Organ-contour-driven auto-matching algorithm in image-guided radiotherapy.

PURPOSE: This study aimed to demonstrate the potential clinical applicability of an organ-contour-driven auto-matching algorithm in image-guided radiotherapy. METHODS: This study included eleven consecutive patients with cervical cancer who underwent radiotherapy in 23 or 25 fractions. Daily and reference magnetic resonance images were converted into mesh models. A weight-based algorithm was implemented to optimize the distance between the mesh model vertices and surface of the reference model during the positioning process. Within the cost function, weight parameters were employed to prioritize specific organs for positioning. In this study, three scenarios with different weight parameters were prepared. The optimal translation and rotation values for the cervix and uterus were determined based on the calculated translations alone or in combination with rotations, with a rotation limit of ±3°. Subsequently, the coverage probabilities of the following two planning target volumes (PTV), an isotropic 5 mm and anisotropic margins derived from a previous study, were evaluated. RESULTS: The percentage of translations exceeding 10 mm varied from 9% to 18% depending on the scenario. For small PTV sizes, more than 80% of all fractions had a coverage of 80% or higher. In contrast, for large PTV sizes, more than 90% of all fractions had a coverage of 95% or higher. The difference between the median coverage with translational positioning alone and that with both translational and rotational positioning was 1% or less. CONCLUSION: This algorithm facilitates quantitative positioning by utilizing a cost function that prioritizes organs for positioning. Consequently, consistent displacement values were algorithmically generated. This study also revealed that the impact of rotational corrections, limited to ±3°, on PTV coverage was minimal.

The IGF-Independent Role of IRS-2 in the Secretion of MMP-9 Enhances the Growth of Prostate Carcinoma Cell Line PC3.

Insulin receptor substrate-2 (IRS-2), a substrate of the insulin-like growth factor (IGF)-I receptor, is highly expressed in the prostate cancer cell line, PC3. We recently demonstrated that extracellular signal-regulated kinase (Erk1/2), a kinase downstream of IGF signaling, is activated in PC3 cells under serum starvation, and this activation can be inhibited by IRS-2 knockdown. Here, we observed that adding an IGF-I-neutralizing antibody to the culture medium inhibited the activation of Erk1/2. Suppression of Erk1/2 in IRS-2 knockdown cells was restored by the addition of a PC3 serum-free conditioned medium. In contrast, the IRS-2-silenced PC3 conditioned medium could not restore Erk1/2 activation, suggesting that IRS-2 promotes the secretion of proteins that activate the IGF signaling pathway. Furthermore, gelatin zymography analysis of the conditioned medium showed that matrix metalloproteinase-9 (MMP-9) was secreted extracellularly in an IRS-2 dependent manner when PC3 was cultured under serum starvation conditions. Moreover, MMP-9 knockdown suppressed Erk1/2 activation, DNA synthesis, and migratory activity. The IRS-2 levels were positively correlated with Gleason grade in human prostate cancer tissues. These data suggest that highly expressed IRS-2 activates IGF signaling by enabling the secretion of MMP-9, which is associated with hyperproliferation and malignancy of prostate cancer cell line, PC3.

Levodopa-Carbidopa Intestinal Gel Injection for Patient with Severe Parkinson's Disease Followed by Total Hip Arthroplasty: A Case Report and Literature Review.

