Prognostic role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with non-metastatic and metastatic prostate cancer:A meta-analysis and systematic review

Objective: To analyze data available in the literature regarding a possible prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in prostate cancer (PCa) patients stratified in non-metastatic and metastatic diseases.Methods: A literature search process was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. In our meta-analysis, the pooled event rate estimated and the pooled hazard ratio were calculated using a random effect model.Results: Forty-two articles were selected for our analysis. The pooled risk difference for non-organ confined PCa between high and low NLR cases was 0.06 (95% confidence interval [CI]: −0.03-0.15) and between high and low PLR cases increased to 0.30 (95% CI: 0.16-0.43). In non-metastatic PCa cases, the pooled hazard ratio for overall mortality between high and low NLR was 1.33 (95% CI: 0.78-1.88) and between high and low PLR was 1.47 (95% CI: 0.91-2.03), whereas in metastatic PCa cases, between high and low NLR was 1.79 (95% CI: 1.44-2.13) and between high and low PLR was 1.05 (95% CI: 0.87-1.24).Conclusion: The prognostic values of NLR and PLR in terms of PCa characteristics and responses after treatment show a high level of heterogeneity of results among studies. These two ratios can represent the inflammatory and immunity status of the patient related to several conditions. A higher predictive value is related to a high NLR in terms of risk for overall mortality in metastatic PCa cases under systemic treatments.

Conformational Radiotherapy of Prostatic Adenocarcinoma at the Dalal Jamm Hospital, Senegal—(Retrospective Analysis of a Series of 62 Cases)

Aim: We endeavored to describe the epidemiological profile of prostatic cancer, and to evaluate its diagnostic and therapeutic aspects. Method: We conducted a descriptive retrospective study on the conformational radiotherapy of prostatic adenocarcinoma at the Dalal Jamm University Hospital, Senegal from June 2018 to December 2019. We included 62 consecutive patients. The average age of the patients was 68.9 years. The average consultation time was 7.6 months. Results: Symptom manifestation and high PSA triggered the diagnosis of cancer in 74.2% and 25.8% of patients, respectively. Symptoms: pollakiuria (72.3%), bone pain (8%) and erectile dysfunction (4.8%). The digital rectal examination: normal (33.8%), nodular (30.6%), induration (24.1%), and shielding (11.3%). The mean PSA level was 90.6 ng/ml. Histology: adenocarcinoma was the most common (98.6%). The Gleason score: <7 (45.1%), =7 (35.5%), and >7 (19.4%). The majority of patients were in the high-risk group (70.9%) and 7 patients (11.2%) were metastatic at diagnosis. Therapy: first radical prostatectomy (20.9%), first-line curative radiotherapy (67.8%), adjuvant (21%) and palliative radiotherapy in 7 patients (11.2%): patients having received palliative radiotherapy had an estimated decline in symptoms of 80%. Hormone therapy was performed in 88.8% of patients, with average duration of 12.5 months. After a mean follow-up of 15 months, 59 patients were alive, including 45 cases (81.8%) in complete remission;3 patients with metastasis at the first visit (having received palliative radiotherapy) died. Conclusion: The collected data show a profile of prostate cancer that is specific to the sub-Saharan context in which the discovery is still late. Also in comparison to developed countries, the therapeutic means necessary to fight against this cancer are limited, even though three-dimensional conformational radiotherapy remains an effective and essential treatment;this study provided fundamental data in the area of insufficient data/tools.

KAI1/CD82 gene expression in benign prostatic hyperplasia and late-stage prostate cancer in Chinese

Aim: To evaluate KAII/CD82 expression in Chinese patients with benign prostatic hyperplasia (BPH) and late-stage carcinoma of prostate (CaP). Methods: Thirty Chinese patients with benign prostatic hyperplasia and 34 withCaP (adenocarcinoma clinical stage C and D) were analyzed by means of immunohistochemical methods. Results:The KAII/CD82 expression in BPH tissue was all positive, which was uniformly located on the glandular cell mem-brane at the cell-to-cell borders, but KAII/CD82 expression in metastasis CaP tissues was either significantly lower thanthat of BPH or negative, and the immunostaining pattern was not continuous. In late-stage CAP KAII/CD82 expressionwas correlated inversely to the pathological grade ( P < 0.05), but not to clinical stage ( P > 0.05). Conclusion:The authors believe that decreased and negative KAII/CD82 expression in late-stage CaP may be related to tumor pro-gression and metastasis, and appears to be a prognostic marker.

