Background/Objectives: The aim of this study was to determine the oncologic outcomes for adult patients with primary extremity soft tissue sarcoma (ESTS) treated at the sarcoma referral center in the Republic of Slovenia. Methods: Patients from a prospectively maintained institutional database treated between January 2009 and December 2023 were retrospectively analyzed. The cohort was stratified into a high-risk group (HRG) and a low-risk group (LRG). Survival analyses focused on the HRG. Multivariable Cox models were constructed for local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS), and predictors of major wound complications were evaluated using multivariable logistic regression. Results: Among 315 included patients, 242 (76.8%) were in the HRG. In this group the median age was 61.5 years, 82.6% of tumors were in the lower extremity, and median tumor size was 9.0 cm. The most common histological subtype was undifferentiated pleomorphic sarcoma (28.5%). Clear margins were achieved in 86.8%, major postoperative complications occurred in 19.0%, and 60.7% of patients underwent radiotherapy. Local recurrence developed in 11.2%, regional recurrence in 5.0%, and distant metastasis in 32.6%. The corresponding 5-year overall survival, disease-specific survival, LRFS, and DMFS were 69.8%, 73.7%, 87.9%, and 66.8% in the HRG, respectively. In the LRG, only one local recurrence occurred and the 5-year LRFS was 100.0%. Preoperative radiotherapy showed a borderline association with major wound complications in the HRG (OR 2.70, 95% CI 1.00-7.28, p = 0.050). Tumor grade and size remained independent predictors of distant metastases, whereas margin status was not significantly associated with LRFS or DMFS. The primary amputation rate in the whole series was 2.9%. Conclusions: Treatment of primary ESTS patients in a specialized national referral cancer center achieved good overall survival (69.8%), a high limb-salvage rate (97.1%), and good local control, affirming that routine primary amputation is rarely needed. Outcomes in high-risk histologies remained driven mainly by distant metastases and showed clear histology-specific differences, whereas low-risk histologies had excellent outcomes with surgery alone. Preoperative radiotherapy was associated with a higher risk of major wound complications.

PurposeTo describe real-world treatment patterns and outcomes among patients with extensive-stage small cell lung cancer (ES-SCLC) treated with first-line chemotherapy plus durvalumab as in CASPIAN trial within Expanded Access Program, with a focus on the use and impact of consolidation (cRT) and salvage radiotherapy (sRT).Patients and methodsThis retrospective, multicenter cohort study included patients with ES-SCLC treated with durvalumab plus platinum–etoposide between September 2019 and December 2022 across 11 academic centers in Israel, Poland, Portugal, and Slovenia. Patients characteristics, radiotherapy use, adverse events (AE), and outcomes were collected using a standardized form. Radiotherapy was categorized as cRT, sRT, or palliative RT (pRT). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier methods and compared using log-rank testing. Multivariable Cox regression evaluated predictors of survival.ResultsA total of 133 patients were included (median age 65 years; 74% ECOG PS 0–1). Radiotherapy was administered to 58.6% of patients (cRT 28.2%, sRT 24.3%, pRT 47.4%). Median (m) PFS and mOS for the entire cohort were 6.9 months (m) and 15.9 m, respectively. Patients receiving cRT achieved the longest mPFS (11.7 m) and a mOS of 19.5 m; sRT was associated with an mOS of 20.4 m. Continuation of durvalumab beyond progression combined with RT was associated with improved survival (p = 0.024). Treatment-related AEs occurred in 38.3% of patients, immune-related toxicities were infrequent, and pneumonitis was rare.ConclusionIn this multinational real-world cohort, outcomes with first-line chemo-immunotherapy were consistent with CASPIAN trial. The addition of cRT or sRT appeared feasible, safe, and associated with clinically meaningful survival improvements. Prospective trials are needed to define optimal integration of radiotherapy with chemo-immunotherapy in ES-SCLC.

