Curative Radiotherapy For Prostate Cancer Research Articles

Patient-reported lower limb edema after primary radiotherapy for prostate cancer

Background Secondary lymphedema is a known side effect to radiotherapy (RT), but limited information regarding prevalence and risk factors for lower limb edema (LLE) after curative radiotherapy in patients with prostate cancer (PCa) is available. This study provides a descriptive analysis of patient-reported LLE with analysis of risk factors in a cohort of patients with PCa treated with curative RT. Material and methods A total of 302 patients with PCa with prospective registration of patient-reported LLE (EORTC QLQ-PR25 (Question 46)) were included. Analysis of LLE was done with the calculation of prevalence rates and Kaplan-Meier statistics. Risk factors for LLE were analyzed multivariate with Cox regression analysis. Results At a median follow-up of 15 (3–51) months, the overall crude incidence of patients reporting ‘quite a bit’ or ‘a lot’ of LLE was 49 (16.2%) and 21 (7.0%), respectively. The baseline prevalence rate of ‘quite a bit’ and ‘a lot’ of LLE was 5.0% and 0.8%, respectively. During follow-up the prevalence rate for ‘quite a bit’ or ‘a lot’ of LLE increased significantly and remained constant from 6 months where 11.5% (±1.7%) reported ‘quite a bit’ and 2.9% (±0.5%) reported ‘very much’ LLE (p < 0.001), respectively. Significant risk factors (p < 0.10) for LLE in univariate analysis included lymph node irradiation (HR:2.325), baseline Body Mass Index (BMI) (HR:1.100), Charlson Comorbidity Index (HR:1.227), Androgen Deprivation Therapy (HR:2,979), and Performance Status (HR:0.594). Only high BMI (HR:1.091) remained significant in multivariate analysis with a three-fold increase in LLE in patients with BMI ≥ 30 compared to normal weight patients. Conclusion Severe patient-reported LLE after curative RT for PCa is rare. Significantly more patients with a high BMI report ‘quite a bit’ or ‘very much’ LLE compared to patients with a normal BMI. Obese PCa patients could be offered a rehabilitation program for early detection and management of LLE.

PD-0571 Patient reported lower limb edema after curative radiotherapy for prostate cancer

PD-0571 Patient reported lower limb edema after curative radiotherapy for prostate cancer

Linac-based stereotactic salvage reirradiation for intraprostatic prostate cancer recurrence: toxicity and outcomes

BackgroundThe rates of local failure after curative radiotherapy for prostate cancer (PC) remain high despite more accurate locoregional treatments available, with one third of patients experiencing biochemical failure and clinical relapse occurring in 30–47% of cases. Today, androgen deprivation therapy (ADT) is the treatment of choice in this setting, but with not negligible toxicity and low effects on local disease. Therefore, the treatment of intraprostatic PC recurrence represents a challenge for radiation oncologists. Prostate reirradiation (Re-I) might be a therapeutic possibility. We present our series of patients treated with salvage stereotactic Re‑I for intraprostatic recurrence of PC after radical radiotherapy, with the aim of evaluating feasibility and safety of linac-based prostate Re‑I.Materials and methodsWe retrospectively evaluated toxicities and outcomes of patients who underwent salvage reirradiation using volumetric modulated arc therapy (VMAT) for intraprostatic PC recurrence. Inclusion criteria were age ≥ 18 years, histologically proven diagnosis of PC, salvage Re‑I for intraprostatic recurrence after primary radiotherapy for PC with curative intent, concurrent/adjuvant ADT with stereotactic body radiation therapy (SBRT) allowed, performance status ECOG 0–2, restaging choline/PSMA-PET/TC and prostate MRI after biochemical recurrence, and signed informed consent.ResultsFrom January 2019 to April 2022, 20 patients were recruited. Median follow-up was 26.7 months (range 7–50). After SBRT, no patients were lost at follow-up and all are still alive. One- and 2‑year progression free survival (PFS) was 100% and 81.5%, respectively, while 2‑year biochemical progression-free survival (bFFS) was 88.9%. Four patients (20%) experienced locoregional lymph node progression and were treated with a further course of SBRT. Prostate reirradiation allowed the ADT start to be postponed for 12–39 months. Re‑I was well tolerated by all patients and none discontinued the treatment. No cases of ≥ G3 genitourinary (GU) or gastrointestinal (GI) toxicity were reported. Seven (35%) and 2 (10%) patients experienced acute G1 and G2 GU toxicity, respectively. Late GU toxicity was recorded in 10 (50%) patients, including 8 (40%) G1 and 2 (10%) G2. ADT-related side effects were found in 7 patients (hot flashes and asthenia).ConclusionLinac-based SBRT is a safe technique for performing Re‑I for intraprostatic recurrence after primary curative radiotherapy for PC. Future prospective, randomized studies are desirable to better understand the effectiveness of reirradiation and the still open questions in this field.