Clinical Characteristics and Outcome of Gleason Score 10 Prostate Cancer on Core Biopsy Treated by External Radiotherapy and Hormone Therapy

Objective To evaluate the clinical characteristics and outcomes of patients with Gleason score 10 prostate cancer treated by external radiotherapy and hormone therapy. Methods From January 2003 to March 2014, 1832 patients with prostate cancer were treated, among which 9 patients(represented 0.49%) were identified as Gleason score 10 disease on prostate core biopsy without distant metastases when first diagnosed. All 9 patients were treated by whole pelvic external radiotherapy(The whole pelvic dose was 50.0 Gy and the boost dose ranged from 76.2 to 78.0 Gy) and long-term hormone therapy. We assessed the clinical characteristics, treatment outcomes and treatment toxicities. Survival curves were calculated using the Kaplan-Meier method. Results The median follow-up was 4.8 years. Six patients' pre-treatment prostate-specific antigen(PSA) levels were lower than 20.0 μg/L and three patients' pre-treatment PSA levels were higher than 70.0 μg/L. The median percentage of positive biopsy cores was 91%. Three, four and two cases were classified as T2 c, T3 a and T3 b stage, respectively. Three cases were assessed as N1 stage. The 5-year biochemical failure-free survival, distant metastasis-free survival, cancer specific survival and overall survival rates were 28.6%, 57.1%, 66.7% and 57.1%, respectively. Five patients experienced grade 1-2 acute gastrointestinal toxicities and six patients complained of grade 1-2 acute genitourinary toxicities. No bone fracture or cardiovascular disease was detected. Conclusions Gleason score 10 prostate cancer on core biopsy is usually combined with other high risk factors. The pre-treatment PSA levels lie in two extremes. Timely and active treatments are urgent needed because unfavourable oncological outcomes are often presented.

Magnetic resonance imaging for prostate cancer before radical and salvage radiotherapy: What radiation oncologists need to know

External beam radiotherapy(EBRT) is one of the principal curative treatments for patients with prostate cancer(PCa). Risk group classification is based on prostate-specific antigen(PSA) level, Gleason score, and T-stage. After risk group determination, the treatment volume and dose are defined and androgen deprivation therapy is prescribed, if appropriate. Traditionally, imaging has played only a minor role in T-staging due to the low diagnostic accuracy of conventional imaging strategies such as transrectal ultrasound, computed tomography, and morphologic magnetic resonance imaging(MRI). As a result, a notable percentage of tumours are understaged, leading to inappropriate and imprecise EBRT. The development of multiparametric MRI(mp MRI), an imaging technique that combines morphologic studies with functional diffusion-weighted sequences and dynamic contrastenhanced imaging, has revolutionized the diagnosis and management of PCa. As a result, mpM RI is now used in staging PCa prior to EBRT, with possible implications for both risk group classification and treatment decisionmaking for EBRT. mpM RI is also being used in salvageradiotherapy(SRT), the treatment of choice for patients who develop biochemical recurrence after radical prostatectomy. In the clinical context of biochemical relapse, it is essential to accurately determine the site of recurrence-pelvic(local, nodal, or bone) or distant-in order to select the optimal therapeutic management approach. Studies have demonstrated the value of mpM RI in detecting local recurrences-even in patients with low PSA levels(0.3-0.5 ng/m L)-and in diagnosing bone and nodal metastasis. The main objective of this review is to update the role of mpM RI prior to radical EBRT or SRT. We also consider future directions for the use and development of MRI in the field of radiation oncology.

