Objectives: To examine the efficacy and prognostic benefits of radiotherapy (RT) in patients who have unresectable advanced hepatocellular carcinoma (HCC) with invasion to intrahepatic large vessels (IHLVs). Methods: Sixty-eight patients who had advanced HCC with invasion to IHLVs were studied. Thirty-two consecutive patients initially received 3-dimensional conformal RT for HCC invasion to IHLVs. Tumor response, prognostic factors, and survival were studied in the patients given RT. Prognostic factors and survival were assessed in the study group as a whole. Data were analyzed using the Kaplan-Meier method, univariate analysis, and a Cox model. Results: The rate of objective response to RT was 48%. Predictors of survival in the patients who received RT were a hepatic function of Child-Pugh class A (p = 0.0263) and a response to RT (p = 0.0121). In the study group as a whole, independent predictors of survival in a Cox model were multinodular HCC (p = 0.007), inferior vena caval invasion (p = 0.001), a serum α-fetoprotein level of >1,000 ng/ml (p = 0.032), and the performance of RT (p < 0.001). Notably, the median survival of the nonresponders to RT (n = 15) was significantly longer than that of the patients who received no treatment for HCC (n = 21; 7.0 vs. 3.4 months, p = 0.0014). Conclusion: RT is considered an effective initial treatment for HCC invasion to IHLVs, and may offer survival benefits, even in nonresponders, because of the induction of stable disease.

No abstract

The purpose of this study was to report the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) for National Comprehensive Cancer Network (NCCN) criteria-defined high-risk (HR) and very high-risk (VHR) prostate cancer. Data from 178 HR (n = 96, 54%) and VHR (n = 82, 46%) prostate cancer patients who underwent 192Ir-HDR brachytherapy and hypofractionated EBRT with long-term ADT between 2003 and 2008 were retrospectively analyzed. The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After five fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administered. All patients initially underwent ≥6 months of neoadjuvant ADT, and adjuvant ADT was continued for 36 months after EBRT. The median follow-up was 61 months (range, 25–94 months) from the start of radiotherapy. The 5-year biochemical non-evidence of disease, freedom from clinical failure and overall survival rates were 90.6% (HR, 97.8%; VHR, 81.9%), 95.2% (HR, 97.7%; VHR, 92.1%), and 96.9% (HR, 100%; VHR, 93.3%), respectively. The highest Radiation Therapy Oncology Group-defined late genitourinary toxicities were Grade 2 in 7.3% of patients and Grade 3 in 9.6%. The highest late gastrointestinal toxicities were Grade 2 in 2.8% of patients and Grade 3 in 0%. Although the 5-year outcome of this tri-modality approach seems favorable, further follow-up is necessary to validate clinical and survival advantages of this intensive approach compared with the standard EBRT approach.

Lower T levels at cessation of ADT were associated with prolonged T recovery in the long-term usage group. Five years after cessation of long-term ADT, approximately one-fifth of patients still had castrate T levels. When determining the therapeutic effect, especially biochemical control, we should consider this delay in T recovery.

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.

No abstract

Background:The optimal protocol for combining high dose rate brachytherapy and external beam irradiation as treatment for localized prostate cancer is unknown. Toxicity rates and clinical and biochemical outcomes should be evaluated to validate the current treatment protocol. Methods: Fifty-eight patients were treated for prostate cancer with high dose rate brachytherapy followed by 30 Gy of external beam radiation therapy. Toxicity during treatment and for 12-18 months thereafter, and treatment-related morbidity, were evaluated. Physician-assessed treatment-related toxicity was graded at the time of occurrence using the Radiation Therapy Oncology Group morbidity criteria. Four separate self-administered questionnaires were used to collect longitudinally demographic data and general and prostate disease-related measures of quality of life. Results: Various degrees of rectal bleeding due to radiation proctitis were experienced by 13 patients (22%) at a median time of 11 months. Two of these patients needed hospitalization to undergo laser coagulation of the rectal mucosa. Study patients had statistically significant decreases in five SF-36 domains during the first month of treatment. All measures recovered by 12 months. Sexual function was not affected by irradiation. Lower urinary tract symptoms assessed by IPSS/QOL scores worsened significantly during the first month of treatment but later recovered to baseline levels. Physician-assessed RTOG scores failed to detect these changes. Conclusions: Morbidity associated with combined radiation therapy was greatest during the first month of treatment and affected quality of life significantly. Most measures recovered to baseline levels by 12 months following radiation therapy. Although the current protocol appears acceptable, measures should be taken to decrease treatment-related morbidity further. Key words: prostate cancer -high dose rate brachytherapy -external beam radiotherapy -quality of life

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.