Major and minor salivary gland tumours Gatta, Gemma; Guzzo, Marco; Locati, Laura D. ...
Critical reviews in oncology/hematology,
August 2020, 2020-08-00, 20200801, Volume:
152
Journal Article
Peer reviewed
Salivary glands carcinomas are very rare epithelial malignant tumors. In 2013 in Europe, 7800 new diagnoses were estimated, 8.5 % of all head and neck cancer. The last WHO classification (2017) ...counts more than 20 malignant histotypes, this variety as well as the rarity of some of them needs a skilled pathologist for diagnosis. Surgery remains the mainstay of management followed by radiation in high-grade and high-risk pathological features cases. The intensity modulated radiotherapy (IMRT) should be preferred over conformational radiotherapy techniques as adjuvant and exclusive treatment in advanced cases. Particle radiotherapy (i.e. protons, carbon ions) can have a role in advanced/unresectable disease since it was proved to have better results over photons in loco-regional control both in adenoid cystic carcinoma and in other histotypes. Although chemotherapy is still the most frequent treatment for metastatic patients, several new compounds (i.e. anti-angiogenic agents, tailored agents, checkpoint inhibitors) are under investigation.
Highlights • This is a review on systemic treatments in salivary gland carcinomas. • ACC and non-ACC histotypes have been considered separately. • Updates on chemotherapy and tailored treatments have ...been provided.
Major and minor salivary gland tumors Guzzo, Marco; Locati, Laura D; Prott, Franz J ...
Critical reviews in oncology/hematology,
05/2010, Volume:
74, Issue:
2
Journal Article
Peer reviewed
Abstract Malignant salivary gland tumors are rare. The most common tumor site is the parotid. Aetiologic factors are not clear. Nutrition may be a risk factor, as well as irradiation or a ...long-standing histologically benign tumor that occurs at youth. Painless swelling of a salivary gland should always be considered as suspicious, especially if no sign of inflammation is present. Signs and symptoms related to major salivary gland tumors differ from those concerning minor salivary gland tumors, as they depend on the different location of the salivary gland. Surgical excision represents the standard option in the treatment of resectable tumors of both major and minor salivary glands. Neutron, heavy ions or proton radiotherapy may be a treatment option for inoperable locoregional disease. Surgery, irradiation or re-irradiation are treatment options for local relapse, whereas radical neck dissection is indicated for regional relapses. Metastatic disease may be either treated with radiotherapy or palliative chemotherapy, depending on the site of metastases. For highly selected patients the employment of anti-androgen therapy is indicated.
Assessing tumour response using a traditional phase I, II and III trial approach is not without limitations, particularly when targeted therapies are involved. Window of opportunity trials, performed ...presurgically but differing from neoadjuvant studies, were developed in an attempt to overcome the limitations of the traditional approach. A recent window of opportunity trial, the EORTC 90111-24111-NOCI-HNCG study, evaluated afatinib in treatment-naive patients with squamous cell carcinoma of the head and neck. While this study was the first to demonstrate the activity of afatinib in this setting and to define its potential predictive biomarkers, it also highlighted the challenges associated with the window of opportunity trial design, including the impact of patient selection, tumour site, and other organisational issues. This report details the key learnings from the EORTC 90111-24111-NOCI-HNCG study and provides recommendations to overcome the challenges of this particular trial design.
•The benefits of window of opportunity studies to oncologic research, specifically the testing of new compounds within a specific tumour type.•The primary end-point must be well defined and evaluable by imaging or molecular response criteria.•The timing of drug administration, sample collection and technical investigations should be determined upfront.•The resection plan should not be modified even when tumour size regression occurs.•Multidisciplinary teamwork is mandatory with such a study design.
•Anti-PD-1 agents are active and safe in recurrent/metastatic head and neck cancer.•Combinations of immune checkpoint inhibitors are under evaluation in RM HNSCC.•The role of immunotherapy in locally ...advanced HNSCC deserves to be explored.•We lack affordable and universal predictive factor of response.
