A robust treatment planning approach for chest motion in postmastectomy chest wall intensity modulated radiation therapy.

PURPOSE: Chest wall postmastectomy radiation therapy (PMRT) should consider the effects of chest wall respiratory motion. The purpose of this study is to evaluate the effectiveness of robustness planning intensity modulated radiation therapy (IMRT) for respiratory movement, considering respiratory motion as a setup error. MATERIAL AND METHODS: This study analyzed 20 patients who underwent PMRT (10 left and 10 right chest walls). The following three treatment plans were created for each case and compared. The treatment plans are a planning target volume (PTV) plan (PP) that covers the PTV within the body contour with the prescribed dose, a virtual bolus plan (VP) that sets a virtual bolus in contact with the body surface and prescribing the dose that includes the PTV outside the body contour, and a robust plan (RP) that considers respiratory movement as a setup uncertainty and performs robust optimization. The isocenter was shifted to reproduce the chest wall motion pattern and the doses were recalculated for comparison for each treatment plan. RESULT: No significant difference was found between the PP and the RP in terms of the tumor dose in the treatment plan. In contrast, VP had 3.5% higher PTV Dmax and 5.5% lower PTV V95% than RP (p < 0.001). The RP demonstrated significantly higher lung V20Gy and Dmean by 1.4% and 0.4 Gy, respectively, than the PP. The RP showed smaller changes in dose distribution affected by chest wall motion and significantly higher tumor dose coverage than the PP and VP. CONCLUSION: We revealed that the RP demonstrated comparable tumor doses to the PP in treatment planning and was robust for respiratory motion compared to both the PP and the VP. However, the organ at risk dose in the RP was slightly higher; therefore, its clinical use should be carefully considered.

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.

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.

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.

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.

Comparison of the Diagnostic Performance of Newly Designed 21-Gauge and Standard 22-Gauge Aspiration Needles in Patients with Solid Pancreatic Masses.

BACKGROUND: Although endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been widely used for the diagnosis of pancreatic tumors, the ability to obtain adequate pancreatic tumor tissue needs to be improved. AIMS: This study was performed to compare a newly designed 21-gauge needle (EUS Sonopsy CY; Hakko Medical, Nagano, Japan) and a standard 22-gauge needle for tissue sampling of solid pancreatic masses. METHODS: Consecutive patients with solid pancreatic masses who underwent EUS-FNA with either the EUS Sonopsy CY or the 22-gauge needle from June 2014 to December 2016 were enrolled. The primary outcome was comparison of the diagnostic yield of the FNA samples. The secondary outcomes were comparison of technical success, diagnostic ability for malignancy, and complications. RESULTS: A total of 93 patients (40.9% female; mean age, 70.1 years) underwent EUS-FNA with the EUS Sonopsy CY (n = 47) or the standard 22-gauge needle (n = 46). The technical success rate was 100% in both groups, and the overall diagnostic accuracy for malignancy was similar between the groups (100% in the EUS Sonopsy CY group vs. 95.7% in the 22-gauge needle group, P = 0.242). Nevertheless, the EUS Sonopsy CY resulted in significantly higher scores for cellularity (P = 0.006) and lower scores for blood contamination (P < 0.001). The procedure-related complication rate was comparable between the groups (P = 0.148). CONCLUSIONS: The EUS Sonopsy CY provided higher-quality specimens for histological evaluation in terms of both sample cellularity and blood contamination for the diagnosis of solid pancreatic masses. TRIAL REGISTRATION: The study was registered in a clinical trial registry, No. UMIN000032598.

Organ-preserving approach via radiotherapy for small cell carcinoma of the bladder: an analysis based on the Japanese Radiation Oncology Study Group (JROSG) survey.

