Introduction:The best tissue sample is still very important for the diagnosis of mesothorax lymphadenopathy. In the past 20 years endobronchial ultrasound (EBUS) has been used efficiently in most cases of primary lung cancer disease or metastatic disease. Several new type of needles have been created such 19G, 18G and hybrid biopsies with cryoprobes. Rapid on-site evaluation (ROSE) is used as an additional initial diagnostic tool. Confocal microscopy is a method of rapid on-site evaluation. Patients and Methods:One hundred patients with mesothorax lymphadenopathy were biopsied with ebus and two groups were created one with rapid on-site evaluation with confocal microscopy and one by an operator with microscopic evaluation with sample preparation on cytoglasses. Our main objective was to assess parameters such as time, false negative results between the two techniques and technical issues such as the accessibility and evaluation between the two techniques. Safety was also evaluated. Results:Rapid on-site evaluation is more cost efficient with a cytologist on site, however; with a higher rate of false negative results. Accessibility with the Cellvizio® catheter was less possible in a few cases due to rigid angles within the airways especially for small lymphnodes ≤ 1.5 cm (L4L mainly). Discussion:Confocal is a safe and time-efficient technique for mesothorax lymphadenopathy. A high level of training is required for pulmonary physicians in order to assess the novel imaging technique. Definitely different parts of the lymphnode have to reached and evaluated in order to have a proper initial evaluation.

Tarlatamab, a bispecific T-cell engager (BiTE) immunotherapy, demonstrated promising activity in patients (pts) with previously treated small cell lung cancer (SCLC) in phase 1/2 trials. We report results from the primary analysis of the randomized controlled, phase 3 DeLLphi-304 study, evaluating tarlatamab versus (vs) CTx (topotecan, lurbinectedin, or amrubicin) in pts with SCLC following progression on or after platinum-based chemotherapy.

LBA8008 Background: Tarlatamab, a bispecific T-cell engager (BiTE) immunotherapy, demonstrated promising activity in patients (pts) with previously treated SCLC in phase 1/2 trials. We report results from the primary analysis of the randomized controlled, phase 3 DeLLphi-304 study, evaluating tarlatamab vs CTx in pts with SCLC following progression on or after platinum-based chemotherapy. Methods: Pts were randomized 1:1 to tarlatamab or CTx (topotecan, lurbinectedin or amrubicin), stratified by prior treatment with a PD-(L)1 inhibitor, chemotherapy-free interval, brain metastases, and intended CTx. Primary endpoint was overall survival (OS). Key secondary endpoints were progression-free survival (PFS) and patient-reported outcomes (PRO). Other secondary endpoints included objective response rate (ORR), duration of response (DOR), disease control rate (DCR), and safety. Results: 509 pts were randomized (254, tarlatamab; 255, CTx). At median follow-up of 11.2 months (mo) for tarlatamab and 11.7 mo for CTx, pts in the tarlatamab arm had significantly longer OS (median OS: 13.6 vs 8.3 mo; hazard ratio [HR], 0.60 [95% CI: 0.47, 0.77]; P < 0.001) and PFS (median PFS: 4.2 vs 3.2 mo; HR, 0.72 [95% CI: 0.59, 0.88]; P < 0.001) vs pts in the CTx arm. Tarlatamab improved cancer-related symptoms of dyspnea and cough compared to CTx (Table). Lower rates of grade (Gr) ≥3 treatment-related adverse events (TRAEs) occurred with tarlatamab vs CTx (27% vs 62%); discontinuations due to TRAEs were lower with tarlatamab (3% vs 6%). The most common Gr ≥3 TRAEs were neutropenia (4%) and lymphopenia (4%) with tarlatamab and anemia (28%) and neutropenia (22%) with CTx. Cytokine release syndrome with tarlatamab was primarily low grade (42% Gr1; 13% Gr2; 1% Gr3) and manageable. Conclusions: The DeLLphi-304 trial showed tarlatamab significantly improved OS, PFS, and PROs, with a favorable safety and tolerability profile compared to CTx in pts with SCLC that progressed on or after initial platinum-based CTx, defining a new standard of care for these patients. Clinical Trial Information: NCT05740566; Legal entity responsible: Amgen Inc.; Funding: Amgen Inc.; Editorial acknowledgement: Medical writing support for the development of this abstract was provided by Sukanya Raghuraman, PhD, of Cactus Life Sciences, part of Cactus Communications, and was funded by Amgen Inc. Clinical trial information: NCT05740566 . Tarlatamab (n=254) CTx*(n=255) Tarlatamab treatment effect ( P -value) Median OS, mo (95% CI) 13.6 (11.1-NE) 8.3 (7.0-10.2) HR = 0.60 ( P < 0.001) Median PFS, mo (95% CI) 4.2 (3.0-4.4) 3.2 (2.9-4.2) HR = 0.72 ( P < 0.001) ORR, % (95% CI) 35 (29-41) 20 (16-26) Odds ratio = 2.13 Median DOR, mo (95% CI) 6.9 (4.5-12.4) 5.5 (4.2-5.7) — DCR, % (95% CI) 68 (62-74) 64 (58-70) — Dyspnea score, change from baseline after18 wks † , mean (95% CI) -1.94 (-4.32, 0.45) 7.20 (4.58-9.81) MD = -9.14 ( P < 0.001) Cough score, pts with improvement 18 wks after baseline ‡ , n (%) 41 (16) 23 (9) OR = 2.04 ( P = 0.012) Chest pain score, pts with improvement 18 wks after baseline ‡ , n (%) 22 (9) 9 (4) OR = 1.84 ( P = 0.100 § ) MD: mean difference; NE: not estimable; wks, weeks. *Topotecan (n=185), lurbinectedin (n=47), or amrubicin (n=23). †EORTC QLQ-C30 scale. ‡EORTC QLQ-LC13 scale. §Non-significant.

