Lung cancer and type 2 diabetes experience in Dolj County (southwest region of Romania) - a clinical, bioclinical and pathological study.

BACKGROUND AND AIM: Type 2 diabetes (T2D) and cancer, the most important public health problems nowadays, and the mechanisms between the presence of diabetes and the development of malignancies remain unclear. The leading cause of cancer death in 2020 is attributed to lung cancer. This study aimed to highlight the impact of the association of these two diseases and the predominant histopathological type of lung cancer in the selected group, glycemic imbalance, and information about the course and outlook for these patients. PATIENTS, MATERIALS AND METHODS: The authors proposed a case-control 10-year period study, between 2007 and 2017, of two groups of patients diagnosed with T2D and lung cancer who underwent hospitalization at the Clinic of Medical Oncology, Emergency County Hospital, Craiova, Romania. RESULTS: Our study showed a higher incidence of lung adenocarcinoma in patients diagnosed with T2D. The inflammatory syndrome is more pronounced in the diabetic group, which is supported by correlations between lactate dehydrogenase (LDH), albumin, and hemoglobin levels. CONCLUSIONS: The duration of cancer treatment in lung cancer and the survival rate is strongly influenced by the presence of diabetes as a concomitant disease.

Implications of diabetes in head and neck cancer - A single center real-world data.

Diabetes mellitus (DM) and altered glucose metabolism have been associated with carcinogenesis, but also with prognosis and tolerance to treatment in different types of cancer. Head and neck cancers (HNC), the sixth most common malignancy worldwide, require a multimodal approach, especially in advanced stages and cancer specific treatment is often associated with therapeutic failure and severe toxicities even if it is delivered according to current standards. The aim of the study was to evaluate the clinical, biological and outcomes implications of DM in patients with HNC. The cases diagnosed with HNC associated with DM between January 2008 and December 2016 were selected from the database of the oncology clinic and the oncology outpatient clinic of the Craiova County Hospital. Under the limits of a relatively reduced patient lot of 23 cases, certain particular aspects of these cases are highlighted possibly due to the association of DM with HNC. This category of patients should not be treated differently even if a precaution is necessary due to the increased risk of complications related to treatment. The use of Metformin could bring outcome benefit and the treatment of DM with insulin could be associated with a worst prognostic. The use of poly-chemotherapy regimens (platinum double or triple combination including platinum salts) demonstrates the feasibility of using chemotherapy for these subtypes of patients. A tendency to de-escalate the treatment by omitting radiotherapy for this category of patients should also be noted. Neutrophil to lymphocyte ratio (NLR), a less specific biomarker could be less useful than the Glasgow Prognostic Score (GPS) which can be considered an accessible biomarker. A large percent of sinonasal cancers compared to the data reported in the literature could be also related to DM. Both this possible association and the benefit of Metformin and 5-Flurouracil must be reevaluated in studies in larger groups of patients (Ref. 25). Keywords: diabetes, head and neck cancers, metformin, toxicity, outcomes, chemotherapy.

Immunotherapy and radiotherapy - a future partnership Focus on radiation induced lymphopenia (RIL) implications.

The hematological toxicity associated with radiotherapy is represented by neutropenia, anemia, thrombocytopenia, being associated with the increased risk of infection with opportunists, with fatigue and intolerance to effort, but also with the increased risk of bleeding. In the context of the preclinical and clinical results that mention the synergistic effect of the immunotherapy-radiotherapy association, radiation-induced lymphopenia (RIL) becomes an immunosuppression factor, a factor that would tip the fragile antitumor immunopotentiation-immunosuppression balance in favor of the immunosuppressive effect. Both the number of lymphocytes and the neutrophil/lymphocyte ratio (NLR) are prognostic and predictive biomarkers, providing information on the immune status of the host and on a possible response of the tumor to immunotherapy. Modern radiation techniques can increase the risk of lymphopenia by irradiating large volumes of tissue with low doses of radiation. In this context, a redefinition of the dose-volume constraints and the definition of bone marrow, lymphoid organs and lymph nodes not involved in tumors as organs at risk (OARs) is strictly necessary in the case of using irradiation through intensity-modulated radiation therapy (IMRT) techniques or volumetric modulated arc therapy (VMAT) for solid tumors that benefit from immune checkpoint inhibitor (ICI) therapy (Ref. 22). Text in PDF www.elis.sk Keywords: lymphopenia, immunotherapy, radiotherapy, toxicity, spleen, nodes irradiation.

Hypofractionated Whole-Breast Irradiation Focus on Coronary Arteries and Cardiac Toxicity-A Narrative Review.

Breast cancer is the most common cancer among women worldwide, which is often treated with radiotherapy. Whole breast irradiation (WBI) is one of the most common types of irradiation. Hypo-fractionated WBI (HF-WBI) reduces the treatment time from 5 to 3 weeks. Recent radiobiological and clinical evidence recommended the use of HF-WBI regardless of the age or stage of disease, and it is proven that hypo-fractionation is non-inferior to conventional fractionation regimen irradiation. However, some studies report an increased incidence of heart-related deaths in the case of breast irradiation by hypo-fractionation, especially in patients with pre-existing cardiac risk factors at the time of treatment. Due to the new technical possibilities of radiotherapy techniques, HF-WBI can reduce the risk of cardiac toxicity by controlling the doses received both by the heart and by the anatomical structures of the heart. The radiobiological "double trouble", in particular "treble trouble", for hypo-fractionated regimen scan be avoided by improving the methods of heart sparing based on image-guided irradiation (IGRT) and by using respiration control techniques so that late cardiac toxicity is expected to be limited. However, long-term follow-up of patients treated with HF-WBI with modern radiotherapy techniques is necessary considering the progress of systemic therapy, which is associated with long-term survival, and also the cardiac toxicity of new oncological treatments. The still unknown effects of small doses spread in large volumes on lung tissue may increase the risk of second malignancy, but they can also be indirectly involved in the later development of a heart disease. It is also necessary to develop multivariable radiobiological models that include histological, molecular, clinical, and therapeutic parameters to identify risk groups and dosimetric tolerance in order to limit the incidence of late cardiac events. MR-LINAC will be able to offer a new standard for reducing cardiac toxicity in the future, especially in neoadjuvant settings for small tumors.

