QUAD SHOT - an effective hypofractionated palliative radiotherapy in patients with non-melanoma skin cancer. A single-institution experience.

Introduction: The primary approach for managing skin cancer involves surgery, although radical radiotherapy (RT) may be considered as an alternative option in cases where patients decline the treatment themselves or are not eligible for surgical intervention. Herein we assess single-institution material in terms of the use of hypofractionated QUAD SHOT RT in patients disqualified from surgery. Material and methods: Between December 2019 and December 2022, nine patients with locally advanced non-melanoma skin cancer were disqualified from surgery and as a result were treated at the Radom Oncology Centre, Poland. Patients were treated with the Radiation Therapy Oncology Group 8502 QUAD SHOT regimen (14.8 Gy/4 fractions, twice-daily treatment with a 6 h interval, on 2 consecutive days). Courses were repeated every 4 weeks 3 times using volumetric modulated arc therapy (VMAT). Results: Grade 2 toxicities were observed in 4 of 9 (44.4%) patients, no grade ≥ 3 acute toxicity was observed. The median age was 79.1 (60-98) years. Irradiated areas were as follows: nose skin (2), cheek (2), eyebrow with eyelid (1), forehead (1), temple (1), sternum (1), and scapula (1). Performance status was as follows: WHO II - 5 patients (55.6%), WHO I - 3 patients, WHO III - one patient. One patient underwent 3 RT courses in 2 areas for a total of 6 treatment courses, 6 patients received 3 courses of treatment, and 2 patients received 2 courses. Additionally, as of 14 March 2023, four patients died of non-malignant causes. Conclusions: QUAD SHOT schedule with VMAT RT may be an effective palliative treatment method with a good response rate, which positively affects patients' quality of life in locally advanced non-melanoma skin cancer patients disqualified from surgery.

Screening for EGFR amplifications with a novel method and their significance for the outcome of glioblastoma patients.

Glioblastoma is a highly aggressive tumour of the central nervous system, characterised by poor prognosis irrespective of the applied treatment. The aim of our study was to analyse whether the molecular markers of glioblastoma (i.e. TP53 and IDH1 mutations, CDKN2A deletion, EGFR amplification, chromosome 7 polysomy and EGFRvIII expression) could be associated with distinct prognosis and/or response to the therapy. Moreover, we describe a method which allows for a reliable, as well as time- and cost-effective, screening for EGFR amplification and chromosome 7 polysomy with quantitative Real-Time PCR at DNA level. In the clinical data, only the patient's age had prognostic significance (continuous: HR = 1.04; p<0.01). At the molecular level, EGFRvIII expression was associated with a better prognosis (HR = 0.37; p = 0.04). Intriguingly, EGFR amplification was associated with a worse outcome in younger patients (HR = 3.75; p<0.01) and in patients treated with radiotherapy (HR = 2.71; p = 0.03). We did not observe any difference between the patients with the amplification treated with radiotherapy and the patients without such a treatment. Next, EGFR amplification was related to a better prognosis in combination with the homozygous CDKN2A deletion (HR = 0.12; p = 0.01), but to a poorer prognosis in combination with chromosome 7 polysomy (HR = 14.88; p = 0.01). Importantly, the results emphasise the necessity to distinguish both mechanisms of the increased EGFR gene copy number (amplification and polysomy). To conclude, although the data presented here require validation in different groups of patients, they strongly advocate the consideration of the patient's tumour molecular characteristics in the selection of the therapy.

Response to postoperative radiotherapy as a prognostic factor for patients with low-grade gliomas.

Due to the favorable natural history in patients with low-grade gliomas (LGGs), there is no consensus on the treatment strategy following maximal safe surgical resection. A number of studies have been conducted to identify prognostic factors in patients treated for LGG. The present study evaluated the treatment outcomes as well as prognostic factors and their impact on overall survival (OS) and disease-free survival (DFS). We retrospectively reviewed 30 consecutive patients treated for LGG at the Department of Radiotherapy from February 2008 to July 2011. The patients underwent surgical intervention and postoperative radiotherapy. The response to radiotherapy was evaluated from six to eight weeks after the end of treatment using MRI analysis. Kaplan-Maier analysis was used for OS and DFS estimation. The endpoint was mortality as a result of any cause. Within a median follow-up of 21.8 months, 9 patients (30%) with disease progression were reported. The two- and five-year DFS and OS was 85.2 and 68.3% for DFS, and 84.3 and 63.4% for OS, respectively. The response to radiotherapy, evaluated in an MRI study, was found to be highly correlated with OS (p<0.0001). We also observed a significantly higher OS in patients with disease progression treated with salvage chemotherapy after the end of radiotherapy (p=0.08). Improved outcome among patients with LGG may be predicted by response to radiotherapy evaluated by MRI following termination of treatment.

Solitary brain metastasis of an occult and stable small-cell lung cancer in a schizophrenic patient: a 3-year control.

Small-cell lung cancer is a highly aggressive carcinoma, with poorer prognosis in patients with brain metastases. We present the case of a 49-year-old woman diagnosed with a cerebellar tumour which, following surgery, was revealed to be a metastatic small-cell lung carcinoma. Subsequent CT and PET scanning showed a small, isolated 8 mm nodule in the upper lobe of the right lung. The patient was suffering from schizophrenia and has been treated with clozapine for 17 years. Because of the unusual presentation, there was no therapy given for the primary tumour at the time, and systemic therapy or surgery was discussed. However, 18 months later, the nodule was slightly larger (14 mm), and surgery was performed. On pathology examination, the tumour was presented as a typical small-cell carcinoma. Standard chest irradiation with systemic chemotherapy was given. At the time of writing, 39 months after diagnosis of metastatic small-cell carcinoma, the patient is disease free. However, this case is unusual in that a long-term observation of a small stable primary tumour in the lung took place without any therapy being given. This case strongly supports the thesis that small-cell lung cancer may comprise a heterogeneous group of tumours with different biological properties. The proapoptotic effect of clozapine may be also taken into account.

High incidence of MGMT promoter methylation in primary glioblastomas without correlation with TP53 gene mutations.

O(6)-methylguanine DNA methyltransferase (MGMT) reduces cytotoxicity of therapeutic or environmental alkylating agents. MGMT promoter methylation has been associated with TP53 G: C to A:T transition mutations in various types of cancers, and with poor prognosis in patients who did not receive chemotherapy. Mutations of TP53 are more frequent in secondary than in primary glioblastoma, thus the expected MGMT promoter methylation was low in primary glioblastoma. Glioblastoma patients with MGMT promoter methylation showed better response to chemotherapy based on alkylating agents and longer survival than patients without MGMT methylation. We examined 32 primary glioblastomas, treated with radiotherapy and surgery, for TP53 mutation by direct sequencing and MGMT promoter methylation by methylation-specific PCR. MGMT promoter methylation and TP53 mutations were detected in 72% and 31% of primary glioblastoma, respectively. Although not statistically significant, the frequency of TP53 G:C to A:T mutations were higher in cases with (26%) than without (11%) MGMT promoter methylation (p=0.376). MGMT promoter methylation had no impact on patient survival. Our data indicate that MGMT promoter methylation occurs frequently in primary glioblastoma, but does not lead to G:C to A:T TP53 mutations, has no independent prognostic value and is not a predictive marker unless glioblastoma patients are treated with chemotherapy.