scholarly journals The feasibility of a dose painting procedure to treat prostate cancer based on mpMR images and hierarchical clustering

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Seyed Masoud Rezaeijo ◽  
Bijan Hashemi ◽  
Bahram Mofid ◽  
Mohsen Bakhshandeh ◽  
Arash Mahdavi ◽  
...  

Abstract Background We aimed to assess the feasibility of a dose painting (DP) procedure, known as simultaneous integrated boost intensity modulated radiation Therapy (SIB-IMRT), for treating prostate cancer with dominant intraprostatic lesions (DILs) based on multi-parametric magnetic resonance (mpMR) images and hierarchical clustering with a machine learning technique. Methods The mpMR images of 120 patients were used to create hierarchical clustering and draw a dendrogram. Three clusters were selected for performing agglomerative clustering. Then, the DIL acquired from the mpMR images of 20 patients were categorized into three groups to have them treated with a DP procedure being composed of three planning target volumes (PTVs) determined as PTV1, PTV2, and PTV3 in treatment plans. The DP procedure was carried out on the patients wherein a total dose of 80, 85 and 91 Gy were delivered to the PTV1, PTV2, and PTV3, respectively. Dosimetric and radiobiologic parameters [Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP)] of the DP procedure were compared with those of the conventional IMRT and Three-Dimensional Conformal Radiation Therapy (3DCRT) procedures carried out on another group of 20 patients. A post-treatment follow-up was also made four months after the radiotherapy procedures. Results All the dosimetric variables and the NTCPs of the organs at risks (OARs) revealed no significant difference between the DP and IMRT procedures. Regarding the TCP of three investigated PTVs, significant differences were observed between the DP versus IMRT and also DP versus 3DCRT procedures. At post-treatment follow-up, the DIL volumes and apparent diffusion coefficient (ADC) values in the DP group differed significantly (p-value < 0.001) from those of the IMRT. However, the whole prostate ADC and prostate-specific antigen (PSA) indicated no significant difference (p-value > 0.05) between the DP versus IMRT. Conclusions The results of this comprehensive clinical trial illustrated the feasibility of our DP procedure for treating prostate cancer based on mpMR images validated with acquired patients’ dosimetric and radiobiologic assessment and their follow-ups. This study confirms significant potential of the proposed DP procedure as a promising treatment planning to achieve effective dose escalation and treatment for prostate cancer. Trial registration: IRCT20181006041257N1; Iranian Registry of Clinical Trials, Registered: 23 October 2019, https://en.irct.ir/trial/34305.

2021 ◽  
Author(s):  
Seyed Masoud Rezaeijo ◽  
Bijan Hashemi ◽  
Bahram Mofid ◽  
Mohsen Bakhshandeh ◽  
Arash Mahdavi ◽  
...  

Abstract BackgroundWe aimed to assess the feasibility of a novel dose painting (DP) procedure for treating prostate cancer with dominant intraprostatic lesions (DILs) based on mpMR images and hierarchical clustering with a machine learning technique. MethodsThe mpMR images of 120 patients were used to create hierarchical clustering and draw a dendrogram. Three clusters were selected for performing agglomerative clustering. Then, the DIL acquired from the mpMR images of 20 patients were categorized into three groups to have them treated with a novel DP procedure being composed of three planning target volumes (PTVs) determined as PTV1, PTV2, and PTV3 in treatment plans. The DP procedure was carried out on the patients wherein a total dose of 80, 85, and 91 Gy were delivered to the PTV1, PTV2, and PTV3, respectively. Dosimetric and radiobiologic parameters (TCP & NTCP) of the DP procedure were compared with those of the conventional IMRT and 3DCRT procedures carried out on another group of 20 patients. A post-treatment follow-up was also made four months after the radiotherapy procedures.ResultsAll the dosimetric variables and the NTCPs of the organs at risks revealed no significant difference between the DP and IMRT procedures. Regarding the TCP of three investigated PTVs, significant differences were observed between the DP vs. IMRT and also DP vs. 3DCRT procedures. At post-treatment follow-up, the DIL volumes and ADC values in the DP group differed significantly (p-value<0.001) from those of the IMRT. However, the whole prostate ADC and PSA indicated no significant difference (p-value>0.05) between the DP vs. IMRT. ConclusionsThe results of this comprehensive clinical trial illustrated the feasibility of our novel DP procedure for treating prostate cancer based on mpMR images validated with acquired patients’ dosimetric and radiobiologic assessment and their follow-ups. This study confirms significant potential of the proposed DP procedure as a promising treatment planning to achieve effective dose escalation and treatment for prostate cancer.Trial registrationIRCT20181006041257N1; Iranian Registry of Clinical Trials, Registered: 23 Oct. 2019, https://en.irct.ir/trial/34305


