Effects of parenteral nutrition on the immune system in patients with head and neck squamous cell carcinoma

Oncologic patients often face malnutrition, particularly in the case of head and neck squamous cell carcinoma(HNSCC), due to the site of the lesion that may hinder swallowing. Malnutrition is associated with immunosuppression and increased incidence of infections and mortality, and improving the nutritional status with support regimes, such as parenteral nutrition (PN) can restore immune competence.The bags destined for PN contain mostly lipids and are enriched with essential fatty acids, specifically polyunsaturated fatty acids (PUFAs) ω3 and ω6. It is now clear that lipids, including PUFAs, influence the immune system: ω3 have an anti-inflammatory effect, thus repressing the immune response, whereas ω6 promote Th1-like responses.Although current guidelines suggest caution in the use lipid emulsions of ω6 in patients with uncontrolled inflammatory responses, such as those underlying autoimmune diseases, these may instead be advisable in patients unable to develop an adequate antitumoral response.Thegoal of clinical research is the personalization of therapies which include supportive therapies, such as nutritional support. It is indeed possible to predict that, in the near future, the individualized choice of specific nutrients could allow the patient not only to deal with chemotherapy with less toxicity, but also to promote advantageous immune responses and, therefore, survival

Outcome of T1N0M0 breast cancer in relation to St. Gallen risk assignment criteria for adjuvant therapy

T1N0M0 (stage 1) breast cancer (BC) has been increasing in recent decades but the optimal adjuvant approach remains controversial. To assess the outcome of BC patients stratified and treated with multimodal therapies according to St. Gallen consensus meeting recommendations, we retrospectively evaluated an unselected cohort of T1N0M0 BC patients, with respect to the St. Gallen criteria. At a median follow-up of 5 years, the recurrence rate, recurrence-free survival and overall survival were 7%, 94% and 96% respectively, and 60% of relapses were locoregional. No statistically significant difference was observed between T1a,b/T1c groups, or among risk categories (high/intermediate/low). The very low rate of distant recurrences even in patients with unfavorable prognostic factors seems to support the use of adjuvant systemic therapies but better prognostic and predictive factors are strongly needed for this subset of patients

Influence of different lipid emulsions on specific immune cell functions in head and neck cancer patients receiving supplemental parenteral nutrition: An exploratory analysis

Objectives: The effect of diet on immune responses is an area of intense investigation. Dietary lipids have been shown to differently influence and fine-tune the reactivity of immune cell subsets, thus potentially affecting clinical outcomes. Patients with head and neck squamous cell carcinoma face malnutrition, due to swallowing impairment related to the tumor site or to treatment sequalae, and may need supplemental parenteral nutrition (SPN) in addition to oral feeding when enteral nutrition is not feasible. Additionally, immune depression is a well-known complication in these patients. Parenteral nutrition (PN) bags contain amino acids, minerals, electrolytes and mostly lipids that provide calories in a concentrated form and are enriched with essential fatty acids. The aim of this study was to investigate multiple parameters of the immune responses in a cohort of patients with head and neck squamous cell carcinoma undergoing supplemental PN with bags enriched in ω-3 or ω-9 and ω-6 fatty acids. Methods: To our knowledge, this was the first exploratory study to investigate the effects of two different PN lipid emulsions on specific immune cells function of patients with advanced head and neck squamous carcinoma. ω-3-enriched fish-oil-based- and ω-6- and ω-9-enriched olive-oil-basedSPN was administered to two groups of patients for 1 wk in the context of an observational multicentric study. Polychromatic flow cytometry was used to investigate multiple subsets of leukocytes, with a special focus on cellular populations endowed with antitumor activity. Results: Patients treated with olive-oil-based PN showed an increase in the function of the innate (natural killer cells and monocytes) and adaptive (both CD4 and CD8 cells) arms of the immune response. Conclusion: An increase in the function of the innate and adaptive arms of the immune response may favor antitumoral responses

Progetto IMI Tele-consulenza genetica: un approccio combinato di Telemedicina e Next-Generation Sequencing nel percorso diagnostico delle sindromi di predisposizione al Melanoma

N

Single agent panitumumab in kras wild-type metastatic colorectal cancer patients following cetuximab-based regimens

Background. Few data are available outlining outcomes of panitumumab in advanced colorectal cancer patients benefiting from prior cetuximab-based regimens. Patients and methods. Thirty patients with KRAS wild type metastatic colorectal cancer with clinical benefit from prior cetuximab-based regimens between May 2004 and October 2011 were reviewed at nine Italian Institutions. Inclusion key criteria included interruption of cetuximab for reasons other than progressive disease. Patients were classified according to prior regimens (0 or =1), prior response or stabilization, surgery of metastases, and Kohne prognostic score. At the time of subsequent progression, patients were treated with single agent panitumumab until progressive disease, unacceptable toxicity, or consent withdrawal. Results. Panitumumab obtained 67% disease control rate and 30% objective response rate, with median PFS of 4.2 and median OS of 9.6 mo. Patients with BRAF/NRAS/PI3KCA and KRAS (by mutant enriched technique) wild-type tumors had the best chance of response to panitumumab. Conclusions. Single agent panitumumab provided significant clinical benefit in heavily pretreated patients without acquired resistance to prior cetuximab-based regimens

