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• Localised recurrent glioblastoma (recGBM) should be considered for local treatment. • An overview on the use of reirradiation or second surgery in recGBM is herein provided. • A simple and practical algorithm to choose surgery versus RT for recGBM is proposed. • Estimation of life expectancy, prognostic score systems and predictive factors, and expected toxicity are its keypoints. In case of circumscribed recurrent glioblastoma (rec-GBM), a second surgery (Re-S) and reirradiation (Re-RT) are local strategies to consider. The aim is to provide an algorithm to use in the daily clinical practice. The first step is to consider the life expectancy in order to establish whether the patient should be a candidate for active treatment. In case of a relatively good life expectancy (>3 months) and a confirmed circumscribed disease(i.e. without multiple lesions that are in different lobes/hemispheres), the next step is the assessment of the prognostic factors for local treatments. Based on the existing prognostic score systems, patients who should be excluded from local treatments may be identified; based on the validated prognostic factors, one or the other local treatment may be preferred. The last point is the estimation of expected toxicity, considering patient-related, tumor-related and treatment-related factors impacting on side effects. Lastly, patients with very good prognostic factors may be considered for receiving a combined treatment. [ABSTRACT FROM AUTHOR]

International and national oncology societies had released recommendations in favor of COVID-19 vaccination in cancer patients. In the context of the national vaccination campaign targeting the so called extremely vulnerable, we aimed to assess the safety and efficacy of the mRNA vaccines in a cohort of 623 patients. Between March 26 and April 04, 2021, the Pfizer and BioNTech BNT162b2 mRNA and the Moderna mRNA-1273 vaccines were given as a two-dose prime-boost regimen. Starting on September 25th 2021 a third dose was offered to patients in whom a suboptimal immunogenicity with COVID-19 vaccination could be expected. Safety assessments were performed by phone call 7 days after each dose. Electronic health records were accessed to review demographic information, disease history, treatment detail, and outcome events of participants patients'. No toxicities were reported in 63.7%, 54%, and in 48.7% patients with cancer after each dose. Mild-to-moderate pain at the injection site was the most commonly adverse event. After the second dose, 46% of the 610 patients reported toxicity, with more systemic side-effects observed. Fever was reported in 45% of patients, with a temperature ≥ 38 °C in 21.4% of them. Of the 335 patients receiving a third vaccine dose, 51% reported toxicity, with 13% of patients reporting more than one effect. Logistic regression analysis reported mixed results, with limited variables or categories reporting a significant odd ratio. The type of vaccine reported a significant value at first dose (OR = 0.12; CI 0.52, 0.26; p = 0.00). Thirty-four cases of COVID-19 infection were reported with only one patient requiring a short-term hospitalization for monitoring. The safety profile of the mRNA vaccines does not raise any specific concerns and support prioritization of vaccination for cancer patients. • COVID-19 vaccination is recommended in patients with cancer. • We observed a first dose-refusal rate of 4.5%. • No safety concerns have emerged in our cohort of patients. • After two-dose prime-boost vaccination 6 cases of COVID-19 infection were reported. [ABSTRACT FROM AUTHOR]

