Hormone Ablation Therapy Research Articles

Pharmacotherapy Options in Cancer Treatment-induced Bone Loss: Focus on Bisphosphonates

Bone loss and its associated risk of fracture is a serious long-term health issue for breast cancer and prostate cancer survivors. Hormone ablation therapy, in particular aromatase inhibitors (AIs) for breast cancer and androgen deprivation therapy (ADT) for prostate cancer, causes marked reduction in circulating estrogen or testosterone levels, resulting in increased bone resorption, decreased bone mineral density (BMD), and an increased risk of fragility fracture. In several clinical trials with small sample sizes and short follow-up periods, oral and intravenous bisphosphonates have been shown to improve BMD, but not actual fracture rates, in cancer patients on hormone ablation therapy. A number of professional organizations and expert panels recommend the use of bisphosphonates for selected patients at risk. Although bisphosphonates are generally well tolerated, physicians should be aware of safety concerns, including the risk of osteonecrosis of the jaw. With the growing number of older breast and prostate cancer survivors, additional research is needed to characterize patients who would benefit from pharmacotherapy and optimize strategies to prevent cancer treatment-induced bone loss.

Hat die Systemtherapie von Lymphknotenmetastasen einen kurativen Wert?

Can systemic treatment for lymph node metastasis be given with curative intention? The answer to this question depends on the tumor entity. Therefore we want to give an overview about the role of systemic therapy in the curative treatment of locally advanced urological cancers, such as germ cell tumors, urothelial, renal cell, and prostate cancer. In the case of germ cell tumors cure can be achieved by platinum-based polychemotherapy without any additional treatment modality. This is also true for high-risk germ cell tumors, in which complete remissions and long-term survival are observed following polychemotherapy. In contrast, the role for chemotherapy in locally advanced urothelial cancers so far seems to be confined to (neo-)adjuvant treatment in concert with surgery. Further clinical trials are warranted to standardize and optimize this strategy. So far, renal cell cancer can only be cured by surgery. Cytokines and novel targeted therapies provide a therapeutic option in advanced renal cell cancers. A possible role of the latter modality in adjuvant treatment following resection of high-risk renal cell cancer is currently being tested in randomized trials. The same is true for hormone ablation therapy in locally advanced prostate cancer. In summary, as of today medical therapy can provide cure in advanced germ cell cancers. Its role in all other urological cancers is confined to palliative treatment of non-resectable disease. A possible contribution in the (neo-)adjuvant setting is presently a matter of clinical research.

Neoadjuvant hormonal deprivation for patients undergoing radical prostatectomy

The purpose of this study is to evaluate the therapeutic effect of radical prostatectomy combined with preoperative neoadjuvant hormonal ablation therapy for prostate cancer (PCa). In this study, a total of 31 patients with local PCa underwent radical prostatectomy; of these, 12 patients underwent preoperative hormonal deprivation with a combination of goserelin and flutamide for a period of 5.6 months. Data regarding clinical characteristics were compared between the neoadjuvant therapy and radical prostatectomy groups. A total of 31 patients received pelvic lymph node clearance, and the rate of positive lymph nodes was 12.9% (4/31). Serum prostate-specific antigen (PSA) was 8.9 +/- 1.2 microg L(-1) after the neoadjuvant therapy and 0.4 +/- 0.3 microg L(-1) one month after the radical prostatectomy. There were significant differences in the positive surgical margins, seminal vesicle invasion and lymph node metastasis between the neoadjuvant therapy group (n = 12) and the radical prostatectomy group (n = 19, P < 0.01). The resulsts indicates that preoperative hormonal deprivation induced by goserelin and flutamide can decrease clinical and pathological staging, but assessment of its influence on long-term prognosis requires further study.

Estrogen receptor in breast cancer of the Japanese.

