Abstract
The aim of the study was to investigate the effect of chemo-radiation on the genetic and immunological status of rectal cancer patients who were treated with preoperative chemoradiotherapy ...(CRT). The expression of immune response-associated genes was compared between rectal cancer patients treated (n = 9) and not-treated (n = 10) with preoperative CRT using volcano plot analysis. Apoptosis and epithelial-to-mesenchymal transition (EMT) marker genes were analysed by quantitative PCR (qPCR). Other markers associated with the tumor microenvironment (TME), such as tumor-infiltrating lymphocytes (TIL) and immune checkpoint molecules, were investigated using immunohistochemistry (IHC). The clinical responses of preoperative CRT for 9 rectal cancer patients were all rated as stable disease, while the pathological tumor regression score (TRG) revealed 6 cases of grade2 and 3 cases of grade1. According to the genetic signature of colon cancers, treated tumors belonged to consensus molecular subtype (CMS)4, while not-treated tumors had signatures of CMS2 or 3. CRT-treated tumors showed significant upregulation of EMT-associated genes, such as CDH2, TGF-beta and FGF, and cancer stem cell-associated genes. Additionally, qPCR and IHC demonstrated a suppressive immunological status derived from the upregulation of inflammatory cytokines (IL-6, IL-10 and TGF-beta) and immune checkpoint genes (B7-H3 and B7-H5) and from M2-type macrophage accumulation in the tumor. The induction of EMT and immune-suppressive status in the tumor after strong CRT treatment urges the development of a novel combined therapy that restores immune-suppression and inhibits EMT, ultimately leading to distant metastasis control.
A commercially available flat bolus (commercial bolus) would not fully fit the irregular surfaces of the scalp. We developed a transparent and flexible material with good fitting properties, analyzed ...its physical characteristics, and evaluated the clinical feasibility of the bolus fabricated using a three-dimensional (3D) printer (3D bolus). To evaluate the physical characteristics of the new material, treatment plans with virtual, 3D, and commercial boluses were created for water-equivalent phantoms using a radiation treatment planning system (RTPS). Using a head phantom and the dose volume histogram calculated with RTPS, dose distributions for total scalp irradiation were compared between the three treatment plans. To evaluate the clinical feasibility, the fitness and reproducibility of the 3D bolus were compared with the head phantom and clinical cases using dice similarity coefficient (DSC) measurements. A good agreement was observed between the percentage depth dose (PDD) curves for the virtual, 3D, and commercial boluses. The homogeneity indexes of the planning target volume (PTV) for the 3D and commercial boluses were 0.083 and 0.153, respectively, proving that the former achieved a better dose uniformity of PTV than the latter. Good fitness and reproducibility with the 3D bolus were observed in both the head phantom and two clinical cases, with mean DSC values of 0.854, 0.829, and 0.843, respectively. These results successfully demonstrated and verified the utility of the 3D bolus for total scalp irradiation.
We present high-contrast observations of 68 young stellar objects (YSOs) that have been explored as part of the Strategic Exploration of Exoplanets and Disks with Subaru (SEEDS) survey on the Subaru ...telescope. Our targets are very young (<10 Myr) stars, which often harbor protoplanetary disks where planets may be forming. We achieve a typical contrast of ∼10−4-10−5.5 at an angular distance of 1″ from the central star, corresponding to typical mass sensitivities (assuming hot-start evolutionary models) of ∼10 MJ at 70 au and ∼6 MJ at 140 au. We detected a new stellar companion to HIP 79462 and confirmed the substellar objects GQ Lup b and ROXs 42B b. An additional six companion candidates await follow-up observations to check for common proper motion. Our SEEDS YSO observations probe the population of planets and brown dwarfs at the very youngest ages; these may be compared to the results of surveys targeting somewhat older stars. Our sample and the associated observational results will help enable detailed statistical analyses of giant planet formation.
After stereotactic radiosurgery (SRS) for brain metastases, delayed radiation effects with mass effect may occur from several months to years later, when tumors may also recur. Aggressive salvage ...treatment would be beneficial for patients with recurrence, but may be contraindicated for those with dominant radiation effect. Conventional magnetic resonance (MR) imaging does not provide sufficient information to differentiate delayed radiation effects from tumor recurrence. Positron emission tomography, MR spectroscopy, and other modalities sometimes may lead to false findings of tumor recurrence. We prospectively applied perfusion MR imaging for the management strategy after SRS because it gives microvascular information about the lesions. Twenty-eight lesions were enlarged on serial MR images in 27 patients 2–35 months (median: 11.8 months) after SRS for metastatic brain tumors. Each patient underwent MR perfusion imaging within a month after appearance of the growing enhanced lesion. To calculate the relative cerebral blood volume ratio (rCBV ratio), the regions of interest were located in the enhanced areas on the contrast-enhanced T1-weighted images and compared with the corresponding contralateral normal brain tissue. They were then followed-up with scheduled MR images with gadolinium enhancement at 1 to 2-month intervals afterward. Lesions which progressively increased in size on MR images were diagnosed as recurrences; lesions which disappeared or decreased in size were diagnosed as radiation necrosis. In addition, two lesions surgically removed were diagnosed by pathological examination. Follow-up MR images revealed that 21 of 28 lesions were radiation necrosis. Five lesions were diagnosed as recurrence on MR images, and the other two lesions were revealed as recurrence by pathological examination. An rCBV ratio of greater than 2.1 provided the best sensitivity and specificity for identifying recurrent metastatic tumors, at 100 and 95.2%, respectively. Perfusion MR imaging provides useful, less invasive and in-vivo information for management of growing lesions after SRS, and rCBV may be a valuable index for this diagnostic purpose.
