Long-Term Clinical Results of IGRT in Prostate Cancer Treatment.

BACKGROUND: The combination of intensity modulated radiation therapy (IMRT) and image guided radiotherapy (IGRT) plays a significant role in sparing normal tissue during prostate cancer treatment. We report the clinical outcomes of 260 patients treated with high-dose IGRT as well as the toxicity of high-dose IGRT in these patients. MATERIALS AND METHODS: From September 2008 to February 2012, 260 men with clinically localized prostate cancer underwent radical radiotherapy. Two hundred patients were treated with IMRT (78 Gy in 39 fractions) to the prostate and base of seminal vesicles using an adaptive protocol combining cone-beam computed tomography (CBCT) and kilovoltage image matching with individualized safety margin calculation. Sixty patients underwent treatment with the same prescribed dose using RapidArc with a reduced safety margin of 6 mm and daily online matching using CBCT. Late toxicity was scored prospectively according to the RTOG/FC-LENT scale. RESULTS: Eighteen patients (6.9%) experienced acute grade 2 gastrointestinal toxicity. There was no acute grade 3 or 4 gastrointestinal toxicity. Thirty-nine patients (15%) experienced acute grade 2 genitourinary toxicity and 6 patients (2.3%) had grade 3 gerourinary toxicity. Genitourinary toxicity grade 4 was observed in 5 (1.9%) patients, due to installation of a urinary catheter. At a median follow up of 84.2 months, the estimated 7-year cumulative incidences of grade 2 gastrointestinal and genitourinary toxicity were 4.4 and 7.1% respectively. The estimated 7-year prostate specific antigen relapse free survival was 97.1% for low-risk disease, 83.6% for intermediate-risk disease and 75% for high-risk patients. CONCLUSION: The use of IMRT in combination with IGRT results in a low rate of late toxicity. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 8. 9. 2019 Accepted: 25. 10. 2019.

[Five-year results of IMRT for prostate cancer - tumor control]. / Petileté výsledky IMRT karcinomu prostaty - kontrola nádoru.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) is the method of choice in external-beam radiotherapy tolocalized prostate cancer. This work analyses five year results of IMRT with a dose of 78/82 Gy. PATIENTS AND METHODS: From June 2003 to December 2007, the IMRT technique was employed to treat 233 patients with T1-3 N0 M0 prostate cancer. It was supplemented by hormone therapy especially in high-risk patients. Two IMRT techniques were applied - IMRT with a dose of 78 Gy in 39 fractions to prostate and seminal vesicles (SV) (IMRT 78) and IMRT with simultaneous integrated 82 Gy boost to prostate concurrently with 73,8 Gy in 41 fractions to SV (IMRT SIB 82). The IMRT 78 technique was used in 160 patients (69%). Seventy-three (31%) patients with intermediate (IR) or high-risk (HR) prostate cancer without SV involvement were treated with IMRT SIB 82 technique. The PSA relapse was defined as an increase in PSA of at least 2.0 ng/mL above the nadir or in comparison to the value at the initiation of hormone therapy. Clinical relapse was defined as an occurence of distant metastases and/or local recurrence. RESULTS: The median follow-up of our patients´ population was 4.3 years (range 0.6-8.9 years). The estimated 5-year PSA relapse-free survival in low-risk (LR), IR and HR patients was 86%, 89% and 83%, respectively (p = NS). In a multivariate analysis, Gleason score (GS) 8-10 was associated with significantly higher risk of PSA relapse (RR 2.76), while higher age at the time of diagnosis significantly decreased the PSA relapse risk (RR 0.94). The estimated 5-year clinical relapse-free survival in LR, IR and HR patients was 100%, 99% and 95%, respectively (p = NS). In a univariate analysis, both GS and PSA had a significant impact on the 5-year clinical relapse-free survival - GS 2-7 97 % vs GS 8-10 88 % (p = 0.03), PSA 20 98 % vs PSA > 20 85 % (p < 0.01). CONCLUSION: Treatment of localized prostate cancer using IMRT with a dose 78/82 Gy yielded an excellent 5-year tumour control with a risk of clinical relapse being less than 5%.

