Quality assurance audit in an Australasian phase III trial of accelerated radiotherapy for head and neck cancer (TROG 91.01). Trans-Tasman Radiation Oncology Group

The Trans-Tasman Radiation Oncology Group (TROG) initiated a randomized trial, testing accelerated (twice daily) radiotherapy against conventional radiotherapy for stage III and stage IV squamous cell carcinoma of the head and neck in 1991. In 1996, the Trial Management Committee arranged for a technical audit of 76 cases from 11 institutions, conducted by investigators from interstate institutions. A 10% unacceptable protocol violation rate was detected, which compares favourably with initial Radiation Therapy Oncology Group (RTOG) experience in the late 1970s. Infrastructural deficits with poor quality of documentation, incomplete retrieval of films and document return have been demonstrated in some cases. The Trans-Tasman Radiation Oncology Group is actively pursuing procedural and resourcing issues in order to redress this and is actively expanding its Quality Assurance (QA) Programme with an intercentre dosimetry study. Ultimately, comprehensive clinical and technical QA site visits are planned.     

MRI-based sector analysis enhances prostate palladium-103 brachytherapy quality assurance in a phase II prospective trial of men with intermediate-risk localized prostate cancer

PurposePalladium-103 (¹⁰³Pd) may be superior to other isotopes in brachytherapy for localized intermediate-risk prostate cancer because of its relatively short half-life, higher initial dose rate, and greater dose heterogeneity within the target volume; these properties also underscore the need for accurate target delineation and postimplant quality assurance. We assessed the use of prostate sector analysis based on MRI for quality assurance after ¹⁰³Pd monotherapy.Methods and MaterialsFifty men with intermediate-risk prostate cancer underwent ¹⁰³Pd monotherapy in a prospective phase II trial at MD Anderson Cancer Center. Dosimetric analyses on day 30 after the implant were done using both CT and fused CT/MRI scans. Dosimetric variables were assessed for the entire prostate and for each of three or six sectors. Volumes and dosimetric variables were compared with paired t tests.ResultsPostimplant dosimetric variables for the entire prostate were significantly different on CT vs. CT/MRI (p = 0.019 for V₁₀₀ and p < 0.01 for D₉₀). Prostate volumes were smaller on the CT/MRI scans (p < 0.00001). The base sector contributed the greatest difference, with doses based on CT/MRI lower than those based on CT (p < 0.01 for V₁₀₀ and D₉₀). To date, these lower base doses have not affected biochemical outcomes for patients with disease in prostate base biopsy samples.ConclusionsCT/MRI is more precise than CT for prostate volume delineation and dosimetric quality assessment and thus provides superior heterogeneity control assessment after ¹⁰³Pd monotherapy implants.     

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.     

Four prognostic indices in advanced prostate cancer patients, under palliative androgen deprivation treatment

Prostate cancer (PCa) is the second leading cause of death in men aged 40 years and older ]and prognostic indices are useful in suggesting its proper treatment. The aim of this study was to evaluate the prognostic value of Gleason score (GS), TNM staging system, initial serum prostate specific antigen (PSA) and bone scintigraphy (BS) in patients with PCa under hormonal palliative treatment, in the development and progression of recurrent PCa. Our methods were as follows: Between January 2005 and December 2007, we have studied at the University General Hospital of Alexandroupolis fourty patients of mean age 77+/-7.2 years with advanced PCa under palliative treatment with antiandrogens and luteinizing hormone-releasing hormone analogues. PCa was diagnosed histologically, based on the TNM system after transrectal ultrasonography guided biopsy. The Gleason score assessment was made as described by others. Metastases were confirmed by a positive bone scintigraphy with 925 MBq (99m)Tc-MDP using a tomographic gamma camera, computerized axial tomography or magnetic resonance imagining. Measurements of PSA were conducted by the radioimmunoassay method. We also examined 20 healthy blood donors (median age 45+/-6.1 years) as controls, in order to estimate the cut-off value of PSA. Our results show the following: Thirteen of our patients had 1-6 "hot" spots and 27 had more than 6 "hot" spots in the bone scan. The median Gleason score was 7 (modal Gleason score 3+4). Serum PSA levels were higher in patients with PCa and bone metastases in comparison to those with PCa without bone metastases. Very high values of PSA (more than 50 ng/ml) were found in patients with multiple bone metastases (>6 "hot" spots). In conclusion, our findings demonstrate that the prognostic value of GS (P=0.043), TNM staging (P=0.1410), serum PSA levels (P=0.002) and BS (P=0.0135) when used alone, not always improve the prognosis to hormone indepentent but when combined (P<0.001) increase the prognosis in patients with advanced PCa under hormonal palliative treatment.     

