Pain response in single-fraction 8-Gy radiotherapy for painful non-bone-metastasis tumors: a single-center retrospective study.

The effectiveness of single-fraction 8-Gy radiotherapy for painful bone metastases has been verified in numerous randomized controlled trials. However, few reports have described the effectiveness of single-fraction 8-Gy radiotherapy in painful tumors other than bone metastases. We conducted a retrospective analysis to evaluate the pain response to single-fraction 8-Gy radiotherapy in painful non-bone-metastasis tumors. We included patients who had received single-fraction 8-Gy radiotherapy for such tumors between January 2017 and December 2022, excluding those with brain metastases, hematological tumors and those who received re-irradiation. Pain response assessment was based on the best responses documented in the medical records and conducted by two radiation oncologists. A total of 36 eligible patients were included in this study. The irradiation sites included primary lesions in eight patients, lymph node metastases in eight, muscle metastases in seven, pleural dissemination in four, skin/subcutaneous metastases in four and other sites in five. Pain response was assessed in 24 patients after radiotherapy. Pain response rate was 88% in evaluable patients; 21 of the 24 patients experienced response. The median assessment date for pain response was 37 days (range: 8-156 days) after radiotherapy. Re-irradiation was performed in four patients (11%). Single-fraction 8-Gy radiotherapy seemed to be a promising treatment option for painful non-bone-metastasis tumors and warrants further investigation.

Outcomes of 30 Gy/5 Fr Hypofractionated Stereotactic Radiation Therapy for Small Brain Metastases (≤2 cm).

BACKGROUND/AIM: Stereotactic radiosurgery (SRS)-used for brain metastases (BMs) with a tumor diameter of ≤2 cm-has a high local control rate, however, it can cause symptomatic radiation-induced brain necrosis. Hypofractionated stereotactic radiation therapy (HFSRT) is not commonly used for such lesions and its effectiveness remains unknown. Herein, the efficacy of 30 Gy 5-fraction HFSRT for treating BMs of <2 cm was retrospectively evaluated. PATIENTS AND METHODS: Patients who received HFSRT and had a gross tumor volume (GTV) of ≤2 cm in maximum diameter were included in the study (49 patients; 179 BMs; median follow-up period, 11.9 months). RESULTS: The mean GTV Peripheral Dose (D95) was 36.2 Gy. The local control (LC) rates at 1 and 2 years were 93.0% and 81.5%, respectively, for all lesions. The 1-year LC rates were 93.6% and 92.0% for ≤1.0-cm and 1.0-2.0-cm lesions, respectively. Multivariate analysis revealed that the only significant difference was in GTV maximal tumor diameter (HR=1.961, p=0.0002). Notably, only one patient had asymptomatic radiation necrosis. CONCLUSION: Owing to the high toxicity of SRS, 5-fraction HFSRT can be an effective treatment strategy for BMs of <2 cm.

Lipid Polyunsaturated Fatty Acid Chains in Mouse Kidneys Were Increased within 5 min of a Single High Dose Whole Body Irradiation.

To understand the ultra-early reaction of normal organ lipids during irradiation, we investigated the response of lipids, including polyunsaturated fatty acid (PUFA) chains, which are particularly susceptible to damage by ROS, in mice's kidneys, lungs, brains, and livers within 5 min of single high-dose irradiation. In this study, we set up three groups of C56BL/6 male mice and conducted whole-body irradiation with 0 Gy, 10 Gy, and 20 Gy single doses. Kidney, lung, brain, and liver tissues were collected within 5 min of irradiation. PUFA-targeted and whole lipidomic analyses were conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results showed that PUFA chains of kidney phosphatidylcholine (PC), phosphatidylethanolamine (PE), and triacylglycerol (TG) significantly increased within 5 min of 10 Gy and 20 Gy irradiation. The main components of increased PUFA chains in PC and PE were C18:2, C20:4, and C22:6, and in TG the main component was C18:2. The kidney lipidomes also showed significant changes from the perspective of lipid species, mainly dominated by an increase in PC, PE, TG, and signal lipids, while lipidomes of the lung, brain, and liver were slightly changed. Our results revealed that acute PUFA chains increase and other lipidomic changes in the kidney upon whole-body irradiation within 5 min of irradiation. The significantly increased lipids also showed a consistent preference for possessing PUFA chains. The lipidomic changes varied from organ to organ, which indicates that the response upon irradiation within a short time is tissue-specific.

Impact of Radiation Dose on Treatment of Maxillary Cancer With Superselective Intra-arterial Cisplatin With Radiotherapy.

