맥락막 흑색종 환자에서 루테늄-106 브라키테라피를 이용한 안구보존적 치료의 임상적 결과

의과대학/석사Purpose: In our institution, patients with choroidal melanoma have been treated with ruthenium-106 (Ru-106) brachytherapy with or without additional local therapy since 2006. The aim of this study is to report early clinical outcomes of eye-preserving treatment strategy for choroidal melanoma of variable size Patients and methods: Ninety-three consecutive patients diagnosed of uveal malignant melanoma were treated with Ru-106 brachytherapy between October, 2006 and December, 2012. Patients with iris and ciliary body tumor were excluded (n = 5), leaving 88 patients for analysis. In our institution, malignant melanomas of variable size were treated with Ru-106 brachytherapy and most of the medium to large sized tumor (height ≥6 mm) received combined therapy adding local excision and/or transpupillary thermotherapy (TTT). In general, 85-95 Gy was prescribed to the apex of the tumor for patients without local excision, and 100 Gy to the 2-mm point from the outer surface of the sclera for patients undergoing tumor excision. Results: Median follow-up was 30 months. The median age of all cohort was 50 years (range 19-82 years). Median basal diameter was 11.4 mm (range 2.96-17.28 mm) and tumor height was 6.79 mm (range 1.73-13.66 mm). The actuarial 3-year local control rate was 80%. Distant metastases were diagnosed in 12 patients and a total of 11 patients died. Actuarial metastases-free survival rate was 84% and overall survival rate was 90.3% at 3 years. Among the 88 patients, 13 patients eventually underwent enucleation, resulting in a 3-year eye-preservation rate of 80%: 12 patients underwent enucleation for local recurrence and 1 for complication. Significant prognostic factor for eye-preservation rate was tumor height (p = 0.042). The number of patients with tumor height ≥6 mm was 50 (57%) and additional local therapy was used in the treatment of 94% (n=47) of these patients. Three-year eye-preservation rate was 94% for tumor height <6 mm, and 70% for tumor height ≥6 mm (p = 0.047). Only 1 patients with tumor size <6 mm (n = 38) experienced distant metastasis and eventually died of disease. Conclusion: Ru-106 brachytherapy for choroidal melanoma of variable size showed favorable outcome. Additional local treatment may improve eye preservation rate in medium to large size tumor.ope

Kilovoltage radiotherapy for companion animals: dosimetric comparison of 300 kV, 450 kV, and 6 MV X-ray beams

Radiotherapy for the treatment of cancer in companion animals is currently administered by using megavoltage X-ray machines. Because these machines are expensive, most animal hospitals do not perform radiotherapy. This study evaluated the ability of relatively inexpensive kilovoltage X-ray machines to treat companion animals. A simulation study based on a commercial treatment-planning system was performed for tumors of the brain (non-infectious meningoencephalitis), nasal cavity (malignant nasal tumors), forefoot (malignant muscular tumors), and abdomen (malignant intestinal tumors). The results of kilovoltage (300 kV and 450 kV) and megavoltage (6 MV) X-ray beams were compared. Whereas the 300 kV and 6 MV X-ray beams provided optimal radiation dose homogeneity and conformity, respectively, for brain tumors, the 6 MV X-rays provided optimal homogeneity and radiation conformity for nasal cavity, forefoot, and abdominal tumors. Although megavoltage X-ray beams provided better radiation dose distribution in most treated animals, the differences between megavoltage and kilovoltage X-ray beams were relatively small. The similar therapeutic effects of the kilovoltage and 6 MV X-ray beams suggest that kilovoltage X-ray beams may be effective alternatives to megavoltage X-ray beams in treating cancers in companion animals.ope

A phase II study of intraoperative radiotherapy using a low-energy x-ray source for resectable pancreatic cancer: a study protocol

BACKGROUND: The current standard treatment for resectable pancreatic cancer is surgical resection followed by adjuvant chemotherapy. Local recurrence rates are high even after curative resection; thus, the long-term outcome of locally advanced pancreatic cancer remains poor. Intraoperative radiotherapy (IORT) uses a low-energy x-ray source to deliver a single fraction of high-dose radiation to the tumor bed during a surgical procedure, while effectively sparing the surrounding normal tissues. IORT has the potential to improve the efficacy of radiation therapy for pancreatic cancer. METHODS/DESIGN: This prospective, one-armed, phase II study will investigate the role of IORT in improving local control in patients with resectable pancreatic adenocarcinoma. The patients will receive surgery and IORT of 10 Gy prescribed at a 5-mm depth of the tumor bed, followed by adjuvant gemcitabine chemotherapy according to the current standard of care. The aim is to enroll 42 patients. DISCUSSION: The primary endpoint of this trial is to evaluate the feasibility of IORT and the local recurrence rate after one year. The secondary endpoints include the acute and late toxicities, and disease-free survival and overall survival rates. TRIAL REGISTRATION: The trial was prospectively registered at Clinicaltrials.gov NCT03273374 on September 6, 2017.ope

