Real-world data on the comprehensive genetic profiling test for Japanese patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: comprehensive genomic profiling test has been covered by Japanese health insurance since June 2019. However, no real-world data on the test have been reported with a focus on Japanese patients with prostate cancer. METHODS: we retrospectively reviewed the data of 45 consecutive patients with metastatic castration-resistant prostate cancer, who underwent the comprehensive genomic profiling tests at Kitasato University Hospital between August 2019 and December 2022. Patients' characteristics, prevalence of gene alterations and therapeutic impact of genotype-matched therapy were assessed. RESULTS: genomic data were obtained using a tissue-based test (n = 32) and liquid-based test (n = 13). Actionable genomic alternations were identified in 51.1% of patients, and 22.2% were treated with genotype-matched therapy. The main reason for not receiving genotype-matched therapy was disease progression, accounting for 46.2% (6/13). Kaplan-Meier analysis showed significantly longer overall survival after the comprehensive genomic profiling tests in patients with genotype-matched therapy under public insurance (17.8%, n = 8) than those without it (median: not reached vs. 18.1 months; P = 0.003). Five (62.5%) out of the eight patients with genotype-matched therapy under public insurance had BRCA1 or 2 deleterious alteration. Multivariate analyses showed that BRCA deleterious alteration (17.8%, n = 8) was an independent risk factor for shorter time to castration-resistant prostate cancer (hazard ratio: 2.46, 95% confidence interval: 1.04-5.87; P = 0.041), and no patients with the alteration had ≤5 bone metastases. CONCLUSIONS: the results of this study showed the promising survival outcomes in patients with genotype-matched therapy under public insurance, even in the castration-resistant prostate cancer setting. Further detection of promising therapeutic target gene is expected to increase the number of patients who reach genotype-matched therapies.

Cancer-specific and net overall survival in older patients with de novo metastatic prostate cancer initially treated with androgen deprivation therapy.

OBJECTIVE: This study aimed to assess survival outcomes in older patients with de novo metastatic prostate cancer who initially received androgen deprivation therapy. METHODS: The retrospective multicenter study included 2784 men with metastatic prostate cancer who were treated with androgen deprivation therapy between 2008 and 2017. Patients were classified into <75, 75-79, and ≥80 age groups. Propensity score matching was conducted to assess the cancer-specific survival of the groups. The 5-year net overall survival of each group was derived to evaluate relative survival compared with the general population using the Pohar-Perme estimator and the 2019 Japan Life Table. RESULTS: During the follow-up (median, 34 months), 1014 patients died, of which 807 died from metastatic prostate cancer progression. Compared with the <75 group, the cancer-specific survival of the 75-79 group was similar (hazard ratio 1.07; 95% confidence interval 0.84-1.37; P = 0.580), whereas that of the ≥80 group was significantly worse (hazard ratio 1.41; 95% confidence interval 1.10-1.80; P = 0.006). The 5-year net overall survival of the <75, 75-79, and ≥80 age groups were 0.678, 0761, and 0.718, respectively. The 5-year net overall survival of patients aged ≥80 years with low- and high-volume disease were 0.893 and 0.586, respectively, which was comparable with those in patients aged <75 years (0.872 and 0.586, respectively). CONCLUSIONS: Older metastatic prostate cancer patients aged ≥80 years had poorer cancer-specific survival compared with younger patients. Conversely, 5-year net overall survival in older patients aged ≥80 years was comparable with that in younger patients aged <75 years.

Efficacy of combined androgen blockade therapy in patients with metastatic hormone-sensitive prostate cancer stratified by tumor burden.

