Intracranial metastatic disease is rarely found in head and neck cancer (HNC), in particular, cavernous sinus (CS) involvement is difficult to recognize, because of its rarity, not specific symptoms ...associated and challenging imaging features. We report our experience in 4 cases, reviewing also the English literature. We analysed data from 21 patients showing that CS metastasis is a dramatic event, with rapid onset, usually starting with neurological manifestations (ophthalmoplegia, headache and trigeminal dysesthesia) and almost unavoidable outcome (DOD in 18/21 patients). Furthermore, we assessed that the diagnostic confirmation could be difficult to perform because of the need for multiple exams and time consuming procedures. Unfortunately, usual antineoplastic therapies seem to be not effective in prolonging survival, also because patients are already weakened by primary tumour treatments. The only option that seems useful in improving outcomes is immunotherapy.
B490 (EudraCT# 2011-002564-24) is a randomized, phase 2b, noninferiority study investigating the efficacy and safety of first-line cetuximab plus cisplatin with/without paclitaxel (CetCis versus ...CetCisPac) in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
Eligible patients had confirmed R/M SCCHN (oral cavity/oropharynx/larynx/hypopharynx/paranasal sinus) and no prior therapy for R/M disease. Cetuximab was administered on day 1 (2-h infusion, 400mg/m2), then weekly (1-h infusions, 250mg/m2). Cisplatin was given as a 1-h infusion (CetCis arm: 100mg/m2; CetCisPac arm: 75mg/m2) on day 1 of each cycle for a maximum of six cycles. Paclitaxel was administered as a 3-h infusion (175mg/m2) on day 1 of each cycle. After six cycles, maintenance cetuximab was administered until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). We assumed a noninferiority margin of 1.40 as compatible with efficacy.
A total of 201 patients were randomized 1 : 1 to each regimen; 191 were assessable. PFS with CetCis (median, 6months) was noninferior to PFS with CetCisPac (median, 7months) HR for CetCis versus CetCisPac 0.99; 95% CI: 0.72–1.36,P=0.906; margin of noninferiority (90% CI of 1.4) not reached. Median overall survival was 13 versus 11months (HR=0.77; 95% CI: 0.53–1.11,P=0.117). The overall response rates were 41.8% versus 51.7%, respectively (OR=0.69; 95% CI: 0.38–1.20,P=0.181). Grade≥3 adverse event rates were 76% and 73% for CetCis versus CetCisPac, respectively, while grade 4 toxicities were lower in the two-drug versus three-drug arm (14% versus 33%,P=0.015). No toxic death or sepsis were reported and cardiac events were negligible (1%).
The two-drug CetCis regimen proved to be noninferior in PFS to a three-drug combination with CetCisPac. The median OS of both regimens is comparable with that observed in EXTREME, while the life-threatening toxicity rate appeared reduced.
EudraCT# 2011-002564-24.
Effective immunotherapy requires thorough knowledge of the tumour microenvironment. Indeed, the interplay among the immune system, the tumour and treatment is conditioned by the composition of the ...tumour microenvironment. In addition, it must be taken into account that homeostasis of the tumour microenvironment is highly dynamic and changes rapidly in function of many factors, such as inflammation, hypoxia, tumour volume, all of which change over time, and the effect of treatments. All these elements interact with each other and with conditions related to the tumour (i.e. mutational load, rate of clonal and subclonal mutations) and to host (life style, diet, obesity, age). All these factors as well as their interplay, affect the response to immunotherapy. The target of this short review is to summarise some of the major aspects that impact the homeostasis of the tumour microenvironment and how its structure can drive treatment choice.
Highlights•Interceptor trial compared concurrent chemoradiotherapy with induction chemotherapy followed by Cetuximab RT. We reported difficulty in data collection among centers with low experience. ...Expertise is needed in the treatment of LASCCHN. •Differences in accrual and quality of data reflect expertice of participating centers and number of published papers of each PI.
Trastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate (ADC), has altered the treatment landscape in breast cancer (BC), irrespective of ...the HR-receptor status. The use of the agent is increasing, however, exposure to T-DXd increases the risk of interstitial lung disease (ILD), particularly in BC patients. Although T-DXd-related ILD can be potentially severe and life-threatening, most low-grade cases can be treated safely using a multidisciplinary approach comprising early and accurate diagnosis, effective management, close monitoring, and the prompt administration of steroids. Additionally, increasing patients' education on ILD symptoms ensures close attention and enables prompt reporting, enhancing patient outcomes. It is recommended to assess predictive biomarkers in patients with risk factors for developing ILD. Currently, diagnostic criteria comprise newly identified pulmonary opacities, the relation of symptom onset to medication initiation, and the exclusion of other causes of ILD. The general condition of patients is weakened during the management of ILD (BC progression and corticosteroid treatment). Consequently, BC chemotherapy might be attenuated. This highlights the importance of preventing (high-grade) ILD, especially since its use is expanded. However, identifying high-risk patients, diagnosing, and customizing treatment is challenging and additional information on patient selection is often not fully clarified. In this paper, we provide updated multidisciplinary clinical guidance for patient selection, proactively monitoring, early diagnosing, and effectively managing T-DXd-induced ILD in HER2-positive BC patients. We describe the risk factors for developing ILD, patients’ characteristics of ILD, and the histopathological and radiographic characteristics of ILD, including real-world clinical practice report. These recommendations provide a structured step-by-step approach for managing each suspected BC-related ILD grade.
•Identifying risk factors for developing ILD is crucial in assessing suitability for T-DXd therapy and managing ILD.•Grade 4 ILD can appear as diffuse and bilateral GGOs and local parenchymal consolidation or thickened interlobular.•In cases of symptomatic ILD, treatment with T-DXd should be discontinued immediately.•The five “S” rules help enhance patient outcomes by reducing the severity of ILD and fatal outcomes.•Implementing a supportive reference chest CT image retrieval system with deep learning enhances the diagnostic ability.
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