Stereotactic body radiation therapy for Japanese patients with localized prostate cancer: 2-year results and predictive factors for acute genitourinary toxicities.

OBJECTIVE: We aimed to report the 2-year results of stereotactic body radiation therapy for prostate cancer and identify the clinical and dosimetric factors that predict acute genitourinary toxicities. METHODS: We retrospectively reviewed the medical records of patients with non-metastatic prostate cancer treated at Toyota Memorial Hospital between 2017 and 2020. The patients were treated with stereotactic body radiation therapy with a total dose of 36.25 Gy in five fractions on consecutive weekdays. While low-risk patients received radiotherapy alone, intermediate- to high-risk patients also received androgen deprivation therapy. RESULTS: We analysed a total of 104 patients, including 10, 60 and 34 low-, intermediate- and high-risk patients, respectively. The median follow-up duration was 2 years. We did not observe biochemical/clinical recurrence, distant metastasis or death from prostate cancer. One patient died of another cause. Grade 2 acute genitourinary toxicity was observed in 40 (38%) patients. Age (P = 0.021), genitourinary toxicity of grade ≥1 at baseline (P = 0.023) and bladder mean dose (P = 0.047) were significantly associated with the incidence of grade 2 acute genitourinary toxicity. The cut-off value of 65 years for age and 10.3 Gy for the bladder mean dose were considered the most appropriate. Grade 2 acute gastrointestinal toxicity was observed in five (5%) patients. None of the patients experienced grade ≥3 acute or late toxicity. CONCLUSIONS: Stereotactic body radiation therapy is feasible for Japanese patients with prostate cancer, with acceptable acute toxicity. Age, genitourinary toxicity at baseline and bladder mean dose predict grade 2 acute genitourinary toxicity.

Role of high-dose salvage radiotherapy for oligometastases of the localised abdominal/pelvic lymph nodes: a retrospective study.

BACKGROUND: Abdominal/pelvic lymph node (LN) oligometastasis, a pattern of treatment failure, is observed occasionally, and radiotherapy may work as salvage therapy. The optimal prescription dose, however, is yet to be determined. This study assessed the efficacy of high-dose radiotherapy. METHODS: The medical records of 113 patients at 4 institutes were retrospectively analysed who had 1 to 5 abdominal/pelvic LN oligometastases and were treated with definitive radiotherapy between 2008 and 2018. The exclusion criteria included non-epithelial tumours, uncontrolled primary lesions, palliative intent, and re-irradiation. The prescription dose was evaluated by using the equivalent dose in 2 Gy fractions (EQD2). Patients receiving EQD2 ≥ 60 Gy were placed into the high-dose group, and the remaining others the low-dose group. Kaplan-Meier analyses were performed to evaluate overall survival (OS), local control (LC), and progression-free survival (PFS). Univariate log-rank and multivariate Cox proportional hazards model analyses were performed to explore predictive factors. Adverse events were compared between the high-dose and low-dose groups. RESULTS: The primary tumour sites included the colorectum (n = 28), uterine cervix (n = 27), endometrium (n = 15), and ovaries (n = 10). The rate of 2-year OS was 63.1%, that of LC 59.7%, and that of PFS 19.4%. On multivariate analyses, OS were significantly associated with solitary oligometastasis (hazard ratio [HR]: 0.48, p = 0.02), LC with high-dose radiotherapy (HR: 0.93, p < 0.001), and PFS with long disease-free interval (HR: 0.59, p = 0.01). Whereas high-dose radiotherapy did not significantly improve 2-year OS in the entire cohort (74.8% in the high-dose vs. 52.7% in the low-dose; p = 0.08), it did in the subgroup of solitary oligometastasis (88.8% in the high-dose vs. 56.3% in the low-dose; p = 0.009). As for Late grade ≥ 3 adverse event, ileus was observed in 7 patients (6%) and gastrointestinal bleeding in 4 (4%). No significant association between the irradiation dose and adverse event incidence was found. CONCLUSIONS: As salvage therapy, high-dose radiotherapy was recommendable for oligometastasis in the abdominal/pelvic LNs. For solitary oligometastasis, LC and OS were significantly better in the high-dose group.