OBJECTIVE: To determine the effect of combined androgen blockade with a first-generation anti-androgen on the prognoses of metastatic hormone-sensitive prostate cancer patients stratified by tumor burden. METHODS: We retrospectively analyzed the cases of metastatic hormone-sensitive prostate cancer patients who were treated with androgen deprivation therapy in 2008-2017 at 30 institutions in Japan. To compare the overall survival and progression-free survival rates of the patients treated with castration monotherapy and combined androgen blockade, we carried out a Cox proportional hazards regression analysis using both inverse probability of treatment weighting and instrumental variables methods. High-burden disease was defined as the presence of four or more bone metastases and/or visceral metastasis. RESULTS: Of 2048 patients, 702 (34.3%) and 1346 (65.7%) patients were classified as the low- and high-burden groups, respectively. In each group, >80% of the patients were treated with combined androgen blockade. Although there was no significant between-group difference in the overall survival according to the androgen deprivation therapy method, in the high-burden group the progression-free survival of the combined androgen blockade-treated patients was significantly better than that of patients treated with castration monotherapy: inverse probability of treatment weighting method, hazard ratio 0.49, 95% confidence interval 0.34-0.71; instrumental variables method, hazard ratio 0.80, 95% confidence interval 0.60-0.98. CONCLUSION: In the high-burden group, combined androgen blockade with a first-generation anti-androgen resulted in superior progression-free survival compared with castration monotherapy. For well-selected metastatic hormone-sensitive prostate cancer patients, the use of combined androgen blockade might still have some suitable scenarios.

Novel metastatic burden-stratified risk model in de novo metastatic hormone-sensitive prostate cancer.

The metastatic burden is a critical factor for decision-making in the treatment of metastatic hormone-sensitive prostate cancer (HSPC). This study aimed to develop and validate a novel risk model for survival in patients with de novo low- and high-burden metastatic HSPC. The retrospective observational study included men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We created a risk model for overall survival (OS) in the discovery cohort (n = 1449) stratified by the metastatic burden (low vs high) and validated its predictive ability in a separate cohort (n = 951). Based on multivariate analyses, lower hemoglobin levels, higher Gleason grades, and higher clinical T-stage were associated with poor OS in low-burden disease. Meanwhile, lower hemoglobin levels, higher Gleason grade group, liver metastasis, and higher extent of disease scores in bone were associated with poor OS in patients with high-burden disease. In the discovery and validation cohorts, the risk model using the aforementioned parameters exhibited excellent discriminatory ability for progression-free survival and OS. The predictive ability of this risk model was superior to that of previous risk models. Our novel metastatic burden-stratified risk model exhibited excellent predictive ability for OS, and it is expected to have several clinical uses, such as precise prognostic estimation.

Differential prognostic factors in low- and high-burden de novo metastatic hormone-sensitive prostate cancer patients.

Metastatic burden is a critical factor for therapy decision-making in metastatic hormone-sensitive prostate cancer. The present study aimed to identify prognostic factors in men with high- or low-metastatic burden treated with primary androgen-deprivation therapy. The study included 2450 men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We investigated the prognostic value of various clinicopathological parameters for progression-free survival (PFS) and overall survival (OS) in patients stratified by low- or high-metastatic burden. Among the 2450 men, 841 (34.3%) and 1609 (65.7%) were classified as having low- and high-metastatic burden, respectively. Median PFS of the low- and high-burden groups were 44.5 and 16.1 months, respectively, and the median OS was 103.2 and 62.7 months, respectively. Percentage of biopsy-positive core, biopsy Gleason grade group, T-stage, and N-stage were identified to be differentially prognostic. M1a was associated with worse PFS than was M1b in the low-burden group, whereas lung metastasis was associated with better PFS and OS than was M1b in the high-burden group. Differential prognostic factors were identified for patients with low- and high-burden metastatic prostate cancer. These results may assist in decision-making to select the optimal therapeutic strategies for patients with different metastatic burdens.

Efficacy and safety of darolutamide in Japanese patients with nonmetastatic castration-resistant prostate cancer: a sub-group analysis of the phase III ARAMIS trial.

