Angiogenesis inhibition in lung cancer: emerging novel strategies.

PURPOSE OF REVIEW: In the current review, we will explore the molecular bases that have determined the design of clinical trials exploring the efficacy of antivascular agents in combination with chemotherapy, immune check point inhibitors and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with advanced nonsmall cell lung cancer. RECENT FINDINGS: Recent clinical trials have demonstrated the synergistic effect of antivascular agents with immune checkpoint inhibitors and EGFR-TKIs, despite no molecular marker has been identified yet to select patients. SUMMARY: Lung cancer remains one of the first causes of cancer-related death. However, thanks to the development of stratified molecular medicine and the introduction of immune checkpoint inhibitors, patients' survival has significantly improved. Due to the critical role of pro-angiogenic factors in cancer progression, antivascular agents targeting the vascular endothelial growth factor (VEGF) and its receptor (VEGFR) have been developed. Their efficacy has been explored in combination with chemotherapy, and immune checkpoint inhibitors, with promising but not definitive conclusions about their impact on prolonging patients' survival.

Prognostic role of pre-treatment magnetic resonance imaging (MRI)-based radiomic analysis in effectively cured head and neck squamous cell carcinoma (HNSCC) patients.

OBJECTIVES: To identify and validate baseline magnetic resonance imaging (b-MRI) radiomic features (RFs) as predictors of disease outcomes in effectively cured head and neck squamous cell carcinoma (HNSCC) patients. MATERIALS AND METHODS: Training set (TS) and validation set (VS) were retrieved from preexisting datasets (HETeCo and BD2Decide trials, respectively). Only patients with both pre- and post-contrast enhancement T1 and T2-weighted b-MRI and at least 2 years of follow-up (FUP) were selected. The combination of the best extracted RFs was used to classify low risk (LR) vs. high risk (HR) of disease recurrence. Sensitivity, specificity, and area under the curve (AUC) of the radiomic model were computed on both TS and VS. Overall survival (OS) and 5-year disease-free survival (DFS) Kaplan-Meier (KM) curves were compared for LR vs. HR. The radiomic-based risk class was used in a multivariate Cox model, including well-established clinical prognostic factors (TNM, sub-site, human papillomavirus [HPV]). RESULTS: In total, 57 patients of TS and 137 of VS were included. Three RFs were selected for the signature. Sensitivity of recurrence risk classifier was 0.82 and 0.77, specificity 0.78 and 0.81, AUC 0.83 and 0.78 for TS and VS, respectively. VS KM curves for LR vs. HR groups significantly differed both for 5-year DFS (p<.0001) and OS (p=.0004). A combined model of RFs plus TNM improved prognostic performance as compared to TNM alone, both for VS 5-year DFS (C-index: 0.76 vs. 0.60) and OS (C-index: 0.74 vs. 0.64). CONCLUSIONS: Radiomics of b-MRI can help to predict recurrence and survival outcomes in HNSCC.

Low skeletal muscle mass as predictor of postoperative complications and decreased overall survival in locally advanced head and neck squamous cell carcinoma: the role of ultrasound of rectus femoris muscle.

PURPOSE: Skeletal muscle mass (SMM) depletion and sarcopenia as predictors of postoperative complications and poorer overall survival (OS) have been validated in many surgical fields through cross-sectional imaging (CT, MRI), with potential limitations. We evaluated it in a stage III-IV head and neck squamous cell carcinoma (HNSCC) surgical cohort through ultrasound (US) of rectus femoris muscle (RF), a quick, cheap, repeatable alternative. METHODS: Patients submitted to surgical treatment with curative purpose were recruited and prospectively evaluated through clinical, biometric, biochemical, surgical, pathological and functional prognosticators and with preoperative US of RF with regards to 30-day complications and OS. RESULTS: Forty-seven patients completed the study. RF cross-sectional area (RF-CSA) was used to identify patients with low SMM (CSA ≤ 0.97 cm2: 18/47, 38.3%). RF-CSA was lower in complicated cases (0.95 ± 0.48 vs 1.41 ± 0.49 cm2; p = 0.003), remaining the only independent predictor of postoperative complications at multivariate analysis, with a model including ASA score and modified Frailty index (OR 9.84; p = 0.004). SMM depletion significantly impaired OS (13.6 ± 2.9 vs 26.3 ± 2.1 months; p = 0.017), being its only independent prognosticator at multivariate Cox regression analysis (OR 4.42; p = 0.033). CONCLUSION: RF-CSA, evaluated with US, seems a reliable method for identification of patients with low SMM in a stage III-IV HNSCC cohort, defining a subset at high-risk of 30-day complications and poorer OS.