BACKGROUND: Patients with Parkinson's disease have a high dislocation rate after total hip arthroplasty (THA). This study describes a case with severe Parkinson's disease who developed rapidly destructive coxarthrosis (RDC) and underwent THA using a dual mobility cup after a levodopa-carbidopa intestinal gel (LCIG) infusion. CASE PRESENTATION: The patient is a 59-year-old female with a ten-year history of Parkinson's disease, which was first treated with oral levodopa. The patient developed RDC of the right hip joint. However, THA was difficult owing to Parkinson's disease and its treatment side effects, such as wearing-off, dyskinesia, and freezing of the gait, Thus, LCIG was initiated, and improvement in wearing-off and dyskinesia was observed. Two months after the LCIG therapy, the disease was controlled well. THA was subsequently performed using a dual mobility cup to prevent postoperative dislocation. Postoperatively, LCIG therapy was continuously administered to carefully manage the disease, which was controlled well with no increase in wearing-off and dyskinesia after surgery. At 1 year after surgery, the walking speed, stride length, and the Harris hip score improved compared to preoperatively. The UPDRS III motor score improved to eight without signs of wearing-off or dyskinesia. The Hoehn-Yahr scale was II in the "on" period and remained unchanged 1 year after surgery. The patient could walk without a cane and had satisfactory functional outcomes. CONCLUSION: This case proved that LCIG treatment performed preoperatively, followed by THA using a dual mobility cup, and strict management of Parkinson's disease could result in a satisfactory clinical course without recurrence of wearing-off and dyskinesia. Similar procedures may benefit other patients with Parkinson's disease who have previously been deemed unsuitable for THA.

Three-dimensional assessment of interfractional cervical and uterine motions using daily magnetic resonance images to determine margins and timing of replanning.

PURPOSE: This study was conducted to determine the margins and timing of replanning by assessing the daily interfractional cervical and uterine motions using magnetic resonance (MR) images. METHODS: Eleven patients with cervical cancer, who underwent intensity-modulated radiotherapy (IMRT) in 23-25 fractions, were considered in this study. The daily and reference MR images were converted into three-dimensional (3D) shape models. Patient-specific anisotropic margins were calculated from the proximal 95% of vertices located outside the surface of the reference model. Population-based margins were defined as the 90th percentile values of the patient-specific margins. The expanded volume of interest (expVOI) for the cervix and uterus was generated by expanding the reference model based on the population-based margin to calculate the coverage for daily deformable mesh models. For comparison, expVOIconv was generated using conventional margins: right (R), left (L), anterior (A), posterior (P), superior (S), and inferior (I) were (5, 5, 15, 15, 10, 10) and (10, 10, 20, 20, 15, 15) mm for the cervix and uterus, respectively. Subsequently, a replanning scenario was developed based on the cervical volume change. ExpVOIini and expVOIreplan were generated before and after replanning, respectively. RESULTS: Population-based margins were (R, L, A, P, S, I) of (7, 7, 11, 6, 11, 8) and (14, 13, 27, 19, 15, 21) mm for the cervix and uterus, respectively. The timing of replanning was found to be the 16th fraction, and the volume of expVOIreplan decreased by >30% compared to that of expVOIini . However, margins cannot be reduced to ensure equivalent coverage after replanning. CONCLUSION: We determined the margins and timing of replanning through detailed daily analysis. The margins of the cervix were smaller than conventional margins in some directions, while the margins of the uterus were larger in almost all directions. A margin equivalent to that at the initial planning was required for replanning.

Impact of interstitial lung abnormality on survival after adjuvant durvalumab with chemoradiotherapy for locally advanced non-small cell lung cancer.

INTRODUCTION: Concurrent chemoradiotherapy (CCRT) has been the standard of care for patients with locally advanced non-small cell lung cancer (LA-NSCLC). BACKGROUND AND PURPOSE: The results of the PACIFIC trial established the use of consolidative durvalumab after concurrent chemoradiotherapy (CCRT) as the standard of care for patients with locally advanced non-small cell lung cancer (LA-NSCLC). A subgroup analysis of the PACIFIC trial reported a better progression-free survival (PFS) in Asians. Although real-world data on LA-NSCLC patients who received CCRT plus durvalumab have been reported, there have been few large-scale reports on Asians. In this study, we investigated prognostic factors in the largest real-world data set in Asia of only Japanese LA-NSCLC patients treated with CCRT plus durvalumab. MATERIALS AND METHODS: One hundred and thirteen LA-NSCLC patients who received definitive CCRT and consolidative durvalumab at our institution between May 2018 and April 2021 were analyzed. Overall survival (OS), cause-specific survival (CSS), PFS, distant metastasis-free survival (DMFS), and in-field progression-free survival (IFPFS) were investigated as treatment outcomes using competing risk analyses. RESULTS: During a median follow-up of 24 months (range, 5-47) after the initiation of durvalumab therapy, 31 patients died, of whom 23 died of lung cancer. In the multivariate analysis, the pretreatment factors that correlated with OS were ILA scores, adenocarcinoma, and performance status at the initiation of durvalumab. Furthermore, ILA score and programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 1 % were significantly correlated with CSS, and PD-L1 TPS ≥ 1 % was significantly correlated with PFS and IFPFS. CONCLUSION: Pretreatment ILA, adenocarcinoma, and performance status may have an impact on OS of LA-NSCLC patients receiving CCRT plus durvalumab.