The estrogen receptor was assayed, using the 2,000g supernatant and dextran-coated charcoal method, in 243 tissue samples from human breast cancer, benign breast diseases, macroscopically normal breast tissues, normal uterine myometrium, and uterine myoma. The estrogen receptor was found to be positive in 52.1% of 98 primary breast cancer and in 54.1% of 24 metastatic tumors. The receptor in the breast cancer was found to be similar to that in normal uterine myometrium in the binding character; that is, the dissociation constant of 10(-9) approximately 10(-11) M and number of binding sites of 0 approximately 2,800 fmol/mg protein. There was no correlation between the presence of the receptor and some clinical factors such as menopausal status, age of the patient, urinary 17-ketosteroid excretion, clinical stage of cancer, tumor size, positive or negative axillary lymph node metastasis, histological type, metastatic site of the cancer, or disease-free interval. The estrogen receptor appeared to be retained by metastasis of cancer, and this may lead to the use of the receptor assay with mastectomy specimens for the prediction of response to hormonal therapy in future recurrence of malignancy. Furthermore, it may be possible by this assay to select patients suitable for adjuvant therapy with hormones at the time of mastectomy. A good correlation was found between the presence of the receptor and response to the major endocrine ablation therapy in patients with advanced or metastatic breast cancer. When the receptor was negative in the cancer tissue, the change of response to the endocrine therapy was minimum. On the other hand, if the cancer contained the receptor, approximately 60% of the patients with metastatic or advanced breast cancer responded well to the major endocrine ablation therapy. Thus, the estrogen receptor of breast cancer in Japanese patients appears to bear a close resemblance to that reported in Western patients in its incidence and the correlation to some biological characteristics of the cancer.

Immunomodulatory properties of omega-3 fatty acids: a possible explanation for their systemic, anti-carcinogenic effects

The recent article by Zapata-Gonzalez et al. [1] was highly interesting. The authors have clearly demonstrated the immunomodulatory effects of docosahexaenoic acid on dendritic cells. Data from recent clinical studies suggest that omega-3 fatty acids exhibit potent, anti-carcinogenic properties. I personally believe that immunomodulation has a major role to play in these systemic, anti-carcinogenic effects exhibited by omega-3 fatty acids. The findings of Zapata-Gonzalez et al. [1] may very well explain these anti-tumerogenic effects of omega-3 fatty acids in various systemic tissues. For instance, Hall et al. [2] have shown that omega-3 fatty acids decrease the risk for colorectal cancer. Similarly, a dietary increase in omega-3 fatty acids, resulting in increased tissue levels of eicosapentaenoic acid, results in an accentuated response to hormone ablation therapy in prostate cancer cells [3]. In fact, Mina [4] has shown that consumption of preserved fish, rich in omega-3 fatty acids, may prevent the evolution and development of prostate carcinomas. Similarly, eicosapentaenoic acid attenuates proliferation in pancreatic tissue by altering angiogenesis by decreasing the expression of cyclooxygenase-2 (COX2) [5]. In fact, omega fatty acids are even effective in inducing apoptosis in chemo-resistant pancreatic carcinomatous tissue [6]. Omega-3 fatty acids also inhibit growth in choloangiocarcinoma cells by accentuated expression of the natural COX2 antagonist, 15-hydroxyprostaglandin dehydrogenase [7].

What is the role of androgen deprivation therapy in the treatment of locally advanced prostate cancer?

This Practice Point commentary discusses the paper by Horwitz and colleagues, which reported the long-term results of the RTOG 92-02 trial in which patients with locally advanced, node-negative prostate cancer who were treated with neoadjuvant-concurrent hormone ablation therapy and external beam radiation therapy (70 Gy) were subsequently randomized to receive either no further androgen deprivation or long-term (2-year) goserelin therapy. The results at 10 years confirm biochemical and clinical outcome benefits with the use of long-term androgen deprivation therapy for patients treated with conventional-dose radiotherapy. How these results should best be incorporated into dose-escalated radiotherapeutic approaches remains unclear, however, and this issue requires further investigation.