BACKGROUND:Despite improved efficacy with first-line immune checkpoint inhibitors plus platinum-based chemotherapy for extensive-stage small-cell lung cancer (ES-SCLC), survival remains poor. In this study, we aimed to compare lurbinectedin plus atezolizumab and atezolizumab alone as maintenance therapies in patients with ES-SCLC without progression after induction therapy with atezolizumab, carboplatin, and etoposide. METHODS:IMforte was a randomised, open-label, phase 3 trial done at 96 hospitals and medical centres in 13 countries (Belgium, Germany, Greece, Hungary, Italy, Mexico, Poland, South Korea, Spain, Taiwan, Türkiye, the UK, and the USA). Eligible patients were aged 18 years or older with treatment-naive ES-SCLC. Patients received four 21-day cycles of induction treatment (atezolizumab, carboplatin, and etoposide). After completing induction treatment, eligible patients without disease progression were randomly assigned (1:1) using permuted blocks (Interactive Voice/Web Response System) to receive maintenance treatment intravenously every 3 weeks with lurbinectedin (3·2 mg/m2; with granulocyte colony-stimulating factor prophylaxis) plus atezolizumab (1200 mg) or atezolizumab (1200 mg). The two primary endpoints were independent review facility-assessed (IRF) progression-free survival and overall survival, measured from randomisation into the maintenance phase. Efficacy endpoints were assessed in the full analysis set, which included all patients who were randomly assigned to maintenance phase treatment, regardless of whether they received their assigned study treatment. Safety was assessed in all patients who received at least one dose of lurbinectedin or atezolizumab, and was analysed according to the treatment received. This study is registered with ClinicalTrials.gov, NCT05091567, and is closed for recruitment. FINDINGS:Between Nov 17, 2021, and Jan 11, 2024, 895 patients were screened for enrolment, of whom 660 (74%) were enrolled into the induction phase. Between May 24, 2022, and April 30, 2024, 483 (73%) of 660 patients entered the maintenance phase and were randomly assigned to lurbinectedin plus atezolizumab (n=242) or atezolizumab (n=241). At the data cutoff (July 29, 2024), IRF progression-free survival was longer in the lurbinectedin plus atezolizumab group than the atezolizumab group (stratified hazard ratio [HR] 0·54 [95% CI 0·43-0·67]; p<0·0001), as was overall survival (stratified HR 0·73 [0·57-0·95]; p=0·017). 92 (38%) of 242 patients in the lurbinectedin plus atezolizumab group and 53 (22%) of 240 patients in the atezolizumab group had grade 3-4 adverse events. The most common grade 3-4 events in the lurbinectedin plus atezolizumab group were anaemia (20 [8%] of 242 patients), decreased neutrophil count (18 [7%] patients), and decreased platelet count (18 [7%] patients) and the most common events in the atezolizumab group were hyponatremia (five [2%] of 240 patients), dyspnoea (four [2%] patients), and pneumonia (four [2%] patients). Grade 5 adverse events occurred in 12 (5%) of 242 patients in the lurbinectedin plus atezolizumab group and six (3%) of 240 patients in the atezolizumab group. The incidence of myelosuppressive toxicities (eg, neutropenia and leukopenia) was higher in the lurbinectedin plus atezolizumab group than the atezolizumab group. INTERPRETATION:IRF progression-free survival and overall survival were longer in the lurbinectedin plus atezolizumab group than the atezolizumab group for patients with ES-SCLC, albeit with a higher incidence of adverse events. Lurbinectedin plus atezolizumab represents a novel therapeutic option for first-line maintenance treatment in this setting. FUNDING:F Hoffmann-La Roche and Jazz Pharmaceuticals.