Prevalence, characteristics, and treatment of fatigue in oncological cancer patients in Italy: a cross-sectional study of the Italian Network for Supportive Care in Cancer (NICSO).

BACKGROUND: Fatigue is one of the most distressing symptoms of cancer patients. Its characteristics and impact on quality of life have not been fully explored and treatment of cancer-related fatigue in Italian oncological centers has not been codified. METHODS: A cross-sectional study was carried out on all patients attending for any reason the 24 participating centers in two non-consecutive days. Patients with fatigue filled out the Brief Fatigue Inventory (BFI) questionnaire and reported any pharmacological or non-pharmacological treatment for fatigue. RESULTS: From October 2014 to May 2015, 1394 cancer patients agreed to participate in the study. Fatigue was referred by 866 (62.1%) of patients; its duration was > 4 months in 441 patients (50.9%). In the investigators' opinion, the most important (probable or almost sure) determinants of fatigue were reduced physical activity (271 patients), anxiety (149), pain (131), insomnia (125), anemia (123), and depression (123). Fatigue of moderate/severe intensity was reported by 43%/29.2% of patients, while usual fatigue in the last 24 h by 45%/33.1%, and the worst fatigue in the last 24 h by 33%/54.8%, respectively. Concerning the impact on quality of life, fatigue interfered moderately/severely with general activity in 30.8%/38.6% of patients, with mood in 26.1%/32.8%, with the ability to work in 27.9%/35.6%, with normal work in 26.7%/38.9%, with relationships with others in 21%/23.4% and with the ability to amuse themselves in 22.2%/33.1%. Only 117/866 patients (13.5%) received a pharmacological treatment represented by a corticosteroid in 101 patients (86.3%) while 188 patients (21.7%) received a non-pharmacological treatment such as physical exercise (120 patients, 63.8%) and various alimentary supplements (52 patients, 27.6%). CONCLUSIONS: Cancer-related fatigue is frequently reported by oncological patients; its intensity and impact on quality of life is relevant.

Predictors of Patient-Reported Dysphagia Following IMRT Plus Chemotherapy in Oropharyngeal Cancer.

The aim of this cross-sectional study is to evaluate the factors associated with patient-reported dysphagia in patients affected by locally advanced oropharyngeal cancer (OPC) treated with definitive intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy (CHT), with or without induction CHT. We evaluated 148 OPC patients treated with IMRT and concurrent CHT, without evidence of disease and who had completed their treatment since at least 6 months. At their planned follow-up visit, patients underwent clinical evaluation and completed the M.D. Anderson dysphagia inventory (MDADI) questionnaire. The association between questionnaire composite score (MDADI-CS) and different patients' and tumor's characteristics and treatments (covariates) was investigated by univariable and multivariable analyses, the latter including only covariates significant at univariable analysis. With a median time from treatment end of 30 months [range 6-74 months, interquartile range (IQR) 16-50 months], the median (IQR) MDADI-CS was 72 (63-84). The majority of patients (82.4%) had a MDADI-CS ≥ 60. At multivariable analysis, female gender, human papilloma virus (HPV)-negative status, and moderate and severe clinician-rated xerostomia were significantly associated with lower MDADI-CS. Patient-perceived dysphagia was satisfactory or acceptable in the majority of patients. HPV status and xerostomia were confirmed as important predictive factors for swallowing dysfunction after radiochemotherapy. Data regarding female gender are new and deserve further investigation.

