O Impacto dos Sintomas Orais Gerados por Quimioterapia e Radioterapia / The Impact of Oral Symptoms Generated by Chemotherapy and Radiotherapy

Os primeiros efeitos da radioterapia e da quimioterapia antineoplásica acontecem sobre as células do epitélio oral, as quais sofrem rápida proliferação. O tamanho destes efeitos depende de muitos fatores ligados ao tratamento, ao paciente e ao tumor. No que se trata do paciente, interferem nesse processo o seu estado geral de saúde, presença de comorbidades, sexo, estado nutricional, idade, fatores sociais e psicológicos, além de hábitos deletérios e patologias orofaciais preexistentes. Esses adoecimentos na integridade bucal devem-se a veracidade de que a radioterapia e quimioterapia não são capazes de destruir as células tumorais sem lesionar células normais. O tratamento oncológico pode provocar reações adversas na cavidade oral, e é comum, em pacientes oncológicos submetidos ao tratamento antineoplásico, o desenvolvimento de agravamentos orais agudos ou tardios.---The first effects of radiotherapy and antineoplastic chemotherapy happen on the cells of the oral epithelium, which quickly notice proliferation. The size of these effects depends on many factors related to the treatment, the patient, and the tumor. With regard to the patient, this process interferes with their general health status, presence of comorbidities, gender, nutritional status, age, social and psychological factors, in addition to deleterious habits and pre-existing orofacial pathologies. These illnesses in the oral integrity are due to the veracity that radiotherapy and chemotherapy are not capable of destroying tumor cells without normal cells. Oncological treatment can cause adverse reactions in the oral cavity, and it is common, in cancer patients, to antineoplastic treatment, to develop acute or late oral aggravations.

Treatment-induced sarcoidosis in a patient with metastatic clear cell ovarian cancer

Sarcoidosis is a granulomatous disease that commonly presents with lung or lymphatic system manifestations. Diagnosis is often delayed due to variable clinical presentation. This is a case of a patient with metastatic clear cell ovarian cancer who developed disease reoccurence after definitive treatment with surgery and adjuvant chemotherapy. She was treated with multiple lines of therapy, including investigational agents. During this time, she developed mediastinal lymphadenopathy and hypercalcaemia. Due to suspicion that her presentation was not a manifestation of her malignancy, she underwent two lymph node biopsies revealing granulomatous disease. She was initiated on prednisone for management of sarcoidosis, which led to radiologic, laboratory and symptomatic improvement. Although the precipitating factor for this patient’s sarcoidosis cannot be definitively determined, nivolumab is a possible culprit. This case highlights the importance of a broad differential diagnosis when a patient undergoing antineoplastic treatment develops mediastinal lymphadenopathy or hypercalcaemia.

Late dental effects of chemotherapy and radiotherapy in childhood cancer survivor: case report

Chemotherapy drugs and radiotherapy in the head and neck region are considered possible to interfere with odontogenesis. Patients may present alterations such as tooth agenesis, shortening or root malformation, enamel hypoplasia and microdontia. Such effects do not occur in adults, as they already have the dental structures formed. The objective of this study is to describe, through a case report, the dental alterations and implications for the clinical practice of a patient who received chemotherapy and radiotherapy in childhood. A 12- year-old female patient was diagnosed with embryonal rhabdomyosarcoma in the right parotid gland region at 5 years of age. Antineoplastic treatment consisted of IRS IV chemotherapy protocol: ifosfamide (IFO) - doxorubicin (DOXO) - etoposide (VP16) followed by vincristine - dactinomycin - cyclophosphamide (VAC) / vincristine - ifosfamide - etoposide (VIE) alternated, in addition to conventional radiotherapy, with a total dose of 45 Gy. The patient developed important dental alterations, such as root malformation in most teeth, microdontia and enamel hypoplasia, being essential the role of the dentist. Currently, after 6 years of anticancer treatment, she has regular dental follow-up.

Impact of the absence of dental support on cancer patients during the COVID-19 pandemic

Purpose With the suspension of routine services due to the coronavirus disease-2019 (COVID-19) pandemic, a significant number of the population has been presenting acute oral alterations without proper treatment. Through telecontact, this study aimed to identify individuals in treatment and had been treated for cancer who had their clinical dental care interrupted by the COVID-19 pandemic. Methods Individuals with oncologic diseases were selected from a telephone list of a clinical research center specializing in the care of cancer patients. We included those who answered an online questionnaire about their general health status and oral problems when they were unable to access dental care during the pandemic. Statistical analysis was performed using Fisher and Chi-square tests. The significance level was set at 5% (p<0.05). Results Of the 280 patients recruited, 104 answered the questionnaire. There were 75 (72.1%) were women, of which 22 (36.7%) were under antineoplastic treatment, and 30 (68.2%) had already been treated; 29 (27.9%) were men, of which 15 (25.0%) were under antineoplastic treatment and 14 (31.8%) had already been treated. Of the universal sample, 64 (61.5%) had no complaints regarding their general health, and 74 (71.1%) had no difficulties in their daily activities due to teeth/mouth problems. However, the rates of oral problems were not statistically significant (p=NS). Conclusion In dentistry, telephone support and digital tools are useful and necessary instruments for the follow-up of cancer patients during the pandemic.