Chemoimmunotherapy (CT/IO) with immune checkpoint inhibitors has recently become the standard of care for extensive-stage small cell lung cancer (ES-SCLC). Given the uncertain role of consolidation thoracic radiotherapy (cTRT) in this setting, we conducted a real-world study to evaluate the efficacy and safety of cTRT in ES-SCLC patients receiving first-line CT/IO. We performed a retrospective analysis of ES-SCLC patients treated with first-line CT/IO in Slovenia from December 2019 to June 2024. Patient characteristics, treatment patterns, survival outcomes, and adverse events were analyzed, with subgroup comparisons based on cTRT administration. Among 208 patients (median age: 66 years), median overall survival was 12.1 months (95% CI: 10.6-13.7). cTRT was administered to 46 patients (22.1%), who had fewer metastases. cTRT was associated with improved OS (17.0 vs. 10.8 months; p < 0.001) and was an independent OS predictor (HR = 0.58, p = 0.035). Grade ≥ 3 adverse events were similar (26.1% vs. 21.3%), though pneumonitis occurred more frequently with cTRT (6.5% vs. 0%, p = 0.001). cTRT may improve survival in ES-SCLC patients treated with CT/IO, with no significant increase in toxicity apart from pneumonitis. Further prospective studies are needed.

There is an emerging group of distinct vascular neoplasms with NFATC1/2 fusions, involving bones and soft tissues and often displaying focal epithelioid morphology, variable atypia of endothelial cells, predominantly vasoformative and in some cases focal solid growth. Although they may show aggressive local growth and may recur locally, malignant behaviour has not been documented. We present a case of a 35-year-old woman with multiple vascular neoplasms with a EWSR1::NFATC2 fusion involving the lungs, multiple bones (vertebra, femurs, tibia, pelvis) and probably the liver. The bone lesions were locally aggressive and recurred after surgical treatment. Nine years after the first manifestation, there was progression to an epithelioid angiosarcoma. The patient died 3 months after the diagnosis of epithelioid angiosarcoma with massive lung and liver involvement(metastases). In addition to the EWSR1::NFATC2 fusion, an activating PIK3CA gene mutation was identified in the angiosarcoma but not in the previously diagnosed bone tumours. To the best of our knowledge, this is the first documentation of malignant progression of a vascular neoplasm with NFATC1/2 fusion as well as visceral (lung) involvement.

Lung cancer remains the leading cause of cancer-related deaths in Europe, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. NSCLC is a heterogeneous disease encompassing various oncogenic alterations. Among them, EGFR exon 20 insertion mutations, constituting 0.3–2.2% of NSCLC cases, rank as the third most common EGFR alteration after exon 19 deletions and the L858R point mutation in exon 21, also known as “typical” EGFR alterations. Recent advancements in understanding the molecular pathogenesis of NSCLC have led to significant breakthroughs in targeted therapies, revolutionizing treatment options for patients with specific genetic alterations. This article presents the outcomes of a Virtual Meeting conducted on the online platform (provided Within3©) from September 19 to October 30, 2022. The meeting focused on addressing the challenges in the diagnosis and treatment of NSCLC patients with EGFR exon 20 insertion mutations. The participants consisted of healthcare professionals from ten Central and Eastern European countries who shared their experiences and opinions on various aspects, including epidemiology, treatment options, and diagnostic approaches employed in their respective healthcare institutions. The discussions were facilitated through open-ended and multiple-choice questions. The primary objective of this article is to provide an overview of the identified challenges associated with the diagnosis and treatment of this heterogeneous disease, based on the assessments of the meeting participants. Among the major emerging challenges discussed, the reimbursement issues concerning next-generation sequencing (NGS), a recommended method in NSCLC molecular diagnosis, and the availability of approved targeted treatments to enhance patient outcomes were of paramount importance. Furthermore, fostering community awareness of lung cancer and promoting harmonized lung cancer care were identified as areas deserving greater attention. Notably, the rapidly evolving treatment landscape, particularly with NGS for NSCLC patients with genomic alterations like EGFR , ALK , RET , MET , NTRK , and ROS1 , necessitates prioritizing the development of new drugs, even for the relatively smaller subgroup with exon 20 insertion mutations.