Radiotherapy activity in the COVID 19 pandemic: Brazil's operational national-level study

PurposeDuring the COVID-19 pandemic, patients with cancer are at increased risk of not having timely diagnosis and access to cancer treatment. The present study evaluated the COVID-19 pandemic impact on radiotherapy activity in Brazil. MethodsA national-level study was performed to evaluate the RT utilization for prostate, breast, head & neck (HN), Gynecology (GYN), Gastrointestinal (GI), lung cancers, and bone/brain metastases. The data on the RT executed was extracted from the Brazilian Ministry of Health database. The NON-COVID period was considered the control group, and the comparison groups were COVID-2020 (without vaccine) and COVID-2021 (with vaccine). ResultsWe collected the data of 238,355 procedures executed on three periods. Significant difference in the RT utilization between NON-COVID and COVID-2020 were observed for prostate cancer, bone and brain metastases (−12.3 %, p = 0.02, +24 %, p = 0.02 and +14 %, p = 0.04, respectively). Comparing 2 equivalents months from NON-COVID-2019 (ref), COVID-2020, and COVID-2021, a significant increase was identified for bone and brain metastases (2020 +21 %, and 2021 +32 %), and (2020 +20 %, and 2021 +14 %). A stable drop occurred for prostate cancer (2020 −11 % and 2021 −10 %), and a variation was observed for breast (2020 +8 %, and 2021 −1 %) and lung cancer (2020 +10 %, and 2021 −3 %). For other cancers, non-significant changes were observed when comparing 2020 and 2021. ConclusionThe RT activity was heterogeneously affected with a substantial increase for bone and brain metastases and a meaningful decline for prostate cancer. Policy summaryWith a significant increase in the use of palliative radiotherapy for bone and brain metastases and a meaningful reduction in curative radiotherapy for prostate cancer, we hope these findings can help governments, RT services, medical communities, and other stakeholders develop strategies to mitigate the impact of the present and future pandemics. Finally, despite the changes imposed by the COVID pandemic, it is imperative to enhance screening, increase cancer diagnosis at an early stage, and improve access to all cancer treatments, including radiotherapy.

Radiotherapy planning parameters correlate with changes in the peripheral immune status of patients undergoing curative radiotherapy for localized prostate cancer

PurposeThe influence of radiotherapy on patient immune cell subsets has been established by several groups. Following a previously published analysis of immune changes during and after curative radiotherapy for prostate cancer, this analysis focused on describing correlations of changes of immune cell subsets with radiation treatment parameters.Patients and methodsFor 13 patients treated in a prospective trial with radiotherapy to the prostate region (primary analysis) and five patients treated with radiotherapy to prostate and pelvic nodal regions (exploratory analysis), already published immune monitoring data were correlated with clinical data as well as radiation planning parameters such as clinical target volume (CTV) and volumes receiving 20 Gy (V20) for newly contoured volumes of pelvic blood vessels and bone marrow.ResultsMost significant changes among immune cell subsets were observed at the end of radiotherapy. In contrast, correlations of age and CD8+ subsets (effector and memory cells) were observed early during and 3 months after radiotherapy. Ratios of T cells and T cell proliferation compared to baseline correlated with CTV. Early changes in regulatory T cells (Treg cells) and CD8+ effector T cells correlated with V20 of blood vessels and bone volumes.ConclusionsPatient age as well as radiotherapy planning parameters correlated with immune changes during radiotherapy. Larger irradiated volumes seem to correlate with early suppression of anti-cancer immunity. For immune cell analysis during normofractionated radiotherapy and correlations with treatment planning parameters, different time points should be looked at in future projects.Trial registration number:NCT01376674, 20.06.2011

Can Comprehensive Geriatric Assessment Predict Tolerance of Radiotherapy for Localized Prostate Cancer in Men Aged 75 Years or Older?

