Six-year outcomes of robot-assisted radical prostatectomy versus volumetric modulated arc therapy for localized prostate cancer: A propensity score-matched analysis.

BACKGROUND: Although robot-assisted radical prostatectomy (RARP) and intensity-modulated radiotherapy are the leading respective techniques of prostatectomy and radiotherapy for localized prostate cancer, almost no study has directly compared their outcomes; none have compared mortality outcomes. METHODS: We compared 6­year outcomes of RARP (n = 500) and volumetric modulated arc therapy (VMAT, a rotational intensity-modulated radiotherapy, n = 360) in patients with cT1-4N0M0 prostate cancer. We assessed oncological outcomes, namely overall survival (OS), cancer-specific survival (CSS), radiological recurrence-free survival (rRFS), and biochemical recurrence-free survival (bRFS), using propensity score matching (PSM). We also assessed treatment-related complication outcomes of prostatectomy and radiotherapy. RESULTS: The median follow-up duration was 79 months (> 6 years). PSM generated a matched cohort of 260 patients (130 per treatment group). In the matched cohort, RARP and VMAT showed equivalent results for OS, CSS, and rRFS: both achieved excellent 6­year outcomes for OS (> 96%), CSS (> 98%), and rRFS (> 91%). VMAT had significantly longer bRFS than RARP, albeit based on different definitions of biochemical recurrence. Regarding complication outcomes, patients who underwent RARP had minimal (2.6%) severe perioperative complications and achieved excellent continence recovery (91.6 and 68.8% of the patients achieved ≤ 1 pad/day and pad-free, respectively). Patients who underwent VMAT had an acceptable rate (20.0%) of grade ≥ 2 genitourinary complications and a very low rate (4.4%) of grade ≥ 2 gastrointestinal complications. CONCLUSION: On the basis of PSM after a 6-year follow-up, RARP and VMAT showed equivalent and excellent oncological outcomes, as well as acceptable complication profiles.

Classification of chest X-ray images by incorporation of medical domain knowledge into operation branch networks.

BACKGROUND: This study was conducted to alleviate a common difficulty in chest X-ray image diagnosis: The attention region in a convolutional neural network (CNN) does not often match the doctor's point of focus. The method presented herein, which guides the area of attention in CNN to a medically plausible region, can thereby improve diagnostic capabilities. METHODS: The model is based on an attention branch network, which has excellent interpretability of the classification model. This model has an additional new operation branch that guides the attention region to the lung field and heart in chest X-ray images. We also used three chest X-ray image datasets (Teikyo, Tokushima, and ChestX-ray14) to evaluate the CNN attention area of interest in these fields. Additionally, after devising a quantitative method of evaluating improvement of a CNN's region of interest, we applied it to evaluation of the proposed model. RESULTS: Operation branch networks maintain or improve the area under the curve to a greater degree than conventional CNNs do. Furthermore, the network better emphasizes reasonable anatomical parts in chest X-ray images. CONCLUSIONS: The proposed network better emphasizes the reasonable anatomical parts in chest X-ray images. This method can enhance capabilities for image interpretation based on judgment.

Mixed Reality Visualization of Radiation Dose for Health Professionals and Patients in Interventional Radiology.

For interventional radiology, dose management has persisted as a crucially important issue to reduce radiation exposure to patients and medical staff. This study designed a real-time dose visualization system for interventional radiology designed with mixed reality technology and Monte Carlo simulation. An earlier report described a Monte-Carlo-based estimation system, which simulates a patient's skin dose and air dose distributions, adopted for our system. We also developed a system of acquiring fluoroscopic conditions to input them into the Monte Carlo system. Then we combined the Monte Carlo system with a wearable device for three-dimensional holographic visualization. The estimated doses were transferred sequentially to the device. The patient's dose distribution was then projected on the patient body. The visualization system also has a mechanism to detect one's position in a room to estimate the user's exposure dose to detect and display the exposure level. Qualitative tests were conducted to evaluate the workload and usability of our mixed reality system. An end-to-end system test was performed using a human phantom. The acquisition system accurately recognized conditions that were necessary for real-time dose estimation. The dose hologram represents the patient dose. The user dose was changed correctly, depending on conditions and positions. The perceived overall workload score (33.50) was lower than the scores reported in the literature for medical tasks (50.60) for computer activities (54.00). Mixed reality dose visualization is expected to improve exposure dose management for patients and health professionals by exhibiting the invisible radiation exposure in real space.