Clinical significance of local control of primary tumour in definitive radiotherapy for scalp angiosarcomas.

INTRODUCTION: Scalp angiosarcoma is a rare and aggressive cancer. Definitive radiotherapy is a treatment option for localised scalp angiosarcoma patients. Although definitive surgical resection reportedly prolongs overall survival (OS), whether initial local treatment effect affects OS when definitive radiotherapy is administered is unclear. Therefore, this study analysed whether local recurrence within 6 months of irradiation correlates with OS and cancer-specific survival (CSS). Furthermore, how local control affects patients' quality of life was investigated. MATERIALS AND METHODS: Thirty-one localised scalp angiosarcoma patients who had received definitive radiotherapy at our institution between October 2010 and July 2021 were analysed retrospectively. The most commonly used dose fractionation was 70 Gy in 35 fractions (83.9%). Local recurrence within 6 months of radiotherapy and other clinical factors were examined in univariate and subsequent multivariate analyses for correlation with OS and CSS. RESULTS: The median follow-up period was 16 months (range, 6-45 months). Local recurrence was detected in 16 patients (51.6%), 12 of whom had recurrence within 6 months. In multivariate analyses, the presence of local recurrence within 6 months of radiotherapy was significantly associated with OS and CSS (p = 0.003, 0.0001, respectively). Ten of the 16 patients with local recurrence had severe symptoms such as bleeding, pain, difficulty opening the eye and malodour. CONCLUSIONS: The initial local treatment effect was significantly associated with OS and CSS after definitive radiotherapy. Furthermore, local recurrence after radiotherapy resulted in a variety of symptoms, including bleeding and pain, which reduced the patient's quality of life.

Is it time to modify the Japanese Uterine Cervical Cancer Guidelines to recommend a higher dose for radio-resistant tumors?

Compared with the European or the United States' uterine cervical cancer management guidelines, which aim to deliver >85 Gy EQD2 (the equivalent effective dose in 2 Gy per fraction) to the high-risk clinical target volume (CTVHR) D90 (minimal dose of 90% of the CTVHR), the dose goal of the corresponding Japanese guidelines does not recommend delivering such a high dose to the CTVHR D90. Subsequently, while the rate of late radiation-induced toxicities is reported to be much lower in the Japanese schedule, the local control rate is relatively inferior to that of clinical results reported by the IntErnational study on MRI-guided BRAchytherapy in CErvical cancer study (EMBRACE-I) in which the dose goal for CTVHR D90 was >85 Gy and showed >90% local control regardless of tumor stage. In daily clinical practice, patients with residual disease supposedly due to insufficient total dose delivery are occasionally referred to our hospital for the possibility of re-irradiation, which is not usually recommended because the risk of late severe radiation-induced toxicity is high. In this report, the authors hope to raise a discussion in our community about modifying our treatment guidelines to recommend a higher dose at least for patients with poor response.

Clinical impact of p16 positivity in nasopharyngeal carcinoma.