To review the current status of, and labor expended for (in terms of time required), intracavitary brachytherapy (ICBT) in definitive radiotherapy/chemoradiotherapy for cervical cancer patients, two ...national surveys were performed. The first survey was conducted between July and August 2016 and consisted of a questionnaire of 12 items regarding ICBT procedures for cervical cancer, which was sent to 173 centers installed with high-dose-rate remote after-loading brachytherapy systems. Between November and December 2016, another survey was performed in 79 centers to evaluate labor required for ICBT procedures in terms of time spent and number of staff involved. In the first survey, the response rate was 77% of the 173 centers. ICBT was performed for cervical cancer in 118 (89%) centers. Imaging modalities used after applicator insertion were X-ray alone in 46 (40%), computed tomography in 69 (60%) and magnetic resonance imaging in 5 (4%) centers. Three-dimensional (3D) planning was performed in 55 centers (48%). Fifty-five (70%) centers responded to the second survey regarding ICBT-mandated labor. The median cumulative duration of the entire ICBT procedure was 330 min (the sum of the times spent by each staff member) and was longer in the 3D image-guided brachytherapy (3D-IGBT) (405 min) than in the X-ray group (230 min). This trend was significant for the specific processes of image acquisition and treatment planning, especially for radiation oncologists. In definitive radiotherapy/chemoradiotherapy for cervical cancer patients, 3D-IGBT use has been gradually spreading in Japan. The present survey revealed that ICBT, especially 3D-IGBT, requires substantial labor and time from staff.
Patterns of cancer incidence and radiotherapy use are similar in Korea and Japan, with differences in radiotherapy infrastructure.
The authors surveyed the megavoltage machines in 91 radiotherapy ...centers in Korea and published data in Japan. The number of megavoltage machines per center was used as an indicator of the fragmentation of radiotherapy services using four as the threshold, and the number of megavoltage machines per million people was compared. The practice pattern of intensity-modulated radiation therapy was analyzed.
There were 91 centers in Korea and 825 in Japan. The number of megavoltage machines per center was 1.3 in Japan and 2.3 in Korea. Radiotherapy infrastructure showed fragmentation in Korea and hyperfragmentation in Japan. In Japan, 75% of radiotherapy centers operated with one megavoltage machine, whereas in Korea, 47% megavoltage machines per center was 3.2 in Seoul, while that in the non-capital area was 1.8, constituting a mixed pattern of centralization and fragmentation. In Japan, megavoltage machines per center in Tokyo, Kanagawa and Osaka, was 1.5, 1.3 and 1.2, respectively, indicating no concentration in the metropolis. The number of megavoltage machines per million in Korea was 4.0, whereas that in Seoul was 8.7, constituting capital concentration. In Japan, the number of megavoltage machines per million was 8.7, whereas in Tokyo, Kanagawa and Osaka, it was is 9.3, 6.3 and 9.0, showing uniform distribution. intensity-modulated radiation therapy utilization is increasing, accounting for 15% and 23% of radiotherapy patients in Japan and Korea, respectively.
The fragmentation of radiotherapy services in Korea and Japan might affect radiotherapy quality.
ABSTRACT
We analyzed 428 femoral metastases initially treated with radiotherapy between 2002 and 2011 to clarify the clinical details of post-irradiation fractures of femoral metastasis. Patients ...included 161 men and 167 women, with a mean age of 62 years. Fracture incidence, fracture site, fracture risk based on X-ray images before radiotherapy, and interval from completion of radiotherapy to fracture occurrence were assessed. In addition, 24 pathological specimens obtained during 27 surgeries for these fractures were examined. Fractures occurred in 7.7% of 428 femoral metastases (total 33: 28 actual fractures and five virtual fractures with progressive pain and bone destruction). The fracture rate was 7.8% in the proximal femur and 1.5% in the shaft (P = 0.001). Fractures occurred a median of 4.4 months after radiotherapy, with 39.4% occurring within 3 months and 63.6% within 6 months. Among femurs with high fracture risk according to Harrington’s criteria or Mirels’ score, the fracture rate was 13.9% and 11.8%, respectively. Viable tumor cells were detected in all five patients with painful virtual fracture, in 85.7% of femurs with actual fractures that occurred within 3 months, and in only 25.0% of actual fractures occurring after 3 months. Post-irradiation fractures of femoral metastasis most frequently occurred within 3 months after radiotherapy, and were more common in the peritrochanteric area than in the shaft. Radiological evidence of impending fracture did not correlate with a high fracture rate. Actual fractures occurring after more than 3 months were likely caused by post-irradiation fragility of the femur, without viable tumor cells.