Updated evidence on oncological outcomes of surgery versus external beam radiotherapy for localized prostate cancer.

Radical prostatectomy and external beam radiotherapy are recognized as comparable treatment options for localized prostate cancer. Previous studies of oncological outcomes of surgery versus radiotherapy have reported their comparability or possible superiority of surgery. However, the issue of which treatment is better remains controversial. Several factors make fair comparison of their outcomes difficult: different patient backgrounds caused by selection bias, different definitions of biochemical recurrence and different complication profiles between the treatment modalities. In 2016, the first large randomized controlled trial was published, which compared radical prostatectomy, external beam radiotherapy and active monitoring in localized prostate cancer. More recently, another study has reported comparative outcomes of robot-assisted radical prostatectomy and volumetric modulated arc therapy, as the leading surgery and radiotherapy techniques, respectively. Furthermore, there has been a trend toward combining external beam radiotherapy with brachytherapy boost, especially in patients with high-risk prostate cancer. This review summarizes the updated evidence on oncological outcomes of surgery versus external beam radiotherapy for localized prostate cancer.

Classification of optical coherence tomography images using a capsule network.

BACKGROUND: Classification of optical coherence tomography (OCT) images can be achieved with high accuracy using classical convolution neural networks (CNN), a commonly used deep learning network for computer-aided diagnosis. Classical CNN has often been criticized for suppressing positional relations in a pooling layer. Therefore, because capsule networks can learn positional information from images, we attempted application of a capsule network to OCT images to overcome that shortcoming. This study is our attempt to improve classification accuracy by replacing CNN with a capsule network. METHODS: From an OCT dataset, we produced a training dataset of 83,484 images and a test dataset of 1000 images. For training, the dataset comprises 37,205 images with choroidal neovascularization (CNV), 11,348 with diabetic macular edema (DME), 8616 with drusen, and 26,315 normal images. The test dataset has 250 images from each category. The proposed model was constructed based on a capsule network for improving classification accuracy. It was trained using the training dataset. Subsequently, the test dataset was used to evaluate the trained model. RESULTS: Classification of OCT images using our method achieved accuracy of 99.6%, which is 3.2 percentage points higher than that of other methods described in the literature. CONCLUSION: The proposed method achieved classification accuracy results equivalent to those reported for other methods for CNV, DME, drusen, and normal images.

Calculating and estimating second cancer risk from breast radiotherapy using Monte Carlo code with internal body scatter for each out-of-field organ.

Out-of-field organs are not commonly designated as dose calculation targets during radiation therapy treatment planning, but they might entail risks of second cancer. Risk components include specific internal body scatter, which is a dominant source of out-of-field doses, and head leakage, which can be reduced by external shielding. Our simulation study quantifies out-of-field organ doses and estimates second cancer risks attributable to internal body scatter in whole-breast radiotherapy (WBRT) with or without additional regional nodal radiotherapy (RNRT), respectively, for right and left breast cancer using Monte Carlo code PHITS. Simulations were conducted using a complete whole-body female model. Second cancer risk was estimated using the calculated doses with a concept of excess absolute risk. Simulation results revealed marked differences between WBRT alone and WBRT plus RNRT in out-of-field organ doses. The ratios of mean doses between them were as large as 3.5-8.0 for the head and neck region and about 1.5-6.6 for the lower abdominal region. Potentially, most out-of-field organs had excess absolute risks of less than 1 per 10,000 persons-year. Our study surveyed the respective contributions of internal body scatter to out-of-field organ doses and second cancer risks in breast radiotherapy on this intact female model.

