Translational research has revolutionized how we develop new treatments for cancer patients. The change from an organ-centric concept guiding treatment choice towards deep molecular analysis, driving ...a personalized approach, is one of the most important advances of modern oncology. Several tools such as next generation sequencing and RNA sequencing have greatly improved the capacity to detect predictive and prognostic molecular alterations. Detection of gene mutations, amplifications, and fusions has therefore altered the history of several diseases in both a localized and metastatic setting. This shift in perspective, in which attention is focused on the specific molecular alterations of the tumor, has opened the door to personalized treatment. This situation is reflected in the increasing number of basket trials selecting specific molecular targets. Nonetheless, some weaknesses need to be addressed. The complexity of cancer cells enriched with concomitant molecular alterations complicates identification of the driver. Moreover, tumor heterogeneity could be responsible for the lack of benefit when targeted agents are used. In light of this, there is growing interest in the role of multidisciplinary committees or molecular tumor boards to try to enhance selection. The aim of this review is to critically analyze the evolution of cancer treatment towards a precision approach, underlining some recent successes and unexpected failures.
•Neophobia–neophilia forces affecting Italians food choice were analysed.•Attitudes to new food technologies were used to predict food choice of Italians.•FTNS scale performs properly with Italian ...consumers.•FTNS contribute to the understanding of the Italians’ behavioural responses.•The results support the value that FTNS can provide to food companies.
Food choice and consumption behaviour are influenced by many interacting factors. In this paper we present an empirical effort to enhance understanding of the neophobia–neophilia forces affecting food choice. Starting from the analysis of consumer preferences for some of the most familiar highly processed foods, namely fat-reduced, functional (enriched drinks and yogurt) and ready-to-eat frozen food, our study investigates the role of traditional demographic variables vs attitudes to new food technologies in predicting the consumption behaviour of a sample of Italians buying such products. Consumer attitudes toward food technologies were collected by means of the Food Technology Neophobia Scale (FTNS). Moreover, this paper explicitly analyses the value of the information provided by the FTNS. Underlying the research is the hypothesis that the FTNS may contribute to provide a comprehensive picture of the driving forces behind consumers’ behavioural responses towards processed foods which are the end-result of mature technologies. The four FTNS components, once measured and used independently, help clarify the influence on food choices of each neophobia–neophilia force (risk perception and novelty seeking, media influence, own health and environmental concerns) into a single, comprehensive framework.
Background
Immunotherapy with immune checkpoint inhibitors (ICIs) is highly effective in microsatellite instability–high (MSI‐H) metastatic colorectal cancer (mCRC); however, specific predictive ...biomarkers are lacking.
Patients and Methods
Data and samples from 85 patients with MSI‐H mCRC treated with ICIs were gathered. Tumor infiltrating lymphocytes (TILs) and tumor mutational burden (TMB) were analyzed in an exploratory cohort of “super” responders and “clearly” refractory patients; TILs were then evaluated in the whole cohort of patients. Primary objectives were the correlation between the number of TILs and TMB and their role as biomarkers of ICI efficacy. Main endpoints included response rate (RR), progression‐free survival (PFS), and overall survival (OS).
Results
In the exploratory cohort, an increasing number of TILs correlated to higher TMB (Pearson's test, p = .0429). In the whole cohort, median number of TILs was 3.6 in responders compared with 1.8 in nonresponders (Mann‐Whitney test, p = .0448). RR was 70.6% in patients with high number of TILs (TILs‐H) compared with 42.9% in patients with low number of TILs (odds ratio = 3.20, p = .0291). Survival outcomes differed significantly in favor of TILs‐H (PFS: hazard ratio HR = 0.42, p = .0278; OS: HR = 0.41, p = .0463).
Conclusion
A significant correlation between higher TMB and increased number of TILs was shown. A significantly higher activity and better PFS and OS with ICI in MSI‐H mCRC were reported in cases with high number of TILs, thus supporting further studies of TIL count as predictive biomarker of ICI efficacy.
