survival.