Predictive Value of PTEN and AR Coexpression of Sustained Responsiveness to Hormonal Therapy in Prostate Cancer—A Pilot Study

One limitation of current biochemical or histologic analysis of advanced prostate cancer (PC; T3/T4 ±Nx Mx) is the ability to identify on first diagnostic biopsy patients who will make a durable response to hormone ablation therapy. The aim of this study was to assess the predictive value (sustained response to hormonal therapy and clinical outcome (relapse-free and overall survival)) of phosphatase and tensin homolog (PTEN) and the androgen receptor (AR) immunoexpression in the presenting biopsy. Analysis was performed on 47 samples (10 cases of benign prostatic hyperplasia and 37 hormone-naive PCs). Patients selected represented two stages in the natural history of PC: The “clinical metastatic androgen–responsive” (androgen-dependent PC, ADPC) and the “clinical metastatic androgen–resistant” (androgen-independent PC, AIPC). Reduced immunoreactivity (IR) of either or both PTEN/AR in the initial hormone-naive PC samples was observed with increased frequency in AIPCs. In the ADPC group, low PTEN and/or AR-IR was associated with a shorter median relapse-free survival, i.e., at 30 months after surgery, the probability of relapse-free survival for high expressors of PTEN and AR was 85.7% (SEM = 9.3) compared with only 16.6% (SEM = 15.2) in low expressors. At 36 months, only 28.5% (SEM = 9.3) of ADPC high expressors had experienced a biochemical relapse compared with 100% of low expressors (hazard ratio, 4.6; 95% confidence interval, 4.7-146.8). Further studies analyzing the coexpression of PTEN and AR should be undertaken to validate this pilot study and the utility of these biomarkers in routine histopathologic workup of patients with PC.

Effects of diallyl disulfide (DADS) on expression of apoptosis associated proteins in androgen independent human prostate cancer cells (PC-3)

Prostate cancer is a leading cause of death among the aging men. Surgical or radiotherapy is effective when the cancer is confined to the prostate gland but once the cancer spreads beyond the pelvis even chemotherapy and hormonal ablation therapy fails in curing this disease. Our previous studies have shown that diallyl disulfide (DADS) induces cell cycle arrest and also induces apoptosis in PC-3 cells. And now the present study is focused to see whether there is an activation of caspase cascade pathway. Hence, in the present study the apoptotic effect of DADS is studied by Western blot analysis of caspase-3, -9, -10 and Bcl-2, Bad, and Bax protein. The Apoptotic cells were assessed by Hoechst 33342 staining with 25 and 40 microM concentrations of DADS for 24 h. The results have shown that DADS at 25 and 40 microM concentrations has induced the activation of caspases. There is a significant increase in the expression of caspases (3, 9, and 10). The proapoptotic protein Bax has significantly increased at 40 microM of DADS treatment and there is significant increase of Bad protein at both the concentration. Bcl-2 protein has significantly decreased in DADS treated cells. Therefore, the present investigation serves as evidence that DADS may be a therapeutic drug in the treatment of prostate cancer.

Bicalutamide inhibits androgen‐mediated adhesion of prostate cancer cells exposed to ionizing radiation

Cell adhesion plays an important role in proliferation, metastasis, and tumor growth and may represent a potential vulnerability in treatment of prostate cancer patients. Bicalutamide (Casodex) has been used as an anti-androgen agent for prostate cancer patients during hormone ablation therapy. This study focuses on the effect of Bicalutamide on cell adhesion to fibronectin (FN) in prostate cancer cells. Androgen-dependent LNCaP prostate cancer cells were stimulated with androgen before being irradiated with doses of 0, 5, 10, or 15 Gy. Cell adhesion to fibronectin was then measured to ascertain androgen's role in integrin mediated prostate cancer cell adhesion. Flow cytometry was used to analyze surface expression of integrin subtypes in LNCaP cells. LNCaP cell adhesion to FN was significantly increased by stimulation with androgen when treated with 10 or 15 Gy ionizing radiations but not at 0 or 5 Gy. This increase was inhibited by treatment with Bicalutamide. LNCaP cells exposed to high dose radiation showed an increased expression of alpha(V) and beta(1) integrins in response to androgen treatment while Bicalutamide abolished this effect. Our data show that Bicalutamide inhibits the effect of androgen on cell adhesion to FN through changes of integrin subtypes in cells given high dose radiation. This suggests new molecular targets and possible treatment strategies for prostate cancer patients to improve the outcome during hormone ablation therapy and radiation therapy.