2020 ◽  
Vol 38 (26) ◽  
pp. 3032-3041 ◽  
Author(s):  
Wanling Xie ◽  
Meredith M. Regan ◽  
Marc Buyse ◽  
Susan Halabi ◽  
Philip W. Kantoff ◽  
...  

PURPOSE Recently, we have shown that metastasis-free survival is a strong surrogate for overall survival (OS) in men with intermediate- and high-risk localized prostate cancer and can accelerate the evaluation of new (neo)adjuvant therapies. Event-free survival (EFS), an earlier prostate-specific antigen (PSA)–based composite end point, may further expedite trial completion. METHODS EFS was defined as the time from random assignment to the date of first evidence of disease recurrence, including biochemical failure, local or regional recurrence, distant metastasis, or death from any cause, or was censored at the date of last PSA assessment. Individual patient data from trials within the Intermediate Clinical Endpoints in Cancer of the Prostate–ICECaP–database with evaluable PSA and disease follow-up data were analyzed. We evaluated the surrogacy of EFS for OS using a 2-stage meta-analytic validation model by determining the correlation of EFS with OS (patient level) and the correlation of treatment effects (hazard ratios [HRs]) on both EFS and OS (trial level). A clinically relevant surrogacy was defined a priori as an R2 ≥ 0.7. RESULTS Data for 10,350 patients were analyzed from 15 radiation therapy–based trials enrolled from 1987 to 2011 with a median follow-up of 10 years. At the patient level, the correlation of EFS with OS was 0.43 (95% CI, 0.42 to 0.44) as measured by Kendall’s tau from a copula model. At the trial level, the R2 was 0.35 (95% CI, 0.01 to 0.60) from the weighted linear regression of log(HR)-OS on log(HR)-EFS. CONCLUSION EFS is a weak surrogate for OS and is not suitable for use as an intermediate clinical end point to substitute for OS to accelerate phase III (neo)adjuvant trials of prostate cancer therapies for primary radiation therapy–based trials.


2012 ◽  
Vol 1 (3) ◽  
Author(s):  
Moamen A. Amin ◽  
Suganthiny Jeyaganth ◽  
Nader Fahmy ◽  
Louis Bégin ◽  
Samuel Aronson ◽  
...  

Introduction: To evaluate the predictors of prostate cancer in follow-up of patientsdiagnosed on initial biopsy with high-grade prostatic intraepithelial neoplasia(HGPIN) or atypical small acinar proliferation (ASAP).Methods: We studied 201 patients with HGPIN and 22 patients with ASAPon initial prostatic biopsy who had subsequent prostatic biopsies. The meantime of follow-up was 17.3 months (range 1–62). The mean number of biopsy sessions was 2.5 (range 2–6), and the median number of biopsy cores was10 (range 6–14).Results: On subsequent biopsies, the rate of prostate cancer was 21.9% (44/201)in HGPIN patients. Of these, 32/201 patients (15.9%), 9/66 patients (13.6%)and 3/18 patients (16.6%) were found to have cancer on the first, second and third follow-up biopsy sessions, respectively. In ASAP patients, the cancer detectionrate was 13/22 (59.1%), all of whom were found on the first follow-upbiopsy. There was a statistically significant difference between the cancer detectionrate in ASAP and HGPIN patients (p < 0.001). Multivariate analysis showedthat the independent predictors of cancer were the number of cores in theinitial biopsy, the number of cores (> 10) in the follow-up biopsy and a prostate specific antigen (PSA) density of ≥ 0.15 (odds ratio 0.77, 3.46 and 2.7,8 respectively;p < 0.04). Conversely, in ASAP patients none of these variables werefound to be associated with cancer diagnosis.Conclusion: ASAP is a strong predictive factor associated with cancer when comparedwith HGPIN. The factors predictive of cancer on follow-up biopsy ofHGPIN are number of cores on initial biopsy, more than 10 cores in rebiopsyand elevated PSA density. As the cancer detection rate on repeated biopsy of HGPIN patients is the same as that of patients without HGPIN, perhaps the standard of repeat biopsy in all patients with HGPIN should be revisited.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 196-196
Author(s):  
W. Tristram Arscott ◽  
Leonard Chen ◽  
Nathan Wilson ◽  
Aditi Bhagat ◽  
Joy S. Kim ◽  
...  