BACKGROUND: Darolutamide, an oral androgen receptor inhibitor, has been approved for treating nonmetastatic castration-resistant prostate cancer (nmCRPC), based on significant improvements in metastasis-free survival (MFS) in the ARAMIS clinical trial. Efficacy and safety of darolutamide in Japanese patients are reported here. METHODS: In this randomized, double-blind, placebo-controlled phase III trial, 1509 patients with nmCRPC and prostate-specific antigen (PSA) doubling time ≤ 10 months were randomized 2:1 to darolutamide 600 mg twice daily or matched placebo while continuing androgen deprivation therapy. The primary endpoint was MFS. RESULTS: In Japan, 95 patients were enrolled and randomized to darolutamide (n = 62) or placebo (n = 33). At the primary analysis (cut-off date: September 3, 2018), after 20 primary end-point events had occurred, median MFS was not reached with darolutamide vs. 18.2 months with placebo (HR 0.28, 95% CI 0.11-0.70). Median OS was not reached due to limited numbers of events in both groups but favored darolutamide in the Japanese subgroup. Time to pain progression, time to PSA progression, and PSA response also favored darolutamide. Among Japanese patients randomized to darolutamide vs. placebo, incidences of treatment-emergent adverse events (TEAEs) were 85.5 vs. 63.6%, and incidences of treatment discontinuation due to TEAEs were 8.1 vs. 6.1%. CONCLUSIONS: Efficacy outcomes favored darolutamide in Japanese patients with nmCRPC, supporting the clinical benefit of darolutamide in this patient population. Darolutamide was well tolerated; however, due to the small sample size, it is impossible to conclude with certainty whether differences in the safety profile exist between Japanese and overall ARAMIS populations.

Long-term outcomes of combining prostate brachytherapy and metastasis-directed radiotherapy in newly diagnosed oligometastatic prostate cancer: A retrospective cohort study.

BACKGROUND: Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trial showed the survival benefit for prostate radiotherapy in newly diagnosed prostate cancer patients with a low metastatic burden. The result raises the next question whether additional radiotherapy to metastatic sites could improve the survival in those with a low metastatic burden. METHODS: We evaluated the efficacy and safety of prostate-directed radiotherapy (PDRT) with or without metastasis-directed radiotherapy (MDRT) in newly diagnosed oligometastatic patients who underwent combination of high-dose-rate prostate brachytherapy, external beam radiotherapy, and androgen deprivation therapy. Forty patients with bone metastasis and node positive prostate cancer were retrospectively analyzed. Of these, 22 (55%), 3 (7%), and 15 (38%) patients had N1M0, M1a, and M1b, respectively. Eighteen patients (45%) received MDRT to all metastatic sites. All patients initially underwent ≧6 months of androgen deprivation therapy. Oligometastatic disease was defined as presence of five or fewer metastatic lesions. Median follow-up period was 62.5 months. RESULTS: Of the 40 patients, the 5-year castration-resistant prostate cancer (CRPC)-free survival rate and cancer-specific survival was 64.4% and 87.9%, respectively. Pre- or post-treatment predictive value including prostate-specific antigen (PSA) at diagnosis ≥20 ng/mL, Gleason grade group 5, positive biopsy core rate ≥51%, PSA nadir level of ≥0.02 ng/mL after the radiotherapy, and no MDRT were significantly associated with progression to CRPC. Patients with MDRT had significantly higher probability of achieving a PSA level of <0.02 ng/mL than those without the therapy (88.8% vs 54.5%, P = 0.0354) and consequently had a better CRPC-free survival than those without the therapy (HR 0.319, 95%CI: 0.116-0.877). Comparing PDRT alone, PDRT with MDRT did not significantly increase the incidences of genitourinary and gastrointestinal toxicities. CONCLUSIONS: This single-institutional study revealed the feasibility of combining prostate brachytherapy and MDRT for newly diagnosed oligometastatic prostate cancer. This combined approach has potential to prolong CRPC-free survival.

Quality of life outcomes after low dose-rate brachytherapy for localized prostate cancer: Current status and future perspectives.

The present review summarizes data from studies reporting on health-related quality of life after brachytherapy and competing modalities. There are various therapeutic modalities for localized prostate cancer, including radical surgery, external beam radiotherapy and active surveillance. Advances in surgical and radiation treatment have entered clinical practice in the form of robot-assisted surgery or intensity-modulated radiotherapy. Brachytherapy remains the main treatment option for patients with localized prostate cancer, with 10-year survival data showing favorable outcomes. Because each treatment modality has achieved favorable survival outcomes, focus in determining appropriate treatment has shifted toward health-related quality of life, where each treatment has a different profile and/or adverse symptoms. The development of health-related quality of life assessment tools has allowed the creation of a pool of specific health-related quality of life data across many studies. The present article reviews the impact of brachytherapy and other modalities on quality of life, as well as future directions.