Dietary n-3 Polyunsaturated Fatty Acids Enhance Hormone Ablation Therapy in Androgen-Dependent Prostate Cancer

Hormone ablation therapy typically causes regression of prostate cancer and represents an important means of treating this disease, particularly after metastasis. However, hormone therapy inevitably loses its effectiveness as tumors become androgen-independent, and this conversion often leads to death because of subsequent poor responses to other forms of treatment. Because environmental factors, such as diet, have been strongly linked to prostate cancer, we examined the affects of dietary polyunsaturated fatty acids (PUFAs; at 1.5 wt%) on growth of androgen-dependent (CWR22) and androgen-independent (CWR22R) human prostatic cancer xenografts, the acute response of CWR22 tumors to ablation therapy, and their progression to androgen independence. Significant diet-induced changes in tumor n-3 or n-6 PUFA content had no affect on CWR22 or CWR22R tumors growing with or without androgen support, respectively. However, dietary changes that increased tumor eicosapentaenoic acid and linoleic acid content enhanced responses to ablation therapy, measured by cancer cell apoptosis and mitosis. In addition, relapse to androgen-independent growth (measured by renewed increases in tumor volume and serum prostate-specific antigen after ablation) positively correlated with tumor arachidonic acid content. There was no correlation between expression of 15-lipoxygenase isozymes or their products and tumor growth or responses to ablation. In conclusion, dietary n-3 PUFA may enhance the response of prostate cancer to ablation therapy and retard progression to androgen-independent growth by altering tumor PUFA content.

Risk Stratification for Positive Lymph Nodes in Prostate Cancer

To evaluate the risk of positive lymph nodes using preoperative clinical parameters. We reviewed our prospectively collected database for all patients who received RRP and PLND between January 1993 and November 2005 as primary therapy for prostate cancer. We excluded patients who had hormonal ablation or radiation therapy prior to surgery and patients with missing PSA, clinical stage, or biopsy Gleason score. We evaluated risk for nodal disease using the following definitions: low risk: PSA <or=10 ng/mL, clinical stage <or=T(2a), and Gleason score <or=6; intermediate risk: PSA 10 to 20 ng/mL, clinical stage >or=T(2b), or Gleason score of 7; and high risk: PSA >or=20 ng/mL, or clinical stage >or=T(2c), or Gleason score >or=8. Logistic regression was used to determine the association between the risk groups and pathologic lymph node involvement, and a receiver operating characteristics (ROC) curve was constructed to evaluate the performance of the stratification scheme in detecting nodal disease. A total of 760 patients with 43 (5.7%) patients with node-positive disease were available for analysis. Risk classification was significantly associated with positive nodes (P<0.001), even after controlling for year of surgery and age. The area under the ROC curve was 0.77 (95% CI: 0.69, 0.83). Omitting PLND in the low-risk group would have spared 368 (49.2%) of the entire cohort with a false-negative rate of 5/369 (1.3%) for the low-risk group, and 5/760 (0.7%) for the entire cohort. Sensitivity was 88.4%, and negative predictive value was 98.7%. Patients can be risk stratified for node-positive disease and potentially excluded from lymphadenectomy with minimal risk.

Effects of Exercise on Bone Loss and Functional Capacity During Prostate Cancer Treatment

Men with localized prostate cancer (PC) frequently receive months of hormone ablation (HA+) therapy plus radiation therapy (RT). These patients experience significant bone loss; those receiving HA+ therapy experience even greater bone loss of 4–13% yearly which can affect functional status and symptoms. Despite strong evidence demonstrating exercise benefits during treatment for breast cancer, there has been little investigation of exercise to reduce losses in bone mineral density (BMD) and functional status among PC patients.

Gibt es eine Indikation für eine adjuvante oder neoadjuvante Systemtherapie beim Prostatakarzinom?

In the meantime prostate cancer has become the most common malignancy in the male population. Due to the shift in age at the time of first diagnosis in favour of younger men with a high life expectancy and a maximum of physical and sexual activity it would be desirable to have neoadjuvant or adjuvant therapy concepts at hand which lead to an improvement of therapeutic success. So far the results of studies for adjuvant and neoadjuvant hormonal ablation therapy concepts have not led to a clear therapeutic reference. Only before radiation therapy is neoadjuvant hormonal ablation a standard part of therapy at most centres. Existing data for chemotherapeutic concepts are limited to androgen-independent advanced prostate cancer. An international study using docetaxel as an adjuvant drug is currently being performed, but the results are not yet available.