The biochemical efficacy of primary cryoablation combined with prolonged total androgen suppression compared with radiotherapy on high-risk prostate cancer： a 3-year pilot study

To gain beneficial effects in the management of high-risk prostate cancer, an integrated approach that combines local therapy and androgen deprivation therapy （ADT） was used. We compared biochemical responses between primary cryosurgical ablation of the prostate （CSAP） combined with prolonged ADT and radiation combined with ADT, which is the established modality in high-risk disease. A total of 33 high-risk patients received CSAP combined with ADT for 3 months before and up to 24 months after treatment. This patient group was matched with another 33 patients who had undergone three-dimensional conformal radiation therapy （3D-CRT） with the same protocol for ADT. Biochemical recurrence （BCR） was assessed by the American Society for Therapeutic Radiation Oncology （ASTRO） definition, the Phoenix definition and a prostate-specific antigen （PSA） cutoff of 0.5 ng mL^-1. Median follow-up was 61.0 ± 11.9 months for the CSAP ＋ ADT group and 86.0±15.8 months for the 3D-CRT ＋ ADT group. In the CSAP group, major complications including rectourethral fistula and incontinence were not noted. In the CSAP ＋ ADT group, 57.0% had BCR using the ASTRO definition, 21.2% using the Phoenix definition and 54.5% using a PSA cutoff of 0.5 ng mL^-1. In the 3D-CRT ＋ ADT group, 54.5%, 21.2% and 54.5% had BCR using the ASTRO, Phoenix and PSA definition, respectively. In the CSAP ＋ ADT group, the BCR-free survival （BRFS） was 54 ± 10 months using the ASTRO definition, 65 ± 5 months using the Phoenix definition and 51 ± 4 months using a PSA cutoff of 0.5 ng mL-1. In the 3D-CRT ＋ ADT group, the BRFS was 68 ± 12, 93 ± 19 and 70 ± 18 months using the ASTRO, Phoenix and PSA definition, respectively. By the log-rank test, the BRFS values for each group were not statistically different. This intermediate-term result indicated that primary CSAP combined with prolonged ADT offers a parallel biochemical response compared with radiotherapy in high-risk prostate cancer.

Outcomes of T3a Prostate Cancer with Unfavorable Prognostic Factors Treated with Brachytherapy Combined with External Radiotherapy and Hormone Therapy

Objective To evaluate the outcomes of T3 a prostate cancer with unfavorable prognostic factors treated with permanent interstitial brachytherapy combined with external radiotherapy and hormone therapy.Methods From January 2003 to December 2008,38 patients classified as T3 a prostate cancer with unfavorable prognostic factors were treated with trimodality therapy(brachytherapy + external radiotherapy + hormone therapy).The prescription dose of brachytherapy and external radiotherapy were 110 Gy and 45 Gy,respectively.The duration of hormone therapy was 2-3 years.The endpoints of this study included biochemical failure-free survival(BFFS),distant metastasis-free survival(DMFS),cancer-specific survival(CSS),and overall survival(OS).Survival curves were calculated using the Kaplan-Meier method.The Log-rank test was used to identify the prognostic predictors for univariate analysis.Results The median follow-up was 71 months.The serum pre-treatment prostate-specific antigen(PSA) level ranged from 10.0 to 99.8 ng/ml(mean 56.3 ng/ml),the Gleason score ranged from 5 to 9(median 8),and the percentage of positive biopsy cores ranged from 10% to 100%(mean 65%).The 5-year BFFS,DMFS,CSS,and OS rates were 44%,69%,82%,and 76%,respectively.All biochemical failures occurred within 40 months.The percentage of positive biopsy cores was significantly correlated with BFFS,DMFS,and OS(all P=0.000),and the Gleason score with DMFS(P=0.000) and OS(P=0.001).Conclusions T3 a prostate cancer with unfavorable prognostic factors presents not so optimistic outcome.Hormone therapy should be applied to prolong the biochemical progression-free or metastasis-free survival.The percentage of positive biopsy cores and the Gleason score are significant prognostic factors.

Current role of spacers for prostate cancer radiotherapy

Radiotherapy is an established curative treatment method for prostate cancer. Optimal tumor control rates can only be achieved with high local doses,associated with a considerable risk of rectal toxicity. Apart from already widely adapted technical advances,as intensitymodulated radiation therapy,the application of spacers placed between the prostate and rectum has been increasingly used in the last years. Biodegradable spacers,including hydrogel,hyaluronic acid,collagen or an implantable balloon,can be injected or inserted in a short procedure under transrectal ultrasound guidance via a transperineal approach. A distance of about 1.0-1.5 cm is usually achieved between the rectum and prostate,excluding the rectal wall from the high isodoses. Several studies have shown well tolerated injection procedures and treatments. Apart from considerable reduction of rectal irradiation,a prospective randomized trial demonstrated a reduction of rectal toxicity after hydrogel injection in men undergoing prostate image-guided intensity-modulated radiation therapy. The results are encouraging for continuing evaluation in dose escalation,hypofractionation,stereotactic radiotherapy or re-irradiation trials in the future.