Purpose: The clinical characteristics and prognosis of HPV-related nasopharyngeal cancer (NPC) remain controversial. The relationship between p16 status and outcome was retrospectively investigated in the NPC patients. Materials and Methods: Between May 2009 and May 2019, 81 NPC patients who received definitive radiation therapy, in a hospital in Japan, were identified and the prognosis was investigated. p16, p53, and Epstein-Barr virus (EBV) status were assessed. Also, circumferential tumor extent in the nasopharyngeal cavity was assessed on a 5-point scale. Results: Nine and 72 patients were p16-positive and p16-negative, respectively. Fewer patients were EBV-encoded RNA in situ hybridization (EBER-ISH)-positive in the p16-positive group than in the p16-negative group (p < .01). Seventy-five patients were nonkeratinizing NPCs, and six patients were keratinizing NPCs. There were two p16-positive patients among the keratinizing NPCs.The mean circumferential tumor extent scores of 16-positive and p16-negative NPCs were 4.2 and 3.2, respectively with a statistically significant difference (p = .02). Two-year progression-free survival (PFS) of p16-positive and p16-negative patients undergoing chemoradiation therapy were 100% and 69%, respectively (p = .13). Conclusion: In this study conducted in Japan, p16-positive NPC patients are minor but not very low, and the proportion of keratinizing NPCs was small. p16-positive NPCs were seen both in keratinizing and nonkeratinizing NPCs. P16-positive NPC had a tendency of better PFS than p16-negative NPC. This better prognosis might be due to the higher radiosensitivity of the p16-positive cell. Additionally, p16-positive NPCs seemed to spread more extensively in circumference along the nasopharyngeal mucosa than p16-negative NPCs.

Effect of Hyaluronate Acid Injection on Dose-Volume Parameters in Brachytherapy for Cervical Cancer.

Purpose: Hyaluronate gel has been injected as a spacer into the rectovaginal fossa and vesicouterine fossa during brachytherapy for patients with cervical cancer at our institution. The effect of hyaluronate gel injection (HGI) on dose-volume parameters was investigated in this study. Methods and Materials: Between July 2008 to January 2020, a total of 104 patients (non-HGI group: 52 patients; HGI group: 52 patients) who underwent curative radiation therapy for cervical cancer were selected. The total doses of external beam radiation therapy and brachytherapy for high-risk clinical target volume (CTVHR) D90, bladder D2cc, and rectal D2cc were converted to the equivalent dose in 2 Gy fractions (EQD2) and were analyzed for association with HGI. Results: Median CTVHR D90 (EQD2) in the non-HGI group was 76.0 Gy (63.7-99.5 Gy), and in the HGI group it was 79.4 Gy (52.6-97.5 Gy) (P = .017). The median bladder D2cc and rectal D2cc (EQD2) were 62.9 Gy and 56.0 Gy in the non-HGI group and 63.7 Gy and 54.8 Gy in the HGI group, which had no significant difference. Conclusions: In cases with HGI, a significant CTVHR D90 dose increase was obtained with sufficient bladder and rectal doses suppression.

Salvage image-guided freehand interstitial brachytherapy for pelvic sidewall recurrence after hysterectomy for uterine malignancies.

PURPOSE: Pelvic sidewall recurrence after hysterectomy for uterine malignances has a poor prognosis, and the salvage therapy for this type of recurrence is still challenging. The purpose of this study was to investigate the efficacy of freehand high-dose-rate interstitial brachytherapy (HDR-ISBT) through the perineum using transrectal ultrasonography for this disease. METHODS AND MATERIALS: We retrospectively evaluated 42 patients with pelvic sidewall recurrence after hysterectomy for uterine cervical and endometrial cancers. We investigated patients' characteristics, the 2-year local control and survival rates, and late adverse events of the rectum and bladder. RESULTS: The 2-year overall survival, local control, and progression-free survival rates were 73.7% (95% confidence interval [CI], 60.8-89.3%), 69.4% (95% CI, 55.4-80.1%), and 37.3% (95% CI, 24.6-56.5%), respectively. In Cox multivariate analysis, tumor size at recurrence (<45 mm vs. ≥45 mm) (p = 0.04) and disease-free periods after hysterectomy (<10 months vs. ≥10 months) (p < 0.01) were significant prognostic factors for overall survival. Lymph node metastasis at recurrence (p < 0.01) was also a significant prognostic factor for progression-free survival. Three patients experienced Grade 3-4 late proctitis (7%). CONCLUSIONS: Transperineal freehand salvage HDR-ISBT using transrectal ultrasonography was demonstrated to be a curative treatment option for patients with pelvic sidewall recurrence following hysterectomy. Based on the findings of this study, we emphasize the importance of HDR-ISBT for pelvic sidewall recurrence.

