Trends in specialized palliative care referrals at an oncology center from 2007 to 2019.

BACKGROUND: Early referral to palliative care, at least 3 months before death, should be a standard of care in oncological practice. Real life data in this setting are invaluable since they provide a picture of everyday practice and serve as the basis for future improvements. METHODS: We conducted a retrospective cohort assessment of all patients referred to our specialized palliative care (SPC) services at the Institute of Oncology, Ljubljana, Slovenia. Our analysis includes patient referrals between 2007 and 2019. RESULTS: During the above-specified time period of 13 years, 3234 patients were referred for SPC services at our institution. The median age at SPC referral was 67 years. The majority of patients (63%) were assessed only once, while 31% of patients were seen on more than one occasion. Median time from SPC referral to death was 25 days for the whole group. 1693 patients (52.7%) were referred to SPC in the last 30 days before death, 785 (25.8%) patients between 31 and 90 days and 652 (21.4%) patients more than 3 months before death. Neither age nor sex correlated with the duration of referral time. However, there was a strong correlation between the year of referral to palliative care and the duration of palliative care service (ρ = 0.19, p < 0.001). The median referral to death interval for lymphoma patients and breast cancer patients were 15 and 18 days, respectively, and the median referral to death interval for colorectal cancer and lung tumor patients were 34 and 26 days before death, respectively. CONCLUSION: Throughout the existence of our SPC services we have observed a positive trend in the number of referrals, a lengthening of time between referral and death, as well as an increase in the proportion of patients with an early referral to SPC (more than 3 months before death). Neither age nor sex correlated with the length of referral time.

Prevalence of BRAF, NRAS and c-KIT mutations in Slovenian patients with advanced melanoma.

Background BRAF, NRAS and c-KIT mutations are characteristics of tumour tissues that influence on treatment decisions in metastatic melanoma patients. Mutation frequency and their correlation with histological characteristics in Slovenian population have not been investigated yet. Patients and methods In our retrospective analysis we analysed mutational status of BRAF, NRAS and c-KIT in 230 pathological samples of patients who were intended to be treated with systemic therapy due to metastatic disease at the Institute of Oncology Ljubljana between 2013 and 2016. We collected also histological characteristics of primary tumours and clinical data of patients and correlated them with mutational status of tumour samples. Results The study population consisted of 230 patients with a mean age 59 years (range 25-85). 141 (61.3%) were males and 89 (38.7%) females. BRAF mutations were identified in 129 (56.1%), NRAS in 31 (13.5%) and c-KIT in 3 (1.3%) tissue samples. Among the 129 patients with BRAF mutations, 114 (88.4%) patients had V600E mutation and 15 (11.6%) had V600K mutation. Patients with BRAF mutations tended to be younger at diagnosis (52 vs. 59 years, p < 0.05), patients with NRAS mutations older (61 vs. 55 years, p < 0.05). Number of c-KIT mutations were too low for any statistical correlation, but there was one out of 3 melanoma located in mucus membranes. Conclusions The analysis detected high rate of BRAF mutations, low NRAS mutations and low c-KIT mutations compared to previously published studies in Europe and North America. One of the main reasons for this observation is specific characteristics of study population.

Bevacizumab plus chemotherapy in elderly patients with previously untreated metastatic colorectal cancer: single center experience.

BACKGROUND: Metastatic colorectal cancer (mCRC) is mainly a disease of elderly, however, geriatric population is underrepresented in clinical trials. Patient registries represent a tool to assess and follow treatment outcomes in this patient population. The aim of the study was with the help of the patients' register to determine the safety and efficacy of bevacizumab plus chemotherapy in elderly patients who had previously untreated metastatic colorectal cancer. PATIENTS AND METHODS: The registry of patients with mCRC was designed to prospectively evaluate the safety and efficacy of bevacizumab-containing chemotherapy as well as selection of patients in routine clinical practice. Patient baseline clinical characteristics, pre-specified bevacizumab-related adverse events, and efficacy data were collected, evaluated and compared according to the age categories. RESULTS: Between January 2008 and December 2010, 210 patients with mCRC (median age 63, male 61.4%) started bevacizumab-containing therapy in the 1(st) line setting. Majority of the 210 patients received irinotecan-based chemotherapy (68%) as 1(st) line treatment and 105 patients (50%) received bevacizumab maintenance therapy. Elderly (≥ 70 years) patients presented 22.9% of all patients and they had worse performance status (PS 1/2, 62.4%) than patients in < 70 years group (PS 1/2, 35.8%). Difference in disease control rate was mainly due to inability to assess response in elderly group (64.6% in elderly and 77.8% in < 70 years group, p = 0.066). The median progression free survival was 10.2 (95% CI, 6.7-16.2) and 11.3 (95% CI, 10.2-12.6) months in elderly and < 70 years group, respectively (p = 0.58). The median overall survival was 18.5 (95% CI, 12.4-28.9) and 27.4 (95% CI, 22.7-31.9) months for elderly and < 70 years group, respectively (p = 0.03). Three-year survival rate was 26% and 37.6% in elderly vs. < 70 years group (p = 0.03). Overall rates of bevacizumab-related adverse events were similar in both groups: proteinuria 21/22 %, hypertension 25/19 %, haemorrhage 2/4 % and thromboembolic events 10/6 %, for elderly and < 70 years group, respectively. CONCLUSIONS: In routine clinical practice, the combination of bevacizumab and chemotherapy is effective and well-tolerated regimen in elderly patients with metastatic colorectal cancer.

Bevacizumab and irinotecan in recurrent malignant glioma, a single institution experience.

BACKGROUND: Treatment options of recurrent malignant gliomas are very limited and with a poor survival benefit. The results from phase II trials suggest that the combination of bevacizumab and irinotecan is beneficial. PATIENTS AND METHODS: The medical documentation of 19 adult patients with recurrent malignant gliomas was retrospectively reviewed. All patients received bevacizumab (10 mg/kg) and irinotecan (340 mg/m(2) or 125 mg/m(2)) every two weeks. Patient clinical characteristics, drug toxicities, response rate, progression free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Between August 2008 and November 2011, 19 patients with recurrent malignant gliomas (median age 44.7, male 73.7%, WHO performance status 0-2) were treated with bevacizumab/irinotecan regimen. Thirteen patients had glioblastoma, 5 anaplastic astrocytoma and 1 anaplastic oligoastrocytoma. With exception of one patient, all patients had initially a standard therapy with primary resection followed by postoperative chemoradiotherapy. Radiological response was confirmed after 3 months in 9 patients (1 complete response, 8 partial responses), seven patients had stable disease and three patients have progressed. The median PFS was 6.8 months (95% confidence interval [CI]: 5.3-8.3) with six-month PFS rate 52.6%. The median OS was 7.7 months (95% CI: 6.6-8.7), while six-month and twelve-month survival rates were 68.4% and 31.6%, respectively. There were 16 cases of hematopoietic toxicity grade (G) 1-2. Non-hematopoietic toxicity was present in 14 cases, all G1-2, except for one patient with proteinuria G3. No grade 4 toxicities, no thromboembolic event and no intracranial hemorrhage were observed. CONCLUSIONS: In recurrent malignant gliomas combination of bevacizumab and irinotecan might be an active regimen with acceptable toxicity.