Dosimetric outcomes in prostate brachytherapy: Is downsizing the prostate with androgen deprivation necessary?

ObjectivesA large prostate volume has historically been a relative contraindication to prostate brachytherapy (PB) because of concerns of toxicity and potential pubic arch interference. Common practice has been to downsize large prostates with androgen deprivation therapy (ADT) before proceeding with brachytherapy. The present study compares postimplant dosimetry in patients with prostate volumes >50 cc with those with prostate volumes ≤50 cc.MethodsA review of all patients who underwent PB at our institution from 2001 to 2006 was performed. Postimplant dosimetry was obtained approximately 4 weeks after brachytherapy.ResultsOne-hundred forty-five out of a total of 148 patients had available dosimetry. In the 113 patients with prostate volumes ≤50 cc (mean, 35.4 cc, range, 14.2–49.7 cc); the mean D₉₀ (dose which covers 90% of the prostate), V₁₀₀ (volume of prostate receiving 100% of the prescribed dose), V₁₅₀ (volume of prostate receiving 150% of the prescribed dose), and V₂₀₀ (volume of prostate receiving 200% of the prescribed dose) was 128.9%, 95.6%, 73.9%, and 51.2%, respectively. In the 32 patients with prostate volumes >50 cc (mean 58.1 cc, range 50.2–86.0 cc); the mean D₉₀, V₁₀₀, V₁₅₀, and V₂₀₀ was 125.1%, 95.2%, 68.2%, and 41.7%, respectively. The rectal V₁₀₀ was 1.0 cc for both cohorts. There was no statistically significant difference between the cohorts with respect to postimplant dosimetry for D₉₀, V₁₀₀, and V₁₅₀. The V₂₀₀ for prostate volumes >50 cc was significantly lower (p < 0.05).ConclusionsIn the present study, patients with prostate volumes >50 cc have postimplant dosimetry parameters similar to patients with prostate volumes ≤50 cc for D₉₀, V₁₀₀, and V₁₅₀; and significantly lower values for V₂₀₀. These results suggest that patients with large prostate volumes may not need to be routinely placed on hormonal therapy; sparing patients the side effects of hormonal therapy, and sparing the health care system the costs of luteinizing hormone-releasing hormone agonist injections.     

Factors impacting all-cause mortality in prostate cancer brachytherapy patients with or without androgen deprivation therapy

PurposeCertain subsets of patients have an increased risk of all-cause mortality when androgen deprivation therapy (ADT) is used with definitive radiotherapy. We evaluated the relationship between pretreatment serum testosterone, age, and comorbidities on survival after prostate brachytherapy in men treated with and without ADT.Methods and MaterialsFrom October 2001 to September 2005, 803 patients underwent brachytherapy and 720 had a pretreatment serum testosterone. Comorbidities were prospectively recorded for each patient (body mass index > 30, hypertension, diabetes, current smoker). Median followup was 5.0 years. 34.2% of the patients received ADT. Focus was on subset of men who might be expected to have more significant side effects associated with ADT.ResultsADT did not significantly impact overall survival (OS) in men <65 years, >65 years, with one or no comorbidities, with more than one comorbidity, or with normal/high testosterone level. ADT use in men with low testosterone level was associated with decreased OS (83.6% vs. 93.1%, p = 0.01). The adverse impact of ADT in men with low testosterone level was restricted to men with low testosterone level and more than one comorbidity (OS of 71.3% vs. 92.8%, p < 0.01), with death from cardiovascular diseases accounting for almost all of the excess mortality. The subset of men with multiple comorbidities and normal/high testosterone level did not experience adverse OS with ADT.ConclusionsLow pretreatment testosterone level may be a marker for men at increased risk of premature death with ADT. The combination of low pretreatment serum testosterone level and multiple preexisting comorbidities is associated with decreased OS when ADT is incorporated into treatment.     

