Edaravone Exerts Protective Effects on Mice Intestinal Injury without Interfering with the Anti-Tumor Effects of Radiation.

The appropriate dosage of edaravone-a radioprotective agent-and its effect on tumors are unknown. This study evaluated the effects of edaravone on intestinal injuries and tumors in mice induced by whole body X-ray irradiation. Small intestinal mucositis was induced in C3H/HeNSlc mice using a single X-ray dose (15 Gy). Edaravone (15, 30, and 100 mg/kg) was administered 30 min before irradiation to evaluate its protective effect. After 3.5 days, the jejunum was removed and the histological changes were evaluated. Next, C3H/HeNSlc mice with squamous cell carcinoma VII tumors were provided the same single X-ray dose and 100 mg/kg edaravone; further, the tumors were immediately induced after irradiation. The tumor cell viability was detected using an in vivo-in vitro colony formation assay. We found that the intestinal colony-forming ability after irradiation was significantly higher in the 100 mg/kg edaravone group than that in the control group. Moreover, the apoptotic cells in the villi immunohistochemically stained with cleaved caspase-3 were significantly lower in the 100 mg/kg edaravone group than in the control group. We found no radioprotective effects of intraperitoneally inoculated edaravone in both hind legs on squamous cell carcinoma VII tumors. These findings suggest that 100 mg/kg edaravone exerts protective effects on small intestinal injuries without interfering with the antitumor effects of radiation.

A prospective feasibility study of a 1-mm bolus for postmastectomy radiotherapy.

BACKGROUND: The optimal chest wall bolus regimen for postmastectomy radiotherapy (PMRT) remains unknown. We aimed to prospectively evaluate the use of a 1-mm-thick daily tissue-equivalent bolus in patients who received PMRT using thermoluminescent dosimeters (TLDs) and skin toxicity assessment. METHODS: Patients with a 1-mm-thick daily bolus during PMRT were prospectively enrolled at The Juntendo University Hospital. The surface dose was measured in vivo under the 1-mm-thick bolus on the chest wall. We assessed the acute skin toxicity weekly during PMRT, and 1, 2, 4, and 12 weeks after the completion of PMRT. RESULTS: A total of 19 patients aged 32-79 years old received PMRT from July 2019 to January 2020. All patients completed the protocol treatment without interruptions, and the median follow-up was 32 weeks. In vivo dosimetry analysis revealed surface doses between 77 and 113% of the prescribed dose, with a mean of 92% of the prescribed radiation dose, and a standard deviation of 7% being delivered. Grade 2 dermatitis was found in 10 patients (53%), and Grade 3 dermatitis was found in one patient (5%). All cases of Grade 2 and 3 dermatitis were improved 4 weeks after PMRT. There were no cases of Grade 4 dermatitis and no chest wall recurrences during the treatment or follow-up period. CONCLUSIONS: Results confirmed the feasibility of using a 1-mm-thick daily bolus for PMRT, exhibiting an appropriate dose buildup and acceptable skin toxicity without treatment interruptions. TRIAL REGISTRATION: The University Hospital Medical Information Network Clinical Trials Registry, UMIN000035773 . Registered 1 July 2019.

Trajectory log analysis and cone-beam CT-based daily dose calculation to investigate the dosimetric accuracy of intensity-modulated radiotherapy for gynecologic cancer.