BACKGROUND:The standard first-line systemic treatment for patients with non-oncogene addicted advanced nonsquamous non-small cell lung cancer (NSCLC) is immunotherapy with immune checkpoint inhibitors (ICI) and/or chemotherapy (ChT). Therapy after failing ICI +/- ChT remains an open question, and docetaxel plus nintedanib represent a valid second line option. PATIENTS AND METHODS:A multicenter retrospective trial of real-life treatment patterns and outcomes of patients with advanced lung adenocarcinoma treated with docetaxel plus nintedanib after the failure of ICI and/or ChT was performed. Patients from 2 Slovenian and 1 Croatian oncological center treated between June 2014 and August 2022 were enrolled. We assessed objective response (ORR), disease control rate (DCR), median progression free survival (PFS), median overall survival (OS), and safety profile of treatment. RESULTS:There were 96 patients included in the analysis, with ORR of 18.8%, DCR of 57.3%, median PFS of 3.0 months (95% CI: 3.0-5.0 months), and a median OS of 8.0 months (95% CI: 7.0-10.0 months). The majority of patients (n = 47,49%) received docetaxel plus nintedanib as third-line therapy. The ORR for this subset of patients was 19.1%, with a DCR of 57.4%. The highest response rate was observed in patients who received second-line docetaxel plus nintedanib after first-line combination of ChT-ICI therapy (n = 24), with an ORR of 29.2% and DCR of 66.7% and median PFS of 4.0 months (95% CI: 3.0-8.0 months). Fifty-three patients (55.2%) experienced adverse events (AEs), most frequently gastrointestinal; diarrhea (n = 29, 30.2%), and increased liver enzyme levels (n = 17, 17.7%). CONCLUSIONS:The combination of docetaxel and nintedanib can be considered an effective therapy option with an acceptable toxicity profile for patients with advanced NSCLC after the failure of ICI +/- ChT.

Gastrointestinal stromal tumors (GISTs) are soft tissue sarcomas that mostly derive from Cajal cell precursors. They are by far the most common soft tissue sarcomas. Clinically, they present as gastrointestinal malignancies, most often with bleeding, pain, or intestinal obstruction. They are identified using characteristic immunohistochemical staining for CD117 and DOG1. Improved understanding of the molecular biology of these tumors and identification of oncogenic drivers have altered the systemic treatment of primarily disseminated disease, which is becoming increasingly complex. Gain-of-function mutations in KIT or PDGFRA genes represent the driving mutations in more than 90% of all GISTs. These patients exhibit good responses to targeted therapy with tyrosine kinase inhibitors (TKIs). Gastrointestinal stromal tumors lacking the KIT/PDGFRA mutations, however, represent distinct clinico-pathological entities with diverse molecular mechanisms of oncogenesis. In these patients, therapy with TKIs is hardly ever as effective as for KIT/PDGFRA-mutated GISTs. This review provides an outline of current diagnostics aimed at identifying clinically relevant driver alterations and a comprehensive summary of current treatments with targeted therapies for patients with GISTs in both adjuvant and metastatic settings. The role of molecular testing and the selection of the optimal targeted therapy according to the identified oncogenic driver are reviewed and some future directions are proposed.

In 2019, the Recommendations for the management of patients with lung cancer were published bringing much-needed standardisation of diagnosis and treatment to improve survival of patients with lung cancer. Three years after the original Recommendations were published, the update of the Recommendations brings the most innovations in the chapter on systemic treatment of patients with lung cancer. This reflects the remarkable progress made in the field of understanding the oncogenesis and biology of lung cancer and thus the development of new drugs. The burden of lung cancer remains high, as lung cancer is still the most common cause of cancer related death in our country and worldwide. Lung cancer is responsible for one of five cancer-related deaths. Almost one third of patients with lung cancer do not receive any oncological treatment, either because of poor performance status, comorbidities or the extent of the disease. Half of the patients have metastatic disease at diagnosis, resulting in only small improvements in survival despite advances in the treatment of lung cancer patients. These data remind us that if we are to make major shifts in the management of lung cancer patients, we will need to take different approaches. The most promising seems to be the detection of early stages of lung cancer which offers the best treatment results. The Recommendations written here are guidelines for the management of patients with lung cancer. Only with comprehensive multidisciplinary treatment approach, the best outcome from the prognostically unfavourable disease can be offered.

