The impact of androgen deprivation therapy on setup errors during external beam radiation therapy for prostate cancer

Purpose

To determine whether setup errors during external beam radiation therapy (RT) for prostate cancer are influenced by the combination of androgen deprivation treatment (ADT) and RT.

Materials and methods

Data from 175 patients treated for prostate cancer were retrospectively analyzed. Treatment was as follows: concurrent ADT plus RT, 33 patients (19%); neoadjuvant and concurrent ADT plus RT, 91 patients (52%); RT only, 51 patients (29%). Required couch shifts without rotations were recorded for each megavoltage (MV) cone beam computed tomography (CBCT) scan, and corresponding alignment shifts were recorded as left–right (x), superior–inferior (y), and anterior–posterior (z). The nonparametric Mann–Whitney test was used to compare shifts by group. Pearson’s correlation coefficient was used to measure the correlation of couch shifts between groups. Mean prostate shifts and standard deviations (SD) were calculated and pooled to obtain mean or group systematic error (M), SD of systematic error (Σ), and SD of random error (σ).

Results

No significant differences were observed in prostate shifts in any direction between the groups. Shifts on CBCT were all less than setup margins. A significant positive correlation was observed between prostate volume and the z?direction prostate shift (r = 0.19, p = 0.04), regardless of ADT group, but not between volume and x? or y?direction shifts (r = 0.04, p = 0.7; r = 0.03, p = 0.7). Random and systematic errors for all patient cohorts and ADT groups were similar.

Conclusion

Hormone therapy given concurrently with RT was not found to significantly impact setup errors. Prostate volume was significantly correlated with shifts in the anterior–posterior direction only.

     

Australian prostate-specific antigen outcome and toxicity following radiation therapy for localized prostate cancer

The objective of the present study was to examine prostate-specific antigen relapse free survival (PSA-RFS) and morbidity following 'conventional' radical radiation therapy for prostate cancer in two Australian regional treatment services. Four hundred and eighty men with clinically localized prostate cancer were treated between 1993 and 1997 at Liverpool and Westmead Hospitals using a standardized 4-field, CT-planned radiotherapy technique. Principal endpoints were PSA-RFS (American Society for Therapeutic Radiology and Oncology guidelines definition) and late rectal and urinary morbidity (Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria). The median follow up of patients from the end of RT was 55 months. Prospectively, they were divided into three prognostic categories: (i) high risk T3 or 4 and/or PSA > 20 ng/mL and/or Gleason score 8-10 (40% of cohort); (ii) intermediate risk T1 or 2 and PSA 10-20 ng/mL and/or Gleason score 7 (33% of cohort); and (iii) low risk T1 or 2 and PSA < 10 ng/mL and Gleason score < 6 (27% of cohort). The 5-year actuarial PSA-RFS was 53% for the whole patient group. The 4-year rates were 32, 56 and 75% for high, intermediate and low risk groups, respectively. On multivariate analysis, T-stage, Gleason score, pre-RT-PSA were strong independent predictors of PSA-defined outcome. Late (grade 2) rectal and urinary morbidity occurred at some point in time in the post-RT period in 8.0 and 5.8% of patients, respectively. These results confirm that low Gleason score, low T stage, presenting PSA < 10 ng/mL and nadir < 1 ng/mL remain the strongest predictors of a good outcome. Long-term toxicity was very acceptable. However, further improvement in outcome is desirable, and with the adoption of new technology allowing escalation of radiotherapy doses such an expectation might be achieved.     

Use of androgen deprivation and salvage radiation therapy for patients with prostate cancer and biochemical recurrence after prostatectomy

Aim

Overview on the use of androgen deprivation therapy (ADT) added to salvage radiation therapy (SRT) for prostate cancer patients with biochemical recurrence after prostatectomy.

Methods

The German Society of Radiation Oncology (DEGRO) expert panel summarized available evidence published between January 2009 and May 2017, and assessed the validity of the information on outcome parameters including overall survival (OS) and treatment-related toxicity.

Results

Two randomized controlled trials and nine relevant retrospective analyses were identified. The RTOG 9601 trial showed an OS improvement for the combination of 2 years of bicalutamide and SRT compared to SRT alone after a median follow-up of 13 years. This improvement appeared to be restricted to those patients with a prostate specific antigen (PSA) level before SRT of ≥0.7?ng/mL. The GETUG AFU-16 trial showed that after a median follow-up of 5 years, the addition of 6 months of goserelin to SRT improved progression-free survival (PFS; based on biochemical recurrence) as compared to SRT alone. ADT in both trials was not associated with increased major late toxicities. Results of retrospective series were inconsistent with a suggestion that the addition of ADT improved biochemical PFS especially in patients with high-risk factors such as Gleason Score ≥8 and in the group with initially negative surgical margins.