BACKGROUND:LEAP-008 (NCT03976375) was an open-label, randomized, phase 3 study of lenvatinib plus pembrolizumab versus docetaxel for metastatic NSCLC that progressed on anti‒programmed cell death protein 1 or anti‒programmed cell death ligand 1 therapy and platinum-containing chemotherapy. METHODS:Participants were randomized 4:4:1 to once-daily lenvatinib 20 mg plus pembrolizumab 200 mg every 3 weeks (maximum 35 cycles), docetaxel 75 mg/m2 every 3 weeks, or once-daily lenvatinib 24 mg. Primary end points were overall survival (OS) and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 by central review. The superiority of lenvatinib plus pembrolizumab versus docetaxel was assessed at interim analysis 2 for PFS and final analysis for OS. RESULTS:Participants (N = 422) were randomized to lenvatinib plus pembrolizumab (n = 185), docetaxel (n = 189), or lenvatinib monotherapy (n = 48). The median (95% confidence interval [CI]) PFS was 5.6 (4.2‒6.5) months with lenvatinib plus pembrolizumab and 4.2 (3.2‒5.2) months with docetaxel (hazard ratio, 0.89 [95% CI: 0.70‒1.12]; p = 0.164). The median (95% CI) OS was 11.3 (9.4‒13.2) versus 12.0 (9.6‒13.7) months (hazard ratio, 0.98 [95% CI: 0.78‒1.23]; p = 0.434). Rates of treatment-related adverse events were 91.7%, 91.0%, and 89.4% with lenvatinib plus pembrolizumab, docetaxel, and lenvatinib, respectively; the rates of grade 3 to 5 treatment-related adverse events were 59.7%, 48.6%, and 57.4%. Health-related quality of life scores were similar between treatment arms. CONCLUSION:Lenvatinib plus pembrolizumab did not improve efficacy versus docetaxel in participants with stage IV NSCLC that progressed on anti‒programmed cell death protein 1 or anti-programmed cell death ligand 1 therapy and platinum-containing chemotherapy. There were no unexpected safety signals. More effective therapies are needed for this patient population.

