Stereotactic radiosurgery in the treatment of essential tremor - a systematic review.

Introduction: Essential tremor (ET) is the most common movement disorder in adults, with an estimated incidence of up to 1% of the population and 5% of people older than 65 years of age. ET is manifested primarily by bilateral postural and kinetic tremor of the upper limbs with or without neurological symptoms and cognitive deficits. ET disrupts daily tasks and significantly lowers quality of life. Currently available medications alone are often insufficient to control severe symptoms. Several surgical treatment options are available, including stereotactic radiosurgery (SRS)-a minimally invasive treatment option aimed at relieving and controlling tremors. Methods: We conducted a systematic review of the scientific literature on the use of SRS in the treatment of ET using PubMed, Scopus, Web of Science, Cochrane, ScienceDirect, and ClinicalTrials.gov registry and adhered to the PRISMA guidelines. Results: The results obtained confirm the high efficacy and safety of the SRS procedure in treating drug-resistant intention tremor. The study results present high response rate reaching 80% and achievement of manual task improvement, lessening of the tremor and increase in the quality of life of the majority of the operated patients. The method also stands out for its favorable balance between efficiency and cost. Disscusion: Stereotactic radiosurgery is a favourable, safe, efficient and cost-effective method in treatment of the essential tremor. Ongoing research is crucial to refine patient selection criteria for this procedure and further improve the effectiveness of the technique.

Enhancing glioblastoma treatment through the integration of tumor-treating fields.

Glioblastoma (GBM) represents a significant therapeutic challenge due to its aggressive nature. Tumor Treating Fields (TTFields) present a promising approach to GBM therapy. The primary mechanism of TTFields, an antimitotic effect, alongside numerous indirect effects including increased cell membrane permeability, signifies their potential in combination with other treatment modalities. Current combinations often include chemotherapy, particularly with temozolomide (TMZ), however, emerging data suggests potential synergy with targeted therapies, radiotherapy, and immunotherapy as well. TTFields display minimal side effects, predominantly skin-related, posing no significant barrier to combined therapies. The effectiveness of TTFields in GBM treatment has been demonstrated through several post-registration studies, advocating for continued research to optimize overall survival (OS) and progression-free survival (PFS) in patients, as opposed to focusing solely on quality of life.

Brachytherapy in the Treatment of Non-Melanoma Skin Peri-Auricular Cancers-A Retrospective Analysis of a Single Institution Experience.

The location of skin neoplasms in the area of the ears qualifies patients to the so-called high-risk group. The location of neoplasms within the auricle and around the ear often causes many problems in surgical treatment. This is due to the presence of cartilage, the difficulty of performing procedures with obtaining a visually satisfactory cosmetic effect, especially in the presence of extensive lesions and can lead to positive surgical margins which leads to a high risk of recurrence. In such cases, the use of brachytherapy, both as an independent method and as a complementary method after surgery, may be an effective method of local control with an acceptable risk of radiation complications. However, there are no large retrospective studies on the use of brachytherapy in this anatomical region. The aim of the study was to analyse the effectiveness, toxicity profile, and cosmetic effect of two different brachytherapy techniques (contact and interstitial brachytherapy). Methods: This paper presents the results of a retrospective analysis of 33 patients treated with contact or interstitial high-dose-rate (HDR) brachytherapy for skin cancers of the outer ear, involving the auricle and the skin of the adjacent area. Brachytherapy was used both as a definitive treatment (15 patients­43%) and adjuvant treatment after surgery (18 patients­57%). The basic criterion for adjuvant treatment was a positive or narrow (<1 mm) resection margin. Fraction doses from 3 to 7 Gy per fraction were used at intervals from six hours (interstitial brachytherapy) to a maximum of seven days (contact brachytherapy). The treatment time ranged from 1 to 42 days, and the total dose range was 7 to 49 Gy. The follow-up was 29.75 months (range 2−64). Results: In the group of patients treated with adjuvant therapy, in the patients with post-radiation reaction, the mean time from surgery to the start of brachytherapy was 7.72 ± 3.05 weeks, the median was 8 (6−12) weeks, and in the group without post-radiation reaction, the mean time was 11.13 ± 4.41 weeks, the median time was 11 weeks (8−14). The risk of a post-radiation reaction increased significantly more often in patients with more advanced disease. In the case of contact brachytherapy, the post-radiation reaction occurred significantly more often (14/21 patients­43%) than in the case of interstitial brachytherapy (3/11 patients­9.4%). In patients with post-radiation reactions, a significantly larger volume of the skin receiving a dose of 200% was found, and the volume receiving a dose of 150% was close to statistical significance. The mean volume of the skin receiving a 200% dose in the group with post-radiation reactions was 28.05 ± 16.56 cm3, the median was 24.86 (0.5−52.3) cm3, and the mean volume in the group without post-radiation reaction was 17.98 ± 10.96 cm3, median 14.95 (3.9−44.96) cm3. The result was statistically significant (Z = 2.035, p = 0.041). Conclusion: Interstitial HDR (high-dose-rate) brachytherapy for non-melanoma skin cancers around the ear is highly effective, short, and has a relatively low burden on the patient. The toxicity of the treatment was low. In the case of contact brachytherapy, the toxicity profile is slightly higher but acceptable for patients. This method is preferred in patients in whom interstitial brachytherapy is impossible to perform due to anatomical and logistical reasons. The unquestionable advantage of contact brachytherapy is its ability to be performed on an outpatient basis without the need to stay in the hospital. No severe and late CTCAE ≥III and late RTOG ≥III toxicity was observed. In patients after surgery, in order to minimise the risk of radiation reaction, it is optimal to start treatment at least eight weeks after surgery. In the presence of extensive lesions, the use of interstitial brachytherapy seems to be more advantageous, especially when the expected volume of healthy skin in the dose range of 200% and 150% is above 15 cm3 and 50 cm3, respectively.