Small cell carcinoma of the bladder is extremely rare, accounting for <1% of all malignant tumours in the urinary tract. Thus, no standard therapy modality for this malignancy has been established. This study aimed to retrospectively analyse the clinical outcomes associated with definitive radiotherapy for small cell carcinoma of the bladder. A questionnaire-based survey of patients with pathologically proven small cell carcinoma of the bladder treated with definitive radiation therapy between 1990 and 2010 was conducted by the Japanese Radiation Oncology Study Group. The clinical records of 12 eligible patients were collected from nine institutions. The median age of the patients was 70.5 years (range: 44-87 years), and the median follow-up period was 27.3 months (range: 3.3-117.8 months). The median prescribed dose was 60 Gy (range: 50.0-61.0 Gy), and a median of 2.0 Gy (range: 1.2-2.0 Gy) was administered per fraction. Systemic chemotherapy combined with radiotherapy was performed in eight cases (66.7%). The 3- and 5-year overall survival rates were 50.0% and 33.3%, respectively. And the 3- and 5-year local control rates were 66.7% and 55.6%, respectively. Chemotherapy significantly improved overall survival and relapse-free survival (P = 0.006 and 0.001, respectively). No serious adverse events occurred in the observation period. All patients who achieved local control maintained functional bladders. In conclusion, radiotherapy is a potential local treatment option and has an important role in maintaining quality of life. Systemic chemotherapy combined with local radiotherapy seems to be effective in improving survival.

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.

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.

First experience of carbon-ion radiotherapy for early breast cancer.

Breast cancer is increasingly being detected at earlier stages, and partial breast irradiation for patients with low-risk-group tumor has come to be applied in the US and Europe as an alternative to whole-breast irradiation. Based on those experiences, some institutes have tried using particle beams for partial breast irradiation for postoperative or radical intent for early breast cancer, but technical difficulties have hindered its progress. The National Institute of Radiological Sciences has been preparing for carbon-ion radiotherapy (C-ion RT) with radical intent for stage I breast cancer since 2011, and we carried out the first treatment in April 2013. In this case report, we explain our first experience of C-ion RT as a treatment procedure for breast tumor and present the radiation techniques and preliminary treatment results as a reference for other institutes trying to perform the same kind of treatment.

Relationship between serum reactive oxidative metabolite level and skin reaction in an irradiated rat model.

PURPOSE: Ionizing radiation generates free radicals and reactive oxygen species that induce DNA damage in vivo. This study aimed to determine the relationship between serum reactive oxygen metabolite (ROM) levels and skin reaction after irradiation in a rat model. METHODS AND MATERIALS: I. Female Wistar rats were classified into 0 Gy (control), 2 Gy, and 30 Gy groups; serum ROM levels were measured in the very acute phase. II. Other female Wistar rats were classified into 0 Gy (control), 30 Gy, 50 Gy, and 70 Gy groups; serum ROM levels were measured before and 3, 7, 16, 24, 31, and 38 days after irradiation. Skin reaction was evaluated according to the SRS (0-5) twice every week. RESULTS: Serum ROM levels in the subacute phase were significantly higher in the 50 and 70 Gy groups than in the 0 and 30 Gy groups [p = 0.029, repeated-measure analysis of variance (ANOVA)]. As expected, SRSs increased in the order of the 0 Gy, 30 Gy, 50 Gy, and 70 Gy groups and differed significantly among these groups (p < 0.001, repeated-measure ANOVA). Peak serum ROM levels were observed 16 days after irradiation in all irradiated groups and corresponded with the appearance of visible skin reaction after irradiation. CONCLUSIONS: Serum ROM levels may be useful for evaluating radiation damage in mammals. Further investigations are required to investigate changes in intracellular metabolism after irradiation at gene and protein levels.

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.

Multiple early gastric cancer with gastritis cystica profunda showing various histological types.

We report a case of multiple early gastric cancer showing varied histological types associated with gastritis cystica profunda (GCP). A 61-year-old man who had early gastric cancer associated with GCP underwent a distal gastrectomy with lymphadenectomy. Histological examination showed various histological types of cancer -well differentiated, moderately differentiated, poorly differentiated adenocarcinoma, mucinous adenocarcinoma and signet ring cell carcinoma- that had developed independently in the mucosal and submucosal layers of the resected specimen. Furthermore, multiple cysts with a single layer of columnar epithelium were present in the submucosa around the cancerous lesions. However, no neoplastic changes were found in those epithelial cells. Helicobacter pylori was detected in the residual stomach 3 months after surgery. Although the mechanism of the relationship between gastric carcinoma and GCPs is obscure, we speculate that repeated erosion and regeneration induced by chronic inflammation causes multicentric carcinogenesis as well as an aberration of the gastric glands. GCPs may be a risk factor for multiple gastric cancer.

