Daily irradiation versus irradiation at two- to three-day intervals in stereotactic radiotherapy for patients with 1-5 brain metastases: study protocol for a multicenter open-label randomized phase II trial.

BACKGROUND: Radiobiological daily changes within tumors are considered to be quite different between stereotactic radiotherapy (SRT) (e.g., 50 Gy in 4 fractions) and conventional radiotherapy (e.g., 60 Gy in 30 fractions). We aim to assess the optimal interval of irradiation in SRT and compare outcomes of daily irradiation with irradiation at two- to three-day intervals in SRT for patients with one to five brain metastases (BM). METHODS: This study is conducted as a multicenter open-label randomized phase II trial. Patients aged 20 or older with one to five BM, less than 3.0 cm diameter, and Karnofsky Performance Status ≥70 are eligible. A total of 70 eligible patients will be enrolled. After stratifying by the number of BMs (1, 2 vs. 3-5) and diameter of the largest tumor (< 2 cm vs. ≥ 2 cm), we randomly assigned patients (1:1) to receive daily irradiation (Arm 1), or irradiation at two- to three-day intervals (Arm 2). Both arms are performed with total dose of 27-30 Gy in 3 fractions. The primary endpoint is an intracranial local control rate, defined as intracranial local control at initially treated sites. We use a randomized phase II screening design with a two-sided α of 0∙20. The phase II trial is positive with p < 0.20. All analyses are intention to treat. This study is registered with the UMIN-clinical trials registry, number UMIN000048728. DISCUSSION: This study will provide an assessment of the impact of SRT interval on local control, survival, and toxicity for patients with 1-5 BM. The trial is ongoing and is recruiting now. TRIAL REGISTRATION: UMIN000048728. Date of registration: August 23, 2022. https://center6.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000055515 .

Stereotactic Radiotherapy for Cervical Spinal Intramedullary Metastasis and Multiple Brain Metastases: A Case Report.

A case of cervical (C) spinal intramedullary metastasis and multiple small brain metastases from papillary thyroid carcinoma was presented. Spinal metastasis caused posterior neck and left shoulder pain, dysesthesia in both legs, and motor weakness in both legs and left arm, though the brain metastases were asymptomatic. Both the spinal and brain metastases were successfully treated by frameless stereotactic radiotherapy (SRT)/stereotactic radiosurgery (SRS). The patient's symptoms were almost entirely relieved within two months. A 76-year-old woman was diagnosed as having a thyroid tumor and lung metastasis by roentgenography and computed tomography. Biopsy of the thyroid tumor extending into the mediastinum revealed papillary thyroid carcinoma. She underwent surgical resection of thyroid with dissection of the mediastinum lymph node area. Internal oral radioisotope therapy was not effective for the multiple small lung metastases. She did well for 15 months, but later developed posterior neck and left shoulder pain and dysesthesia in the right leg and then dysesthesia and motor weakness in both legs. Then she experienced weakness in the left upper extremity. Magnetic resonance imaging (MRI) disclosed a small cervical spinal intramedullary mass lesion at the level of C6 and C7 on the left side as well as nine small brain lesions. The cervical spinal intramedullary metastatic tumor was treated by volumetric modulated arc radiotherapy (VMAT) SRT and the nine small brain metastatic tumors were treated by dynamic conformal arc (DCA) SRS uneventfully. A total dose of 39 Gy (100% dose) was delivered in 13 fractions for the spinal lesion (prescription, D95=95% dose; maximum dose=46.3 Gy). Single fraction SRS of 22 Gy (prescription, D95=100% dose) was performed for each of the nine small brain tumors. The spinal tumor was decreased in size on follow-up MRI two months after SRT. Three of the nine brain lesions had disappeared and six were decreased in size on follow-up MRI two months after SRS. Motor weakness in the left extremities and right leg was fully improved, and she could walk again without a cane within two months after SRT. She had only slight dysesthesia in the right leg, possibly due to lumbar spondylosis at the end of the six-month follow-up after SRT. The spinal tumor continued to decrease in size on follow-up MRI five months after SRT. Eight of the nine brain lesions had disappeared and one was decreased in size on follow-up MRI five months after SRS.

