Conventionally fractionated radiotherapy versus CyberKnife hypofractionated radiotherapy for painful vertebral haemangiomas - A randomized clinical trial.

BACKGROUND AND PURPOSE: The outcomes of conventional radiotherapy for painful vertebral haemangiomas have been improved through dose escalation at the expense of overall treatment time. We hypothesized that with the aid of precise hypofractionated radiotherapy, it is possible to safely deliver a similar biological equivalent dose over a significantly shorter course of treatment with a comparable efficacy and safety. MATERIALS AND METHODS: In this prospective, single-institution unblinded randomized clinical trial (NCT02332408) patients with painful vertebral haemangiomas were allocated one-to-one either to 25 Gy delivered in five fractions (CK) or conventionally fractionated radiotherapy up to 36 Gy (conv.). The main endpoint was pain relief at two years, measured on a subjective and numerical scale (NRS). RESULTS: The trial was finished yielding 74 evaluable patients, including 38 in the CK arm. Adverse events were infrequent and the treatment was well tolerated. The overall treatment time was significantly shorter in the CK arm (median of 13 days vs 25 days). At two years, more than half of the patients reported improvement (46; 62.2 %) , in 21 cases the pain symptoms were stable (28.4 %), and in seven cases worse (9.5 %). There were significantly more patients reporting improvement in the CK arm (73.7 % vs 50 %; p = 0.036). The median decrease in NRS was 4 (IQR 1-5) or 59 % (IQR 20-86 %), and the difference between arms was not statistically significant. CONCLUSION: Five fractions hypofractionated radiotherapy for painful vertebral haemangiomas up to a total dose of 25 Gy is a safe treatment modality, significantly shorter compared to conventional fractionation, and possibly more effective.

Ultra-Hypofractionated Stereotactic Body Radiotherapy for Localized Prostate Cancer: Clinical Outcomes, Patterns of Recurrence, Feasibility of Definitive Salvage Treatment, and Competing Oncological Risk.

A cohort of 650 patients treated for localized prostate cancer (PCa) with CyberKnifeTM ultra-hypofractionated radiotherapy between 2011 and 2018 was retrospectively analyzed in terms of survival, patterns of failure, and outcomes of second-line definitive salvage therapies. The analysis was performed using survival analysis including the Kaplan-Meier method and Cox regression analysis. At a median follow-up of 49.4 months, the main pattern of failure was local-regional failure (7.4% in low-, and 13% in intermediate/high-risk group at five years), followed by distant metastases (3.6% in low-, and 6% in intermediate/high-risk group at five years). Five-year likelihood of developing a second malignancy was 7.3%; however, in the vast majority of the cases, the association with prior irradiation was unlikely. The 5-year overall survival was 90.2% in low-, and 88.8% in intermediate/high-risk patients. The independent prognostic factors for survival included age (HR 1.1; 95% CI 1.07-1.14) and occurrence of a second malignancy (HR 3.67; 95% CI 2.19-6.15). Definitive local salvage therapies were feasible in the majority of the patients with local-regional failure, and uncommonly in patients with distant metastases, with an estimated second-line progression free survival of 67.8% at two years. Competing oncological risks and age were significantly more important for patients' survival compared to primary disease recurrence.

The Prognostic Value of PI-RADS Score in CyberKnife Ultra-Hypofractionated Radiotherapy for Localized Prostate Cancer.

Prostate Imaging-Reporting and Data System (PI-RADS) has been widely implemented as a diagnostic tool for significant prostate cancer (PCa); less is known about its prognostic value, especially in the setting of primary radiotherapy. We aimed to analyze the association between PI-RADS v. 2.1 classification and risk of metastases, based on a group of 152 patients treated with ultra-hypofractionated stereotactic CyberKnife radiotherapy for localized low or intermediate risk-group prostate cancer. We found that all distant failures (n = 5) occurred in patients diagnosed with a PI-RADS score of 5, and axial measurements of the target lesion were associated with the risk of developing metastases (p < 0.001). The best risk stratification model (based on a combination of greatest dimension, the product of multiplication of PI-RADS target lesion axial measurements, and age) achieved a c-index of 0.903 (bootstrap-validated bias-corrected 95% CI: 0.848−0.901). This creates a hypothesis that PI-RADS 5 and the size of the target lesion are important prognostic factors in early-stage PCa patients and should be considered as an adverse prognostic measure for patients undergoing early treatment such as radiation or focal therapy.