Non-Robustness of Ang's Risk Classification in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma in Japanese Patients.

BACKGROUND: Validity of the risk classification by Ang for human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) remains to be studied in the patients treated by modalities other than chemoradiotherapy and in Japanese patients. MATERIALS AND METHODS: Between 2010 and 2018, 122 patients with HPV-related OPSCC in stages III and IV by the TNM classification 7th edition (TNM-7) were treated curatively at a single institution in Japan. The median age was 62.7 years. Over 50% of the patients underwent surgery with or without adjuvant therapy. The influence of multiple factors on survival was analyzed. RESULTS: The amount of smoking dichotomized at 10 pack-year, which was used in Ang's risk classification, was not predictive of prognosis, and Ang's risk classification was not significantly influential on prognosis in multivariate analysis. In the patients treated with definitive radiation therapy, Ang's risk classification was not predictive of the prognosis in univariate analysis. The impact of smoking was significant only in the patients undergoing the definitive operation. CONCLUSIONS: Ang's risk classification was not robust in predicting the prognosis of general Japanese HPV-related OPSCC patients. The amount of smoking might have different prognostic influences depending on the therapeutic method.

Scalp angiosarcoma treated with linear accelerator-based boron neutron capture therapy: A report of two patients.

PURPOSE: This study reports the first-in-human use of a linear accelerator-based boron neutron capture therapy (BNCT) system and the first treatment of patients with scalp-angiosarcoma with accelerator-based BNCT. PATIENTS AND METHODS: A single-center open-label phase I clinical trial has been conducted using the system since November 2019. Patients with a localized node-negative scalp-angiosarcoma along with the largest diameter of the tumor ≤ 15 cm who refused primary surgery and chemotherapy were enrolled. After administration of boronophenylalanine (BPA), a single treatment of BNCT with the maximum dose delivered to the skin being 12 Gy-Eq was performed. The safety and effectiveness of accelerator-based BNCT therapy for localized scalp angiosarcoma were evaluated. RESULTS: Scalp-angiosarcoma of the two patients did not develop the dose-limiting toxicity in the clinical trial. They reached CR within half a year and did not exhibit in-field failure 20 months after BNCT without any severe treatment-related adverse events. Although a grade 3 adverse event of an asymptomatic but increased serum amylase level was noted in both patients, it relieved without any treatment. Additionally, no severe acute dermatitis was observed for both patients, which is typically seen with conventional primary radiotherapy. CONCLUSIONS: It was suggested that BNCT would be a promising treatment modality for scalp-angiosarcoma, which is difficult to treat.

Prognostic factor analysis of definitive radiotherapy using intensity-modulated radiation therapy and volumetric modulated arc therapy with boluses for scalp angiosarcomas.

Cutaneous angiosarcomas is a rare cancer with poor prognoses. The common radiotherapy techniques that have been reported so far are two pairs of lateral X-ray and electron fields. However, it is quite difficult to irradiate scalp angiosarcomas (SAs) homogeneously with this technique. In this study, safety, effectiveness, and risk factors were assessed for localized SAs ≥ 5 cm treated with intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) with boluses. Sixty-eight angiosarcoma patients who had received radiotherapy in our institution between January 2007 and November 2020 were retrieved from our radiotherapy database. Of these patients, 27 localized SA patients were included in the retrospective analysis. The 2-year overall survival, local progression-free rate, and distant metastases-free survival were 41.8%, 48.4%, and 33.1%. All the patients experienced acute radiation dermatitis ≥ grade 2, with18 (66.7%) ≥ grade 3. No nodule lesion was a significant unfavorable predictive factor of acute radiation dermatitis ≥ grade 3. Tumor bleeding at the initiation of radiotherapy and tumor invasion to the face were significant predictive factors of overall survival, and tumor bleeding at the initiation of radiotherapy was also a significant predictive factor of local progression-free rate.