Effects of strength training on muscle cellular outcomes in prostate cancer patients on androgen deprivation therapy

Androgen deprivation therapy (ADT) improves life expectancy in prostate cancer (PCa) patients, but is associated with adverse effects on muscle mass. Here, we investigated the effects of strength training during ADT on muscle fiber cross‐sectional area (CSA) and regulators of muscle mass. PCa patients on ADT were randomized to 16 weeks of strength training (STG) (n = 12) or a control group (CG; n = 11). Muscle biopsies were obtained from m. vastus lateralis and analyzed by immunohistochemistry and western blot. Muscle fiber CSA increased with strength training (898 μm², P = 0.04), with the only significant increase observed in type II fibers (1076 μm², P = 0.03). There was a trend toward a difference in mean change between groups myonuclei number (0.33 nuclei/fiber, P = 0.06), with the only significant increase observed in type I fibers, which decreased the myonuclear domain size of type I fibers (P = 0.05). Satellite cell numbers and the content of androgen receptor and myostatin remained unchanged. Sixteen weeks of strength training during ADT increased type II fiber CSA and reduced myonuclear domain in type I fibers in PCa patients. The increased number of satellite cells normally seen following strength training was not observed.     

The effect of androgen deprivation therapy on 68 Ga-PSMA tracer uptake in non-metastatic prostate cancer patients

To evaluate the effect of neoadjuvant androgen deprivation treatment (ADT) on prostate-specific membrane antigen (PSMA) tracer uptake demonstrated in 68Ga-PSMA-positron emission tomography (PET/CT) in non-metastatic hormone-naïve prostate cancer (PC) patients. The clinical data of 108 PC patients who received neoadjuvant ADT were retrospectively analyzed. All patients had a baseline 68Ga-PSMA-PET/CT scan, and a second scan was delivered median of 2.9 months after the initiation of ADT. The maximum standardized uptake value (SUVmax) of primary tumor (SUVp) and metastatic lymph nodes (SUVln) as well as PSA response were assessed between pre- and post-ADT 68Ga-PSMA-PET/CT scans. There were significant decreases in posttreatment serum PSA, SUVp, and SUVln. A decrease in SUVp was seen in 91 patients (84%) with a median value of 66% (range, 5–100%), while 17 patients (16%) had no change in or an increase in PSMA tracer uptake with a median value of 24% (range, 0–198%). Patients with Gleason score (GS) of 7 had significantly higher metabolic response rates compared to other patients. The disease progression was significantly higher only in patients with GS > 7 disease compared to GS 7 disease. The PSA response to ADT was the lowest in patients with ISUP high-grade tumors. A total of 16 patients (15%) had progressive disease, and in 9 patients (8%), radiotherapy decisions were modified according to posttreatment 68Ga-PSMA-PET/CT scans. The current study includes the largest number of patients analyzed to date and demonstrates that ADT causes a significant decrease in serum PSA values and SUVp and SUVln. The authors demonstrate that 68Ga-PSMA-PET/CT may be used as a quantitative imaging modality after neoadjuvant ADT in hormone-naïve non-metastatic PC patients.     

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)....     

Three linked nomograms for predicting biochemical failure in prostate cancer treated with radiotherapy plus androgen deprivation therapy

Background

Nomograms were established to predict biochemical recurrence (BCR) after radiotherapy (RT) with a low weight of the characteristic variables of RT and androgen deprivation therapy (ADT). Our aim is to provide a new stratified tool for predicting BCR at 4 and 7 years in patients treated using RT with radical intent.

Materials and methods

A retrospective, nonrandomized analysis was performed on 5044 prostate cancer (PCa) patients with median age 70 years, who received RT—with or without ADT—between November 1992 and May 2007. Median follow-up was 5.5 years. BCR was defined as a rise in serum prostate-specific antigen (PSA) of 2 ng/ml over the post-treatment PSA nadir. Univariate association between predictor variables and BCR was assessed by the log-rank test, and three linked nomograms were created for multivariate prognosis of BCR-free survival. Each nomogram corresponds to a category of the Gleason score—either 6,7, or 8–10—and all of them were created from a single proportional hazards regression model stratified also by months of ADT (0, 1–6, 7–12, 13–24, 25–36, 36–60). The performance of this model was analyzed by calibration, discrimination, and clinical utility.