Antineoplastics Encapsulated in Nanostructured Lipid Carriers

Ideally, antineoplastic treatment aims to selectively eradicate cancer cells without causing systemic toxicity. A great number of antineoplastic agents (AAs) are available nowadays, with well-defined therapeutic protocols. The poor bioavailability, non-selective action, high systemic toxicity, and lack of effectiveness of most AAs have stimulated the search for novel chemotherapy protocols, including technological approaches that provide drug delivery systems (DDS) for gold standard medicines. Nanostructured lipid carriers (NLC) are DDS that contain a core of solid and lipid liquids stabilised by surfactants. NLC have high upload capacity for lipophilic drugs, such as the majority of AAs. These nanoparticles can be prepared with a diversity of biocompatible (synthetic or natural) lipid blends, administered by different routes and functionalised for targeting purposes. This review focused on the research carried out from 2000 to now, regarding NLC formulations for AAs (antimetabolites, antimitotics, alkylating agents, and antibiotics) encapsulation, with special emphasis on studies carried out in vivo. NLC systems for codelivery of AAs were also considered, as well as those for non-classical drugs and therapies (natural products and photosensitisers). NLC have emerged as powerful DDS to improve the bioavailability, targeting and efficacy of antineoplastics, while decreasing their toxic effect in the treatment of different types of cancer.

Expanded access to anticancer treatments from conversion to biosimilar pegfilgrastim-cbqv in US breast cancer patients

Aim: To estimate cost-savings from conversion to biosimilar pegfilgrastim-cbqv that could be reallocated to provide budget-neutral expanded access to AC (doxorubicin/cyclophosphamide) and TCH (docetaxel/carboplatin/trastuzumab) in breast cancer (BC) patients. Methods: Simulation modeling in panels of 20,000 BC and 5000 HER2-positive (HER2+ BC) patients, varying treatment duration (one–six cycles) and conversion rates (10–100%), to estimate cost-savings and additional AC and TCH treatment that could be provided. Results: In 20,000 patients, cost-savings of $1,083 per-patient per-cycle translate to $21,652,064 (one cycle) to $129,912,397 (six cycles). Savings range from $5,413,016 to $32,478,097, respectively, in the 5000-patient HER2+ BC panel. Conclusion: Conversion to pegfilgrastim-cbqv could save up to $130 million and provide more than 220,000 additional cycles of antineoplastic treatment on a budget-neutral basis to BC patients.

Heterogeneity of Cancer Stem Cells in Tumorigenesis, Metastasis, and Resistance to Antineoplastic Treatment of Head and Neck Tumours

The discovery of a small subset of cancer cells with self-renewal properties that can give rise to phenotypically diverse tumour populations has shifted our understanding of cancer biology. Targeting cancer stem cells (CSCs) is becoming a promising therapeutic strategy in various malignancies, including head and neck squamous cell carcinoma (HNSCC). Diverse sub-populations of head and neck cancer stem cells (HNCSCs) have been identified previously using CSC specific markers, the most common being CD44, Aldehyde Dehydrogenase 1 (ALDH1), and CD133, or by side population assays. Interestingly, distinct HNCSC subsets play different roles in the generation and progression of tumours. This article aims to review the evidence for a role of specific CSCs in HNSCC tumorigenesis, invasion, and metastasis, together with resistance to treatment.

Crosstalk between autophagy inhibitors and endosome-related secretory pathways: a challenge for autophagy-based treatment of solid cancers

Autophagy is best known for its role in organelle and protein turnover, cell quality control, and metabolism. The autophagic machinery has, however, also adapted to enable protein trafficking and unconventional secretory pathways so that organelles (such as autophagosomes and multivesicular bodies) delivering cargo to lysosomes for degradation can change their mission from fusion with lysosomes to fusion with the plasma membrane, followed by secretion of the cargo from the cell. Some factors with key signalling functions do not enter the conventional secretory pathway but can be secreted in an autophagy-mediated manner.Positive clinical results of some autophagy inhibitors are encouraging. Nevertheless, it is becoming clear that autophagy inhibition, even within the same cancer type, can affect cancer progression differently. Even next-generation inhibitors of autophagy can have significant non-specific effects, such as impacts on endosome-related secretory pathways and secretion of extracellular vesicles (EVs). Many studies suggest that cancer cells release higher amounts of EVs compared to non-malignant cells, which makes the effect of autophagy inhibitors on EVs secretion highly important and attractive for anticancer therapy. In this review article, we discuss how different inhibitors of autophagy may influence the secretion of EVs and summarize the non-specific effects of autophagy inhibitors with a focus on endosome-related secretory pathways. Modulation of autophagy significantly impacts not only the quantity of EVs but also their content, which can have a deep impact on the resulting pro-tumourigenic or anticancer effect of autophagy inhibitors used in the antineoplastic treatment of solid cancers.

Cannabinoids: an Effective Treatment for Chemotherapy-Induced Peripheral Neurotoxicity?

Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most frequent side effects of antineoplastic treatment, particularly of lung, breast, prostate, gastrointestinal, and germinal cancers, as well as of different forms of leukemia, lymphoma, and multiple myeloma. Currently, no effective therapies are available for CIPN prevention, and symptomatic treatment is frequently ineffective; thus, several clinical trials are addressing this unmet clinical need. Among possible pharmacological treatments of CIPN, modulation of the endocannabinoid system might be particularly promising, especially in those CIPN types where analgesia and neuroinflammation modulation might be beneficial. In fact, several clinical trials are ongoing with the specific aim to better investigate the changes in endocannabinoid levels induced by systemic chemotherapy and the possible role of endocannabinoid system modulation to provide relief from CIPN symptoms, a hypothesis supported by preclinical evidence but never consistently demonstrated in patients. Interestingly, endocannabinoid system modulation might be one of the mechanisms at the basis of the reported efficacy of exercise and physical therapy in CIPN patients. This possible virtuous interplay will be discussed in this review.