RESUMEN
BACKGROUND: Thymic carcinoma (TC) is a rare tumor with aggressive behavior. Chemotherapy with carboplatin plus paclitaxel represents the treatment of choice for advanced disease. Antiangiogenic drugs, including ramucirumab, have shown activity in previously treated patients. The RELEVENT trial was designed to evaluate the activity and safety of ramucirumab plus chemotherapy as first-line treatment in advanced TC. PATIENTS AND METHODS: This phase II trial was conducted within the Italian TYME network. Eligible patients had treatment-naïve advanced TC. They received ramucirumab, carboplatin and paclitaxel for six cycles, followed by ramucirumab maintenance until disease progression or intolerable toxicity. Primary endpoint was objective response rate (ORR) according to RECIST v1.1 as assessed by the investigator. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Centralized radiologic review was carried out. RESULTS: From November 2018 to June 2023, 52 patients were screened and 35 were enrolled. Median age was 60.8 years, 71.4% of patients were male and 85.7% had Masaoka-Koga stage IVB. The Eastern Cooperative Oncology Group performance status was 0 in 68.5% and 1 in 31.4% of patients. At the present analysis carried out some months after the interim analysis (earlier than expected) on 35 patients, ORR was 80.0% [95% confidence interval (CI) 63.1% to 91.6%]. At the centralized radiological review of 33/35 assessable patients, ORR was 57.6% (95% CI 39.2% to 74.5%). After a median follow-up of 31.6 months, median PFS was 18.1 months (95% CI 10.8-52.3 months) and median OS was 43.8 months (95% CI 31.9 months-not reached). Thirty-two out of 35 patients (91.4%) experienced at least one treatment-related adverse event (AE), of which 48.6% were AE ≥ grade 3. CONCLUSIONS: In previously untreated advanced TC, the addition of ramucirumab to carboplatin and paclitaxel showed the highest activity compared to historical controls, with a manageable safety profile. Despite the small number of patients, given the rarity of the disease, the trial results support the consideration of this combination as first-line treatment in TC.
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BACKGROUND: Information about the adherence to scientific societies guidelines in the 'real-world' therapeutic management of oncological patients are lacking. This multicenter, prospective survey was aimed to improve the knowledge relative to 2017-2018 recommendations of the Italian Association of Medical Oncology (AIOM). PATIENTS AND METHODS: Treatment-naive adult patients with pancreatic adenocarcinoma were enrolled. Group A received adjuvant therapy, group B received primary chemotherapy, and group C had metastatic disease. The results on patients accrued until 31 October 2019 with a mature follow-up were presented. RESULTS: Since July 2017, 833 eligible patients of 923 (90%) were enrolled in 44 Italian centers. The median age was 69 years (range 36-89 years; 24% >75 years); 48% were female; 93% had Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; group A: 16%, group B: 30%; group C: 54%; 72% Nord, 13% Center, 15% South. In group A, guidelines adherence was 68% [95% confidence interval (CI) 59% to 76%]; 53% of patients received gemcitabine and 15% gemcitabine + capecitabine; median CA19.9 was 29 (range 0-7300; not reported 15%); median survival was 36.4 months (95% CI 27.5-47.3 months). In group B, guidelines adherence was 96% (95% CI 92% to 98%); 55% of patients received nab-paclitaxel + gemcitabine, 27% FOLFIRINOX, 12% gemcitabine, and 3% clinical trial; median CA19.9 was 337 (range 0-20220; not reported 9%); median survival was 18.1 months (95% CI 15.6-19.9 months). In group C, guidelines adherence was 96% (95% CI 94% to 98%); 71% of patients received nab-paclitaxel + gemcitabine, 16% gemcitabine, 8% FOLFIRINOX, and 4% clinical trial; liver and lung metastases were reported in 76% and 23% of patients, respectively; median CA19.9 value was 760 (range 0-1374500; not reported 9%); median survival was 10.0 months (95% CI 9.1-11.1 months). CONCLUSIONS: The GARIBALDI survey shows a very high rate of adherence to guidelines and survival outcome in line with the literature. CA19.9 testing should be enhanced; nutritional and psychological counseling represent an unmet need. Enrollment to assess adherence to updated AIOM guidelines is ongoing.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adulto , Humanos , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Neoplasias Pancreáticas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Estudios Prospectivos , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/etiología , Carcinoma Ductal Pancreático/patología , Gemcitabina , Neoplasias PancreáticasRESUMEN
