From targeting the tumor to targeting the immune system: Transversal challenges in oncology with the inhibition of the PD-1/PD-L1 axis

After that the era of chemotherapy in the treatment of solid tumors have been overcome by the "translational era", with the innovation introduced by targeted therapies, medical oncology is currently looking at the dawn of a new "immunotherapy era" with the advent of immune checkpoint inhibitors(CKI) antibodies.The onset of PD-1/PD-L1 targeted therapy has demonstrated the importance of this axis in the immune escape across almost all human cancers.The new CKI allowed to significantly prolong survival and to generate durable response, demonstrating remarkable efficacy in a wide range of cancer types.The aim of this article is to review the most up to date literature about the clinical effectiveness of CKI antibodies targeting PD-1/PD-L1 axis for the treatment of advanced solid tumors and to explore transversal challenges in the immune checkpoint blockade.

Review on radiological evolution of COVID-19 pneumonia using computed tomography

BACKGROUND Pneumonia is the main manifestation of coronavirus disease 2019(COVID-19)infection.Chest computed tomography is recommended for the initial evaluation of the disease;this technique can also be helpful to monitor the disease progression and evaluate the therapeutic efficacy.AIM To review the currently available literature regarding the radiological follow-up of COVID-19-related lung alterations using the computed tomography scan,to describe the evidence about the dynamic evolution of COVID-19 pneumonia and verify the potential usefulness of the radiological follow-up.METHODS We used pertinent keywords on PubMed to select relevant studies;the articles we considered were published until October 30,2020.Through this selection,69 studies were identified,and 16 were finally included in the review.RESULTS Summarizing the included works’findings,we identified well-defined stages in the short follow-up time frame.A radiographic deterioration reaching a peak roughly within the first 2 wk;after the peak,an absorption process and repairing signs are observed.At later radiological follow-up,with the limitation of little evidence available,the lesions usually did not recover completely.CONCLUSION Following computed tomography scan evolution over time could help physicians better understand the clinical impact of COVID-19 pneumonia and manage the possible sequelae;a longer follow-up is advisable to verify the complete resolution or the presence of long-term damage.

Differential diagnosis of COVID-19 at the chest computed tomography scan:A review with special focus on cancer patients

BACKGROUND Given the several radiological features shared by coronavirus disease 2019 pneumonia and other infective or non-infective diseases with lung involvement,the differential diagnosis is often tricky,and no unequivocal tool exists to help the radiologist in the proper diagnosis.Computed tomography is considered the gold standard in detecting pulmonary illness caused by severe acute respiratory syndrome coronavirus 2.AIM To conduct a systematic review including the available studies evaluating computed tomography similarities and discrepancies between coronavirus disease 2019 pneumonia and other pulmonary illness,then providing a discussion focus on cancer patients.METHODS Using pertinent keywords,we performed a systematic review using PubMed to select relevant studies published until October 30,2020.RESULTS Of the identified 133 studies,18 were eligible and included in this review.CONCLUSION Ground-glass opacity and consolidations are the most common computed tomography lesions in coronavirus disease 2019 pneumonia and other respiratory diseases.Only two studies included cancer patients,and the differential diagnosis with early lung cancer and radiation pneumonitis was performed.A single lesion associated with pleural effusion and lymphadenopathies in lung cancer and the onset of the lesions in the radiation field in the case of radiation pneumonitis allowed the differential diagnosis.Nevertheless,the studies were heterogeneous,and the type and prevalence of lesions,distributions,morphology,evolution,and additional signs,together with epidemiological,clinical,and laboratory findings,are crucial to help in the differential diagnosis.

First-line pazopanib in patients with advanced non-clear cell renal carcinoma:An Italian case series

BACKGROUND Non-clear cell(ncc)metastatic renal-cell carcinoma(RCC)has dismal results with standard systemic therapies and a generally worse prognosis when compared to its clear-cell counterpart.New systemic combination therapies have emerged for metastatic RCC(mRCC),but the pivotal phase III trials excluded patients with nccRCC,which constitute about 30%of metastatic RCC cases.AIM To provide a piece of real-life evidence on the use of pazopanib in this patient subgroup.METHODS The present study is a multicenter retrospective observational analysis aiming to assess the activity,efficacy,and safety of pazopanib as first-line therapy for advanced nccRCC patients treated in a real-life setting.RESULTS Overall,48 patients were included.At the median follow-up of 40.6 mo,the objective response rate was 27.1%,the disease control rate was 83.3%,and the median progression-free survival and overall survival were 12.3(95%confidence interval[CI]:3.6-20.9)and 27.7(95%CI:18.2-37.1)mo,respectively.Grade 3 adverse events occurred in 20%of patients,and no grade 4 or 5 toxicities were found.CONCLUSION Pazopanib should be considered as a good first-line option for metastatic RCC with variant histology.

Renal cell carcinoma and viral infections:A dangerous relationship?

Virus-related cancers in humans are widely recognized,but in the case of renal cancer,the link with the world of viruses is not clearly established in humans,despite being known in animal biology.In the present review,we aimed to explore the literature on renal cell carcinoma(RCC)for a possible role of viruses in human RCC tumorigenesis and immune homeostasis,hypothesizing the contribution of viruses to the immunogenicity of this tumor.A scientific literature search was conducted using the PubMed,Web of Science,and Google Scholar databases with the keywords“virus”or“viruses”or“viral infection”matched with(“AND”)“renal cell carcinoma”or“kidney cancer”or“renal cancer”or“renal carcinoma”or“renal tumor”or“RCC”.The retrieved findings evidenced two main aspects testifying to the relationship between RCC and viruses:The presence of viruses within the tumor,especially in non-clear cell RCC cases,and RCC occurrence in cases with pre-existing chronic viral infections.Some retrieved translational and clinical data suggest the possible contribution of viruses,particularly Epstein-Barr virus,to the marked immunogenicity of sarcomatoid RCC.In addition,it was revealed the possible role of endogenous retrovirus reactivation in RCC oncogenesis,introducing new fascinating hypotheses about this tumor’s immunogenicity and likeliness of response to immune checkpoint inhibitors.

Clinical resistance predictors to first-line VEGFR-TKI monotherapy for metastatic renal cell carcinoma: a retrospective multicenter real-life case series

Aim:For many years,systemic treatment of metastatic Renal Cell Carcinoma(mRCC)was based on sequential targeted agent monotherapies.In this real-life case series,we evaluated easily accessible clinical factors useful for disease course prediction.Methods:We exploited patients'clinical pathological characteristics and systemic treatment outcomes in a real-world population of 365 mRCC patients who received sequential monotherapies in the targeted therapy era,and we identified an early progressors subpopulation,resistant to first-line VEGFR-TKI monotherapy in less than 6 months.Results:Early progressors(n=124)show a far worse OS compared with patients progressing beyond the sixth month of therapy(13.5 vs.44.8 months,P-value<0.0001,HR=0.41,95%CI:0.29-0.53).However,these patients did not show far worse performance in second and third-line settings compared to first-line responders.In the univariate analysis,IMDC risk class,sarcomatoid features,and Systemic Inflammation Index(SII)were correlated with first-line therapy Progression-Free Survival(PFS1).In multivariate analysis,variables correlated with first-line outcome were IMDC risk class,histotype,and number of metastatic sites at the diagnosis.Conclusion:Real-world data can contribute to developing easy-to-use prognostic factors associated with refractory disease that could support clinicians in identifying the most appropriate treatment strategy for each patient.