Comparison of 116 Radiosurgery Treatment Plans for Multi-Leaf and Cone Collimator on a Varian Edge Linac: Are Cones Superior in the Daily Routine?

Delivering focused radiation doses via linear accelerators is a crucial component of stereotactic radiosurgery (SRS) for brain metastases. The Varian Edge linear accelerator provides highly conformal radiation therapy through a high-definition multi-leaf collimator (HD120 MLC) and conical collimator (CC). HD120 MLC adapts to the shape of the target volume using movable tungsten leaves, while CC has a block of conical shape (cones). CC in SRS treatments of small brain metastases is preferred due to its mechanical stability and steeper dose fall-off, potentially sparing organs at risk (OARs) and the brain better than HD120 MLC. This study aims to determine if CC offers significant advantages over HD120 MLC for SRS treatments. For 116 metastatic lesions, CC and HD120 MLC treatment plans were created in Varian Eclipse TPS and compared based on various dose parameters, robustness tests, and QA measurements. The results indicate that CC provides no significant advantages over HD120 MLC, except for slight, clinically insignificant benefits in brain sparing and dose fall-off for the smallest lesions. HD120 MLC outperforms CC in almost every aspect, making it a better choice for irradiating brain metastases with 0.1 cm3 or higher volumes.

18F-FET and 18F-choline PET-CT in patients with MRI-suspected low-grade gliomas: a pilot study.

AIM: To investigate the diagnostic accuracy of O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) and fluoromethyl-(18F)-dimethyl-2-hydroxyethyl-ammonium chloride (18F-FCH) computed tomography (CT) in patients with primary low-grade gliomas (LGG). METHODS: The study enrolled patients with magnetic resonance imaging (MRI)-suspected LGG. Patients underwent both 18F-FET and 18F-FCH positron emission tomography (PET)-CT. Brain PET-CT was performed according to standard protocol - 20 minutes after intravenous injection of 185 MBq of 18F-FET and 185 MBq of 18F-FCH PET. Surgery and pathohistological diagnosis were performed in the next two weeks. RESULTS: We observed significantly better concordance between tumor histology and 18F-FET PET (weighted Kappa 0.74) compared with both 18F-FCH (weighted Kappa 0.15) and MRI (weighted Kappa 0.00). Tumor histology was significantly associated with 18F-FET (odds ratio 12.87; 95% confidence interval [CI], 0.49-333.70; P=0.013, logistic regression analysis). Receiver operating characteristic curve analysis comparing 18F-FCH (area under the curve [AUC] 0.625, 95% CI 0.298-0.884) and 18F-FET (AUC 0.833, 95% CI 0.499-0.982) showed better diagnostic properties of 18F-FET (AUC difference 0.208, 95% CI -0.145 to 0.562, P=0.248). CONCLUSION: Performing PET-CT in patients with newly diagnosed LGG should be preceded by a selection of an appropriate radiopharmaceutical. 18F-FET seems to be more accurate than 18F-FCH in the LGG diagnosis.

Primary leptomeningeal melanomatosis successfully treated with PD-1 inhibitor pembrolizumab: A case report.

RATIONALE: Primary leptomeningeal melanoma is an extremely rare disease of the central nervous system. There are no standard treatment protocols with a poor prognosis in very few reported cases. Immunotherapy in primary brain melanoma has not been successfully applied so far. PATIENT CONCERNS: We describe a female patient 72-year-old diagnosed in the Neurosurgery Department which presented with generalized seizures. DIAGNOSES: Histological examination confirmed atypical melanocytes immunohistochemically positive for melan A, HMB45 and S-100 protein in the meninges, BRAF V600E negative. Dermatological, ophthalmological examinations, and 18-FDG PET/CT were negative. INTERVENTIONS: The patient was successfully treated with pembrolizumab 2 mg/kg every 3 weeks for 2 years. OUTCOMES: The disease was stable for 2 years and the patient had no significant toxicity. LESSONS: Our report describes durable intracranial tumor response suggesting the efficacy of PD-1 inhibitor pembrolizumab for central nervous system primary leptomeningeal melanoma.

Malignant brain neoplasms incidence and mortality trends in Croatia from 2001 to 2014.

AIM: To analyze the sex-specific incidence and mortality trends of brain malignancies in Croatia from 2001 to 2014. METHODS: Incidence and mortality rates per 100000 population were calculated using data obtained from the Croatian National Cancer Registry and the Croatian Bureau of Statistics. Rates were age-standardized to the European Standard Population, and trends were assessed using joinpoint regression. RESULTS: In the observed period there were 6634 new brain malignancy cases (52% men) and 5379 deaths due to this diagnosis (52% men). Age-standardized incidence rates ranged from 9.2-11.5 per 100000 in men and from 7-8.8 per 100000 in women. Mortality rates ranged from 7.5-8.7 per 100 000 in men and from 5-6.5 in women. Incidence trends in men, mortality in men, and mortality in women were not statistically significant, while a significant trend was observed in incidence in women (annual percent change -1.5; 95% confidence interval -2.3 to -0.6). No joinpoints were observed in any of the joinpoint analyses by sex for incidence and mortality. Age-specific incidence and mortality rates in both sexes indicate a trend shift toward older age. The proportion of morphologically verified cases ranged from 40.2%-62.4% in men and from 38.6%-56.3% in women; the proportion of death-certificate-only cases ranged from 3.3%-9.4% in men and from 3.3%-17.5% in women. CONCLUSION: Incidence and mortality of brain malignancies in Croatia are among the highest in Europe, while reporting on brain malignancies is still poor. There is a need for improved care of patients with brain malignancies and detailed and accurate data reporting.