The role of radiotherapy in localised and locally advanced prostate cancer

For a patient suffering from non-metastatic prostate cancer,the individualized recommendation of radiotherapy has to be the fruit of a multidisciplinary approach in the context of a Tumor Board,to be explained carefully to the patient to obtain his informed consent.External beam radiotherapy is now delivered by intensity modulated radiotherapy,considered as the gold standard.From a radiotherapy perspective,low-risk localized prostate cancer is treated by image guided intensity modulated radiotherapy,or brachytherapy if patients meet the required eligibility criteria.Intermediate-risk patients may benefit from intensity modulated radiotherapy combined with 4e6 months of androgen deprivation therapy;intensity modulated radiotherapy alone or combined with brachytherapy can be offered to patients unsuitable for androgen deprivation therapy due to co-morbidities or unwilling to accept it to preserve their sexual health.High-risk prostate cancer,i.e.high-risk localized and locally advanced prostate cancer,requires intensity modulated radiotherapy with long-term(≥2 years)androgen deprivation therapy with luteinizing hormone releasing hormone agonists.Post-operative irradiation,either immediate or early deferred,is proposed to patients classified as pT3pN0,based on surgical margins,prostate-specific antigen values and quality of life.Whatever the techniques and their degree of sophistication,quality assurance plays a major role in the management of radiotherapy,requiring the involvement of physicians,physicists,dosimetrists,radiation technologists and computer scientists.The patients must be informed about the potential morbidity of radiotherapy and androgen deprivation therapy and followed regularly during and after treatment for tertiary prevention and evaluation.A close cooperation is needed with general practitioners and specialists to prevent and mitigate side effects and maintain quality of life.

Stereotactic radiotherapy for prostate cancer:A review and future directions

Prostate cancer affects over 200000 men annually in the United States alone.The role of conventionally fractionated external beam radiation therapy (RT) is well established as a treatment option for eligible prostate cancer patients; however,the use of stereotactic body radiotherapy (SBRT) in this setting is less well defined.Within the past decade,there have been a number of studies investigating the feasibility of SBRT as a potential treatment option for prostate cancer patients.SBRT has been well studied in other disease sites,and the shortened treatment course would allow for greater convenience for patients.There may also be implications for toxicity as well as disease control.In this review we present a number of prospective and retrospective trials of SBRT in the treatment of prostate cancer.We focus on factors such as biochemical progression-free survival,prostate specific antigen (PSA) response,and toxicity in order to compare SBRT to established treatment modalities.We also discuss future steps that the clinical community can take to further explore this new treatment approach.We conclude that initial studies examining the use of SBRT in the treatment of prostate cancer have demonstrated impressive rates of biochemical recurrencefree survival and PSA response,while maintaining a relatively favorable acute toxicity profile,though long-term follow-up is needed.

Using CT imaging to delineate the prostatic apex for radiation treatment planning

Background and Objective: In computed tomography (CT)-based radiotherapy planning for prostate cancer, it is difficult to precisely delineate the prostatic apex because of its relationship with the urogenital diaphragm and bulbospongiosus musculature. In this retrospective study, we analyzed the magnetic resonance imaging (MRI) and CT scans of the patients with prostate cancer to investigate the relationship between the prostatic apex and the anatomic structure visible on CT, and to provide evidence for localizing the prostatic apex in radiotherapy planning. Methods: MRI and CT scans of 108 patients with prostate cancer were analyzed to measure the distances between the prostatic apex and the bottom of ischial tuberosities, the bottom of obturator foramen, the bottom of pubic symphysis, and the bulb of the penis. The volume of the prostate was measured to analyze its relationship with the localization of the prostatic apex. Results: The prostatic apex was located (13.1 ± 3.3) mm above the bulb of the penis, (11.0 ± 5.4) mm above the bottom of the obturator foramen, (31.3 ± 5.5) mm above the ischial tuberosities, and (7.1 ± 4.7) mm above the bottom of the symphysis pubis. There was no correlation between the size of the prostate and the localization of the prostatic apex. Conclusions: The variance of the distance between the prostatic apex and the bulb of the penis is smaller than that of the distance between the apex and bony anatomy. Delineating the target to 6 mm above the bulb of the penis can cover the prostatic apex in 95% of the patients with prostate cancer, delineating to the bottom of obturator foramen can cover the prostatic apex in 100% of the patients.