[Recurrent Urothelial Carcinoma in the Uretero-Vesical Junction Treated with Partial Ureterectomy and Ureteroneocystostomy during Long-Term Follow-Up : A Case Report].

A 54-year-old woman who had been treated with transurethral resection of bladder tumor for nonmuscle invasive urothelial carcinoma approximately nine years before presented with gross hematuria. Cystoscopy demonstrated a papillary tumor at the left side of the ureteral orifice. Magnetic resonance imaging showed a 1.3 cm non-muscle invasive lesion in the lower ureter from the ureteral orifice. She suffered from connective tissue disease treated with steroids. To avoid renal failure, we performed partial ureterectomy and ureteroneocystostomy. Pathological findings revealed pT1 urothelial carcinoma with negative surgical margin. There have been no signs of recurrence during eight years of follow-up after the last treatment.

Impact of five-tiered Gleason grade groups on prognostic prediction in clinical stage T3 prostate cancer undergoing high-dose-rate brachytherapy.

BACKGROUND: We evaluated a five-tiered Gleason grade groups arising from the 2014 International Society of Urological Pathology consensus conference on prognostic prediction in clinical stage T3a (extracapsular invasion) and T3b (seminal vesicle involvement) prostate cancer undergoing high-dose-rate brachytherapy (HDR-BT). METHODS: From November 2003 to December 2012, 283 patients with stage T3 prostate cancer received HDR-BT and external beam radiation therapy (EBRT) with long-term androgen deprivation therapy (ADT). Of these, 203 (72%) and 80 (28%) patients had stage T3a and T3b disease, respectively. The mean dose to 90% of the planning target volume was 7.5 Gy/fraction of HDR-BT. After five fractions, EBRT with 10 fractions of 3 Gy was administered. All patients first underwent ≥6 months of neoadjuvant ADT, and adjuvant ADT continued for 36 months. Median follow-up was 74 months from the start of radiotherapy. RESULTS: The 10-year biochemical recurrence (BCR) -free rate for stage T3a and T3b disease was 79% and 64%, respectively (P = 0.0083). The 10-year cancer-specific survival (CSS) rate for stage T3a and T3b was 96% and 91%, respectively (P = 0.0305). Although grade groups ≥4 were independent predictors for BCR in cT3a patients (P = 0.0270), they failed to significantly predict prostate cancer-specific mortality (PCSM) among cT3a patients. Among cT3b patients, grade group 5 was a significant predictor of both BCR (P = 0.0017) and PCSM (P = 0.0233). Among stage T3a patients, no significant difference existed in 10-year CSS between grade groups 5 and 4 (94% vs 97%, P = 0.3960). In contrast, grade group 5 had a significantly worse outcome in 10-year CSS than grade group 4 among stage T3b patients (74% vs 100%, P = 0.0350). CONCLUSIONS: Stage T3a patients with grade groups 4/5 and stage T3b with grade group 4 had fairly low PCSM risk. Approximately one of four patients among stage T3b patients with grade group 5 showed PCSM after combined HDR-BT and EBRT with long-term ADT. Stage T3b patients with grade group 5 may have a greater risk for PCSM.

Perioperative Search for Circulating Tumor Cells in Patients Undergoing Prostate Brachytherapy for Clinically Nonmetastatic Prostate Cancer.

Despite the absence of local prostate cancer recurrence, some patients develop distant metastases after prostate brachytherapy. We evaluate whether prostate brachytherapy procedures have a potential risk for hematogenous spillage of prostate cancer cells. Fifty-nine patients who were undergoing high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy participated in this prospective study. Thirty patients with high-risk or locally advanced cancer were treated with HDR brachytherapy after neoadjuvant androgen deprivation therapy (ADT). Twenty-nine patients with clinically localized cancer were treated with LDR brachytherapy without neoadjuvant ADT. Samples of peripheral blood were drawn in the operating room before insertion of needles (preoperative) and again immediately after the surgical manipulation (intraoperative). Blood samples of 7.5 mL were analyzed for circulating tumor cells (CTCs) using the CellSearch System. While no preoperative samples showed CTCs (0%), they were detected in intraoperative samples in 7 of the 59 patients (11.8%; preoperative vs. intraoperative, p = 0.012). Positive CTC status did not correlate with perioperative variables, including prostate-specific antigen (PSA) at diagnosis, use of neoadjuvant ADT, type of brachytherapy, Gleason score, and biopsy positive core rate. We detected CTCs from samples immediately after the surgical manipulation. Further study is needed to evaluate whether those CTCs actually can survive and proliferate at distant sites.