High-Dose-Rate Interstitial Brachytherapy for Deeply Situated Gynecologic Tumors Guided by Combination of Transrectal and Transabdominal Ultrasonography: A Technical Note.

BACKGROUND AND PURPOSE: High-dose-rate interstitial brachytherapy (HDR-ISBT) is recommended to obtain a better local tumor control for uterine cancer patients in specific situations such as bulky lesions, an extension to the lateral parametrium, or tumors with irregular shapes. Our group uses real-time transrectal ultrasonography (TRUS) to guide freehand interstitial needle insertion. Occasionally, target tumors locate deeper beyond the rectum and cannot be visualized by TRUS. CT can guide needles to deeply located tumors, but in such cases, repeated image obtainment is required to achieve ideal needle localization. In this report, we present nine cases of patients who underwent HDR-ISBT for deeply situated tumors guided by a combination of transrectal and transabdominal ultrasonography (TR/TA-US). MATERIAL AND METHODS: Nine uterine cancer patients whose tumors were located deeper than the reach of TRUS and underwent HDR-ISBT guided by TR/TA-US were presented. All nine cases had no distal organ metastasis and underwent external beam radiation therapy (EBRT) to the pelvic region for 45-50.4 Gy in 25-28 fractions followed by boost HDR-ISBT for deeply situated tumors guided by TR/TA-US. RESULTS: There were seven cervical cancer and two endometrial cancer patients: six with extensive uterine corpus invasion, one cervical cancer with massive pelvic lymph node metastasis, one cervical cancer with postoperative pelvic recurrence, and one with left ovarian direct tumor invasion. The median follow-up period was 15 months (range 3-28 months). The average clinical target volume at the time of first HDR-ISBT was 131 ml (range 44-335 ml). The linear distance from the vaginal entrance to the deepest part of the tumor at first time brachytherapy of nine cases was 14.0 (9.0-17.0) cm. HDR-ISBT dose fractionation was 24-30 Gy in four or five fractions. Seven out of nine cases had no local recurrence in the follow-up period. One had local in-field recurrence 25 months after HDR-ISBT. Another case with carcinosarcoma could not obtain local control and underwent salvage hysterectomy for a residual uterine tumor 11 months after HDR-ISBT. Four cases had extra-field recurrence in lymph nodes or distant organs. CONCLUSIONS: In brachytherapy for gynecologic malignancies, deeply situated tumors located out of reach of TRUS may obtain favorable local control by HDR-ISBT guided with TR/TA-US.

The use of hyperbaric oxygen to treat actinic rectal fistula after SpaceOAR use and radiotherapy for prostate cancer: a case report.

BACKGROUND: In definitive radiation therapy for prostate cancer, the SpaceOAR® System, a hydrogel spacer, is widely used to decrease the irradiated dose and toxicity of rectum. On the other hand, periprostatic abscesses formation and rectal perforation are known as rare adverse effects of SpaceOAR. Nevertheless, there is a lack of reports clarifying the association between aggravation of abscesses and radiation therapy, and hyperbaric oxygen therapy (HBOT) is effective for a peri-SpaceOAR abscess and rectal perforation. CASE PRESENTATION: We report a case of a 78-year-old high-risk prostate cancer patient. After SpaceOAR insertion into the correct space, he started to receive external beam radiation therapy (EBRT). He developed a fever, perineal pain and frequent urination after the completion of EBRT, and the magnetic resonance imaging (MRI) revealed a peri-SpaceOAR abscess. Scheduled brachytherapy was postponed, administration of antibiotics and opioid via intravenous drip was commenced, and transperineal drainage was performed. After the alleviation of the abscess, additional EBRT instead of brachytherapy was performed with MRI-guided radiation therapy (MRgRT). On the last day of the MRgRT, perineal pain reoccurred, and MRI and colonoscopy detected the rectal perforation. He received an intravenous antibiotics drip and HBOT, and fully recovered from the rectal perforation. CONCLUSIONS: Our report indicates that EBRT can lead to a severe rectum complication by causing inflammation for patients with a peri-SpaceOAR abscess. Furthermore, HBOT was effective for the peri-SpaceOAR abscess and rectal perforation associated with EBRT.