Stereotactic Ablative Radiotherapy for Prostate Cancer-The Treatment Results of 500 Patients and Analysis of Failures.

OBJECTIVE: Stereotactic ablative radiotherapy is a very promising approach for the treatment of patients with prostate cancer. The aim of this study was to evaluate the clinical tolerance, effectiveness, patterns of failure, and attempt to define predictive factors based on our experience. METHODS: The cohort consists of 264 low-risk and 236 intermediate-risk consecutive patients treated at one institution. Prostate-specific antigen (PSA), adverse effects, and androgen deprivation therapy (ADT) usage were noted. RESULTS: Median follow-up was 31.3 months. Over 90% of the patients reported no gastrointestinal toxicity. There were 4 occurrences of G3+ sequelae. 75% patients had no genitourinary toxicity at first month, and up to 90% during the rest of follow-up, with only 1 case of G3 adverse event. The toxicity was more pronounced in patients with higher PSA concentrations. Prior to stereotactic ablative radiotherapy, the mean PSA was 7.59 and 277 patients used ADT. The PSA decreased for up to 20 months before reaching a plateau. The decline was slower, and PSA levels were higher in patients without ADT. A total of 15 treatment failures occured in a median time of 19.9 months. Higher PSA concentrations were connected with higher failure rates, even in the first month and prior to reaching Phoenix criterion. CONCLUSION: CyberKnife-based stereotactic ablative radiotherapy of low-risk and intermediate-risk prostate cancer patients is an effective and well-tolerated modality of treatment. PSA is the most important predictive factor. The evolution of PSA concentration in a particular subgroup of patients suggests that ADT in intermediate-risk cases could improve long-term results.

A comparison of treatment outcome between fiducial-based and bone-based image guided radiotherapy in prostate cancer patients.

BACKGROUND AND PURPOSE: To compare the clinical outcome in prostate cancer patients treated with radiotherapy using two forms of image guidance: bone-based (BB) or fiducial-based (FB). MATERIAL AND METHODS: This retrospective study consisted of 180 patients treated with kV-kV image-guided radiotherapy (IGRT) between the years 2008 and 2011. A total of 89 patients were aligned to pelvic bone (Group BB) and 91 patients to the fiducial implanted into prostate for image guidance (Group FB). Patients were treated to a total dose of 76 Gy in 38 fractions. The Cox Regression Model was used to evaluate the influence of clinical and treatment-related parameters on overall survival, biochemical progression and progression-free survival. Acute and late toxicity were evaluated based on the RTOG/EORTC criteria. Sexual function was assessed with QLQ PR-25 (EORTC QLQ forms). An assessment of the differences in patient daily set-up from the time of simulation was performed. RESULTS: The incidence of acute G2/G3 genitourinary (GU) and gastrointestinal (GI) toxicity was similar between groups. In the BB group, 34 patients had G2 and 5 had G3 GU acute toxicity - compared to 40 patients with G2 and 2 with G3 in the FB group. G2 and G3 GI acute toxicity was observed respectively in 24 patients and in 1 patient in the BB group compared to 18 patients with G2 and 1 patient with G3 toxicity in the FB group. The five-year incidence of late ≥G2 GU toxicity was 12% in both groups (p = 0.98) and ≥ G2 GI toxicity 19% (BB) vs 15% (FB, p = 0.55), respectively. The five-year progression-free survival rate was 87% in BB and 81% in the FB Group (p = 0.15). The 5-year Overall Survival rate (OS) was 80% (BB) vs 91% % (FB, p = 0.20), but the difference was most pronounced in the intermediate-risk group: 5-year OS of 93% (FB) and 75% (BB), respectively (p = 0.06). No significant changes were observed in sexual or erectile functioning as compared to that specified at the beginning of radiotherapy and between the FB and BB Groups. CONCLUSION: When comparing bone-based to fiducial-based techniques, no differences in clinical outcomes or late toxicity were seen in this population. However, intermediate risk prostate cancer patients are those who might benefit most from implementation of fiducial-based IGRT.