Report from European Association for the Study of the Liver: HCC Summit, Geneva, Switzerland, 2-5 February 2017.

The European Association for the Study of the Liver Hepatocellular Carcinoma (HCC) international meeting held in Geneva in February 2017 focused on the state of the art of HCC management, from diagnosis to treatment and the potential development of clinical research in this field. This report reviews some of the most interesting topics discussed at the meeting such as the role of hepatitis C viral infection treatment with direct-acting antivirals in enhancing HCC risk, current prognostic systems, early diagnosis techniques, curative therapies for early HCC and the systemic treatments for advanced disease with a look into future perspectives.

Evaluation of an every-other-day palonosetron schedule to control emesis in multiple-day high-dose chemotherapy.

AIM: Efficacy of intermittent palonosetron dosing in patients undergoing multiple-day, high-dose chemotherapy (HDC) was investigated. PATIENTS & METHODS: Fifty-eight patients received palonosetron (0.25 mg intravenous [iv.]) every other day plus daily dexamethasone (8 mg iv. twice daily) dosing. The primary end point was complete control (CC; no emesis, no rescue anti-emetics, and no more than mild nausea) in the overall acute-period (until 24 h after chemotherapy completion). RESULTS: Acute-period CC occurred in 81% and 50% of patients receiving palonosetron and ondansetron (historical control cohort), respectively. Palonosetron (odds ratio [OR]: 4.37; p = 0.001) and a longer duration of HDC regimen (OR: 3.47; p = 0.011) independently predicted a better anti-emetic outcome. CONCLUSION: Palonosetron every other day plus daily dexamethasone is an effective anti-emetic coverage in patients undergoing HDC.

Impact of low skeletal muscle mass in oropharyngeal cancer patients treated with radical chemo-radiotherapy: A mono-institutional experience.

AIMS: Low skeletal muscle mass index (SMI) has recently emerged as an independent prognostic factor in oncological patients and it is linked with poor survival and higher treatment toxicity. The present study aims to determine the possible impact of low SMI on survival and acute toxicity in oropharyngeal patients. METHODS: Seventy-six patients with locally advanced oropharyngeal squamous cell carcinoma (stage III-IVC) were treated in our institution with Helical TomoTherapy® (HT - Accuray, Maddison, WI, USA) between 2005 and 2021. All patients received concomitant platinum-based chemotherapy (CT) (at least 200 mg/m2). The SMI was determined using the calculation of cross-sectional area at C3. Twenty patients (26%) presented pre-treatment low SMI, according to Chargi definitions. RESULTS: All patients concluded the treatment. Thirteen patients with low SMI (65%) and 22 patients with normal SMI (39%) presented acute toxicity greater than or equal to grade 3, but this difference was not statistically significant (p-value = 0.25). Overall survival was analyzed in 65 patients, excluding those who finished CT-RT less than six months before the analysis. Overall survival was significantly lower in low SMI versus normal SMI patients (p-value = 0.035). Same difference was observed in N0-N2a patients, suggesting an important role of SMI also in lower nodal burden and putatively better prognosis. CONCLUSIONS: Although the results are limited to a small population, our case series has the advantage to be very homogeneous in patients and treatment characteristics. In our setting, SMI demonstrated a crucial impact on overall survival. Further investigation with larger samples is necessary to confirm our results to improve patient outcomes.