Factors influencing comfort level in head and neck neoplasm patients receiving radiotherapy

Objective:To determine factors that influence comfort in head and neck neoplasm patients receiving radiotherapy.Methods:In total,200 head and neck neoplasm patients receiving radiotherapy were recruited from three tertiary first class hospitals.They were assessed by Radiotherapy Comfort Questionnaire for patients with head and neck neoplasm,Social Support Scale,and Medical Coping Modes Questionnaire.Results:The total score of comfort was 60.54±8.32.Multiple linear regression analysis indicated that number of radiation treatments,family accompaniment,educational level,resignation coping mode,complications due to diabetes,accompanying chemotherapy,and the utilization of social support significantly influenced comfort level(p<0.05).Among these,number of radiation treatments,complications due to diabetes,accompanying chemotherapy,and resignation coping were negative factors.Conclusion:Encouraging utilization of social support systems and a positive coping mode is important for increasing comfort level in head and neck neoplasm patients during radiotherapy.Nurses should pay particular attention to those patients during later stages of radiotherapy or chemotherapy,with diabetes,without family accompaniment,and with lower education level.

Loss of NEIL3 activates radiotherapy resistance in the progression of prostate cancer

Objective:To explore the genetic changes in the progression of castration-resistant prostate cancer(CRPC)and neuroendocrine prostate cancer(NEPC)and the reason why these cancers resist existing therapies.Methods:We employed our CRPC cell line microarray and other CRPC or NEPC datasets to screen the target gene NEIL3.Lentiviral transfection and RNA interference were used to construct overexpression and knockdown cell lines.Cell and animal models of radiotherapy were established by using a medical electron linear accelerator.Flow cytometry was used to detect apoptosis or cell cycle progression.Western blot and qPCR were used to detect changes in the protein and RNA levels.Results:TCGA and clinical patient datasets indicated that NEIL3 was downregulated in CRPC and NEPC cell lines,and NEIL3 was correlated with a high Gleason score but a good prognosis.Further functional studies demonstrated that NEIL3 had no effect on the proliferation and migration of PCa cells.However,cell and animal radiotherapy models revealed that NEIL3 could facilitate the radiotherapy sensitivity of PCa cells,while loss of NEIL3 activated radiotherapy resistance.Mechanistically,we found that NEIL3 negatively regulated the expression of ATR,and higher NEIL3 expression repressed the ATR/CHK1 pathway,thus regulating the cell cycle.Conclusions:We demonstrated that NEIL3 may serve as a diagnostic or therapeutic target for therapy-resistant patients.

Glycolytic potential enhanced by blockade of pyruvate influx into mitochondria sensitizes prostate cancer to detection and radiotherapy