This study evaluated unexpected dosimetric errors caused by machine control accuracy, patient setup errors, and patient weight changes/internal organ deformations. Trajectory log files for 13 gynecologic plans with seven- or nine-beam dynamic multileaf collimator (MLC) intensity-modulated radiation therapy (IMRT), and differences between expected and actual MLC positions and MUs were evaluated. Effects of patient setup errors on dosimetry were estimated by in-house software. To simulate residual patient setup errors after image-guided patient repositioning, planned dose distributions were recalculated (blurred dose) after the positions were randomly moved in three dimensions 0-2 mm (translation) and 0°-2° (rotation) 28 times per patient. Differences between planned and blurred doses in the clinical target volume (CTV) D98% and D2% were evaluated. Daily delivered doses were calculated from cone-beam computed tomography by the Hounsfield unit-to-density conversion method. Fractional and accumulated dose differences between original plans and actual delivery were evaluated by CTV D98% and D2% . The significance of accumulated doses was tested by the paired t test. Trajectory log file analysis showed that MLC positional errors were -0.01 ± 0.02 mm and MU delivery errors were 0.10 ± 0.10 MU. Differences in CTV D98% and D2% were <0.5% for simulated patient setup errors. Differences in CTV D98% and D2% were 2.4% or less between the fractional planned and delivered doses, but were 1.7% or less for the accumulated dose. Dosimetric errors were primarily caused by patient weight changes and internal organ deformation in gynecologic radiation therapy.

The effects of rotational setup errors in total body irradiation using helical tomotherapy.

PURPOSE: Helical tomotherapy (HT) is a form of intensity-modulated radiation therapy that is employed in total body irradiation (TBI). Because TBI targets the whole body, accurate setup positioning at the edge of the treatment volume is made difficult by the whole-body rotational posture. The purpose of this study is to clarify the tolerance for rotational setup error (SE) in the vertical direction. In addition, we perform a retrospective analysis of actually irradiated dose distributions using previous patients' irradiation data. METHODS: To clarify the effects of rotational SE on the dose distribution, the planned CT images of 10 patients were rotated by 1-5° in the vertical (pitch) direction to create a pseudo-rotational SE image. Then, the effect of the magnitude of the rotational SE on the dose distribution was simulated. In addition, the irradiated dose to the patients was analyzed by obtaining recalculated dose distributions using megavoltage CT images acquired before treatment. RESULTS: The simulation results showed that the average value of the lung volume receiving at least 10 Gy did not exceed the allowable value when the SE value was ≤2°. When the rotational SE was ≤3°, it was possible to maintain the clinical target volume dose heterogeneity within ±10% of the prescribed dose, which is acceptable according to the guidelines. A retrospective analysis of previous patients' irradiation data showed their daily irradiation dose distribution. The dose to the clinical target volume was reduced by up to 3.4% as a result of the residual rotational SE. Although whole-course retrospective analyses showed a statistically significant increase in high-dose areas, the increase was only approximately 1.0%. CONCLUSIONS: Dose errors induced by rotational SEs of ≤2° were acceptable in this study.

Intrafraction stability using full head mask for brain stereotactic radiotherapy.

PURPOSE: We investigated the immobilization accuracy of a new type of thermoplastic mask-the Double Shell Positioning System (DSPS)-in terms of geometry and dose delivery. METHODS: Thirty-one consecutive patients with 1-5 brain metastases treated with stereotactic radiotherapy (SRT) were selected and divided into two groups. Patients were divided into two groups. One group of patients was immobilized by the DSPS (n = 9). Another group of patients was immobilized by a combination of the DSPS and a mouthpiece (n = 22). Patient repositioning was performed with cone beam computed tomography (CBCT) and six-degree of freedom couch. Additionally, CBCT images were acquired before and after treatment. Registration errors were analyzed with off-line review. The inter- and intrafractional setup errors, and planning target volume (PTV) margin were also calculated. Delivered doses were calculated by shifting the isocenter according to inter- and intrafractional setup errors. Dose differences of GTV D99% were compared between planned and delivered doses against the modified PTV margin of 1 mm. RESULTS: Interfractional setup errors associated with the mouthpiece group were significantly smaller than the translation errors in another group (p = 0.03). Intrafractional setup errors for the two groups were almost the same in all directions. PTV margins were 0.89 mm, 0.75 mm, and 0.90 mm for the DSPS combined with the mouthpiece in lateral, vertical, and longitudinal directions, respectively. Similarly, PTV margins were 1.20 mm, 0.72 mm, and 1.37 mm for the DSPS in the lateral, vertical, and longitudinal directions, respectively. Dose differences between planned and delivered doses were small enough to be within 1% for both groups. CONCLUSIONS: The geometric and dosimetric assessments revealed that the DSPS provides sufficient immobilization accuracy. Higher accuracy can be expected when the immobilization is combined with the use of a mouthpiece.