Curative radiotherapy for prostate cancer is common in the elderly. However, concerns about potential toxicity have inhibited access to radiotherapy for this population, for whom preserving quality of life (QoL) is crucial. The primary endpoint was to identify predictors of impaired QoL in men aged 75 years or older treated with curative intent radiotherapy with or without androgen deprivation therapy (ADT) for localized prostate cancer. We prospectively performed comprehensive geriatric assessment (CGA) and administered QoL questionnaires to 208 elderly (>75 years) patients prior to, plus two and six months after, radiotherapy (NCT 02876237). The median age of the patients was 77 years (range 75–89). At the start of the study, comorbidities were highlighted in 65% of patients: 23% were depressed, 23% had cognitive impairment, and 16% had reduced independence. At six months, 9% of patients had a consistently decreased QoL (>20 points), and a further 16% had a more moderate reduction (10 to 20 points) in QoL. None of the parameters studied (tumor characteristic, treatment, or oncogeriatric parameters) were predictive of a reduced QoL following radiotherapy. Though co-existing geriatric impairment was common, QoL was maintained for 75% of patients six months after radiotherapy. CGA was poorly predictive of tolerance of prostatic radiotherapy. Geriatric assessments dedicated to quality of life following radiotherapy need to be developed.

Good prognosis following a PSA bounce after high dose rate brachytherapy and external radiotherapy in prostate cancer

BackgroundPSA kinetics after curative radiotherapy for prostate cancer is an important part of the posttreatment evaluation. We analysed PSA bounce occurrence after combined high dose rate brachytherapy (HDR-BT) and external radiotherapy (ERT). Material & methodsWe analysed 623 patients treated from 1995 to 2008. The median age was 66 years (47–79). The median initial PSA was 12 ng/ml (0.1–224). Neoadjuvant endocrine therapy was given to 429 patients. ERT was given with 2 Gy fractions to 50 Gy and HDR-BT in two 10 Gy fractions. The median follow-up was 11 years (range 2–266 months). PSA bounce was defined as a temporary rise in PSA >0.2 ng/ml. PSA failure was defined according to the Phoenix definition. ResultsPSA bounce occurred in 159 patients (26%), where 56 patients had a bounce amplitude >2 ng/ml and 31 patients had multiple bounces. Median time to bounce peak was 15 (3–103) months with a median bounce value of 1.5 (0.3–12)ng/ml. Younger age and lower Gleason scores were associated with PSA bounce. In a Cox regression analysis with PSA bounce as a time-dependent covariate and adjusted for other prognostic factors, PSA bounce was associated with a lower risk for PSA failure (HR = 0.42; 95% confidence interval 0.26–0.70). ConclusionPSA bounce after HDR-BT combined with ERT is common and associated with a good prognosis. As the relapse risk after an early bounce is very low, the findings should alert clinicians not to initiate salvage treatment too early. Research in prospective identification of PSA bounce is clinically relevant.

Radiotherapy for prostate cancer – Does daily image guidance with tighter margins improve patient reported outcomes compared to weekly orthogonal verified irradiation? Results from a randomized controlled trial

BackgroundNovel cancer drugs are subject to strict scientific evaluation of safety and efficacy and usually undergo a cost effectiveness analysis before approval for use in clinical practice. For new techniques in radiotherapy (RT) such as image-guided radiotherapy (IGRT), this is often not the case. We performed a randomized controlled trial to compare daily cone beam computer tomography (CBCT) IGRT with reduced planning target volume (PTV) margins vs weekly orthogonal portal imaging with conventional PTV margins. The primary aim of the study was to investigate the effect of two different image guidance techniques on patient reported outcome (PRO) using early side effects as proxy outcome of late rectal side effects in patients receiving curative RT for prostate cancer. MethodsThis open label, phase 3 trial conducted at two RT centers in Norway enrolled men aged 18 years or older with previously untreated histologically proven intermediate or high-risk adenocarcinoma of the prostate. Patients eligible for radical RT received it after 3 months of total androgen blockage and were randomly assigned to 78 Gy in 39 fractions guided either by weekly offline orthogonal portal imaging (15 mm margins to PTV) or by daily online CBCT IGRT (7 mm margins to PTV). Based on previous results indicating that acute rectal side effects are a valid proxy outcome for late rectal side effects, the primary outcome was acute rectal toxicity at end of RT as evaluated by rectal bother scale (five of the items from PRO’s QUFW94). The RIC-trial is registered with ClinicalTrials.gov, number NCT01550237. FindingsBetween October 2012 and June 2015, 257 patients were randomly assigned to weekly offline portal imaging (n = 129) or daily online CBCT IGRT (n = 128). Out of 250 evaluable patients, 96% completed PROs at baseline and 97% at end of RT. Baseline analyses demonstrated balance between groups for baseline characteristics as well as for PROs. In general, patients reported a small degree of side effects at end of RT, and there was no difference between groups for primary outcome (rectal bother scale of QUFW94 1.871 vs 1.884, p = 0.804). In addition, there were no significant differences between groups for any other gastrointestinal or urinary symptom as reported by QUFW94. Health related quality of life analyses (EORTC QLQ 30) demonstrated no differences between groups. InterpretationIn radical RT for prostate cancer, daily CBCT IGRT with reduced PTV margins demonstrated no advantage with respect to patient reported side effects at end of RT as compared to weekly orthogonal offline portal imaging with standard PTV margins.