Objective:This study aimed to evaluate the effects of mitochondrial pyruvate carrier(MPC)blockade on the sensitivity of detection and radiotherapy of prostate cancer(PCa).Methods:We investigated glycolysis reprogramming and MPC changes in patients with PCa by using metabolic profiling,RNASeq,and tissue microarrays.Transient blockade of pyruvate influx into mitochondria was observed in cellular studies to detect its different effects on prostate carcinoma cells and benign prostate cells.Xenograft mouse models were injected with an MPC inhibitor to evaluate the sensitivity of 18F-fluorodeoxyglucose positron emission tomography with computed tomography and radiotherapy of PCa.Furthermore,the molecular mechanism of this different effect of transient blockage towards benign prostate cells and prostate cancer cells was studied in vitro.Results:MPC was elevated in PCa tissue compared with benign prostate tissue,but decreased during cancer progression.The transient blockade increased PCa cell proliferation while decreasing benign prostate cell proliferation,thus increasing the sensitivity of PCa cells to 18F-PET/CT(SUVavg,P=0.016;SUVmax,P=0.03)and radiotherapy(P<0.01).This differential effect of MPC on PCa and benign prostate cells was dependent on regulation by a VDAC1-MPC-mitochondrial homeostasis-glycolysis pathway.Conclusions:Blockade of pyruvate influx into mitochondria increased glycolysis levels in PCa but not in non-carcinoma prostate tissue.This transient blockage sensitized PCa to both detection and radiotherapy,thus indicating that glycolytic potential is a novel mechanism underlying PCa progression.The change in the mitochondrial pyruvate influx caused by transient MPC blockade provides a critical target for PCa diagnosis and treatment.

Undescended epididymo-testicular metastasis from prostatic carcinoma

Dear Sir, Metastasis of prostatic carcinoma to testis is un- common in the clinical situation, and the involvement of the epididymis is even rarer. Heidrich et al. [1] found only 80 cases of testicular involvement in prostate cancer in published reports. In 1993, Wiebe et al. [2] found only 14 previous cases of epididymal metastasis from prostatic carcinoma in published work. The simulta- neous involvement of testis and epididymis was reported by Suhler and Blanchard in 1980 [3]. To our knowledge, this was the first documented case of a prostatic carcinoma metastasizing to undescended testis and epididymis.

Analysis on chromosome 8 heterozygosity loss in humanprostate carcinoma and high grade prostaticintraepithelial neoplasia

Objective: To analysis the chromosome 8 heterozygosity loss in human prostate carcinoma and high grade prostatic intraepithelial neoplasia. Methods: Pure DNA was obtained from prostate neoplasms and normal tissues by tissue microdissection. The chromosome 8 heterozygosity loss was detected by PCR based micro-satellite polymorphism analysis technique using 14 pairs of microsatellite primers in 10 samples of prostate carcinoma and 10 samples of high grade prostatic intraepithelial neoplasia. Results: There were different frequencies of chromosome 8 heterozygosity loss in 10 samples of prostate carcinoma. 8p23.1-p23.2 and p21-p22 were two high frequency heterozygosity loss regions. Chromosome 8 heterozygosity loss was detected in 3 samples of high grade prostatic intraepithelial neoplasia. Conclusion: There were high frequency heterozygosity loss regions on chromosome 8 of prostate carcinoma, located at 8p23.1-p23.2 and p21-p22. The high grade prostatic intraepithelial neoplasia and prostate carcinoma share the same allelic loss on 8p. Tumor suppressor genes located at these two regions may be potentially involved in the initiation and progression of prostate carcinoma.

Are all prostate cancer patients "fit" for salvage radiotherapy?

The indication for salvage radiotherapy(RT)(SRT)in patients with biochemically-recurrent prostate cancer after surgery is based on prostate-specific antigen(PSA)levels at the time of biochemical recurrence.Although there are clear criteria(pT3-pT4 disease and/or positive margins)for the use of adjuvant radiotherapy,no specific clinical or tumour-related criteria have yet been defined for SRT.In retrospective series,5-year biochemical progression-free survival(PFS)ranges from 35%-85%,depending on the PSA level at the start of RT.Two phase 3 trials have compared SRT with and without androgen deprivation therapy(ADT),finding that combined treatment(SRT+ADT)improves both PFS and overall survival.Similar to adjuvant RT,the indication for ADT is based on tumour-related factors such as PSA levels,tumour stage,and surgical margins.The number of patients referred to radiation oncology departments for SRT continues to rise.In the present article,we define the clinical,therapeutic,and tumour-related factors that we believe should be evaluated before prescribing SRT.In addition,we propose a decision algorithm to determine whether the patient is fit for SRT.This algorithm will help to identify patients in whom radiotherapy is likely to improve survival without significantly worsening quality of life.

