Inverse planning in high-dose rate brachytherapy improves quality of life of prostate cancer patients compared with forward planning.

OBJECTIVES: To understand differences in quality of life outcomes between cases with forward planning and cases with inverse planning, we examine patients undergoing high-dose rate brachytherapy combined with external beam radiotherapy for localized prostate cancer. METHODS: We prospectively identified 283 patients with localized prostate cancer and divided them into forward planning and inverse planning groups. We extracted data on doses to the prostate, rectum and urethra that could potentially affect quality of life. We also evaluated quality of life using the Japanese version of Medical Outcome Study 8-Items Short Form Health Survey and Expanded Prostate Cancer Index Composite at pre-treatment and at 3, 6, 12 and 24 months after treatment. Wilcoxon signed rank test and Bonferroni correction were used to analyze the irradiation dose and any change in quality of life. RESULTS: Doses to the prostate and rectum were not significantly different between the two groups. Notably, however, doses to the urethra were significantly lower in the inverse planning group than in the forward planning group. Patients in the forward planning group had significantly poorer physical component summary scores at 3 months according to survey results. In Expanded Prostate Cancer Index Composite, patients in the forward planning group had statistically significant poorer urinary, bowel and sexual scores than those in the inverse planning group. Quality of life related to decline in sexual function was significantly reduced in the inverse planning group. CONCLUSIONS: Inverse planning in high-dose rate brachytherapy could significantly improve quality of life of patients with prostate cancer.

Impact of age on quality of life in patients with localized prostate cancer treated with high-dose rate brachytherapy combined with external beam radiotherapy.

OBJECTIVES: To evaluate age-related quality of life changes in patients with localized prostate cancer treated by high-dose rate brachytherapy combined with external beam radiation therapy. METHODS: A total of 172 patients with clinically localized prostate cancer were categorized to age groups <75 years and ≥75 years. Changes in their quality of life were evaluated using the Japanese version of Medical Outcome Study 8-Items Short Form Health Survey, Expanded Prostate Cancer Index Composite and International Index of Erectile Function-5 at baseline, and followed up to 24 months after treatment. RESULTS: There were no significant differences in Medical Outcome Study 8-Items Short Form Health Survey scores, and urinary and bowel scores of the Expanded Prostate Cancer Index Composite for older men after treatment. International Index of Erectile Function-5 summary scores were significantly decreased in both groups. Although sexual function and sexual bother scores were decreased in patients aged <75 years, these scores were maintained in patients aged ≥75 years. CONCLUSIONS: Quality of life of prostate cancer patients undergoing high-dose rate brachytherapy combined with external beam radiation therapy does not seem to be significantly affected by age.

Brainstem Infiltration Predicts Survival in Patients With High-grade Gliomas Treated With Chemoradiotherapy.

BACKGROUND/AIM: High-grade gliomas have a poor prognosis despite standard treatment. The aim of the study was to identify new prognostic factors to select patients who need more intense treatment. PATIENTS AND METHODS: Forty-three consecutive patients underwent surgery plus chemoradiotherapy for pathologically diagnosed high-grade gliomas (grade III, IV). RESULTS: The median survival time was 989 days, and the 1-year survival rate was 87.6%. Among patients with grade IV disease, the median survival time, 1-year, and 2-year survival rate were 814 days, 82.6%, and 58.7%, respectively. In the univariate analysis, unmethylated MGMT promoter (p=0.0495), brainstem infiltration (p=0.0004), basal ganglia as the primary lesion site (p=0.0056), 3-dimensional conformal radiotherapy (p=0.0286), and <50 Gy (p=0.0049) were associated with a poor prognosis. In the multivariate analysis, only brainstem infiltration retained significance (HR for death, 0.21; 95% CI=0.06-0.70; p=0.011). CONCLUSION: Brainstem infiltration is a novel prognostic factor for poor prognosis in patients with high-grade gliomas.