Conclusions

ADT combined with SRT appears to improve OS in patients with a PSA level before SRT of ≥0.7?ng/mL. In patients without persistent PSA after prostatectomy and PSA levels of <0.7?ng/mL, ADT should not routinely be used, but may be considered in patients with additional risk factors such as Gleason Score ≥8 and negative surgical margins.

     

前列腺癌放射治疗进展

现代计算机技术推动医学影像技术高速发展,高水平的图像技术又推动放射治疗计划系统进入到更复杂、更高水平。放射治疗计划的设计由原来的二维图像和人工计算发展到了X射线图像和复杂的计算机运算。在治疗过程中,由于肿瘤代谢、抗原的差别,已经考虑到其与正常组织不同的生物学变量,使执行治疗计划时更加精确,如摆位误差、器官运动等已被全面系统地考虑,故又称四维放射治疗。     

High-dose-rate interstitial brachytherapy in combination with androgen deprivation therapy for prostate cancer

Background and purpose

To evaluate the effectiveness of high-dose-rate interstitial brachytherapy (HDR-ISBT) as the only form of radiotherapy for high-risk prostate cancer patients.

Patients and methods

Between July 2003 and June 2008, we retrospectively evaluated the outcomes of 48 high-risk patients who had undergone HDR-ISBT at the National Hospital Organization Osaka National Hospital. Risk group classification was according to the criteria described in the National Comprehensive Cancer Network (NCCN) guidelines. Median follow-up was 73 months (range 12–109 months). Neoadjuvant androgen deprivation therapy (ADT) was administered to all 48 patients; 12 patients also received adjuvant ADT. Maximal androgen blockade was performed in 37 patients. Median total treatment duration was 8 months (range 3–45 months). The planned prescribed dose was 54 Gy in 9 fractions over 5 days for the first 13 patients and 49 Gy in 7 fractions over 4 days for 34 patients. Only one patient who was over 80 years old received 38 Gy in 4 fractions over 3 days. The clinical target volume (CTV) was calculated for the prostate gland and the medial side of the seminal vesicles. A 10-mm cranial margin was added to the CTV to create the planning target volume (PTV).

Results

The 5-year overall survival and biochemical control rates were 98 and 87?%, respectively. Grade 3 late genitourinary and gastrointestinal complications occurred in 2 patients (4?%) and 1 patient (2?%), respectively; grade 2 late genitourinary and gastrointestinal complications occurred in 5  patients (10?%) and 1 patient (2?%), respectively.

Conclusion

Even for high-risk patients, HDR-ISBT as the only form of radiotherapy combined with ADT achieved promising biochemical control results, with acceptable late genitourinary and gastrointestinal complication rates.     

Multiplanar arc boost radiation therapy for prostate cancer

Localized prostatic carcinoma may be treated with either radical surgery or radiation therapy. Radiation therapy techniques for localized prostatic carcinoma include mega-voltage external irradiation or interstitial implantation, usually with iodine-125 seeds. Two external-beam techniques, multiplanar arc and biplanar arc, are additional options for the treatment of localized prostatic carcinoma. Film dosimetry measurements were made in pelvic phantoms to compare the isodose distributions of various external-beam radiation therapy techniques for boost treatment of prostate target volumes. Idealized calculations were performed to determine the isodose distribution of an I-125 implant. A comparison of these techniques shows that the multiplanar and biplanar arc techniques produce isodose distributions that may be useful in the treatment of prostate carcinoma.     

Spinal multiparametric MRI and DEXA changes over time in men with prostate cancer treated with androgen deprivation therapy: a potential imaging biomarker of treatment toxicity

Objectives

To explore changes in bone mineral density (BMD) measured by DEXA and MRS fat fraction (FF), Dixon FF, and ADC in lower spinal vertebral bodies in men with prostate cancer treated with androgen deprivation therapy (ADT).

Methods

Twenty-eight men were enrolled onto a clinical trial. All received ADT. DEXA imaging was performed at baseline and 12 months. L-spine MRI was done at baseline and 6 months.