Perioperative interstitial CT-based brachytherapy boost in breast cancer patients with breast conservation after neoadjuvant chemotherapy.

Intraoperative placement of catheters in the tumor bed during breast-conserving surgery (BCS) enables postponed targeted boost irradiation in high risk breast cancer patients. Twenty-three patients with high risk breast cancer underwent neoadjuvant chemotherapy and multifractionated perioperative brachytherapy as a boost to the tumor bed using three-dimensional (3D) CT-based planning. Plastic catheters for brachytherapy were implanted during surgery and targeted irradiation was delivered in the course of 2-3 weeks. Acute and late toxicities were scored according to the RTOG Common Toxicity Criteria. Cosmetic outcomes were assessed using the Harvard criteria. No major perioperative complications were recorded. Circumscribed wound infection occurred in one patient (4.3%). Only 3 patients (13%) experienced acute skin toxicity Grade 1. We observed no teleangiectasias or pigmentations. The cosmetic outcome at last follow-up visit was rated as excellent/good, in 82.6%, fair, in 13% and poor in 4.4% of patients, respectively. There was no evidence of disease recurrence after median follow-up of 43. 4 months. Systematic integration of the perioperative fractionated 3D CT-based HDR brachytherapy as a boost for patients with breast cancer after BCS is feasible and seems safe. It might be beneficial especially for women with high risk of local recurrence.

MRI-based pre-planning in patients with cervical cancer treated with three-dimensional brachytherapy.

OBJECTIVE: The aim of this study was to analyse the feasibility and determine the benefits of MRI-based pre-planning with CT/MRI data fusion in patients with cervical cancer treated with radical radiotherapy. METHODS: Patients underwent MRI examination prior to external beam radiotherapy and prior to the first and fourth fraction of brachytherapy with applicators in place. Insertion of applicators at the radiology department was performed under paracervical anaesthesia. The benefit of MRI pre-planning was determined by comparing conventional treatment planning with dose specification to "point A" and dose specification to 90% of the high-risk clinical target volume (HR-CTV D90). Tolerance of MRI evaluation with applicators, coverage of HR-CTV and dose-volume parameters for organs at risk (OAR) has been assessed in 42 brachytherapy procedures. RESULTS: Insertion of applicators at the radiology department was successful in all patients and there were no complications. The target dose was higher for MRI planning than for conventional planning (5.3 Gy vs 4.5 Gy). Maximum doses in the bladder and rectum were significantly lower (p<0.05) for MRI planning than for the conventional approach (6.49 Gy vs 7.45 Gy for bladder; 4.57 Gy vs 5.06 Gy for rectum). We found no correlation between the International Commission on Radiation Units (ICRU) point dose for OAR and the maximum dose in OAR. Nevertheless, a strong correlation between the maximum dose in OAR and the minimal dose in a volume of 2 cm(3) has been observed. CONCLUSION: MRI-based pre-planning with consecutive CT/MRI data fusion is feasible and safe, with the advantage of increasing the dose to the tumour and decreasing the dose to the organs at risk.

Time course of late rectal toxicity after radiation therapy for prostate cancer.