BACKGROUND/AIM: Maxillary sinus cancer is a relatively rare disease, and treatment is still evolving. We compared the efficacy of superselective intra-arterial infusion of high-dose cisplatin (CDDP) with concomitant radiotherapy (RADPLAT) using three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) and analyzed the relationship between the total radiation dose and the treatment outcome in localized maxillary sinus cancer. PATIENTS AND METHODS: We reviewed the cases of 58 patients with localized maxillary sinus cancer treated with RADPLAT at our institution from March 2004 to November 2020. These 58 patients included 34 who received 3DCRT and 24 who received IMRT. RESULTS: The median follow-up period was 38.4 months. The median prescribed dose to the local lesion was 66 Gy in the 3DCRT group and 70 Gy in the IMRT group. CDDP (100-120 mg/m2) was administered once a week for a median of 6 cycles. The 5-year local control rate and overall survival rate were 69.9% and 72.2%, respectively. The patients treated with 70 Gy had a significantly higher local control rate (87.7%) than those treated with 60 Gy or less (41.0%) (p=0.011). No late grade 3 or higher eye disorders except for cataracts developed in the IMRT group, while grade 4 eye disorders occurred in four patients receiving 3DCRT. CONCLUSION: IMRT can escalate radiation dose safely with acceptable toxicities. The total dose may have an impact on the local control rate in RADPLAT.

Rectourethral fistula after external beam radiotherapy for prostate cancer in a patient with thromboangiitis obliterans: A case report.

INTRODUCTION: Thromboangiitis obliterans (TAO) is a rare disease of unknown cause that causes segmental vasculitis in peripheral blood vessels. It is uncertain whether its presence causes serious adverse events in patients receiving external beam radiotherapy. PATIENT CONCERNS: A 73-year-old Japanese man with prostate cancer underwent external beam radiotherapy. DIAGNOSIS: After completion of radiotherapy, fingertip pain occurred, leading to the diagnosis of TAO. INTERVENTIONS: The patient was instructed to stop smoking, but was unable to do so. OUTCOMES: Nine months after the completion of radiotherapy, fecaluria appeared, and a rectourethral fistula was diagnosed by contrast enema. The patient's TAO was poorly controlled, and the patient died from aspiration pneumonia 33 months after completion of the radiotherapy regimen. No tumor recurrence was observed during this process, and there were no risk factors other than TAO that may have formed a rectourethral fistula. LESSONS: This is the first report of rectourethral fistula caused by external beam radiotherapy for prostate cancer in which TAO was suspected to be involved. Although little is known about the relationship between TAO and radiotherapy, it should be noted that radiotherapy itself may increase the risk of normal tissue toxicity in patients with TAO.

A newly developed patient fixation system using a dedicated mouthpiece and dental impression materials for head and neck radiotherapy: a preliminary study.

We evaluated the basic characteristics and efficacy of our newly developed patient fixation system for head and neck radiotherapy that uses a dedicated mouthpiece and dental impression materials. The present investigation demonstrated that with this system, the changes in the absorbed dose to water depending on the material of the mouthpiece were small, with a maximum of 0.32% for a 10-MV photon beam. For the dental impression material, we selected a silicone material with the lowest Hounsfield unit (HU) value that had little effect on the generation of artifacts and the quality of the X-ray beam. Multiphase magnetic resonance imaging (MRI) revealed that the head-up and -down motions in the thermoplastic shell without the mouthpiece were 5.76 ± 1.54 mm, whereas the motion with the mouthpiece decreased significantly to 1.72 ± 0.92 mm (P = 0.006). Similarly, the head-left and -right motion displacement decreased from 6.32 ± 1.86 mm without the mouthpiece to 1.80 ± 0.42 mm with the mouthpiece (P = 0.003). Regarding the tongue depressor function of the mouthpiece, the median distance from the hard palate to the surface of the tongue was 28.42 mm. The present results indicate that the new immobilization device developed herein that uses a mouthpiece and a thermoplastic shell is useful for suppressing patients' head motions and tongue positions.

Development of a novel airbag system of abdominal compression for reducing respiratory motion: preliminary results in healthy volunteers.

