Pencil-beam scanning proton therapy for the treatment of glomus jugulare tumours.

INTRODUCTION: Glomus jugulare tumours (GJT) are benign tumours that arise locally and destructively in the base of the skull and can be successfully treated with radiotherapy. Patients have a long-life expectancy and the late effects of radiotherapy can be serious. Proton radiotherapy reduces doses to critical organs and can reduce late side effects of radiotherapy. The aim of this study was to report feasibility and early clinical results of 12 patients treated using proton therapy. METHODS: Between December 2013 and June 2019, 12 patients (pts) with GJT (median volume 20.4 cm3 ; range 8.5-41 cm3 ) were treated with intensity modulated proton therapy (IMPT). Median dose was 54 GyE (Gray Equivalents) (50-60 GyE) with daily fractions of 2 GyE. Twelve patients were analysed with a median follow-up time of 42.2 months (11.3-86.7). Feasibility, dosimetric parameters, acute and late toxicity and local effect on tumour were evaluated in this retrospective study. RESULTS: All patients finished treatment without interruption, with excellent dosimetric parameters and mild acute toxicity. Stabilisation of tumour size was detected on MRI in all patients. No changes in symptoms were observed in comparison with pre-treatment conditions. No late effects of radiotherapy were observed. CONCLUSION: Pencil-beam scanning proton radiotherapy is highly feasible in the treatment of large GJT with mild acute toxicity and promising short-term results. Longer follow-up and larger patient cohorts are required to further identify the role of pencil-beam scanning (PBS) for this indication.

Ultrahypofractionated Proton Radiation Therapy in the Treatment of Low and Intermediate-Risk Prostate Cancer-5-Year Outcomes.

PURPOSE: To analyze the 5-year biochemical disease-free survival (bDFS) and late toxicity profile in patients with prostate cancer treated with pencil beam scanning (PBS) proton radiation therapy. METHODS AND MATERIALS: Between January 2013 and March 2016, 284 patients with prostate cancer were treated using intensity modulated proton therapy (IMPT), with an ultrahypofractionated schedule (36.25 GyE in 5 fractions). Five patients were immediately lost from follow-up and thus were excluded from analysis. Data for 279 patients were prospectively collected and analyzed with a median follow-up time of 56.5 (range, 3.4-87.5) months. The mean age at time of treatment was 64.5 (40.1-85.7) years, and the median prostate-specific antigen (PSA) value was 6.35 µg/L (0.67-17.3 µg/L). A total of 121 (43.4%) patients had low-risk, 125 patients (44.8%) had favorable, and 33 (11.8%) unfavorable intermediate-risk cancer. In addition, 49 (17.6%) patients underwent neoadjuvant hormonal therapy, and no patients had adjuvant hormonal therapy. bDFS and late toxicity profiles were evaluated. RESULTS: The median treatment time was 9 days (range, 7-18 days). The 5-year bDFS was 96.9%, 91.7%, and 83.5% for the low-, favorable, and unfavorable intermediate-risk group, respectively. Late toxicity (Common Terminology Criteria for Adverse Events v.4) was as follows: gastrointestinal: grade 1, 62 patients (22%), grade 2, 20 patients (7.2%), and grade 3, 1 patient (0.36%); genitourinary: grade 1, 80 patients (28.7%), grade 2, 14 patients (5%), and grade 3, 0 patients. PSA relapse was observed in 17 patients (6.1%), and lymph node or bone recurrence was detected in 11 patients. Four (1.4%) local recurrences were detected. Nine patients (3.2%) died of causes unrelated to prostate cancer. No deaths related to prostate cancer were reported. CONCLUSION: Ultrahypofractionated proton beam radiation therapy for prostate cancer is effective with long-term bDFS comparable with other fractionation schedules and with minimal serious long-term GI and GU toxicity.

Pencil Beam Scanning (PBS) Intensity-Modulated Proton Therapy (IMPT) Chemoradiotherapy for Anal Canal Cancer-Single Institution Experience.

