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.

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.

Diagnosis and treatment of primary seminoma of the prostate:A case report and review of literature

BACKGROUND Primary seminoma of the prostate(PSP)is a rare type of extragonadal germ cell tumour that is easily misdiagnosed,owing to the lack of specific clinical features.It is therefore necessary for clinicians to work toward improving the accuracy of PSP diagnosis.CASE SUMMARY A 59-year-old male patient presenting with acute urinary retention was admitted to a local hospital.A misdiagnosis of benign prostatic hyperplasia led to an improper prostatectomy.Histopathology revealed PSP invading the bladder neck and bilateral seminal vesicles.Further radiotherapy treatment for the local lesion was performed,and the patient had a disease-free survival period of 96 mo.This case was analysed along with 13 other cases of PSP identified from the literature.Only four of the cases(28.6%)were initially confirmed by prostate biopsy.In these cases,imaging examinations showed an enlarged prostate(range 6-11 cm)involving the bladder neck(13/14).Of the 14 total cases,11(78.6%)presented typical pure seminoma cell features,staining strongly positive for placental alkaline phosphatase,CD117,and OCT4.The median age at diagnosis was 51(range 27-59)years,and patients had a median progression-free survival time of 48(range 6-156)mo after treatment by cisplatin-based chemotherapy combined with surgery or radiotherapy.The remaining three were cases of mixed embryonal tumours with focal seminoma,which had clinical features similar to those of pure PSP,in addition that they also had elevated serum alpha fetoprotein,beta-human chorionic gonadotropin,and lactose dehydrogenase.CONCLUSION PSP should be considered in patients younger than 60 years with an enlarged prostate invading the bladder neck.Further prostate biopsies may aid in proper PSP diagnosis.Cisplatin-based chemotherapy is still the main primary therapy for PSP.

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.

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.

Signal intensity changes of dentate nucleus on plain MR T1WI innasopharyngeal carcinoma patients after radiotherapy andmultiple injections of gadolinium-base contrast agent

Objective To observe changes of plain MR T1WI signal intensity of dentate nucleus in nasopharyngeal carcinoma patients after radiotherapy and multiple times of intravenous injection of gadolinium-based contrast agent(GBCA).Methods Fifty patients with pathologically confirmed nasopharyngeal carcinoma and received intensity-modulated radiotherapy were retrospectively enrolled as the nasopharyngeal carcinoma group,and 50 patients with other malignant tumors and without history of brain radiotherapy were retrospectively enrolled as the control group.All patients received yearly GBCA enhanced MR examinations for the nasopharynx or the head.T1WI signal intensities of the dentate nucleus and the pons on same plane were measured based on images in the year of confirmed diagnosis(recorded as the first year)and in the second to the fifth years.T1WI signal intensity ratio of year i(ranging from 1 to 5)was calculated with values of dentate nucleus divided by values of the pons(ΔSI i),while the percentage of relative changes of year j(ranging from 2 to 5)was calculated withΔSI j compared toΔSI 1(Rchange j).The values of these two parameters were compared,and the correlation ofΔSI and GBCA injection year-time was evaluated within each group.Results No significant difference of gender,age norΔSI 1 was found between groups(all P>0.05).The second to the fifth yearΔSI and Rchange in nasopharyngeal carcinoma group were all higher than those in control group(all P<0.05).Within both groups,ΔSI was positively correlated with GBCA injection year-time(both P<0.05).Conclusion Patients with nasopharyngeal carcinoma who underwent radiotherapy and multiple times of intravenous injection of GBCA tended to be found with gradually worsening GBCA deposition in dentate nucleus,for which radiotherapy might be a risk factor.

Comprehensive treatment for metastatic castration-resistant prostate cancer with neuroendocrine differentiation:a case report

Retrospective analysis of the progression of a case of metastatic castration-resistant prostate cancer with neuroendocrine differentiation:the patient was a 65 year old man with prostate adenocarcinoma on prostate biopsy,Gleason 4+4 score=8,70%,ISUP4 group,localized invasion of nerves.Progressed to metastatic castration-resistant prostate cancer after 8 months of novel endocrine therapy,persistent elevated PSA after endocrine therapy,chemotherapy,and radiation,abdominal metastasis,brain metastasis,gastric metastasis,and staging as neuroendocrine differentiation after second prostate biopsy,which is a highly malignant subtype and has been concerned as a mechanism of resistance to targeted therapies.We discuss how to choose a more optimal treatment plan and outline the patient's diagnostic and therapeutic course.We provide a reflection for the clinical study of metastatic castration-resistant prostate cancer with neuroendocrine type.

