A systematic review and meta-analysis of trials assessing PD-1/PD-L1 immune checkpoint inhibitors activity in pre-treated advanced stage malignant mesothelioma.

INTRODUCTION: Advanced stage malignant mesothelioma (asMM) patients have poor prognosis. Several trials investigated the role of programmed cell death protein-1 (PD-1) and its ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) in pre-treated asMM. METHODS: A systematic review of the literature of clinical trials testing single-agent anti PD-1/PD-L1 ICIs in pre-treated asMM was performed. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) data were extracted. The predictive role of PD-L1 was assessed. RESULTS: We selected 13 studies including 888 patients. ORR and DCR were 18.1% (95% confidence interval [CI] 13.9-22.8%) and 55.4% (95% CI: 48.1-62.5%), respectively. Median PFS and OS ranged from 2.1 to 5.9 and from 6.7 to 20.9 months, respectively. ORR according to PD-L1 was 27.0% (95% CI: 18.7-36.2%). CONCLUSIONS: Anti-PD-(L)1 ICIs might be considered a treatment option for chemotherapy-resistant asMM, even if reliable predictive factors are still lacking.

Italian survey on the clinical management of non-small cell lung cancer patients during the COVID-19 pandemic: A lesson for the second wave.

This study investigated the clinical management of non small cell lung cancer (NSCLC) patients during the first wave of coronavirus disease 2019 (COVID-19) outbreak in Italy. A 29-questions survey was sent to 95 Italian thoracic oncologists, with 77 % of them declaring significant changes in the outpatients management and treatment. The results of this survey pointed out a significant delay of lung cancer diagnosis along with a relevant reduction of patients' accrual within clinical trials. Telemedicine emerged as a valid support for patient-healthcare interactions. Therapeutic indications followed the guidelines for adjuvant chemotherapy and concurrent chemo-radiation. Clinical indications to first-line therapies were largely confirmed, while major changes regarded the selection of second line treatment options as well as the management of elderly population. This work may represent a valid source of information to improve the clinical management of NSCLC patients during second wave of COVID-19 pandemic.

SARS-CoV-2 Infection in Cancer Patients: A Picture of an Italian Onco-Covid Unit.

Background: The world, and Italy on the front lines, has experienced a major medical emergency due to the novel coronavirus outbreak. Cancer patients are one of the potentially most vulnerable cohorts of people, but data about their management are still few. Patients and Methods: In this monocentric retrospective study we included all SARS-CoV-2 oncological patients accepted, between March 27th and April 19th 2020, at the Onco-COVID Unit at San Luigi Gonzaga Hospital, one of the few Italian oncological-COVID wards. Data were obtained from medical records. Results: Eighteen cancer patients with COVID-19 were included. The mean (±SD) age of patients was 67 ± 14 years, 89% were men. Seven (39%) developed infection in communities and 11 (61%) during hospitalization. Lung cancer was the most frequent type of cancer (10, 56%). Seven patients (39%) were symptomatic for COVID-19 at the time of diagnosis and symptoms began 2 (±2) days before. The most common were shortness of breath and diarrhea. Fever was present in 5 patients (28%). Among the 11 asymptomatic patients, 8 (73%) became symptomatic during the hospitalization (mean time of symptoms onset 4 days ±4). Six patients (33%) were on active anti-tumor treatment: 2 (33%) received anti-tumor therapy within 2 weeks before the infection diagnosis and 2 (33%) continued oncological treatment after SARS-CoV-2 positivity. Eight (44%) patients died within a mean of 12 days (±8) from the infection diagnosis. Conclusions: Our series confirms the high mortality among cancer patients with COVID-19. The presence of asymptomatic cases evidences that typical symptoms and fever are not the only parameters to suspect the infection. The Onco-Covid unit suggests the importance of a tailored and holistic approach, even in this difficult situation.

Transfection of human monocyte-derived dendritic cells with native tumor DNA induces antigen-specific T-cell responses in vitro.