Impact of Gleason pattern 5 including tertiary pattern 5 on outcomes of salvage treatment for biochemical recurrence in pT2-3N0M0 prostate cancer.

BACKGROUND: Gleason pattern 5 (GP5), including tertiary GP5, at radical prostatectomy has reportedly been associated with poorer clinical outcome. However, it is undetermined how tertiary GP5 is handled in the new Gleason grade grouping starting in 2016, and its prognostic value in patients undergoing salvage treatment for postoperative biochemical recurrence (BCR) remains unclear. METHODS: We retrospectively reviewed 116 patients with pT2-3N0M0 prostate cancer (PC) who received salvage treatment for BCR after radical prostatectomy between 2003 and 2014. The primary endpoint was failure of salvage treatment, defined as a single prostate-specific antigen (PSA) value ≥0.2 ng/ml after PSA nadir following salvage treatment. Associations of various clinicopathological factors, including GP5, with failure-free survival were assessed. Cox proportional hazards model was used for multivariate analysis. RESULTS: Patients received salvage treatment with either radiotherapy (n = 48), androgen-deprivation therapy (n = 61), or both (n = 7) for BCR. Twenty-three patients (19.8 %) experienced failure of salvage treatment, with a median follow-up period of 79 months. Univariate analysis associated GP5, Gleason score-based parameters, lymphovascular invasion, and PSA doubling time <6 months with poorer failure-free survival. Receiver operating characteristic curve analyses identified the area under the curve for GP5 (0.654) as the largest among those parameters (P = 0.0060). Multivariate analysis demonstrated that GP5 was the only independent predictor of poor outcome. CONCLUSIONS: The presence of GP5 is an independent predictor of poor prognosis in patients with pT2-3N0M0 PC undergoing salvage treatment for BCR after radical prostatectomy. GP5 may thus be a more useful marker than conventional Gleason score in this setting.

Cell and Tissue Damage after Skin Exposure to Ionizing Radiation: Short- and Long-Term Effects after a Single and Fractional Doses.

Ionizing radiation is often used to treat progressive neoplasms. However, the consequences of long-term radiation exposure to healthy skin tissue are poorly understood. We aimed to evaluate the short- and long-term radiation damage to healthy skin of the same irradiation given either as single or fractional doses. C57BL/J6 mice were randomly assigned to one of three groups: a control and two exposure groups (5 Gy ×2 or 10 Gy ×1). The inguinal area was irradiated (6-MeV beam) 1 week after depilation in the treatment groups. Skin samples were evaluated macroscopically and histologically for up to 6 months after the final exposure. After anagen hair follicle injury by irradiation, hair cycling resumed in both groups, but hair graying was observed in the 10 Gy ×1 group but not in the 5 Gy ×2 group, suggesting the dose of each fractional exposure is more relevant to melanocyte stem cell damage than the total dose. On the other hand, in the long term, the fractional double exposures induced more severe atrophy and capillary reduction in the dermis and subcutis, suggesting fractional exposure may cause more depletion of tissue stem cells and endothelial cells in the tissue. Thus, our results indicated that there were differences between the degrees of damage that occurred as a result of a single exposure compared with fractional exposures to ionizing radiation: the former induces more severe acute injury to the skin with irreversible depigmentation of hairs, while the latter induces long-term damage to the dermis and subcutis.

Prospective analysis of factors precluding the initiation of durvalumab from an interim analysis of a phase II trial of S-1 and cisplatin with concurrent thoracic radiotherapy followed by durvalumab for unresectable, locally advanced non-small cell lung cancer in Japan (SAMURAI study).