Radiobiological approach to treatment gaps in locally advanced head and neck cancers radical radiotherapy arising from the COVID-19 pandemic.

Gaps of radiotherapy treatment are one of the factors recognized as unfavorable in terms of tumor control and disease prognosis. All strategies for compensating the negative effect of radiotherapy treatment gaps are based on radiobiological models. Using the modified square linear formalism (Dale`s equation) it is possible to calculate the additional dose in order to compensate the accelerated tumor repopulation effect. SARS-CoV-2 infection is an important factor that can lead to an interruption of irradiation for medium and long- term intervals. We aim to present the radiobiological data underlying the recalculation of radiotherapy treatment and exemplification for different clinical scenarios in the case of head and neck cancers (Ref. 17). Keywords: adiobiology, treatment gaps, locally advanced head and neck cancers, radical radiotherapy, COVID-19 pandemic.

Synergies Radiotherapy-Immunotherapy in Head and Neck Cancers. A New Concept for Radiotherapy Target Volumes-"Immunological Dose Painting".

The combination of immune checkpoint inhibitors and definitive radiotherapy is investigated for the multimodal treatment of cisplatin non-eligible locally advanced head and neck cancers (HNC). In the case of recurrent and metastatic HNC, immunotherapy has shown benefit over the EXTREME protocol, being already considered the standard treatment. One of the biggest challenges of multimodal treatment is to establish the optimal therapy sequence so that the synergistic effect is maximal. Thus, superior results were obtained for the administration of anti-CTLA4 immunotherapy followed by hypofractionated radiotherapy, but the anti-PD-L1 therapy demonstrates the maximum potential of radio-sensitization of the tumor in case of concurrent administration. The synergistic effect of radiotherapy-immunotherapy (RT-IT) has been demonstrated in clinical practice, with an overall response rate of about 18% for HNC. Given the demonstrated potential of radiotherapy to activate the immune system through already known mechanisms, it is necessary to identify biomarkers that direct the "nonresponders" of immunotherapy towards a synergistic RT-IT stimulation strategy. Stimulation of the immune system by irradiation can convert "nonresponder" to "responder". With the development of modern techniques, re-irradiation is becoming an increasingly common option for patients who have previously been treated with higher doses of radiation. In this context, radiotherapy in combination with immunotherapy, both in the advanced local stage and in recurrent/metastatic of HNC radiotherapy, could evolve from the "first level" of knowledge (i.e., ballistic precision, dose conformity and homogeneity) to "level two" of "biological dose painting" (in which the concept of tumor heterogeneity and radio-resistance supports the need for doses escalation based on biological criteria), and finally to the "third level" ofthe new concept of "immunological dose painting". The peculiarity of this concept is that the radiotherapy target volumes and tumoricidal dose can be completely reevaluated, taking into account the immune-modulatory effect of irradiation. In this case, the tumor target volume can include even the tumor microenvironment or a partial volume of the primary tumor or metastasis, not all the gross and microscopic disease. Tumoricidal biologically equivalent dose (BED) may be completely different from the currently estimated values, radiotherapy treating the tumor in this case indirectly by boosting the immune response. Thus, the clinical target volume (CTV) can be replaced with a new immunological-clinical target volume (ICTV) for patients who benefit from the RT-IT association (Image 1).

Radiomic Machine Learning and Texture Analysis - New Horizons for Head and Neck Oncology.

Radiomics is a relatively new concept that consists of extracting data from images and applies advanced characterization algorithms to generate imaging features. These features are biomarkers with prognostic and predictive value, which provide a characterization of tumor phenotypes in a non-invasive manner. The clinical application of radiomics is hampered by challenges such as lack of image acquisition and analysis standardization. Textural features extracted from computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT) images of patients diagnosed with head and neck cancers can be used in the pre-therapeutic evaluation of the response to multimodal chemo-radiotherapy. For patients with positive HPV-oropharyngeal cancers, the correlation of the radiomic textural features from the tumor with p16 values from the pathological sample can identify tumor specific signatures in CT imaging, an entity with favorable prognosis and a better response to chemo-radiotherapy. Pretreatment contrast CT-scans were extracted and radiomics analysis of gross tumor volume were performed using MaZda package apart from MaZda software containing B11 program for texture analysis and visualization. Data set was randomly divided into a training dataset and a test dataset and machine learning algorithms were applied to identify a textural radiomic signature. Radiomic texture analysis and machine learning algorithms demonstrate a predictive potential related to the capability of stratification for subclasses of platinum-chemotherapy resistance and radioresistant head and neck cancers requiring an intensification of multimodal treatment.