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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

Robot-assisted radical prostatectomy versus volumetric modulated arc therapy: Comparison of front-line therapies for localized prostate cancer.

BACKGROUND: Although radical prostatectomy and external beam radiotherapy are recognized as comparable treatment options for localized prostate cancer, robot-assisted radical prostatectomy (RARP) and volumetric modulated arc therapy (VMAT) as the leading respective techniques have yet to be compared. METHODS: We retrospectively analyzed 860 patients with cT1-4N0M0 prostate cancer who underwent RARP (n = 500) or VMAT (n = 360) between 2011 and 2016. Biochemical recurrence-free survival (bRFS; two consecutive prostate-specific antigen measurements ≥0.2 ng/ml for RARP and Phoenix definition for VMAT) and radiological recurrence-free survival (rRFS; radiologically diagnosed distant metastasis or local recurrence) were compared between the two modalities. Cox proportional hazards model was used for multivariate analysis. RESULTS: The median follow-up durations were 30 and 47.5 months, and median ages were 67 and 71 years (both P < 0.0001) in the RARP and VMAT groups, respectively. VMAT patients had significantly better bRFS than RARP patients, though their definitions of biochemical recurrence differed. If a unified definition of biochemical recurrence (two consecutive prostate-specific antigen measurements ≥0.2 ng/ml) was applied, RARP patients had significantly better bRFS than VMAT patients. Regarding rRFS, RARP patients had significantly better outcomes than VMAT patients, however, multivariate analysis together with D'Amico's risk classification, age-adjusted Charlson's comorbidity index, and concomitant androgen-deprivation therapy, demonstrated no significant difference between RARP and VMAT. CONCLUSIONS: The rRFS outcomes of RARP and VMAT after a medium-term follow-up period were similar, despite their different patient backgrounds. Further studies with a longer follow-up period are needed to compare these techniques in terms of cancer-specific and overall survivals.

Results of a nationwide survey on Japanese clinical practice in breast-conserving radiotherapy for breast cancer.

The Breast Cancer Group of the Japanese Radiation Oncology Study Group conducted a nationwide questionnaire survey on the clinical practice of postoperative radiotherapy for breast-conserving treatment for breast cancer. This questionnaire consisted of 18 questions pertaining to the annual number of treated patients, planning method, contouring structure, field design, dose-fractionated regimen, application of hypofractionated radiotherapy, boost irradiation, radiotherapy for synchronously bilateral breast cancer, and accelerated partial breast irradiation. The web-based questionnaire had responses from 293 Japanese hospitals. The results indicated the following: treatment planning is performed using relatively similar field designs and delivery methods; the field-in-field technique is used at more than one-third of institutes; the commonest criteria for boost irradiation is based on the surgical margin width (≤5 mm) and the second commonest criteria was age (≤40 or ≤50 years), although some facilities applied a different age criterion (>70 years) for omitting a tumor bed boost; for conventional fractionation, almost all institutes delivered 50 Gy in 25 fractions to the conserved whole breast and 10 Gy in 5 fractions to the tumor bed. This survey revealed that 43% of hospitals offered hypofractionated radiotherapy, and the most common regimens were 42.56 Gy in 16 fractions for whole-breast irradiation and 10.64 Gy in 4 fractions for boost irradiation. Almost all of the facilities irradiated both breasts simultaneously for synchronously bilateral breast cancer, and accelerated partial breast irradiation was rarely offered in Japan. This survey provided an overview of the current clinical practice of radiotherapy for breast-conserving treatment of breast cancer in Japan.

Identification of the active portion of the CCL3 derivative reported to induce antitumor abscopal effect.

BACKGROUND AND PURPOSE: Intravenous administration of a single amino acid-substituted chemokine CCL3 derivative named eMIP elicits the abscopal effect (an effect distal to the target), after local irradiation at a tumor-bearing site. To distinguish the active portion of eMIP, we tested the antitumor activity of chemically synthesized partial peptides of eMIP. Synthetic peptide has various advantages in its clinical application. MATERIAL AND METHODS: Colon26 adenocarcinoma cells were implanted subcutaneously in the right and left flanks of mice. eMIP, CCL3 or any of synthesized peptides was administered intravenously, either after irradiating the right flank. The effect was evaluated by tumor-growth inhibition. RESULTS: Q/C peptide, a synthetic peptide of amino acids 22-51 of eMIP has no chemotaxis-inducing ability but yet enhanced tumor growth inhibition at the non-irradiated sites, recapitulating the effect of eMIP with local irradiation. Co-administration of this peptide and HSP70 also inhibited tumor growth. CONCLUSIONS: Q/C peptide maps to the eMIP ß-sheet: 3 adjacent anti-parallel strands connected by the ß-hairpins, is the active portion of eMIP necessary for an immunomodulatory antitumor effect. This experimental reduction furthers our understanding of the underlying mechanism of the abscopal effect. The data will open the way for therapeutic application of like peptides.

Evaluation of a commercial automatic treatment planning system for prostate cancers.