Results

Initial PSA, clinical stage, and RT dose were significant variables (p?<?0.01). The model showed a good calibration. The concordance probability was 0.779, improving those obtained with other nomograms (0.587, 0.571, 0.554) in the database. Survival curves showed best clinical utility in a comparison with National Comprehensive Cancer Network (NCCN) risk groups.

Conclusion

For each Gleason score category, the nomogram provides information on the benefit of adding ADT to a specific RT dose.

     

DCE and DW MRI in monitoring response to androgen deprivation therapy in patients with prostate cancer: a feasibility study

Androgen deprivation therapy (ADT) is a key primary treatment for advanced and metastatic prostate cancer and is an important neoadjuvant before radiotherapy. We evaluated 3.0 T dynamic contrast-enhanced MRI and diffusion-weighted (DW) MRI in monitoring ADT response. Twenty-three consecutive patients with prostate cancer treated by primary ADT were included. Imaging was performed at baseline and 3 months posttreatment with ADT. After 3 months therapy there was a significant reduction in all dynamic contrast-enhanced MRI parameters measured in tumor regions of interest (K(trans), k(ep), v(p), IAUGC-90); P < 0.001. Areas of normal-appearing peripheral zone showed no significant change; P = 0.285-0.879. Post-ADT, there was no significant change in apparent diffusion coefficient values in tumors, whilst apparent diffusion coefficient values significantly decreased in areas of normal-appearing peripheral zone, from 1.786 × 10(-3) mm(2) /s to 1.561 × 10(-3) mm(2) /s; P = 0.007. As expected the median Prostate-Specific Antigen (PSA) significantly reduced from 30 ng/mL to 1.5 ng/mL posttreatment, and median prostate volume dropped from 47.6 cm(3) to 24.9 cm(3) ; P < 0.001. These results suggest that dynamic contrast-enhanced MRI and diffusion-weighted MRI offer different information but that both could prove useful adjuncts to the anatomical information provided by T2-weighted imaging. dynamic contrast-enhanced as a marker of angiogenesis may help demonstrate ADT resistance and diffusion-weighted imaging may be more accurate in determining presence of tumor cell death versus residual tumor.     

Impact of long-term androgen deprivation therapy on PSMA ligand PET/CT in patients with castration-sensitive prostate cancer

Purpose

Since the introduction of PSMA PET/CT with ⁶⁸Ga-PSMA-11, this modality for imaging prostate cancer (PC) has spread worldwide. Preclinical studies have demonstrated that short-term androgen deprivation therapy (ADT) can significantly increase PSMA expression on PC cells. Additionally, retrospective clinical data in large patient cohorts suggest a positive association between ongoing ADT and a pathological PSMA PET/CT scan. The present evaluation was conducted to further analyse the influence of long-term ADT on PSMA PET/CT findings.

Methods

A retrospective analysis was performed of all 1,704 patients who underwent a ⁶⁸Ga-PSMA-11 PET/CT scan at our institution from 2011 to 2017 to detect PC. Of 306 patients scanned at least twice, 10 had started and continued ADT with a continuous clinical response between the two PSMA PET/CT scans. These ten patients were included in the current analysis which compared the tracer uptake intensity and volume of PC lesions on PSMA PET/CT before and during ongoing ADT.

Results

Overall, 31 PC lesions were visible in all ten patients before initiation of ADT. However, during ongoing ADT (duration 42–369 days, median 230 days), only 14 lesions were visible in eight of the ten patients. The average tracer uptake values decreased in 71% and increased in 12.9% of the PC lesions. Of all lesions, 33.3% were still visible in six patients with a complete PSA response (≤0.1 ng/ml).

Conclusion

Continuous long-term ADT significantly reduces the visibility of castration-sensitive PC on PSMA PET/CT. If the objective is visualization of the maximum possible extent of disease, we recommend referring patients for PSMA PET/CT before starting ADT.

