Electrochemotherapy is increasingly entering into national and international guidelines, requiring formal evaluation of treatment costs and cost-effectiveness to ensure that its uptake provides value ...to budget-constrained health care systems. This study analyzed the early cost-effectiveness of electrochemotherapy in patients with Stage IIIc/IV skin melanoma in clinical practice in Slovenia. The costs of electrochemotherapy were compared to those of the standard of care, consisting of palliative treatment and therapy for symptoms.
wThe study enrolled 23 patients treated with electrochemotherapy at the Institute of Oncology (Ljubljana, Slovenia). The mean cost of electrochemotherapy was estimated using patient-specific cost data on electrochemotherapy procedures and subsequent follow-up. Quality-adjusted life-years (QALYs) were estimated by collecting EQ-5D-3L questionnaires at baseline, after complete or partial response following the treatment, and after a relapse of skin lesions. A discrete-time Markov model was built to estimate the lifetime costs and consequences of using electrochemotherapy compared to standard of care, from the perspective of the Slovenian health care system. The analysis was conducted separately in the whole patient sample and in the subset of patients with bleeding lesions. Deterministic and probabilistic sensitivity analyses were conducted to test model assumptions and to characterize the uncertainty around model parameters.
In the whole patient population, electrochemotherapy for skin melanoma Stage IIIc/IV was expected to increase QALYs by 0.29 (95% credible interval CrI, 0.10–0.50), at the higher cost of 6568 EUR (95% CrI, 4593–8928) in comparison to the standard of care. At the cost-effectiveness threshold of 20,000 EUR/QALY, the estimated probabilities of electrochemotherapy being cost-effective compared to standard of care were 0.30 and 0.91 in the whole patient sample and in patients with bleeding lesions, respectively. In the whole sample population, a 50% reduction in the price of the electrodes was expected to increase the probability of electrochemotherapy being cost-effective from 0.30 to ~0.64.
The findings from this cost-effectiveness analysis of data from clinical practice were based on a small sample size (ie, 23 patents), which made the subgroup of patients with bleeding lesions very small. Therefore, the findings in this patient population should be carefully interpreted.
•With the development of the electroporation and new delivery systems, questions regarding cost-effectiveness needs to be addressed.•The average cost of single electrochemotherapy procedure was estimated to €2757.00 with the standard deviation €707.30.•Electrochemotherapy is slightly less cost-effective compared to standard of care, but the uncertainty over this estimate is large.•The probability of electrochemotherapy being cost-effective is estimated to be 30% for the whole sample, and 91% in patients with bleeding lesions.•The cost of the electrodes has a considerable impact when considering the whole patient sample.
Most data related to cutaneous melanoma survivors' health behaviour comes from epidemiological studies and is predominantly concerned with safe-sun behaviour and self-examination. Data regarding ...other changes of health behaviour are scarce and so are qualitative studies in this realm. The aim of our research is to acquire insight into the experiences of patients with cutaneous melanoma in Slovenia. How did they react to the diagnosis, which changes did they introduce in their health behaviour and how do they assess the role of family doctors?
Using the qualitative approach of collective case reports, a demographically diverse group of patients with different forms and stages of cutaneous melanoma was selected. Semi-structured interviews conducted by a psychologist were recorded and transcribed verbatim. For data processing, the approach of Qualitative Content Analysis was applied.
We integrated interviewees' experiences after the diagnosis of cutaneous melanoma in several subcategories: either they did not introduce any changes or they mentioned changing their habits when exposed to the sun and performing skin self-examination; they also emphasized their ways of dealing with stress and raising awareness about melanoma among family members and friends. The role of family doctors in the prevention and care appears unclear; even contradictory.
We obtained insight into the experiences of Slovenian patients with cutaneous melanoma. The interviewees prioritised safe behaviour in the sun, strengthening of psychological stability and raising awareness about melanoma. Findings will be used in the creation of a structured questionnaire for national epidemiological survey.