This study used cine-magnetic resonance imaging (cine-MRI) to evaluate the safety and efficacy of a novel airbag system combined with a shell-type body fixation system in reducing respiratory motion in normal volunteers. The airbag system consists of a six-sided polygon inflatable airbag, a same shape plate, a stiff air supply tube, an air-supply pump and a digital pressure load cell monitor. Piezoelectric sensors were installed in the plate to detect compression pressure load changes; pressure load data were transferred to the digital pressure load cell monitor through Bluetooth. Five volunteers underwent cine-MRI with and without airbag compression to detect differences in the respiratory motion of the organs. The volunteers' physiologic signs were stable during the experiment. The maximum inspiration pressure load was 4.48 ± 0.86 kgf (range, 4.00-6.00 kgf), while the minimum expiration pressure load was 3.69 ± 0.95 kgf (range, 2.8-5.3 kgf). Under airbag compression, the right diaphragm movement was reduced from 19.50 ± 6.43 mm to 9.60 ± 3.61 mm (P < 0.05) in the coronal plane and 23.12 ± 6.30 mm to 11.00 ± 3.69 mm (P < 0.05) in the sagittal plane. The left diaphragm, pancreas and liver in the coronal plane and the right kidney and liver in the sagittal plane also showed significant movement reduction. This novel airbag abdominal compression system was found to be safe during the experiment and successful in the reduction of internal organ respiratory motion and promises to be a convenient and efficient tool for clinical radiotherapy.

The relationship between the quantitative evaluation of thyroid bed uptake and the disappearance of accumulation in adjuvant radioactive iodine therapy for differentiated thyroid cancer.

OBJECTIVE: Iodine-131 (I-131) radioactive iodine therapy (RAI) after total thyroidectomy is the standard treatment for patients with differentiated thyroid cancer (DTC). We investigated the relationship between the quantitative parameters of the iodine uptake and the disappearance of the accumulation in the thyroid bed in adjuvant therapy using a 1.11 GBq or 3.70 GBq dose of I-131. METHODS: We retrospectively analyzed the cases of 40 patients with DTC who were treated with RAI at our institution between April 2017 and August 2019. The patients were treated with the I-131 dose of 1.11 GBq (n = 25) or 3.70 GBq (n = 15) after total thyroidectomy. The I-131 whole-body scan and hybrid single-photon emission computed tomography/X-ray computed tomography (SPECT/CT) were performed 3 days after RAI. Using image analysis software, we measured the standardized uptake value (SUV) and absolute radioactivity concentration (kBq/ml) on the target lesions with the highest uptake in the thyroid bed. RESULTS: The median period from RAI to the evaluation of the absence of uptake of the thyroid bed was 6.75 months. After RAI, uptake of the thyroid bed disappeared in 26 of the 40 patients. The disappearance rate was significantly higher in the 3.70 GBq group than in the 1.11 GBq group (86.7% vs. 52.0%, respectively; p = 0.029). However, there were no significant differences in the values of kBq/ml or SUV between the 1.11 GBq group and 3.70 GBq group. On the other hand, the group in which the uptake disappeared after RAI showed significantly higher kBq/ml max and kBq/ml mean values than the group in which the uptake did not disappear after RAI (p = 0.028, p = 0.032, respectively). The SUVmax and SUVmean also tended to be higher in the disappeared-uptake group than the not-disappeared-uptake group, but the differences were not significant (p = 0.166, p = 0.176, respectively). CONCLUSIONS: The quantitative evaluation might be useful as one of the predictive indicators of the disappearance of the accumulation of radioactive iodine in the thyroid bed.

Radical Radiation Therapy for Radiation-Induced Angiosarcoma with Local Control.

Angiosarcoma is believed to be refractory to radical radiotherapy. Although no effective treatment for radiation-induced angiosarcoma has been established, surgery is generally chosen. We report a case of unresectable radiation-induced angiosarcoma after breast cancer surgery that responded remarkably to radical radiotherapy alone. A 78-year-old Japanese female had a large mass in her right breast that was diagnosed as angiosarcoma after biopsy and considered to be a radiation-induced angiosarcoma because the patient had been treated with postoperative irradiation to the right breast cancer 8 years earlier. There were no findings suggestive of lymphadenopathy or distant metastasis. Since the tumor was widely infiltrated to the skin and the muscle layer, radical radiotherapy (total dose 66 Gy) was performed. At this radiotherapy completion, the tumor was remarkably reduced, and there were no acute adverse effects except for grade 2 dermatitis. Pazopanib was started after radiotherapy but was discontinued since necrosis of the wound with hemorrhage was observed. External pneumothorax occurred due to the marked tumor shrinkage, but it was cured by conservative care. Although angiosarcoma is well known to be radioresistant, excellent local control may be obtained by radical radiotherapy in some cases. Radiotherapy should be considered as a treatment option in inoperable cases.

National survey of radiation oncologists' practice patterns regarding hormone-naïve prostate cancer with bone metastases.