Intra-arterial chemoradiotherapy for oral cancer: Superiority of intensity-modulated radiation therapy over three-dimensional conformal radiation therapy.

PURPOSE: To determine the superiority of intensity-modulated radiation therapy (IMRT) over three-dimensional conformal radiation therapy (3DCRT) in patients who underwent intra-arterial chemoradiotherapy for oral cancer. METHODS: We retrospectively analyzed patients with locally advanced oral cancer curatively treated with intra-arterial chemoradiotherapy at a single institution between 2010 and 2021. All patients treated after May 2015 underwent IMRT. Docetaxel (12 mg/m2/week) and nedaplatin (5 mg/m2/day) were administered through a shallow temporal artery using a catheter. RESULTS: In total, 143 patients (IMRT: 71; 3DCRT: 72) were included in this study. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 75.7 % and 59.8 %, respectively, with no significant differences between the irradiation methods. In multivariate analysis, cervical lymph node metastasis (LNM) was the only significant poor prognostic factor contributing to OS, PFS, locoregional control (LRC), and local control (LC). In multivariate subgroup analysis of LNM cases (n = 90), IMRT contributed to favorable LRC (hazard ratio [HR]=0.4, P = 0.01) and LC (HR=0.4, P = 0.006). There was no difference in the incidence of grade ≥2 osteonecrosis of the jaw (4.2 % vs. 12.5 %, P = 0.13), xerostomia (75 % vs. 82 %, P = 0.316), or dysgeusia (80 % vs. 82 %, P = 0.834) between the IMRT and 3DCRT groups. However, the rates of xerostomia at 6 months and dysgeusia at 3 months were lower in the IMRT group (both P < 0.001). CONCLUSION: IMRT neither improved patient survival nor significantly reduced the incidence of osteonecrosis of the jaw. However, it demonstrated favorable LRC and LC in patients with LNM, suggesting an advantage in early recovery from xerostomia and dysgeusia.

Solid tumours showing oligoprogression to immune checkpoint inhibitors have the potential for abscopal effects.

PURPOSE: Given the uncertainty surrounding the abscopal effect (AE), it is imperative to identify promising treatment targets. In this study, we aimed to explore the incidence of AE when administering radiotherapy to patients with oligoprogressive solid tumours while they are undergoing treatment with immune checkpoint inhibitors (ICIs). MATERIALS AND METHODS: In this multicentre prospective observational study, oligoprogressive disease was defined as a < 20% increase in lesions compared to > 2 months before enrolment. We enrolled patients who requested radiotherapy during the ICI rest period between 2020 and 2023. AE was considered present if ≥ 1 non-irradiated lesion decreased by ≥ 30% before the next line of systemic therapy started. RESULTS: Twelve patients were included in this study; the common primary lesions were in the lungs (four patients) and kidneys (three patients). AEs were observed in six (50%) patients, with a median time to onset of 4 (range 2-9) months after radiotherapy. No significant predictors of AEs were identified. Patients in the AE group had a significantly better 1-year progression-free survival (PFS) rate than those in the non-AE group (p = 0.008). Two patients from the AE group were untreated and progression-free at the last follow-up. Four (33%) patients experienced grade 2 toxicity, with two cases attributed to radiotherapy and the other two to ICI treatment. No grade 3 or higher toxicities were observed in any category. CONCLUSION: Patients with oligoprogressive disease may be promising targets with potential for AEs. AEs can lead to improved PFS and, in rare cases, to a certain progression-free period without treatment. Irradiating solid tumours in patients with oligoprogressive disease during immune checkpoint inhibitor therapy may be a promising target with the potential for abscopal effects (AEs). AEs can lead to improved progression-free survival and, in rare cases, to a certain progression-free period without treatment.

