National reference levels of CT procedures dedicated for treatment planning in radiation oncology.

OBJECTIVE: To present results of the first national survey on reference levels of CT imaging performed for the treatment planning purposes in radiation oncology in Croatia. METHODS: Data for CT protocols of five anatomical regions including head, head and neck, pelvis, breast, and thorax were collected at eight radiation oncology departments in Croatia. Data included volume CT dose index (CTDIvol), dose-length product (DLP), scan length and set of acquisition and reconstruction parameters. Data on a total of 600 patients were collected. Median values of scan length, DLP and CTDIvol were calculated for each acquisition protocol. Third quartiles of the median CTDIvol and DLP values were proposed as the national radiotherapy planning reference levels (RPRL). RESULTS: The largest CoV were assessed for RT Breast (63.8% for CTDIvol), RT Thorax (79.7% for DLP) and RT H&N (21.2% for scan length). RT Head had the lowest CoV for CTDIvol (1,9%) and DLP (17,2%), while RT Breast had the lowest coefficient of variation for scan length (12.8%). Proposed national RPRLs are: for RT Head CTDIvol16cm = 62 mGy and DLP16cm = 1738 mGy.cm; for RT H&N CTDIvol16cm = 35 mGy and DLP16cm = 1444 mGy.cm; for RT Breast CTDIvol32cm = 16 mGy and DLP32cm = 731 mGy.cm; for RT Thorax CTDIvol32cm = 17 mGy and DLP32cm = 865 mGy.cm; for RT Pelvis CTDIvol32cm = 20 mGy and DLP32cm = 1133 mGy.cm. CONCLUSIONS: Results of this study show variations in CT imaging for treatment planning practice at the national level which call for optimization of procedures.

DOSIMETRIC VERIFICATION OF INTENSITY MODULATED RADIOTHERAPY (IMRT) TREATMENT PLANS FOR PROSTATE CANCER PATIENTS.

Intensity modulated radiotherapy (IMRT) has become widely used as a standard radiation therapy technique for the treatment of localized prostate cancer. The transition from conformal radiotherapy (3D CRT) to a more complex IMRT technique triggered the need for more thorough verification of the accuracy in the dose delivery. In this work we present the clinical workflow and the results of patient specific quality assurance (PSQA) procedures for 40 prostate cancer patients who have been treated with step and shot IMRT ever since its implementation in our routine clinical practice. PSQA procedures include dosimetric verification of each treatment plan with dedicated rotational phantom and high-resolution matrix detector system Octavius 4D (PTW Freiburg) that allows three-dimensional comparison of the calculated and delivered radiation dose distribution. Our results proved the compliance with the universal tolerance limits recommended for those procedures (1), assuring the safety of the treatment and providing the possibility for the adoption of more stringent constraints in the future.

MRI-GUIDED RADIOTHERAPY FOR PROSTATE CANCER: A NEW PARADIGM.

Radiotherapy is one of the key treatment modalities for primary prostate cancer. During the last decade, significant advances were made in radiotherapy technology leading to increasing both physical and biological precision. Being a loco-regional treatment approach, radiotherapy requires accurate target dose deposition while sparing surrounding healthy tissue. Conventional radiotherapy is based on computerized tomography (CT) images both for radiotherapy planning and image-guidance, however, shortcomings of CT as soft tissue imaging tool are well known. Nowadays, our ability to further escalate radiotherapy dose using hypofractionation is limited by uncertainties in CT-based image guidance and verification. Magnetic resonance imaging (MRI) is a well established imaging method for pelvic organs. In prostate cancer specifically, MRI accurately depicts prostate zonal anatomy, rectum, bladder, and pelvic floor structures with previously unseen precision owing to its sharp soft tissue contrast. The advantages of including MRI in the clinical workflow of prostate cancer radiotherapy are multifold. MRI allows for true adaptive radiotherapy to unfold based on daily MRI images taken before, during and after each radiotherapy fraction. It enables accurate dose escalation to the prostate and intraprostatic tumor lesions. Technically, MRI high-strength magnetic field and linear accelerator high energy electromagnetic beams are hardly compatible, and important efforts were made to overcome these technical challenges and integrate MRI and linear accelerator into one single treatment device, called MRI-linac. Different systems are produced by two leading vendors in the field and currently, there are around 100 MRI-linacs worldwide in clinical operations. In this narrative review paper, we discuss historical perspective of image guidance in radiotherapy, basic elements of MRI, current clinical developments in MRI-guided prostate cancer radiotherapy, and challenges associated with the use of MRI-linac in clinical practice.

Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience.