Primary hepatic low-grade B-cell lymphoma of MALT-type associated with Helicobacter pylori infection.

Primary marginal zone B-cell lymphoma of mucosa associated tissue (MALT) type in the liver is extremely rare, and the etiology of this disease is yet to be clarified. We present the first report of a primary hepatic low-grade lymphoma of MALT-type associated with Helicobacter pylori (H. pylori) infection. A 64-year-old man was referred to our hospital for the treatment of early gastric carcinoma. He underwent distal gastrectomy with regional lymph node dissection. In the operation, several small nodules were recognized at the surface of the liver, and one of these hepatic nodules was resected as biopsy. The hepatic lesion exhibited a nodular growth pattern consisting of centrocyte-like cells and intermediate lymphocytes, which were stained with CD20 and CD79a, but not with CD43 or CD45RO. The neoplastic cells form lymphoepithelial lesions infiltrating bile ducts. From these findings the liver lesion was diagnosed as marginal zone B-cell lymphoma of MALT type. Histological examinations of resected stomach and residual stomach showed H. pylori infection. There is a strong association between the presence of H. pylori in the stomach and in the bile, and therefore, the H. pylori may be related to the etiology of primary hepatic MALT type lymphoma.

Clinical significance of intracytoplasmic nm23-H1 expression in diffuse large B-cell lymphoma.

PURPOSE: Recently, we established an ELISA technique for measuring nm23-H1 protein in serum and found that the serum nm23-H1 level is a potential prognostic factor for patients with non-Hodgkin's lymphoma. EXPERIMENTAL DESIGN: We used immunohistochemistry to examine the expression of nm23-H1 by the lymphoma cells in patients with diffuse large B-cell lymphoma (DLBCL). RESULTS: By analyzing a consecutive series of 172 untreated DLBCL patients, we found that 100 (58.1%) were strongly positive. The cytoplasmic nm23 expression in lymphoma cells correlated significantly with the serum nm23-H1 level. There was a significant correlation between patients with cytoplasmic nm23-positive lymphoma and those with performance status 2-4, stage III/IV, bulky mass, B symptoms, elevated serum level of soluble interleukin 2 receptor, and elevated serum level of C-reactive protein. Overall and progression-free survival rates were significantly lower in patients with nm23-H1-positive lymphomas than in those with nm23-H1-negative lymphomas. Similar difference was seen between patients with high and low serum levels of nm23-H1. Thus, the correlation between presence or absence of cytoplasmic nm23-H1 expression and serum nm23-H1 levels suggests that serum nm23-H1 is produced directly by lymphoma cells. CONCLUSION: We suggest that nm23-H1 expression is a prognostic factor for DLBCL, and that it is as important as serum nm23-H1, both of which are useful for planning a treatment strategy.

Expression of nm23-H1 is associated with poor prognosis in peripheral T-cell lymphoma.

We have reported previously that the serum nm23-H1 level is a prognostic factor for non-Hodgkin's lymphoma. In this study, we examined nm23-H1 expression in T- and natural killer (NK)-cell lymphoma in order to evaluate whether lymphoma cells produce the protein. The clinical significance of the cytotoxic molecules, T-cell intracellular antigen-1 (TIA-1) and granzyme B and nm23-H1 expression were also examined. Expression of nm23-H1, TIA-1, or granzyme B was examined by immunohistochemistry in 137 previously untreated lymphoma patients. The relationship between the results and clinical outcome was examined in 81 patients with angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, or peripheral T-cell lymphoma, unspecified. The neoplastic cells of some lymphomas produced nm23-H1 and the expression rates of nm-23-H1, TIA-1 and granzyme B were 36.5%, 78.8% and 32.8% respectively. The nm23-H1-positive or TIA-1-positive groups had significantly shorter overall and disease-free survivals. Multivariate analysis confirmed nm23-H1 expression to be an independent prognostic factor. The nm23-H1 protein can be an important prognostic factor in the lymphomas studied here. New treatments that target nm23 overexpression could be developed as a result of nm23-HI production by lymphoma cells.