     

中等大分割调强放疗联合内分泌治疗局部晚期前列腺癌的疗效分析

目的探讨中等大分割调强放疗(IMRT)联合内分泌治疗局部晚期前列腺癌的疗效和不良反应。方法回顾性选取大连医科大学附属第二医院肿瘤放疗科2014至2020年收治的40例局部晚期前列腺腺癌患者的病例资料。前列腺及精囊腺计划肿瘤靶区(PGTV)剂量:64.8～70.0 Gy/25～28次, 2.4～2.8 Gy/次, 其中, 20例盆腔阳性淋巴结同步加量PGTVnd剂量:60.0～64.4 Gy/25～28次, 2.3～2.4Gy/次。盆腔淋巴结引流区计划靶区(PTV)剂量为45.0～50.4 Gy/25～28次。入组患者采用长程内分泌治疗, 包括新辅助、同期及辅助治疗。评价疗效及不良反应, 并分析影响无生化失败生存(BFFS)的预后相关因素。结果中位随访时间为31个月, 全组患者2、3年的总生存(OS)率分别为100.0%、96.9%, 1 、2 、3年的BFFS率分别为90%、76.8%、72%, 无远处转移生存(DMFS)率分别为92.2%、82.8%、75.1%。Gleason(GS)评分高低(χ2=10.00, P<0.05)和有无邻近组织受侵(χ2=8.85, P<0...     

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.

     

Overall survival comparison between androgen deprivation therapy (ADT) plus external beam radiation therapy (EBRT) vs ADT plus EBRT with brachytherapy boost in clinically node-positive prostate cancer

PurposeOptimal therapy for clinically node-positive, nonmetastatic (cN1) prostate cancer (PC) patients remains controversial, ranging from aggressive local therapy to palliative systematic therapy alone. Despite guideline support, it is unclear if a brachytherapy (BT) boost should be considered for cN1 patients as these patients were excluded from randomized trials establishing its benefit. Herein, we compare definitive radiation therapy (RT) with or without a BT boost in cN1 PC.Methods and materialsThe National Cancer Database was used to identify men with cN1 PC treated with definitive RT and concomitant androgen deprivation therapy between 2004 and 2013. Overall survival (OS) was compared between those who received external beam RT (EBRT) or combination EBRT plus BT boost (EBRT + BT) using Kaplan–Meier with propensity score matching and Cox proportional hazards.ResultsWith a median followup of 48.5 months, 1,650 patients were eligible for this analysis, 103 (6.2%) of whom received EBRT + BT. Younger age, no medical comorbidities, and Gleason score of six were associated with higher likelihood of receiving EBRT + BT over EBRT alone. The mean (median) OS for EBRT and EBRT + BT was 99.0 (110.6) months vs 109.2 (not reached) months, respectively (p = 0.048). However, no significance difference in OS was observed between the groups after propensity score matching. On multivariable analysis, EBRT + BT was not significantly associated with improved OS (adjusted HR 0.67, 95% CI, 0.41–1.07, p = 0.098).ConclusionsIn this retrospective, observational study of patients with cN1 PC treated with definitive RT and concomitant androgen deprivation therapy, EBRT + BT had an unadjusted improvement in OS compared with EBRT alone that lost statistical significance after multivariable adjustment and propensity score matching.     

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.

     

MRI-assisted radiosurgery: A quality assurance nomogram for palladium-103 and iodine-125 prostate brachytherapy

PurposeWe sought to develop an activity nomogram for magnetic resonance (MR)–planned permanent seed prostate brachytherapy to improve quality assurance through a secondary dosimetric check.Methods and MaterialsPatients undergoing MRI-assisted radiosurgery (MARS), whereby MRI is used for preoperative planning and postimplant dosimetry, were reviewed from May 2016 to September 2018. Planned activity (U) was fitted by MR-prostate volume (cc) via simple linear regression. Resulting monotherapy nomograms were compared with institutional nomograms from an ultrasound-planned cohort. Dosimetric coverage and external urinary sphincter (EUS) dose were also assessed for MR-planned patients.ResultsWe identified 183 patients treated with MARS: 146 patients received palladium-103 (¹⁰³Pd; 102 monotherapy and 44 boost), and 37 received iodine-125 (¹²⁵I) monotherapy. Median prostate volume was 28 cc (interquartile range: 22–35). Lines of best fit for implant activity were U = 4.344 × (vol) + 54.13 (R²: 95%) for ¹⁰³Pd monotherapy, U = 3.202 (vol) + 39.72 (R²: 96%) for ¹⁰³Pd boost and U = 0.684 (vol) + 13.38 (R²: 96%) for ¹²⁵I monotherapy. Compared with ultrasound, MR-planned nomograms had lower activity per volume (p < 0.05) for both ¹⁰³Pd monotherapy (∼6%) and ¹²⁵I monotherapy (∼11%), given a median size (30 cc) prostate. Across all MARS implants, postimplant dosimetry revealed a median V100% of 94% (interquartile range: 92–96%). Median EUS V125 was <1 cc for all patients, regardless of isotope.ConclusionsWe developed a quality assurance nomogram for MR-planned prostate brachytherapy. When compared with ultrasound-planned, MR-planned monotherapy resulted in a lower activity-to-volume ratio while maintaining dosimetric coverage, likely secondary to EUS-sparing and reduced planning target margins.     

