CNS Tumors - clinical and radiological aspects.

Tumors of the central nervous system (CNS) include primary tumors - itraaxial, growing from brain and spinal cord cells (neuroepithelial tumors) or extraaxial, growing from surrounding structures (brain and spinal cord, nerve sheaths, vascular structures, lymphatic tissue, germ cells, malformations, pituitary glands). Much more often they are located in the intracranial space a solitary or multiple metastatic spread of malignancy originating from another organ (eg lung, breast, malignant melanoma, Grawitzs tumor). The occurrence of metastases of solid tumors is then in the intraaxial or extraaxial region, leptomeningeal or dural. Even morphologically benign tumors with their occurrence in a closed CNS compartment can have malignant behaviour and cause severe slowly developing to acute neurological symptoms, including intracranial hypertension. Primary tumors of the central nervous system present 1-2% of all cancers, with a higher incidence in adults after the age of 60, with a slight predominance in men, with higher mortality in men than in women. About 5% of CNS tumors are hereditary (e.g., Li-Fraumeni syndrome, neurofibromatosis type I, II). The causes of most brain and spinal cord tumors are unclear, the effect of radiation has been definitely demonstrated, there is an increased risk in transplant patients and AIDS (Acquired Immune Deficiency Syndrome) patients, and the potentiating effects of some chemicals and viruses on the development of CNS neoplasms are uncertain. The effectiveness of treatment of brain and spinal cord tumors is influenced by the existence of the so-called hematoencephalic barrier, which protects the brain from the penetration of toxic substances, but at the same time prevents the penetration of most cytostatics to the tumor target. Another obstacle may be the localization of the tumor in areas difficult to access for histological verification (brain stem, optical chiasma) due to the high risk of complications even after stereotactic biopsy. In some cases, in an effort not to cause an irreversible neurological deficit by inconsiderate tissue collection, the sample of histological material can then become inconclusive to tumor cells, i.e., tumor cells are not captured. Last but not least, the radiosensitivity of some brain structures is also limiting, which makes it impossible to apply a higher dose of ionizing radiation to a tumor affecting sensitive tissues or located near of these sensitive tissues. The rapid development of immunohistochemical (IHC) and molecular genetic analysis methods has significantly refined diagnostics and thus theoretically facilitates the choice of the optimal treatment procedure for the individual patient. While advances in modern conformal photon and particle (currently the most frequently proton) radiotherapy, stereotactic radiosurgery has enabled accurately targeted irradiation of the CNS tumor site and at the same time spare the high-risk brain structures, thereby significantly reduce the risk of acute and late neurotoxicity, pharmacotherapy options are still limited. Just molecular-genetic knowledge already provides us with predictive and prognostic information. They should increasingly stratify patients for targeted therapy.

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.

The evolution of rectal and urinary toxicity and immune response in prostate cancer patients treated with two three-dimensional conformal radiotherapy techniques.

BACKGROUND: Our research compared whole pelvic (WP) and prostate-only (PO) 3-dimensional conformal radiotherapy (3DCRT) techniques in terms of the incidence and evolution of acute and late toxicity of the rectum and urinary bladder, and identified the PTV-parameters influencing these damages and changes in antitumor immune response. METHODS: We analyzed 197 prostate cancer patients undergoing 3DCRT for gastrointestinal (GI) and genitourinary (GU) toxicities, and conducted a pilot immunological study including flow cytometry and an NK cell cytotoxicity assay. Acute and late toxicities were recorded according to the RTOG and the LENT-SOMA scales, respectively. Univariate and multivariate analyses were conducted for factors associated with toxicity. RESULTS: In the WP group, an increase of acute rectal toxicity was observed. A higher incidence of late GI/GU toxicity appeared in the PO group. Only 18 patients (WP-7.76% and PO-11.11%) suffered severe late GI toxicity, and 26 patients (WP-11.21% and PO-16.05%) severe late GU toxicity. In the majority of acute toxicity suffering patients, the diminution of late GI/GU toxicity to grade 1 or to no toxicity after radiotherapy was observed. The 3DCRT technique itself, patient age, T stage of TNM classification, surgical intervention, and some dose-volume parameters emerged as important factors in the probability of developing acute and late GI/GU toxicity. The proportion and differentiation of NK cells positively correlated during 3DCRT and negatively so after its completion with dose-volumes of the rectum and urinary bladder. T and NKT cells were down-regulated throughout the whole period. We found a negative correlation between leukocyte numbers and bone marrow irradiated by 44-54 Gy and a positive one for NK cell proportion and doses of 5-25 Gy. The acute GU, late GU, and GI toxicities up-regulated the T cell (CTL) numbers and NK cytotoxicity. CONCLUSION: Our study demonstrates the association of acute and late damage of the urinary bladder and rectum, with clinical and treatment related factors. The 3DCRT itself does not induce the late GI or GU toxicity and rather reduces the risk of transition from acute to late toxicity. We have described for the first time the correlation between organs at risk, dose-volume parameters, and the immunological profile.