Objective:
To evaluate the consistency of the quantitative imaging decision support (QIDSTM) tool and radiomic analysis using 594 metrics in lung carcinoma on chest CT scan.
Materials and Methods:
We ...included, retrospectively, 150 patients with histologically confirmed lung cancer who underwent chemotherapy and baseline and follow-ups CT scans. Using the QIDSTM platform, 3 radiologists segmented each lesion and automatically collected the longest diameter and the density mean value. Inter-observer variability, Bland Altman analysis and Spearman’s correlation coefficient were performed. QIDSTM tool consistency was assessed in terms of agreement rate in the treatment response classification. Kruskal Wallis test and the least absolute shrinkage and selection operator (LASSO) method with 10-fold cross validation were used to identify radiomic metrics correlated with lesion size change.
Results:
Good and significant correlation was obtained between the measurements of largest diameter and of density among the QIDSTM tool and the radiologists measurements. Inter-observer variability values were over 0.85. HealthMyne QIDSTM tool quantitative volumetric delineation was consistent and matched with each radiologist measurement considering the RECIST classification (80-84%) while a lower concordance among QIDSTM and the radiologists CHOI classification was observed (58-63%). Among 594 extracted metrics, significant and robust predictors of RECIST response were energy, histogram entropy and uniformity, Kurtosis, coronal long axis, longest planar diameter, surface, Neighborhood Grey-Level Different Matrix (NGLDM) dependence nonuniformity and low dependence emphasis as Volume, entropy of Log(2.5 mm), wavelet energy, deviation and root man squared.
Conclusion:
In conclusion, we demonstrated that HealthMyne quantitative volumetric delineation was consistent and that several radiomic metrics extracted by QIDSTM were significant and robust predictors of RECIST response.
Immunotherapy in Small Cell Lung Cancer Esposito, Giovanna; Palumbo, Giuliano; Carillio, Guido ...
Cancers,
09/2020, Letnik:
12, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Small-cell lung cancer (SCLC) is an aggressive tumor type with limited therapeutic options and poor prognosis. Chemotherapy regimens containing platinum represent the cornerstone of treatment for ...patients with extensive disease, but there has been no real progress for 30 years. The evidence that SCLC is characterized by a high mutational burden led to the development of immune-checkpoint inhibitors as single agents or in combination with chemotherapy. Randomized phase III trials demonstrated that the combination of atezolizumab (IMpower-133) or durvalumab (CASPIAN) with platinum-etoposide chemotherapy improved overall survival of patients with extensive disease. Instead, the KEYNOTE-604 study demonstrated that the addition of pembrolizumab to chemotherapy failed to significantly improve overall survival, but it prolonged progression-free survival. The safety profile of these combinations was similar with the known safety profiles of all single agents and no new adverse events were observed. Nivolumab and pembrolizumab single agents showed anti-tumor activity and acceptable safety profile in Checkmate 032 and KEYNOTE 028/158 trials, respectively, in patients with SCLC after platinum-based therapy and at least one prior line of therapy. Future challenges are the identification predictive biomarkers of response to immunotherapy in SCLC and the definition of the role of immunotherapy in patients with limited stage SCLC, in combination with radiotherapy or with other biological agents.
Herein, we describe three patients affected by metastatic colorectal cancer (mCRC) experiencing infection by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) and reduction of disease ...burden during coronavirus disease 2019 (COVID-19) course. Insights into tumor-associated angiotensin-converting enzyme (ACE)-2 expression and lymphocyte function suggest a correlation between host/SARS-Cov-2 infection and tumor burden reduction. This may shed new light into (a) the infection mechanism of SARS-CoV-2 virus and (b) the multiple aspects of a composite antiviral immune response with potential paradoxical and unexpected applications.
RET rearrangements are observed in 1–2% of non-small-cell lung cancer (NSCLC) patients and result in the constitutive activation of downstream pathways normally implied in cell proliferation, growth, ...differentiation and survival. In NSCLC patients, RET rearrangements have been associated with a history of non-smoking, a higher rate of brain metastasis at initial diagnosis and a low immune infiltrate. Traditionally, RET fusions are considered mutually exclusive with other oncogenic drivers, even though a co-occurrence with EGFR mutations and MET amplifications has been observed. Cabozantinib, vandetanib and lenvatinib are the first multi-kinase inhibitors tested in RET-rearranged NSCLC patients with contrasting results. More recently, two selective RET inhibitors, selpercatinib and pralsetinib, demonstrated higher efficacy rates and good tolerability and they were approved for the treatment of patients with metastatic RET fusion-positive NSCLC on the bases of the results of phase II studies. Two ongoing phase III clinical trials are currently comparing selpercatinib or pralsetinib to standard first line treatments and will definitively establish their efficacy in RET-positive NSCLC patients.