Clinical impact of baseline renal function on the safety of radiotherapy with concurrent docetaxel for esophageal cancer in elderly patients.

BACKGROUND: We aimed to compare the safety of radiotherapy with concurrent docetaxel (DOC-RT) for esophageal cancer (EC) in elderly patients who were divided into a creatinine clearance (Ccr) < 60 mL/min (Ccr-L) group and a Ccr ≥ 60 mL/min (Ccr-H) group. METHODS: Eligible patients included those aged ≥ 76 years who were diagnosed with esophageal squamous cell carcinoma. The patients received radiotherapy (60 Gy in 30 fractions) and concurrent docetaxel (10 mg/m2 weekly for six cycles), after which toxicity and treatment completion rates were retrospectively evaluated. RESULTS: The 73 elderly EC patients receiving DOC-RT were divided into two groups for evaluation: the Ccr-L group (49 patients) and the Ccr-H group (24 patients). The median survival time for patients in the Ccr-L and Ccr-H groups was 21 and 20 months, respectively (p = 0.2). The incidence of grade 1 acute kidney injury was 8% vs. 8% (p = 1) in the Ccr-L and Ccr-H groups, respectively. No other hematological or nonhematological toxicities differed between patients in the two groups. No grade 4 or 5 toxicities were observed in the two groups. No significant difference was observed in the treatment completion rates (88% vs. 92%, p = 1) between patients in the Ccr-L and Ccr-H groups. CONCLUSIONS: Regardless of baseline renal function, DOC-RT is a safe regimen for elderly patients with EC.

Development of a rotational set-up correction device for stereotactic head radiation therapy: A performance evaluation.

We developed a new head supporting device to provide accurate correction of rotational setup during image-guided radiation therapy (IGRT), evaluating its correction performance and the efficacy of dose distribution in stereotactic radiotherapy (SRT) using a helical tomotherapy (HT) system. The accuracy of rotational motion was measured using an electronic inclinometer; we compared device angles and measurement values from 0.0° to 3.0°. The correction accuracy was investigated based on the distance between rotational centers in the device and on megavoltage computed tomography (MVCT); the correction values were compared using distances in the range of 0.0-9.0 cm using a head phantom with a rotational error of 1.5°. For an SRT with a simultaneous integrated boost plan and a rotational error of 3.0° in yaw angle using a head phantom, and for a single-isocenter SRT for multiple brain metastases in the data of three patients, dosimetric efficacy of the HT unit was evaluated for calculated dose distributions with MVCT after rotational correction. This device can correct pitch and yaw angles within 0.3° and can be corrected to within 0.5° for each rotational angle according to the result of MVCT correction regardless of the rotational center position. In the head phantom study, the device had a beneficial impact on rotational correction; D99% for the target improved by approximately 10% with rotational correction. Using patient data with the device, the mean difference based on the treatment planning data was 0.3% for D99% and -0.1% for coverage index to the target. Our rotational setup correction device has high efficacy, and can be used for IGRT.

Clinical outcomes and prognostic factors of chemoradiotherapy for postoperative lymph node recurrence of esophageal cancer.