Emergency Department Visits among Cancer Patients during SARS-CoV-2 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has had a global impact. Patients with cancer, their caregivers, and physicians need to balance the challenges associated with COVID-19 while ensuring cancer care. Nevertheless, emotional distress and hospital departmental reorganization could have led to a decrease in ED admissions even among oncological patients. Methods: We compared the 72 days of the pandemic in 2020 with the same calendar days in 2019 and 2021, defining a 20% decrease in ED visits as clinically significant. We studied the cause for visit, its severity, outcome (admission vs. discharge vs. death vs. hospice/palliative care), the tumor site, and method of arrival to the ED for the 3 time periods. Results: A significant decrease in ED oncological visits was found in 2020 compared to 2019, before returning to similar numbers in 2021. Fear, anxiety, and worry, in addition to hospital departmental reorganization, surely had an important role in the delay of ED visits, which resulted in irreparable consequences.

Acute kidney injury and acute kidney disease in high-dose cisplatin-treated head and neck cancer.

Background: In locally advanced head and neck squamous cell carcinoma (LA-SCCHN) at least 200mg/m2 (standard dose 300 mg/m2) of cisplatin concomitant with radiotherapy represents the standard of care, both in postoperative and conservative settings. Nevertheless, high dose administration every 3 weeks is often replaced with low dose weekly cisplatin to avoid toxicities like kidney injury, though often failing to reach the therapeutic dose. Our aim was to investigate the incidence of renal impairment in the real-life setting, integrating high dose cisplatin with adequate supportive therapy, and to explore both Acute Kidney Injury (AKI) and Acute Kidney Disease (AKD), a recently described clinical renal syndrome that encompasses functional alterations of the kidney lasting fewer than 3 months. Methods: One hundred and nine consecutive patients affected by LA-SCCHN and treated with at least a cumulative dosage of 200 mg/m2 of cisplatin concomitant with radiotherapy were enrolled in this prospective observational study. Results: AKI was reported in 12.8% of patients, 50% of whom were stage 1 (KDIGO criteria), while 25.7% of the cohort developed AKD. Patients with baseline estimated Glomerular Filtration Rate (eGFR) < 90 ml/min showed a higher incidence of AKD (36.2% vs 17.7%). Hypertension, baseline eGFR, and therapy with Renin-angiotensin-aldosterone system inhibitors proved to be significant factors associated with both AKI and AKD. Conclusion: AKI and AKD are not rare complications of high-dose cisplatin, but an appropriate prevention strategy and accurate monitoring of patients during treatment could lead to a reduction of the burden of these conditions.

Prevalence of Serum Antibody Titers against Core Vaccine Antigens in Italian Cats.

Feline core vaccines strongly recommended for all cats are against Feline panleukopenia virus (FPV), Felid herpesvirus type 1 (FeHV-1), and Feline calicivirus (FCV), but cats can be classified as low- and high-risk based on their lifestyle. The aim of this study was to determine the actual seroprotection against FPV, FeHV-1, and FCV in a large cohort of Italian cats by using the VacciCheck test. A total of 740 cats (567 owned and 173 stray cats; 435 vaccinated and 305 unvaccinated) were analyzed for Protective Antibody Titers (PATs). Differences related to origin, sex, age, breed, FIV/FeLV status, health status, and time elapsed since last vaccination were evaluated. Less than half of the entire cohort (36.4%) had PATs for all three diseases simultaneously, increasing to 48.6% if weak positive values were also considered and 50.3% when considering only the 435 vaccinated cats. Particularly, antibodies were detected against FCV, FPV, and FeHV-1 at protective titers (PATs) in 78.6%, 68.1, and 49.1% of the cats, respectively. In general, owned, neutered, and adult FIV- and/or FeLV-negative cats were the most protected categories, even if not always for the three viruses. Most cats maintained high PATs for 3 years or longer after vaccination against FPV and FCV but not FeHV-1. Long-lasting protective immunity persisted for many years after the last vaccination (more than 18 years in the oldest cats). Nevertheless, since not all cats were protected after so many years and for all pathogens, checking protection via antibody titration could be the best choice to prevent immunity breakdowns. The discussion also focuses on the reliability of antibody titration for the two URTD (upper respiratory tract disease) viruses which, unlike for FPV, is not widely accepted as a valid index of protection.