Skull metastases are malignant bone tumors which are increasing in incidence. The objectives of this study were to characterize the MR imaging features, locations, and extent of metastatic skull ...tumors to determine the frequency of the symptomatic disease, and to assess patient outcomes. Between September 2002 and March 2008, 175 patients undergoing routine head MR imaging were found to have metastatic skull tumors. Contrast-enhanced study with fat suppression was used in some cases when required. Classification of metastases was simplified to three yes/no questions: first, with regard to location (either in the calvarium or in the cranial base); second, with regard to distribution within the plane of the cranial bone (either “circumscribed” meaning clearly demarcated and confined to one bone, or “diffuse” and likely to spread across a suture to another bone); and third, with regard to invasion (“intraosseous” in cranial bones only, or “invasive” spreading from the skull, either out into the scalp or inward to the dura and perhaps further in). Primary sites were breast cancer (55%), lung cancer (14%), prostate cancer (6%), malignant lymphoma (5%), and others (20%). The mean time from primary diagnosis to skull metastasis diagnosis was 71 months for cases of breast cancer, 26 months for prostate cancer, 9 months for lung cancer, and 4 months for malignant lymphoma. Calvarial circumscribed intraosseous metastases were found most frequently (27%). The patients were mainly asymptomatic. However, some patients suffered from local pain or cranial nerve palsies that harmed their quality of life. Treatment, mainly for symptomatic cases, was by local or whole-skull irradiation. Metastatic skull tumors are not rare, and most are calvarial circumscribed intraosseous tumors. MR images contribute to understanding their type, location, and multiplicity, and their relationship to the brain, cranial nerves, and dural sinuses. Radiation therapy improved the QOL of patients with neurological symptoms.
Background
There has been a paradigm shift in cancer treatment from curing disease to both curing disease and caring for patients. In terms of care for patients, the opinions of patients and their ...families are important for improving medical services.
Aim
The opinions of patients and families were collected at Shizuoka Cancer Center (SCC) and examined from the standpoint of characteristics, response status, and temporal changes.
Methods
Patients' and families' opinions submitted to suggestion boxes at SCC over an 11‐year period (2005–2015) were analyzed. Opinions were categorized as complaints or compliments, with sub‐categories including “facilities, goods, and medical care,” “people,” “time,” and “other.” The status of facilities' response to complaints was categorized as “responded,” “did not respond”, and “difficult to respond”.
Results
Changes in the number of opinions and content over time were examined. In total, 3419 opinions were collected; 69.1% were complaints, and 30.5% were compliments. Of the complaints, 53.4% were related to “facilities, goods, and medical care” (mainly focusing on “poor product quality” and “shortage of goods”), 38.7% were related to “people,” and 7.7% to “time.” Of the compliments, 82.4% were about “people,” all of which concerned facility staff. Facilities' responses to complaints were as follows: “responded” (42.4%), “did not respond” (14.3%), and “difficult to respond” (43.3%).
Conclusion
Understanding patients' and families' opinions is effective for strengthening trust between patients and healthcare professionals, promoting holistic care.
Linac-based fractionated stereotactic radiotherapy (fSRT) and stereotactic radiosurgery (SRS) are increasingly being used to manage patients with multiple metastases. This retrospective cohort study ...aimed to compare the outcomes after linac-based fSRT and SRS between three patient groups classified based on the number of brain metastases (BMs): 1 BM, 2-4 BM, 5-10 BM.
The data of consecutive patients with 1-10 BMs treated with fSRT or SRS between July 2016 and June 2018 at a single institution were collected. Patients with previous whole-brain radiotherapy (WBRT), concurrent use of WBRT, or surgical resection were excluded from the analysis. A total of 176 patients were classified into three groups according to the number of BMs: 78, 67, and 31 patients in 1 BM, 2-4 BM, and 5-10 BM, respectively. The Kaplan-Meier method was used to estimate overall survival (OS) curves, and the cumulative incidence with competing risks was used to estimate local control (LC), distant intracranial failure (DIF), and radiation necrosis (RN).
Median OS was 19.8 months (95% confidence interval CI 10.2-27.5), 7.3 months (4.9-11.1), and 5.1 months (4.0-9.0) in 1 BM, 2-4 BM, and 5-10 BM, respectively. Compared to 2-4 BM, 1 BM had significantly better OS (hazard ratio HR 0.59, 95% CI 0.40-0.87; p = 0.0075); however, 5-10 BM had comparable OS (HR 1.36, 95% CI 0.85-2.19; p = 0.199). There was no significant difference in LC, DIF, and RN between tumor number groups, but DIF was lower in 1 BM. RN of grade 2 or higher occurred in 21 patients (13.5%); grade 4 and 5 RN were not observed.
The linac-based fSRT and SRS for patients with 5-10 BMs is comparable to that for patients with 2-4 BMs in OS, LC, DIF, and RN. It seems reasonable to use linac-based fSRT and SRS in patients with 5-10 BMs.
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