Implications for Practice
Microsatellite instability is the result of mismatch repair protein deficiency, caused by germline mutations or somatic modifications in mismatch repair genes. In metastatic colorectal cancer (mCRC), immunotherapy (with immune checkpoint inhibitors ICIs) demonstrated remarkable clinical benefit in microsatellite instability–high (MSI‐H) patients. ICI primary resistance has been observed in approximately 25% of patients with MSI‐H mCRC, underlining the need for predictive biomarkers. In this study, tumor mutational burden (TMB) and tumor infiltrating lymphocyte (TIL) analyses were performed in an exploratory cohort of patients with MSI‐H mCRC treated with ICIs, demonstrating a significant correlation between higher TMB and increased number of TILs. Results also demonstrated a significant correlation between high number of TILs and clinical responses and survival benefit in a large data set of patients with MSI‐H mCRC treated with ICI. TMB and TILs could represent predictive biomarkers of ICI efficacy in MSI‐H mCRC and should be incorporated in future trials testing checkpoint inhibitors in colorectal cancer.
This article explores the role of tumor mutational burden and number of tumor infiltrating lymphocytes in determining response and outcome of patients with microsatellite high metastatic colorectal cancer treated with immune checkpoint inhibitors.
Background
An accurate risk‐stratification is key to optimize the benefit‐to‐risk ratio of palliative treatment in advanced biliary cancer. We aimed at assessing the impact of the prognostic ...nutritional index (PNI) on survival and treatment response in advanced biliary cancer (ABC) receiving first‐line chemotherapy.
Methods
Medical records of ABC treated with standard chemotherapy at the Modena Cancer Centre were retrospectively reviewed for variables deemed of potential interest, including the PNI. Univariate and multivariate analyses were performed to investigate the association between the covariates and overall survival (OS).
Results
114 ABC fulfilled the inclusion criteria and made up the training cohort. A PNI cut‐off value of 36.7 was established using the receiver operating characteristic (ROC) analysis. At both the univariate and the multivariate analysis, low PNI value (<36.7) was associated with shorter OS (P = .0011), together with increased NLR (P = .0046) and ECOG >1 (P < .0001). The median OS was 5.4 vs 12.1 months in the low‐ vs high PNI‐group. Moreover, a PNI value >36.7 resulted in a higher disease control in patients treated with gemcitabine/platinum combination (61.4% vs 34.3%). These results were validated in an independent cohort of 253 ABC.
Conclusions
We demonstrated and externally validated a prognostic role for the PNI in ABC treated with first‐line chemotherapy. Although the PNI turned out to be predictive in the subset of patients receiving platinum/gemcitabine combination, future prospective confirmation is needed.
(1) Background: Precision oncology is opening new treatment opportunities for patients suffering from solid tumors. In the last two decades, the advent of CDK4/6 inhibitors, immunotherapy, and ...antibody-drug conjugates (ADC) improved survival outcomes for advanced or metastatic breast cancers (BC). Nevertheless, some patients progress to approved therapies and still maintain good clinical conditions. (2) Methods: With the aim to estimate the accrual rate to experimental precision oncology treatments, we collected molecular and clinical characteristics of BC patients evaluated at Phase 1 Unit of Fondazione Policlinico Gemelli. Clinical data were retrieved from hospital records. Molecular analysis was performed using Next-Generation Sequencing (NGS) FoundationOne CDx on tissue or blood. (3) Results: Among the 38 BC patients referred to our unit, 35 completed the genomic analysis. All patients were female with advanced (mean number of metastatic sites: 3, range 1-6) BC. Median age at our evaluation was 52 (IQR, 48-59). ECOG PS was good in 97% of the study population, although heavily pre-treated (median number of systemic treatments: 5, IQR 3-7). Half of referred patients were HR
/HER2
BC, with 39% triple negative breast cancer (TNBC). NGS testing was performed on relapsed disease among most (71%) participants, in particular lymph nodes and soft tissue. Liquid biopsy was requested in 23% of cases. The median time from sample collection to NGS testing was 1 month and from diagnosis 54 months. The median value of mutations, VUS, and TMB were 6, 11, and 5, respectively.