e20654 Background: Non-small-cell lung cancer (NSCLC) is the most common histological subtype of lung cancer and the leading cause of cancer-related deaths worldwide. Targeted therapies and immunotherapies have significantly increased the treatment options for patients with advanced NSCLC and have also improved their progression-free survival (PFS). In this study molecular profiling in 4088 NSCLC patients, using NGS analysis, reveals actionable mutations in lung cancer and the eligibility of these patients in receiving targeted therapy. Methods: DNA and RNA extraction from embedded paraffin tissue samples was performed, using the Qiasymphony DSP DNA Mini Kit (Qiagen) and the RNeasy FFPE Kit (Qiagen) respectively. Μutation hotspot regions of 27 genes are amplified using a custom DNA panel (Thermo Fisher Scientific). Copy number variations, SNPs, and indels are analysed. Additionally, ALK, ROS1, RET, and NTRK1-3 fusions and expression and MET exon 14 skipping were tested using a custom Fusion Panel (Thermo Fisher Scientific). Sequencing was carried out using the Next Generation Sequencing platform Ion GeneStudio S5 Prime System (Thermo Fisher Scientific). Results : The NGS analysis detected actionable mutations in 92,6% of the tested samples, while 31,4% of these patients were eligible for on label therapy. The most common mutated gene was found to be KRAS (31,8%). The hotspot KRAS mutation G12C was detected in 10,3% of cases and it is associated with response to the FDA approved drugs Sotorasib and Adagrasib. The second most mutated gene was EGFR (12,1%). 11,7% of the patients harbored an EGFR mutation and were eligible for anti-EGFR therapies. Additionally, ALK fusion was detected in 2,2% of patients offering response to on label therapies like Brigatinib and Lorlatinib. Other findings that are associated with on label therapy include BRAF mutations (1,6%), MET exon 14 skipping (1,1%), ERBB2 mutations (0,8%), ROS1 fusions (0,8%) and RET fusions (0,5%). Finally, 61,6% of cases were also tested for PDL-1 expression, and 40,9% of them were predicted to have a positive response to immunotherapy. Notably, 20,8% of PDL-1 positive patients carried a mutation in STK11 gene, which is associated to resistance to immunotherapy. Conclusions: The findings described above underline the necessity of a multigene analysis for patients with NSCLC, in order to benefit from the available targeted therapies. PDL-1 testing increases this benefit as it is a positive predictive biomarker for immunotherapy, even for patients harboring no driver mutations.

BACKGROUND:Tarlatamab, a bispecific delta-like ligand 3-directed T-cell engager immunotherapy, received accelerated approval for the treatment of patients with previously treated small-cell lung cancer. Whether tarlatamab is more effective than chemotherapy in the treatment of patients whose small-cell lung cancer has progressed during or after initial platinum-based chemotherapy is not known. METHODS:We conducted a multinational, phase 3, open-label trial to compare tarlatamab with chemotherapy as second-line treatment in patients with small-cell lung cancer whose disease had progressed during or after platinum-based chemotherapy. Patients were randomly assigned to receive tarlatamab or chemotherapy (topotecan, lurbinectedin, or amrubicin). The primary end point was overall survival. Key secondary end points were investigator-assessed progression-free survival and patient-reported outcomes. Results of the prespecified interim analysis (data-cutoff date, January 29, 2025) are reported. RESULTS:A total of 509 patients were randomly assigned to receive tarlatamab (254 patients) or chemotherapy (255 patients). Treatment with tarlatamab resulted in significantly longer overall survival than chemotherapy (median, 13.6 months [95% confidence interval {CI}, 11.1 to not reached] vs. 8.3 months [95% CI, 7.0 to 10.2]; stratified hazard ratio for death, 0.60; 95% CI, 0.47 to 0.77; P<0.001). Tarlatamab treatment also had a significant benefit with respect to progression-free survival and cancer-related dyspnea and cough as compared with chemotherapy. The incidence of adverse events of grade 3 or higher was lower with tarlatamab than with chemotherapy (54% vs. 80%), as was the incidence of adverse events resulting in treatment discontinuation (5% vs. 12%). CONCLUSIONS:Treatment with tarlatamab led to longer overall survival than chemotherapy among patients with small-cell lung cancer whose disease had progressed during or after platinum-based chemotherapy. (Funded by Amgen; DeLLphi-304 ClinicalTrials.gov number, NCT05740566.).