BACKGROUND: The therapeutic strategies and prognostic risk factors in patients with lymph node (LN) recurrence of esophageal cancer remain controversial. We assessed clinical outcomes and prognostic factors related to the use of chemoradiotherapy (CRT) for LN recurrence of esophageal squamous cell carcinoma (ESCC) after curative resection. METHODS: We retrospectively evaluated survival and prognostic factors in 57 patients with LN recurrence of ESCC after curative resection. Patients received CRT using 5-fluorouracil plus cisplatin (FP) or docetaxel. Radiotherapy was delivered at 2 Gy (total dose, 60-66 Gy; median, 60 Gy). RESULTS: The median follow-up duration was 24 (range, 3-116) months. The overall survival (OS) rates at 2, 3 and 5 years were 43.7%, 36.9% and 27.6%, respectively. In the univariate analysis of OS, treatment with FP, a single LN recurrence, and a single regional recurrence were associated with a significantly better prognosis (P = 0.04, P = 0.027 and P = 0.0001, respectively). In the multivariate analysis, the combination chemotherapy regimen [hazard ratio (HR), 2.50; 95% confidence interval (CI), 1.23-5.07] and the number of the regional LNs with recurrence (HR, 5.76; 95% CI, 1.22-27.12) were independent prognostic factors. CONCLUSION: Approximately 28% of ESCC patients with LN recurrence after curative resection could achieve long-term survival with CRT. Treatment with FP or patients with a single regional recurrence might improve the treatment outcome.

Palliative radiotherapy and chemoradiotherapy in stage IVA/B esophageal cancer patients with dysphagia.

BACKGROUND: Palliative therapeutic strategies in esophageal squamous cell carcinoma (ESCC) patients with dysphagia remain controversial. Only few studies have assessed therapeutic effect factors related to improvement in dysphagia score and nutrition-support-free survival (NSFS). OBJECTIVE: The present study assessed the efficacy and therapeutic effect factors related to the use of palliative radiotherapy (RT) and chemoradiotherapy (CRT) in ESCC patients with dysphagia. METHODS: We retrospectively evaluated 70 patients with stage IVA/B ESCC. Patients received RT of 30 Gy in 10 fractions or concurrent CRT using 5-fluorouracil plus cisplatin of 40 Gy in 20 fractions. The change in the dysphagia score from before to after treatment was assessed, and NSFS was evaluated. RESULTS: The median follow-up duration was 6 months (range 1-41 months). The overall rate of improvement in the dysphagia score was 60%. The median NSFS was 7.5 months. Craniocaudal tumor length < 6 cm, tumor circumference < 3/4, and CRT of 40 Gy in 20 fractions were associated with a significant improvement in the dysphagia score (p = 0.0036, p = 0.0069, and p = 0.03, respectively). NSFS was significantly longer with CRT than with RT (p = 0.048). CONCLUSION: Palliative RT and CRT are effective treatment options for ESCC patients with dysphagia. Craniocaudal tumor length < 6 cm, tumor circumference < 3/4, and CRT of 40 Gy in 20 fractions may improve dysphagia. CRT of 40 Gy in 20 fractions may improve NSFS.

[A Case of Pelvic Metastasis of Rectal Cancer That Developed Ten Years after Curative Resection].

We report a case of pelvic metastasis of rectal cancer that developed 10 years after curative resection. An 81-year-old woman underwent intersphincteric resection for lower rectal cancer 10 years previously. The tumor was pathologically diagnosed as T2N0M0, Stage Ⅰ. Nine years after the curative resection, serum carcinoembryonic antigen(CEA)levels were slightly elevated, but no recurrence was found on computed tomography(CT). Eleven months after CT, serum CEA levels elevated to 15.9 ng/mL. Pelvic metastasis in the piriformis muscle was detected on positron emission tomography(PET)-CT. Following CT-guided biopsy, she was pathologically diagnosed with metastatic rectal cancer. Radiotherapy (60 Gy/30 Fractions) was administered. Ten months after radiotherapy, PET-CT revealed no relapse in the pelvis with lung metastases.

Involved-field chemoradiotherapy for postoperative solitary lymph node recurrence of esophageal cancer.