,
,
,
, and
were the genes with the highest number of molecular alterations. In 5 patients (14%), the molecular analysis was helpful to assign targeted therapy in the context of clinical trials with a median progression-free survival of 5 months. (4) Conclusions: HR
/HER2
and TNBC were the most frequent subtypes referred for NGS testing. Tissue biopsy of relapsed disease was feasible in 71% of cases. The molecular analysis offered a new treatment opportunity in 14% of patients. The real benefit of these treatments remains to be evaluated in larger cohorts.
Molecular-matched therapies have revolutionized cancer treatment. We evaluated the improvement in clinical outcomes of applying an in-house customized Next Generation Sequencing panel in a single ...institution.
Patients with advanced solid tumors were molecularly selected to receive a molecular-matched treatment into early phase clinical trials versus best investigators choice, according to the evaluation of a multidisciplinary molecular tumor board. The primary endpoint was progression-free survival (PFS) assessed by the ratio of patients presenting 1.3-fold longer PFS on matched therapy (PFS2) than with prior therapy (PFS1).
Of a total of 231 molecularly screened patients, 87 were eligible for analysis. Patients who received matched therapy had a higher median PFS2 (6.47 months; 95% CI, 2.24-14.43) compared to those who received standard therapy (2.76 months; 95% CI, 2.14-3.91, Log-rank p = 0.022). The proportion of patients with a PFS2/PFS1 ratio over 1.3 was significantly higher in the experimental arm (0.33 vs 0.08; p = 0.008).
We demonstrate the pivotal role of the institutional molecular tumor board in evaluating the results of a customized NGS panel. This process optimizes the selection of available therapies, improving disease control. Prospective randomized trials are needed to confirm this approach and open the door to expanded drug access.
•QoL assessment is crucial for a complete evaluation of anticancer treatments.•We described QoL adoption and reporting in randomized phase III lung cancer trials.•QoL is not assessed in a high ...proportion of trials, even in metastatic setting.•Timely inclusion of QoL results in primary publications is worsening in last years.•QoL is a tool for the selection of the most tailored therapy for every patient.
We previously reported that quality of life (QoL) is not included among trial endpoints and QoL results are underreported in a significant proportion of phase III oncology trials. Here we describe QoL adoption, reporting and methodology of QoL analysis in lung cancer trials.
We selected all primary publications of lung cancer phase III trials assessing anticancer drugs published between 2012 and 2018 by 11 major journals.
122 publications were included. In 39 (32.0%) publications, QoL was not listed among endpoints: in 10/17 (58.8%) early stage/locally advanced NSCLC, in 15/54 (27.8%) first-line of advanced NSCLC; in 10/41 (24.4%) second and further lines of advanced NSCLC, in 4/10 (40.0%) SCLC. Proportion of trials not including QoL was similar over time: 32.9% publications in 2012–2015 vs. 30.6% in 2016–2018. Out of 83 trials including QoL among endpoints, QoL results were absent in 36 primary publications (43.4%). Proportion of trials without QoL results in primary publication increased over time (30.6% 2012–2015 vs. 61.8% 2016–2018, p = 0.005). Overall, QoL data were not available in 75/122 (61.5%) primary publications, due to the absent endpoint or unpublished results. QoL data were lacking in 48/68 (70.6%) publications of trials with overall survival as primary endpoint, 27/54 (50.0%) with other primary endpoints and 28/54 (51.9%) publications with a positive result. For trials including QoL among endpoints but lacking QoL results in primary publication, probability of secondary publication was 6.3%, 30.1% and 49.8% after 1, 2 and 3 years respectively, without evidence of improvement comparing 2012–2015 vs. 2016–2018.
QoL is not assessed or published in many phase III lung cancer trials, a setting where QoL value should be highly considered, due to high symptom burden and generally limited life expectancy. Timely inclusion of results in primary publications is worsening in recent years.
Background
Skin toxicity in patients affected by metastatic colorectal cancer (mCRC) treated with epidermal growth factor receptor (EGFR) inhibitors is well known. However, ad hoc ESMO guidelines ...have only recently been published.
