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52. Immune RECIST criteria and symptomatic pseudoprogression in non-small cell lung cancer patients treated with immunotherapyMartina Vrankar, Mojca Unk, 2018, review article Abstract: Uncommon responses during immunotherapy is a new challenging issue in oncology practice. Recently, new criteria for evaluation of response to immunotherapy immune response evaluation criteria solid tumors (iRECIST) were accepted. According to iRECIST, worsening of performance status (PS) accompanied to pseudoprogression reflects most probably the true progression of the malignant disease. Methods. A systematic review of the literature was made by using several electronic database with the following search criteria: symptomatic pseudoprogression, atypical response, immunotherapy and lung cancer. Results. In the literature, we identified five reports of seven patients treated with immunotherapy that met the inclusion criteria. We also report our experience of patient with pseudoprogression and almost complete response after one dose of immunotherapy. Conclusions. As seen from our review, iRECIST criteria might be insufficient in distinguishing true progression from pseudoprogression in some patients with advanced NSCLC treated with immunotherapy. More precise assessment methods are urgently needed.
Keywords: symptomatic pseudoprogression, atypical response, immunotherapy, lung cancer
Published in DiRROS: 11.06.2024; Views: 43; Downloads: 18
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53. Evaluation of two-dimensional dose distributions for pre-treatment patient-specific IMRT dosimetryĐeni Smilović Radojčić, David Rajlić, Božidar Casar, Manda Švabić Kolacio, Nevena Obajdin, Dario Faj, Slaven Jurković, 2018, original scientific article Abstract: The accuracy of dose calculation is crucial for success of the radiotherapy treatment. One of the methods that represent the current standard for patient-specific dosimetry is the evaluation of dose distributions measured with an ionization chamber array inside a homogeneous phantom using gamma method. Nevertheless, this method does not replicate the realistic conditions present when a patient is undergoing therapy. Therefore, to more accurately evaluate the treatment planning system (TPS) capabilities, gamma passing rates were examined for beams of different complexity passing through inhomogeneous phantoms. Materials and methods The research was performed using Siemens Oncor Expression linear accelerator, Siemens Somatom Open CT simulator and Elekta Monaco TPS. A 2D detector array was used to evaluate dose distribution accuracy in homogeneous, semi-anthropomorphic and anthropomorphic phantoms. Validation was based on gamma analysis with 3%/3mm and 2%/2mm criteria, respectively. Results Passing rates of the complex dose distributions degrade depending on the thickness of non-water equivalent material. They also depend on dose reporting mode used. It is observed that the passing rate decreases with plan complexity. Comparison of the data for all set-ups of semi-anthropomorphic and anthropomorphic phantoms shows that passing rates are higher in the anthropomorphic phantom. Conclusions Presented results raise a question of possible limits of dose distribution verification in assessment of plan delivery quality. Consequently, good results obtained using standard patient specific dosimetry methodology do not guarantee the accuracy of delivered dose distribution in real clinical cases
Keywords: IMRT, 2D dose verification, gamma method, antropomorphic phantom
Published in DiRROS: 10.06.2024; Views: 62; Downloads: 40
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54. Interval cancers after negative immunochemical test compared to screen and non-respondersʼ detected cancers in Slovenian colorectal cancer screening programmeDominika Novak-Mlakar, Tatjana Kofol-Bric, Ana Lucija Škrjanec, Mateja Krajc, 2018, original scientific article Abstract: We assessed the incidence and characteristics of interval cancers after faecal immunochemical occult blood test and calculated the test sensitivity in Slovenian colorectal cancer screening programme. Patients and methods. The analysis included the population aged between 50 to 69 years, which was invited for screening between April 2011 and December 2012. The persons were followed-up until the next foreseen invitation, in average for 2 years. The data on interval cancers and cancers in non-responders were obtained from cancer registry. Gender, age, years of schooling, the cancer site and stage were compared among three observed groups. We used the proportional incidence method to calculate the screening test sensitivity. Results. Among 502,488 persons invited for screening, 493 cancers were detected after positive screening test, 79 interval cancers after negative faecal immunochemical test and 395 in non-responders. The proportion of interval cancers was 13.8%. Among the three observed groups cancers were more frequent in men (p = 0.009) and in persons aged 60+ years (p < 0.001). Comparing screen detected and cancers in non-responders with interval cancers more interval cancers were detected in persons with 10 years of schooling or more (p = 0.029 and p = 0.001), in stage III (p = 0.027) and IV (p < 0.001), and in right hemicolon (p < 0.001). Interval cancers were more frequently in stage I than non-responders cancers (p = 0.004). Test sensitivity of faecal immunochemical test was 88.45%. Conclusions. Interval cancers in Slovenian screening programme were detected in expected proportions as in similar programmes. Test sensitivity was among the highest when compared to similar programmes and was accomplished using test kit for two stool samples.