Background: The standard of care for unresectable, locally advanced non-small cell lung cancer (LA-NSCLC) is chemoradiotherapy (CRT) followed by durvalumab, based on the PACIFIC trial. Disease progression and pneumonitis were reported as the main reasons to preclude the initiation of durvalumab in multiple retrospective studies. However, the transition rate and the reasons for failure to proceed to consolidation therapy with durvalumab after CRT were not evaluated prospectively. Although phase II studies in Japan have shown high efficacy and tolerability of CRT with cisplatin + S-1 (SP), no prospective study using durvalumab after SP-based CRT has yet been reported. We therefore conducted a phase II study to verify the efficacy and safety of durvalumab following SP-based CRT. In this interim analysis, we report the transition rate and the reasons for its failure. Methods: In treatment-naïve LA-NSCLC, cisplatin (60 mg/m2, day 1) and S-1 (80-120 mg/body, days 1-14) were administered with two 4-week cycles with concurrent thoracic radiotherapy (60 Gy) followed by durvalumab every 2 weeks for up to 12 months. The primary endpoint was 12 month progression-free survival rate. Results: Fifty-nine patients were enrolled, of whom 86.4% (51/59) proceeded to durvalumab. All of them initiated durvalumab within 42 days after CRT [median 18 days (range: 3-38)], including 27.5% (14/51) in <14 days. Common reasons for failure to proceed to durvalumab were disease progression (2/59, 3.4%) and adverse events (6/59, 10.2%). Among the latter cases, four resumed treatment and proceeded to durvalumab within 42 days on off-protocol. The objective response rate and the disease control rate were 62.7% and 93.2%, respectively. The incidences of ⩾grade 3 pneumonitis, febrile neutropenia, and esophagitis were 0%, 8.5%, and 3.4%, respectively. Conclusion: Regarding durvalumab after CRT, this interim analysis of the SAMURAI study clarified the high transition rate, early introduction, and reasons for failure to proceed to consolidation therapy, which were not determined in the PACIFIC trial. Trial registration: Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127.

A phase II study of S-1 and cisplatin with concurrent thoracic radiotherapy followed by durvalumab for unresectable, locally advanced non-small-cell lung cancer in Japan (SAMURAI study): primary analysis.

Background: The standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC) is chemoradiotherapy (CRT) followed by durvalumab, based on the PACIFIC study. Although multiple Japanese phase II studies have shown high efficacy and tolerability of CRT with cisplatin plus S-1 (SP), no prospective study using durvalumab after SP-based CRT has been reported. Objectives: We conducted a multicenter phase II study of this approach, the interim analysis of which showed a high transition rate to durvalumab consolidation therapy. Here, we report the primary analysis results. Design: In treatment-naïve LA-NSCLC, cisplatin (60 mg/m2, day 1) and S-1 (80-120 mg/body, days 1-14) were administered with two 4-week cycles with concurrent thoracic radiotherapy (60 Gy) followed by durvalumab (10 mg/kg) every 2 weeks for up to 1 year. Methods: The primary endpoint was 1-year progression-free survival (PFS). The expected 1-year PFS and its lower limit of the 80% confidence interval (CI) were set as 63% and 47%, respectively, based on the results of TORG1018 study. Results: In all, 59 patients were enrolled, with 51 (86.4%) proceeding to durvalumab. The objective response rate throughout the study was 72.9% (95% CI: 59.7-83.6%). After median follow-up of 21.9 months, neither median PFS nor OS was reached. The 1-year PFS was 72.5% (80% CI: 64.2-79.2%, 95% CI: 59.1-82.2%), while the 1-year overall survival was 91.5% (95% CI: 80.8-96.4%). No grade 5 adverse events were observed throughout the study. The most common adverse event during the consolidation phase was pneumonitis (any grade, 78.4%; grade ⩾3, 2.0%). Eventually, 52.5% of patients completed 1-year durvalumab consolidation therapy from CRT initiation. Conclusion: This study of durvalumab after SP-based CRT met its primary endpoint and found a 1-year PFS of 73% from CRT initiation. This study provides the first prospective data on the prognosis and tolerability of durvalumab consolidation from the initiation of CRT. Trial registration: Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127.

A phase I study of vaccination with NY-ESO-1f peptide mixed with Picibanil OK-432 and Montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen.