New Directions in the Therapy of Glioblastoma.

Glioblastoma is the most common histologic type of all gliomas and contributes to 57.3% of all cases. Despite the standard management based on surgical resection and radiotherapy, it is related to poor outcome, with a 5-year relative survival rate below 6.9%. In order to improve the overall outcome for patients, the new therapeutic strategies are needed. Herein, we describe the current state of knowledge on novel targeted therapies in glioblastoma. Based on recent studies, we compared treatment efficacy measured by overall survival and progression-free survival in patients treated with selected potential antitumor drugs. The results of the application of the analyzed inhibitors are highly variable despite the encouraging conclusions of previous preclinical studies. This paper focused on drugs that target major glioblastoma kinases. As far, the results of some BRAF inhibitors are favorable. Vemurafenib demonstrated a long-term efficacy in clinical trials while the combination of dabrafenib and trametinib improves PFS compared with both vemurafenib and dabrafenib alone. There is no evidence that any MEK inhibitor is effective in monotherapy. According to the current state of knowledge, BRAF and MEK inhibition are more advantageous than BRAF inhibitor monotherapy. Moreover, mTOR inhibitors (especially paxalisib) may be considered a particularly important group. Everolimus demonstrated a partial response in a significant proportion of patients when combined with bevacizumab, however its actual role in the treatment is unclear. Neither nintedanib nor pemigatinib were efficient in treatment of GBM. Among the anti-VEGF drugs, bevacizumab monotherapy was a well-tolerated option, significantly associated with anti-GBM activity in patients with recurrent GBM. The efficacy of aflibercept and pazopanib in monotherapy has not been demonstrated. Apatinib has been proven to be effective and tolerable by a single clinical trial, but more research is needed. Lenvatinib is under trial. Finally, promising results from a study with regorafenib may be confirmed by the ongoing randomized AGILE trial. The studies conducted so far have provided a relatively wide range of drugs, which are at least well tolerated and demonstrated some efficacy in the randomized clinical trials. The comprehensive understanding of the molecular biology of gliomas promises to further improve the treatment outcomes of patients.

Interstitial HDR Brachytherapy in the Treatment of Non-Melanocytic Skin Cancers around the Eye.

BACKGROUND: Eyelid tumors are rare skin cancers, the most common of which is basal cell carcinoma characterized primarily by local growth. In addition to surgery, radiotherapy is among the basic methods of treatment. External beam radiotherapy is associated with the risk of complications within ocular structures, especially the lens. In the case of interstitial brachytherapy, it is possible to administer a high dose to the clinical target volume (CTV), while reducing it in the most sensitive structures. METHODS: This paper presents the results of an analysis of 28 patients treated with interstitial high dose rate (HDR) brachytherapy for skin cancers of the upper and lower eyelid; medial and lateral canthus; and the cheek, nose and temples with the infiltration of ocular structures. The patients were treated according to two irradiation schedules: 49 Gy in 14 fractions of 3.5 Gy twice a day for 7 days of treatment, and 45 Gy in 5 Gy fractions twice a day for 5 days. The mean follow-up was 22 months (3-49 months). RESULTS: two patients (6%) had a relapse: a local recurrence within the irradiated area in one of them, and metastases to lymph nodes in the other. The most common early complication was conjunctivitis (74%), and the most common late complication was dry eye syndrome (59%). CONCLUSIONS: Interstitial HDR brachytherapy for skin cancers of the upper and lower eyelid; medial and lateral cants; and the cheek, nose and temples with infiltration of ocular structures is a highly effective, short and relatively low burden type of treatment.