OBJECTIVE: To explore radiation oncologists' attitudes and practice patterns of radiotherapy for hormone-naïve prostate cancer with bone metastases in Japan. METHODS: An internet-based survey was distributed to board-certified radiation oncologists of the Japanese Society of Radiation Oncology. Three hypothetical cases were assumed: hormone-naïve prostate cancer with single, three or multiple non-symptomatic bone metastases. The respondents described their attitude regarding such cases, treatment methods and the radiotherapy dose fractionation that they would recommend. RESULTS: Among the 1013 board-certified radiation oncologists in Japan, 373 (36.8%) responded to the questionnaire. Most of the respondents (85.0%) believed that radiotherapy may be applicable as a primary treatment for hormone-naïve prostate cancer with bone metastases in some circumstances. For Case 1 (single bone metastasis), 55.0% of the respondents recommended radiotherapy for the prostate and bone metastasis. For Case 2 (three bone metastases), only 24.4% recommended radiotherapy for all lesions, and 31.4% recommended radiotherapy for the prostate only. For Case 3 (multiple bone metastases), 49.1% of the respondents stated that there was no indication for radiotherapy. However, 34% of the respondents still preferred to administer radiotherapy for the prostate. The radiotherapy techniques and dose fractionations varied widely among the respondents. CONCLUSION: Most of the respondent radiation oncologists believed that radiotherapy may be beneficial for hormone-naïve prostate cancer with bone metastases.

[Clinical Complete Response to Definitive Chemoradiotherapy for Advanced Lower Rectal Cancer-A Case Report].

A man in his 80s was admitted to our hospital with a chief complaint of bloody stools. He was diagnosed with cT2N0M0, cStage Ⅰ rectal cancer. As the patient was of advanced age and had multiple comorbidities, definitive chemoradiotherapy was administered. Immediately after treatment, the patient achieved a complete clinical response, and recurrence has not been detected for 2 years and 3 months since treatment.

Quality of life after external beam radiotherapy for localized prostate cancer: Comparison with other modalities.

In external beam radiotherapy for localized prostate cancer, acute toxicities are typically transient and mild. These symptoms will disappear within 4-8 weeks after external beam radiotherapy. Some patients might suffer from proctitis with bloody stools as late rectal toxicity. Therefore, it has been shown that external beam radiotherapy has a more pronounced negative impact on bowel function compared with other treatment modalities. However, the recent development of modern beam delivery techniques, including intensity-modulated radiotherapy, allows us not only to deliver higher doses to the prostate, but also to decrease the doses to the critical organs, resulting in the maintenance of patients' quality of life within satisfactory levels. Patients' quality of life after external beam radiotherapy is also strongly related to the total dose, fractionation regimens, dose parameters of the critical organs and treatment plan quality, with a trade-off between the radicality of external beam radiotherapy and potentially increased toxicity. Radiation oncologists should choose treatment parameters carefully to achieve a reasonable balance between a good oncological outcome and the patient's quality of life.

Radiation-induced sarcoma after radiation therapy for prostate adenocarcinoma.

INTRODUCTION: Radiation therapy is widely used for prostate cancer, but radiation-induced sarcomas have been rarely reported. CASE PRESENTATION: A 77-year-old Japanese male was diagnosed with prostate cancer and received a combined androgen blockade and radiation therapy (total dose of 76 Gy). Five years after the radiation therapy, testicular pain and dysuria appeared. Computed tomography showed a soft tissue dense mass with invasion to the right subpubic ramus and prostate, mainly to the perineum. A needle biopsy revealed the pathological features of high-grade sarcoma. The patient was diagnosed with radiation-induced sarcoma based on the cancer's occurrence in the vicinity of the radiation field. CONCLUSION: Although irradiation is one of the important treatments for prostate cancer, the risk of radiation-induced malignancy should be considered.

Combined radiotherapy with nivolumab for extracranial metastatic malignant melanoma.

PURPOSE: We retrospectively evaluated the tumor regression after radiotherapy in combination with the immune checkpoint inhibitor nivolumab for metastatic melanoma. MATERIALS AND METHODS: We evaluated the extracranial metastatic melanoma lesions to which concomitant radiotherapy with nivolumab was administered from June 2015 to February 2017. Tumor volume and maximum diameter were measured at the time of pre-radiotherapy and best response, and the tumor reduction rate was assessed in two ways that our hospital adopts: tumor volume and diameter. RESULTS: Seven lesions in five patients were evaluated. The median time from the start of nivolumab treatment to the start of radiotherapy was 5 months (range 0-22 months). The objective response rate was 85.7% in the evaluation by tumor volume and 42.9% by maximum diameter of the tumor. The objective complete response rate was 28.6% in evaluation by tumor volume and 14.3% by maximum dia. The 1-year tumor control rate was 62.5%. The 1- and 2-year overall survival rate after nivolumab treatment were 75% and 50%, respectively. Two patients who obtained a complete response had presented with vitiligo. CONCLUSION: The combination of radiotherapy and nivolumab treatment produced favorable responses. Vitiligo may be correlated with a good response to concomitant radiotherapy with nivolumab.