According to the new determinants of cancer immunity, head and neck squamous cell cancer (HNSCC) has to be considered as an immunogenic tumor for the relatively high number of somatic mutations giving rise to neoantigens recognized by T cell. HNSCC develop at a significant rate despite the antitumoral immune response indicating the existence of effective escape mechanisms. The lack of antigen presentation or co-stimulatory molecules required and immunosuppressive phenomena established by the tumor or the host microenvironment impair immune-mediated recognition and cancer control. Echoing the success in melanoma and NSCLC, strategies aimed to reverse this process and enhance the antitumor immunity are rapidly developing in HNSCC, as monotherapies, multidrug immunotherapies or associations with well-recognized treatments, like radiation and systemic therapies.
According to the first published data, immunotherapy has shown promising results in the management of recurrent and metastatic (r/m) HNSCC. Anti-PD-1 blockers have been recently approved by US and EU regulatory agencies in this setting. The encouraging results in r/m HNSCC prompted the incorporation of this approach also in the treatment of locally advanced disease. However, the strategies for the rational and evidence-based combinations to maximize clinical benefit are only starting to emerge. In this view, knowing in depth the specific properties of HNSCC and the underlying immunological conditions of the bearing hosts is an essential step. The role of immune system in the development and the management of HNSCC, the main mechanisms of tumor escape and the most recent results from clinical trials will be discussed herein.
The purpose of this article is to discuss the published evidence related to quality of life (QoL) and financial toxicity (FT) differences between female and male head and neck cancer patients treated ...with (chemo)radiotherapy. There is a need of promoting methods for assessing QoL difference between female and male patients in order to set up early rehabilitation, psychosocial care, and lifestyle interventions, as well as setting up specific interventions for minimizing financial stress.
Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequent cancers in humans, with cumulative ultraviolet radiation exposure, aging, and immunodepression as the ...main risk factors. In most cases, these malignancies arise in the head and neck area, and they can be treated with locoregional therapies. A minority of cases require systemic therapy. Currently, Sonic Hedgehog inhibitors (i.e., vismodegib and sonidegib) have been approved for advanced BCC, while the PD-1 checkpoint inhibitor cemiplimab has been approved as a first-line treatment for cSCC and as a second-line treatment for BCC. Nevertheless, there is a clinical need for an effective and safe systemic therapies for advanced synchronous (syn) BCC/cSCC not amenable to local treatments. International guidelines do not provide specific recommendations for patients affected by this condition, and no case reports on the full-dose association of these medications have been previously reported. Here, we present the cases of two elderly patients affected by synBCC/cSCC of the head and neck, who received combined therapy with cemiplimab and sonidegib at full dose and standard schedule, achieving remarkable clinical benefit and long-term responses, without major adverse events. The instance of a feasible treatment for patients with advanced synBCC/cSCC will become increasingly frequent with the advancement of life expectancy in the global population, and the synergistic activity of targeted therapies and immunotherapy-administered either in association or sequentially-deserves to be further explored.
The activity of androgen-deprivation therapy (ADT) in androgen receptor-positive (AR+) salivary gland carcinomas (SGCs) has been established in the past few years. Second-line treatment in ...castration-resistant patients is still unknown. We investigated the activity of abiraterone acetate as second-line treatment in ADT-resistant, AR+ patients with SGC.
This was a single-institution phase II trial. A two-stage Simon's design was applied. The primary end point was confirmed objective response rate. Secondary end points were disease control rate, safety, progression-free survival, and overall survival. Patients were eligible when the following criteria were met: histologic diagnosis of AR-overexpressing SGC, measurable disease according to RECIST 1.1, clinical and/or radiologic progression on ADT, suppressed serum testosterone, and no limits for the number of previous chemotherapy lines. All patients received abiraterone 1 g daily plus prednisone 10 mg and luteinizing hormone-releasing hormone agonist until progression or unacceptable toxicities.
From 2015 to 2019, 24 AR+ patients with SGC (23 men; median age 65.8 years) were treated within the study. The overall response rate was 21% (5 partial responses), with a disease control rate of 62.5%. The median duration of response was 5.82 months. Median progression-free survival was 3.65 months (95% CI, 1.94 to 5.89), and median overall survival was 22.47 months (95% CI, 6.74 to not reached). Objective response to previous ADT did not correlate with the activity of abiraterone. Adverse events (AEs) were recorded in 22 cases (92%) with grade 3 AEs in six patients (25%): fatigue (two), flushing (one), supraventricular tachycardia (one), and two non-drug-related AEs. No drug-related grade 4 or 5 AEs were recorded.