Keywords: cancer screening, colorectal cancer, faecal immunochemical test, test sensitivity
Published in DiRROS: 10.06.2024; Views: 60; Downloads: 21
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55. Prevalence of BRAF, NRAS and c-KIT mutations in Slovenian patients with advanced melanomaMaja Ebert Moltara, Srdjan Novaković, Marko Boc, Marina Bučić, Martina Reberšek, Vesna Zadnik, Janja Ocvirk, 2018, original scientific article Abstract: 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.
Keywords: BRAF, NRAS, c-KIT, melanoma
Published in DiRROS: 10.06.2024; Views: 60; Downloads: 42
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56. Ocular changes in metastatic melanoma patients treated with MEK inhibitor cobimetinib and BRAF inhibitor vemurafenibAna Uršula Gavrič, Janja Ocvirk, Polona Jaki Mekjavić, 2018, original scientific article Abstract: Mitogen-activated protein kinase kinase (MEK) inhibitor cobimetinib and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor vemurafenib have significantly improved the prognosis of BRAF-mutated metastatic melanoma. Some ocular symptoms and signs were recently recognized to follow this treatment. The study was aimed to investigate ocular toxicity in patients with metastatic melanoma treated with cobimetinib in combina-tion with vemurafenib.Patients and methods. In the prospective, observational study, patients with BRAF-mutated metastatic melanoma treated with cobimetinib in combination with vemurafenib at the Institute of Oncology Ljubljana were asked to par-ticipate. Ophthalmic examination was performed including measurement of visual acuity and intraocular pressure, slit lamp examination, funduscopy (CF), infrared-reflectance (IR) imaging and optical coherence tomography (OCT). Results. Five out of 7 patients noticed changes in vision few days after starting the therapy with cobimetinib. In all patients, small circular lesions, described as MEKAR lesions, were documented in outer retinal layers demonstrated with OCT, IR, and CF. Changes were in the center and/or scattered over the retina almost symmetrical in both eyes in 6 patients, and asymmetrical in one patient, the latter presented also with unilateral anterior uveitis and cystoid macular edema.Conclusions. Multiple bilateral foveal and extrafoveal small retinal lesions in the outer retinal layers develop in patients treated with MEK inhibitor in combination with BRAF inhibitor. Ophthalmologists and oncologists need to be aware of this common, yet relatively benign and often transient ocular side effect to avoid needless intervention, including the discontinuance of a potentially life-prolonging therapy.