BACKGROUND: For patients with postoperative lymph node (LN) recurrent esophageal cancer, the appropriate irradiation field in chemoradiotherapy (CRT) remains controversial. We assessed the clinical outcomes and prognostic factors related to involved-field CRT for postoperative solitary LN recurrence of esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively evaluated 21 patients who had received curative resection, with LN recurrence of ESCC. Patients received CRT using 5-fluorouracil plus cisplatin or docetaxel, prescribed at 60 Gy in 30 fractions. We evaluated the pattern of failure, toxicities, survivals, and prognostic factors. We defined elective nodal failure (ENF) as recurrence in a regional LN without involved-field failure. RESULTS: The median follow-up duration was 32 months (range, 4-106 months). Nine patients experienced failure-4 (19%) within involved-field and 5 (24%) with distant metastasis. No patients had ENF. We observed no severe toxicities. The 2-year overall survival (OS) rate was 78%. In the univariate analysis of OS, two factors, the maximal diameter of the metastatic LN < 25 mm and the absence of serum p53 antibodies (s-p53-Abs), were associated with a significantly better prognosis (p = 0.025 and p = 0.01, respectively). CONCLUSIONS: Involved-field CRT for postoperative solitary LN recurrence of ESCC did not cause ENF and was without severe toxicities. Two factors, a length of the metastatic LN < 25 mm and the absence of s-p53-Abs may improve the treatment outcome. Involved-field CRT is a treatment option worthy of consideration for postoperative solitary LN recurrence of ESCC.

Calculation Accuracy of Gross Tumor Volume at the Diaphragm Boundary Evaluated Using Respiratory-gated PET/CT.

OBJECTIVE: The present study aimed to clarify gross tumor volume (GTV) contouring accuracy at the diaphragm boundary using respiratory-gated PET/CT. METHODS: The lung/diaphragm boundary was simulated using a phantom containing 18F solution (10.6 kBq/mL). Tumors were simulated using spheres (diameter, 11-38 mm) containing 18F and located at the positions of the lungs and liver. The tumor background ratios (TBR) were 2, 4, and 8. The phantom was moved from the superior to inferior direction with a 20-mm motion displacement at 3.6 s intervals. The recovery coefficient (RC), volume RC (VRC), and standardized uptake value (SUV) threshold were calculated using stationary, non-gated (3D), and gated (4D) PET/CT. RESULTS: In lung cancer simulation, RC and VRC in 3D PET images were, respectively, underestimated and overestimated in smaller tumors, whereas both improved in 4D PET images regardless of tumor size and TBR. The optimal SUV threshold was about 30% in 4D PET images. In liver cancer simulation, RC and VRC were, respectively, underestimated and overestimated in smaller tumors, and when the TBR was lower, but both improved in 4D PET images when tumors were >17 mm and the TBR was >4. The optimal SUV threshold tended to depend on the TBR. CONCLUSIONS: The contouring accuracy of GTV was improved by considering TBR and using an optimal SUV threshold acquired from 4D PET images.

[Impact of the Infrared Monitor Signal Pattern on Accuracy of Target Imaging in 4-dimensional Cone-beam Computed Tomography].

To realize the high precision radiotherapy, localized radiation field of the moving target is very important, and visualization of a temporal location of the target can help to improve the accuracy of the target localization. However, conditions of the breathing and the patient's own motion differ from the situation of the treatment planning. Therefore, positions of the tumor are affected by these changes. In this study, we implemented a method to reconstruct target motions obtained with the 4D CBCT using the sorted projection data according to the phase and displacement of the extracorporeal infrared monitor signal, and evaluated the proposed method with a moving phantom. In this method, motion cycles and positions of the marker were sorted to reconstruct the image, and evaluated the image quality affected by changes in the cycle, phase, and positions of the marker. As a result, we realized the visualization of the moving target using the sorted projection data according to the infrared monitor signal. This method was based on the projection binning, in which the signal of the infrared monitor was surrogate of the tumor motion. Thus, further major efforts are needed to ensure the accuracy of the infrared monitor signal.

Radiation Therapy for Sister Mary Joseph's Nodule: A Review.