INTRODUCTION:Patients with thoracic malignancies are at increased risk for mortality from coronavirus disease 2019 (COVID-19), and a large number of intertwined prognostic variables have been identified so far. METHODS:Capitalizing data from the Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry, a global study created with the aim of describing the impact of COVID-19 in patients with thoracic malignancies, we used a clustering approach, a fast-backward step-down selection procedure, and a tree-based model to screen and optimize a broad panel of demographics and clinical COVID-19 and cancer characteristics. RESULTS:As of April 15, 2021, a total of 1491 consecutive eligible patients from 18 countries were included in the analysis. With a mean observation period of 42 days, 361 events were reported with an all-cause case fatality rate of 24.2%. The clustering procedure screened 73 covariates in 13 clusters. A further multivariable logistic regression for the association between clusters and death was performed, resulting in five clusters significantly associated with the outcome. The fast-backward step-down selection procedure then identified the following seven major determinants of death: Eastern Cooperative Oncology Group-performance status (ECOG-PS) (OR = 2.47, 1.87-3.26), neutrophil count (OR = 2.46, 1.76-3.44), serum procalcitonin (OR = 2.37, 1.64-3.43), development of pneumonia (OR = 1.95, 1.48-2.58), C-reactive protein (OR = 1.90, 1.43-2.51), tumor stage at COVID-19 diagnosis (OR = 1.97, 1.46-2.66), and age (OR = 1.71, 1.29-2.26). The receiver operating characteristic analysis for death of the selected model confirmed its diagnostic ability (area under the receiver operating curve = 0.78, 95% confidence interval: 0.75-0.81). The nomogram was able to classify the COVID-19 mortality in an interval ranging from 8% to 90%, and the tree-based model recognized ECOG-PS, neutrophil count, and c-reactive protein as the major determinants of prognosis. CONCLUSIONS:From 73 variables analyzed, seven major determinants of death have been identified. Poor ECOG-PS was found to have the strongest association with poor outcome from COVID-19. With our analysis, we provide clinicians with a definitive prognostication system to help determine the risk of mortality for patients with thoracic malignancies and COVID-19.

Background Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective treatments for EGFR mutation-positive (EGFRm) non-small cell lung cancer (NSCLC). However, routine clinical practice is different between countries/institutions. Patients and methods The REFLECT study (NCT04031898) is a retrospective medical chart review that explored real-life treatment and outcomes of EGFRm NSCLC patients receiving first-line (1L) first-/second-generation (1G/2G) EGFR TKIs in 8 countries. This study included adult patients with documented advanced/metastatic EGFRm NSCLC with 1L 1G/2G EGFR TKIs initiated between Jan 2015 - Jun 2018. We reviewed data on clinical characteristics, treatments, EGFR/T790M testing patterns, and survival outcomes. Here, we report data from 120 medical charts in 3 study sites from Slovenia. Results The Slovenian cohort (median age 70 years, 74% females) received 37% erlotinib, 32% afatinib, 31% gefitinib. At the time of data collection, 94 (78%) discontinuations of 1L TKI, and 89 (74%) progression events on 1L treatment were reported. Among patients progressing on 1L, 73 (82%) were tested for T790M mutation yielding 50 (68%) positive results, and 62 (85%) received 2L treatment. 82% of patients received osimertinib. Attrition rate between 1L and 2L was 10%. The median (95% CI) real-world progression free survival on 1L EGFR TKIs was 15.6 (12.6, 19.2) months; median overall survival (95% CI) was 28.9 (25.0, 34.3) months. Conclusions This real-world study provides valuable information about 1G/2G EGFR TKIs treatment outcomes and attrition rates in Slovenian EGFRm NSCLC patients. The reduced attrition rate and improved survival outcomes emphasize the importance of 1L treatment decision.