Rectum and bladder are the crucial organs at risk for curative radiation therapy of localized prostate cancer. We analyzed the incidence, profile and time course of late rectal radiation toxicity. A total of 320 patients with T1-3 prostate cancer were treated with three-dimensional conformal radiation therapy (3D-CRT). The prescription dose was 70 Gy for T1 and T2 patients (n=230) and 74 Gy for patients with locally advanced T3 tumors (n=90). Late rectal toxicity was graded according to the Fox Chase modification of the Radiation Therapy Oncology Group (RTOG) and Late Effects Normal Tissue Task Force (LENT) criteria. The median follow-up time was 6.2 years (range 0.2-10.7 years). At 5 years, the risk for the development of grade 2 and 3 rectal toxicities was 15.6 and 7.0%, respectively. All new cases of grade 2 and 3 rectal toxicities were observed within 5 years after treatment. Prevalence of grade 2 and 3 rectal symptoms showed fluctuation with maximum at 1.5 years and the minor peak at 4.5 years. Toxicity profile changed significantly over time. The proportion of rectal bleeding within grade 2 and 3 toxicity decreased from 85% at 1.5 years to 46% at 4.5 years. Conversely, the proportion of fecal incontinence among grade 2 and 3 rectal symptoms gradually increased (0% at 1.5 years vs 27% at 4.5 years). Late rectal radiation toxicity represents a dynamic process. Rectal bleeding decreases and fecal incontinence increases over time.

Clinical results of intensity-modulated radiation therapy (IMRT) for tumors of the head and neck region.

Intensity-modulated radiation therapy (IMRT) is an advanced form of the three-dimensional conformal radiation therapy (3D-CRT). Highly conformal dose distribution is the basic feature of IMRT. The head and neck region is suitable for this new technology since the primary tumor is often surrounded by several critical structures. IMRT offers the ability of dose escalation due to steep dose gradient towards healthy tissues. In this review, clinical results of IMRT in several head and neck sites are presented, including intracranial tumors. Parotid-sparing strategies and patterns of local-regional failures are analyzed. The possibilities of irradiation of recurrent malignancies are mentioned. In perspective, the potential of IMRT should be explored in conjunction with altered fractionation regimens, including simultaneous integrated boost (SIB). Particularly, studies with dose escalation are desirable.

Perioperative fractionated high-dose rate brachytherapy in the treatment of soft tissue sarcomas.

The purpose of the study was to investigate the viability of perioperative fractionated high dose rate brachytherapy (HDR BT) for primary and reccurent soft tissue sarcomas (STS). From February 1998 through June 2002, 21 adult patients, 11 females and 10 males with either low grade or high grade soft tissue sarcomas were treated by perioperative HDR BT. Surgical margin was negative in 10 cases, close in 4 and positive in 4 in cases. In 3 cases it was not described. BT was used as a part of primary treatment in 10 cases and for the treatment of reccurent tumor in 11 cases. The localisation of the tumor was the extremity in 16 patients and the trunk in 5 patients. Ten patients were treated with HDR BT alone (total mean dose 40 Gy) and 11 were treated with combination of external beam radiotherapy (EBRT) (40-50 Gy) and brachytherapy (total mean dose 24 Gy). Hyperfractionation 2.4-3 Gy twice daily at 10 mm from the source was used for BT. Follow-up periods were between 7--48 months (median: 20 months). Local control in patients treated pro primary STS was 100%.The pulmonal metastases were a cause of death in one case, one patient was alive with dissemination and one patient was disease free after salvage surgery and chemotherapy for lung metastases. Local control was achieved only in 3 of 11 patients treated for reccurent tumor (27%). Six patients were disease free after salvage surgery, 2 patients died of disease progression, one patient died of toxicity of chemotherapy without evidence of disease and 2 patients are alive with distant metastases. Local control was achieved in 5 of 11 (45%) patients with positive, close or not stated surgical margin and in 5 of 10 (50%) patients with negative margin. Local control was 100% in patients treated by EBRT + BT, but only 20% in patients treated by BT alone. No infection or delayed wound healing has occurred after BT. Soft tissue necrosis was seen in 4 cases, subcutanous fistula in one case and peripheral nerve palsy in one case. Despite small number of patients and short follow up our study suggest that perioperative HDR BT is easy and promissing when used as a part of primary treatment for STS. The treatment results for recurrence are poor and in a lot of cases radical surgical approach should have been considered for the salvage.