Brain metastases (BrMs) are associated with significant morbidity and are found in up to 50% of patients with advanced non-small cell lung cancer (NSCLC). Most of the literature focuses on symptomatic BrMs, with a lack of baseline brain imaging in asymptomatic patients. Unfortunately, much of the data on local treatments with or without systemic treatment is retrospective. Clinical trials of systemic treatments largely exclude patients with BrMs. Chemotherapy is an active treatment for BrM with response rates in the brain similar to other sites of disease. Targeted systemic treatments in patients with driver mutations (EGFR and ALK-MET to date) have impressive central nervous system (CNS) penetrance and response rates. Unfortunately, no prospective data can currently guide the timings or modality of local therapies with systemic treatments in these patients who have a high incidence of CNS disease, but retrospective data suggest that early local therapies may give better intracranial progression-free survival (ICPFS). Recent immunotherapy trials have included patients with BrMs. These patients have largely been pre-treated with local therapies and are asymptomatic. Thus, the current standard is becoming, early local therapies before or in conjunction with immunotherapy agents. The approach seems to be safe. Prospective studies are needed in NSCLC BrMs patients to make sure any benefit from local therapies on the ICPFS and quality of life is not overlooked. Here we report what we think are reasonable conclusions from the available data and make suggestions for future clinical trials in the management of NSCLC BrMs. • Brain metastases occur in 30% of patients with advanced NSC lung cancer. This percentage can be higher in those with driver mutations. • Whether asymptomatic disease progresses to symptomatic disease is not known. • We do not know if asymptomatic disease should be treated early. • There are many reported series of patients, but most are retrospective with mixed patient populations. • Prospective CTs are needed to ensure we are not missing benefit from addition of local therapy to systemic therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: As of today, salvage surgery regarding head and neck cancer remains a challenge for patients, surgeons, and oncologists. Indeed, even though several advances have been made in the last few years, the results in terms of both survival and complications are disappointing. Therefore, it remains important to be aware of the latest emerging techniques and understand their limits to make progress in this field. In addition, the patient's conditions play a major role in the outcome of salvage surgery, so identifying the various factors influencing the results can help improve these approaches. This review will walk us through the latest literature on salvage surgery, and it will help us understand the several difficulties touching this last treatment resort. Salvage surgeries of head and neck cancer are often complicated and do not always show decent results. This type of procedure is tough on the patient, as many crucial organs can be affected. A long period of reeducation usually follows the surgery because of the need to rehabilitate functions such as speech or swallowing. In order to lighten the journey of the patients, it is important to develop new technologies and techniques to ease the surgery and limit its damages. This seems even more crucial since progress has been made in the past years, allowing more salvage therapy to take place. This article aims at showing the available tools and procedures for salvage surgeries, such as transoral robotic surgery, free-flap surgery, sentinel node mapping, and many others, that help the work of the medical team to operate or obtain a better understanding of the status of the cancer when taken in charge. Yet, the surgical procedure is not the only thing determining the outcome of the operation. The patient themself and their cancer history also play an important part in the care and must be acknowledged. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is characterized by a broad spectrum of clinical symptoms. After acute infection, some subjects develop a post-COVID-19 syndrome known as long-COVID. This study aims to recognize the molecular and functional mechanisms that occur in COVID-19 and long-COVID patients and identify useful biomarkers for the management of patients with COVID-19 and long-COVID. Here, we profiled the response to COVID-19 by performing a proteomic analysis of lymphocytes isolated from patients. We identified significant changes in proteins involved in iron metabolism using different biochemical analyses, considering ceruloplasmin (Cp), transferrin (Tf), hemopexin (HPX), lipocalin 2 (LCN2), and superoxide dismutase 1 (SOD1). Moreover, our results show an activation of 5-lipoxygenase (5-LOX) in COVID-19 and in long-COVID possibly through an iron-dependent post-translational mechanism. Furthermore, this work defines leukotriene B4 (LTB4) and lipocalin 2 (LCN2) as possible markers of COVID-19 and long-COVID and suggests novel opportunities for prevention and treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: The treatment of advanced NSCLC patients unfit for a platinum combination is challenging and no clear evidence is available. We retrospectively collected data on advanced NSCLC not receiving a first-line platinum combination, focusing on clinical selection criteria. Up to 30% of newly diagnosed advanced EGFR/ALK negative and PD-L1 < 50% NSCLC patients do not receive a first-line platinum doublet. Main clinical selection criteria were older age (>70 years), comorbidities and poor performance status. A single agent chemotherapy was offered with the prevalence of oral metronomic vinorelbine. In the whole population, progression-free survival and overall survival ranged from 4.5 to 5 months and from 9 to 10.5 months, respectively. Limited evidence is available concerning the selection criteria and the outcomes of platinum unfit newly diagnosed advanced NSCLC patients receiving single-agent chemotherapy. We retrospectively collected data on consecutive, stage IIIB-IV, EGFR/ALK negative and PD-L1 < 50% NSCLC patients treated with first-line single agent chemotherapy. Baseline characteristics, outcome measures and toxicities were recorded, as well as criteria according to which treatment selection was made and what percentage of patients did not receive a first-line platinum-based chemotherapy. Two-hundred and twenty-one patients were included. Median age was 79 (range 56–92) years, M/F 165(74.6%)/56(25.4%), ECOG performance status (PS) 0/1/ ≥ 2 23(10.9%)/94(42.5%)/103(46.6%), with a median of two serious comorbidities. A median of 25% (range 10%-30%) of newly diagnosed NSCLC did not receive a first-line platinum combination. Clinical criteria according to which decision was made were older age (76.5%), comorbidities (72%), poor PS (55.2%) and familiar or social issues (10%). Single-agent treatment consisted of oral metronomic vinorelbine (MetV 78.6%), gemcitabine (Gem 10%), oral standard vinorelbine (Vin 8.2%) and other (O 3.2%). Median progression-free survival (PFS) and overall survival (OS) of single agent treatments ranged from 4.5 to 5 months and from 9 to 10.5 months, respectively. All grade toxicities did not differ among single agents, while grade 3–4 toxicities were less frequent with MetV. Up to 30% of newly diagnosed advanced EGFR/ALK negative and PD-L1 < 50% NSCLC patients do not receive a first-line platinum doublet. Main clinical selection criteria were older age (>70 years), comorbidities and poor PS. An oral treatment was frequently proposed with MetV being the most frequent choice according to its safety profile. [ABSTRACT FROM AUTHOR]