BAP1 cancer syndrome is a rare and highly penetrant hereditary cancer predisposition. Uveal melanoma, mesothelioma, renal cell carcinoma (RCC) and cutaneous melanoma are considered BAP1 cancer ...syndrome core cancers, whereas association with breast cancer has previously been suggested but not confirmed so far. In view of BAP1 immunomodulatory functions,
BAP1
alterations could prove useful as possible biomarkers of response to immunotherapy in patients with BAP1-associated cancers. We present a case of a patient with BAP1 cancer syndrome who developed a metastatic breast cancer with loss of BAP1 demonstrated on immunohistochemistry. She carried a germline
BAP1
likely pathogenic variant (c.898_899delAG p.(Arg300Glyfs*6)). In addition, tumor tissue sequencing identified a concurrent somatic variant in
BAP1
(partial deletion of exon 12) and a low tumor mutational burden. As her triple negative tumor was shown to be PD-L1 positive, the patient was treated with combination of atezolizumab and nab-paclitaxel. She had a complete and sustained response to immunotherapy even after discontinuation of nab-paclitaxel. This case strengthens the evidence for including breast cancer in the BAP1 cancer syndrome tumor spectrum with implications for future cancer prevention programs. It also indicates immune checkpoint inhibitors might prove to be an effective treatment for BAP1-deficient breast cancer.
The life expectancy in the Western world is increasing for a long time, which is the courtesy of a higher life standard, a more thorough hygiene, and, of course, the progress of modern medicine. ...Nevertheless, one of the illnesses that still proves to be a great challenge regardless of the recent advancements in medicine is cancer. Skin cancer is, according to the World Health Organization, the most common malignancy for the white population. The beginning of the paper offers a brief overview of the latest available information concerning epidemiology, aetiology, diagnostics, and treatment options for skin cancer, whereas the rest of the article deals with modern approaches to skin cancer treatment, highlighting recent development of nanotechnology based treatment approaches. Among these, we focus especially on the newest nanotechnological approaches combined with chemotherapy, a field which specialises in target specificity, drug release control, and real time monitoring with the goal being to diminish unwanted side effects and their severity, achieving a cheaper treatment and a generally more efficient chemotherapy. The field of nanotechnology is a rapidly developing one, judging by already approved clinical studies or by new theranostic agents that combine both the therapeutic and diagnostic modalities.
To determine the frequency and type of RET mutation in Slovenian medullary thyroid cancer (MTC) patients and estimate the crude annual incidence of MTC in Slovenia.
This referral-center retrospective ...analysis involved 186 MTC patients diagnosed between 1995 and 2015 and their relatives who underwent genetic counseling and testing. The crude incidence rate of MTC was estimated with the joinpoint regression analysis. Genomic DNA was isolated, and exons 10, 11, 13, 14, 15, and 16 of the RET proto-oncogene were amplified with polymerase chain reaction. Point mutations of the RET gene were detected by single-strand conformation analysis and DNA sequencing. Detected mutations were confirmed by restriction enzymes.
The average crude annual incidence rate of MTC in Slovenia was 0.34/100,000. A germline mutation in the RET proto-oncogene was identified in 25.9% of MTC patients. The most frequently altered codons were codons 634 and 618, followed by codon 790, codon 804, and codon 918.
Annual incidence increase and nation-specific frequency of RET mutations justify the future use of genetic counseling and testing of MTC patients in Slovenia.
Axillary ultrasound (US) with fine needle aspiration biopsy (FNAB) of suspicious lymph nodes helps identify patients with axillary metastases preoperatively avoiding a 2-step axillary procedure. ...However, it does not accurately differentiate between low and high axillary tumour burden. Our aim was to determine the rationale of preoperative axillary US in screen-detected breast cancer.
We retrospectively analysed patients, aged between 50 and 69 years, which had an invasive breast cancer diagnosed in the Slovenian National Breast Cancer Screening program between January 2012 and June 2017. Proportion of patients that proceeded directly to ALND and the proportion of patients with unnecessary ALND as a result of positive US-FNAB were calculated.
Altogether 892 patients were eligible for analysis. Preoperative US of the axilla was performed in 856/892 (96%) patients, while 36/892 patients (4%) did not undergo US of the axilla. We have found out that upfront ALND due to positive US-FNAB was performed in 91/856 (10.6%) patients. 116/856 patients (13.6%) had tumours in inner quadrants and maximal mammographic tumour size ≤ 2 cm. Among them only 1/116 (0.9%) proceeded directly to ALND due to positive US-FNAB.The final pathology of those who underwent upfront ALND due to positive US-FNAB showed low axillary tumour burden not meeting the indications for ALND in 13/91 (14.3%) patients.Among patients without preoperative axillary US, only 1/36 (2.8%) met the indications for ALND.
Our results showed that performing US of the axilla is not justified in screen detected breast cancer patients.