Purpose: To assess the efficacy of radiomics features obtained by computed tomography (CT) examination as biomarkers in order to select patients with lung adenocarcinoma who would benefit from ...immunotherapy. Methods: Seventy-four patients (median age 63 years, range 42–86 years) with histologically confirmed lung cancer who underwent immunotherapy as first- or second-line therapy and who had baseline CT studies were enrolled in this approved retrospective study. As a control group, we selected 50 patients (median age 66 years, range 36–86 years) from 2005 to 2013 with histologically confirmed lung adenocarcinoma who underwent chemotherapy alone or in combination with targeted therapy. A total of 573 radiomic metrics were extracted: 14 features based on Hounsfield unit values specific for lung CT images; 66 first-order profile features based on intensity values; 43 second-order profile features based on lesion shape; 393 third-order profile features; and 57 features with higher-order profiles. Univariate and multivariate statistical analysis with pattern recognition approaches and the least absolute shrinkage and selection operator (LASSO) method were used to assess the capability of extracted radiomics features to predict overall survival (OS) and progression free survival (PFS) time. Results: A total of 38 patients (median age 61; range 41–78 years) with confirmed lung adenocarcinoma and subjected to immunotherapy satisfied inclusion criteria, and 50 patients in a control group were included in the analysis The shift in the center of mass of the lesion due to image intensity was significant both to predict OS in patients subjected to immunotherapy and to predict PFS in patients subjected to immunotherapy and in patients in the control group. With univariate analysis, low diagnostic accuracy was reached to stratify patients based on OS and PFS time. Regarding multivariate analysis, considering the robust (two morphological features, three textural features and three higher-order statistical metrics) application of the LASSO approach and all patients, a support vector machine reached the best results for stratifying patients based on OS (area under curve (AUC) of 0.89 and accuracy of 81.6%). Alternatively, considering the robust predictors (six textural features and one higher-order statistical metric) and application of the LASSO approach including all patients, a decision tree reached the best results for stratifying patients based on PFS time (AUC of 0.96 and accuracy of 94.7%). Conclusions: Specific radiomic features could be used to select patients with lung adenocarcinoma who would benefit from immunotherapy because a subset of imaging radiomic features useful to predict OS or PFS time were different between the control group and the immunotherapy group.
Abstract
Background
Radiomics is an emerging field and has a keen interest, especially in the oncology field. The process of a radiomics study consists of lesion segmentation, feature extraction, ...consistency analysis of features, feature selection, and model building. Manual segmentation is one of the most critical parts of radiomics. It can be time-consuming and suffers from variability in tumor delineation, which leads to the reproducibility problem of calculating parameters and assessing spatial tumor heterogeneity, particularly in large or multiple tumors. Radiomic features provides data on tumor phenotype as well as cancer microenvironment. Radiomics derived parameters, when associated with other pertinent data and correlated with outcomes data, can produce accurate robust evidence based clinical decision support systems. The principal challenge is the optimal collection and integration of diverse multimodal data sources in a quantitative manner that delivers unambiguous clinical predictions that accurately and robustly enable outcome prediction as a function of the impending decisions.
Methods
The search covered the years from January 2010 to January 2021. The inclusion criterion was: clinical study evaluating radiomics of liver colorectal metastases. Exclusion criteria were studies with no sufficient reported data, case report, review or editorial letter.
Results
We recognized 38 studies that assessed radiomics in mCRC from January 2010 to January 2021. Twenty were on different tpics, 5 corresponded to most criteria; 3 are review, or letter to editors; so 10 articles were included.
Conclusions
In colorectal liver metastases radiomics should be a valid tool for the characterization of lesions, in the stratification of patients based on the risk of relapse after surgical treatment and in the prediction of response to chemotherapy treatment.
TAS-102 (Lonsurf
) is an oral fluoropyrimidine consisting of a combination of trifluridine (a thymidine analog) and tipiracil (a thymidine phosphorylation inhibitor). The drug is effective in ...metastatic colorectal cancer (mCRC) patients refractory to fluorouracil, irinotecan and oxaliplatin. This study is a real-world analysis, investigating the interplay of genotype/phenotype in relation to TAS-102 sensitivity.
Forty-seven consecutive mCRC patients were treated with TAS-102 at the National Cancer Institute of Naples from March 2019 to March 2021, at a dosage of 35 mg/m
, twice a day, in cycles of 28 days (from day 1 to 5 and from day 8 to 12). Clinical-pathological parameters were described. Activity was evaluated with RECIST criteria (v1.1) and toxicity with NCI-CTC (v5.0). Survival was depicted through the Kaplan-Meyer curves. Genetic features of patients were evaluated with Next Generation Sequencing (NGS) through the Illumina NovaSeq 6000 platform and TruSigt™Oncology 500 kit.