Expression and Implication of Hypoxia Inducible Factor-1α in Prostate Neoplasm

Summary: To study the expression of hypoxia inducible factor-1α (HIF-1α) protein in prostate cancer (Pca) and its biological significance, the expression of HIF-1α was assayed by means of immunohistochemical technique in 42 prostate cancer, 12 prostatic intraepithelial neoplasm (PIN) and 9 normal prostate tissue (NP) specimens. Western blot was used to examine the expression of HIF-1α in prostate cancer cell line (PC-3M) induced by different oxygen tension. HIF-1α expression was positive in 33 Pca and 9 PIN specimens, and the positive rate of HIF-1α was higher in distant metastasis patients than in patients without metastasis of prostate cancer (P<0.05), while there was no expression of HIF-1α in NP. The level of HIF-1α in PC-3M significantly increased with the decrease of oxygen tension (P<0.01). Overexpression of HIF-1α is the preliminary event of the formation of Pca, which may induce carcinoma into malignant phenotype. Thus it may serve as an early diagnosis marker and the novel target for Pca treatment.

The Effect of Treatment Position on Rectal and Bladder Dose-Volume Histograms for Prostate Radiotherapy Planned with 3-Dimensional Conformal Radiotherapy, Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy

Purpose: To compare target coverage and organ at risk (OAR) sparing in the supine and prone positions with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) in low- and high-risk prostate radiotherapy cases. Materials and Methods: Using magnetic resonance images of five healthy volunteers, six treatment plans (supine 3DCRT, prone 3DCRT, supine IMRT, prone IMRT, supine VMAT and prone VMAT) were generated. Planning target volume 1 (PTV1) was defined as the prostate gland plus the seminal vesicles with adequate margins in a high-risk setting, while PTV2 was defined as prostate only with margins in a low-risk setting. The mean dose for both PTV1 and PTV2 was set at 78 Gy. Plans generated by each of the 3 techniques were compared between the supine and prone positions using dose-volume histograms (DVHs). Results: For PTV1, prone 3DCRT provided a significantly higher D98% than did supine 3DCRT, and its homogeneity index (HI) was significantly better. IMRT and VMAT values did not differ significantly between the prone and supine positions. For PTV2, no values differed significantly between the supine and prone positions under any treatment plan. With respect to OAR, the rectal D mean, D2%, V50, and V60 values of PTV1 were statistically higher in supine 3DCRT than in prone 3DCRT, while there were no significant differences in rectal values between the supine and prone positions with IMRT or VMAT. The rectal Dmean, V50, V60, V70, and V75 values of prone 3DCRT were significantly higher than those of supine IMRT or supine VMAT. There were no significant differences in any values for the rectum and bladder for PTV2. Conclusion: Although prone 3DCRT was found to be superior to supine 3DCRT in terms of rectal sparing in high-risk prostate cancer, IMRT and VMAT techniques could possibly cover this disadvantage.

Image-Guided Radiotherapy Dose Escalation in Intermediate and High Risk Cancer Prostate Patients and Its Effect on Treatment Toxicity

Purpose: To study the effect of escalating radiation dose;in intermediate and high risk prostate cancer patients;via online image-guidance on acute toxicities. Patients and Methods: thirty-eight prostate cancer patients were treated by using simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) with online image guided correction via kilo voltage cone beam computed tomography (KV-CBCT)/electronic portal imaging device (EPID) of trans-rectal ultrasound (TRUS)-inserted intraprostatic gold fiduciary markers. High-risk patients received a median dose of 80.5 Gy to prostate and 56 Gy to pelvic nodes in 35 fractions over 7 weeks. Intermediate-risk patients received a similar prostate dose over the same overall treatment time. Acute toxicity (bladder, rectal and bowel symptoms) was reported once weekly during the radiation course and up to 3 months from the end of the radiation course. Results: The image guided (IG)-IMRT allows escalating the radiation dose delivered to the prostate through minimizing the margin of setup error to less than 0.5 cm with subsequent sparing of nearby organs at risk. Out of thirty-eight patients, no patient developed >grade 1 acute rectal toxicity, 7.9% of patients experienced grade 3 urinary toxicity and there was no reported small intestinal toxicity. Conclusion: Escalating the radiation dose more than 80 Gy in intermediate and high risk prostate cancer patients was safe and not associated with grade 3 - 4 RTOG toxicity when guided by online verification of intra-prostatic fiducial markers.