Reduction of toxicity in brachytherapy using a new technique.

PURPOSE: The purpose of the study was to elucidate the usefulness of a dose evaluation method for reducing late genitourinary (GU) toxicity in high-dose-rate brachytherapy (HDR-BT) of prostate cancer. METHODS AND MATERIALS: GU toxicity was scored in accordance with the Common Terminology Criteria for Adverse Events version 4.0. The prostatic urethra was divided into three segments (base = B, midgland = M, apex = A), which were subclassified into seven subgroups (B, M, A, BM, BA, MA, BMA) using a D10% color map of the urethra. Significance testing was conducted on urethral D0.1% and D10% among the seven subgroups. Grade < 2 GU toxicity was also implemented. RESULTS: Data of 174 patients with localized prostate cancer treated with HDR-BT combined with external beam radiotherapy between November 2011 and July 2014 were analyzed retrospectively. Median age was 74 (53-84) years, and median followup period was 44 (6-69) months. The number of Grade < 2 and Grade ≥ 2 toxicity was significantly different in the M subgroup than in the other subgroups (p < 0.05), suggesting increased radioresistance in the midgland urethra. CONCLUSIONS: A high-dose-area evaluation method using a urethral D10% color map may be helpful in reducing late GU toxicity in HDR-BT for prostate cancer.

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.

Radiation dose to rectum in high-dose-rate brachytherapy with a single implant and two fractions for prostate cancer, and its prediction by prostate volume.

We aimed to clarify the differences between the estimated rectal dose (ERD) and the first measured dose (FMD) and second measured dose (SMD) to the rectum during high-dose-rate (HDR) brachytherapy, and to predict FMD from the prostate volume (PV) or the rectal dose-volume parameters (RDVPs). ERD, FMD, and SMD were assessed with a rectal dosimeter during HDR brachytherapy of 18 Gy given in two fractions to 110 patients (48 hormone recipients, 62 hormone-naïve patients) with prostate cancer. The correlations between FMD and PV, and between FMD and RDVP (D 2ml-D 5ml) were investigated. ERD (mean ± SD) was 219 ± 44 cGy, FMD was 255 ± 52 cGy, and SMD was 298 ± 63 cGy, which differed significantly (p < 0.001). The correlation coefficients between ERD and FMD, and between FMD and SMD, were 0.82 and 0.78, respectively. SMD was equivalent to 118 ± 16 % FMD. The measured doses were significantly greater in the hormone recipients than in the hormone-naïve patients (p < 0.001). The increase in FMD correlated with the increases in PV and in RDVPs. The correlation coefficients between PV and FMD in all of the patients, in the hormone recipients, and in the hormone-naïve patients were 0.61, 0.64, and 0.64, respectively, whereas that between RDVPs and FMD was <0.53. In conclusion, the dose to the rectum increased with time and was correlated with the increases in PV and RDVPs. The correlation coefficient between FMD and PV was greater than that between FMD and RDVPs.

Experimental fascioliasis in the rat-like hamster, Tscherskia triton, and other rodent hosts.

Experimental infection with Fasciola hepatica and parthenogenetic Fasciola sp. in laboratory animals have been conducted in rats and rabbits. Inoculation of less than 5 metacercariae into rat-like hamsters, Tscherskia triton, is sufficient to establish Fasciola infections. The prepatent period of F. hepatica and the parthenogenetic Fasciola sp. in T. triton was shorter than that in rats and rabbits, suggesting that T. triton is a suitable experimental model for these flukes. In contrast, F. gigantica infection in T. triton did not yield adult flukes; T. triton, is therefore, considered to be an unsuitable host for F. gigantica. The cotton rat, Sigmodon hispidus, was an unsuitable host for the parthenogenetic Fasciola sp.

The rat-like hamster, Tscherskia triton, as a host for the parthenogenetic liver fluke Fasciola sp.

