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The aggressive nature of gastric cancer often leads to late diagnosis and poor prognosis. Chemotherapy and the more recently added immunotherapy remain key treatments for this disease. Several studies have focused on identifying tissue biomarkers with prognostic and/or predictive roles and therefore the therapeutic options are rapidly growing. In this narrative review, we summarize the major tissue biomarkers routinely assessed in clinical practice. In addition, we focus on new evidence about emerging tissue biomarkers that could have a predictive role in future therapeutic approaches and also on the potential role of liquid biopsy in this neoplasm.

Purpose: To describe various clinical pictures of posterior scleritis following pembrolizumab therapy for metastatic cutaneous melanoma. Methods: Description of the clinical case with data from patient presentation and recurrences, diagnostic examinations, treatment, and six-months follow up. Clinical presentation of previous reports of pembrolizumab related of eye inflammation are discussed. Results: A 49-year-old patient underwent resection of metastatic melanoma of the skin with sentinel lymph nodes removal and pembrolizumab adjuvant therapy every three weeks. Nine months after pembrolizumab initiation the patient accessed ophthalmology emergency service complaining one week vision loss on her right eye associated with pain on eye movement. Ocular examination revealed right eye papillitis and posterior scleritis. Intravenous corticosteroid treatment was started associated with topical prednisolone drops, after which complete resolution of the subretinal fluid was seen. During the six months follow up one episode of posterior scleritis was observed in the contralateral eye and resolved after peribulbar corticosteroid injection and oral therapy and one recurrence of intermediate scleritis in the right eye which resolved after oral therapy. Conclusion: Posterior and intermediate scleritis may be added to the spectrum of pembrolizumab related eye inflammation; in the case presented posterior scleritis occurred asymmetrically in both eyes suggesting chronic features, importance of steroid tapering and follow up.

Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer. BCCs are categorized into “easy-to-treat” and “difficult-to-treat” groups, with the latter including all BCCs that are challenging to manage due to technical, patient-related, or tumor-related factors, such as locally advanced BCCs. In this report, we describe an 84-year-old patient with an extensive, unilateral BCC. Following a decision by the multidisciplinary skin cancer board, the patient was successfully treated with a daily dose of 200 mg of sonidegib, an inhibitor of the Hedgehog pathway, for eight months, acquiring complete clinical and histopathological remission. No significant side effects were reported. The follow-up period of 24 months has shown no negative results.

BackgroundMalnutrition, defined as weight loss and unsatisfactory nutrient intake, is very common in patients with head and neck squamous cell carcinoma (HNSCC) in either the early or palliative setting. Despite increased awareness, nutritional programs are not yet adequately implemented in these patients. There are several reasons for this delay: differences in composition, the expertise of the multidisciplinary teams involved in HNSCC patients’ treatment, and economic and network resources conditioning faster or slower nutritional supply delivery. This situation affects the outcomes and the quality of life of HNSCC patients.Materials and methodsWe investigated available literature about nutritional support in HNSCC patients and its impact on outcomes, prognosis, and quality of life, and we focused on the role of the multidisciplinary team. We considered 8,491 articles, and after excluding duplicates and manuscripts not written in English, 1,055 were analyzed and 73 were deemed eligible for the present work.ResultsAfter the literature review, we can state that malnutrition, sarcopenia, and cachexia are associated with systemic inflammation and closely correlated with poor outcomes. An evaluation of the nutritional status of the multidisciplinary team before, during, and after therapy could improve patient outcomes, as the goal of the therapeutic approach is widely designed.ConclusionsWe suggest that the treatment workflow definition is fundamental and propose a tailored nutritional approach that could benefit HNSCC patients’ outcomes and quality of life. These results could be achieved by a multidisciplinary team.