Keywords: metastatic malignant melanoma, eye, MEK inhibitor, MEKAR
Published in DiRROS: 10.06.2024; Views: 52; Downloads: 18
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57. Is postmastectomy radiotherapy really needed in breast cancer patients with many positive axillary lymph nodes?Tanja Marinko, Karmen Stanič, 2018, original scientific article Abstract: Postmastectomy radiotherapy (PMRT) improves survival by eliminating potential occult lesions in the chest wall and lymphatic drainage area. Meta-analysis has shown that PMRT reduces mortality and local recurrence of patients with node positive breast cancer (but there is no specific data about the effectiveness of PMRT in a subgroup of patients with a high number of positive axillary lymph nodes (PALN). The aim of the study was to analyse the impact of the number of PALN on local and distant metastasis occurrence, overall survival (OS) and distant metastases free survival (DMFS) in patients treated with PMRT. Patients and methods. We reviewed medical records of 129 consecutive breast cancer patients with PALN, treated at Institute of Oncology Ljubljana with PMRT between January 2003 and December 2004. We grouped patients according to the number of PALN as follows: Group 1 (less than 15 PALN) and Group 2 with more than 15 PALN. All patients received adjuvant systemic therapy according to the clinical guidelines. We analysed number of locoregional (LR) recurrences, distant metastasis, overall survival, progression free survival (PFS) and DMFS. Results. After the median follow-up time of 11.5 years, the Kaplan-Meier survival analysis of PALN showed significantly shorter OS (p = 0.006), shorter PFS (p = 0.002) and shorter DMFS (p < 0.001) in the group of > 15 PALN. Only one LR was found in the group of patients with more than 15 PALN. In multivariate analysis more than 15 PALN and treatment with anthracycline chemotherapy statistically significantly influenced OS and DMFS. For PFS presence of more than 15 PALN were the only independent factor of shorter survival. Conclusions. Patients with more than 15 PALN have shorter DMFS, PFS and OS as compared to patients with less than 15 PALN, though they receive the same LR treatment. More studies with higher number of patients included are needed to further evaluate our findings.
Keywords: radiotherapy, postmastectomy, axillary limph nodes, breast cancer
Published in DiRROS: 10.06.2024; Views: 61; Downloads: 39
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58. Early cardiotoxicity after adjuvant concomitant treatment with radiotherapy and trastuzumab in patients with breast cancerTanja Marinko, Simona Borštnar, Rok Blagus, Jure Dolenc, Cvetka Bilban-Jakopin, 2018, original scientific article Keywords: radiotherapy, adjuvant radiotherapy, cardiotoxicity, breast cancer
Published in DiRROS: 10.06.2024; Views: 49; Downloads: 19
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60. Long-term survival of locally advanced stage III non-small cell lung cancer patients treated with chemoradiotherapy and perspectives for the treatment with immunotherapyMartina Vrankar, Karmen Stanič, 2018, original scientific article Abstract: Standard treatment for patients with inoperable locally advanced non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CCRT). Five-year overall survival rates range between 15 and 25%, while long term survival data are rarely reported. Patients and methods A total of 102 patients with stage III NSCLC treated between September 2005 and November 2010 with induction chemotherapy and CCRT were included in this long term survival analysis. All patients were tested for PD-L1 status and expression of PD-L1 was correlated with overall survival (OS), progression free survival (PFS) and toxicities. Results The median OS of all patients was 24.8 months (95% CI 18.7 to 31.0) with 10 year-survival rate of 11.2%. The median OS of patients with PD-L1 expression was 12.1 months (95% CI 0.1 to 26.2), while in patients with negative or unknown PD-L1 status was significantly longer, 25.2 months (95% CI 18.9 to 31.6), p = 0.005. The median PFS of all patients was 16.4 months (95% CI 13.0 to 19.9). PFS of patients with PD-L1 expression was 10.1 months (95% CI 0.1 to 20.4) and in patients with negative or unknown PD-L1 status was 17.9 months (95% CI 14.2 to 21.7), p = 0.003. Conclusions 10-year overall survival of stage III NSCLC patients after CCRT is 11.2%. PFS and OS differ with regard to PD-L1 status and are significantly shorter for patients with PD-L1 expression. New treatment with check-point inhibitors combined with RT therefore seems reasonable strategy to improve these results.
Keywords: NSCLC, non-small cell lung cancer, locally advanced, immunotherapy, chemoradiotherapy
Published in DiRROS: 10.06.2024; Views: 52; Downloads: 41
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