Clinical efficacy of alternating chemoradiotherapy by conformal radiotherapy combined with intracavitary brachytherapy for high-risk cervical cancer.

OBJECTIVE: The purpose of this study was to assess the outcome of alternating chemoradiotherapy in patients with high-risk cervical cancer. METHODS: We performed definitive alternating chemoradiotherapy in cervical cancer patients with at least one high-risk factor such as International Federation of Gynecology and Obstetrics III or IVA disease, primary tumor diameter ≥50 mm, positive pelvic node, and positive para-aortic node. Our chemoradiotherapy protocol was as follows: (i) alternating chemoradiotherapy with 5-fluorouracil and nedaplatin; (ii) whole pelvic radiotherapy with the dynamic conformal technique combined with intracavitary brachytherapy; (iii) prophylactic irradiation to the para-aortic region for International Federation of Gynecology and Obstetrics III/IVA or positive pelvic node and full-dose radiotherapy for positive para-aortic node. Between 1998 and 2010, 121 patients were treated with this protocol. RESULTS: The median follow-up period was 53.7 months (7.6-162.2). International Federation of Gynecology and Obstetrics stages were IB; (9.1%), IIA; 6 (5.0%), IIB; 53 (43.8%), IIIA; 7 (5.8%), IIIB; 37 (30.6%) and IVA; 7 (5.8%), respectively. Nodal involvement was reported in 77 patients (63.6%) at the pelvis and 25 (20.7%) at the para-aortic region. The 5-year overall survival and progression-free survival rates were 80.0 and 63.4%, respectively. Regarding Grade ≥3 late toxicities, three patients developed urinary and three developed intestinal toxicities. We encountered no treatment-related death. CONCLUSIONS: The clinical results of our alternating chemoradiotherapy protocol for high-risk cervical cancer are promising.

Preliminary analysis of risk factors for late rectal toxicity after helical tomotherapy for prostate cancer.

The purpose of this study is to examine risk factors for late rectal toxicity for localized prostate cancer patients treated with helical tomotherapy (HT). The patient cohort of this retrospective study was composed of 241 patients treated with HT and followed up regularly. Toxicity levels were scored according to the Radiation Therapy Oncology Group grading scale. The clinical and dosimetric potential factors increasing the risk of late rectal toxicity, such as age, diabetes, anticoagulants, prior abdominal surgery, prescribed dose, maximum dose of the rectum, and the percentage of the rectum covered by 70 Gy (V70), 60 Gy (V60), 40 Gy (V40) and 20 Gy (V20) were compared between ≤ Grade 1 and ≥ Grade 2 toxicity groups using the Student's t-test. Multivariable logistic regression analysis of the factors that appeared to be associated with the risk of late rectal toxicity (as determined by the Student's t-test) was performed. The median follow-up time was 35 months. Late Grade 2-3 rectal toxicity was observed in 18 patients (7.4%). Age, the maximum dose of the rectum, V70 and V60 of the ≥ Grade 2 toxicity group were significantly higher than in those of the ≤ Grade 1 toxicity group (P = 0.00093, 0.048, 0.0030 and 0.0021, respectively). No factor was significant in the multivariable analysis. The result of this study indicates that the risk of late rectal toxicity correlates with the rectal volume exposed to high doses of HT for localized prostate cancer. Further follow-up and data accumulation may establish dose-volume modeling to predict rectal complications after HT.

Preliminary results of intensity-modulated radiation therapy with helical tomotherapy for prostate cancer.