The observational clinical registry (cohort design) of the European Reference Network on Rare Adult Solid Cancers: The protocol for the rare head and neck cancers.

INTRODUCTION: Care for head and neck cancers is complex in particular for the rare ones. Knowledge is limited and histological heterogeneity adds complexity to the rarity. There is a wide consensus that to support clinical research on rare cancer, clinical registries should be developed within networks specializing in rare cancers. In the EU, a unique opportunity is provided by the European Reference Networks (ERN). The ERN EURACAN is dedicated to rare adults solid cancers, here we present the protocol of the EURACAN registry on rare head and neck cancers (ClinicalTrials.gov Identifier: NCT05483374). STUDY DESIGN: Registry-based cohort study including only people with rare head and neck cancers. OBJECTIVES: to help describe the natural history of rare head and neck cancers;to evaluate factors that influence prognosis;to assess treatment effectiveness;to measure indicators of quality of care. METHODS: Settings and participants It is an hospital based registry established in hospitals with expertise in head and neck cancers. Only adult patients with epithelial tumours of nasopharynx; nasal cavity and paranasal sinuses; salivary gland cancer in large and small salivary glands; and middle ear will be included in the registry. This registry won't select a sample of patients. Each patient in the facility who meets the above mentioned inclusion criteria will be followed prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for the patient follow-up. Variables Data will be collected on patient characteristics (eg. patient demographics, lifestyle, medical history, health status); exposure data (eg. disease, procedures, treatments of interest) and outcomes (e.g. survival, progression, progression-free survival, etc.). In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will be also collected. Statistical methods The data analyses will include descriptive statistics showing patterns of patients' and cancers' variables and indicators describing the quality of care. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause specific mortality will be used to determine independent predictors of overall survival, recurrence etc. Variables to include in the multivariable regression model will be selected based on the results of univariable analysis. The role of confounding or effect modifiers will be evaluated using stratified analysis or sensitivity analysis. To assess treatment effectiveness, multivariable models with propensity score adjustment and progression-free survival will be performed. Adequate statistical (eg. marginal structural model) methods will be used if time-varying treatments/confounders and confounding by indication (selective prescribing) will be present. RESULTS: The registry initiated recruiting in May 2022. The estimated completion date is December 2030 upon agreement on the achievement of all the registry objectives. As of October 2022, the registry is recruiting. There will be a risk of limited representativeness due to the hospital-based nature of the registry and to the fact that hospital contributing to the registry are expert centres for these rare cancers. Clinical Follow-up could also be an issue but active search of the life status of the patients will be guaranteed.

Skeletal Muscle Depletion and Major Postoperative Complications in Locally-Advanced Head and Neck Cancer: A Comparison between Ultrasound of Rectus Femoris Muscle and Neck Cross-Sectional Imaging.

Skeletal muscle mass (SMM) depletion has been validated in many surgical fields as independent predictor of complications through cross-sectional imaging. We evaluated SMM depletion in a stage III-IV head and neck cancer cohort, comparing the accuracy of CT/MRI at C3 level with ultrasound (US) of rectus femoris muscle (RF) in terms of prediction of major complications. Patients submitted to surgery were recruited from 2016 to 2021. SMM was estimated on CT/MRI by calculating the sum of the cross-sectional area (CSA) of the sternocleidomastoid and paravertebral muscles at C3 level and its height-indexed value (cervical skeletal muscle index, CSMI) and on US by computing the CSA of RF. Specific thresholds were defined for both US and CT/MRI according to ROC curve in terms of best prediction of 30-day major complications to detect sarcopenic subjects (40-53%). Sixty-five patients completed the study. At univariate analysis, major complications were associated to lower RF CSA, lower CSA at C3 level and lower CSMI, together with previous radiotherapy, higher ASA score and higher modified frailty index (mFI). At multivariate analysis RF CSA (OR 7.07, p = 0.004), CSA at C3 level (OR 6.74, p = 0.005) and CSMI (OR 4.02, p = 0.025) were confirmed as independent predictors in three different models including radiotherapy, ASA score and mFI. This analysis proved the value of SMM depletion as predictor of major complications in a head and neck cancer cohort, either defined on cross-sectional imaging at C3 or on US of RF.