Concurrent chemotherapy and radiotherapy (cCRT) is considered the standard treatment of locally advanced non-small cell lung cancer (LA-NSCLC). Unfortunately, management is still heterogeneous across different specialists. A multidisciplinary approach is needed in this setting due to recent, promising results obtained by consolidative immunotherapy. The aim of this survey is to assess current LA-NSCLC management in Italy. From January to April 2018, a 15-question survey focusing on diagnostic/therapeutic LA-NSCLC management was sent to 1,478 e-mail addresses that belonged to pneumologists, thoracic surgeons, and radiation and medical oncologists. 421 answers were analyzed: 176 radiation oncologists, 86 medical oncologists, 92 pneumologists, 64 thoracic surgeons and 3 other specialists. More than a half of the respondents had been practicing for >10 years after completing residency training. Some discrepancies were observed in clinical LA-NSCLC management: the lack of a regularly planned multidisciplinary tumor board, the use of upfront surgery in multistation stage IIIA, and territorial diffusion of cCRT in unresectable LA-NSCLC. Our analysis demonstrated good compliance with international guidelines in the diagnostic workup of LA-NSCLC. We observed a relationship between high clinical experience and good clinical practice. A multidisciplinary approach is mandatory for managing LA-NSCLC. [ABSTRACT FROM AUTHOR]

• Data on immunoresponse to COVID vaccines in patients treated with exclusive radiotherapy are scarce. • MORA trial analyzed immune response after second and third dose of mRNA vaccines. • Breast site and comorbidity influenced the seroconversion rate after second dose. • Type of vaccine and site were associated with lower IgG titers after third dose. • Three mRNA vaccine doses guaranteed robust humoral response and clinical protection from severe disease. Data on immunoresponse after SARS-CoV-2 vaccines for patients treated with exclusive radiotherapy (RT) are scarce. Since RT may affect the immune system, we conducted the MORA trial (Antibody response and cell-mediated immunity of MOderna mRNA-1273 vaccine in patients treated with RAdiotherapy). Data regarding humoral and cellular immune response of patients treated with RT were prospectively collected after the second and third dose of mRNA vaccines. Ninety-two patients were enrolled. With a median of 147 days after the second dose, the median SARS-CoV-2 IgG titer was 300 BAU/mL: six patients were seronegative (Spike IgG titer ≤ 40 BAU/mL), whereas 24, 46 and 16 were poor responders (Spike IgG titer:41–200 BAU/mL), responders (Spike IgG titer:201–800 BAU/mL) and ultraresponders (Spike IgG titer > 800 BAU/mL), respectively. Among seronegative patients, two patients were negative also for cell mediated response, as tested with IFN-γ release Assay (IGRA) test. With a median of 85 days after the third dose, the median SARS-CoV-2 IgG titer was 1632 BAU/mL in 81 patients: only two patients were seronegative, whereas 16 and 63 patients were responders and ultraresponders, respectively. Among the 2 persistently seronegative patients, IGRA test was negative in one who had previously received anti-CD20 therapy. Documented paucisymptomatic (n = 3) or asymptomatic (n = 4) infection occurred after the third dose, during the Omicron wave. In patients treated with exclusive RT, even during the Omicron breakthrough, robust humoral response and clinical protection from severe SARS-CoV-2 disease were achievable with three doses of mRNA vaccine. [ABSTRACT FROM AUTHOR]

Aim: stereotactic ablative radiotherapy (SABR) has been shown to increase survival in oligometastatic patients. Few studies actually depicted the oligometastatic disease (OMD) evolution after SABR. There is few evidence on which patient will remain disease-free after SABR and which will develop rapidly a polymetastatic disease (PMD) therefore apart from the number of active metastases, there are no clues on which proven factor should be taken into account for prescribing local treatment in OMD. The aim of the present preliminary study based on a large retrospective database is to identify predictive factors of polymetastatic evolution in lung oligometastatic colorectal cancer patients to tailor SABR prescription. Methods: the study involved 23 centers, and was approved by the Ethical Committee (Prot. Negrar 2019- ZT). The data of 367 lung oligometastatic patients were reported. Primary end-point was the time to the polymetastatic conversion (tPMC), defined as the first occurrence of >5 simultaneous new metastases after SABR. Additionally, oligometastases number and cumulative gross tumor volume (GTV) were used as combined predictive factors of tPMC. Oligometastases number was stratified as 1, 2-3, and 4-5; cumulative GTV was dichotomized to the median value of 15.6 cc. The 6 groups are reported in table 1. Results: the median tPMC in the overall population was 26.1 months. The median tPMC stratified for the 6 groups is reported in table 1 (p=0.00). After data checking we were able to classify patients according to their median tPMC in 4 risk classes: low risk (group 1+3), favorable intermediate (group 2), unfavorable intermediate (group 4), high risk (group 5+6). The median tPMC for the 4 risk classes was: 34.6, 19.3, 12, and 6.7 months, respectively (figure 1; p=0.00). Conclusion: the present study identified predictive factors of polymetastatic evolution after SABR in lung oligometastatic colorectal cancer. The results demonstrated that the sole numerical number is not enough to define the OMD since patients identified as oligometastatic from a numerical point of view might rapidly progress to the PMD when the cumulative tumor volume is high. A tailored approach in SABR prescription should be pursued considering the expected disease evolution after SABR, with the aim to avoid unnecessary treatment and side effect in those at high risk of polymetastatic spread, and maximize local treatment in those with a favorable disease evolution. [ABSTRACT FROM AUTHOR]