Objectives: Canakinumab, an interleukin-1 beta inhibitor, previously showed reduced lung cancer incidence and mortality (CANTOS). Here, we compare the efficacy/safety of canakinumab versus placebo in patients with advanced non-small cell lung cancer (NSCLC) who had progressed after platinum-based doublet chemotherapy (PDC) and immunotherapy. Materials and methods: CANOPY-2, a randomized, double-blind, phase 3 trial, enrolled adult patients with stage IIIB/IV NSCLC, without EGFR or ALK alterations, who had received one prior PDC regimen and one prior programmed death-1/programmed death-ligand 1 inhibitor and experienced subsequent disease progression. Patients were randomized to canakinumab plus docetaxel or placebo plus docetaxel. Results: A total of 237 patients were randomly allocated: 120 (51 %) to canakinumab and 117 (49 %) to placebo, stratified by histology and prior lines of therapy. Three patients in the placebo arm did not receive study treatment. The trial did not meet its primary endpoint of overall survival: median 10.6 months (95 % confidence interval [CI], 8.2-12.4) for the canakinumab arm and 11.3 months (95 % CI, 8.5-13.8) for the placebo arm (hazard ratio, 1.06 [95 % CI, 0.76-1.48]; one-sided P-value = 0.633). AEs (any grade) were reported in 95 % of patients in the canakinumab group and in 98 % of patients in the placebo group. Grade 3-4 AEs were experienced by 62 % and 64 % of patients in the canakinumab and placebo groups, respectively, and grade 5 AEs were experienced by 8 % and 5 %. Prespecified, post-hoc subgroup analyses showed that patients with undetected circulating tumor DNA (ctDNA) and/or lower levels (< 10 mg/L) of C-reactive protein (CRP) achieved longer progression-free and overall survival than those with detected ctDNA or higher (>= 10 mg/L) CRP levels. There was no association with treatment arm. Conclusion: Adding canakinumab to docetaxel did not provide additional benefit for patients with advanced NSCLC who had progressed after PDC and immunotherapy.

Purpose of review Despite recent advances in immunotherapy treatment for metastatic, early-stage nonsmall cell lung cancer (NSCLC), palliative, adjuvant, neoadjuvant, and perioperative treatment options, further development is needed. Exploring new frontiers of immuno-oncology is necessary. Researchers are interested in a therapeutic vaccination model. Recent findings In this paper, we provide a review of the latest lung cancer therapeutic vaccines. We describe strategies for antigen selection and delivery platforms. As of 5th of August 2024, we have reviewed ongoing clinical trials and results. We summarize most of the important clinical trials of novel vaccines, the way of action, and available clinical data. We also discuss the pros and cons of various types of therapeutic vaccines. Summary Until recently, clinical trial results were mixed regarding the efficacy of therapeutic vaccines in lung cancer. Developing next-generation sequencing and bioinformatic technologies has helped identify suitable antigens. New personalized vaccines are based on neoantigens specific to unique tumor mutations. Neoantigens, instead of tumor-associated antigens, better delivery systems and adjuvants will improve antigen presentation and immune system activation. Combining these therapeutic vaccines with other therapeutic approaches will improve and prolong the response.