Purpose: Umbilical metastasis, known as Sister Mary Joseph's nodule (SMJN), is a manifestation of advanced malignant disease. Patients with SMJN usually require supportive care or palliative systemic chemotherapy. However, with the increasing number of older and infirm patients, radiation therapy for SMJN is needed more frequently. Therefore, we conducted this review to provide insights into radiation treatment for this rare condition. Methods and Materials: We searched PubMed on October 16, 2022, and obtained 275 articles that described SMJN or metastatic tumors within or near the umbilicus, as well as 255 case reports or case series (298 patients) and 20 reviews, original articles, or other study types, 1 of which also described a case. Results: The prognosis of patients with SMJN is extremely poor. However, some patients can survive for more than 2 years. The primary organs of the umbilical metastasis are mainly in the gastrointestinal tract, including the stomach, colon, and pancreas. In addition to these organs, the ovaries, uterine corpus, and breasts are the major organs affected in women. Metastasis may be divided into 4 types according to the tumor location and mechanism of the extension: within the umbilicus, not within although existing near or adjacent to the umbilicus, in the umbilical or paraumbilical hernia sac, and iatrogenic disease. Only 7 reports described patients who received radiation therapy in detail. The patients were divided into 2 groups: a relatively long course and high total dose (approximately 45 Gy) group, and a short course and low total dose group. Conclusions: Umbilical metastasis, known as SMJN, is a rare disease and is divided into 4 types based on the location of the disease and extent mechanism. Although the prognosis of the disease is poor, some patients survive for more than 2 years. Only 7 case reports precisely described radiation therapy. Half of the patients were treated with a short course, whereas the other half were treated with relatively high doses of up to 45 Gy.

Autologous Peripheral Blood Stem Cell Transplantation and Timing of Local Radiation Therapy in Patients With Malignant Lymphoma: Results of the Japanese Radiation Oncology Study Group Questionnaire Survey.

BACKGROUND/AIM: Malignant lymphoma (ML) including Hodgkin's lymphoma and non-Hodgkin's lymphoma is often treated with local radiation therapy (RT) in combination with autologous hematopoietic stem cell transplantation (ASCT) to prevent relapse; however, the efficacy and optimal timing of this approach is unclear. In this study, a national survey conducted by the Japanese Radiation Oncology Study Group reviewed ML cases from 2011 to 2019 to determine whether RT should be added to ASCT, focusing on the use of autologous peripheral blood stem cell transplantation (auto-PBSCT), a predominant form of ASCT. PATIENTS AND METHODS: The survey encompassed 92 patients from 11 institutes, and assessed histological ML types, treatment regimens, timing of RT relative to auto-PBSCT, and associated adverse events. RESULTS: The results indicated no significant differences in adverse events, including myelosuppression, based on the timing of RT in relation to auto-PBSCT. However, anemia was more prevalent when RT was administered before auto-PBSCT, and there was a higher incidence of neutropenia recovery delay in patients receiving RT after auto-PBSCT. CONCLUSION: This study provides valuable insights into the variable practices of auto-PBSCT and local RT in ML treatment, emphasizing the need for optimized timing of these therapies to improve patient outcomes and reduce complications.

Efficacy and safety of FDG-PET for determining target volume during intensity-modulated radiotherapy for head and neck cancer involving the oral level.

PURPOSE: To determine the efficacy and safety of target volume determination by 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) for intensity-modulated radiation therapy (IMRT) for locally advanced head and neck squamous cell carcinoma (HNSCC) extending into the oral cavity or oropharynx. METHODS: We prospectively treated 10 consecutive consenting patients with HNSCC using IMRT, with target volumes determined by PET-CT. Gross tumor volume (GTV) and clinical target volume (CTV) at the oral level were determined by two radiation oncologists for CT, magnetic resonance imaging (MRI), and PET-CT. Differences in target volume (GTVPET, GTVCT, GTVMRI, CTVPET, CTVCT, and CTVMRI) for each modality and the interobserver variability of the target volume were evaluated using the Dice similarity coefficient and Hausdorff distance. Clinical outcomes, including acute adverse events (AEs) and local control were evaluated. RESULTS: The mean GTV was smallest for GTVPET, followed by GTVCT and GTVMRI. There was a significant difference between GTVPET and GTVMRI, but not between the other two groups. The interobserver variability of target volume with PET-CT was significantly less than that with CT or MRI for GTV and tended to be less for CTV, but there was no significant difference in CTV between the modalities. Grade ≤ 3 acute dermatitis, mucositis, and dysphagia occurred in 55%, 88%, and 22% of patients, respectively, but no grade 4 AEs were observed. There was no local recurrence at the oral level after a median follow-up period of 37 months (range, 15-55 months). CONCLUSIONS: The results suggest that the target volume determined by PET-CT could safely reduce GTV size and interobserver variability in patients with locally advanced HNSCC extending into the oral cavity or oropharynx undergoing IMRT. Trial registration UMIN, UMIN000033007. Registered 16 jun 2018, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037631.