Metacercariae of parthenogenetic Fasciola sp. triploid were inoculated into the rat-like hamster Tscherskia triton. Flukes at various stages of growth were found in the bile ducts of all 8 (50%) animals that survived from 42 to 90 days. The body length to width ratio ranged from 1.8 to 2.9, and flukes with the highest ratio were passed 68 days after inoculation. Our results indicate that T. triton is a suitable host for experimental infection when induced by a small number of metacercariae (less than 5) of Fasciola sp.

Incorporating GSA-SPECT into CT-based dose-volume histograms for advanced hepatocellular carcinoma radiotherapy.

In single photon emission computed tomography-based three-dimensional radiotherapy (SPECT-B-3DCRT), images of Tc-99m galactosyl human serum albumin (GSA), which bind to receptors on functional liver cells, are merged with the computed tomography simulation images. Functional liver is defined as the area of normal liver where GSA accumulation exceeds that of hepatocellular carcinoma (HCC). In cirrhotic patients with a gigantic, proton-beam-untreatable HCC of ≥ 14 cm in diameter, the use of SPECT-B-3DCRT in combination with transcatheter arterial chemoembolization achieved a 2-year local tumor control rate of 78.6% and a 2-year survival rate of 33.3%. SPECT-B-3DCRT was applied to HCC to preserve as much functional liver as possible. Sixty-four patients with HCC, including 30 with Child B liver cirrhosis, received SPECT-B-3DCRT and none experienced fatal radiation-induced liver disease (RILD). The Child-Pugh score deteriorated by 1 or 2 in > 20% of functional liver volume that was irradiated with ≥ 20 Gy. The deterioration in the Child-Pugh score decreased when the radiation plan was designed to irradiate ≤ 20% of the functional liver volume in patients given doses of ≥ 20 Gy (FLV20Gy). Therefore, FLV20Gy ≤ 20% may represent a safety index to prevent RILD during 3DCRT for HCC. To supplement FLV20Gy as a qualitative index, we propose a quantitative indicator, F 20Gy, which was calculated as F 20Gy = 100% × (the GSA count in the area irradiated with ≥ 20 Gy)/(the GSA count in the whole liver).

Reirradiation of paraaortic lymph node metastasis by brachytherapy with hyaluronate injection via paravertebral approach: With DVH comparison to IMRT.

UNLABELLED: PURPOSE/INTRODUCTION: To safely irradiate retroperitoneal targets as paraaortic lymph node by separating abdominal at-risk organs from the target during irradiation, we created a percutaneous paravertebral approach of high-dose-rate brachytherapy with hyaluronate gel injection (HGI). We report a case treated with this technique. METHODS AND MATERIALS: We encountered a patient with symptomatic regrowth of paraaortic lymph node metastasis from prostatic cancer. He had previously received 58.4Gy of radiotherapy to the same region 12 months prior. Brachytherapy needles and a HGI needle were deployed via the paravertebral approach under local anesthesia at our outpatient clinic. RESULTS: A single dose of 22.5Gy (equivalent to 60.94Gy in 2Gy per fraction schedule calculated at α/ß=10) was delivered to the target, with preservation of the surrounding small intestine by HGI with D(2cc) (minimum dose to the most irradiated volume of 2mL) of 5.05Gy. Therapeutic ratio was 3.64 times higher for this brachytherapy plan compared with an intensity-modulated radiation therapy plan. At followup at 1 year after brachytherapy, the symptoms had disappeared, tumor size had reduced with no fluorodeoxyglucose accumulation, and prostate-specific antigen level had decreased. CONCLUSION: We consider that high-dose-rate brachytherapy with the HGI procedure offers effective treatment even in this type of reirradiation situation.

Clinical significance of endoleaks characterized by computed tomography during aortography performed immediately after endovascular abdominal aortic aneurysm repair: prediction of persistent endoleak.

