Long-term outcomes of salvage transurethral high-dose-rate brachytherapy combined with external beam radiation therapy for anastomotic recurrence of prostate cancer after radical prostatectomy: A retrospective analysis.

BACKGROUND: High-dose-rate brachytherapy (HDR-BT) delivers high-dose radiation to local lesions within a short treatment period. There are no reports of salvage transurethral HDR-BT for biochemical recurrence (BCR) after radical prostatectomy. Thus, we aimed to evaluate the usefulness of salvage transurethral HDR-BT with external beam radiation therapy (EBRT) for anastomotic prostate cancer recurrence. METHODS AND MATERIALS: Patients with postoperative prostate cancer who underwent salvage transurethral HDR-BT with EBRT for anastomotic recurrence at our hospital between January 2002 and July 2009 were retrospectively evaluated. The Kaplan-Meier method was used to estimate biochemical freedom from failure (bFFF), cause-specific survival (CSS), and overall survival (OS) rates. RESULTS: Nine patients were included in this study. The median follow-up period and age were 13.1 (range 4.3-18.4) years and 67 (range 63-78) years, respectively. The dose of HDR-BT ranged from 13 to 24 Gy per 2 to 5 fractions, while that of EBRT ranged from 30 to 44 Gy per 15 to 22 fractions. The 1-year, 5-year, and 10-year bFFF rates were 77.8%, 41.7%, and 13.9%, respectively. The 10-year and 15-year CSS rates were 100% each. The 10-year and 15-year OS rates were 100% and 64.3%, respectively. Six patients were diagnosed with BCR. Two patients experienced Grade 3 hematuria as a late adverse event. There was no exacerbation of urinary incontinence. CONCLUSIONS: No prostate cancer-related deaths were observed, even after a long-term follow-up. Salvage transurethral HDR-BT after radical prostatectomy is safe and feasible and may be a useful treatment option.

Feasibility of magnetic resonance imaging-ultrasound guided high-dose-rate brachytherapy for localized prostate cancer: Preliminary results from a prospective study.

OBJECTIVE: This study aimed to investigate preliminary outcomes of a prospective trial of magnetic resonance imaging-ultrasound fusion-guided ultrafocal high-dose-rate brachytherapy in localized prostate cancer. METHODS: In our prospective study, data from patients who underwent this treatment between April 1, 2020 and March 31, 2021 were analyzed. In the procedure, the applicator needle was inserted through the perineum to target the lesion on the multiparametric magnetic resonance imaging, which was fused onto the transrectal ultrasound image. The prescription dose was set at a single fraction of 19 Gy. Data from patients who received whole-gland high-dose-rate brachytherapy were extracted and compared with data from patients who received ultrafocal high-dose-rate brachytherapy, to evaluate the frequency of acute adverse events. RESULTS: Eight patients underwent ultrafocal high-dose-rate brachytherapy with a median observation period of 7.75 months (range 5.96-15.36 months). No acute genitourinary or gastrointestinal adverse events were observed in this cohort. The planned procedure was completed in all patients, and no unexpected adverse events were observed; however, prostate-specific antigen failure was detected in one patient. In the 25 patients who underwent whole-gland high-dose-rate brachytherapy, acute genitourinary and gastrointestinal adverse events were observed in 88% and 20% of the patients, respectively. Ultrafocal high-dose-rate brachytherapy was a significant factor in avoiding acute adverse genitourinary events in univariate and multivariate analyses (P < 0.001 and P = 0.032, respectively). CONCLUSIONS: Magnetic resonance imaging-ultrasound fusion-guided ultrafocal high-dose-rate brachytherapy in localized prostate cancer is a safe and feasible treatment without acute genitourinary and gastrointestinal adverse events. Long-term observation and further investigation are warranted.

Hypercalcemia Associated with Extramammary Paget's Disease.

Hypercalcemia of malignancy occurs in up to one third of patients at some point during the course of their advanced stage. The majority of them is caused by humoral hypercalcemia of malignancy due to systemic secretion of parathyroid hormone-related protein (PTHrP) by tumor cells. Extramammary Paget's disease is a slow-growing cutaneous malignancy commonly limited to the epidermis of the anogenital region, but rarely becomes invasive and metastatic to distant sites. Herein, we report a 70-year-old male patient with metastatic extramammary Paget's disease. He consulted our hospital with altered consciousness and tumor in his genital area. Physical examination revealed erythematous plaque with a tumor on the scrotum and perineum. It was diagnosed as extramammary Paget's disease (multiple liver metastases and multiple lymph node metastases by skin biopsy and image examination). Increases in serum-corrected calcium and PTHrP-intact levels (15.3 mg/dL and 66.1 pg/L, respectively) were confirmed. PTHrP immunohistochemistry showed positive staining in the tumor cells. We diagnosed humoral hypercalcemia of malignancy. We treated hypercalcemia with saline, furosemide, zoledronic acid, and elcatonin. Regarding the local control of the tumor, 30 Gy/10 Fr electron beam therapy was performed. However, treatment with zoledronic acid was only temporally effective to correct hypercalcemia, and an increased serum calcium level developed again. Concurrently, the liver metastases were rapidly enlarged, and his general condition gradually deteriorated. The patient died on day 55. When patients with extramammary Paget's disease show unconsciousness, serum calcium level should be measured and PTHrP-producing tumor distinguished.