Proton MR spectroscopy of the prostate

Purpose To summarize current technical and biochemical aspects and clinical applications of proton magnetic resonance spectroscopy (MRS) of the human prostate in vivo. Material and methods Pertinent radiological and biochemical literature was searched and retrieved via electronic media (medline ®, pubmed ®). Basic concepts of MRS of the prostate and its clinical applications were extracted. Results Clinical MRS is usually based on point resolved spectroscopy (PRESS) or spin echo (SE) sequences, along with outer volume suppression of signals from outside of the prostate. MRS of the prostate detects indicator lines of citrate, choline, and creatine. While healthy prostate tissue demonstrates high levels of citrate and low levels of choline that marks cell wall turnover, prostate cancer utilizes citrate for energy metabolism and shows high levels of choline. The ratio of (choline + creatine)/citrate distinguishes between healthy tissue and prostate cancer. Particularly when combined with magnetic resonance (MR) imaging, three-dimensional MRS imaging (3D-CSI, or 3D-MRSI) detects and localizes prostate cancer in the entire prostate with high sensitivity and specificity. Combined MR imaging and 3D-MRSI exceed the sensitivity and specificity of sextant biopsy of the prostate. When MRS and MR imaging agree on prostate cancer presence, the positive predictive value is about 80–90%. Distinction between healthy tissue and prostate cancer principally is maintained after various therapeutic treatments, including hormone ablation therapy, radiation therapy, and cryotherapy of the prostate. Conclusions Since it is non-invasive, reliable, radiation-free, and essentially repeatable, combined MR imaging and 3D-MRSI of the prostate lends itself to the planning of biopsy and therapy, and to post-therapeutic follow-up. For broad clinical acceptance, it will be necessary to facilitate MRS examinations and their evaluation and make MRS available to a wider range of institutions.

Murine Cell Lines Derived from Pten Null Prostate Cancer Show the Critical Role of PTEN in Hormone Refractory Prostate Cancer Development

PTEN mutations are among the most frequent genetic alterations found in human prostate cancers. Our previous works suggest that although precancerous lesions were found in Pten heterozygous mice, cancer progression and metastasis only happened when both alleles of Pten were deleted. To understand the molecular mechanisms underlying the role of PTEN in prostate cancer control, we generated two pairs of isogenic, androgen receptor (AR)-positive prostate epithelial lines from intact conditional Pten knock-out mice that are either heterozygous (PTEN-P2 and -P8) or homozygous (PTEN-CaP2 and PTEN-CaP8) for Pten deletion. Further characterization of these cells showed that loss of the second allele of Pten leads to increased anchorage-independent growth in vitro and tumorigenesis in vivo without obvious structural or numerical chromosome changes based on SKY karyotyping analysis. Despite no prior exposure to hormone ablation therapy, Pten null cells are tumorigenic in both male and female severe combined immunodeficiency mice. Furthermore, knocking down PTEN can convert the androgen-dependent Myc-CaP cell into androgen independence, suggesting that PTEN intrinsically controls androgen responsiveness, a critical step in the development of hormone refractory prostate cancer. Importantly, knocking down AR by shRNA in Pten null cells reverses androgen-independent growth in vitro and partially inhibited tumorigenesis in vivo, indicating that PTEN-controlled prostate tumorigenesis is AR dependent. These cell lines will serve as useful tools for understanding signaling pathways controlled by PTEN and elucidating the molecular mechanisms involved in hormone refractory prostate cancer formation.