This case series highlights the complexity of sarcoidosis-like reactions (SLRs) during cancer treatment, specifically in patients receiving immunotherapy or targeted therapies for melanoma. SLRs can either mimic disease progression or present as part of the clinical manifestation, making diagnosis and treatment challenging. Our study reviewed the medical records of 31 patients who were candidates for postoperative treatment between June 2022 and June 2024. Out of these, three patients developed SLRs during their treatment. A 55-year-old woman with Stage IIIb cutaneous melanoma, receiving adjuvant therapy with anti-PD-1, after seven cycles of pembrolizumab, developed mediastinal node enlargement and skin hypodermic nodes. A biopsy of the hypodermic node revealed granulomatous infiltrates with sparse lymphocytes, consistent with sarcoidosis. A low dose of steroids was administered, resulting in a dramatic improvement. A 48-year-old woman with Stage IIIb BRAF wild-type melanoma, receiving nivolumab every 4 weeks, developed systemic sarcoidosis after seven cycles, primarily affecting extrapulmonary sites. Despite the immune-induced sarcoidosis, her treatment was not stopped, as decided by the multidisciplinary team (MDT). A 65-year-old man with Stage IIIb BRAF-mutant melanoma, receiving dabrafenib and trametinib, developed lung and cutaneous sarcoidosis, presenting with symptoms that led to emergency department admission. In all cases, the MDT played a crucial role in determining the course of treatment and balancing the risks of continuing or suspending cancer therapies while managing SLRs. National and international guidelines were consulted, but tailored decisions by the MDT were essential for optimizing patient care.

Background Immune checkpoint inhibitors have been approved and currently used in the clinical management of recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. The reported benefit in clinical trials is variable and heterogeneous. Our study aims at exploring and comparing the predictive role of gene-expression signatures with classical biomarkers for immunotherapy-treated R/M HNSCC patients in a multicentric phase IIIb trial.Methods Clinical data were prospectively collected in Nivactor tiral (single-arm, open-label, multicenter, phase IIIb clinical trial in platinum-refractory HNSCC treated with nivolumab). Findings were validated in an external independent cohort of immune-treated HNSCC patients, divided in long-term and short-term survivors (overall survival >18 and

Cholangiocarcinomas and urothelial carcinomas are lethal tumors worldwide and only a minority of patients are eligible for surgery at diagnosis. Moreover, patients are poorly responsive to current therapeutic strategies, including chemotherapy, radiotherapy, immunotherapy, and multimodality treatments. Recently, several advances have been made in precision medicine and these results are modifying the treatment paradigm for patients diagnosed with cholangiocarcinomas and urothelial carcinoma. These histotypes exhibit a high rate of multiple fibroblast growth factor receptor (FGFR) genetic alterations and numerous preclinical and clinical studies support FGFR as a highly attractive novel therapeutic target. Moreover, identifying specific genetic alterations may predict the tumor's response to conventional and novel FGFR-targeted drugs. Recent clinical studies showed promising data for FGFR-targeted therapy in reducing tumor volume and led to the United States Food and Drug Administration (FDA) approval of, e.g., pemigatinib, infigratinib, futibatinib, and erdafitinib. Moreover, FGFR inhibitors show promising results in the first-line setting of cholangiocarcinomas and urothelial carcinomas. Pemigatinib (FIGHT-302) and futibatinib (FOENIX-CAA3) are being evaluated in phase III trials that compare these agents to current first-line gemcitabine and cisplatin in FGFR2-rearranged cholangiocarcinoma. However, complexity in targeting the FGFR signaling pathway is observed. Herein, we describe the characteristics of the FDA-approved and other investigational FGFR-targeted therapeutics, evaluate the most recent preclinical and clinical studies focusing on targeting FGFR genomic alterations in the treatment of cholangiocarcinomas and urothelial cancer, and provide insight into factors involved in response and (acquired) resistance to FGFR inhibition.

Basosquamous carcinoma (BSC), an uncommon and aggressive nonmelanoma skin cancer exhibiting characteristics ranging from basal cell carcinoma (BCC) to squamous cell carcinoma (SCC), is a subject of controversy in terms of its classification, pathogenesis, histologic morphology, biologic behavior, prognosis, and management. This narrative review is based on an electronic search of English-language articles in PubMed that included the terms “basosquamous carcinoma” and/or “metatypical carcinoma of the skin” in their titles. The review aims to succinctly present and assess current data on the epidemiology, clinical presentation, dermoscopic, LC-OCT, and histopathologic characteristics, as well as the genetics and management of BSC, providing insight into this intriguing entity. As a conclusion, dermoscopy, deep incisional biopsies, and immunohistologic techniques should be applied in clinically suspicious lesions to achieve an early diagnosis and better prognosis of this tumor. Surgical treatments, including wide excision and Mohs’ micrographic surgery, remain the treatment of choice. Finally, Hedgehog pathway inhibitors and checkpoint inhibitors, must be thoroughly investigated with large controlled trials, since they may offer an alternative solution to irresectable or difficult-to-treat locally advanced cases of basosquamous carcinoma.