Background: A favourable dose distribution has been described for proton beam therapy (PBT) of anal cancer in dosimetric studies. The relationship between dosimetric parameters in bone marrow and haematologic toxicity, treatment interruptions, and treatment efficacy has also been documented. There are only few references on clinical results of PBT for anal cancer. The primary objective of the retrospective study was to assess the efficacy of pencil beam scanning intensity-modulated proton therapy (PBS IMPT) in the definitive chemoradiotherapy of anal cancer. Secondary objectives were established to identify the risks of acute chronic toxicity risks and to assess colostomy rates. Materials and methods: Patients were treated for biopsy-proven squamous cell cancer (SCC) of the anus at initial or advanced stages. Eligible patients received PBS IMPT at a single institution. Treatment was administered in two volumes: 1-tumour with margins plus involved lymph nodes; 2-regional lymph node groups: perirectal (mesorectal), obturatory, inguinal, internal, external, and common iliac. The total doses of 57.5 GyE and 45 GyE, respectively, were administered in volumes 1 and 2 in 25 fractions, 5 fractions per week, respectively (a simultaneous integrated boost). Concomitant chemotherapy cisplatinum (CDDP) plus 5-FU or CDDP plus capecitabine was administered as per protocol. The treatment effect was assessed using DRE (digital rectal examination) and MRI (magnetic resonance imaging) within the follow-up period. Toxicity was scaled using CTCAE version 4.0 criteria. Results: 39 of 41 patients treated during the period of February 2014-August 2021 were eligible for analysis. All patients completed treatment, 76.9% without interruption. The median treatment time was 35 days (32-35). The median follow-up period was 30 months, 34 patients are alive to-date, 5 patients died prior to the date of analysis, and 2 deaths were unrelated to the primary disease. The 2-year overall survival, relapse-free survival, and colostomy-free survival were 94.2%, 93.8%, and 91.0%, respectively. Complete regression was achieved in 36 patients (92.3%), partial regression was achieved in 2 (5.1%), and immediate progression at end of treatment occurred in 1 patient (2.6%). Salvage resection was indicated for two patients in partial regression and due to severe chronic dermatologic toxicity. The grade 3 and 4 haematological toxicity rates were 7.7% and 5.1%, respectively. The most frequent non-haematological acute toxicities of grade 3-4 observed were dermatitis (23.1%), diarrhoea (7.7%), and dehydration (7.7%). Chronic toxicity emerged predominantly as skin atrophy/ulceration grade 2 (26.5%) and grade 3-4 (5.8%), and radiation proctitis grade 2 (38.2%) and grade 3 (2.9%). Discussion, conclusions: This single-institution study showed the high efficacy of PBS IMPT, achieving a high rate of complete regression. The haematological acute toxicity of grade 3-4 remained low; however, the impact of altered chemotherapy (CDDP instead of mitomycin C) remains unclear. The incidence of other acute toxicities shares similarity with photon therapy investigated in large studies. The acute toxicity completely resolved in all patients, had no lethal outcomes, and never resulted in the necessity for colostomy. By contrast, it was chronic toxicity, skin ulceration, perirectal fistulation, and fibrosis that resulted in salvage surgery and/or the need for a colostomy. A challenging question remains: to what extent can PBT prevent chronic toxicity? Longer follow-up remains necessary.

Chitosan-Based Aerogel Particles as Highly Effective Local Hemostatic Agents. Production Process and In Vivo Evaluations.

Chitosan aerogels with potential applications as effective local hemostatic agents were prepared using supercritical carbon dioxide drying to preserve the chitosan network structure featuring high internal surfaces and porosities of up to 300 m²/g and 98%, respectively. For the first time, hemostatic efficacy of chitosan-based aerogel particles was studied in vivo on a model of damage of a large vessel in the deep wound. Pigs were used as test animals. It was shown that primary hemostasis was achieved, there were no signs of rebleeding and aerogel particles were tightly fixed to the walls of the wound canal. A dense clot was formed inside the wound (at the femoral artery), which indicates stable hemostasis. This study demonstrated that chitosan-based aerogel particles have a high sorption capacity and are highly effective as local hemostatic agents which can be used to stop massive bleeding.