BACKGROUND: Malignant pleural mesothelioma (MPM) is a cancer with a high mortality rate and few therapeutic options. After platinum-pemetrexed combination, no further promising drug seems to be effective. Immune checkpoint inhibitors may have some activity in pretreated patients and no data are available in this population about durvalumab. MATERIALS AND METHODS: DIADEM was a multicenter, open-label, single-arm, phase II trial aimed at evaluating the efficacy and safety of durvalumab. Patients with locally advanced/metastatic MPM who progressed after platinum-pemetrexed chemotherapy were enrolled to receive durvalumab (1500 mg, intravenously Q4W) for 12 months or until evidence of disease progression or unacceptable toxicity. The primary endpoint was the proportion of patients alive and free from progression at 16 weeks (PFS16wks) calculated from treatment initiation. Secondary endpoints were progression-free survival, overall survival, overall response rate, and safety. RESULTS: Sixty-nine patients with a median age of 69 years (range 44-82 years) were enrolled; 62 patients (89.9%) had epithelioid histotype. As first-line treatment, all patients received platinum derivatives-pemetrexed combination (60.9% with carboplatin and 39.1% with cisplatin). As of March 2021, the median follow-up was 9.2 months (interquartile range 5.2-11.1 months). Six patients (8.7%) completed the 12-month treatment; 60 patients discontinued, of whom 42 for progressive disease, and 4 died. Seventeen patients (28.3%; 95% confidence interval 17.5% to 41.4%) were alive or free from progression at 16 weeks. Eleven patients (18.6%) had a grade 3 or 4 treatment-related adverse event (AE), and one (1.4%) had a grade ≥3 immune-related, treatment-related AE. There was one drug-related death. CONCLUSION: Durvalumab alone in pretreated non-selected MPM did not reach a meaningful clinical activity, showing any new major safety issue signals.
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Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Mesotelioma Maligno/tratamiento farmacológico , Mesotelioma Maligno/etiología , Pemetrexed/farmacología , Pemetrexed/uso terapéutico , Mesotelioma/patología , Platino (Metal)/uso terapéutico , Neoplasias Pleurales/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Immunotherapy has dramatically changed the therapeutic scenario in treatment naïve advanced non-small cell lung cancer (NSCLC). While single agent pembrolizumab has become the standard therapy in patients with PD-L1 expression on tumor cellsâ¯≥â¯50%, the combination of pembrolizumab or atezolizumab and platinum-based chemotherapy has emerged as an effective first line treatment regardless of PD-L1 expression both in squamous and non-squamous NSCLC without oncogenic drivers. Furthermore, double immune checkpoint inhibition has shown promising results in treatment naïve patients with high tumor mutational burden (TMB). Of note, the presence of both negative PD-L1 expression and low TMB may identify a subgroup of patients who has little benefit from immunotherapy combinations and for whom the best treatment option may still be platinum-based chemotherapy. To date, first-line single agent immune checkpoint blockade has demonstrated limited activity in EGFR mutated NSCLC and the combination of immunotherapy and targeted agents has raised safety concerns in both EGFR and ALK positive NSCLC patients. Finally, in EGFR mutated or ALK rearranged NSCLC, atezolizumab in combination with platinum-based chemotherapy and bevacizumab is emerging as a potential treatment option upon progression to first line tyrosine kinase inhibitors.
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Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/terapia , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antígeno B7-H1/metabolismo , Bevacizumab/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Humanos , Factores Inmunológicos/metabolismo , Inmunoterapia/métodos , Neoplasias Pulmonares/metabolismoRESUMEN
Multinucleated cells in the retinal pigment epithelium of the albino rat are shown with the scanning electron microscope beside normal mononucleated cells. We suggest that such elements are formed during foetal life, owing to the absence of any mitotic activity in adult rats.
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Epitelio Pigmentado Ocular/ultraestructura , Animales , Núcleo Celular/ultraestructura , Citoplasma/ultraestructura , Microscopía Electrónica de Rastreo , RatasAsunto(s)
Ritmo Circadiano , Órgano Eléctrico/ultraestructura , Glándula Pineal/ultraestructura , Retina/ultraestructura , Vesículas Sinápticas/ultraestructura , Animales , Humanos , Microscopía Electrónica , Polimorfismo Genético , Vesículas Sinápticas/fisiología , Vestíbulo del Laberinto/ultraestructuraRESUMEN
Synaptic ribbons of the outer plexiform layer in the retina of albino rats are examined, with particular regard to their ultrastructure and to their chronobiological behaviour. As to the ultrastructure, aside from the typical lamellar and granular morphology, synaptic ribbons, whose central bar is roundish and granular, delaminate or furnished with enlarged extremities, are shown. As to the chronobiological pattern, synaptic ribbons undergo to circadian changes in their absolute number, being particularly numerous during the light phase, and few during darkness. It is also considered the morphology (ratio between granular and lamellar) and the size (long, intermediate and short) during the 24-hour cycle; in both cases, diphasic curves are observed. On the basis of these results, in the junction photoreceptors-bipolar cells, synaptic ribbons are polymorphic, dynamic structures, whose number and morphology strictly depend on environmental light conditions.