Background: NUT carcinoma is a highly aggressive and rare subset of squamous cell carcinoma with grim prognosis. It is under-recognized by both pathologists and oncologists. Recognition is challenging due to its rareness and the fact that its clinical and laboratory features as well as morphological and immunohistochemical characteristics may mimic other malignancies. Case presentation: An interesting case of NUT carcinoma in a 47-year-old male with a large tumor mass in the inferior part of the mediastinum and left lung and increased levels of serum alpha fetoprotein (AFP) is described. Immunohistochemical analysis of both the primary tumor in a bronchoscopy specimen and an excisional biopsy of a subcutaneous metastasis showed positivity for AFP and leukocyte common antigen (LCA) that were misleading and resulted in diagnostic pitfalls of mediastinal germ cell tumor (clinically) and hematolymphoid neoplasm (pathologic report). Immunohistochemical demonstration of NUT protein expression revealed the proper diagnosis, which was further confirmed by RNA sequencing revealing a BRD4-NUTM1 gene fusion.Conclusions: Since NUT carcinoma can show a wide spectrum of histological and immunophenotypic features and can clinically mimic other tumors, use of RNA sequencing with identification of specific NUTM1 fusion partner could be crucial when there are discrepant clinical and histopathological findings. As well, since the category of so-called NUTM1-rearranged neoplasms is rapidly expanding, identification of NUTM1 fusion partner may be essential for the appropriate clinical management.

In patients with gastrointestinal stromal tumors (GIST), it has become mandatory to determine the driver mutation in order to predict the response to standard treatment with tyrosine kinase inhibitors (TKI). A total of 10-15% of all GIST lack activating mutations in KIT proto-oncogene, receptor tyrosine kinase (KIT)/platelet-derived growth factor receptor alpha (PDGFRA) and have been classified as KIT/PDGFRA wild-type (WT) GIST. They are characterized by poor response to TKI. From a group of 119 metastatic GIST patients, 17 patients with KIT/PDGFRA/BRAF WT GIST as determined by reverse transcription-quantitative (RT-q) PCR and Sanger sequencing were profiled by a targeted next-generation sequencing (NGS) approach and their treatment outcome was assessed. In the present study, 41.2% of patients as KIT/PDGFRA/BRAF WT GIST examined with RT-qPCR and Sanger sequencing were confirmed to be carriers of pathogenic KIT/PDGFRA mutations by NGS and were responsive to TKI. The percentage of genuinely KIT/PDGFRA WT GIST in the present study thereby dropped from the initial 14.3% detected with the RT-qPCR and Sanger sequencing to 7.6% after NGS. Their outcome was universally poor. The reliability of RT-qPCR and direct Sanger sequencing results in this setting is therefore insufficient and it is recommended that NGS becomes a requirement for treatment decision at least in KIT/PDGFRA/BRAF WT GIST as determined by RT-qPCR and Sanger sequencing.

Abstract Background Immune checkpoint inhibitors have changed the paradigm of cancer treatment; however, non-invasive biomarkers of response are still needed to identify candidates for non-responders. We aimed to investigate whether immunotherapy [18F]FDG PET radiomics signature (iRADIOMICS) predicts response of metastatic non-small-cell lung cancer (NSCLC) patients to pembrolizumab better than the current clinical standards. Patients and methods Thirty patients receiving pembrolizumab were scanned with [18F]FDG PET/CT at baseline, month 1 and 4. Associations of six robust primary tumour radiomics features with overall survival were analysed with Mann-Whitney U-test (MWU), Cox proportional hazards regression analysis, and ROC curve analysis. iRADIOMICS was constructed using univariate and multivariate logistic models of the most promising feature(s). Its predictive power was compared to PD-L1 tumour proportion score (TPS) and iRECIST using ROC curve analysis. Prediction accuracies were assessed with 5-fold cross validation. Results The most predictive were baseline radiomics features, e.g. Small Run Emphasis (MWU, p = 0.001; hazard ratio = 0.46, p = 0.007; AUC = 0.85 (95% CI 0.69–1.00)). Multivariate iRADIOMICS was found superior to the current standards in terms of predictive power and timewise with the following AUC (95% CI) and accuracy (standard deviation): iRADIOMICS (baseline), 0.90 (0.78–1.00), 78% (18%); PD-L1 TPS (baseline), 0.60 (0.37–0.83), 53% (18%); iRECIST (month 1), 0.79 (0.62–0.95), 76% (16%); iRECIST (month 4), 0.86 (0.72–1.00), 76% (17%). Conclusions Multivariate iRADIOMICS was identified as a promising imaging biomarker, which could improve management of metastatic NSCLC patients treated with pembrolizumab. The predicted non-responders could be offered other treatment options to improve their overall survival.