Stereotactic body radiation therapy for prostate cancer: a study comparing 3-year genitourinary toxicity between CyberKnife and volumetric-modulated arc therapy by propensity score analysis.

BACKGROUND: To investigate whether the rate of stereotactic body radiation therapy-related (SBRT-related) genitourinary (GU) toxicity is lower in patients with prostate cancer treated with CyberKnife. METHODS: We retrospectively reviewed the medical records of patients with nonmetastatic prostate cancer at two institutions between 2017 and 2020. We analyzed 70 patients who were extracted by propensity score matching based on age, pre-treatment International Prostate Symptom Score (IPSS), and prostate volume. The patients were treated with SBRT, with a total dose of 36.25 Gy in five fractions over five consecutive weekdays, using CyberKnife or volumetric-modulated arc therapy (VMAT). RESULTS: The low-, medium-, and high-risk patients were 2, 19, and 14, respectively, in the CyberKnife group and 4, 17, and 14, respectively, in the VMAT group. The median follow-up time in both groups was 3 years. One patient with CyberKnife died of unrelated causes. No biochemical or clinical recurrence, distant metastases, or death from prostate cancer was observed. The peak values of IPSS in the acute phase (< 3 months) were significantly lower in the CyberKnife than in the VMAT group (CyberKnife:16.2 vs VMAT:20.2, p = 0.025). In multiple regression analyses, the treatment modality (p = 0.03), age (p = 0.01), bladder medication pre-irradiation (p = 0.03), and neoadjuvant androgen deprivation therapy (p = 0.04) contributed to the peak value of the acute-phase IPSS. The incidence of treatment-related grade 2 acute GU toxicity tended to be lower in the CyberKnife than the VMAT group (CyberKnife: 22.9% vs. VMAT: 45.7%, p = 0.077). No difference was noted between the groups with regard to late IPSS or GU toxicity and gastrointestinal toxicity in all phases. Toxicities of grade ≥ 3 have not been observed to date. CONCLUSIONS: Regardless of treatment modality, SBRT is effective in treating prostate cancer without serious toxicity. However, CyberKnife has an advantage over VMAT in terms of acute prostate symptoms.

Subpleural fibrotic interstitial lung abnormalities are implicated in non-small cell lung cancer radiotherapy outcomes.

BACKGROUND: The relationship between interstitial lung abnormalities (ILAs) and the outcomes of lung cancer radiotherapy is unclear. This study investigated whether specific ILA subtypes are risk factors for radiation pneumonitis (RP). PATIENTS AND METHODS: This retrospective study analysed patients with non-small cell lung cancer treated with radical-intent or salvage radiotherapy. Patients were categorised into normal (no abnormalities), ILA, and interstitial lung disease (ILD) groups. The ILA group was further subclassified into non-subpleural (NS), subpleural non-fibrotic (SNF), and subpleural fibrotic (SF) types. The Kaplan-Meier and Cox regression methods were used to determine RP and survival rates and compare these outcomes between groups, respectively. RESULTS: Overall, 175 patients (normal, n = 105; ILA-NS, n = 5; ILA-SNF, n = 28; ILA-SF, n = 31; ILD, n = 6) were enrolled. Grade ≥2 RP was observed in 71 (41%) patients. ILAs (hazard ratio [HR]: 2.33, p = 0.008), intensity-modulated radiotherapy (HR: 0.38, p = 0.03), and lung volume receiving 20 Gy (HR: 54.8, p = 0.03) contributed to the cumulative incidence of RP. Eight patients with grade 5 RP were in the ILA group, seven of whom had ILA-SF. Among radically treated patients, the ILA group had worse 2-year overall survival (OS) than the normal group (35.3% vs 54.6%, p = 0.005). Multivariate analysis revealed that the ILA-SF group contributed to poor OS (HR: 3.07, p =0.02). CONCLUSIONS: ILAs, particularly ILA-SF, may be important risk factors for RP, which can worsen prognosis. These findings may aid in making decisions regarding radiotherapy.