Determinants of prostate volume changes following iodine-125 interstitial prostate implant

15563 Purpose: Prostate brachytherapy (PB) has been linked with increase in prostate volume (PV). This study evaluates post- operative PV changes and the variables that might affect prostate swelling. Methods: Twenty four patients (pts) were analyzed. Twelve were treated with PB only, 8 with external beam radiation (EBRT) prior to implant, and 4 with EBRT after PB. Pre-treatment PSA and Gleason score ranges were 1.9–10.8 and 5–8 respectively. Pre- implant and post-implant day 1, 9, 30, and 60 (PV0, PV1, PV9, PV30, and PV60) measurements were done using computed tomography. Univariate analysis of PV change and the following was done: PV0, number of needles, seeds, and needle insertion attempts, seed activity (0.3 vs 0.5mCi), hormonal ablation therapy, and prior EBRT. Urinary symptoms were assessed using International Prostate Scoring System (IPSS). Results: Ninety six PV measurements were done by a single observer. PV0 ranged from 27.1 to 89.4 cc (mean 48.2). Largest PV was observed on day 1 (40.1–118.7, mean 67.1). Successive PV measurements afterwards continued to decrease. Mean PV values on day 9, 30, and 60 were 58.6, 51.5, and 42.3cc respectively. The differences between PV0 and all successive PV’s were statistically significant. Mean increase in PV1 from PV0 was 18.9±16.8cc (p&lt;0.001), PV0 and PV9 9.7cc, PV0 and PV30 2.6cc. PV60 was smaller than PV0 by an average of 6.6cc. Statistically significant positive correlation was found between PV increase and seed activity (p=0.02) while treatment with EBRT prior to PB was associated with less prostate swelling (p=0.043). Other variables were not significantly correlated with PV changes. Although the mean IPSS score increased from pre-implant value of 9.2 to 13.7 on day 60, the differences between IPSS values were not statistically significant. Conclusions: Maximum prostate size is observed on the first day after implant. Prostate begins to decrease in size between day 1 and day 9 and reaches pre-procedure volume after day 30. Higher seed activity results in greater prostate swelling, while less brachytherapy- induced swelling is observed in patients treated with external radiation prior to implant. Resolution of prostate swelling does not appear to parallel with improvement in urinary symptoms in the first 2 months after implant. No significant financial relationships to disclose.

Androgen-regulated genes differentially modulated by the androgen receptor coactivator L-dopa decarboxylase in human prostate cancer cells

BackgroundThe androgen receptor is a ligand-induced transcriptional factor, which plays an important role in normal development of the prostate as well as in the progression of prostate cancer to a hormone refractory state. We previously reported the identification of a novel AR coactivator protein, L-dopa decarboxylase (DDC), which can act at the cytoplasmic level to enhance AR activity. We have also shown that DDC is a neuroendocrine (NE) marker of prostate cancer and that its expression is increased after hormone-ablation therapy and progression to androgen independence. In the present study, we generated tetracycline-inducible LNCaP-DDC prostate cancer stable cells to identify DDC downstream target genes by oligonucleotide microarray analysis.ResultsComparison of induced DDC overexpressing cells versus non-induced control cell lines revealed a number of changes in the expression of androgen-regulated transcripts encoding proteins with a variety of molecular functions, including signal transduction, binding and catalytic activities. There were a total of 35 differentially expressed genes, 25 up-regulated and 10 down-regulated, in the DDC overexpressing cell line. In particular, we found a well-known androgen induced gene, TMEPAI, which wasup-regulated in DDC overexpressing cells, supporting its known co-activation function. In addition, DDC also further augmented the transcriptional repression function of AR for a subset of androgen-repressed genes. Changes in cellular gene transcription detected by microarray analysis were confirmed for selected genes by quantitative real-time RT-PCR.ConclusionTaken together, our results provide evidence for linking DDC action with AR signaling, which may be important for orchestrating molecular changes responsible for prostate cancer progression.

ErbB-2 Induces the Cyclin D1 Gene in Prostate Epithelial Cells In vitro and In vivo