196 Background: Obstructive urinary symptoms are common following prostate cancer treatment with radiation therapy. Given the higher dose of radiation per fraction using stereotactic body radiation therapy (SBRT) there is concern that post-SBRT obstructive urinary symptoms would be more severe. This study sought to evaluate obstructive urinary symptoms and urinary retention requiring catheterization following SBRT for prostate cancer. Methods: Patients treated with SBRT monotherapy for localized prostate cancer from August 2007 to July 2011 at Georgetown University Hospital with a minimum of two years of follow-up were included in this study. Treatment was delivered using the CyberKnife with doses of 35 Gy to 36.25 Gy in five fractions. Urinary retention was recorded and scored using the CTCAE v.4. Patient-reported urinary symptoms were assessed using the International Prostate Symptom Score (IPSS) before treatment and at months 1, 3, 6, 9, and 12 and every six months thereafter. Results: Two hundred sixty nine patients at a median age of 69 received SBRT with a median follow-up of three years. Prior to treatment, 32.1% of patients utilized alpha-antagonists and 17.8% were dissatisfied with their urinary function. The two-year actuarial incidence rates of acute and late urinary retention greater than or equal to grade 2 were 39.5% and 41.4%. Alpha-antagonist utilization rose at one month (57.9%) and 18 months (48.0%) post-treatment. However, grade 3 urinary retention was low with four men (1.5%) requiring catheterization and/or transurethral resection of the prostate. A mean baseline IPSS obstructive symptom score of 3.6 significantly increased to 5.0 at one month (p < 0.0001), however returned to baseline at three months (p = 0.74). Late IPSS increases were common, but transient. The IPSS obstructive symptom score returned to baseline in 79.6% of patients by six months and 92.6% by two years. Dissatisfaction with urinary function declined to 14% by two years post treatment (p < 0.05). Conclusions: Treatment of prostate cancer with SBRT resulted in an acute increase in obstructive urinary symptoms, which peaked at one month post-treatment. However, the risk of acute urinary retention requiring catheterization was low. Obstructive urinary symptoms returned to baseline in the majority of patients by six months and in more than 90% by two years.


2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 289-289
Author(s):  
Jason Homza ◽  
John T. Nawrocki ◽  
Harmar D. Brereton ◽  
Christopher A. Peters

289 Background: Salvage radiotherapy (SRT) may be employed as a potentially curative intervention for patients experiencing biochemical failure (serum prostate-specific antigen [PSA] ≥ 0.2 ng/mL) after prostatectomy for localized prostate cancer. Patients not showing a favorable response to SRT alone may require additional therapies and may benefit from earlier identification of this need. Methods: 131 consecutive patients received SRT during the timeframe of this study. 76 were deemed eligible based on the following criteria: prostatic adenocarcinoma diagnosis receiving SRT, no clinical evidence of metastasis, no hormone use prior to/during SRT, serum PSA measurement halfway through SRT, and minimum follow-up time of 3 months. Median follow-up time was 51.6 months. Eligible patients were divided into three groups based on PSA response by the midpoint of treatment: no change, decrease, or increase in PSA. The primary endpoint of the study was clinical failure (measured from SRT completion), defined as serum PSA value ≥0.2ng/mL above the post-radiotherapy nadir, initiation of androgen deprivation therapy, development of bone metastasis, or death from prostate cancer. Results: 13.1% experienced no change in PSA halfway through SRT (group 0), 68.4% of patients experienced a decrease (group 1), 18.4% experienced an increase (group 2). Four-year freedom from clinical failure was 60.0% for group 0, 58.3% for group 1, and 41.7% for group 2. Median time to clinical failure was 71.7 months for group 1, 26.8 months for group 2, and was not reached for group 0. Pairwise multiple comparison demonstrated a significant difference in four-year freedom from clinical failure between groups 1 and 2 (p = 0.036). Conclusions: These data strongly suggest that changes in PSA are apparent midway through SRT and are associated with 4-year freedom from clinical failure. Further study is warranted to determine whether mid-treatment PSA during SRT may be used to identify a subset of patients that may benefit from treatment intensification.