Parg deficiency confers radio-sensitization through enhanced cell death in mouse ES cells exposed to various forms of ionizing radiation.

Poly(ADP-ribose) glycohydrolase (Parg) is the main enzyme involved in poly(ADP-ribose) degradation. Here, the effects of Parg deficiency on sensitivity to low and high linear-energy-transfer (LET) radiation were investigated in mouse embryonic stem (ES) cells. Mouse Parg(-/-) and poly(ADP-ribose) polymerase-1 deficient (Parp-1(-/-)) ES cells were used and responses to low and high LET radiation were assessed by clonogenic survival and biochemical and biological analysis methods. Parg(-/-) cells were more sensitive to γ-irradiation than Parp-1(-/-) cells. Transient accumulation of poly(ADP-ribose) was enhanced in Parg(-/-) cells. Augmented levels of phosphorylated H2AX (γ-H2AX) from early phase were observed in Parg(-/-) ES cells. The induction level of p53 phophorylation at ser18 was similar in wild-type and Parp-1(-/-) cells and apoptotic cell death process was mainly observed in the both genotypes. These results suggested that the enhanced sensitivity of Parg(-/-) ES cells to γ-irradiation involved defective repair of DNA double strand breaks. The effects of Parg and Parp-1 deficiency on the ES cell response to carbon-ion irradiation (LET13 and 70 keV/µm) and Fe-ion irradiation (200 keV/µm) were also examined. Parg(-/-) cells were more sensitive to LET 70 keV/µm carbon-ion irradiation than Parp-1(-/-) cells. Enhanced apoptotic cell death also accompanied augmented levels of γ-H2AX in a biphasic manner peaked at 1 and 24h. The induction level of p53 phophorylation at ser18 was not different between wild-type and Parg(-/-) cells. The augmented level of poly(ADP-ribose) accumulation was noted after carbon-ion irradiation compared to γ-irradiation even in the wild-type cells. An enhanced poly(ADP-ribose) accumulation was further observed in Parg(-/-) cells. Both Parg(-/-) cells and Parp-1(-/-) cells did not show sensitization to Fe-ion irradiation. Parg deficiency sensitizes mouse ES cells to a wide therapeutic range of LET radiation through the effects on DNA double strand break repair responses and enhanced cell death.

Relationship between cognitive impairment and white-matter alteration in Parkinson's disease with dementia: tract-based spatial statistics and tract-specific analysis.

OBJECTIVES: We investigated the relationship between white-matter alteration and cognitive status in Parkinson's disease (PD) with and without dementia by using diffusion tensor imaging. METHODS: Twenty PD patients, 20 PDD (Parkinson's disease with dementia) patients and 20 age-matched healthy controls underwent diffusion tensor imaging. The mean diffusivity and fractional anisotropy (FA) map of each patient group were compared with those of the control group by using tract-based spatial statistics. Tractography images of the genu of the corpus callosum fibre tracts were generated, and mean diffusivity and FA were measured. RESULTS: FA values in many major tracts were significantly lower in PDD patients than in control subjects; in the prefrontal white matter and the genu of the corpus callosum they were significantly lower in PDD patients than in PD patients. There was a significant correlation between the Mini-Mental State Examination (MMSE) scores and the FA values of the prefrontal white matter and the genu of the corpus callosum in patients with PD. CONCLUSIONS: Our study shows a relationship between cognitive impairment and alteration of the prefrontal white matter and genu of the corpus callosum. These changes may be useful in assessing the onset of dementia in PD patients. KEY POINTS: • Dementia is a common and important non-motor sign of Parkinson's disease (PD). • The neuropathological basis of dementia in PD is not clear. • DTI shows abnormalities in the prefrontal white matter in PD with dementia. • Prefrontal white matter alteration may be useful biomarker of dementia in PD.

