High-dose-rate intensity-modulated brachytherapy with external beam radiotherapy for prostate cancer: California endocurietherapy's 10-year results.

PURPOSE: To present the long-term outcome and morbidity of high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT) for localized prostate cancer. METHODS AND MATERIALS: Between September 1991 and December 1998, 209 consecutive patients with no prior androgen suppression were treated with HDR-BT plus EBRT. The median follow-up was 7.25 years (range, 5-12 years). The patients were stratified into three risk groups: low (Stage T2a or less, Gleason score 20). Four definitions of PSA progression were compared with the general clinical failure outcome: the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, nadir plus 2.0 ng/mL, two consecutive rises >/=0.5 ng/mL, and PSA level >0.2 ng/mL. Morbidity was scored using Radiation Therapy Oncology Group criteria. RESULTS: The general clinical control rate was 90% (188 of 209), and the general clinical failure rate was 10% (21 of 209). The overall survival rate was 79%, and the cause-specific survival rate was 97%. The PSA progression-free survival (ASTRO definition) rate was 90%, 87%, and 69% for the low-, intermediate-, and high-risk groups, respectively. The nadir plus 2 ng/mL and two rises >/=0.5 definitions correlated better with the actual clinical outcome than did the ASTRO and PSA >0.2 ng/mL definitions. The rate of Grade 3 and 4 late urinary morbidity was 6.7% and 1%, respectively, mostly occurring in patients who had undergone post-RT transurethral prostate resection. No late Grade 3 or 4 rectal morbidity developed. The sexual potency preservation rate was 67%. CONCLUSION: Our 10-year results have demonstrated HDR-BT plus EBRT is a proven treatment for all stages of localized prostate cancer. The morbidity was low, but post-RT transurethral resection should be avoided.

Lack of benefit of pelvic radiation in prostate cancer patients with a high risk of positive pelvic lymph nodes treated with high-dose radiation.

PURPOSE: The use of pelvic radiation for patients with a high risk of lymph node (LN) metastasis (>15%) remains controversial. We reviewed the data at three institutions treating patients with a combination of external-beam radiation therapy and high-dose-rate brachytherapy to address the prognostic implications of the use of the Roach formula and the benefit of pelvic treatment. METHODS AND MATERIALS: From 1986 to 2003, 1,491 patients were treated with external-beam radiation therapy and high-dose-rate brachytherapy. The Roach formula [2/3 prostate-specific antigen + (Gleason score -6) x 10] could be calculated for 1,357 patients. Group I consisted of patients having a risk of positive LN < or = 15% (n = 761), Group II had a risk >15% and < or = 30% (n = 422), and Group III had a risk of LN disease >30% (n = 174). A >15% risk of having positive LN was found in 596 patients and was used to determine the benefit of pelvic radiation. The pelvis was treated at two of the cancer centers (n = 312), whereas at the third center (n = 284) radiation therapy was delivered to the prostate and seminal vesicles alone. Average biologic effective dose was > or = 100 Gy (alphabeta = 1.2). Biochemical failure was as per the American Society for Therapeutic Radiology and Oncology definition. Statistics included the log-rank test as well as Cox univariate and multivariate analysis. RESULTS: For all 596 patients with a positive LN risk >15%, median follow-up was 4.3 years, with a mean of 4.8 years. For all cases, median follow-up was 4 years and mean follow-up was 4.4 years. Five-year results for the three groups based on their risk of positive LN were significantly different in terms of biochemical failure (p < 0.001), clinical control (p < 0.001), disease-free survival excluding biochemical failure (p < 0.001), cause-specific survival (p < 0.001), and overall survival (p < 0.001). For all patients with a risk of positive LN >15% (n = 596), Group II (>15-30% risk), or Group III (>30% risk), no benefit was seen in the 5-year rates of clinical failure, cause-specific survival, or overall survival with pelvic radiation. In the Cox multivariate analysis for cause-specific survival, Gleason score (p = 0.009, hazard ratio [HR] 3.1), T stage (p = 0.03, HR 1.8), and year of treatment (p = 0.05, HR 1.1) were significant. A log-rank test for cause-specific survival for all patients (n = 577) by the use of pelvic radiation was not significant (p = 0.99) accounting for high-dose-rate brachytherapy dose, neoadjuvant hormones, Gleason score, prostate-specific antigen, T stage, and year of treatment as covariates. CONCLUSIONS: The use of the Roach formula to stratify patients for clinical and biochemical outcomes is excellent. Pelvic radiation added to high prostate radiation doses did not show a clinical benefit for patients at a high risk of pelvic LN disease (>15%) selected using the Roach formula.