Skeletal Muscle Depletion Predicts the Prognosis of Patients With Hepatocellular Carcinoma Treated With Radiotherapy

Background: Sarcopenia is gaining attention as a poor prognostic factor for various types of malignancies. This study evaluated the prevalence and prognostic significance of sarcopenia and its association with survival in hepatocellular carcinoma (HCC) patients who underwent radiotherapy (RT) to the primary site. Materials and Methods: Between January 2009 and November 2016, 156 patients with HCC that underwent RT to the liver were retrospectively studied. Sarcopenia was defined as an L3 skeletal muscle index of <49 cm2/m2 for men and <41 cm2/m2 for women as proposed by Korean-specific cut-off value. Sarcopenia was identified pre- and post-RT (within 3 months from the end of RT). Results: Pre-RT sarcopenia occurred in 99 (63.5%) patients and was significantly associated with higher levels of protein induced by vitamin K absence or antagonist-II (PIVKA-II), lower percentage of overweight/obesity (body-mass index), higher percentage of previous systemic chemotherapy, and lower total RT dose. At a median follow-up of 9.3 months, median overall survival (OS) was significantly lower in patients with pre-RT sarcopenia than in those without (7.1 vs. 15.3 months, p < 0.001). In multivariate analysis [reporting hazard ratio (HR): 95% confidence interval (CI)], albumin-bilirubin score (2.35: 1.33-4.17; p = 0.003), total dose (0.44: 0.27-0.71; p = 0.001), and pre-RT sarcopenia (2.38: 1.53-3.70; p < 0.001) were independent OS prognostic factors. Among patients without pre-RT sarcopenia, 20 newly developed sarcopenia after RT and showed significantly lower OS compared to those without sarcopenia after RT (n = 35) (median 14.1 vs. 17.5 months, p = 0.018). Multivariate logistic regression analysis [reporting odds ratio (OR)] demonstrated older age (310.190; p = 0.007), Child-Pugh classification B or C (15.239; p = 0.047), higher alpha-fetoprotein (128.486; p = 0.008), higher PIVKA-II (118.536; p = 0.027), and larger planning target volume (51.310; p = 0.026) as significant factors for newly developed post-RT sarcopenia. Conclusion: Newly developed sarcopenia after RT, as well as pre-RT sarcopenia, were associated with poor survival for HCC patients who underwent RT to the liver. This result suggests the possibility that early intervention such as nutritional support and exercise therapies before and during RT could prevent muscle wasting and may be effective in improving the prognosis of HCC patients.ope

Clinical Implications of Geometric and Dosimetric Uncertainties of Inter- and Intra-Fractional Movement during Volumetric Modulated Arc Therapy for Breast Cancer Patients

With the introduction of modern sophisticated radiotherapy (RT) techniques, the significance of accuracy has increased considerably. This study evaluated the necessity of pre-treatment and intra-fractional cone-beam computed tomography (CBCT) by analyzing inter- and intra-fractional CBCT images of breast cancer patients receiving RT. From 57 patients, 1206 pre-treatment CBCT and 1067 intra-fractional CBCT images were collected. Geometric movements of patients were measured quantitively in both inter- and intra-fractional CBCT, and changes in dosimetric parameters were evaluated in selected patients with extreme intra-fractional movement. For right-sided breast cancer patients, left-sided breast cancer patients treated using deep-inspiration breath hold (DIBH), and left-sided breast cancer patients treated using continuous positive airway pressure (CPAP), median inter-fractional deviations were 0.53 (range 0.06-2.98) cm, 0.66 (range 0.08-4.41) cm, and 0.69 (range 0.04-3.80) cm, and median intra-fractional deviations were 0.14 (range 0.00-0.62) cm, 0.23 (range 0.02-0.96) cm, and 0.24 (0.00-1.15) cm, respectively. Modified plans reflecting large changes in intra-fractional position in 10 selected cases revealed insufficient target coverage in seven cases and more than 20-fold increase in the volume of heart receiving at least 25 Gy in two cases. Intra-fractional verification, as well as pre-treatment verification, might be considered in patients using DIBH or CPAP.ope