Clinical outcomes of hypofractionated image-guided multifocal irradiation using volumetric-modulated arc therapy for brain metastases.

Volumetric-modulated arc therapy (VMAT) can be used to design hypofractionated radiotherapy treatment plans for multiple brain metastases. The purpose of this study was to evaluate treatment outcomes of hypofractionated image-guided multifocal irradiation using VMAT (HFIGMI-VMAT) for brain metastases. From July 2012 to December 2016, 67 consecutive patients with 601 brain metastases were treated with HFIGMI-VMAT at our institution. The prescribed dose was 50 Gy to a 95% volume of the planning target volume in 10 fractions. Fifty-five of the 67 patients had non-small-cell lung cancer, and the remaining 12 had other types of cancer. The median number of brain metastases was five, and the median maximum diameter was 1.2 cm. The median duration of follow-up was 12.0 months (range, 1.9-44.8 months), and the median survival time 18.7 months. Four patients with six lesions had local recurrences. The local control rate in the 64 assessed patients was 98.4% and 95.3% at 6 and 12 months, respectively (three died before assessment). The local control rate for the 572 assessed lesions was 99.8% and 99.3% at 6 and 12 months, respectively. Thirty-nine patients developed distant brain metastases, the distant brain control rate being 59.7% and 40.5% at 6 and 12 months, respectively. Acute toxicities were generally mild (Grade 1-2). Three patients (4.5%) developed radiation necrosis requiring corticosteroid therapy. The HFIGMI-VMAT technique with flat dose delivery was well tolerated and achieved excellent local control. This technique is a promising treatment option for patients with multiple and large brain metastases.

Increased (18)F-fluorodeoxyglucose accumulation in bilateral adrenal glands of the patients suffering from vasovagal reaction due to blood vessel puncture.

OBJECTIVE: The purpose of the study was to evaluate the hypothesis that patients having a vasovagal reaction (VVR) after blood vessel puncture show increased FDG accumulation in bilateral adrenal glands. METHODS: Over the past 8 years, 26 patients experienced a VVR after blood vessel puncture following intra-venous injection of FDG at our institution. Of the 26 patients, 16 underwent multiple-occasion FDG-PET/CT scans while suffering a VVR at only one examination. All 16 patients had no morphological abnormality in the adrenal glands on FDG-PET/CT and follow-up examination. For the 16, we retrospectively reviewed the FDG-PET/CT scan with respect to the adrenal glands and compared the result to that for the FDG-PET/CT scan of the same patient when there was no VVR event. We used both visual analysis and semi-quantitative analysis employing either maximum standardized uptake value (SUVmax) or adrenal-to-liver (A/L) SUVmax ratio. RESULTS: On visual analysis of the FDG-PET/CT with VVR, accumulations in both of the adrenal glands was judged positive, defined as higher than the hepatic accumulation, in 84 % of the cases. The SUVmax in the right adrenal gland was 2.79 ± 0.69 with VVR and 1.92 ± 0.33 without VVR; this value in the left adrenal gland was 3.07 ± 0.71 with VVR and 2.05 ± 0.39 without. Mean SUVmax of both adrenal glands was 2.93 ± 0.66 with VVR and 1.98 ± 0.35 without. The A/L SUVmax ratio in the right adrenal gland was 1.02 ± 0.26 with VVR and 0.69 ± 0.11 without; this value in the left was 1.11 ± 0.23 with VVR and 0.74 ± 0.15 without. The mean A/L SUVmax ratio of both adrenal glands was 1.06 ± 0.24 with VVR and 0.72 ± 0.13 without. Each parameter with VVR was significantly higher than that without. For the two adrenal glands, the mean SUVmax with VVR was 48 % higher than that without VVR. CONCLUSIONS: We confirmed the hypothesis that patients having a VVR after blood vessel puncture show increased FDG accumulation in their bilateral adrenal glands. This may reflect hyper-metabolism of the adrenal glands in synthesizing and secreting catecholamine.