Cutaneous melanoma is a highly aggressive form of skin cancer. The development of immune checkpoint inhibitors (ICIs) has revolutionized the management of advanced melanoma, led to durable responses, ...and improved overall survival. However, the success of ICIs in melanoma treatment is influenced by the tumor microenvironment (TME) which plays a critical role in regulating the immune response to the tumor. Understanding the mechanisms underlying this interaction is crucial to optimizing the efficiency of ICIs. Electrochemotherapy (ECT) has been shown to enhance the efficacy of ICIs in melanoma treatment by inducing tumor cell death and facilitating the release of tumor antigens which can subsequently be recognized and targeted by the immune system. Moreover, ECT has been reported to modulate the TME, leading to increased infiltration of immune cells and a more favorable immunological profile. In this review, we summarize the available knowledge of changes in TME after ECT of melanoma cutaneous metastasis and highlight the differences in tumor-infiltrating immune cells between immunocompetent and immunosuppressed organisms. In addition, we showed that ECT can be an effective and safe procedure for organ transplant recipients. Furthermore, repeated ECT may enhance immune activation and probably induce a bystander effect by trained immunity.
Background: Medullary thyroid cancer (MTC) is a rare endocrine tumour that is sporadic in 75% of cases and occurs as a part of inherited cancer syndromes in approximately 25% of cases. The aim of ...this study was to determine the frequency and type of RET pathogenic variants (PVs) in the Slovenian MTC patient population diagnosed between 1995 and 2021 and to elucidate the full range of associated endocrinopathies. Methods: A retrospective analysis of medical records of 266 MTC patients and their relatives seen in a tertiary centre between 1995 and 2021 was performed. Sequence analysis of exons 10, 11, 13, 14, 15, and 16 of the RET gene was analysed in most patients using Sanger sequencing. From 2017, the entire sequence of RET gene was analysed in most patients using targeted next-generation sequencing. Results: Germline PVs in the RET proto-oncogene were identified in 21.6% probands from 21 different MTC families. Of their tested relatives, 65% (67/103) were RET-positive and 35% (36/103) were RET-negative. PVs were detected in codon 618 and codon 634 in 28.6%, and in codon 790 in 23.8%. The RET-positive group consisted of 52 MTC patients, 13 patients with C cell hyperplasia and 2 individuals with neither. Associated endocrinopathies were diagnosed in 8/21 families: primary hyperparathyroidism (PHPT) in six families and pheochromocytoma (PHEO) in five families. In 62% of RET-positive families (13/21), no associated endocrinopathies were diagnosed. PHEO was most commonly associated with C634R (6/13) and PHPT with C634R (4/7). Hirschsprung’s disease appeared in one patient with RET PV in codon 618. Based on data from the Cancer Registry of Republic of Slovenia, only individual cases of common cancers with well understood environmental risk factors were discovered; lung cancer in 2/21 of families, papillary thyroid cancer in 3/21 of families, cutaneous melanoma in 2/21 of families, cervical cancer in 1/21 families, and lymphoma in 1/21 families. Conclusions: Analysis of prospectively collected MTC cases during a 27-year period revealed that 21.6% of Slovenian patients are RET PV carriers. Sixty-two percent of families had none of the associated endocrinopathies, confirming the thesis that FMTC is the most common presentation. This could suggest using risk-stratified management approaches when screening for PHEO and PHPT in RET PV carriers. However, more studies are needed to evaluate potential genetic risk modifiers as well as safety, improved quality of life, and medical cost reduction in the case of a patient-oriented approach.
Aim of this study was to investigate changes in health behavior of melanoma survivors with emphasis on safe sun behavior (SSB) and skin self-examination (SSE). We also identified factors with ...significant impact on SSE improvement. We performed a cross-sectional (epidemiological) survey based on a structured questionnaire. 150 patients from three medical institutions were invited and 144 patients responded. Statistical analysis was performed with SPSS version 23.0, with the level of significance set to 0.05. After being diagnosed with cutaneous melanoma, patients significantly improved preventive health behavior: 68.1% showed improvement in SSE, and 91.5% of patients improved SSB. There was statistically significant (P<0.001) improvement in the frequency of skin examination, examination of poorly visible areas (between the toes, genitals), and obtaining help in examination. Use of melanoma images remained scarce. Results for SSB were even better, and statistically significant improvement was recorded in all areas: using higher UV protection filters, wearing sunglasses, headgear, long sleeves, and trousers, and especially in staying in deep shade during hours of heavy UV radiation. The only factor with a positive influence on expected improvement in SSE was female gender. On the other hand, there were two factors that had a negative impact on SSE: patients with melanoma stage 1 and patients who had already self-examined themselves before their melanoma diagnosis. Preventive health behavior improved significantly after diagnosis of cutaneous melanoma. Patients markedly improved SSB and substantially enhanced SSE. We believe that it is reasonable to improve SSE further, encouraging patients by increasing their feeling of self-efficacy.
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