PURPOSE: This study aimed to predict the persistence of endoleaks (ELs) using patterns and volumes evaluated by computed tomography during aortography (CTDA) performed immediately after endovascular abdominal aortic aneurysm repair (EVAR). MATERIALS AND METHODS: CTDA immediately after EVAR and at the 6-month follow-up CT were performed in 52 patients. ELs were classified as localized-type pattern (LTP; <180° around the center of the aneurysmal lumen) or circumferential-type pattern (CTP; >180°). The proportion of EL volume in the aneurysmal sac, excluding mural thrombus, was classified as grade A (≤5 %), B (5-10 %), or C (≥10 %). The 6-month follow-up residual rates were evaluated, and volume ratios (follow-up CT aneurysmal volume including mural thrombus/CTDA aneurysmal volume) were calculated. RESULTS: The residual rate (5.3 %) and mean volume ratio (83.9 %) of ELs with LTP were significantly lower than those of ELs with CTP (72.2 and 99.3 %, respectively); there was no significant difference in residual rate or mean volume ratio among EL grades (A: 17.6, 88.1 %; B: 55.6, 89.7 %; C: 54.5, 97.8 %). CONCLUSION: ELs with LTP generally disappear over time after EVAR, with a concomitant reduction in aneurysm volume, whereas those with CTP persist, indicating that patients with EL with a CTP should be followed up carefully.

Eradicative brachytherapy with hyaluronate gel injection into pararectal space in treatment of bulky vaginal stump recurrence of uterine cancer.

The purpose of this study is to develop a procedure for eradicative brachytherapy that can deliver a curative boost dose to bulky (>4 cm) vaginal stump recurrence of uterine cancer without risk of damaging surrounding organs. We separated risk organs (the rectum and sigmoid) from the target during brachytherapy, with a hyaluronate gel injection into the pararectal space via the percutaneous paraperineal approach under local anesthesia. The rectum anchored to the sacrum by native ligament was expected to shift posteriorly. We encountered a patient with bulky stump recurrence of uterine cancer, approximately 8 cm in maximum diameter. She was complaining of abdominal pain and constipation due to bowel encasement. Following 50 Gy of external beam radiotherapy, we applied a single fraction of brachytherapy under gel separation and delivered 14.5 Gy (50.8 GyE: equivalent dose in 2-Gy fraction calculated with linear quadratic model at α/ß = 3) to the target. The gel injection procedure was completed in 30 min without complications. A total irradiation dose of 100.8 GyE was delivered to the target and the cumulative minimum dose to the most irradiated rectosigmoidal volume of 2 cc (cumulative D(2cc)) was calculated as 58.5 GyE with gel injection, and was estimated to be 96 GyE without. Over three years, the local stump tumor has completely disappeared, with no complications. Brachytherapy with a pararectal gel injection can be a safe and effective eradicative option for bulky vaginal stump recurrence.

Novel eradicative high-dose rate brachytherapy for internal mammary lymph node metastasis from breast cancer.

AIM: To develop a method of delivering an eradicative high radiotherapeutic dose safely preserving the surrounding skin in the treatment of internal mammary lymph node metastasis (IMLNM) of breast cancer. METHODS: We report a 38-year-old female patient with a solo IMLNM showing no response to 60 Gy in 2.5 Gy fractions of external beam radiotherapy. To eradicate this tumor, a boost brachytherapy plan was created after percutaneous insertion of an applicator needle into the IMLNM lesion avoiding the pleura and vessels under ultrasound monitoring. According to the dose distribution, the required thickness of a spacer between the skin and the tumor was determined, and hyaluronic gel was injected up to this thickness under ultrasound monitoring. We evaluated skin doses, target doses and clinical outcome. RESULTS: All procedures were performed easily. Sixteen Gy (34.7 Gy equivalent in 2 Gy fractions calculated by the linear quadratic model at α/ß = 10: EQD(2, α/ß = 10), cumulative total was 101.9 Gy EQD10) to 100% of the target volume was irradiated with cumulative maximum skin dose of 70 Gy EQD(2, α/ß = 3) which was 98.7 Gy EQD(2, α/ß = 3) without spacer. No procedure related- or late complications and no local recurrence at the treated site were observed for three years until expiration. CONCLUSION: We consider that this procedure will provide an eradicative high-dose irradiation to IMLNM of breast cancer, preserving skin from overdose complications.