Recent developments in Radiation Oncology treatment planning have led to the development of software packages that facilitate automated intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) planning. Such solutions include site-specific modules, plan library methods, and algorithm-based methods. In this study, the plan quality for prostate cancer generated by the Auto-Planning module of the Pinnacle3 radiation therapy treatment planning system (v9.10, Fitchburg, WI) is retrospectively evaluated. The Auto-Planning module of Pinnacle3 uses a progressive optimization algorithm. Twenty-three prostate cancer cases, which had previously been planned and treated without lymph node irradiation, were replanned using the Auto-Planning module. Dose distributions were statistically compared with those of manual planning by the paired t-test at 5% significance level. Auto-Planning was performed without any manual intervention. Planning target volume (PTV) dose and dose to rectum were comparable between Auto-Planning and manual planning. The former, however, significantly reduced the dose to the bladder and femurs. Regression analysis was performed to examine the correlation between volume overlap between bladder and PTV divided by the total bladder volume and resultant V70. The findings showed that manual planning typically exhibits a logistic way for dose constraint, whereas Auto-Planning shows a more linear tendency. By calculating the Akaike information criterion (AIC) to validate the statistical model, a reduction of interoperator variation in Auto-Planning was shown. We showed that, for prostate cancer, the Auto-Planning module provided plans that are better than or comparable with those of manual planning. By comparing our results with those previously reported for head and neck cancer treatment, we recommend the homogeneous plan quality generated by the Auto-Planning module, which exhibits less dependence on anatomic complexity.

Optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy: is ultra-early salvage radiotherapy beneficial?

BACKGROUND: The optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy is controversial. In particular, the prognostic significance of salvage radiotherapy delivered before a current definition of biochemical recurrence, i.e. ultra-early salvage radiotherapy, is unclear. METHODS: We reviewed 76 patients with pT2-3N0M0 prostate cancer who underwent salvage radiotherapy for post-prostatectomy biochemical recurrence at the following three timings: ultra-early salvage radiotherapy (n = 20) delivered before meeting a current definition of biochemical recurrence (two consecutive prostate-specific antigen [PSA] values ≥0.2 ng/mL); early salvage radiotherapy (n = 40) delivered after meeting the definition but before PSA reached 0.5 ng/mL; and delayed salvage radiotherapy (n = 16) delivered after PSA reached 0.5 ng/mL. The primary endpoint was failure of salvage radiotherapy, defined as a PSA value ≥0.2 ng/mL. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. RESULTS: During the follow-up period (median: 70 months), four of 20 (20 %), nine of 40 (23 %) and seven of 16 (44 %) patients failed biochemically in the ultra-early, early and delayed salvage radiotherapy groups, respectively. On univariate analyses, the outcome of delayed salvage radiotherapy was worse than the others, while there was no significant difference between ultra-early and early groups. Multivariate analysis demonstrated the presence of Gleason pattern 5, perineural invasion and delayed salvage radiotherapy as independent predictors of poorer survival. CONCLUSIONS: No survival benefit of ultra-early salvage radiotherapy was demonstrated, whereas delayed salvage radiotherapy was associated with worse outcome as reported in previous studies. Our results may support the current recommendations that salvage radiotherapy should be undertaken after two consecutive PSA values ≥0.2 ng/mL and before reaching 0.5 ng/mL.

Radiation-induced low-grade fibromyxoid sarcoma of the chest wall nine years subsequent to radiotherapy for breast carcinoma: A case report.

The present study reports a case of low-grade fibromyxoid sarcoma that occurred in a 62-year-old woman 9 years subsequent to whole breast irradiation for a carcinoma of the left breast, and 18 years following chemotherapy and radiotherapy (RT) for non-Hodgkin's lymphoma (NHL; diagnosed at the age of 43). The patient was 53 years of age when a cT2N0M0 stage IIA breast tumor was identified and excised. A 2.5 cm diameter nodule with dimpling in the upper-outer region of the left breast was detected. Pathological examination revealed that the tumor was an invasive ductal carcinoma, of a solid tubular type. The patient was treated with post-surgical whole breast RT. The left breast received 46 Gy in 23 fractions (2 Gy per fraction) for 4 weeks and 3 days, followed by a cone down boost of 14 Gy in 7 fractions (2 Gy per fraction); therefore a total dose of 60 Gy in 30 fractions was administered. In total, 9 years subsequent to RT, the patient observed a small lump in the left chest wall. The patient underwent excision of the tumor and pectoralis major fascia. Microscopically, the tumor consisted of atypical spindle cells with myxoid stroma. Pathologists concluded that the tumor was a low-grade fibromyxoid sarcoma. Since the tumor developed from tissue in a previously irradiated region, it was considered to be RT-induced, and was classified using the radiation-induced sarcoma (RIS) criteria as dictated by Cahan. Although the majority of RIS cases are angiosarcomas, a rare, low-grade fibromyxoid sarcoma was observed in the present study. The present study hypothesizes that there may have been an overlap region between the RT for supraclavicular nodes of NHL and the whole breast RT for primary breast cancer, due to the results of a retrospective dose reconstruction undertaken by the present study. The patient remained clinically stable for 4 years thereafter, until 2008 when the patient experienced a local relapse and underwent surgery. On 19 October 2011, the patient succumbed to RIS. The current study suggests that the RT history of a patient requires consideration due to the possible development of RIS, including the development of a low-grade fibromyxoid sarcoma, which may lead to a poor prognosis.