Olfactory Sensations During Radiation Sessions: A Review.

Purpose: During radiation therapy sessions, certain patients may perceive smells, particularly in younger populations. The sense of smell generally does not interrupt treatment; hence, it has attracted limited attention from oncologists worldwide. However, in certain cases, the prevention of smell perception may be necessary when treating pediatric patients. In this regard, this study reviewed previous studies pertaining to this unusual phenomenon of smell perception during radiation sessions. Methods and Materials: A PubMed search using the terms "radi*" AND ("olfaction" OR "odor" OR "smell" OR "phantosmia") was performed, and 9 articles related to this sensation were identified. Furthermore, through the references in these 9 articles, 3 additional related studies were identified. Results: Perception of smell during radiation treatment sessions was first reported in 1989. This phenomenon entails the perception of a pungent, repulsive, and unpleasant smell and is generally only observed in the presence of radiation beams. Occasionally, these smell perceptions are also accompanied by visual and gustatory sensations. Patients complain about this sensation more frequently when their olfactory regions are irradiated. Nevertheless, some patients have also reported experiencing this sensation when these areas are not included in the radiation field. Although the intensity of this sensation is low, intervention is required to prevent it. The cause of this perception remains unclear and requires further investigation. Conclusions: Conclusions: During radiotherapy sessions, certain patients may perceive smells. The cause of this perception remains unclear and requires further investigation.

Dosimetric investigation of whole-brain radiotherapy with helical intensity modulated radiation therapy and volumetric modulated arc therapy for scalp sparing.

Objective: Intensity-modulated radiotherapy (IMRT) is a well-established radiotherapy technique for delivering radiation to cancer with high conformity while sparing the surrounding normal tissue. Two main purposes of this study are: (1) to investigate dose calculation accuracy of helical IMRT (HIMRT) and volumetric-modulated arc therapy (VMAT) on surface region and (2) to evaluate the dosimetric efficacy of HIMRT and VMAT for scalp-sparing in whole brain radiotherapy (WBRT). Methods: First, using a radiochromic film and water-equivalent phantom with three types of boluses (1, 3, 5 mm), calculation/measurement dose agreement at the surface region in the VMAT and HIMRT plans were examined. Then, HIMRT, 6MV-VMAT and 10MV-VMAT with scalp-sparing, and two conventional three-dimensional conformal radiotherapy plans (6MV-3DCRT and 10MV-3DCRT; as reference data) were created for 30 patients with brain metastasis (30 Gy/10 fractions). The mean dose to the scalp and the scalp volume receiving 24 and 30 Gy were compared. Results: The percentage dose differences between the calculation and measurement were within 7%, except for the HIMRT plan at a depth of 1 mm. The averaged mean scalp doses [Gy], V24Gy [%], and V30Gy [%] (1SD) for 6MV-3DCRT, 10MV-3DCRT, HIMRT, 6MV-VMAT, and 10MV-VMAT were [26.6 (1.1), 86.4 (7.3), 13.2 (4.2)], [25.4 (1.0), 77.8 (7.5), 13.2 (4.2)], [23.2 (1.5), 42.8 (19.2), 0.2 (0.5)], [23.6 (1.6), 47.5 (17.9), 1.2 (1.8)], and [22.7 (1.7), 36.4 (17.6), 0.7 (1.1)], respectively. Conclusion: Regarding the dose parameters, HIMRT achieved a lower scalp dose compared with 6MV-VMAT. However, the highest ability to reduce the mean scalp dose was showed in 10MV-VMAT. Advances in knowledge: Scalp-sparing WBRT using HIMRT or VMAT may prevent radiation-induced alopecia in patients with BM.