Acute toxicity and health-related quality of life outcomes of localized prostate cancer patients treated with magnetic resonance imaging-guided high-dose-rate brachytherapy: A prospective phase II trial

PURPOSETo report acute toxicity and health-related quality of life (HRQoL) outcomes of a phase II clinical trial of magnetic resonance imaging (MRI)-guided prostate high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy.METHODS AND MATERIALSPatients with intermediate- and high-risk prostate cancer (PCa) were eligible. Treatment consisted of a single 15 Gy MRI-guided HDR-BT followed by external beam radiotherapy (37.5–46 Gy depending on their risk category). Dosimetry, toxicity and HRQoL outcomes were collected prospectively at baseline, 1 and 3 months using Common Terminology Criteria for Adverse Events Version 4.0 and the expanded PCa index composite, respectively. General linear mixed modeling was conducted to assess the changes in expanded PCa index composite domain scores over time. A minimally important difference was defined as a deterioration of HRQoL scores at 3 months compared to baseline ≥ 0.5 standard deviation. A p value ≤ 0.05 was considered statistically significant.RESULTSSixty-one patients were included. Acute grade (G)2 urinary toxicity was observed in 18 (30%) patients while 1 (2%) patient had G3 toxicity, and none had G4 toxicity. Two patients had an acute urinary retention. G2 gastrointestinal toxicity was reported by 5 (8%) patients with no G3–4. Compared to baseline, urinary HRQoL scores significantly declined at 1 month (p < 0.001) but recovered at 3 months (p > 0.05). Bowel (p < 0.001) and sexual (p < 0.001) domain scores showed a significant decline over the 3-month follow-up period. At 3 months, 44%, 49% and 57% of patients reported a minimally important difference respectively in the urinary bowel and sexual domains.CONCLUSIONMRI-guided HDR-BT boost is a safe and well tolerated treatment of intermediate- and high-risk PCa in the acute setting. A longer follow-up and a comparison to ultrasound-based HDR-BT are needed to assess the potential benefit of MRI-guided prostate HDR-BT.     

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).     

Impact of treatment planning quality assurance software on volumetric-modulated arc therapy plans for prostate cancer patients

IntroductionSoftware that evaluates the quality of treatment plans (PlanIQ^TM) has become commercially available in recent years. It includes a feasibility assessment tool that provides the ideal dose volume histogram (DVH) for each organ at risk, based on the ideal dose falloff from the prescribed dose at the target boundary. It is important to investigate whether the PlanIQ^TM assessment tool (Feasibility DVH^TM) can assist treatment planners who have limited to no experience in treatment planning. Therefore, the present study aimed to evaluate this tool's usefulness for improving the quality of treatment plans.Materials & MethodsThis study included 5 patients with prostate cancer. The treatment planners were 2 graduate students, 2 undergraduate students, and one clinical planner. All students were radiological technology and medical physics students with no clinical experience. Two different volumetric-modulated arc therapy (VMAT) plans were developed before and after Feasibility DVH^TM. The quality of each treatment plan was evaluated based on a scoring system implemented in PlanIQ^TM.ResultsOf 5 patients included, 4 received improved treatment plans when Feasibility DVH^TM was used. Moreover, 4 of 5 treatment planners showed improvement in treatment planning using Feasibility DVH^TM.ConclusionsThe findings suggest that using the Feasibility DVH^TM tool may improve treatment plans for different planners and patients. However, planners at any level of experience should be trained to check the dose distribution in addition to checking the DVH, which depends on the adequacy of the contours.