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.

Construction of a Simple Rectum Model Using Image Guidance in Prostate Patients Treated with 3D Conformal Radiotherapy

Purpose: To evaluate the performance of a rectum model in predicting late rectal toxicity of prostate patients undergoing 3D conformal radiation therapy while following a dietary protocol combined with image guidance. Methods: A linear accelerator equipped with a Cone Beam Computed Tomography (CBCT) system was used to treat 20 patients who were following a dietary protocol. The set-up was verified by co-registering CBCT scans with the planning CT scan (pCT). A mean dose volume histogram () as the arithmetical mean of the rectum DVHs from each CBCT scan was obtained. A suitably defined 3D rectum model (Average Rectum, AR) was defined and its DVH (DVHAR) was calculated. DVHs were also evaluated for the first five CBCT scans using both methods (5 >?and DVHAR5). The Lyman-Kutcher-Burman NTCP model with QUANTEC parameters was used to compare the calculated DVHs. The QUANTEC dose values were used to describe the time behaviour of the relative volumes using the Gamma Distribution for the frequency of the relative rectum volumes at each QUANTEC dose value. Results: No statistically significant differences between NTCPAR5 and NTCPAR and between NTCP and NTCP were found. The best agreement with the observed toxicity rate (0%) was obtained form DVHAR. The Gamma Distributions of the rectum volumes at the QUANTEC dose levels were found to be highly variable among the patients. Conclusions: Both dietary protocol and image guidance were found effective in limiting late rectal toxicity. AR was a better predictor for late rectal toxicity and better described the rectum volume during the treatment course. Finally, from the Gamma distributions, and from our toxicity data, we can suggest V75 as the best predictor of late rectal toxicity.

Predictability and Management of OARs Toxicity in Patients with Prostate Cancer Treated with High-Dose Radiotherapy

Aim: To evaluate the predictability of toxicity analyzing the dose-volume histograms (DVHs) and to verify the effectiveness of preventive measures limiting side toxicity considering the evolution of the radiation techniques for prostate cancer treatment. Materials and Methods: 208 patients with localized prostate cancer were treated with exclusive radiotherapy until 73.8 Gy (group A) or 79.2 Gy (group B) with the dose escalation technique. Preventive measures to minimize the side effects were recommended in group B. Results: The assessment of genitourinary toxicity was similar while gastrointestinal toxicity was better in group B. Valuating the treatment plans, we found that most of the patients developing toxicity had “borderline” DVHs. Conclusion: Our analysis led to the establishment of a protocol for the management of patients with “border-line” DVH.

Three-Tesla Magnetic Resonance and Computed Tomography Imaging in Three-Dimensional Conformal Radiotherapy for Localized Prostate Cancer

Aims and background: we evaluate CT-3Tesla MRI fusion in conformal radiotherapy for localized prostate cancer.Methods: 18 consecutive patients underwent a 3T MRI scan under radiotherapy planning conditions, after the CT scan. Bowel and bladder preparation were prescribed. CT and MR images were automatically fused;prostate and seminal vesicles were contoured on CT and on MRI, organs at risk were defined on CT-MRI fusion. Late rectal and sexual toxicity, differences in target volume between MRI and CT and differences in rectal and penile bulb dose distribution based on CT only or on CT-MRI fusion were evaluated.Results: one patient experienced a late rectal toxicity;no patient had sexual toxicity. The difference between the mean MRI and CT target volumes was statistically significant (p = 0.0001 paired Student's t-test). The dose-volume histogram (DVH) analysis shows a significant reduction of the dose received by the rectum and the penile bulb in MRI-plans compared to CT-plans.Conclusions: 3 Tesla MRI scan under radiotherapy planning conditions along with bowel preparation significantly improves the definition of the target volume sparing normal tissue irradiation.