Percutaneous interstitial brachytherapy for adrenal metastasis: technical report.

We developed and evaluated the feasibility of a brachytherapy technique as a safe and effective treatment for adrenal metastasis. Adapting a paravertebral insertion technique in radiofrequency ablation of adrenal tumors, we developed an interstitial brachytherapy for adrenal metastasis achievable on an outpatient basis. Under local anesthesia and under X-ray CT guidance, brachytherapy applicator needles were percutaneously inserted into the target. A treatment plan was created to eradicate the tumor while preserving normal organs including the spinal cord and kidney. We applied this interstitial brachytherapy technique to two patients: one who developed adrenal metastasis as the third recurrence of uterine cervical cancer after reirradiation, and one who developed metachronous multiple metastases from malignant melanoma. The whole procedure was completed in 2.5 hours. There were no procedure-related or radiation-related early/late complications. FDG PET-CT images at two and three months after treatment showed absence of FDG uptake, and no recurrence of the adrenal tumor was observed for over seven months until expiration, and for six months until the present, respectively. This interventional interstitial brachytherapy procedure may be useful as a safe and eradicative treatment for adrenal metastasis.

Brachytherapy reirradiation with hyaluronate gel injection of paraaortic lymphnode metastasis of pancreatic cancer: paravertebral approach--a technical report with a case.

Paraaortic lymph nodal (PALN) recurrence is not a rare scenario of abdominal malignancies including pancreas cancer, even after radiotherapy. The role and indication of reirradiation is limited because it is often associated with significant late toxicity in the surrounding normal organs. We developed a new approach and technique of brachytherapy to overcome this difficult situation, with a paravertebral approach and hyaluronate gel injection (HGI). We encountered a patient with pancreatic cancer who developed PALN metastasis as in-field recurrence, 6 months after resection of pancreatic cancer with 50 Gy of preoperative radiotherapy. The applicator brachytherapy needles and gel injection needles were advanced by percutaneous paravertebral approach under local anesthesia, and by injection of a hyaluronate gel to separate the surrounding small intestines and the target. A single fraction of 18 Gy was delivered to the tumor (75.6 Gy equivalent in conventional schedule calculated with LQ model at α/ß = 3) and total estimated D2cc (the minimum dose to the most irradiated volume of 2 cc, calculated at α/ß = 2) in the small intestines was 61.6 GyE with HGI and 80.6 GyE without. No complications have been observed for six months. Three months later, FDG accumulation had disappeared, the tumor size was reduced, and serum CA-19-9 value decreased from 5150 U/mL to 36.6 U/mL (normal range < 37.5). Conclusively, the brachytherapy with the HGI procedure by paravertebral approach was thought safe and effective in reirradiation of PALN recurrence.

Efficacy and safety of high-dose-rate brachytherapy of single implant with two fractions combined with external beam radiotherapy for hormone-naïve localized prostate cancer.