Aim and methods
To describe the management (pre-emptive or reactive) of anti-EGFR-related cutaneous adverse events (AEs), in a real-life clinical context, in a selected population of patients with left-sided, metastatic
RAS/BRAF
wild-type mCRC treated with doublet chemotherapy plus anti-EGFR monoclonal antibody (i.e., panitumumab or cetuximab) as first-line regimen at 22 Institutions. The measured clinical outcomes were treatment-related adverse events, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
Results
Of 515 patients included in the analysis, 173 (33.6%) received a pre-emptive and 342 (66.4%) a reactive treatment. The median follow-up period for the overall population was 30.0 months. A significantly lower incidence of any grade acneiform rash was found in the pre-emptive compared to the reactive cohort both in the overall population (78.6% vs 94.4%,
p
< 0.001) and in patients treated with panitumumab (76.1% vs 93.7%,
p
< 0.001) or cetuximab (83.3% vs 95.4%,
p
= 0.004), respectively. A lower incidence of any grade (41.6% vs 50.9%,
p
= 0.047) but a higher incidence of G3-G4 (9.2% vs 4.7%,
p
= 0.042) paronychia/nail disorders were found in the pre-emptive compared to the reactive cohort. Nevertheless, a lower rate of patients within the reactive compared to the pre-emptive cohort was referred to dermatological counseling (21.4% vs 15.3%, respectively,
p
= 0.001). A higher rate of anti-EGFR therapy modification was needed in the pre-emptive compared to the reactive cohort (35.9% vs 41.6%, respectively,
p
< 0.001). The pre-emptive approach did not reduce the efficacy of antineoplastic therapy compared to the reactive in terms of ORR (69.2% vs 72.8%), median PFS (12.3 vs 13.0 months), and median OS (28.8 vs 33.5 months).
Conclusion
Although recommended by international guidelines, the pre-emptive approach of anti-EGFR-related skin toxicity in mCRC patients still appears less adopted in daily clinical practice, compared to the reactive one. A wider reception and application of this indication is desirable to improve patients’ quality of life without compromising the continuity and efficacy of antineoplastic therapy.
Trophoblast cell surface antigen-2 (Trop-2) is a glycoprotein that was first described as a membrane marker of trophoblast cells and was associated with regenerative abilities. Trop-2 overexpression ...was also described in several tumour types. Nevertheless, the therapeutic potential of Trop-2 was widely recognized and clinical studies with drug-antibody conjugates have been initiated in various cancer types. Recently, these efforts have been rewarded with the approval of sacituzumab govitecan from both the Food and Drug Administration (FDA) and European Medicines Agency (EMA), for metastatic triple-negative breast cancer patients. In our work, we briefly summarize the various characteristics of cancer cells overexpressing Trop-2, the pre-clinical activities of specific inhibitors, and the role of anti-Trop-2 therapy in current clinical practice. We also review the ongoing clinical trials to provide a snapshot of the future developments of these therapies.
Citrus concave-gum associated virus (CCGaV) and citrus virus A (CiVA) are two negative-stranded RNA viruses infecting citrus. Both viruses have been identified by high-throughput sequencing in Italy ...and their simultaneous presence in the same host documented. While CCGaV has been associated with citrus concave gum disease, the association of CiVA with symptoms is still unclear. Since the two virus genomes share about 75% sequence identity, their identification by RT-PCR is not obvious. Here, a multiplex RT-PCR to simultaneously detect and identify them is reported. Amplification of the citrus cytochrome oxidase (COX) gene transcript was included as internal control to minimize the risk of false negatives. Specificity and sensitivity of multiplex RT-PCR were comparable to that of conventional uniplex RT-PCR set up in previous studies for the independent detection of the two viruses. The method was validated by a field survey performed testing almost 300 trees grown in different areas of southern Italy. The assay revealed infection by CCGaV and CiVA in 17.7% and 18.4% of the tested trees, respectively, with mixed infection recorded in 5.0% of the samples. The novel mRT-PCR method saves time and costs and has the potential to be used for large-scale surveys and certification programs.
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