What to Do and What Not to Do in the Management of Cancer Pain: A Physician Survey and Expert Recommendations.

BACKGROUND: Despite the prevalence of pain among patients with cancer and the availability of pertinent guidelines, the clinical management of oncological pain is decisively insufficient. To address this issue, we evaluated current trends in clinical practice and subsequently generated a list of ten corrective actions-five things to do and five things not to do-for the diagnosis, management, and monitoring of cancer pain. METHODS: The survey included 18 questions about clinical practice surrounding background pain and breakthrough cancer pain (BTcP). Survey questions were developed by a scientific board of 10 physician experts and communicated via email to an expanded panel of physicians in Italy. Responses were tabulated descriptively for analysis. RESULTS: Of 51 invited physicians, 32 (63%) provided complete survey responses. The responses revealed several incongruencies with current guideline recommendations: physicians did not always diagnose or monitor pain using diagnostically validated or disease-specific instruments; frequently based clinical decision-making on time availability or convenience; and pharmacological therapy was often inappropriate (eg, prescribing NSAIDs or corticosteroids for BTcP). The list of corrective actions generated by the scientific board favored a guideline-oriented approach that systematically characterizes oncological pain and implements treatment based on pain characteristics (eg, fast-acting transmucosal opioids for BTcP) and evidence-based recommendations. CONCLUSION: Oncologists require better education and training about the diagnosis, treatment, and monitoring of oncological pain. Physicians should be aware of current guideline recommendations as well as available pharmacological tools for BTcP.

History of Extensive Disease Small Cell Lung Cancer Treatment: Time to Raise the Bar? A Review of the Literature.

Several trials have tried for decades to improve the outcome of extensive disease small cell lung cancer (ED-SCLC) through attempts to modify the standard treatments. Nevertheless, platinum/etoposide combination and topotecan have remained respectively the first and the second line standard treatments for the last 40 years. With the advent of immunotherapy, this scenario has finally changed. Our review aims to provide an overview of the primary studies on the actual therapeutic strategies available for ED-SCLC patients, and to highlight emerging evidence supporting the use of immunotherapy in SCLC patients.

Intratumoral Cellular Heterogeneity: Implications for Drug Resistance in Patients with Non-Small Cell Lung Cancer.

Tailored therapies based on the identification of molecular targets currently represent a well-established therapeutic scenario in the treatment of non-small cell lung cancer (NSCLC) patients. However, while aiming to improve patients' response to therapy, development of resistance is frequently observed in daily clinical practice. Intratumoral heterogeneity is a frequent event in NSCLC, responsible for several critical issues in patients' diagnosis and treatment. Advances in single-cell sequencing technologies have allowed in-depth profiling of tumors and attributed intratumoral heterogeneity to genetic, epigenetic, and protein modification driven diversities within cancer cell populations. This review highlights current research on the biological role of tumor heterogeneity and its impact on the development of acquired resistance in NSCLC patients.

A CT-Based Radiomic Signature Can Be Prognostic for 10-Months Overall Survival in Metastatic Tumors Treated with Nivolumab: An Exploratory Study.