Results

The number of patients who underwent DEXA, Dixon, ADC, and MRS at baseline/follow-up were 28/27, 28/26, 28/26, and 22/20. An increase in FF was observed from T11 to S2 (average 1 %/vertebra). There was a positive correlation between baseline MRS FF and Dixon FF (r?=?0.85, p?<?0.0001) and a negative correlation between MRS FF and ADC (r?=?-0.56, p?=?0.036). Over 6 months, MRS FF increased by a median of 25 % in relative values (p?=?0.0003), Dixon FF increased (p?<?0.0001) and ADC values decreased (p?=?0.0014). Men with >5 % BMD loss after 1 year had triple the percentage increase in MRS FF at 6 months (61.1 % vs. 20.9 %, p?=?0.19).

Conclusions

Changes are observed on L-spine MRI after 6 months of ADT. Further investigation is warranted of MRS change as a potential predictive biomarker for later BMD loss.

Key Points

? Spinal marrow fat fraction increases after 6 months of androgen deprivation therapy. ? More inferior vertebral bodies tend to have higher fat fractions. ? MRS fat fraction changes were associated with later changes in DEXA BMD.

     

Palliative radiation therapy for localized prostate symptoms in hormone refractory prostate cancer

Hormone refractory prostate cancer (HRPCa) can cause debilitating local pelvic symptoms including urinary obstruction, pelvic pain, haematuria and obstructive rectal symptoms. High-dose palliative radiation therapy (RT) is used in many centres to relieve these symptoms despite limited published evidence for its efficacy. This study aimed to assess if RT provides effective and durable palliation for local prostate symptoms in HRPCa. Thirty-five HRPCa patients received RT to the prostate for local symptoms between November 2002 and March 2006. The median dose was 60 Gy in 30 fractions (range 30-70 Gy). Response around a 6-month time point was scored as complete resolution, partial resolution, no change or local progression. Time to progression (defined as new or recurrent symptoms) or persistence of symptoms was recorded. Factors influencing outcome, such as dose, type and number of symptoms and previous transurethral resection, were examined. Twenty-one (60%) patients had a complete (n=3) or partial improvement (n=18) in symptoms. All three complete responders had haematuria as their only symptom. In the eight (23%) patients with local progression, half progressed during treatment and all had done so within 3 months. This series represents a bigger cohort than any reported in published works examining this issue. It suggests that radiation is effective in palliating the local pelvic symptoms in HRPCa.     

前列腺癌外放射治疗的靶区勾画

外放射治疗是局限期和局部晚期前列腺癌的主要治疗手段,治疗中靶区的勾画至关重要。前列腺癌外放射治疗中要勾画的靶区包括临床靶区(CTV)、计划靶区(PTV)和盆腔淋巴结引流区。综述目前国内外勾画各靶区的方法,重点分析前列腺癌CTV的勾画,介绍MR与CT影像融合的方法勾画临床靶区的优势,以及如何利用CT影像勾画前列腺癌临床靶区。     

Dosimetric effects of weight loss or gain during volumetric modulated arc therapy and intensity-modulated radiation therapy for prostate cancer

Weight loss or gain during the course of radiation therapy for prostate cancer can alter the planned dose to the target volumes and critical organs. Typically, source-to-surface distance (SSD) measurements are documented by therapists on a weekly basis to ensure that patients' exterior surface and isocenter-to-skin surface distances remain stable. The radiation oncology team then determines whether the patient has undergone a physical change sufficient to require a new treatment plan. The effect of weight change (SSD increase or decrease) on intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) dosimetry is not well known, and it is unclear when rescanning or replanning is needed. The purpose of this study was to determine the effects of weight change (SSD increase or decrease) on IMRT or VMAT dose delivery in patients with prostate cancer and to determine the SSD change threshold for replanning. Whether IMRT or VMAT provides better dose stability under weight change conditions was also determined. We generated clinical IMRT and VMAT prostate and seminal vesicle treatment plans for varying SSDs for 10 randomly selected patients with prostate cancer. The differences due to SSD change were quantified by a specific dose change for a specified volume of interest. The target mean dose, decreased or increased by 2.9% per 1-cm SSD decrease or increase in IMRT and by 3.6% in VMAT. If the SSD deviation is more than 1 cm, the radiation oncology team should determine whether to continue treatment without modifications, to adjust monitor units, or to resimulate and replan.     

