An extranodal NK/T cell lymphoma, nasal type, with specific immunophenotypic and genotypic features

Extranodal NK/T cell lymphoma, ‘nasal type,’ is a rare clinicopathological entity in Europe. The main clinical features are nasal congestion, sore throat, dysphagia and epistaxis, due to a destructive mass involving the midline facial tissues. Pathologically, lymphoma cells exhibit angioinvasion, angiodestruction and coagulative necrosis. We report the case of a patient who presented with fever, dyspnea, nasal congestion, headache, distention of right nasal turbinates and exophytic lower leg ulcerating lesions. A CT scan of visceral scull demonstrated a filling mass of right frontal, ethmoidal and maxillary sinuses with erosion of the wall of right maxillary sinus and ventral portion of the diaphragm. A biopsy was performed in the skin lesion and showed an angioinvasive NK/T cell lymphoma CD56 negative with clonal rearrangement of the T-cell-receptor gamma gene. Up to our knowledge, this is a rare immunophenotype for NK/T-cell, ‘nasal type,’ lymphomas. However, the lymphoma may be classified as extranodal NK/T cell lymphoma, ‘nasal type,’ due to typical clinical presentation, radiologic findings and pathological characteristics of polymorphism, angioinvasion, angiodestruction and coagulative necrosis

Prognostic Role of Circulating Tumor Cells in Patients with Metastatic Castration-Resistant Prostate Cancer Receiving Cabazitaxel: A Prospective Biomarker Study

Rational: Circulating tumor cells (CTCs) appear to be a promising tool for predicting the clinical outcome and monitoring the response to treatment in patients with solid tumors. The current study assessed the clinical relevance of monitoring CTCs in patients with metastatic castration resistant prostate cancer (mCRPC) treated with cabazitaxel. Patients and Methods: Patients with histologically confirmed mCRPC who were previously treated with a docetaxel-containing regimen and experienced disease progression were enrolled in this multicenter prospective study. CTC counts were enumerated using the CellSearch system at baseline (before cabazitaxel initiation), after one cabazitaxel cycle (post 1st cycle) and at disease progression (PD). Patients were stratified into predetermined CTC-positive and CTC-negative groups. The phenotypic characterization was performed using double immunofluorescence staining with anti-CKs and anti-Ki67, anti-M30 or anti-vimentin antibodies. Results: The median PFS and OS were 4.0 (range, 1.0–17.9) and 14.5 (range, 1.2–33.9) months, respectively. At baseline, 48 out of 57 (84.2%) patients had ≥1 CTCs/7.5 mL of peripheral blood (PB) and 37 (64.9%) had ≥5 CTCs/7.5 mL of PB. After one treatment cycle, 30 (75%) out of the 40 patients with available measurements had ≥1 detectable CTC/7.5 mL of PB and 24 (60%) ≥ 5CTCs/7.5 mL of PB; 12.5% of the patients with detectable CTCs at the baseline sample had no detectable CTCs after one treatment cycle. The detection of ≥5CTCs/7.5 mL of PB at baseline and post-cycle 1 was associated with shorter PFS and OS (p = 0.002), whereas a positive CTC status post-cycle 1 strongly correlated with poorer OS irrespective of the CTC cut-off used. Multivariate analysis revealed that the detection of non-apoptotic (CK+/M30−) CTCs at baseline is an independent predictor of shorter OS (p = 0.005). Conclusions: In patients with mCRPC treated with cabazitaxel, CTC counts both at baseline and after the first cycle retain their prognostic significance, implying that liquid biopsy monitoring might serve as a valuable tool for predicting treatment efficacy and survival outcomes

A Real-World, Observational, Prospective Study to Assess the Molecular Epidemiology of Epidermal Growth Factor Receptor (EGFR) Mutations upon Progression on or after First-Line Therapy with a First- or Second-Generation EGFR Tyrosine Kinase Inhibitor in EGFR Mutation-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer: The ‘LUNGFUL’ Study

Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform cobas®EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings

A Real-World, Observational, Prospective Study to Assess the Molecular Epidemiology of Epidermal Growth Factor Receptor (EGFR) Mutations upon Progression on or after First-Line Therapy with a First- or Second-Generation EGFR Tyrosine Kinase Inhibitor in EGFR Mutation-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer: The `LUNGFUL' Study

Simple Summary Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases, with few patients carrying driver mutations in the gene encoding for epidermal growth factor receptor (EGFR). Advances in translational research have established EGFR tyrosine kinase inhibitors (TKIs) as the standard first-line therapy for NSCLC patients with activating EGFR mutations. The aim of our observational study was to assess the frequency of T790M acquired resistance and predictors of its presence, in patients with EGFR-mutated locally advanced or metastatic NSCLC who have progressed in the first-line EGFR-TKI treatment setting with first- or second-generation TKIs and have undergone molecular testing in tissue and/or plasma biopsy. The study highlights the challenges of performing tissue re-biopsy in routine care settings, which can lead to patients considered non-eligible for certain therapies from which they can benefit, and merits further actions from the healthcare community, in order to establish re-biopsy as a standard procedure. Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform cobas EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (>= 2) ECOG performance status and longer (>= 10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings

Observational Study of Clinical Practice in Patients with Pancreatic Adenocarcinoma in Greece

Background. During the last decade, significant improvement was made in systemic therapy of pancreatic adenocarcinoma (PAC). The impact of this progress in everyday clinical practice has not been fully described yet. The aim of the study was to investigate the pattern followed by Greek Medical Oncologists regarding the treatment of patients with PAC. Methods. This observational, noninterventional multicenter study recorded clinical data from the files of 200 active patients (alive and under treatment or follow-up) for a two-year period (November 2015 until November 2017) from 20 oncology centers around Greece. Results. In total, 51 (25.5%) patients underwent radical surgical resection of PAC, and 40 (78.4%) of them received adjuvant and 1 (2.0%) neoadjuvant chemotherapy. The median time to recurrence was 7.9 months, and median overall survival (OS), 20.2 months. First-line chemotherapy was administered to 193 (96.5%) patients. The majority of patients were treated with the combination of nab-paclitaxel-gemcitabine (NPG), 5-fluorouracil, leucovorin, irinotecan, oxaliplatin (FOLFIRINOX), or gemcitabine monotherapy. Of them, 39.5% responded to the treatment. Median OS and PFS were 14.1 months and 7.0 months, respectively. Second-line treatment was administered to 112 patients. The majority received NPG, FOLFIRINOX/capecitabine, oxaliplatin, irinotecan (CAPOXIRI), or 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX)/capecitabine, oxaliplatin (CAPOX). Median OS with second-line treatment was 8.6 months, and median PFS, 5.5 months. The most common chemotherapy sequences were NPG as first-line followed by FOLFIRINOX/CAPOXIRI as second-line, NPG followed by FOLFOX/CAPOX, NPG followed by other regimens, and FOLFIRINOX/CAPOXIRI followed by NPG. Conclusion. This study described the significant improvement in prognosis of PAC patients receiving palliative chemotherapy and the relatively high rate of receipt of second-line chemotherapy, according to real-world data. However, due to the nonrandomized nature of the study, any comparison between different chemotherapy regimens should be regarded with caution