Median age of patients was 65 years (range: 46-77). Forty-one patients had 2 or more metastatic sites and 38 patients underwent to more than 2 previous lines of therapies. ECOG (Eastern Cooperative Oncology Group) Performance Status (PS) was 2 in 19 patients. The median number of TAS-102 cycles was 4 (range: 2-12). The most frequent toxic event was neutropenia (G3/G4 in 16 patients). There were no severe (> 3) non-haematological toxicities or treatment-related deaths. Twenty-six patients experienced progressive disease (PD), 21 stable disease (SD). Three patients with long-lasting disease control (DC: complete, partial responses or stable disease) shared an FGFR4 (p.Gly388Arg) mutation. Patients experiencing DC had more frequently a low tumour growth rate (P = 0.0306) and an FGFR4 p.G388R variant (P < 0.0001). The FGFR4 Arg388 genotype was associated with better survival (median: 6.4 months) compared to the Gly388 genotype (median: 4 months); the HR was 0.25 (95% CI 0.12- 0.51; P = 0.0001 at Log-Rank test).
This phenotype/genotype investigation suggests that the FGFR4 p.G388R variant may serve as a new marker for identifying patients who are responsive to TAS-102. A mechanistic hypothesis is proposed to interpret these findings.
During a spontaneous and autonomous study, we assessed the ultrasound finding of lymphadenopathy after
Pfizer vaccine. We enrolled 18 patients with 58 lymphadenopathies: in 10 patients, they were in ...the laterocervical side, while in 8 patients in the axillar site. The largest diameter was 16 mm with a range from 7 to 16 mm (median value = 10 mm). In the same patient, we found different ultrasound nodal findings. A total of 25 nodes showed eccentric cortical thickening with wide echogenic hilum and oval shape. In total, 19 nodes showed asymmetric eccentric cortical thickening with wide echogenic hilum and oval shape. Overall, 10 nodes showed concentric cortical thickening with reduction in the width of the echogenic hilum and oval shape. A total of four nodes showed huge reduction and displacement of the echogenic hilum and round or oval shape. No anomaly was found at the Doppler echocolor study. In conclusion, eccentric cortical thickening with wide echogenic hilum and oval shape, asymmetric eccentric cortical thickening with wide echogenic hilum and oval shape, concentric cortical thickening with reduction in the width of the echogenic hilum and oval shape, and a huge reduction and displacement of the echogenic hilum and round shape are the features that we found in post
Covid-19 Vaccine lymphadenopathies.
Surgery in Small-Cell Lung Cancer Martucci, Nicola; Morabito, Alessandro; La Rocca, Antonello ...
Cancers,
01/2021, Letnik:
13, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Small-cell lung cancer (SCLC) is one of the most aggressive tumors, with a rapid growth and early metastases. Approximately 5% of SCLC patients present with early-stage disease (T1,2 N0M0): these ...patients have a better prognosis, with a 5-year survival up to 50%. Two randomized phase III studies conducted in the 1960s and the 1980s reported negative results with surgery in SCLC patients with early-stage disease and, thereafter, surgery has been largely discouraged. Instead, several subsequent prospective studies have demonstrated the feasibility of a multimodality approach including surgery before or after chemotherapy and followed in most studies by thoracic radiotherapy, with a 5-year survival probability of 36-63% for patients with completely resected stage I SCLC. These results were substantially confirmed by retrospective studies and by large, population-based studies, conducted in the last 40 years, showing the benefit of surgery, particularly lobectomy, in selected patients with early-stage SCLC. On these bases, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging: in these cases, lobectomy with mediastinal lymphadenectomy is considered the standard approach. In all cases, surgery can be offered only as part of a multimodal treatment, which includes chemotherapy with or without radiotherapy and after a proper multidisciplinary evaluation.
Few treatment options are available for patients with small cell lung cancer (SCLC) in progression after a first-line therapy. A novel therapeutic approach is represented by lurbinectedin, a ...synthetic derivative of trabectedin that works by inhibiting oncogenic transcription and promoting apoptosis in tumor cells. A phase II basket trial demonstrated the activity of lurbinectedin at the dose of 3.2 mg/m
2
in patients with SCLC who had failed a previous chemotherapy, with a response rate of 35.2%, a median progression-free survival (mPFS) of 3.5 months, and a median overall survival (mOS) of 9.3 months. Common severe adverse events (grades 3–4) were hematological disorders, including anemia (9%), leukopenia (29%), neutropenia (46%), and thrombocytopenia (7%). On the basis of the positive results of this phase II study, on June 2020, lurbinectedin was approved by the Food and Drug Administration as second line for SCLC patients in progression on or after platinum-based therapy. The subsequent phase III trial comparing the combination of lurbinectedin plus doxorubicin vs. CAV (cyclophosphamide, Adriamycin, and vincristine) or topotecan did not demonstrate an improvement in overall survival, although the experimental arm showed a superior safety profile. Combinations of lurbinectedin with other drugs, cytotoxic agents and immune checkpoint inhibitors, are currently under investigation. The results of these studies should better define the optimal clinical application of lurbinectedin.
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