Clinical Outcomes of Radiation Therapy for Angiosarcoma of the Scalp and Face: A Multi-Institutional Observational Study.

Angiosarcoma of the scalp and face (ASF) is a rare, aggressive tumor often treated with multimodal therapy, including radiation therapy (RT). This study assessed RT outcomes for ASF and identified prognostic factors. Data from 68 non-metastatic ASF patients undergoing RT with or without other therapies were analyzed. Median radiation dose was 66 Gy in 33 fractions (interquartile range (IQR) 60-70 Gy in 28-35 fractions). Local control (LC), progression-free survival (PFS), and overall survival (OS) rates were calculated using Kaplan-Meier analysis. Multivariate analyses and adverse event evaluation were conducted. Median patient age was 75 years (IQR 71-80 years), with a median follow-up of 17 months (IQR 11-42 months). One-/three-year LC rates were 57/37%, PFS rates were 44/22%, and OS rates were 81/44%. Multivariate analyses showed that an equivalent dose in a 2 Gy fraction (EQD2) >66 Gy correlated with improved LC (HR 2.35, 95% CI 1.03-5.32, p = 0.041). Combining chemotherapy (HR 2.43, 95% CI 1.08-5.46, p = 0.032) or surgery (HR 2.41, 95% CI 1.03-5.59, p = 0.041) improved PFS. No factors influenced OS. Late grade 3+ toxicities occurred in 1%, with one patient developing a grade 4 skin ulcer. These findings suggest that EQD2 > 66 Gy and combining chemotherapy or surgery can enhance LC or PFS in ASF. Further prospective studies are needed to determine the optimal treatment strategy for this rare malignancy, particularly in elderly patients.

Impact of real-time virtual sonography, a coordinated sonography and MRI system that uses an image fusion technique, on the sonographic evaluation of MRI-detected lesions of the breast in second-look sonography.

The aim of this study was to verify the utility of second-look sonography using real-time virtual sonography (RVS)-a coordinated sonography with an MRI system that uses an image fusion technique with magnetic navigation-on the sonographic evaluation of MRI-detected lesions of the breast. Of the 196 consecutive patients who were examined with breast MRI in our hospital from 2006 to 2009, those patients who underwent second-look sonography to identify MRI-detected lesions were enrolled in this study. MRI was performed using a 1.5-T imager with the patient in a supine position. To assess the efficacy benefits of RVS, the correlations between lesion detection rates, MRI features, distribution, and histopathological classification on second-look sonography using conventional B-mode or RVS were analyzed. Of the 196 patients, 55 (28 %) demonstrated 67 lesions initially detected by MRI, followed by second-look sonography. Of the 67 MRI-detected lesions, 18 (30 %) were identified with second-look sonography using conventional B-mode alone, whereas 60 (90 %) lesions were detected with second-look sonography using RVS (p < 0.001). The detection rates of 16 focal lesions, 46 mass lesions, 16 lesions sized <5 mm, 45 lesions sized 5-10 mm, 26 lesions situated within the mammary gland, 41 lesions situated around mammary fascia, 24 malignant lesions, and 43 benign lesions were, respectively, 25, 26, 25, 24, 42, 17, 33, and 23 % by conventional B-mode, and were significantly higher, respectively, at 94, 89, 94, 89, 88, 90, 92, and 88 % by RVS. Of the seven lesions with no sonographic correlates, five could be biopsied by marking MRI information onto the body surface using RVS. Overall, 65 of 67 (97 %) MRI-detected lesions were confirmed by histopathological results. Our results suggest that the additional use of RVS on second-look sonography significantly increases the sonographic detection rate of MRI-detected lesions without operator dependence.