The receptor tyrosine kinase ErbB-2 plays an important role in the regulation of growth factor-induced signal transduction cascades in the epithelium, and ErbB-2 is frequently overexpressed in epithelial tumors. Our previous studies on clinical prostate cancer specimens indicated that ErbB-2 expression was increased in patients undergoing hormone ablation therapy. We had also shown that the critical cell cycle regulatory gene cyclin D1 and its promoter were targets of proliferative signaling in prostate cancer cell lines, and that cyclin D1 was required for ErbB-2-induced mammary tumorigenesis. In the current studies, we found that increased ErbB-2 membrane expression correlated with increased nuclear cyclin D1 staining in clinical prostate cancer specimens, and that expression of ErbB-2 was capable of inducing cell cycle progression in human prostate cancer cell lines. We further showed that ErbB-2 induced the cyclin D1 promoter in DU145 cells, and that small interfering RNA knockdown of cyclin D1 protein levels blocked a significant proportion of the heregulin-induced cell cycle progression in LNCaP cells. Probasin promoter-targeted expression of an activated ErbB-2 isoform induced cyclin D1 expression in the mouse prostate, commensurate with prostate intraepithelial neoplasia. Together, these in vitro and in vivo studies identify cyclin D1 as a critical downstream target of ErbB-2 in the prostate epithelium, both of which are possible therapeutic targets for cancer intervention. Furthermore, our novel mouse model provides a useful platform for ongoing in vivo investigations of ErbB-2 signaling in the prostate epithelium.

Characteristics and Quality of Randomized Controlled Trials in the Treatment of Hepatocellular Carcinoma

Although many randomized controlled trials (RCTs) have been performed to date in the field of the treatment for hepatocellular carcinoma (HCC), there has not been any detailed analysis or evaluation of the quality of these RCTs. This study analyzed the characteristics and quality of RCTs investigating the treatment of HCC. A MEDLINE search was performed to identify prospective RCTs investigating HCC treatment published between 1991 and 2005. Eligible RCTs were analyzed by using several items, such as publication year, geographic area, and study theme. Moreover, all RCTs were evaluated by grading five items, including sample size, calculation of sample size, intention-to-treat analysis, mean observational period, loss to follow-up rate, and summing of each point. Seventy-five articles were eligible for review. Geographically, more than half of RCTs (46 RCTs) were performed in Asia, 25 RCTs in Europe, and 3 RCTs in North America. RCTs concerning transarterial chemoembolization were most frequently performed, and RCTs on hormonal therapy, ablation therapy, and chemotherapy follow thereafter in numerical order. The mean total scores were not high, although scores have recently increased. The six high-grade RCTs were all published in the recent 5 years. Many RCTs on the treatment of HCC have been performed all over the world, especially in Asia and Europe. The quality of these RCTs is, however, unsatisfactory and most of the RCTs are still inadequately performed. High-quality RCTs are needed to establish common therapeutic guidelines.

Biochemical disease-free survival rates following definitive low-dose-rate prostate brachytherapy with dose escalation to biologic target volumes identified with SPECT/CT capromab pendetide

Purpose To report biochemical disease-free survival (bDFS) after conformal brachytherapy with dose escalation to biological target volumes (BTVs) identified by Capromab Pendetide with single photon emission computed tomography and computed tomography image fusion (SPECT/CT). Methods and materials Two hundred thirty-nine (T1c–T3b NxM0) consecutive patients were evaluated by SPECT/CT before treatment. Intraprostatic SPECT/CT BTVs were identified and targeted for 150% dose escalation during brachytherapy seed implant (SI). Patients received either SI alone ( n = 150) or external beam radiation therapy (EBRT) plus SI boost (EBRT + SI) ( n = 89), with ( n = 50) and without ( n = 189) neoadjuvant hormone ablation therapy. Risk factors (RF) (prostate-specific antigen [PSA] >10 ng/mL, Stage ≥T2b, and Gleason grade ≥7) defined risk group (RG) categories [none, 1, and ≥2 RF define low, intermediate, and high RG] for bDFS calculations using four failure criteria: American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definition, PSA >1.0 ng/mL (PSA >1), PSA >0.5 ng/mL after nadir (PSA >0.5), and PSA nadir + 2 ng/mL rise in PSA clinical nadir (CN + 2). Median followup was 47.2 months (range, 24.8–96.1). Results Seven-year actuarial bDFS rates were 88.0%, 82.1%, 80.4%, and 79.9% using the ASTRO, PSA >1, PSA >0.5, and CN + 2 failure criteria, respectively. ASTRO-defined bDFS rates were 96.0%, 87.0%, and 72.5% for low, intermediate, and high RG's. Conclusion The data presented here demonstrate the feasibility of performing SPECT/CT BTV dose escalation in a mature series.