Background: Monolithic chromatography using convective interaction media (CIM) disks or columns can be used in the separation step of speciation analysis. When different monolithic disks are placed in one housing, forming conjoint liquid chromatography (CLC) monolithic column, two-dimensional separation is achieved in a single chromatographic run. Methods: Here, we assembled low-pressure (maximum 50 bar) CLC monolithic column, which consists of two 0.34 mL shallow CIM monolithic disks and high-pressure CLC column (maximum 150 bar) from 0.1 mL analytical high performance short bed CIMac monolithic disks. Both the CLC columns constructed from affinity Protein G and weak anion exchange diethylamine (DEAE) disks, were applied for the speciation of cisplatin, oxaliplatin and carboplatin in spiked standard serum proteins, spiked human serum and serum of cancer patients. The analytical performances of the CLC columns used were evaluated by comparing their robustness, selectivity, repeatability and reproducibility. The separated serum proteins were detected on-line by ultraviolet (UV) and eluted Pt species by inductively coupled plasma mass spectrometry (ICP-MS). For accurate quantification of the separated Pt species (unbound Pt-based chemotherapeutic from species associated to transferrin (Tf), human serum albumin (HSA) and Immunoglobulin G (IgG)), post column isotope dilution (ID)-ICP-MS was used. Results: The data from analyses showed that both tested CLC monolithic columns gave statistically comparable results, with the low-pressure CLC column exhibiting better resolving power and robustness. It also enables more effective cleaning of monolithic disks and to analyse larger series of serum samples than the high-pressure CLC column. Analyses of serum samples of cancer patients treated with cisplatin or carboplatin showed that Pt-hemotherapeutics were bound preferentially to HSA (around 80%). The portion of unbound Pt in general did not exceed 2%, up to 5% of Pt was associated with Tf and approximately 20% with IgG. Column recoveries, calculated as a ratio between the sum of concentrations of Pt species eluted and concentration of total Pt in serum samples, were close to 100%. Conclusions: Low-pressure CLC column exhibited greater potential than high-pressure CLC column, and can be thus recommended for its intended use in speciation analysis of metal-based biomolecules.

Background Uncommon response during immunotherapy is a new challenging issue in oncology practice. Recently, new criteria for evaluation of response to immunotherapy immune response evaluation criteria in 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.

INTRODUCTION:Approximately 1% to 4% of NSCLC tumors harbor erb-b2 receptor tyrosine kinase 2 (ERBB2) mutation; there is no approved targeted treatment for this subgroup. METHODS:Patients with stage IV NSCLC that progressed after clinical benefit on erlotinib/gefitinib and/or had activating EGFR or ERBB2 mutations, had exhausted other treatments, and were ineligible for afatinib trials were enrolled in a named patient use program, receiving afatinib 30 to 50 mg/d on a compassionate basis within routine clinical practice. Efficacy and safety were retrospectively assessed in the subgroup with ERBB2 mutation-positive NSCLC. RESULTS:Twenty-eight heavily pretreated patients in the named patient use program had a documented ERBB2 mutation by local testing. Median time-to-treatment failure (TTF; time from treatment initiation to discontinuation for any reason) was 2.9 months; eight patients (29%) had TTF greater than 1 year. Objective response rate was 19% (3 of 16 patients with response data achieved partial response) and disease control rate (DCR) was 69% (11 of 16). Among 12 patients for whom type of ERBB2 mutation was specified, 10 had a p.A775_G776insYVMA insertion in exon 20, four of whom (40%) remained on afatinib for more than 1 year. This subgroup had median TTF of 9.6 months, objective response rate of 33% (two of six), and disease control rate of 100% (six of six). CONCLUSIONS:This analysis of patients treated in clinical practice provides further evidence of the activity of afatinib in ERBB2 mutation-positive NSCLC, and suggests that identification of specific subgroups with certain mutations, such as p.A775_G776ins/YVMA insertion in exon 20, could help optimize outcomes with ErbB2-targeted treatment.