Melanoma is the most aggressive type of skin cancer. Half of melanoma cases are characterized by the mutation BRAF V600. The case presented concerns a 41-year-old patient with locally advanced melanoma, being positive in mutation BRAF V600. The patient underwent surgery and received additional targeted therapy as part of a clinical study. In subsequent disease progression, immunotherapy was used. When the disease progressed again while the patient was in a good performance status, targeted therapy was administered again, and a good response was noted, making the patient reach a statistically significant overall survival, exceeding four years. Targeted therapy has proven to be an important tool in the treatment of melanoma. The use of BRAFi targeted therapy does not exclude the option of readministration at subsequent disease progression (BRAFi rechallenge). Preclinical models suggest that the resistance mechanism of cancer cells to BRAFi therapy bends, as these cell clones lose their evolutionary advantage after stopping BRAFi. Cell clones sensitive to BRAFi may then outcompete, making the treatment effective again. Therapeutical dilemmas in the management of patients with locally advanced melanoma that progresses to metastatic cancer are discussed.

This study primarily aimed to generate real-world evidence (RWE) on the profile and first-line treatment (1LT) patterns of patients with advanced (unresectable Stage III/metastatic) cutaneous melanoma initiated on immuno-oncology (IO)- or targeted therapy (TT)-based 1LT between 1 January 2015 and 1 January 2018 (index period), in routine settings of Greece. This was a multicenter, retrospective chart review study. Eligible consented (unless deceased, for whom consent was waived by the hospital) patients were consecutively included by six oncology clinics. The look-back period extended from informed consent or death to initial melanoma diagnosis. Between 9 Junuary 2021 and 9 February 2022, 225 eligible patients (all Caucasians; 60.4% male; 35.6% diagnosed with de novo advanced melanoma) were included. At 1LT initiation, median age was 62.6 years; 2.7/6.7/90.7% of the patients had Stage IIIB/IIIC/IV disease and 9.3% were unresected. Most frequent metastatic sites were the lung (46.7%), non-regional nodes (33.8%), and liver (20.9%). Among patients, 98.2% had single primary melanoma, 45.6% had disease localized on the trunk, and 63.6% were BRAF-mutant. Of the patients, 45.3% initiated 1LT with an IO-based, 53.3% with a TT-based regimen, and three patients (1.3%) received TT-based followed by IO-based or vice versa. Most common 1LT patterns (frequency ≥10%) were BRAFi/MEKi combination (31.6%), anti-PD-1 monotherapy (25.3%), BRAFi monotherapy (21.8%), and anti-CTLA-4 monotherapy (17.8%). Most frequent regimens were Dabrafenib+Trametinib in 25.3%, and monotherapies with Pembrolizumab/Ipilimumab/Vemurafenib/Dabrafenib in 23.6/17.8/11.1/10.7% of patients, respectively. SUMMER provides RWE on 1LT strategies and profile of patients initiated 1L IO- or TT-based therapy in Greece during the 3-year index period.

Background/Aim: Real-world data on the EGFR mutational profile upon progression after first/second-generation EGFR-TKI treatment in patients with advanced non-small-cell lung cancer (NSCLC) and treatment strategies employed thereon are needed. Patients and Methods: This observational study was conducted in 23 hospital-based lung cancer Centers in Greece (protocol code: D133FR00126). Ninety-six eligible patients were consecutively enrolled between July-2017 and September-2019. Re-biopsy was performed in 18 of 79 patients who tested T790M-negative in liquid biopsy after progression in the first-line (1L) setting. Results: Of the study population, 21.9% tested T790M-positive, while 72.9% proceeded to 2L treatment, mainly comprising of a third -generation EGFR-TKI (48.6%), a switch to chemotherapy (30.0%), or chemo-immunotherapy (17.1%). The objective response rate (ORR) in 2L was 27.9% in T790M-negative and 50.0% in T790M-positive patients. Of evaluable patients, 67.2% experienced disease progression; median progression -free survival (PFS) was 5.7 and 10.0 months among T790M-negative and positive patients, respectively. Among T790M-negative patients, longer median PFS and post-progression survival were observed with third-generation EGFR-TKI treatment. Conclusion: Mutational status and treatment strategy were identified as critical determinants of clinical outcomes in the 2L-setting of EGFR-mutated NSCLC patients in real-world settings in Greece, with early diagnosis, appropriate molecular testing and high-efficacy treatments at first lines positively affecting ORR and PFS.