The Association Between Pain and Quality of Life for Patients With Cancer in an Outpatient Clinic, an Inpatient Oncology Ward, and Inpatient Palliative Care Units.

PURPOSE: This study was designed to clarify the association between pain and quality of life (QOL) of Japanese patients with cancer using a cancer-specific QOL scale (European Organization for Research and Treatment of Cancer [EORTC] QLQ-C15-PAL) in 3 care settings (outpatient, inpatient, and palliative care units [PCUs]). METHODS: We examined the above-mentioned purpose for the total of 404 patients. RESULTS: In outpatients, physical, emotional functioning (EF), and global health status/QOL (QL item) were significantly correlated with average pain, and their correlation coefficients were -0.37 to -0.46 (P < .0001). In inpatients, they were -0.33 (P = .006), -0.26 (P = .030), and -0.31 (P = .012). In the PCU patients, they were -0.12 (P = .316), -0.30 (P = .009), and -0.28 (P = .015). CONCLUSION: Patients' pain had an association with physical and emotional QOL, and the association was smaller in the PCU patients than the others.

Evaluation of ABCG2 and p63 expression in canine cornea and cultivated corneal epithelial cells.

OBJECTIVE: To examine the expressions of ABCG2 and p63 in canine corneal epithelia and to evaluate their significance in corneal regeneration. PROCEDURES: Canine corneal and limbal epithelial cells were obtained from five healthy beagle dogs. We analyzed the morphological properties of cultivated limbal and corneal epithelial cells. We compared the expressions of ABCG2 and p63 in the limbus and central cornea by immunohistochemistry and real-time quantitative PCR. We analyzed the expression of these markers in cultivated cells by immunocytochemistry and real-time quantitative PCR. RESULTS: The limbal epithelial cells were smaller and proliferated more rapidly than the corneal epithelial cells in primary cultures. The corneal cells failed to be subcultured, whereas the limbal cells could be subcultured with increasing cell size. ABCG2 was localized in the basal layer of the limbal epithelium, and p63 was widely detected in the entire corneal epithelia. ABCG2 expression was significantly higher, and p63 was slightly higher in the limbus compared with the central cornea. ABCG2 was detected only in limbal cells in primary culture, not in corneal cells or passaged limbal cells. p63 was detected in both limbal and corneal cells and decreased gradually in the limbal cells with the cell passages. CONCLUSIONS: ABCG2 was localized in canine limbal epithelial cells, and p63 was widely expressed in canine corneal epithelia. ABCG2 and p63 could prove to be useful markers in dogs for putative corneal epithelial stem cells and for corneal epithelial cell proliferation, respectively.

Lymphangiosarcoma with systemic metastases in a Japanese domestic cat.

A 4-year-2-month-old female Japanese domestic cat was diagnosed with lymphangiosarcoma through tissue biopsy of an amputated leg. Two months later, the cat was euthanized, and postmortem findings revealed edema, and bruising at the caudal region of the trunk, pulmonary hemorrhage, pulmonary nodules and mediastinal lymphadenopathy. Microscopically, neoplastic tissues were observed in the dermis and subcutis of the trunk, lung, mediastinal lymph nodes, diaphragm, omentum and mesentery. The tumor cells were spindle to polygonal-shaped with nuclear pleomorphism aligning along pre-existing collagen bundles and forming irregular vascular channels in which the erythrocytes were rarely observed. These cells were immunopositive for vimentin, von Willebrand factor and CD31. Based on the histopathological and immunohistochemical features, the neoplasia was diagnosed as lymphangiosarcoma with systemic metastases.