Applying physical science techniques and CERN technology to an unsolved problem in radiation treatment for cancer: the multidisciplinary 'VoxTox' research programme.

The VoxTox research programme has applied expertise from the physical sciences to the problem of radiotherapy toxicity, bringing together expertise from engineering, mathematics, high energy physics (including the Large Hadron Collider), medical physics and radiation oncology. In our initial cohort of 109 men treated with curative radiotherapy for prostate cancer, daily image guidance computed tomography (CT) scans have been used to calculate delivered dose to the rectum, as distinct from planned dose, using an automated approach. Clinical toxicity data have been collected, allowing us to address the hypothesis that delivered dose provides a better predictor of toxicity than planned dose.

Evaluation of inflammatory cytokines and oxidative stress markers in prostate cancer patients undergoing curative radiotherapy.

Prostate cancer is the second leading cause of cancer-related death in men. The present study was carried out to investigate the radiation response of serum cytokines and oxidative markers to find out if these novel biomarkers have significant applications regarding radiation outcome in prostate cancer patients. Significant elevations of prostatic specific antigen (PSA), asymmetric dimethyl arginine (ADMA) and nitric oxide (NO) were recorded in cancer prostate patients at the time of diagnosis compared to controls. Patients were subjected to radiotherapy post prostatectomy with a total dose of 66 Gy in 33 fractions (5 sessions/week) for 7 weeks. At the end of the seventh week post radiotherapy, ADMA levels were accentuated while the levels of PSA and NO were lower than before therapy. The level of inflammatory cytokines (interleukins IL-4, IL-5 and interferon-gamma) in post radiation therapy patients were significantly elevated compared to both controls and prostate cancer patients. A significant inverse correlation was observed in prostate cancer patients between ADMA and NO. Moreover, a significant inverse correlation in post radiation therapy patients was observed between IL-5 and PSA. These results are highly suggestive that there is a specific cytokine response in patients undergoing curative radiotherapy for prostate cancer.

Contemporary minimally-invasive extended pelvic lymph node dissection for prostate cancer before curative radiotherapy: prospective standardized analysis of complications.

To prospectively assess contemporary complication rates of minimally-invasive staging pelvic lymph node dissection before curative radiotherapy for prostate cancer using a standardized classification. A total of 100 prostate cancer patients underwent laparoscopic or robot-assisted pelvic lymph node dissection (95% extended). Surgical outcomes were compared with those of 43 patients undergoing open pelvic lymph node dissection (33% extended). Complications were recorded prospectively during hospitalization and follow-up visits, and graded using Clavien-Dindo classification. Lymphocele size was measured on postoperative magnetic resonance imaging or computed tomography. Of the complications recorded, 10% were grade 1, 3% were grade 2 and 6% were grade 3. No grade 4-5 complications occurred. Compared with open pelvic lymph node dissection, minimally-invasive pelvic lymph node dissection was associated with less blood loss (P = 0.001) and shorter hospital stay (median 3 vs 6 days; P < 0.001), but longer operation time (130 vs 98 min; P < 0.001). The complication rate was similar in both groups. For the entire cohort, overall and symptomatic lymphoceles were seen in 91 (64%) and 18 patients (13%), respectively. On multivariate logistic regression, minimally-invasive surgery was the only independent predictor for lymphocele development (odds ratio 3.99; P = 0.015). Minimally-invasive extended pelvic lymph node dissection before curative radiotherapy is associated with low morbidity. Asymptomatic lymphocele development rate is higher compared with open pelvic lymph node dissection.