We conducted a phase I clinical trial of a cancer vaccine using a 20-mer NY-ESO-1f peptide (NY-ESO-1 91-110) that includes multiple epitopes recognized by antibodies, and CD4 and CD8 T cells. Ten patients were immunized with 600 µg of NY-ESO-1f peptide mixed with 0.2 KE Picibanil OK-432 and 1.25 ml Montanide ISA-51. Primary end points of the study were safety and immune response. Subcutaneous injection of the NY-ESO-1f peptide vaccine was well tolerated. Vaccine-related adverse events observed were fever (Grade 1), injection-site reaction (Grade 1 or 2) and induration (Grade 2). Vaccination with the NY-ESO-1f peptide resulted in an increase or induction of NY-ESO-1 antibody responses in nine of ten patients. The sera reacted with recombinant NY-ESO-1 whole protein as well as the NY-ESO-1f peptide. An increase in CD4 and CD8 T cell responses was observed in nine of ten patients. Vaccine-induced CD4 and CD8 T cells responded to NY-ESO-1 91-108 in all patients with various HLA types with a less frequent response to neighboring peptides. The findings indicate that the 20-mer NY-ESO-1f peptide includes multiple epitopes recognized by CD4 and CD8 T cells with distinct specificity. Of ten patients, two with lung cancer and one with esophageal cancer showed stable disease. Our study shows that the NY-ESO-1f peptide vaccine was well tolerated and elicited humoral, CD4 and CD8 T cell responses in immunized patients.

A phase II study of S-1 and cisplatin with concurrent thoracic radiotherapy followed by durvalumab for unresectable, locally advanced non-small-cell lung cancer in Japan (SAMURAI study).

BACKGROUND: Based on the results of the PACIFIC study, chemoradiotherapy followed by 1-year consolidation therapy with durvalumab was established as the standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC). However, some topics not foreseen in that design can be explored, including progression-free survival (PFS) and overall survival (OS) after the start of chemoradiotherapy, the proportion of patients who proceeded to consolidation therapy with durvalumab, and the optimal chemotherapeutic regimens. In Japan, the combination regimen of S-1 + cisplatin (SP), for which the results of multiple clinical studies have suggested a good balance of efficacy and tolerability, is frequently selected in clinical settings. However, the efficacy and safety of consolidation therapy with durvalumab following this SP regimen have not been evaluated. We therefore planned a multicenter, prospective, single-arm, phase II study. METHODS: In treatment-naïve LA-NSCLC, two cycles of combination chemotherapy with S-1 (80-120 mg/body, Days 1-14) + cisplatin (60 mg/m2, Day 1) will be administered at an interval of 4 weeks, with concurrent thoracic radiotherapy (60 Gy). Responders will then receive durvalumab every 2 weeks for up to 1 year. The primary endpoint is 1-year PFS rate. DISCUSSION: Compared with the conventional standard regimen in Japan, the SP regimen is expected to be associated with lower incidences of pneumonitis, esophagitis, and febrile neutropenia, which complicate the initiation of consolidation therapy with durvalumab, and have higher antitumor efficacy during chemoradiotherapy. Therefore, SP-based chemoradiotherapy is expected to be successfully followed by consolidation therapy with durvalumab in more patients, resulting in prolonged PFS and OS. Toxicity and efficacy results of the SP regimen in this study will also provide information important to the future establishment of the concurrent combination of chemoradiotherapy and durvalumab. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127.

Immersive Radiation Experience for Interventional Radiology with Virtual Reality Radiation Dose Visualization Using Fast Monte Carlo Dose Estimation.

For interventional radiology (IR), understanding the precise dose distribution is crucial to reduce the risks of radiation dermatitis to patients and staff. Visualization of dose distribution is expected to support radiation safety efforts immensely. This report presents techniques for perceiving the dose distribution using virtual reality (VR) technology and for estimating the air dose distribution accurately using Monte Carlo simulation for VR dose visualization. We adopted an earlier reported Monte-Carlo-based estimation system for IR and simulated the dose in a geometrical area resembling an IR room with fluoroscopic conditions. Users of our VR system experienced a simulated air dose distribution in the IR room while the irradiation angle, irradiation timing, and lead shielding were controlled. The estimated air dose was evaluated through comparison with measurements taken using a radiophotoluminescence glass dosimeter. Our dose estimation results were consistent with dosimeter readings, showing a 13.5% average mutual difference. The estimated air dose was visualized in VR: users could view a virtual IR room and walk around in it. Using our VR system, users experienced dose distribution changes dynamically with C-arm rotation. Qualitative tests were conducted to evaluate the workload and usability of our VR system. The perceived overall workload score (18.00) was lower than the scores reported in the literature for medical tasks (50.60) and computer activities (54.00). This VR visualization is expected to open new horizons for understanding dose distributions intuitively, thereby aiding the avoidance of radiation injury.