Cyberknife Radioablation of Prostate Cancer ­ Preliminary Results for 400 Patients

Objectives: To evaluate the tolerance and effectiveness of stereotactic ablative radiotherapy (SABR) applied in the treatment of low and intermediate risk (LR & IR) prostate cancer patients (PCP) and provide an evaluation of the level of risk group impact on treatment results. In addition, androgen deprivation therapy (ADT) usage and prostatic specific antigen (PSA) decline after SABR were assessed. Material and Methods: A total of 400 PCP (213 LR and 187 IR, including T2c) were irradiated with a CyberKnife using fd 7.25 Gy to TD 36.25 Gy. At the start of treatment, 60.3% of patients were undergoing ADT and this gradually decreased to 0% after 38 months. Follow-up was for a median of 15.0 months. Patients were monitored on SABR completion and 1, 4, 8 months later and then subsequently every 6 months. GI (Gastro-Intestinal) and GU (Genito-Urinary) acute and late adverse effects, PSA and ADT usage were evaluated. Results: Failure was noted in 9 patients (2.25%) (5 in LR and 4 in IR groups) - 4 relapses and 5 nodal metastases. No G3/4 late adverse effects (EORTC/RTOG) were observed. Some 0.5% of G3 GU and 0.3% of G3 GI acute reactions were noted respectively on the SABR completion day and one month later. The median of PSA declined 1.5 ng/ml during the first month and 0.6 ng/ml during the next three months. No impact of risk groups on treatment results was found. An impact of ADT on PSA decline was only confirmed for time point interactions. Conclusions: SABR for LR and IR PCP is a safe and effective treatment. The inclusion of T2c patients and the low percentage of IR patient failure permit us the assumption that this procedure could be utilized in the treatment of more advanced cases. The results do not allow clear definition of the impact of ADT on radioablation results in LR and IR+ T2c cases.

[CyberKnife for prostate cancer patients. Update of 200 patients treatment results].

Introduction: This is an update regarding the treatment results of 200 prostate cancer patients' (PCP) CyberKnife based radioablation (the first group in Poland). The purpose of this study is reevaluation (after 2 years) of this treatment modality results of low (LR) and intermediate risk (IR) (including T2c) PCP and failure analysis. Material and Methods: 200 PCP (95 LR, 86 IR, 19 T2c) 53 ­ 83 y.o. (mean 69) treated between 2011 and 2014. 48% used neoadjuvant ADT. The patients were irradiated every other day with a fraction dose of 7.25 Gy to the total dose 36.25 Gy (5 fractions in 9 days). Fiducials based tracking was performed. The patients were controlled on the treatment completion day, 1, 4, 8 months later and subsequently every 6 months. The PSA concentration, ADT usage, acute and late adverse effects (EORTC/RTOG) and other symptoms were evaluated. FU ranged from 1 to 63.6 months (mean 32.2, median 32.9). Results: The adverse effects percentage was very low; only 1 month after treatment the percentage of acute urinary reaction exceeded 40%. Only single G3 adverse effects were noted. Over 4 months the median PSA concentration declined from 3.75 to 0.27 ng/ml. 9 failures (4.5%) were noted ­ more among IR and patients without neoadjuvant ADT. No failure in the T2c group was found. Median time to failure was 32.4 months. Cox analysis revealed that the failure risk increases with the value of maximal PSA before treatment. Conclusions: CK based radioablation of LR and IR PCP is a safe and highly effective treatment modality. The main prognostic factor of failure after this treatment is probably the maximal PSA concentration before treatment. The neoadjuvant ADT in IR group should be considered. The lack of failures in the T2c group enables us to suggest that even more locally advanced patients (T3) with low PSA and maximal Gleason 3+4 could be treated with this modality.