Salvage prostate brachytherapy for localized prostate cancer failure after external beam radiation therapy

PURPOSE: To determine the toxicity and clinical outcome of salvage prostate brachytherapy for localized prostate cancer failure after external beam radiation therapy. METHODS AND MATERIALS: Twenty-one patients underwent (103)Pd salvage brachytherapy (median minimum peripheral dose, 90Gy) after local failure after external beam radiation (median dose, 66.6Gy) from 1/21/1998 to 4/5/2005. The median age was 72 years. Six patients had prior transurethral resection of the prostate. The median Gleason score was 7 and the median preimplant prostate-specific antigen was 3.8. Twelve patients received concurrent androgen ablation with prostate brachytherapy. Biochemical failure was defined as three consecutive rises in prostate-specific antigen scored at the call date, initiation of hormone therapy, or clinical failure. Toxicity was defined according to the National Cancer Institute common toxicity criteria and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme. RESULTS: With a median followup of 36 months, the actuarial 3-year and 5-year overall survival rates were 81% and 81%, and the biochemical failure-free survival rates were 94% and 38%, respectively. There was no significant difference in biochemical failure-free survival (p=0.98) and overall survival (p=0.13) for patients who had androgen ablation. Four patients developed biochemical failure and 1 patient developed distant metastasis at 59 months from treatment. Four patients had Grade 2 genitourinary adverse events, 2 patients had Grade 1 genitourinary adverse events, and 1 patient had a Grade 2 gastrointestinal adverse event. There were no Grade 3 or higher adverse events. All three deaths were secondary to other medical comorbidities. CONCLUSIONS: Salvage prostate brachytherapy after external beam radiation failure can be safely performed with acceptable biochemical control. This treatment option should be considered for patients who have prolonged life expectancy after localized external beam radiation failure.     

Cost-effectiveness of prostate boost with high-dose-rate brachytherapy versus intensity-modulated radiation therapy in the treatment of intermediate-high risk prostate cancer

PurposeThe recently published ASCENDE-RT randomized clinical trial demonstrated improved biochemical control, albeit with increased toxicity, for a prostate boost with brachytherapy versus external beam radiation therapy alone in patients with intermediate-high risk prostate cancer. In this study, we investigated the cost-effectiveness of these two modalities in the treatment of intermediate-high risk prostate cancer.Methods and materialsA multistate Markov model was created to model a patient with intermediate-high risk prostate cancer. The two treatment options modeled were (1) 23 fractions of intensity-modulated radiation therapy (IMRT) and two fractions of high-dose-rate prostate brachytherapy (brachytherapy boost) and (2) 44 fractions of IMRT (IMRT alone). Each patient received 1 year of hormone therapy, per the ASCENDE-RT protocol. Model assumptions, including clinical outcomes, toxicity, and utilities were derived from the medical literature. Costs of radiation therapy were estimated using Medicare reimbursement data.ResultsThe estimated expected lifetime cost of brachytherapy boost was $68,696, compared to $114,944 for IMRT alone. Brachytherapy boost significantly lowered expected lifetime treatment costs because it decreased the incidence of metastatic castration-resistant prostate cancer, cutting the use of expensive targeted therapy for metastatic castration-resistant prostate cancer. Brachytherapy boost had an expected quality-adjusted life years of 10.8 years, compared to 9.3 years for IMRT alone. One-way sensitivity analyses of our results found brachytherapy boost to be cost-effective over a wide range of cost, utility, and cancer progression rate assumptions.ConclusionsIMRT with high-dose-rate brachytherapy boost is a cost-effective treatment for intermediate-high risk prostate cancer compared to IMRT alone.     

The effect of concurrent androgen deprivation and 3D conformal radiotherapy on prostate volume and clinical organ doses during treatment for prostate cancer