Background: The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing, paralleling the aging of the population. cSCC predominantly affects chronically sun-exposed areas, such as the head and neck region. At our tertiary center, a multidisciplinary approach to non-melanoma skin cancer is provided for locally advanced cSCC. Methods: We retrospectively revised all patients with locally advanced/metastatic cSCC treated with anti-PD1 antibody (Cemiplimab) at our Institution from January 2020 to March 2023 (minimum follow-up of 4 months on treatment). Results: Overall, we consecutively treated 20 ultra-octogenarian patients, of whom 15 were males and 5 were females (median age: 86.9 years). Despite age, a median number of concomitant drugs, and comorbidities, efficacy, and safety were superimposable with the available literature. No patients reported treatment-related adverse events of grade 3 or higher. Grade 2 adverse events were reported in 25% of patients. Overall, the response rate was 65%, with 50% partial responses and 20% long-lasting stable disease. The median duration of response was 14 months. The G8 elderly score was assessed in all patients, and the median score was 12 (range 9–14). Conclusions: Among ultra-octogenarian patients, a clinical benefit from Cemiplimab was obtained in most, including tumor shrinkage and pain relief. Cemiplimab confirmed its effectiveness in elderly patients in a real-life setting, with no new safety concerns.

Metastatic colorectal cancer is frequently associated with poor clinical conditions that may limit therapeutic options. Regorafenib is a small molecule approved for the treatment of metastatic colorectal cancer, but it is hampered by significative toxicities. Moreover, only a relatively limited number of patients benefit from the treatment. Therefore, the identification of reliable markers for response is an unmet need. Eighteen cytokines, selected based on their prevalent Th1 or Th2 effects, were collected. Peripheral blood samples were gathered at baseline in 25 metastatic colorectal cancer patients treated with regorafenib. Data extracted have been linked to progression-free survival. ROC identified the best cytokines associated with outcome. The relative value of the selected cytokines was determined by PCA. Data analysis identified 8 cytokines (TGF-β, TNF-α, CCL-2, IL-6, IL-8, IL-10, IL-13 and IL-21), used to create a signature (TGF-β, TNF-α high; CCL-2, IL-6, IL-8, IL-10, IL-13 and IL-21 low) corresponding to patients with a significantly longer progression-free survival. This report suggests that the analysis of multiple cytokines might identify a cytokine signature related to a patient’s outcome that is able to recognize patients who will benefit from treatment. If confirmed, future studies, also based on different drugs, using this approach and including larger patient populations, might identify a signature allowing the a priori identification of patients to be treated.

Oxaliplatin-based chemotherapy is extensively used for the treatment of gastrointestinal tumors and other malignancies. Oxaliplatin-related hypersensitivity reactions (HSRs) are common during antitumor treatment. Several studies have been conducted to identify predictive risk factors for oxaliplatin-related HSRs, but findings remain controversial. No definitive approach has been identified to reduce the risk of developing HSRs. The aim of this article is to provide an overview of oxaliplatin-related HSRs, and to report our institution’s experience. With our work, we reviewed available data from the literature and described our case series. A total of 153 patients were treated with oxaliplatin and 17 developed an HSR. On the whole, 70.6% of reactions were Grade 3, mostly with respiratory and cutaneous symptoms. Steroids and antihistamines were administered to reduce hypersensitivity symptoms and prevent further reactions. A stronger premedication and prolonged time of infusion resulted in milder reactions or absence of subsequent reactions. We did not find any clear predictive factor for the development of HSRs. Although it is not possible to cancel the risk of oxaliplatin-based HSRs, strategies to reduce the risk of occurrence could be stronger premedication and prolonged time of infusion.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer. In locally advanced (LA) HNSCC, a multidisciplinary approach consisting of surgery followed by chemoradiation (CRT) or definitive CRT is the mainstay of treatment. In recurrent metastatic (R/M), HNSCC immune checkpoint inhibitors (ICIs) with or without chemotherapy represent the new first-line option. However, cancer will recur in about two out of five patients with LA HNSCC. If progression occurs within six months from platin-radiotherapy treatment, anti-programmed cell death-1 (PD-1) may be prescribed. Otherwise, immunotherapy with or without chemotherapy might be considered if PD-L1 is expressed. Despite several improvements in the outcome of patients with R/M HNSCC, overall survival (OS) remains dismal, equaling a median of 14 months. In-depth knowledge of the tumor microenvironment (TME) would be required to change the course of this complex disease. In recent years, many predictive and prognostic biomarkers have been studied in the HNSCC TME, but none of them alone can select the best candidates for response to ICIs or targeted therapy (e.g., Cetuximab). The presence of cytokines indicates an immune response that might occur, among other things, after tumor antigen recognition, viral and bacterial infection, and physic damage. An immune response against HNSCC results in the production of some cytokines that induce a pro-inflammatory response and attract cells, such as neutrophils, macrophages, and T cell effectors, to enhance the innate and adaptive anti-tumor response. We revised the role of a group of cytokines as biomarkers for treatment response in HNSCC.