Baseline clinical prognostic factors for recurrent and/or metastatic (RM) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy are lacking. CT-based radiomics may provide additional prognostic information. A total of 85 patients with RM-HNSCC were enrolled for this study. For each tumor, radiomic features were extracted from the segmentation of the largest tumor mass. A pipeline including different feature selection steps was used to train a radiomic signature prognostic for 10-month overall survival (OS). Features were selected based on their stability to geometrical transformation of the segmentation (intraclass correlation coefficient, ICC > 0.75) and their predictive power (area under the curve, AUC > 0.7). The predictive model was developed using the least absolute shrinkage and selection operator (LASSO) in combination with the support vector machine. The model was developed based on the first 68 enrolled patients and tested on the last 17 patients. Classification performance of the radiomic risk was evaluated accuracy and the AUC. The same metrics were computed for some baseline predictors used in clinical practice (volume of largest lesion, total tumor volume, number of tumor lesions, number of affected organs, performance status). The AUC in the test set was 0.67, while accuracy was 0.82. The performance of the radiomic score was higher than the one obtainable with the clinical variables (largest lesion volume: accuracy 0.59, AUC = 0.55; number of tumoral lesions: accuracy 0.71, AUC 0.36; number of affected organs: accuracy 0.47; AUC 0.42; total tumor volume: accuracy 0.59, AUC 0.53; performance status: accuracy 0.41, AUC = 0.47). Radiomics may provide additional baseline prognostic value compared to the variables used in clinical practice.

MALT lymphoma and Kaposi sarcoma in an HIV-negative patient.

A 77-year-old caucasian man presented on March 2005 with important epigastric pain without any other significant history of gastritis. Patient refers a history of cutaneous Kaposi's sarcoma (KS) treated since 1974 with surgical excision or oncovorin topical injection. He underwent endoscopic evaluation showing a 1.5-cm ulcerated area at the gastric angulus, associated with edematous and erythematous nodular mucosa (Fig. 1).

Uncommon Site of Metastasis and Prolonged Survival in Patients with Anaplastic Thyroid Carcinoma: A Systematic Review of the Literature.

Anaplastic thyroid carcinoma (ATC) is a very rare, highly aggressive malignant thyroid tumor with an overall survival from 3 to 5 months in most of the cases. Even the modern and intensive treatments seem not to be enough to provide a cure, also for the resectable ones, and the role of chemotherapy is still unclear but does not seem to prolong survival. Nevertheless, some patients survive longer and have a better outcome, even in the presence of metastasis, than what the literature reports. We present the case of a 64-year-old female affected by ATC, treated on February 2018 with surgery followed by chemoradiation. One year after surgery, the patient developed a subcutaneous recurrence that was radically resected and is still alive 29 months after the diagnosis. We propose a systematic review of the literature to deepen the knowledge of the prognostic factors of ATC with the aim to recognize and select the patients with a better outcome, even if metastatic, and to describe a very uncommon site of metastatization.

Metabolism and Immune Modulation in Patients with Solid Tumors: Systematic Review of Preclinical and Clinical Evidence.

Several immunotherapy agents are the standard of care of many solid malignancies. Nevertheless, the majority of patients do not benefit from the currently available immunotherapies. It is therefore of paramount importance to identify the prognostic and predictive factors of tumor response/resistance and to design effective therapeutic strategies to overcome primary resistance and improve the efficacy of immunotherapy. The aim of this review is to underline the influence of the tumor and host metabolism on the antitumor immune response and to discuss possible strategies to improve the efficacy of available treatments by targeting the specific metabolic pathways in tumors or immune cells and by modifying patients' nutritional statuses. A systematic search of the Medline and EMBASE databases was carried out to identify scientific papers published until February 2020, which reported original research articles on the influence of tumor or host metabolism on antitumor immune response. The literature data showed the key role of glycolysis and mitochondrial oxidative phosphorylation, arginine, tryptophan, glutamine, lipid metabolism and microbiome on immune cell function. Moreover, specific nutritional behaviors, such as a low dietary intake of vitamin C, low glycemic index and alpha-linolenic acid, eicosapentenoic acid, docosahexaenoic acid, ornithine ketoglutarate, tryptophan and probiotic supplementation were associated with the potential clinical benefits from the currently available immunotherapies.