Automatic one-click planning for hippocampal-avoidance whole-brain irradiation in RayStation.

This study aimed to verify the accuracy of auto-contouring and auto-dose optimization for hippocampal-avoidance whole-brain radiation therapy (HA-WBRT). Head computed tomography (CT) images of 15 patients were selected. The regions of interest, containing the brain, hippocampus, eyes, and lacrimal glands, were contoured manually and automatically on CT images. They were compared and evaluated for concordance rates using the Simpson coefficient. To verify the performance of dose optimization, auto-dose planning was compared with manual planning for 15 cases. All optimization plans were performed using the volumetric modulated arc therapy technique. The automatically contoured brain showed a very high concordance rate with the manually contoured brain; the Simpson coefficient was 0.990 ± 0.01. Contrastingly, the concordance rate of the hippocampal contour was low at 0.642 ± 0.15 (right) and 0.500 ± 0.16 (left); however, the rate improved to 0.871 ± 0.09 (right) and 0.852 ± 0.11 (left) with an additional 3-mm margin. For 2% of each planning target volume with the prescribed dose (D2%) and Dmean, there was no significant difference between the automatic and manual plans (35.50 Gy vs 35.23 Gy; p = 0.233 and 33.09 Gy vs 32.84 Gy; p = 0.073, respectively). The D98% was significantly better for the manual plan than for the automatic plan (25.49 Gy vs 26.11 Gy; p < 0.01). Dmax and D100% for the hippocampus did not show any significant difference between the automatic and manual plans (15.65, 16.09 Gy (right, left) vs 15.51, 15.80 Gy; p = 0.804, 0.233 and 8.08, 8.03 Gy vs 8.13, 8.01 Gy; p = 0.495, 1 respectively). The accuracy of auto-contouring for HA-WBRT can be guaranteed by providing an appropriate margin, and the precision of the auto-dose optimization was comparable to that of the manual plan.

A Novel Treatment Strategy for Advanced Lacrimal Sac Carcinomas Confirmed by p16 Immunostaining.

This article aims to describe the two cases in which chemotherapy and chemoradiotherapy were effective for advanced HPV-related lacrimal sac squamous cell carcinoma and avoided the need for radical surgery. This was an interventional study of two patients with advanced lacrimal sac squamous cell carcinoma. Two patients with advanced lacrimal sac squamous cell carcinoma were treated at our University Hospital between January 2020 and February 2021. Diagnosis of HPV-related lacrimal sac carcinoma was done by p16 immunostaining and RNA in situ hybridization. Received neoadjuvant chemotherapy and chemoradiotherapy, also minimally invasive surgery to remove any residual tumor if the final response, were unfavorable. HPV-related carcinoma was decided by checking p16 and RNA status. Response was assessed by computed tomography, magnetic resonance imaging, positron emission tomography-computed tomography, and endoscopic images. Both patients had positive p16 staining also HPV RNA in situ hybridization. Received definitive chemoradiotherapy instead of radical surgery after showing a partial response to neoadjuvant chemotherapy. A complete response was achieved in one patient and the other had a partial response, leaving a small residual tumor in the nose that was successfully removed by endonasal endoscopic surgery. Cure was achieved in two patients with HPV-related lacrimal sac squamous cell carcinoma by neoadjuvant chemotherapy followed by definitive chemoradiotherapy, with only one requiring minimally invasive surgery. This is a new direction in the treatment of p16-positive lacrimal sac carcinoma, especially for advanced cases, whereby molecular biological indicators can be used to avoid highly invasive surgery and preserve quality of life without compromising prognosis.

Comparison of Physician-recorded Toxicities and Patient-reported Outcomes of Five Different Radiotherapy Methods for Prostate Cancer.