OBJECTIVE: Nucleofection of genomic tumor (Tu) DNA into human monocyte-derived dendritic cells (hMoDC) was evaluated for use in producing anti-tumor vaccines able to induce effective T-cell specific immune responses. METHODS: Cultured hMoDC obtained from HLA-A2+ normal donors were nucleofected with genomic DNA extracted from an HLA-A2+gp100+ Mel 526 cell line and 3' end-labeled with biotinylated TdT nucleotides or from a genetically-modified Mel 526 expressing enhanced green fluorescent protein (EGFP). An Amaxa Nucleofector system was used for electroporation. Nucleofected hMoDC were matured in the presence of cytokines and examined in ELISPOT assays for the ability to present the gp100(209-217) epitope to epitope-specific T cells or to prime autologous naïve T cells in culture. RESULTS: The nucleofected hMoDC presented gp100 protein to HLA-A2+gp 100-specific T cells as observed in IFN-gamma ELISPOT assays. Spot formation was inhibited by anti-HLA class I and HLA-A2 but not anti-HLA class II antibodies (Abs). Tu DNA-nucleofected hMoDC also primed nasmall yi, Ukrainianve autologous peripheral blood T cells in culture to develop into Tu-reactive effector cells (CTL). These CTL recognized Tu cells which had donated genomic DNA, and these responses were MHC class I- and class II-restricted. The CTL recognized shared Tu antigens encoded in Tu-derived DNA. CONCLUSION: Nucleofection of hMoDC with genomic Tu-derived DNA is a useful strategy for Tu vaccine production: it is feasible, does not require Tu epitope isolation, can be used when few Tu cells are available, and avoids Tu-induced DC suppression.

Paclitaxel and carboplatin in neo-adjuvant and concomitant chemoradiotherapy in locally advanced head and neck squamous cell carcinoma.

AIM AND BACKGROUND: To evaluate feasibility of neoadjuvant chemotherapy (NA-CT) followed by CT + radiotherapy (RT) in locally advanced or unresectable head and neck squamous cell carcinoma (HNSCC). METHODS: 22 HNSCC patients were enrolled (18 males, 4 females; median age, 59.5 years; median ECOG PS, 1). Sites of disease: oral cavity, 18.2%; oropharynx, 40.9%; hypopharynx, 18.2%; larynx, 4.6%, multiple sites, 18.2%. T (tumor) category: T2, 13.6%; T3, 31.8%; T4, 54.5%. N (nodes) category: NO, 9.1%; N1, 18.1%; N2, 40.9%; N3, 31.8%. Stage: III, 4.6%; IVA, 63.6%; IVB, 31.8%. Induction carboplatin (AUC = 6) and paclitaxel (200 mg/m2) x 3 cycles (q21 days) were given. Responders received definitive radiotherapy with concurrent carboplatin (35 mg/m2/day from days 1 to 5 in weeks 1, 3, 5 and 7) and paclitaxel (50 mg/m2 on days 10, 24 and 38). Patients with node involvement were suggested to undergo postradiotherapy neck dissection. RESULTS: NA-CT. 97% of planned chemotherapy cycles were administered. Prevalent toxicity was hematologic: 50% G4 neutropenia and 31.8% G3, one neutropenic fever. All patients had alopecia. Complete responses in T and N were 4 (18.2%) and 3 (15%), respectively. Partial responses were 13(59%) and 9 (45%). There was 1 progressive disease. CT + RT. 79.9% of planned cycles of CT were administered. In 19 patients (86.4%) more than 50% of planned cycles of CT were completed. Median dose of RT was 70.2 Gy on T/N+ and 54 Gy on NO. Limiting toxicity was mucositis in 77.3%, followed by neutropenia (59.1% G3-G4). Median weight loss was 4.9%.18.2% of patients required hospitalization. Complete responses in T and N were 15 (68.1%) and 8 (40%), respectively. Partial responses were 5 (22.7%) and 7 (35%). CONCLUSIONS: The preliminary results of this study are encouraging, despite the toxicity. Adequate follow-up is required to evaluate efficacy in terms of local-regional control and overall survival.