A Rapid Biochemical and Radiological Response to the Concomitant Therapy with Temozolomide and Radiotherapy in an Aggressive ACTH Pituitary Adenoma.

Background and Importance. In the last eight years temozolomide (TMZ) has been used as the last-line treatment modality for aggressive pituitary tumors to be applied after the failure of surgery, medical therapy, and radiotherapy. The objective was to achieve a rapid control of tumor growth and hormone normalization with concurrent chemoradiotherapy in a patient with very aggressive ACTH pituitary adenoma. Clinical Presentation. We describe a patient with an aggressive ACTH-producing adenoma treated with concurrent temozolomide and radiotherapy. The patient suffered from an aggressive ACTH adenoma resistant to surgical and medical treatment. After two months of concurrent temozolomide and radiotherapy, cortisol normalization and significant tumor shrinkage were observed. After 22 months of follow-up, there is still no evidence of tumor recurrence. Conclusion. Concurrent treatment with temozolomide and irradiation appears to be highly effective in the achievement of the tumor volume control as well as in the control of ACTH secretion in aggressive ACTH adenoma.

Sudden bilateral hearing loss in gastric cancer as the only symptom of disease.

This paper reports a case of sudden bilateral deafness as the first symptom of gastric cancer, an extremely rare and atypical clinical situation. Because common signs of stomach cancer were absent, the patient was first evaluated in the Department of Otolaryngology, University Hospital Center, Zagreb. Only after expanded diagnostic evaluation and rapid progression of the disease in such a case is a malignant tumor suspected. Treatment is mostly ineffective. The unusual presentation of the disease and the rapid course may indicate a hereditary predisposition. Inactivation of tumor suppressor gene DFNA5 was found in 50% of gastric cancers, but of a non-metastasized phenotype. Inactivated DFNA5, otherwise described in hereditary bilateral deafness, perhaps favors the development of deafness in patients with gastric cancer. Our patient had a positive multiple viral antibody titer in serum, inactivated DFNA5 in both gastric cancer tissues and cerebellar metastases, and a metastatic form of the disease. If sudden deafness occurs in elderly patients, the possibility of malignant tumor should be taken into consideration. The link between gastric cancer and the DFNA5 gene is unclear and requires further research.

Tamoxifen in trimodal therapy with cytotoxic drugs and hyperthermia in vivo significantly enhance therapeutic efficacy against B16-F10 melanoma.

AIMS AND BACKGROUND: The aim of the study was to investigate whether use of the antiestrogen tamoxifen and heat treatment in combined therapy with the well-known anticancer drugs cisplatin, dacarbazine and cyclophosphamide enhances their therapeutic efficacy on mouse B16-F10 melanoma in vivo. The results of systemic melanoma therapy have been mostly disappointing. Therefore, there is still a great need for strategies that can improve existing chemotherapy options. METHODS AND STUDY DESIGN: The tumor model for the investigation of antitumor activity was a mouse B16-F10 melanoma transplanted into the footpad of C57BL/6 Zgr/Hr mice. Drugs were given intraperitoneally 15 min before the application of local hyperthermia, and tumor growth and mouse survival were followed. RESULTS: Hyperthermia alone determined a significant delay of tumor growth, but mouse survival was not affected. In bimodal combinations with hyperthermia, all the tested antitumor drugs significantly increased both tumor growth delay and mouse survival. Tamoxifen alone did not show any inhibitory effect on B16-F10 melanoma in vivo. However, in the trimodal therapy with a particular drug and hyperthermia, it potentiated the inhibitory effects of the respective bimodal treatments, especially that of cyclophosphamide and hyperthermia. CONCLUSIONS: Our results obtained on the mouse B16-F10 melanoma in vivo confirmed the enhanced therapeutic efficacy of the trimodal therapy tamoxifen, hyperthermia and anticancer drug combinations in melanoma treatment. Further studies should optimize the heat-drug time scheduling and drug doses that will result in the best possible therapeutic achievement for these trimodal therapy options.

Erdheim-Chester disease and concomitant tuberculosis successfully treated with chemotherapy and long-term steroids.

Erdheim-Chester disease (ECD) is a rare histiocytosis usually affecting the skeletal system, but visceral organs and central nervous system involvement are common as well. Probability exists that immunomodulatory therapies and disorders can play a role in clinical course of the disease. Because of rarity of the disorder, it is hard to classify it and standardize the treatment options, but, according to published material and our experience, cytotoxic chemotherapy and long-term steroids have therapeutic benefit. Although this approach can probably be accepted as standard of care management, novel therapeutic modalities should be explored, and pathogenesis and disorder classification should be cleared out as well. The case of ECD affecting skeletal system and lungs and concomitant laryngeal tuberculosis successfully treated with chemotherapy and long-term steroid therapy is presented.