Overall prognostic impact of C-reactive protein level in patients with metastatic renal cell carcinoma treated with sorafenib.

C-reactive protein (CRP) is an independent prognostic factor for renal cell carcinoma (RCC). The aim of the present study was to investigate the overall prognostic impact of CRP in patients with metastatic RCC treated with sorafenib. Between April 2008 and December 2014, 40 consecutive patients with metastatic RCC were treated with sorafenib at our institution. The patients were divided into two cohorts according to the pretreatment CRP level: (i) a normal CRP cohort (≤0.30 mg/dl) and (ii) an elevated CRP cohort (>0.30 mg/dl). Kaplan-Meier overall survival analysis was carried out. The effects of selected variables on survival were assessed by multivariate regression using the Cox proportional hazards model. The normal CRP cohort included 16 patients (40.0%) and the elevated CRP cohort included 24 patients (60.0%). The normal CRP cohort showed significantly longer overall survival than the elevated CRP cohort (median, 52.0 vs. 17.0 months; P=0.0072). On multivariate analysis, normal CRP predicted longer overall survival (hazard ratio, 0.367; 95% confidence interval, 0.147-0.914; P=0.0313). Pretreatment normal CRP predicted better overall survival in patients with metastatic RCC treated with sorafenib and CRP level may be a useful biomarker for predicting overall survival of patients treated with sorafenib.

[A Case of Primary Adrenal Malignant Lymphoma with Inferior Vena Cava Thrombus].

We report a case of primary adrenal malignant lymphoma with inferior vena cava thrombus which was successfully treated by surgical resection and chemotherapy. A 77-year-old woman complained of right back pain. Computed tomography and magnetic resonance imaging showed right adrenal tumor which had a diameter of 27 mm with inferior vena cava thrombus. Under the diagnosis of malignant adrenal tumor, surgical resection and vena cava replacement were performed. Histopathological examination revealed diffuse large B-cell lymphoma. After the operation, she received 6 courses of adjuvant chemotherapy, and has been alive without evidence of recurrence for 3 years.

A multicenter retrospective analysis of sequential treatment of abiraterone acetate followed by docetaxel in Japanese patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: Abiraterone acetate and docetaxel are promising treatment options for metastatic castration-resistant prostate cancer patients. However, the optimal sequencing of these agents is unclear, and no previous reports discuss Japanese metastatic castration-resistant prostate cancer patients. The purpose of this analysis is to reveal the outcomes of Japanese metastatic castration-resistant prostate cancer patients treated with abiraterone acetate followed by docetaxel. METHODS: We retrospectively reviewed Japanese Phase 1 and Phase 2 trials of metastatic castration-resistant prostate cancer patients treated with abiraterone acetate until disease progression and subsequently treated with docetaxel. The primary outcome measure was the rates of prostate-specific antigen declines ≧30 and ≧50%, respectively, with docetaxel. Secondary outcome measures included progression-free survival with docetaxel, and overall survival after initiation of abiraterone acetate and docetaxel. We performed correlation analysis between previous prostate-specific antigen response to abiraterone acetate and subsequent prostate-specific antigen response to docetaxel. RESULTS: We identified 15 patients had experienced disease progression with abiraterone acetate and subsequently were treated with docetaxel. Prostate-specific antigen declines ≧30 and ≧50% with docetaxel were observed in five patients (33%) and two patients (13%), respectively. The median progression-free survival with docetaxel was 3.7 months (95% confidence interval: 2.9-4.6). The median overall survival from initiation of docetaxel and abiraterone acetate were 14.4 months (95% confidence interval: 6.3-22.4), and 25.7 months (95% confidence interval: 20.1-30.7), respectively. No significant correlation was observed between these prostate-specific antigen responses (Pearson r = 0.206, P = 0.46). CONCLUSION: The efficacy of docetaxel in Japanese mCRPC patients that was resistant to abiraterone acetate was modest. The prostate-specific antigen response to previous abiraterone acetate could not predict the efficacy of subsequent docetaxel. Larger prospective trials are needed to validate these findings.