ALK/EML4 Fusion Gene May Be Found in Pure Squamous Carcinoma of the Lung

INTRODUCTION:The report of cases of lung squamous cell cancers harboring anaplastic lymphoma kinase (ALK) gene rearrangements raises the question whether this histologic subtype should be also evaluated for such molecular predictive test.METHODS:A consecutive series of 40 lung pure squamous cell carcinomas were analyzed for ALK gene status by fluorescence in situ hybridization. Squamous differentiation was validated using an immunohistochemical panel including n-p63 (p40), cytokeratin (CK) 5/6, sex-determining region Y (SRY)-Box2 (SOX2), thyroid transcription factor 1, CK7, and Napsin-A.RESULTS:Squamous differentiation was confirmed in all tumors as they stained positive for n-p63 and CK5/6 and negative for thyroid transcription factor 1 and Napsin-A. One of 40 cases (2.5%) showed an ALK rearrangement on fluorescence in situ hybridization analysis.CONCLUSIONS:ALK translocation may be found in lung pure squamous cell carcinomas. Our data suggest the opportunity to test ALK rearrangements on biopsy samples harboring squamous cell cancer differentiation

True 3q Chromosomal Amplification in Squamous Cell Lung Carcinoma by FISH and aCGH Molecular Analysis: Impact on Targeted Drugs

Squamous lung carcinoma lacks specific "ad hoc" therapies. Amplification of chromosome 3q is the most common genomic aberration and this region harbours genes having role as novel targets for therapeutics. There is no standard definition on how to score and report 3q amplification. False versus true 3q chromosomal amplification in squamous cell lung carcinoma may have tremendous impact on trials involving drugs which target DNA zones mapping on 3q. Forty squamous lung carcinomas were analyzed by FISH to assess chromosome 3q amplification. aCGH was performed as gold-standard to avoid false positive amplifications. Three clustered patterns of fluorescent signals were observed. Eight cases out of 40 (20%) showed 658 3q signals. Twenty out of 40 (50%) showed from 3 to 7 signals. The remaining showed two fluorescent signals (30%). When corrected by whole chromosome 3 signals, only cases with 658 signals maintained a LSI 3q/CEP3 ratio >2. Only the cases showing 3q amplification by aCGH (+3q25.3-3q27.3) showed 658 fluorescent signals at FISH evidencing a 3q/3 ratio >2. The remaining cases showed flat genomic portrait at aCGH on chromosome 3. We concluded that: 1) absolute copy number of 3q chromosomal region may harbour false positive interpretation of 3q amplification in squamous cell carcinoma; 2) a case results truly "amplified for chromosome 3q" when showing 658 fluorescent 3q signals; 3) trials involving drugs targeting loci on chromosome 3q in squamous lung carcinoma therapy have to consider false versus true 3q chromosomal amplification

Real world data of cemiplimab in locally advanced and metastatic cutaneous squamous cell carcinoma

Background: Cutaneous squamous cell carcinoma (cSCC) has an overall favourable outcome, except for patients with an advanced stage disease. The programmed death protein-1 (PD-1) inhibitor cemiplimab has been approved for use in advanced cSCC. We report clinical outcomes from the named patient programme-compassionate use of cemiplimab for patients with advanced cSCC in Italy. Methods: This is a retrospective, observational, multicentre study. We analysed medical records of patients with advanced cSCC treated with cemiplimab between May 2019 and February 2020 in 17 referral Italian centres. We assessed the safety profile according to the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v 5.0), the clinical activity in terms of response rate, clinical benefit and duration of response and baseline clinical-pathologic characteristics associated with response. Results: 131 patients were included, with a median age of 79 years. Of them, 9.2% had a concurrent chronic lymphoproliferative disease and 8.5% a concomitant autoimmune disease. Some 42.7% of the total patients had at least one treatment-related adverse events (AEs); out of above, 9.2% had grade 3–4 adverse events, and there were two fatal adverse events. The overall response rate (ORR) was 58%, and the disease control rate (DCR) was 71.7%. Cutaneous squamous cell carcinomas (cSCCs) arising on the head and neck area (p = 0.007) and haemoglobin values in normal range (p = 0.034) were significantly associated with a better response, while cSCCs on the genitalia (p = 0.041), treatment with any systemic antibiotic within 1 month of cemiplimab initiation (p = 0.012), performance status ≥1 (p = 0.012), chronic corticosteroids therapy (p = 0.038), previous radiation therapy to lymph nodes (p = 0.052) and previous chemotherapy (p = 0.0020) were significantly associated with a worse response. Conclusions: Our real-world study showed safety and effectiveness results comparable to those obtained in clinical trials. We identified some clinical and biochemical factors potentially associated with response to cemiplimab