Neural network based ensemble model to predict radiation induced lymphopenia after concurrent chemo-radiotherapy for non-small cell lung cancer from two institutions

The use of adjuvant Immune Checkpoint Inhibitors (ICI) after concurrent chemo-radiation therapy (CCRT) has become the standard of care for locally advanced non-small cell lung cancer (LA-NSCLC). However, prolonged radiotherapy regimens are known to cause radiation-induced lymphopenia (RIL), a long-neglected toxicity that has been shown to correlate with response to ICIs and survival of patients treated with adjuvant ICI after CCRT. In this study, we aim to develop a novel neural network (NN) approach that integrates patient characteristics, treatment related variables, and differential dose volume histograms (dDVH) of lung and heart to predict the incidence of RIL at the end of treatment. Multi-institutional data of 139 LA-NSCLC patients from two hospitals were collected for training and validation of our suggested model. Ensemble learning was combined with a bootstrap strategy to stabilize the model, which was evaluated internally using repeated cross validation. The performance of our proposed model was compared to conventional models using the same input features, such as Logistic Regression (LR) and Random Forests (RF), using the Area Under the Curve (AUC) of Receiver Operating Characteristics (ROC) curves. Our suggested model (AUC=0.77) outperformed the comparison models (AUC=0.72, 0.74) in terms of absolute performance, indicating that the convolutional structure of the network successfully abstracts additional information from the differential DVHs, which we studied using Gradient-weighted Class Activation Map. This study shows that clinical factors combined with dDVHs can be used to predict the risk of RIL for an individual patient and shows a path toward preventing lymphopenia using patient-specific modifications of the radiotherapy plan. © 2023ope

Intraoperative Radiotherapy for Resectable Pancreatic Cancer Using a Low-Energy X-Ray Source: Postoperative Complications and Early Outcomes

Purpose: We evaluated the safety, feasibility, and early treatment outcomes of intraoperative radiotherapy (IORT) using a low-energy X-ray source. Materials and methods: Patients with resectable pancreatic cancer were enrolled in this single-institution, prospective, single-arm, phase II trial. Patients underwent surgery and IORT with 10 Gy prescribed at a 5-mm depth from the tumor bed using a 50 kV X-ray source (Intrabeam, Carl Zeiss). Six cycles of adjuvant gemcitabine-based chemotherapy were administered 8-12 weeks after surgery. Results: A total of 41 patients were included. Thirty-one patients (75.6%) underwent wide R0 resection, while 5 (12.2%) underwent R1 resection and 5 (12.2%) underwent narrow R0 resection (retroperitoneal margin <1 mm). Grade 3 postoperative complications were reported in only one patient (4.9%) who needed additional surgery due to ulcer perforation. At a median follow-up of 9 months, four patients showed local-only recurrence, nine had distant metastases, and two showed both local and distant recurrence. The 1-year local control rate was 76.4%. Conclusion: Our preliminary report suggests that IORT is well-tolerated and feasible in patients with resectable pancreatic cancer. Further follow-up is needed to confirm the clinical benefits of IORT in terms of local control and overall survival. Trial registration: Trial Registration: Clinical trial registration No. (NCT03273374).ope

Intraoperative radiation therapy induces immune response activity after pancreatic surgery

Background: Pancreatic cancer has highly aggressive features, such as local recurrence that leads to significantly high morbidity and mortality and recurrence after successful tumour resection. Intraoperative radiation therapy (IORT), which delivers targeted radiation to a tumour bed, is known to reduce local recurrence by directly killing tumour cells and modifying the tumour microenvironment. Methods: Among 30 patients diagnosed with pancreatic cancer, 17 patients received IORT immediately after surgical resection. We investigated changes in the immune response induced by IORT by analysing the peritoneal fluid (PF) and blood of patients with and without IORT treatment after pancreatic cancer surgery. Further, we treated three pancreatic cell lines with PF to observe proliferation and activity changes. Results: Levels of cytokines involved in the PI3K/SMAD pathway were increased in the PF of IORT-treated patients. Moreover, IORT-treated PF inhibited the growth, migration, and invasiveness of pancreatic cancer cells. Changes in lymphocyte populations in the blood of IORT-treated patients indicated an increased immune response. Conclusions: Based on the characterisation and quantification of immune cells in the blood and cytokine levels in the PF, we conclude that IORT induced an anti-tumour effect by activating the immune response, which may prevent pancreatic cancer recurrence. Clinical trial registration: NCT03273374 .ope