2017 ◽  
Vol 66 (4) ◽  
pp. 768-772
Author(s):  
Ziyue Wu ◽  
Mihaela Aslan ◽  
Haiqun Lin ◽  
John Ko ◽  
Krishnan Radhakrishnan ◽  
...  

Prostate-specific antigen (PSA) measurements after primary treatment reflect residual tumor burden among men with prostate cancer. Using a mixture model analysis, we identified distinct trajectories of post-treatment PSA measurements and evaluated their associations with prostate cancer mortality. The study sample included 623 US Veterans treated for prostate cancer with curative intent during 1991–1995; 225 men received surgery and 398 men received radiation therapy. Post-treatment PSA measurements over a 2-year period for each patient were evaluated in latent class mixture models using the SAS TRAJ procedure, and groups of men with distinct trajectories of PSA were identified. These groups were then assessed for associations with 10-year prostate cancer mortality using proportional hazards analysis. Analyses identified three distinct groups—representing patterns of both initial values and changes in PSA over time—after surgery (n=172/31/14) and radiation therapy (n=253/103/22). Men in groups with patterns of higher (compared with the group with lowest) PSA values tended to have worse survival experience: HRs for prostate cancer mortality were 3.45 (P=0.18) and 22.7 (P<0.001) for surgery, and 2.70 (P=0.005) and 18.1 (P<0.001) for radiation therapy. The results indicate that PSA measurements after surgery or radiation therapy with curative intent include groups of men with a diverse spectrum of prognosis for prostate cancer mortality. Although contemporary PSA levels are lower than those observed in the study sample, the corresponding trajectory patterns may become evident shortly after the time of diagnosis and treatment.


2020 ◽  
Vol 13 (6) ◽  
Author(s):  
Farzad Allameh ◽  
Morteza Fallah Karkan ◽  
Amir Hossein Rahavian ◽  
Bahram Mofid ◽  
Samira Azghandi ◽  
...  

Background: At present, there is a lack of evidence concerning urinary complications caused by intensity-modulated radiation therapy (IMRT) used for the management of prostate cancer (PCa). Objectives: This study aimed at identifying the nature and severity of post-IMRT urinary symptoms in patients with PCa. Methods: This prospective study was performed with consecutive patients, who had clinically localized PCa (cT1c-cT2c) and had undergone IMRT treatment from 2016 to 2019. At 1, 6, and 12 months of follow-up, medical history, physical information, prostate-specific antigen values, International Prostate Symptom Score (IPSS), medication use, Radiation Therapy Oncology Group (RTOG), acute and late toxicity, and Q max were collected. Results: A total of 127 patients with a mean age of 71.04 ± 7.1 years received IMRT and underwent 12 months of follow-up. The mean IPSSs at baseline versus those at 1, 6, and 12 months after IMRT was 14.5 ± 6.8 versus 13.3 ± 6.1, 12.3 ± 5.3, and 10.4 ± 4.2, respectively (P < 0.000). The mean prostate volume was 38.2 ± 12.1 cc. At the last follow-up, 31 patients (24.4%) took genitourinary (GU) medications. Conclusions: This study showed that the majority of GU side effects caused by primary IMRT for PCa treatment are transient. Treatment triggered an acute increase in obstructive urinary symptoms, which peaked during the first month after IMRT. In most patients, in the course of 6 months, symptoms returned to baseline.


Author(s):  
Philipp Dahm

This chapter provides a summary of the landmark Prostate Testing for Cancer and Treatment (ProtecT) trial, a three-armed randomized controlled trial of men with clinically localized prostate cancer mostly diagnosed through prostate-specific antigen (PSA) screening comparing radical prostatectomy to radiation therapy or active monitoring. Active monitoring consisted mostly of regular PSA testing. After 10 years of follow-up, very few deaths from prostate cancer occurred, underscoring the very low risk of death from prostate cancer in patients diagnosed by PSA screening irrespective of treatment approach.


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