Cell-cycle gene expression analysis using real time PCR in locally advanced squamous-cell head and neck cancer.

PURPOSE: The analysis of gene expression, especially those involved in cell cycle control, can help to discover mechanisms determining the outcome of radiation treatment. The main purpose of this study was to examine the expression level of genes responsible for cell cycle regulation in samples of the head and neck cancer, obtained during surgery. METHODS: Postsurgical samples of SCC of head and neck region were collected. Over 80 genes were analysed using cell cycle quantitative real-time RT-PCR Array method. Presence of 14 high-risk HPV types DNA in frozen or paraffin-embedded tumour pathological samples was also assessed. To correlate gene expression with selected pathological features and clinical outcome we used different hierarchical clustering method. RESULTS: Hierarchical clustering demonstrated the association between gene expression within certain clusters and gender, tumour site, T stage, N stage, grade, pathological subtype or tumour recurrence. CONCLUSIONS: Despite some limitations we were able to identify gene clusters that allowed to classify patients according to selected clinical features and occurrence of tumour recurrence. The results of the analysis also confirm that the incidence of HPV infection among the patients from Upper Silesia is relatively low, whereas HPV negative tumours, likely associated with smoking, appeared dominant.

Salvage high-dose-rate brachytherapy for locally recurrent prostate cancer after primary radiotherapy failure.

BACKGROUND AND PURPOSE: To evaluate high-dose-rate brachytherapy (HDR BT) as a salvage modality for locally recurrent prostate cancer after primary radiotherapy failure. MATERIALS AND METHODS: Eighty-three prostate cancer patients, who locally relapsed after radiotherapy, were treated with salvage HDR BT. The schedule was three implantations, every two weeks, with 10Gy per implant, to a total dose of 30Gy. Acute and late toxicity rates were evaluated. Overall survival (OS) and biochemical control were calculated using Kaplan-Meier method. RESULTS: Median follow-up after salvage HDR was 41months. The 3-year and 5-year OS were 93% and 86%, respectively. The 3-year and 5-year biochemical disease-free survival (bDFS) were 76% and 67%, respectively. The single factor associated with biochemical control was time to achieve salvage PSA nadir (p-.006). OS was linked significantly with primary nadir level (p-.001) while primary biochemical relapse interval was of borderline significance (p-.07). CONCLUSIONS: Salvage HDR BT is a promising treatment option for patients with localized relapse of previously irradiated prostate cancer. Lower PSA nadir after primary radiotherapy and longer primary disease-free interval influence the outcome.

CyberKnife-based prostate cancer patient radioablation - early results of irradiation in 200 patients.

INTRODUCTION: Prostrate cancer (PC) is one of the most common malignancies and is frequently treated with an 8-week course of radiotherapy. CyberKnife (CK) based radioablation enables completion of therapy within 5-9 days. The aim of this study is an evaluation of the effectiveness and tolerance of CyberKnife-based radioablation in prostate cancer patients. MATERIAL AND METHODS: 200 PC patients (94 low risk [LR], 106 intermediate risk [IR]) underwent CK irradiation every other day (fraction dose [fd] 7.25 Gy, total dose [TD] 36.25 Gy, time 9 days). PSA varied from 1.1 to 19.5 (median 7.7) and T stage from T1c to T2c. The percentage of patients with Androgen Deprivation Therapy (ADT), GI (gastrointestinal) and GU (genitourinary) toxicity (EORTC/RTOG scale), and PSA were checked at 1, 4 and 8 months, and thereafter every 6 months - up to a total of 26 months - post-treatment. RESULTS: The percentage of patients without ADT increased from 47.5% to 94.1% after 26 months. The maximum percentage of acute G3 adverse effects was 0.6% for GI, 1% for GU and G2 - 2.1% for GI and 8.5% for GU. No late G3 toxicity was observed. The maximum percentage of late G2 toxicity was 0.7% for GI and 3.4% for GU. Median PSA decreased from 7.7 to 0.1 ng/ml during FU. One patient relapsed and was treated with salvage brachytherapy. CONCLUSIONS: We conclude that CK-based radioablation in low and intermediate risk PC patients is an effective treatment modality enabling OTT reduction and presents a very low percentage of adverse effects.