LOW DOSE BATH FROM IMPT VS. IMXT FOR THE PELVIC AREA WHEN TREATING ADVANCED PROSTATE CANCER.

Twenty (10 intensity-modulated proton therapy (IMPT) and 10 intensity-modulated x-ray therapy (IMXT) treatment plans for patients with advanced prostate carcinoma were compared in this study. All chosen patients were indicated for prostate and pelvic lymph nodes irradiation using simultaneous integrated boost technique. These patients represent typical specimen for this diagnose. IMPT irradiates just half of the tissue volume with a low dose (up to 10 cobalt gray equivalent) compared to IMXT without compromise in target volumes coverage and in this way reduces the risk of secondary cancer development or other possible complications.

Extreme hypofractionated proton radiotherapy for prostate cancer using pencil beam scanning: Dosimetry, acute toxicity and preliminary results.

INTRODUCTION: Extreme hypofractionated radiotherapy for prostate cancer is a common modality in photon therapy. Pencil beam scanning (PBS) in similar fractionation allows better dose distribution and makes proton therapy more available for such patients. The purpose of this study is the feasibility of extreme proton hypofractionated radiotherapy and publication of early clinical results. METHODS: Two hundred patients with early-stage prostate cancer were treated with IMPT (intensity-modulated proton therapy), extreme hypofractionated schedule (36.25 GyE in five fractions) between February 2013 and December 2015. Mean age of the patients was 64.3 years, and the mean value of prostate-specific antigen (PSA) before treatment was 6.83 µg/L (0.6-17.3 µg/L). Ninety-three patients (46.5%) were in the low-risk group. One hundred and seven patients (53.5%) were in the intermediate-risk group. Twenty-nine patients (14.5%) had neoadjuvant hormonal therapy, and no patients had adjuvant hormonal therapy. Acute toxicity, late toxicity and short-term results were evaluated. RESULTS: All patients finished radiotherapy without interruptions. The median follow-up time was 36 months. The mean treatment time was 9.5 days (median 9 days). Acute toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 was (gastrointestinal toxicity) GI (grade) G1-17%, G2-3.5%; (genitourinary toxicity) GU G1-40%, G2-19%; and no G3 toxicity was observed. Late toxicity was GI G1-19%, G2-5.5%; GU G1-17%, G2-4%; and no G3 toxicity was observed. PSA relapse was observed in one patient (1.08%) in the low-risk group (pelvic lymph node involvement was detected) and in seven patients (6.5%) in the intermediate-risk group (three lymph node metastases, two lymph node and bone metastases, two PSA relapses). No patient died of prostate cancer, and three patients died from other reasons. No local recurrence of cancer in the prostate was observed. CONCLUSIONS: Proton beam radiotherapy for prostate cancer is feasible with a low rate of acute toxicity and promising late toxicity and effectivity.

Effects of early therapeutic administration of interleukin-1beta on survival rate and bone marrow haemopoiesis in irradiated mice.

The study was aimed at the experimental assessment of the efficacy of recombinant interleukin-1beta in the early therapy of haemopoiesis disorders caused by X-ray irradiation. The efficacy of the product was based on the 30-day survival rate and average life expectancy of dead animals. Endogenous and exogenous colony-formations were studied to reveal possible mechanisms of therapeutic effects of interleukin-1beta on the bone marrow. The early administration (10-15 min after exposure to radiation) of recombinant interleukin-1beta in a dose of 50 microg/kg increased the survival rate and prevented the post-irradiation decrease in the number of endogenous and exogenous CFU-S9 in irradiated mice.