Abiraterone plus luteinizing hormone-releasing hormone agonist is active and safe as a second-line option in AR-expressing, castration-resistant SGC.
Anaplastic thyroid carcinoma (ATC) is a rare cancer accounting for 40% of thyroid cancer-specific deaths. In the last 5 years, improved insights into molecular pathways led the Food and Drug ...Administration to license BRAF/MEK inhibitors (B/Mi) in BRAFV600E-mutant ATC, and pembrolizumab in solid cancer with high tumour mutational burden (TMB-H) (≥10 mutations/megabase) (mut/Mb). In Europe, clinicians face challenges in prescribing novel treatments, as the European Medical Association (EMA) has not licensed B/Mi nor immunotherapy (IO) for ATC so far. Some patients manage to receive these drugs through alternative ways. We investigated the extent of this phenomenon launching an online survey from March 12th to 19th 2021 open to 239 Institutions in the EORTC Endocrine and Head & Neck Cancer Groups. Questions enquired about the number of ATC patients evaluated/year, feasibility of BRAF assessment, accessibility to B/Mi-IO, availability of clinical trials and interest in new studies. Colleagues from 94 Institutions (20 Countries) joined: 30 centres evaluated ≥5 ATC patients/year, with an overall incidence >200 patients/year. 80.8% tested BRAF status, 43.6% by next-generation sequencing. 62.7% and 70% of responders reported limitations in prescribing B/Mi and IO, respectively: either the impossibility of offering them, or drugs accessibility exclusively under certain conditions (e.g. health insurance, clinical trials, compassionate use, off-label). Only 13.8% had clinical trials ongoing while 91.5% of sites claimed ATC-dedicated trials. Disparities in access to novel treatments are diffuse. Access to cutting-edge therapies is an urgent issue in this setting, and clinical trials seem feasible within an appropriate network.
•Anaplastic thyroid carcinoma is poorly responsive to chemotherapy and highly lethal.•BRAF/MEKi and immunotherapy have shown promising results in certain subsets of ATC.•International guidelines recommend molecular testing to address appropriate therapy.•In Europe, no innovative treatments have been approved recently for advanced ATC.•This survey captures the diversified scenario of ATC diagnosis/therapy across E.U.
Human papillomavirus (HPV) DNA tumors actively integrating the E6 and E7 oncogenes have a distinct biologic behavior resulting in a more favorable prognosis. To which extent the viral integration by ...itself, and/or the associated wild-type (wt) TP53 status, and/or a functional p16 contribute to prognosis is unclear.
To clarify how the presence of high-risk (HR) -HPV, TP53, and p16INK4a status interact with clinical outcome, we considered a retrospective series of 90 consecutive oropharyngeal cancer patients treated primarily with surgery.
Seventeen (19%) patients showed integrated HPV 16 DNA (HPV positive), wt TP53 in all but two patients, normal p16INK4a in 15 assessable patients, and p16 expression in all 17 patients. Thirty-five patients (39%), two of whom were HPV positive, harbored TP53 mutations. p16INK4a deletion and p16 null immunophenotype occurred in 28 and 58 patients, respectively, and was similarly distributed in both patients with mutated TP53 (48% and 82%, respectively) and in patients with wt TP53 (46% and 77%, respectively). Statistical analysis showed that HPV-positive status significantly affects all investigated end points: overall survival (P = .0018), incidence of tumor relapse (P = .0371), and second tumor (P = .0152), whereas TP53 and p16INK4a status and p16 expression were not prognostic by themselves.
Our molecular and clinical results are in agreement with previous findings but provide additional information into the biologic mechanisms involved in HR-HPV oropharyngeal cancer in comparison to HPV-negative tumors. According to the reduced risk of relapse and second tumors associated with HR-HPV positivity of oropharyngeal cancer, the therapeutic strategy and follow-up procedures should be reviewed.
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