PURPOSE: We present the preliminary results of intensity-modulated radiation therapy with helical tomotherapy (HT) for clinically localized prostate cancer. METHODS: Regularly followed 241 consecutive patients, who were treated with HT between June 2006 and December 2010, were included in this retrospective study. Most patients received both relatively long-term neoadjuvant and adjuvant androgen deprivation therapy (ADT). Patients received 78 Gy in the intermediate high-risk group and 74 Gy in the low-risk group. Biochemical disease-free survival (bDFS) followed the Phoenix definition. Toxicity was scored according to the Radiation Therapy Oncology Group morbidity grading scale. RESULTS: The median follow-up time from the start date of HT was 35 months. The rates of acute Grade 2 gastro-intestinal (GI) and genitor-urinary (GU) toxicities were 11.2 and 24.5 %. No patients experienced acute Grade 3 or higher symptoms. The rates of late Grade 2 and 3 GI toxicities were 6.6 and 0.8 %, and those of late Grade 2 and 3 GU toxicities were 8.3 % and 1.2 %. No patients experienced late Grade 4 toxicity. The 3-year bDFS rates for low, intermediate, and high-risk group patients were 100, 100, and 95.8 %, respectively. We observed clinical relapse in two high-risk patients, resulting in a 3-year clinical DFS of 99.4 %. CONCLUSIONS: This preliminary report confirms the feasibility of HT in a large number of patients. We observed that HT is associated with low rates of acute and late toxicities, and HT in combination with relatively long-term ADT results in excellent short-term bDFS.

Real-time virtual sonography, a coordinated sonography and MRI system that uses magnetic navigation, improves the sonographic identification of enhancing lesions on breast MRI.

This study verified that recently developed real-time virtual sonography (RVS) to coordinate a sonography image and the magnetic resonance imaging (MRI) multiplanar reconstruction (MPR) with magnetic navigation was useful. The purpose of this study was to evaluate the accuracy of RVS to sonographically identify enhancing lesions by breast MRI. Between December 2008 and May 2009, RVS was performed in 51 consecutive patients with 63 enhancing lesions. MRI was performed with the patients in the supine position using a 1.5-T imager with a body surface coil to achieve the same position as with sonography. To assess the accuracy of the RVS, the following three issues were analyzed: (i) The sonographic detection rate of enhancing lesions, (ii) the comparison of the tumor size measured by sonography and the MRI-MPR and (iii) the positioning errors as the distance from the actual sonographic position to the expected MRI position in 3-D. Among the 63 enhancing lesions, 42 (67%) lesions were identified by conventional B-mode, whereas the remaining 21 (33%) initial conventional B-mode occult lesions were identified by RVS alone. The sonographic size of the lesions detected by RVS alone was significantly smaller than that of lesions detected by conventional B-mode (p < 0.001). The mean tumor size provided by RVS was 12.3 mm for real-time sonography and 14.1 mm for MRI-MPR (r = 0.848, p < 0.001). The mean positioning errors for the transverse and sagittal planes and the depth from the skin were 7.7, 6.9 and 2.8 mm, respectively. The overall mean 3D positioning error was 12.0 mm. Our results suggest that RVS has good targeting accuracy to directly compare a sonographic image with MRI results without operator dependence.

Emergent coil embolization for ruptured renal artery aneurysm.

We report a case of ruptured renal artery aneurysm successfully treated by emergent transcatheter embolization with microcoils. A 66-year-old woman was referred for emergency treatment after presenting with sudden-onset left flank pain and vomiting. Blood examination showed anemia. Computed tomography demonstrated a partly calcified mass with massive retroperitoneal hematoma. With the diagnosis of a ruptured left renal artery aneurysm, emergency angiography was performed. Left renal arteriography demonstrated a saccular aneurysm at the lower aspect of the renal hilum. A total of five microcoils were placed at the arterial branch, including the orifice of the aneurysm. The first coil was partly lodged in a branch near the orifice of the aneurysm that was used as an "anchor" to prevent subsequent coils from migrating and effectively occluding the parent artery with a short segment. Two branches originating from the renal hilum were preserved. The postoperative course was favorable. Endovascular treatments, including coil embolization, appear to be effective, safe, and less invasive than surgery. This method should be considered as a treatment of choice for ruptured renal artery aneurysm.