A Molluscum contagiosum fusion protein inhibits CCL1-induced chemotaxis of cells expressing CCR8 and penetrates human neonatal foreskins: clinical applications proposed.

Inflammation in atopic dermatitis is mediated in part by the chemokine CCL1 and its receptor, CCR8. Recombinant Molluscum contagiosum viral protein (rMC148p), a cc-chemokine homolog, inhibits CCL1-induced chemotaxis of cells expressing CCR8. rMC148p was prepared using the baculovirus/Sf9 insect cell expression system. The recombinant MC148 fusion protein (rMC148fp), rMC148-TAT-6xHis, was similarly prepared by adding base sequences onto the PCR primers to fuse TAT and 6xHis to rMC148p at the carboxyl terminus. rMC148fp retains the capacity of rMC148p to inhibit CCL1-induced chemotaxis. Furthermore, unlike rMC148p, topically applied rMC148fp penetrates stratum corneum of human neonatal foreskins and concentrates along the basal and lower spinous cell layers of the epidermis. rMC148fp may be a safe and effective agent in the treatment of atopic dermatitis and other CCR8-mediated disorders.

High-dose-rate monotherapy: safe and effective brachytherapy for patients with localized prostate cancer.

PURPOSE: High-dose-rate (HDR) brachytherapy used as the only treatment (monotherapy) for early prostate cancer is consistent with current concepts in prostate radiobiology, and the dose is reliably delivered in a prospectively defined anatomic distribution that meets all the requirements for safe and effective therapy. We report the disease control and toxicity of HDR monotherapy from California Endocurietherapy (CET) and William Beaumont Hospital (WBH) in low- and intermediate-risk prostate cancer patients. METHODS AND MATERIALS: There were 298 patients with localized prostate cancer treated with HDR monotherapy between 1996 and 2005. Two biologically equivalent hypofractionation protocols were used. At CET the dose was 42 Gy in six fractions (two implantations 1 week apart) delivered to a computed tomography-defined planning treatment volume. At WBH the dose was 38 Gy in four fractions (one implantation) based on intraoperative transrectal ultrasound real-time treatment planning. The bladder, urethral, and rectal dose constraints were similar. Toxicity was scored with the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3. RESULTS: The median follow-up time was 5.2 years. The median age of the patients was 63 years, and the median value of the pretreatment prostate-specific antigen was 6.0 ng/mL. The 8-year results were 99% local control, 97% biochemical control (nadir +2), 99% distant metastasis-free survival, 99% cause-specific survival, and 95% overall survival. Toxicity was scored per event, meaning that an individual patient with more than one symptom was represented repeatedly in the morbidity data table. Genitourinary toxicity consisted of 10% transient Grade 2 urinary frequency or urgency and 3% Grade 3 episode of urinary retention. Gastrointestinal toxicity was <1%. CONCLUSIONS: High disease control rates and low morbidity demonstrate that HDR monotherapy is safe and effective for patients with localized prostate cancer.

High-dose-rate prostate brachytherapy: an excellent accelerated-hypofractionated treatment for favorable prostate cancer.

PURPOSE: The radiobiology of prostate cancer appears to favor large fractions. Accelerated hypofractionation treatments may therefore be used to improve the therapeutic ratio, particularly when the doses to rectum and bladder are kept below the prostate dose. The 5-year experience at William Beaumont Hospital (WBH) and the California Endocurietherapy Center (CET) with accelerated-hypofractionated high-dose-rate (HDR) monotherapy in favorable prostate cancer is presented. MATERIALS AND METHODS: Between 1993 and 2004, 454 patients were treated with brachytherapy of which 248 treated with HDR and 206 patients treated with low-dose-rate Palladium (LDR-Pd¹°³). The WBH-HDR dose was 38 Gy, in 4 fractions, twice a day. The CET-HDR dose was 42 Gy in 6 fractions in 2 separate implants 1 week apart. The WBH-LDR dose was 120 Gy. RESULTS: Median follow-up was 4.8 years. The 5-year Phoenix biochemical control (BC) was 89%, 91%, and 88% for WBH-LDR, WBH- HDR, and CET-HDR, respectively. The majority of complications were grade 1. HDR was associated with less acute grade 1 to 3 dysuria 60% versus 39%, (P < 0.001), urinary frequency/urgency 90% to58% (P < 0.001), and rectal pain 17% to 6.5% (P < 0.001). Long-term urinary frequency/urgency 54% versus 43%, (P = 0.03) and dysuria 22% versus 15% were less with HDR. The 5-year actuarial impotence rate was 30% for LDR and 20% for HDR (P = 0.23). CONCLUSIONS: Although the same 5-year BC rates were achieved with HDR (248 patients) and LDR (206 patients) monotherapy, HDR brachytherapy was associated with less acute and chronic genitourinary and gastrointestinal toxicities. As another accepted standard of care, accelerated hypofractionated HDR monotherapy is target specific and efficient radiobiologically than EBRT which has many smaller doses per fraction. It could be considered today as the best option in accelerated hypofractionated prostate cancer treatment.