Epidermal growth factor receptor (EGFR) pathway has been shown to play a crucial role in several inflammatory conditions and host immune-inflammation status is related to tumor prognosis. This study aims to evaluate the prognostic significance of a four-gene inflammatory signature in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients treated with the EGFR inhibitor cetuximab plus chemotherapy. The inflammatory signature was assessed on 123 R/M HNSCC patients, enrolled in the multicenter trial B490 receiving first-line cetuximab plus platinum-based chemotherapy. The primary endpoint of the study was progression free survival (PFS), while secondary endpoints were overall survival (OS) and objective response rate (ORR). The patient population was subdivided into 3 groups according to the signature score groups. The four-genes-signature proved a significant prognostic value, resulting in a median PFS of 9.2 months in patients with high vs. 6.2 months for intermediate vs. 3.9 months for low values (p = 0.0016). The same findings were confirmed for OS, with median time of 18.4, 13.4, and 7.5 months for high, intermediate, and low values of the score, respectively (p = 0.0001). When ORR was considered, the signature was significantly higher in responders than in non-responders (p = 0.0092), reaching an area under the curve (AUC) of 0.65 (95% CI: 0.55–0.75). Our findings highlight the role of inflammation in the response to cetuximab and chemotherapy in R/M-HNSCC and may have translational implications for improving treatment selection.

Hepatic dysfunction, in the absence of liver metastases, occurs in 10–15% of renal cell carcinoma (RCC) patients, while immune hepatitis due to anti-CTLA4 and anti-PD1 administration affects about 3–9% and 0.7–1.8% of treated patients, respectively. Liver toxicity following combination therapy (anti-CTLA4 and anti-PD1) is seen in 29% of patients overall and grade 3–4 toxicity in 14% of patients. Stauffer’s syndrome is a rare para-neoplastic phenomenon associated with RCC and characterized by abnormal liver function tests, hepato-splenomegaly and histological changes consistent with non-specific hepatitis. We describe a case of RCC treated with anti-CTLA4 and anti-PD1 therapy resulting in immediate liver toxicity and death after 2 months of progressive hepatic impairment. We hypothesize that high IL-6 levels due to Stauffer’s syndrome might have contributed to immune-related hepatic failure.

Chemotherapy is much more effective in immunocompetent mice than in immunodeficient ones, and it is now acknowledged that an efficient immune system is necessary to optimize chemotherapy activity and efficacy. Furthermore, chemotherapy itself may reinvigorate immune response in different ways: by targeting cancer cells through the induction of cell stress, the release of damage signals and the induction of immunogenic cell death, by targeting immune cells, inhibiting immune suppressive cells and/or activating immune effector cells; and by targeting the host physiology through changes in the balance of gut microbiome. All these effects acting on immune and non-immune components interfere with the tumor microenvironment, leading to the different activity and efficacy of treatments. This article describes the correlation between chemotherapy and the immune changes induced in the tumor microenvironment. Our ultimate aim is to pave the way for the identification of the best drugs or combinations, the doses, the schedules and the right sequences to use when chemotherapy is combined with immunotherapy.

Long noncoding RNAs (lncRNAs) are increasingly known to be important in cancer as they directly interact with the cell cycle, proliferation pathways and microbiome balance. Moreover, lncRNAs regulate the immune system: they do not directly encode proteins of innate or adaptive immunity, but regulate immune cell differentiation and function, such as dendritic cell activity, T cell ratio and metabolism. The result of this complex interaction is that lncRNAs regulate cancer processes through a complex multimodal system involving immunity, metabolism and infection. The possible functions of lncRNAs and their roles in the regulation of cancer immunity will be reported and discussed in the present review. Recent studies showed their function as regulators in the tumour microenvironment (TME), epithelial–mesenchymal transition, microbiota, metabolism and immune cell differentiation. However, there is not much knowledge regarding their roles in cancer immunity regulation. Thus, the main aim of this review is to describe lncRNAs that have specifically been associated with immunity, the immune cycle and the TME.