BACKGROUND Gorlin syndrome, also known as basal cell nevus syndrome (BCNS), nevoid basal cell carcinoma syndrome (NBCCS), and Jaw cyst-Basal cell nevus-Bifid rib syndrome, is a rare multisystemic syndrome that can affect a remarkable number of tissues and organs in the human body. Patients with this syndrome are in jeopardy of developing basal cell skin cancer during puberty or early adulthood. CASE REPORT Herein, we report a case of a 58-year-old woman who had multiple pigmented skin lesions and a palpable tumor of the left scapula. The patient underwent surgical excision of the above-mentioned lesions. The histopathological examination revealed that 10 of them were basal cell skin carcinomas (BCCs); therefore, the patient was proven to have the syndrome. She had a history of similar skin lesions, which were removed before the age of 20. CONCLUSIONS This case highlights that rare phenomena, such as the presence of multiple BCCs, require additional investigations and a multidisciplinary approach since a rare and potentially life-threating condition might be the underlying cause. Early diagnosis of Gorlin syndrome is of paramount importance to facilitate the appropriate therapeutic approach, as directed by a multidisciplinary team. Patients with multiple skin lesions need to have regular assessments by their general practitioner or dermatologist, with dermoscopy serving as an important preventive measure. Furthermore, because pathogenesis of the syndrome is characterized by development of basal cell carcinomas, consecutive follow-up is of a great significance.

Introduction: We have been using cryo-biopsy for endobronchial lesions for lung cancer diagnosis and debulking. Cryo-biopsy is also known to be an excellent tool for diagnosis of lung interstitial disease. Recently cryo-biopsy with the 1.1mm probe was used for lymphnode biopsy.Patients and Methods: 311 patients participated with lymphadenopathy and at least one lung lesion. The following tools were used for diagnosis; 22G Mediglobe Sonotip, 22G Medigolbe, 21G Olympus, 19G Olympus and 1.1mm cryo probe ERBE CRYO 2 system (3 seconds froze). A PENTAX Convex-probe EBUS was used for biopsy guidance.Results: Cell-blocks slices had a higher number in the 19G needle group (19G> Cryo Probe>22G Mediglobe Sonotip >21G Olympus >22G Mediglobe).Conclusion: Cryo biopsy of the lymphnodes is safe with the 1.1mm cryo probe. Further studies are needed in order to evaluate new probes and the technique specifications.

Aim: To retrospectively characterize real-world therapeutic strategies, clinical outcomes and attrition rates with EGFR tyrosine kinase inhibitors (TKIs), before first-line osimertinib approval, in EGFR-mutated advanced/metastatic non-small-cell lung cancer patients in Greece. Results: Among 160 patients, the discontinuation rate for first-line first- or second-generation EGFR-TKIs was 85%; among these patients, 43% did not receive any second-line therapy and 9.4% died during an 18.7-month follow-up period. Median progression-free and overall survival were 12.1 and 20.9 months, respectively. Osimertinib was offered as second- and third-line treatment in 69.6 and 21.7% of patients with the T790M mutation, respectively. Brain metastases were recorded in 10.6% of patients during treatment, with median overall survival of 4.9 months. Conclusion: Given the high attrition rates and the impact of CNS progression, offering the most appropriate first-line EGFR-TKI treatment with CNS penetration is key to maximize outcomes.