Excellent results from high dose rate brachytherapy and external beam for prostate cancer are not improved by androgen deprivation.

PURPOSE: Prostate cancer patients treated with high dose rate brachytherapy and external beam radiation therapy were stratified by risk group for analysis to determine whether androgen deprivation therapy (ADT) affected outcome. METHODS: From 1991 through 1998, 411 patients were treated with 4 fractions of 5.5 to 6.0 Gy high dose rate brachytherapy and a total of 36.0 to 39.6 Gy external beam radiation therapy (dose escalation over time). The dataset was prospective. Administration of ADT was not randomized, but it was the primary study variable. During this period, ADT was administered across all risk groups for various indications. It did not necessarily reflect advanced disease or large prostate size. There were 200 patients in the "ADT Group" (20% low, 48% intermediate, and 32% high risk) and 211 in the "No ADT Group" (33% low, 44% intermediate, 23% high risk). The median follow-up was 6.4 years. Cases were grouped according to low, intermediate, and high risk groups to reduce the effects of unrecognized selection bias for or against the ADT group. The prostate specific antigen (PSA) nadir plus 2.0 ng/ml (nadir + 2) was used as the biochemical control end point. Local control, PSA progression-free survival, distant metastasis free survival, and cause-specific survival were compared. RESULTS: The 10 year PSA-PFS (nadir + 2) for all 411 patients was 81%. The results stratified by risk group were: low 92%, intermediate 87%, and high 63%. The low and intermediate risk groups were not statistically different from one another but they were both significantly better than the high risk group. ADT versus No ADT 10-year survival showed no significant differences for any outcome variable: PSA-PFS (83% vs. 81% ns), local control (97% vs. 99%), distant metastasis free survival (94% vs. 97%), and cause-specific survival (97% vs. 97%). A subset analysis of PSA-PFS (nadir + 2) stratified by risk group revealed no difference between the ADT and No ADT groups. CONCLUSIONS: high dose rate brachytherapy and external beam radiation therapy resulted in high rates of local control, PSA progression-free survival, distant metastasis free survival, and cause-specific survival in all risk groups. Improved outcome from the use of androgen deprivation was not observed.

Matched-pair analysis of prostate cancer patients with a high risk of positive pelvic lymph nodes treated with and without pelvic RT and high-dose radiation using high dose rate brachytherapy.

OBJECTIVE: Adding pelvic radiation to high-dose prostate radiation for prostate cancer patients with a >15% risk of positive lymph nodes (LN) is controversial. We performed a matched-pair analysis of patients treated at 2 institutions to assess the impact of pelvic radiotherapy (P-RT). METHODS: From January 1993 to March 2003, 2 institutions treated 1432 prostate cancer patients with combined external beam radiotherapy (EBRT) and high-dose rate (HDR) brachytherapy. Those receiving EBRT were treated either to the prostate and seminal vesicles alone or to the entire pelvis (46 Gy). In all cases, prostate dose (EBRT and HDR) resulted in an average BED >100 Gy (alpha/beta = 1.2). There were 755 cases identified as having a pelvic LN risk >15% using the Roach formula. Of these, 255 cases were treated without pelvic RT and randomly matched by Gleason score, T stage, and pretreatment PSA to 500 cases treated with pelvic RT, resulting in 250 pairs (1:1). RESULTS: Median follow-up was 4.0 years (P = 0.7). The 4-year prostate biochemical failure (22% versus 14%, P = 0.12), distant metastasis (9% versus 4%, P = 0.6), event-free survival (72% versus 78%, P = 0.3), prostate cancer death rate (4% versus 2%, P = 0.9), and overall survival (89% versus 88%, P = 0.7) were not significantly different for patients treated with and without P-RT. Analysis with and without androgen deprivation therapy showed similar results. CONCLUSION: Improved biochemical, clinical, or survival outcomes were not observed for prostate cancer patients at risk for positive pelvic LN >15% when treated with high-dose EBRT and HDR brachytherapy to the prostate with or without pelvic radiation.