[A Case of Emphysematous Pyelonephritis with Pneumoderma Treated by Open Surgical Drainage].

Emphysematous pyelonephritis (EPN) is an acute, severe necrotizing infection of the renal parenchyma and perirenal tissue. A 72-year-old female patient with uncontrolled diabetes mellitus was admitted to a hospital with loss of consciousness and, fever. Laboratory data suggested acute inflammation and hyperosmolar hyperglycemic syndrome. The left EPN was accurately diagnosed after abdominal computed tomographic (CT) scan revealed renal parenchymal gas and fluid within the subcutaneous tissue and mediastinum. The patient was transferred to our institution and underwent emergent open surgical drainage. However, a CT scan performed 3 days after the drainage revealed the presence of fluid in the left perinephric space. CT-guided drainage of the left perinephric fluid was performed. The patient was finally discharged after complete recovery from severe inflammation.

Expression of orphan G-protein coupled receptor GPR174 in CHO cells induced morphological changes and proliferation delay via increasing intracellular cAMP.

We established cell lines that stably express orphan GPCR GPR174 using CHO cells, and studied physiological and pharmacological features of the receptor. GPR174-expressing cells showed cell-cell adhesion with localization of actin filaments to cell membrane, and revealed significant delay of cell proliferation. Since the morphological changes of GPR174-cells were very similar to mock CHO cells treated with cholera toxin, we measured the concentration of intracellular cAMP. The results showed the concentration was significantly elevated in GPR174-cells. By measuring intracellular cAMP concentration in GPR174-cells, we screened lipids and nucleotides to identify ligands for GPR174. We found that lysophosphatidylserine (LysoPS) stimulated increase in intracellular cAMP in a dose-dependent manner. Moreover, phosphorylation of Erk was elevated by LysoPS in GPR174 cells. These LysoPS responses were inhibited by NF449, an inhibitor of Gα(s) protein. These results suggested that GPR174 was a putative LysoPS receptor conjugating with Gα(s), and its expression induced morphological changes in CHO cells by constitutively activating adenylyl cycles accompanied with cell conjunctions and delay of proliferation.

Transversus abdominis plane block provides postoperative analgesic effects after cesarean section: additional analgesia to epidural morphine alone.

AIM: The aim of our study was: (i) to investigate whether transversus abdominis plane (TAP) block confers additional analgesic effects to epidural morphine alone; and (ii) to determine plasma levels of local anesthetics after TAP block in post-cesarean women. MATERIAL AND METHODS: The subjects were parturients undergoing cesarean section under combined spinal-epidural anesthesia. Morphine (2 mg) was administered to the epidural space close to the end of surgery. Women who desired TAP block were allocated to the TAP group. Women who did not undergo TAP block were allocated to the control group. In the TAP group, 20 mL of either 0.375% ropivacaine or 0.3% levobupivacaine was infused to both sides of the transversus abdominis plane after surgery. All patients were placed on a patient-controlled i.v. analgesia regimen with morphine after surgery. Time to the first morphine request and amount of morphine consumption within 24 h after surgery were compared in patients with and without TAP block. Plasma concentrations of local anesthetics were determined at 15, 30 and 60 min after TAP block. RESULTS: Forty and 54 patients were allocated to the control and TAP group, respectively. The median time to the first morphine request was longer (555 vs 215 min), and the median cumulative morphine consumption within 24 h was lower (5.3 vs 7.7 mg) in the TAP group than in the control group. The maximum median concentrations of ropivacaine and bupivacaine after TAP block were 784 and 553 ng/mL, respectively. CONCLUSION: TAP block had additional analgesic effects to epidural morphine alone.

Case Reports of Transdermal Fentanyl Patch Administration Difficulties in Cancer Patients with Excess Sweating.