Long-term outcome of cutaneous melanoma patients treated with boron neutron capture therapy (BNCT).

Our aim was to assess the long-term clinical outcome of boron neutron capture therapy (BNCT) using 10B-para-boronophenylalanine (BPA) as the boron delivery agent for cutaneous melanoma. Eight patients (eight lesions) were treated between October 2003 and April 2014. Their ages ranged from 48 to 86 years at the time of treatment. All of the targets were primary lesions and they were located on the sole or face. No patient had evidence of regional lymph node involvement, distant metastases or an active secondary cancer. The clinical stage was cT1-2N0M0 and performance scores were <2. BNCT was carried out at the Kyoto University Research Reactor (KUR). The patients were irradiated with an epithermal neutron beam between the curative tumor dose and the tolerable skin dose. Eight patients were evaluated and six showed a complete response (CR), while two patients had a partial response (PR). Of the two patients with a PR, one has remained a PR with brown spots persisting for 7.5 years following BNCT. The tumor in the other patient recurred after 6 years at the site of persisting brown macula. The overall control rate (CR + PR without recurrence) for the cohort was 88% (7/8). There have never been any adverse events >Grade 2 for the long follow-up period. Our results suggest that BNCT may be a promising treatment modality in the management of early stage cutaneous melanoma when wide local excision is not feasible.

Boron neutron capture therapy for head and neck cancer: Relevance of nuclear-cytoplasmic volume ratio and anti-tumor effect. -A preliminary report.

BNCT is a type of particle beam radiation therapy that utilizes an α particle and 7Li nucleus generated when a thermal neutron is captured by a 10B nucleus involved in the boron compound that has been taken up into tumor tissue selectively. In this report, the relevance of N/C ratio of tumor cell and anti-tumor effect for BNCT clinical cases of head and neck cancer were verified. Examination of pre-irradiated tumor histopathological specimens of 9 BNCT treated head and neck cancer patients (4 CR patients, 5 non-CR patients) was performed. The statistically significant difference between the CR group and the non-CR group was examined for the physical dose was multiplied by the absolute biological effectiveness (ABE) value determined from the patient's tumor specific N/C ratio. Analysis showed the mean tumor dose could not distinguish between CR and non-CR groups. However, the ABE dose could clearly distinguish between the CR group and the non-CR group (p = 0.0250). The N/C ratio of tumor cell can influence the anti-tumor effect of BNCT for HNC.

Boron neutron capture therapy for vulvar melanoma and genital extramammary Paget's disease with curative responses.

BACKGROUND: Although the most commonly recommended treatment for melanoma and extramammary Paget's disease (EMPD) of the genital region is wide surgical excision of the lesion, the procedure is highly invasive and can lead to functional and sexual problems. Alternative treatments have been used for local control when wide local excision was not feasible. Here, we describe four patients with genital malignancies who were treated with boron neutron capture therapy (BNCT). METHODS: The four patients included one patient with vulvar melanoma (VM) and three with genital EMPD. They underwent BNCT at the Kyoto University Research Reactor between 2005 and 2014 using para-boronophenylalanine as the boron delivery agent. They were irradiated with an epithermal neutron beam between the curative tumor dose and the tolerable skin/mucosal doses. RESULTS: All patients showed similar tumor and normal tissue responses following BNCT and achieved complete responses within 6 months. The most severe normal tissue response was moderate skin erosion during the first 2 months, which diminished gradually thereafter. Dysuria or contact pain persisted for 2 months and resolved completely by 4 months. CONCLUSIONS: Treating VM and EMPD with BNCT resulted in complete local tumor control. Based on our clinical experience, we conclude that BNCT is a promising treatment for primary VM and EMPD of the genital region. Trial registration numbers UMIN000005124.

Efficacy of prophylactic irradiation to the contralateral testis for patients with advanced-stage primary testicular lymphoma: an analysis of outcomes at a single institution.