Prognostic Significance of Sarcopenia in Advanced Biliary Tract Cancer Patients

Background: Sarcopenia, systemic inflammation, and low muscularity significantly impact the survival of cancer patients. However, few studies have investigated how sarcopenia and systemic inflammation affect the prognosis of biliary tract cancer with distant metastasis. In this study, we investigated the association between sarcopenia with systemic inflammation and prognosis of metastatic biliary tract cancer. Materials and Methods: Data collected from 353 metastatic biliary tract cancer patients from 2007 to 2016 were analyzed. To evaluate the skeletal muscle mass, computed tomography images at the upper level of the third lumbar vertebra (L3) were used. Sarcopenia was defined using the Japan Society of Hepatology guideline; L3 muscle index 3 were categorized into the inflammatory category. The overall survival (OS) and progression free survival (PFS) were analyzed. Subgroup analysis was performed on those who received gemcitabine/cisplatin (GP) chemotherapy and depending on the presence of sarcopenia and inflammation. Results: Patients with sarcopenia showed lesser 1-year OS than those without (25.5 vs. 38.2%, p = 0.019). The patients with high NLR (NLR > 3) were associated with a shorter OS than were those with a low NLR (NLR ≤ 3) (21.0 vs. 52.8%, p < 0.001). Based on these results, we categorized the patients into three groups; sarcopenia accompanied by high NLR, no sarcopenia and low NLR, and either sarcopenia or high NLR. The OS of patients was well-stratified according to this grouping (1-year OS; 18.3 vs. 30.3 vs. 55.8%, p < 0.001). Concordant with OS results, the PFS was well-stratified based on the presence of either sarcopenia or high NLR (Sarcopenia; 9.5 vs. 19.4%, p < 0.001, NLR; 10.0 vs. 23.4%, p < 0.001). The PFS was significantly associated with high NLR and sarcopenia (1-year PFS; 7.8 vs. 13.0 vs. 27.9%, p < 0.001). Conclusion: Sarcopenia with inflammation was associated with inferior OS and PFS. In addition, sarcopenia accompanied by inflammation was associated with poor prognosis. Conservative treatments such as nutritional support, exercise, and pharmacologic intervention could help metastatic biliary tract cancer patients to overcome sarcopenia and the inflammatory status.ope

Patient-Specific Quality Assurance Using a 3D-Printed Chest Phantom for Intraoperative Radiotherapy in Breast Cancer

This study aims to confirm the usefulness of patient-specific quality assurance (PSQA) using three-dimensional (3D)-printed phantoms in ensuring the stability of IORT and the precision of the treatment administered. In this study, five patient-specific chest phantoms were fabricated using a 3D printer such that they were dosimetrically equivalent to the chests of actual patients in terms of organ density and shape around the given target, where a spherical applicator was inserted for breast IORT treatment via the INTRABEAM™ system. Models of lungs and soft tissue were fabricated by applying infill ratios corresponding to the mean Hounsfield unit (HU) values calculated from CT scans of the patients. The two models were then assembled into one. A 3D-printed water-equivalent phantom was also fabricated to verify the vendor-provided depth dose curve. Pieces of an EBT3 film were inserted into the 3D-printed customized phantoms to measure the doses. A 10 Gy prescription dose based on the surface of the spherical applicator was delivered and measured through EBT3 films parallel and perpendicular to the axis of the beam. The shapes of the phantoms, CT values, and absorbed doses were compared between the expected and printed ones. The morphological agreement among the five patient-specific 3D chest phantoms was assessed. The mean differences in terms of HU between the patients and the phantoms was 2.2 HU for soft tissue and -26.2 HU for the lungs. The dose irradiated on the surface of the spherical applicator yielded a percent error of -2.16% ± 3.91% between the measured and prescribed doses. In a depth dose comparison using a 3D-printed water phantom, the uncertainty in the measurements based on the EBT3 film decreased as the depth increased beyond 5 mm, and a good agreement in terms of the absolute dose was noted between the EBT3 film and the vendor data. These results demonstrate the applicability of the 3D-printed chest phantom for PSQA in breast IORT. This enhanced precision offers new opportunities for advancements in IORT.ope