The purpose of this study was to evaluate the efficacy and safety of high-dose-rate (HDR) brachytherapy of a single implant with two fractions plus external beam radiotherapy (EBRT) for hormone-naïve prostate cancer in comparison with radical prostatectomy. Of 150 patients with localized prostate cancer (T1c-T2c), 59 underwent HDR brachytherapy plus EBRT, and 91 received radical prostatectomy. The median follow-up of patients was 62 months for HDR brachytherapy plus EBRT, and 64 months for radical prostatectomy. In patient backgrounds between the two cohorts, the frequency of T2b plus T2c was greater in HDR brachytherapy cohort than in prostatectomy cohort (27% versus 12%, p = 0.029). Patients in HDR brachytherapy cohort first underwent 3D conformal RT with four beams to the prostate to an isocentric dose of 50 Gy in 25 fractions and then, a total of 15-18 Gy in two fractions at least 5 hours apart. We prescribed 9 Gy/fraction for target (prostate gland plus 3 mm lateral outside margin and seminal vesicle) using CT image method for radiation planning. The total biochemical failure-free control rates (BF-FCR) at 3 and 5 years for the HDR brachytherapy cohort, and for the prostatectomy cohort were 92% and 85%, and 72% and 72%, respectively (significant difference, p = 0.0012). The 3-and 5-year BF-FCR in the HDR brachytherapy cohort and in the prostatectomy cohort by risk group was 100 and 100%, and 80 and 80%, respectively, for the low-risk group (p = 0.1418); 92 and 92%, 73 and 73%, respectively, for the intermediate-risk group (p = 0.0492); and 94 and 72%, 45 and 45%, respectively, for the high-risk group (p = 0.0073). After HDR brachytherapy plus EBRT, no patient experienced Grade 2 or greater genitourinay toxicity. The rate of late Grade 1 and 2 GI toxicity was 6% (n = 4). No patient experienced Grade 3 GI toxicity. HDR brachytherapy plus EBRT is useful for treating patients with hormone-naïve localized prostate cancer, and has low GU and GI toxicities.

Distribution of functional liver volume in hepatocellular carcinoma patients with portal vein tumor thrombus in the 1st branch and main trunk using single photon emission computed tomography-application to radiation therapy.

PURPOSE: To analyze the distribution of functional liver volume (FLV) in the margin volume (MV) surrounding hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) before radiation therapy (RT) and to verify the safety of single photon emission computed tomography-based three-dimensional conformal radiotherapy (SPECT-B3DCRT) by exploring the relation of FLV in MV to radiation-induced liver disease (RILD). METHODS AND MATERIALS: Clinical target volume (CTV) included main tumor and PVTT, and planning target volume (PTV) included CTV with a 10 mm margin. MV was defined as PTV-CTV. FLV ratio in MV was calculated as FLV in MV/MV × 100 (%). The two high-dose beams were planned to irradiate FLV as little as possible. Fifty-seven cases of HCC (26/57, 46%; Child-Pugh grade B) with PVTT underwent SPECT-B3DCRT which targeted the CTV to a total dose of 45 Gy/18 fractions. The destructive ratio was defined as radiation induced dysfunctional volume/FLV × 100 (%). RESULTS: We observed a significant negative correlation between FLV ratio in MV and CTV (p < 0.001). Three cases with CTVs of 287, 587 and 1184 cm3 experienced transient RILD. The FLV ratio in MV was highest in patients with RILD: nine patients with CTV of 200-300 cm3, three with CTV of 500-600 cm3, and two with CTV of 1100-1200 cm3. The destructive ratio yielded a mean value of 24.2 ± 1.5%. CONCLUSIONS: Radiation planning that takes into account the distribution of FLV appears to result in the least possible RILD.

Pleomorphic carcinoma of the lung with intrapulmonary aerogenic metastases on FDG PET.

A 59-year-old man presented with hemoptysis. Chest x-ray and computed tomography showed a cavitating mass and ground glass opacities in the right lower lobe. Positron emission tomography showed large regions of markedly increased fluorodeoxyglucose uptake in the right lower lobe consistent with primary cancer and intrapulmonary metastases, and several foci of high fluorodeoxyglucose uptake in the mediastinum and left neck consistent with lymph node metastases. We concluded that ground glass opacities were not aspiration of blood but intrapulmonary aerogenic metastases. Continuous active bleeding from the right bronchus (B6) was confirmed by bronchoscopy, and the right lower lobe was resected to remove the bleeding source. Pathologic findings showed pleomorphic carcinoma of the lung with intrapulmonary aerogenic metastases.