(Case 1) A 45-year-old male was diagnosed with prostate cancer. Treatment was administered using bicalutamide and leuprorelin acetate, while a transdermal fentanyl (TDF) was applied for pain relief. However, TDF continued to peel off owing to excessive sweating, even when reinforced by a protective layer. As such, TDF was discontinued and pain control was initiated using other medicines. Sweating occurred irregularly because of hot flashes, approximately four to five times per day. (Case 2) A 37-year-old male was diagnosed with a malignant thymoma and sacral metastasis. For analgesic control, etodolac tablets, carbamazepine tablets, and TDF were administered. Subsequently, the dose of the TDF was gradually increased, but the analgesic effect was low; thus, fentanyl blood concentration was measured. The measurements showed that even higher TDF doses did not increase fentanyl blood levels. During this period, full body sweating began to occur to a large extent due to unknown causes, and it was thought that the absorption of fentanyl decreased. When using a TDF, it is necessary to monitor patients for any sweating during treatment, while also considering changes in medication in some cases. This should promote the maintenance and improvement of the quality of life of the affected patients.

Dosimetric Predictors of Toxicity after Prostate Stereotactic Body Radiotherapy: A Single-Institutional Experience of 145 Patients.

The indications for stereotactic body radiotherapy (SBRT) for prostate cancer have increased. However, the relationships between adverse events and risk factors remain unclear. This study aimed to clarify associations between adverse events and dose index for prostate SBRT. Participants comprised 145 patients irradiated with 32-36 Gy in 4 fractions. Radiotherapy-related risk factors such as dose-volume histogram parameters and patient-related risk factors such as T stage and Gleason score were evaluated in a competing risk analysis. Median follow-up duration was 42.9 months. A total of 9.7% had acute Grade ≥ 2 GU toxicities and 4.8% had acute Grade ≥ 2 GI toxicities. A total of 11.1% had late Grade ≥ 2 GU toxicities and 7.6% had late Grade ≥ 2 GI toxicities. Two (1.4%) patients suffered from late Grade 3 GU toxicities. Similarly, two (1.4%) patients suffered from late Grade 3 GI toxicities. Acute GU and GI events correlated with prostate volume and dose to the hottest 10 cc volume (D10cc)/volumes receiving a minimum of 30 Gy (V30 Gy) of rectum, respectively. Late GI toxicity, frequency, and rectal hemorrhage correlated with rectal D0.1 cc/D1 cc, maximum dose to the bladder, and rectal D0.1 cc, respectively. Toxicities after prostate SBRT using 32-36 Gy/4 fractions were acceptable. Our analysis showed that acute toxicities correlated with volume receiving a medium dose level, and late toxicities correlated with highest point dose of organs at risk.

Erythema multiforme induced by sorafenib for metastatic renal cell carcinoma.

OBJECTIVE: Sorafenib is one of the few standard agents for metastatic renal cell carcinoma. Although sorafenib-induced erythema multiforme is rarely reported, we evaluated the cases of erythema multiforme induced by sorafenib for metastatic renal cell carcinoma. METHODS: From November 2006 to November 2011, 36 eligible patients who had been treated with sorafenib were enrolled in this study. Patients received sorafenib 200 or 400 mg orally, twice daily, at 12 h intervals, on a continuous dosing schedule. All patients who experienced rash or erythema multiforme underwent a skin biopsy, and the histopathological diagnosis was confirmed. RESULTS: Twenty-eight patients (78%) experienced a skin reaction of any toxicity grade. Hand-foot skin reactions occurred in 17 (47%), erythema multiforme in 9 (25%), rash/desquamation in 6 (17%) and alopecia in 9 (25%). Skin biopsy was performed and histopathological diagnosis was confirmed for all nine patients (25%) who experienced erythema multiforme. All nine showed a positive reaction to sorafenib on a subsequent patch test. CONCLUSIONS: Sorafenib-induced erythema multiforme may not be rare in Japanese patients. Patients who once showed erythema multiforme after sorafenib treatment are never to be treated with sorafenib again. Patients treated with sorafenib should be monitored carefully, with a multidisciplinary approach. Consultation with a dermatologist is critical because some cases quickly become severe.