Prognosis in relapsed metastatic head and neck squamous cell cancer (RM-HNSCC) is dismal. Platinum based chemotherapy in combination with Cetuximab is used in first-line setting, while no further validated options are available at progression. Immunotherapy has produced durable clinical benefit in some patients with RM-HNSCC although the premises are several patients are nonresponders. Studies are ongoing to determine predictive factors and the ideal setting/combination of novel immunotherapies. In this paper, we discuss the past and present of immunotherapy in head and neck cancer and provide an up-to-date information regarding the potential ways to improve immunotherapy outcomes in HNSCC.

Introduction and background: Second-line treatment of platinum-resistant relapsed/metastatic (R/M) head and neck cancer (HNC) is a currently unmet clinical need. Clinical trials showed improvement in overall survival and quality of life of R/M-HNC patients treated with anti-PD-1 regardless of the number of prior chemotherapy lines; however, the percentage of long-term survivors remains limited.This study aims to test the hypothesis that attacking the tumor microenvironment at multiple levels can increase immunogenicity of R/M-HNC without worsening the safety profile of immune checkpoint inhibitors. Methods/design: In this open label, multi-center, single-arm, Phase Ib/II, R/M-HNC patients pretreated with at least one line of therapy containing platinum, fluorouracil, and cetuximab will receive a daily metronomic dose of 50 mg cyclophosphamide without a drug-free break, 10 mg/kg avelumab on day 1 and every other week until progression, and a single fraction of 8 Gy radiotherapy on day 8. Discussion: The treatment protocol aims to reverse immune evasion of the tumor through a radiotherapy-induced self-vaccination effect, suppression of CD4+ CD25+ FoxP3+ regulatory T-cell function by metronomic cyclophosphamide, and effector T-cell reactivation owing to the inhibition of the PD-1–PD-L1 axis by avelumab.The immunologic interplay induced by the proposed combined treatment may theoretically improve the activity of avelumab without increasing its toxicity profile.Finally, an ancillary translational study will be extended to all the patients’ population. Trial registration: EudraCT n. 2017-000353-39. Keywords: Head and neck cancer, Avelumab, Cyclophosphamide, Radiotherapy, Clinical trial, Immunotherapy

Cancer induces immune suppression to overcome its recognition and eradication by the immune system. Cytokines are messengers able to modulate immune response or suppression. There is great interest in the evaluation of their changes during treatment in order to identify their relationship with clinical outcome. We evaluated 18 cytokines in breast cancer patients treated with eribulin before starting treatment (T0) and after four courses of therapy (T1). Longitudinal modifications were considered and cytokine clusters through PCA and HCPC correlated to patients’ outcomes were identified. Forty-one metastatic breast cancer patients and fifteen healthy volunteers were included. After clustering, we identified at T0 six patient clusters with different risk of relapse and death. At T1, only four clusters were identified, and three of them accounted for thirty-eight of forty-one patients, suggesting a possible role of treatment in reducing heterogeneity. The cluster with the best survival at T1 was characterized by low levels of IL-4, IL-6, IL-8, IL-10, CCL-2, CCL-4, and TGF-β. The cluster showing the worst survival encompassed high levels of IL-4, IL-6, IL-8, IL-10, CCL-2, and IFN-γ. A subgroup of patients with short progression-free survival (PFS) and long overall survival (OS) was comprised in the cluster characterized by low levels of CCL-2, IL-6, IL-8, IL-10, and IL-12 at T0. Our data support the prognostic significance of longitudinal serum cytokine analysis. This approach may help identify patients for whom early treatment stop avoids needless toxicity or might justify treatment beyond early progression. Further investigations are required to validate this hypothesis.