Patterns of radiotherapy infrastructure in Japan and in other countries with well-developed radiotherapy infrastructures.

BACKGROUND: In high-income countries, the number of radiotherapy machine per population reaches a sufficient level. However, the patterns of infrastructure of radiotherapy in high-income countries are not well known. METHODS: Among 29 high-income countries with gross national income of $25,000 or more per capita, we selected 23 countries whose total number of newly diagnosed cancer patients in 2012 was reported in the Organisation for Economic Co-operation and Development Health Statistics 2017. The numbers of radiotherapy centers and teletherapy machines in each of these 23 countries were collected using the Dictionary of Radiotherapy Centers database. RESULTS: The number of cancer patients per teletherapy machine was 452.35-1398.22 (median 711.66) with a three-fold variation, whereas the number of cancer patients per radiotherapy center varied even more widely, from 826.16 to 5159.86 (median 2259.83) with a six-fold variation. The average number of teletherapy machines per radiotherapy center also ranged widely, from 1.24 to 8.29 (median 3.11) with a seven-fold variation. The number of teletherapy machines in each country was almost proportional to that of cancer patients, and the number of teletherapy machines per radiotherapy center was inversely related to the number of radiotherapy centers per cancer patients. The number of teletherapy machines per radiotherapy center in Japan was 1.24, the most fragmented among the high-income countries. The percentage of large radiotherapy centers having three or more teletherapy machines in Japan was the smallest among 23 high-income countries. CONCLUSIONS: Optimization of the radiotherapy infrastructure in Japan should be carefully considered.

Optimal method of gold nanoparticle administration in melanoma-bearing mice.

The present study assessed different methods of administering gold nanoparticles (GNPs) using different formulations to determine which of the methods achieved optimal radiosensitization. Cells from the B16F10 mouse melanoma cell line were implanted in the femoral area of mice, assigned to one of the eight following groups: i) Control; ii) intravenous (IV) injection of polyethylene glycol (PEG)-binding GNPs (Peg-GNPs) alone; iii) direct intratumoral (IT) injection of Peg-GNPs alone; iv) radiotherapy (RT)-alone; v) Peg-GNP IV + RT; vi) Peg-GNP IT + RT; vii) naked GNP (N-GNPs) IV + RT; and viii) N-GNP IT + RT. Injection volumes of the Peg-GNPs (particle size, 15 nm; dose, 2.8 mg/ml) and N-GNPs (particle size, 15 nm; dose, 200 mg Au/cc) were 0.3 and 0.2 ml per mouse, respectively, for IV and IT. The femoral area was irradiated with a single dose of 10 Gy. To evaluate the effects of GNPs, the current study measured the changes in the tumor volume ratio to the initial tumor volume over time and observed the survival rate. Administration of GNPs with RT did not improve the suppression of tumor growth or survival to a statistically significant extent. The administration of Peg-GNPs alone indicated a slight tumor suppressing effect at the early stage. The current study was not able to confirm the radiosensitization effect of GNPs in melanoma-bearing mice with tumors that were large in comparison to previous studies. Further research is required to validate the radiosensitizing effect on large tumors.

Age-associated effect of kestose on Faecalibacterium prausnitzii and symptoms in the atopic dermatitis infants.

BACKGROUND: Although Faecalibacterium prausnitzii is a major bacterium in the intestine of adults, which is known to have anti-inflammatory effects, the development in infants or the response to prebiotics remains unclear. METHODS: The counts of F. prausnitzii in the feces were examined by real-time polymerase chain reaction (PCR). Fecal samples were obtained from 65 atopic dermatitis (AD) infants who participated in a randomized controlled clinical trial to investigate the therapeutic effect of kestose, the smallest fructooligosaccharide. RESULTS: Although the F. prausnitzii count was undetectable level in most 0- to 1-y-old infants, the count reached a level comparable to that in adults in 2- to 5-y-old infants. The bacterial number increased about 10-fold by oral administration of kestose every day for 12 wk in the younger infants, but not so much in the older infants. This bacterial increase was significantly correlated with an improvement in the AD symptoms in the older infants. CONCLUSION: The F. prausnitzii population in the intestine reaches a level comparable to that in adult at approximately 2 y of age. Kestose efficiently stimulates the growth of this bacterium in the intestine, which might lead to an improvement in AD symptoms in infants.