Castleman disease constitutes a rare class of lymphoproliferative disorders, with an estimated incidence of 21 to 25 per million patient years. The idiopathic subtype exhibits a significantly diverse clinical presentation, which can imitate many autoimmune, malignant, and infectious diseases. Cutaneous manifestations are uncommon and require in-depth investigation, especially when concurrent lymphadenopathy is present. A 79-year-old female, with a chronic, complicated erysipelas-like lesion, presented with bilaterally enlarged inguinal lymph nodes; after surgical excision, their histopathological examination revealed Castleman disease. Even though it is a benign condition, patients are often predisposed to developing certain types of malignancies, which can deteriorate their prognosis. An accurate and early diagnosis, along with effective treatment and prevention of recurrence, is of utmost importance in order to increase the patients' overall survival and quality of life.

Introduction: Endoscopic techniques have been upgraded in the recent 10 years. We can use the radial endobronchial ultrasound to reach distal nodules in the periphery of the lungs, but also we can use it in order to make biopsies in lesions without endobronchial findings. Patients and Methods: We included in our study 248 patients with pulmonary nodules up to 4 cm. We use a radial endobronchial system from FUJI, a PENTAX bronchoscope and a C-ARM. We recorded the cancer type, biopsy method, time of each procedure, cell blocks and slices from cell blocks. Results: Two thirds of patients belonged to males (61.7%), forceps was the main tissue extraction technique (118, 47.6%) and tumors sized 1 to 2 cm were the most encountered (96, 38.7%). Samples with tissue content were present in 175 patients (70.6%) and one cell block dominated in the samples (109, 43.9%). Less than 20 minutes were needed to complete the operative procedure for the half patients (127, 51.2%), the C-Arm implementation concerned 117 persons (47.2%) and the majority of tumors was located in the central area of the lungs (178, 71.8%). Less time was necessary for central lesions and larger biopsy samples were acquired without the extensive use of C-ARM. Conclusion: The larger the nodule ≥2cm and in periphery the less we use the C-ARM and the time of the procedure is between 20-40 minutes. Moreover; we have more tissue sample and cell block slices.

Background: Recently, the Patras Immunotherapy Score (PIOS) has been developed to estimate the survival benefit of patients with advanced non-small-cell lung cancer (aNSCLC) treated with nivolumab or pembrolizumab. The aim of this study was to validate the clinical value of PIOS in an external cohort of aNSCLC patients. Methods: PIOS is a baseline formula produced by the combination of performance status, body mass index, age and line of treatment. In this multicentre study, 626 patients with confirmed NSCLC pathology, who had been treated with nivolumab or pembrolizumab, as well as 444 patients with aNSCLC, who had been managed with chemotherapy alone, were retrospectively enrolled. Predictive and prognostic values of PIOS were finally evaluated. Results: Patients treated with immunotherapy and higher PIOS score had an improved progression-free survival not only in univariate [hazard ratio (HR) = 0.621, p = 0.001], but also in multivariable analysis (HR = 0.651, p = 0.003). In addition, improved overall survival with increasing PIOS score was also observed (HR = 0.608, p < 0.001) with this association remaining statistically significant after adjusting for programmed-cell death ligand 1 (PD-L1) expression (HR = 0.620, p < 0.001). In addition, patients with disease progression (PD) had lower scores compared to those with stable disease (SD), partial response (PR) or complete response (CR) in a two-tier model ( p < 0.001) as well as in a four-tier model (PD, SD, PR and CR; p < 0.001). Prognostic significance of PIOS score also persisted using a binary logistic regression analysis, adjusted for disease stage and PD-L1 status ( p = 0.002, odds ratio: 0.578). Contrarily, PIOS had no prognostic significance in the chemotherapy group; however, upon combined analysis of the two cohorts, PIOS was found to have a significant interaction with the type of treatment (HR = 0.066 with p < 0.001), confirming its predictive value for immunotherapy. Conclusions: This study provides further validation of PIOS in aNSCLC patients treated with anti-PD-1 monotherapy.