Background: nasopharyngeal carcinoma (NPC) is a complex disease entity that mainly predominates in endemic regions. Real-world data with immunotherapy from nonendemic regions are limited. Methods: we collected data from patients with recurrent/metastatic (R/M) NPC treated at a center in Greece and 8 centers in Italy. Between 2016 and 2021, 46 patients who were treated with at least one cycle of immune checkpoint inhibitors (ICI) were identified. Herein, we present our results and a review of the literature. Results: assessment of response was available in 42 patients. Overall, 11 patients responded to immunotherapy (Overall Response Rate-ORR 26.2%). Three patients had complete response (CR), and 8 patients had partial response (PR). Disease control rate (DCR) was 61.9%. Median Progression Free Survival (PFS) was 5.6 months and median Overall Survival (OS) was 19.1 months. Responders to ICI improved PFS and OS as compared to that of nonresponders. A lower probability of responding to ICI was shown in patients with more than three metastatic sites (p = 0.073), metastatic disease at initial diagnosis, (p = 0.039) or EBV DNA positive before ICI initiation, (p = 0.074). Decline in EBV DNA levels was found to be statistically significant associated with best response to ICI (p = 0.049). Safety was manageable. Conclusions: among 46 patients with R/M NPC treated with immunotherapy in two nonendemic regions, ORR was 26.2% and durable responses were observed. Low disease burden could serve as a biomarker for response to ICI.

Published data suggest that immunotherapy plays a role even in patients with very advanced tumours. We investigated the immune profile of end-stage cancer patients treated with immunotherapy to identify changes induced by treatment. Breast, colon, renal and prostate cancer patients were eligible. Treatment consisted of metronomic cyclophosphamide, low-dose interleukin-2 (IL-2) and a single radiation shot. A panel of 16 cytokines was assessed using automated ELISA before treatment (T0), after radiation (RT; T1), at cycle 2 (T2) and at disease progression (TPD). Receiving operating characteristic (ROC) analysis was used to identify cytokine cut-off related to overall survival (OS). Principal component analysis (PCA) was used to identify the immune profile correlating better with OS and progression-free survival. Twenty-three patients were enrolled. High IL-2, low IL-8 and CCL-2 correlated with OS. The PCA identified a cluster of patients, with high IL-2, IL-12 and IFN-γ levels at T0 having longer PFS and OS. In all cohorts, IL-2 and IL-5 increased from T0 to T2; a higher CCL-4 level compared to T2 and a higher IL-8 level compared to T0 were found at TPD. The progressive increase of the IL-10 level during treatment negatively correlated with OS. Our data suggested that baseline cytokine levels may predict patients’ outcome and that the treatment may affect their kinetic even in end-stage patients. Cytokine profiling of end-stage patients might offer a tool for medical decisions (EUDRACT: 2016-000578-39).

As the patients population ages, cancer screening increases, and cancer treatments improve, millions more head and neck carcinoma (HNC) patients will be classified as cancer survivors in the future. Change in epidemiology with human papillomavirus related HNC leads to a number of young treated patients. After treatment for HNC intensive surveillance, including ear, nose and throat (ENT) endoscopy, imaging, and serology, confers a survival benefit that became less evident in unresectable recurrence. We performed a comprehensive revision of literature and analyzed the experience of our centre. We revised publications on this topic and added data derived from the interdisciplinary work of experts within medical oncology, ENT, and radiation oncology scientific societies. We retrospectively collected local and distant recurrence of chemoradiation treated patients at Santa Croce and Carle University Hospital. A HNC follow-up program is not already codified and worldwide accepted. There is a need of scheduled follow-up. We suggest adopting a standardized follow-up guideline, although a multidisciplinary approach is frequently requested to tailor surveillance program and treatment on each patient.

Progress in head and neck cancer (HNC) therapies has improved tumor response, loco-regional control, and survival. However, treatment intensification also increases early and late toxicities. Dysphagia is an underestimated symptom in HNC patients. Impairment of swallowing process could cause malnutrition, dehydration, aspiration, and pneumonia. A comprehensive literature review finalized in May 2012 included searches of electronic databases (Medline, Embase, and CAB abstracts) and scientific societies meetings materials (American Society of Clinical Oncology, Associazione Italiana Radioterapia Oncologica, Associazione Italiana di Oncologia Cervico-Cefalica, American Head and Neck Society, and European Society for Medical Oncology). Hand-searches of HNC journals and reference lists were carried out. Approximately one-third of dysphagia patients developed pneumonia requiring treatment. Aspiration pneumonia associated mortality ranged from 20% to 65%. Unidentified dysphagia caused significant morbidity, increased mortality, and decreased the quality of life. In this review we underline definition, causes, predictive factors of dysphagia and report on pretreatment and on-treatment evaluation, suggesting some key points to avoid underestimation. A multi-parameter assessment of swallowing problems may allow an earlier diagnosis. An appropriate evaluation might lead to a better treatment of both symptoms and cancer.