Clinical outcome of adjuvant radiotherapy for squamous cell carcinoma of the breast; a multicenter retrospective cohort study.

BACKGROUND: Because primary squamous cell carcinoma (SCC) of the breast is a rare disease, the standard therapy has not been established. We examined the clinical outcomes of postoperative adjuvant radiotherapy for breast SCC. MATERIAL AND METHODS: We conducted a multicenter retrospective cohort study. Patients diagnosed with primary breast SCC who received adjuvant radiotherapy as part of their primary definitive treatment were included. Overall survival (OS), breast cancer-specific survival (BCSS), and recurrence-free interval (RFi) were evaluated. RESULTS: Between January 2002 and December 2017, 25 breast SCC patients received adjuvant radiotherapy as a primary treatment were included. Median follow-up time was 43.5 months. Three (12%), fifteen (60%) and seven (28%) patients had clinical stage I, II and III disease, respectively. Fourteen patients underwent breast-conserving surgery and subsequent adjuvant radiotherapy. Eleven patients underwent mastectomy and post-mastectomy radiotherapy. Ten patients received regional lymph node irradiation. Nine (36%) patients had disease recurrence. The first site of recurrence was locoregional in five, but distant metastasis arose in one. Concurrent local and distant metastasis were seen in two. Six cases of local recurrence occurred within the irradiated site. Seven patients died, and six of the deaths were due to breast cancer. Five-year OS, BCSS, and Rfi were 69%, 70%, and 63%, respectively. In multivariate analysis, age and lymphatic invasion were associated with increased risk of recurrence. CONCLUSION: Breast SCC has a high incidence of locoregional recurrence and poor prognosis. Age and lymphatic invasion are significant risk factors for recurrence.

First experience of 192Ir source stuck event during high-dose-rate brachytherapy in Japan.

PURPOSE: To share the experience of an iridium-192 (192Ir) source stuck event during high-dose-rate (HDR) brachytherapy for cervical cancer. MATERIAL AND METHODS: In 2014, we experienced the first source stuck event in Japan when treating cervical cancer with HDR brachytherapy. The cause of the event was a loose screw in the treatment device that interfered with the gear reeling the source. This event had minimal clinical effects on the patient and staff; however, after the event, we created a normal treatment process and an emergency process. In the emergency processes, each staff member is given an appropriate role. The dose rate distribution calculated by the new Monte Carlo simulation system was used as a reference to create the process. RESULTS: According to the calculated dose rate distribution, the dose rates inside the maze, near the treatment room door, and near the console room were ≅ 10-2 [cGy · h-1], 10-3 [cGy · h-1], and << 10-3 [cGy · h-1], respectively. Based on these findings, in the emergency process, the recorder was evacuated to the console room, and the rescuer waited inside the maze until the radiation source was recovered. This emergency response manual is currently a critical workflow once a year with vendors. CONCLUSIONS: We reported our experience of the source stuck event. Details of the event and proposed emergency process will be helpful in managing a patient safety program for other HDR brachytherapy users.

Quality assurance of volumetric modulated arc therapy using Elekta Synergy.