BACKGROUND: Primary testicular lymphoma (PTL) is a rare, extranodal lymphoma that often relapses in the contralateral testis. We evaluated outcomes in patients with any stage of PTL who had received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) with rituximab chemotherapy and prophylactic radiotherapy to the contralateral testis. METHODS: We retrospectively identified 15 patients (median age 66 years; range 39-81) diagnosed with diffuse large B-cell PTL in the period 2000-2014. Characteristics and outcomes of these cases were evaluated. RESULTS: All patients received initial orchiectomy followed by CHOP with or without rituximab. Thirteen patients received prophylactic irradiation to the contralateral testis. During follow-up (median 67 months; range 8-190), one patient died of PTL, three died of other disease, and nine were free from relapse. For stage I-II disease, 5-year progression-free and overall survival rates were 80 and 100%, respectively. For stage III-IV PTL, 5-year progression-free and overall survival rates were 50 and 72%, respectively. Notably, no patient developed contralateral testicular involvement after prophylactic irradiation. CONCLUSIONS: The observed outcomes suggest that the combination of (i) CHOP plus rituximab and (ii) radiotherapy for local recurrence prophylaxis is promising for both stage I-II and stage III-IV PTL.

Nationwide multi-institutional retrospective analysis of high-dose-rate brachytherapy combined with external beam radiotherapy for localized prostate cancer: An Asian Prostate HDR-BT Consortium.

PURPOSE: To report outcomes and risk factors of high-dose-rate (HDR) brachytherapy combined with external beam radiotherapy with or without androgen deprivation therapy (ADT) in prostate cancer patients. MATERIALS AND METHODS: This multi-institutional retrospective analysis comprised 3424 patients with localized prostate cancer at 16 Asian hospitals. One-thirds (27.7%) of patients received only neoadjuvant ADT, whereas almost half (49.5%) of patients received both neoadjuvant and adjuvant ADT. Mean duration of neoadjuvant and adjuvant ADT were 8.6 months and 27.9 months, respectively. Biochemical failure was defined by Phoenix ASTRO consensus. Biochemical control rate, clinical disease-free survival (cDFS), cause-specific survival, and overall survival (OS) were calculated. RESULTS: Median followup was 66 months. Ten-year biochemical control, cDFS, cause-specific survival, and OS rate were 81.4%, 81.0%, 97.2%, and 85.6%, respectively. Receiving both neoadjuvant and adjuvant ADT was detected as a favorable factor for biochemical control, cDFS, and OS, but pelvic irradiation was detected as an adverse factor for cause-specific survival, and OS. Ten-year cumulative rates of late Grade ≥2 genitourinary and gastrointestinal toxicities were 26.8% and 4.1%, respectively; receiving both neoadjuvant and adjuvant ADT was detected as a favorable factor for preventing both toxicities. CONCLUSIONS: HDR combined with external beam radiotherapy was an effective and safe treatment for localized prostate cancer. Combination of long-term ADT was suggested to be necessary, even for HDR brachytherapy, and was useful in suppressing late toxicities. Meanwhile, pelvic irradiation was suggested to have an adverse effect on OS of our study population.

BNCT for advanced or recurrent head and neck cancer.

The therapeutic effect of surgery and/or combination of conventional chemoradiotherapy is limited in the patients with recurrent squamous cell carcinoma (SCC) and locally advanced non-squamous cell carcinoma without malignant melanoma (non-SCC) of the head and neck. Currently, clinical trials of BNCT for head and neck cancers are being conducted in some institutes to verify its the effectiveness. BNCT was performed in 10 patients with recurrent SCC, 7 patients with recurrent non-SCC and 3 patients with newly diagnosed non-SCC in our university between October 2003 and September 2007. Eleven patients showed complete remission and 7 patients showed partial remission of irradiated site. The effective rate [(CR+PR)/total cases] was 90%. No severe acute or chronic normal-tissue reactions were observed in any patients. BNCT is effective and safe in the patients with recurrent SCC and locally advanced non-SCC.

Boron neutron capture therapy for advanced salivary gland carcinoma in head and neck.

PURPOSE: Boron neutron capture therapy (BNCT) is among the radiation treatments known to have a selective lethal effect on tumor cells. This study summarizes the tumor responses and the acute and late adverse effects of BNCT in the treatment of patients with both recurrent and newly diagnosed T4 salivary gland carcinoma. METHODS: Two patients with recurrent cancer and 3 with newly diagnosed T4 advanced malignancy were registered between October 2003 and September 2007, with the approval of the medical ethics committees of Kawasaki Medical School and Kyoto University. BNCT was performed, in a single fraction using an epithermal beam, at Japan Research Reactor 4. RESULTS: All patients achieved a complete response within 6 months of treatment. The median duration of the complete response was 24.0 months; the median overall survival time was 32.0 months. Three of the 5 patients are still alive; the other 2 died of distant metastatic disease. Open biopsy of the parotid gland after BNCT was performed in 1 patient and revealed no residual viable cancer cells and no serious damage to the normal glandular system. Although mild alopecia, xerostomia, and fatigue occurred in all patients, there were no severe adverse effects of grade 3 or greater. CONCLUSIONS: Our preliminary results demonstrate that BNCT is a potential curative therapy for patients with salivary gland carcinoma. The treatment does not cause any serious adverse effects, and may be used regardless of whether the primary tumor has been previously treated.