The Role of Conventionally Fractionated Radiotherapy and Stereotactic Radiotherapy in the Treatment of Carcinoid Tumors and Large-Cell Neuroendocrine Cancer of the Lung.

The occurrence of neuroendocrine tumors among the diagnosed neoplasms is extremely rare and is associated with difficulties in undertaking effective therapy due to the histopathological differentiation of individual subtypes and the scarce clinical data and recommendations found in the literature. The choice of treatment largely depends not only on its type, but also on the location and production of excess hormones by the tumor itself. Common therapeutic approaches include surgical removal of the tumor, the use of chemotherapy, targeted drug therapy, peptide receptor radionuclide therapy, and the use of radiation therapy. This article reviews the current knowledge on the classification and application of radiotherapy in the treatment of lung NETs. Case reports were presented in which treatment with conventional radiotherapy, radical and palliative radiochemotherapy, as well as stereotactic fractionated radiotherapy in the treatment of typical (TC) and atypical (AT) lung carcinoids and large cell neuroendocrine carcinoma (LCNC) were used. We hope that the solutions presented in the literature will allow many radiation oncologists to make the best, often personalized decisions about the therapeutic qualifications of patients.

[Perineural cysts]. / Torbiele okolokorzeniowe.

Perineural cyst (Tarlov cyst) is a lesion in a form of fluid-filled sacks, usually located within the nerve root sheath at the posterior root of a spinal nerve, whose wall is formed by: endoneurium, peripheral nerve fibers and ganglion cells and areolar tissue. Depending on the studied population, the frequency of lesion occurence was estimated at 1.5- 13.2%, with its significant majority occuring in women. Cyst development may be the result of ischemia, hemorrhage, inflammation or trauma. Cysts are usually asymptomatic theefore they are likely to bo detected accidentally. However, in approximately 1/4 of the cases, the cyst puts so much pressure on the nerve and the neighbouring nerve roots that it becomes symptomatic (causes pain). The presence of clinical symptoms may be an indication for conservative treatment (i.e. analgesics, rehablitation, cyst puncture) or surgery (usually laminectomy).

Assessment of peripheral blood and bone marrow T, NK, NKT and dendritic cells in patients with multiple myeloma.

Symptoms of multiple myeloma (MM) include bone destruction with pathological fractures, kidney failure and frequent infections, which are the major causes of patient mortality. In our recent research, we demonstrated that the degree of dendritic cell (DC) subpopulation deficit could be related to MM progression, which in consequence may contribute to the MM-related impairment of the immune responses. In the present study, we determined by flow cytometry the frequencies of CD4+ and CD8+ T cells, NK, and NKT-like cells as well as their correlation with myeloid and lymphoid populations of DCs in patients with MM. The study involved 50 patients diagnosed with MM at the Department of Hematology in the Holycross Cancer Center in Kielce. The research samples were collected after the MM diagnosis and before the initiation of anticancer therapy. The obtained results revealed the relations between the percentages of DC subpopulations and lymphocyte subsets, especially the activated ones, in the peripheral blood (PB) and bone marrow (BM). The described role of DCs in the process of the immunological response, either adaptive or innate, leads us to conclude that the decrease of the number or percentage of these cells may have a negative impact on the process of activation of effector cells and, consequently, on the effectiveness of a response to foreign as well as neoplastic antigens in patients with MM.

[The prognostic value of selected immunological factors in ovarian cancer patients]. / Prognostyczna wartosc wybranych czynników immunologicznych u chorych na raka jajnika.

Ovarian cancer is the most aggressive gynecological cancer and is often diagnosed in advanced stage. Constantly we are looking for new prognostic factors which would enable early diagnosis, increase the effectiveness of therapeutic intervention. There is to little data about immunological predictors in ovarian cancer. The tumor's microenvironment is designated by regulatory T cells, cytotoxic T cells, dendritic cells (DCs), tumor - associated macrophages (TAMs), monocytes, plasma cells and cytokines, such as IL-6, IL-8, IL-10, IL-17 and TGF-beta. Some of them are responsible for the inhibition and others induce tumor growth. Ovarian cancer patients with high ratio of CD8 + TILs to Treg present longer overall survival time (OS). The presence of T helper cells in ascites is associated with longer OS. Furthermore, patients with a lower rate plasmocytoid DCs infiltrating tumor tissue demonstrate longer progression-free survival time (PFS). Women with increased M1/M2 ratio present higher five-year survival rate. The presence of immunologically competent cells and secreted cytokines give motivation to evaluate their prognostic value. Perhaps this strategy will contribute to longer progression-free survival time and overall survival time in those patients.