PURPOSE. Recently, Elekta has supplied volumetric modulated arc therapy (VMAT) in which multi-leaf collimator (MLC) shape, jaw position, collimator angle, and gantry speed vary continuously during gantry rotation. A quality assurance procedure for VMAT delivery is described. METHODS AND MATERIALS. A single-arc VMAT plan with 73 control points (CPs) and 5-degree gantry angle spacing for a prostate cancer patient has been created by ERGO + + treatment planning system (TPS), where MLC shapes are given by anatomic relationship between a target and organs at risk and the monitor unit for each CP is optimized based on given dose prescriptions. Actual leaf and jaw positions, gantry angles and dose rates during prostate VMAT delivery were recorded in every 0.25 seconds, and the errors between planned and actual values were evaluated. The dose re-calculation using these recorded data has been performed and compared with the original TPS plan using the gamma index. RESULTS. Typical peak errors of gantry angles, leaf positions, and jaw positions were 3 degrees, 0.6 mm, and 1 mm, respectively. The dose distribution obtained by the TPS plan and the recalculated one agreed well under 2%-2 mm gamma index criteria. CONCLUSIONS. Quality assurance for prostate VMAT delivery has been performed with a satisfied result.

Enhancement of antitumor radiation efficacy and consistent induction of the abscopal effect in mice by ECI301, an active variant of macrophage inflammatory protein-1alpha.

PURPOSE: We studied whether i.v. administration of a chemokine after local tumor site irradiation could prevent remaining, as well as distant, nonirradiated tumor cell growth by leukocyte recruitment. EXPERIMENTAL DESIGN: Tumors were implanted s.c. in the right or both flanks. After local irradiation at the right flank, ECI301, a human macrophage inflammatory protein-1alpha variant was injected i.v. Tumor volumes were measured every 3 days after treatment. RESULTS: In Colon26 adenocarcinoma-bearing BALB/c mice, repeated daily administration (over 3-5 consecutive days) of 2 mug per mouse ECI301 after local irradiation of 6 Gy prolonged survival without significant toxicity, and in about half of the treated mice, the tumor was completely eradicated. Three weekly administrations of ECI301 after local irradiation also led to significant, although less effective, antitumor radiation efficacy. ECI301 also inhibited growth of other syngenic tumor grafts, including MethA fibrosarcoma (BALB/c) and Lewis lung carcinoma (C57BL/6). Importantly, tumor growth at the nonirradiated site was inhibited, indicating that ECI301 potentiated the abscopal effect of radiation. This abscopal effect observed in BALB/c and C57BL/6 mice was tumor-type independent. Leukocyte depletion studies suggest that CD8+ and CD4+ lymphocytes and NK1.1 cells were involved. CONCLUSIONS: Marked inhibition of tumor growth at the irradiated site, with complete tumor eradication and consistent induction of the abscopal effect, was potentiated by i.v. administration of ECI301. The results of this study may offer a new concept for cancer therapy, namely chemokine administration after local irradiation, leading to development of novel therapeutics for the treatment of advanced metastatic cancer.

Hepatic tumor classification using texture and topology analysis of non-contrast-enhanced three-dimensional T1-weighted MR images with a radiomics approach.

The purpose of this study is to evaluate the accuracy for classification of hepatic tumors by characterization of T1-weighted magnetic resonance (MR) images using two radiomics approaches with machine learning models: texture analysis and topological data analysis using persistent homology. This study assessed non-contrast-enhanced fat-suppressed three-dimensional (3D) T1-weighted images of 150 hepatic tumors. The lesions included 50 hepatocellular carcinomas (HCCs), 50 metastatic tumors (MTs), and 50 hepatic hemangiomas (HHs) found respectively in 37, 23, and 33 patients. For classification, texture features were calculated, and also persistence images of three types (degree 0, degree 1 and degree 2) were obtained for each lesion from the 3D MR imaging data. We used three classification models. In the classification of HCC and MT (resp. HCC and HH, HH and MT), we obtained accuracy of 92% (resp. 90%, 73%) by texture analysis, and the highest accuracy of 85% (resp. 84%, 74%) when degree 1 (resp. degree 1, degree 2) persistence images were used. Our methods using texture analysis or topological data analysis allow for classification of the three hepatic tumors with considerable accuracy, and thus might be useful when applied for computer-aided diagnosis with MR images.