In this study, we investigated the shrinking effect of concurrent three-dimensional conformal radiotherapy (3D-CRT) and androgen deprivation (AD) on prostate volume, and its possible impact on the dose received by the rectum and bladder during the course of 3D-CRT. The difference between the prostatic volumes determined on pre-treatment planning CT (PL-CT) and post-treatment CT (PT-CT) following a 3D-CRT course was assessed in 52 patients with localised prostate carcinoma. The changes in mean prostate volume when compared with PL-CT and PT-CT-based measurements were assessed. The pre- and post-treatment mean prostate volumes for the whole study population were 49.7 cm³ and 41.0 cm³ (p _ 0.02), respectively. The study cohort was divided into two groups depending on the duration of neoadjuvant androgen deprivation (NAD): 23 patients (44.7%) were designated as “short NAD” (≤3 months; SNAD) and the remaining 29 (55.3%) as “long NAD” (>3 months; LNAD). Patients on SNAD experienced a significantly greater reduction in prostate volume compared with those on LNAD (14.1% vs 5.1%; p _ 0.03). A significant increase in rectum V_40–60 values in PT-CT compared with PL-CT was demonstrated. LNAD patients had significantly higher rectal V_50–70 values at PT-CT compared with the SNAD group. There was a significant decline in V₃₀–V₇₅ bladder values in PT-CT compared with PL-CT in the SNAD group. In conclusion, a higher prostate volume reduction during 3D-CRT was demonstrated when RT planning was performed within 3 months of NAD. However, this reduction and daily organ motion may lead to an unpredictable increase in rectal doses.Prostate carcinoma is (in general) a hormone-sensitive disease that has been shown to significantly benefit from androgen deprivation (AD) when added to conventional radiation therapy (RT) doses of 65–70 Gy [1–7]. Results of large randomised clinical trials have demonstrated that AD significantly improves the outcome of patients with locally advanced prostatic carcinoma when treated with external beam RT with regard to local control, biochemical-free survival and freedom from distant metastases [1, 3, 5, 8–10]. Furthermore, in the studies of the European Organization for Research and Treatment of Cancer (EORTC 22961) [1, 3] and the Radiation Therapy Oncology Group (RTOG) protocol 85–31 [2], this improvement turned into a survival advantage.Neoadjuvant androgen deprivation (NAD) before RT has been demonstrated to shrink the prostate volume effectively [11, 12], and thus has became a widely accepted and essential part of locally advanced prostate cancer management. On average, the prostate gland shrinks about 20–50% of its initial volume within 3 months of NAD [11–15] and, although the rate slows down, this shrinking effect continues beyond this period [16–19] The cytoreduction in the prostate provided by NAD may lower the complication rates observed at higher RT doses by reducing the target volumes, depending on the reduced doses received by normal tissues [15, 20].A relatively long treatment interval (7–8 weeks) is usually mandated for three-dimensional conformal radiotherapy (3D-CRT) of prostate carcinoma, and the shrinkage of the prostate gland continues during this period. In this setting, it is reasonable to assume, theoretically, that there is a possibility of a larger than planned volume of surrounding critical organs that may shift into the intermediate or high-dose regions during the RT course, which may unpredictably increase the dose received by the rectum and bladder [11, 12, 21]. Based on the above assumption, we planned to evaluate prostate shrinkage during 3D-CRT in relation to NAD duration, and to investigate the possible impact of this volume reduction on the dose received by the rectum and bladder by comparing the pre- and post-treatment dose volume histograms (DVHs).     

Biologically effective dose and definitive radiation treatment for localized prostate cancer

Background and purpose

It is not clear if prolongation of definitive external radiation therapy for prostate cancer has an effect on biochemical failure. The aim of this work was to evaluate whether the biologically effective dose (BED), and in particular the duration of radiotherapy, intended as overall treatment time, has an effect on biochemical failure rates and to develop a nomogram useful to predict the 6-year probability of biochemical failure.

Patients and methods

A total of 670 patients with T1–3 N0 prostate cancer were treated with external beam definitive radiotherapy, to a total dose of 72–79.2 Gy in 40–44 fractions. The computed BED values were treated with restricted cubic splines. Variables were checked for colinearity using Spearman’s test. The Kaplan–Meier method was used to calculate freedom from biochemical relapse (FFBR) rates. The Cox regression analysis was used to identify prognostic factors of biochemical relapse in the final most performing model and to create a nomogram. Concordance probability estimate and calibration methods were used to validate the nomogram.

Results

Neoadjuvant and concomitant androgen deprivation was administered to 475 patients (70?%). The median follow-up was 80 months (range 20–129 months). Overall, the 6-year FFBR rate was 88.3?%. BED values were associated with higher biochemical failure risk. Age, iPSA, risk category, and days of radiotherapy treatment were independent variables of biochemical failure.

Conclusion

A prolongation of RT (lower BED values) is associated with an increased risk of biochemical failure. The nomogram may be helpful in decision making for the individual patient.     

68Ga-PSMA-11 PET imaging in patients with ongoing androgen deprivation therapy for advanced prostate cancer

Annals of Nuclear Medicine - Prostate-specific membrane antigen (PSMA) targeted positron emission tomography (PET) imaging significantly improved the detection of recurrent prostate cancer (PCa)....