Metsulfuron-methyl-based herbicidal ionic liquids.

Ten sulfonylurea-based herbicidal ionic liquids (HILs) were prepared by combining the metsulfuron-methyl anion with various cation types including quaternary ammonium ([bis(2-hydroxyethyl)methyloleylammonium](+), [2-hydroxyethyltrimethylammonium](+)), pyridinium ([1-dodecylpyridinium](+)), piperidinium ([1-methyl-1-propylpiperidinium](+)), imidazolium ([1-allyl-3-methylimidazolium](+), [1-butyl-3-methylimidazolium](+)), pyrrolidinium ([1-butyl-1-methylpyrrolidinium](+)), morpholinium ([4-decyl-4-methylmorpholinium](+)), and phosphonium ([trihexyltetradecylphosphonium](+) and [tetrabutylphosphonium](+)). Their herbicidal efficacy was studied in both greenhouse tests and field trials. Preliminary results for the greenhouse tests showed at least twice the activity for all HILs when compared to the activity of commercial Galmet 20 SG, with HILs with phosphonium cations being the most effective. The results of two-year field studies showed significantly less enhancement of activity than observed in the greenhouse; nonetheless, it was found that the herbicidal efficacy was higher than that of the commercial analog, and efficacy varied depending on the plant species.

Case presentation - A five-year survival of the patient with glioblastoma brain tumor.

This paper presents an atypical case of a patient with brain tumor of the glioblastoma multiforme (GBM) type who achieved a 5-year survival. Some general information is provided including epidemiology, diagnostic and treatment procedures (surgery and radio-chemo-therapy), and prognosis of survival related to GBM. The course of the disease, including its main symptoms, individual reasons for the delay of adjuvant treatment, after the primary surgical treatment, 37-month period of the decease free survival, as well as comprehensive management after the tumor recurrence are also presented. Histopathology confirming the clinical diagnosis is discussed in a separate chapter.

[Evaluation of GoldAnchorTM fiducial marker migration during the planning of radiation treatment for patients with prostate cancer]. / Ocena migracji znaczników sródtkankowych GoldAnchorTM w czasie planowania leczenia promieniami chorych na raka gruczolu krokowego.

INTRODUCTION: The use of fiducial markers in patients undergoing teleradiotherapy increases the precision of treatment under the condition that the marker does not displace itself during this treatment. In order to determine the accuracy of the verification method used to establish patient position, it is necessary to establish the possible marker migration range during planning and treatment with radiation therapy. MATERIAL AND METHOD: An analysis of the migration of GoldAnchorTM fiducial markers implanted in the prostate conducted on a group of 29 patients treated with image-guided radiation therapy at the Radiotherapy Department of the Cancer Centre and Institute of Oncology in Gliwice. The migration value was determined based on a comparison of the marker's location with the use of spiral computer tomography and cone-beam computer tomography done on the treatment device. RESULTS: The average values of the given fiducial marker's migration in the superior-inferior (SI), left-right (LR) and anterior-posterior (AP) directions were: 0.07 cm (SD=0.1 cm); 0.06 cm (SD=0.07 cm) and 0.11 cm (SD=0.11 cm), respectively. The average value of the displacement vector computed according to the Pythagorean theorem and using the Euclidean norm was 0.17 cm with SD= 0.13 cm. CONCLUSION: The analysis indicates that migration of markers implanted in the prostate occurs during radiation treatment planning but probably it is not clinically relevant. Because a correlation was determined between the migration value and the time of carrying out the CT as well as the time that had passed from the implantation to the CBCT examination, it is reasonable to start radiation therapy promptly and to control the marker's location during radiation therapy.