Grading-System-Dependent Volume Effects for Late Radiation-Induced Rectal Toxicity After Curative Radiotherapy for Prostate Cancer

To assess the association between the dose distributions in the rectum and late Radiation Therapy Oncology Group and the European Organisation for Research and Treatment of Cancer (RTOG/EORTC), Late Effects of Normal Tissue SOMA, and Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 graded rectal toxicity among patients with prostate cancer treated with RT. Included in the study were 124 patients who received three-dimensional conformal RT for prostate cancer to a total dose of 70 Gy in 2-Gy fractions. All patients completed questionnaires regarding rectum complaints before RT and during long-term follow-up. Late rectum Grade 2 or worse toxicity, according to RTOG/EORTC, LENT SOMA, and CTCAE v3.0 criteria, was analyzed in relation to rectal dose and volume parameters. Dose-volume thresholds (V40>or=65%, V50>or=55%, V65>or=45%, V70>or=20%, and a rectum volume<or=140 cm3), significantly discriminated patients with late Grade 0-1 and Grade 2 or worse rectal toxicity, particularly using the LENT SOMA and CTCAE v3.0 systems. The rectum volume receiving>or=70 Gy (V70) was most predictive for late Grade 2 or worse rectal toxicity with each of the grading systems. The associations were strongest, however, with use of the LENT SOMA system. Volume effects for late radiation-induced rectal toxicity are present, but their clinical significance depends on the grading system used. This should be taken into account in the interpretation of studies reporting on radiation-induced rectal toxicity.

535 Verification of Fluence Map (FM) in dynamic radiotherapy techniques

Curative radiotherapy for prostate cancer may lead to anorectal side effects, including rectal bleeding, fecal incontinence, increased stool frequency and rectal pain. The main objective of this study was to develop multivariable NTCP models for these side effects.The study sample was composed of 262 patients with localized or locally advanced prostate cancer (stage T1–3). Anorectal toxicity was prospectively assessed using a standardized follow-up program. Different anatomical subregions within and around the anorectum were delineated. A LASSO logistic regression analysis was used to analyze dose volume effects on toxicity.In the univariable analysis, rectal bleeding, increase in stool frequency and fecal incontinence were significantly associated with a large number of dosimetric parameters. The collinearity between these predictors was high (VIF > 5). In the multivariable model, rectal bleeding was associated with the anorectum (V70) and anticoagulant use, fecal incontinence was associated with the external sphincter (V15) and the iliococcygeal muscle (V55). Finally, increase in stool frequency was associated with the iliococcygeal muscle (V45) and the levator ani (V40). No significant associations were found for rectal pain.Different anorectal side effects are associated with different anatomical substructures within and around the anorectum. The dosimetric variables associated with these side effects can be used to optimize radiotherapy treatment planning aiming at prevention of specific side effects and to estimate the benefit of new radiation technologies.

Influence of transurethral resection on sexual dysfunction in patients with prostate cancer.

To evaluate retrospectively the potential influence of disease-related factors and transurethral resection of the prostate (TURP) on the sexual function of patients who had undergone curative radiotherapy for prostate cancer. The study comprised 104 patients (median age 69.5 years, range 49-81) who had been treated with curative radiotherapy and no first-line hormones: 16, 52, 33 and three patients had T1, T2, T3 and T4 tumours, respectively. TURP was performed in 73 patients before RT, and needle biopsy alone in 31 patients. They were interviewed about their past and present sexual lives using a questionnaire designed to evaluate the potency of the patients at age 45 years, at 1 year before the diagnosis of the disease, before radiotherapy (after TURP or needle biopsy) and at the last follow-up. Information concerning associated diseases, routine medication and the weight of the resected material was also collected. Before diagnosis, 20 patients had no erections while 84 were potent. Of the 60 potent patients undergoing a TURP, 31 (51%) indicated complete impotence immediately thereafter. There was no statistical difference between impotent and potent patients after TURP in age, associated diseases, medical treatment and the weight of the resected material. TURP may lead to impotence in a significant proportion of patients. As TURP is an important component of "conservative' treatment approaches, its potential sexual morbidity should be taken into consideration in the comparative risk-benefit analysis of different therapeutic strategies.

Influence of disease related factors, diagnostic procedures, and transurethral resection in the sexual dysfunction of patients before curative radiotherapy for prostate cancer

Influence of disease related factors, diagnostic procedures, and transurethral resection in the sexual dysfunction of patients before curative radiotherapy for prostate cancer