BACKGROUND/AIM: To compare five radiotherapy methods for prostate cancer. PATIENTS AND METHODS: During 2005-2018, the data of patients with non-metastatic prostate cancer were retrospectively analysed. Patients were treated with high-dose-rate brachytherapy (HDR-BT); low-dose-rate brachytherapy (LDR-BT); or external-beam radiotherapy (EBRT), including conventionally fractionated radiotherapy (CFRT), moderate-hypofractionated radiotherapy (MHRT), and ultra-hypofractionated radiotherapy (UHRT). RESULTS: In total, 496 patients (149, HDR-BT; 100, LDR-BT; 100, CFRT; 97, MHRT, and 50, UHRT) with a median follow-up of 4.3 years were enrolled. The incidence of grade ≥2 acute genitourinary toxicities was significantly lower with HDR-BT (p<0.001) than with any other radiotherapy. The cumulative incidence of late grade ≥2 genitourinary toxicities was the highest with UHRT and significantly higher (p=0.005) with UHRT than with HDR-BT. Higher symptom score peaks were noted 4 weeks after therapy for LDR-BT than for EBRT. CONCLUSION: Physician-recorded toxicities were slightly lower with HDR-BT and patient-reported outcomes tended to be worse with LDR-BT.

Predictive factors of prognosis after radiation and steroid pulse therapy in thyroid eye disease.

To identify predictive factors of prognosis after radiotherapy with concurrent steroid pulse therapy for thyroid eye disease, retrospective analyses were performed among 77 patients. Clinical activity score and magnetic resonance imaging were used to evaluate degrees of orbital inflammation. As a pre-treatment work-up, the thyroid-stimulating antibody (TSAb) level was measured. During a median follow-up of 25.0 months, the 2-year cumulative relapse-free rate (CRFR) was 80.9%. In the univariate analysis, a worse 2-year CRFR was significantly associated with the presence of optic neuropathy (P = 0.001), a higher TSAb rate (P = 0.001), and lower standard deviation (SD) of signal intensity at the extraocular muscle in T2-weighted images (P = 0.006). In the multivariate analysis, TSAb rate and SD affected the CRFR independently. When TSAb activity of 2800% was set as a cut-off at 2 years after treatment, the predictive sensitivity and specificity of relapse were 81.2% and 90.6%, respectively. With regard to SD, the respective sensitivity and specificity values were 81.2% and 82.7% when 100 was set as a cut-off. In conclusion, high TSAb and low SD were significant risk factors for cumulative relapse in orbital radiotherapy. Cut-off values of 2800% for TSAb and 100 for SD may be suitable.

Oblique approach for CT-guided liver radiofrequency ablation using multiplanar reformation images in hepatocellular carcinoma.

PURPOSE: To evaluate the feasibility and safety of CT-guided radiofrequency (RF) ablation by caudal-cranial oblique insertion using multiplanar reformation (MPR) images for hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: Twenty-two HCCs in 19 patients that were difficult to demonstrate on ultrasound (mean tumor diameter was 17.5 mm) were treated with CT-guided RF ablation by caudal-cranial oblique insertion to avoid pneumothorax, using MPR images after transcatheter arterial chemoembolization. The insertion point and direction of insertion, avoiding aerated lung parenchyma, bones, large vessels, and intestine, were sought on the MPR images. Technical success was defined as complete eradication of tumor enhancement in the contrast-enhanced CT. Local tumor progression was defined by the appearance of enhanced tumor adjacent to the zone of ablation. The technical success rate, local tumor progression, and complications were investigated. RESULTS: The coronal plane was used for insertion in 18 tumors, the sagittal plane in 3 tumors, and the oblique plane in 1 tumor. RF electrode placement was successful and complete necrosis was obtained in all cases. During the mean follow-up period of 38.0 months, local tumor progression was not detected in any of the patients. There were no major complications, including pneumothorax. CONCLUSION: CT-guided RF ablation by caudal-cranial oblique insertion using MPR images is a feasible and safe therapeutic option.