Zdravnik vam je gefitinib predpisal, ker imate razsirjenega raka pljuc. Gre za poseben podtip pljucnega raka, ki ima izraženo aktivirajoco mutacijo za t. i. receptor epidermalnega rastnega dejavnika (EGFR). Rak je nastal v pljucnem tkivu in se razsiril na druge organe.

Primary lung cancer is the most common malignancy after non-melanocytic skin cancer, and deaths from lung cancer exceed those from any other malignancy worldwide. In Slovenia, it is the fourth most common cancer in males and in females, and the leading cause of death due to cancer. The historically poor survival rates of lung cancer patients (5-year relative survival of approx. 12 %) are improving, mainly due to the introduction of novel systemic therapies in the treatment algorithms.Systemic treatment is an important part of treatment in all stages of the disease as well as in all pathohistological subtypes of lung cancer. In operable disease, adjuvant systemic therapy with platinum-based schemas is recommended for a vast majority of patients. In locoregional disease, chemotherapy is used as concomitant with radiotherapy. Systemic treatment is the cornerstone of treatment in metastatic disease. The treatment strategy should take into account factors like histology, molecular pathology, age, PS, co-morbidities and the patient's preferences. Systemic therapy should be considered in all stage IV patients with PS 0-2. Treatment decisions should ideally be discussed within a multidisciplinary tumor board, while the systemic treatment has to be performed by a specialist highly educated and skilled in systemic treatment of cancer.Slovenian guidelines for diagnosis, treatment and follow up were last published in 2006. In near future, a new, updated version will be published. Hereby, we only present the updated guidelines for systemic treatment. These guidelines were developed in a collaboration of the specialists from three institutions: Institute of Oncology Ljubljana, University Clinic Golnik, and University Clinical Centre Maribor.

Rak pljuc je najbolj pogost rak (ce upostevamo nemelanocitni rak kože) in smrt zaradi raka pljuc je najbolj pogost vzrok smrti zaradi raka na svetu. V Sloveniji je po pogostosti na 4. Mestu in najbolj pogost vzrok smrti zaradi raka. Slabo preživetje bolnikov z rakom pljuc (5 letno srednje preživetje je okoli 12 %) v preteklosti se z uporabo novih sistemskih zdravljen v zadnjem casu izboljsuje. Sistemsko zdravljenje je pomemeben del zdravljenja raka pljuc v vseh stadijih bolezni in pri vseh patohistoloskih podtipih. Sistemsko zdravljenje na osnovi platine po operaciji v sklopu adjuvantnega zdravljenja se priporoca pri vecini bolnikov. Kemoterapija se uporabija socasno sz radioterapijo pri lokalno napredovali bolezni. Sistemsko zdravljenje je osnova zdravljenja razsirjene bolezni. Vrsta sistemskega zdravljnja je odvisna od patohistoloskega podtipa, molekularne analize, starosti, splosnega stanja zmogljivosti, socasnih obolenj in bolnikovih želja. Sistemsko terapijo naj bi prejeli vsi bolniki z razsirjeno boleznijo s PS 0-2. Zaželjeno je, da se nacin zdravlejnja doloci na multidisciplinarnem konziliju, izvaja pa specialist internist onkolog, z znanjem in izkusnjami glede sistemske terapije. Slovenske smernice obravnave pljucnega raka so bile zadnjic objavljene leta 2006. V pripravi so nove celostne smernice obravnave raka pljuc v Sloveniji. V clanku predstavljamo posodobljenje smernice sistemskega zdravljenja, ki so plod sodelovanja strokovnjakov treh ustanov, ki se ukvarjajo s sistemskim zdravljenjem raka pljuc v Sloveniji: Onkoloski institut Ljubljana, Univerzitetna klinika Golnik in Univerzitetni klinicni center Maribor.