BACKGROUND: Hypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized evidence so far to support it's use. Additionally, patients with persistent PSA after prostatectomy may have aggressive disease and respond less well on standard salvage treatment. Herein we report outcomes for conventionally fractionated (CFR) and hypofractionated radiotherapy (HFR) in patients with persistent postprostatectomy PSA who received salvage radiotherapy to prostate bed. METHODS: Single institution retrospective chart review was performed after Institutional Review Board approval. Between May 2012 and December 2016, 147 patients received salvage postprostatectomy radiotherapy. PSA failure-free and metastasis-free survival were calculated using Kaplan-Meier method. Cox regression analysis was performed to test association of fractionation regimen and other clinical factors with treatment outcomes. Early and late toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. RESULTS: Sixty-nine patients who had persistent PSA (≥ 0.1 ng/mL) after prostatectomy were identified. Median follow-up was 67 months (95% CI 58-106 months, range, 8-106 months). Thirty-six patients (52.2%) received CFR, 66 Gy in 33 fractions, 2 Gy per fraction, and 33 patients (47.8%) received HFR, 52.5 Gy in 20 fractions, 2.63 Gy per fraction. Forty-seven (68%) patients received androgen deprivation therapy (ADT). 5-year PSA failure- and metastasis-free survival rate was 56.9% and 76.9%, respectively. Thirty patients (43%) experienced biochemical failure after salvage radiotherapy and 16 patients (23%) experienced metastatic relapse. Nine patients (13%) developed metastatic castration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72 months (95% CI; 41-72 months), while median metastasis-free survival was not reached. Patients in HFR group were more likely to experience shorter PSA failure-free survival when compared to CFR group (HR 2.2; 95% CI 1.0-4.6, p = 0.04). On univariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (CFR vs HFR, HR 2.2, 95% CI 1.0-4.6, p = 0.04), first postoperative PSA (HR 1.02, 95% CI 1.0-1.04, p = 0.03), and concomitant ADT (HR 3.3, 95% CI 1.2-8.6, p = 0.02). On multivariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (HR 3.04, 95% CI 1.37-6.74, p = 0.006) and concomitant ADT (HR 4.41, 95% CI 1.6-12.12, p = 0.004). On univariate analysis, factors significantly associated with metastasis-free survival were the first postoperative PSA (HR 1.07, 95% CI 1.03-1.12, p = 0.002), seminal vesicle involvement (HR 3.48, 95% CI 1.26-9.6,p = 0.02), extracapsular extension (HR 7.02, 95% CI 1.96-25.07, p = 0.003), and surgical margin status (HR 2.86, 95% CI 1.03-7.97, p = 0.04). The first postoperative PSA (HR 1.04, 95% CI 1.00-1.08, p = 0.02) and extracapsular extension (HR 4.24, 95% CI 1.08-16.55, p = 0.04) remained significantly associated with metastasis-free survival on multivariate analysis. Three patients in CFR arm (8%) experienced late genitourinary grade 3 toxicity. CONCLUSIONS: In our experience, commonly used hypofractionated radiotherapy regimen was associated with lower biochemical control compared to standard fractionation in patients with persistent PSA receiving salvage radiotherapy. Reason for this might be lower biological dose in HFR compared to CFR group. However, this observation is limited due to baseline imbalances in ADT use, ADT duration and Grade Group distribution between two radiotherapy cohorts. In patients with persistent PSA post-prostatectomy, the first postoperative PSA is an independent risk factor for treatment failure. Additional studies are needed to corroborate our observations.

High-dose-rate brachytherapy and concurrent chemoradiotherapy followed by surgery for stage Ib-IIb cervical cancer: single institution experience.

BACKGROUND: There are still controversies about the benefit of surgery after concurrent radiochemotherapy (CRT) for locally advanced cervical cancer. The aim of this study was to evaluate toxicity, local tumor control and overall survival of surgery after CRT in stage IB-IIB cervical cancer. PATIENTS AND METHODS: Between 2002 and 2008, 24 patients with stage IB-IIB cervical cancer were treated with external-beam radiotherapy concomitantly with chemotherapy. High-dose rate brachytherapy fractions were given once weekly. Radical hysterectomy was undertaken after a median of 42 days. RESULTS: Overall survival at five years was estimated at 75% (95% confidence interval=52-88%) and sustained thereafter through to 8.9 years. No patient experienced local failure in the surgical bed. Postoperative complications were recorded in two patients. CONCLUSION: Surgery after CRT in stage IB-IIB cervical cancer is safe and leads to better local control of the disease and overall survival.

Intraluminal brachytherapy in the management of squamous carcinoma of the esophagus.

Intraluminal high dose rate brachytherapy (ILHDR BT) is one of several effective modalities for palliation of advanced esophageal cancer. Thirty patients with endoscopic-proven, mostly locally advanced, squamous cell carcinoma of the esophagus, not involving the gastroesophageal junction and without distant metastases, were included in this analysis. Twenty-nine patients received two ILHDR BT sessions of 8 Gy within a week and one patient received only one session. All patients were followed monthly. Outcomes included quality of life (QOL), symptoms control: dysphagia, regurgitation, odynophagia, and chest or back pain, as well as, overall survival. Through 4 months of follow-up, QOL was statistically improved (having lowered scores) in regards to feelings (P= 0.013), sleeping (P= 0.032), eating (P= 0.020), and social life (P= 0.002). The most significantly improved symptom was dysphagia (P < 0.006), with a reduction of 0.52 units or one-half grade. Regurgitation, odynophagia, and pain were lower during follow-up but were not statistically significant. The median overall survival from death of any cause was 165 days (with a 95% confidence interval of 128-195 days). In conclusion, ILHDR BT of advanced squamous esophageal cancer consisting of two out-patient procedures is very successful in achieving the primary objectives of the patients to reduce dysphagia and improve QOL.