Positive correlation between persistence of medical nutrition therapy and overall survival in patients with head and neck cancer.

Background: Several factors can affect overall survival of head and neck cancer (HNC) patients, including characteristics of the cancer disease and response to treatments. However, patients' nutritional status and the effectiveness of medical nutrition therapy (MNT) can also impact overall survival. The primary goal of our research was to collect real-life data on the use of MNT in HNC patients and to specifically investigate the correlation between survival and the duration of uninterrupted (persistent) nutrition. Method: The data of this retrospective, analytical, cohort study was collected from electronic healthcare records from the Hungarian National Health Insurance Fund Management. Overall, 38,675 HNC patients' data of the period between 2012 and 2021 was used. We applied multi-step exclusions to identify patient groups accurately and to avoid biasing factors. Statistical analysis was done by the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: Throughout the investigated period 16,871 (64%) patients received MNT therapy out of 26,253 newly diagnosed patients (≥18 years). In terms of the persistence of MNT, we divided the patients into three groups (1-3; 4-6; ≥7-month duration of MNT). When comparing these groups, we found that patients receiving long-term (≥7 months) MNT had a significantly longer overall survival (p < 0.0001) than those who received MNT for a shorter duration, both in locally advanced and recurrent/metastatic cases. Conclusion: The main outcome of the study is that there is a positive correlation between the persistence of MNT and the overall survival in HNC patients when nutritional intervention lasts several months. It highlights the responsibility of the specialists during the patient journey to use MNT early and to continue its use for as long as it is beneficial to the patients.

[Effect of long-term medical nutrition therapy on the survival of head and neck cancer patients - based on real-world data]. / Hosszú távú orvosi felügyeletet igénylo táplálásterápia hatása a fej-nyak tumoros betegek túlélésére ­ valós bizonyítékú adatok alapján.

At the 45th Congress of ESPEN (The European Society for Clinical Nutrition and Metabolism), we presented for the first time the initial results of our 2023 oncology research, in which we revealed positive correlations between the persistence of medical nutrition therapy and overall survival, in head and neck cancer patients. Patients who received longterm nutrition therapy (≥7 months) had a significantly longer survival (p<0.0001) than those who received only short-term nutrition therapy intervention, i.e., for 1-3 months. The aim, methodology and results of the Hungarian research aroused the interest of the congress participants; therefore, we also publish it in Hungarian in the form of a short notice.

Evaluating comprehensive cancer networks; a review of standards and evaluation methods for care networks to inform a comparison with the OECI comprehensive cancer network standards.

INTRODUCTION: To ensure that all citizens have equal access to high-quality cancer diagnosis and care, the EU4Health Programme, Europe's Beating Cancer Plan, and Horizon Europe's Cancer Mission propose Comprehensive Cancer Infrastructures in every European Union Member State. It is therefore important to establish the basic principles for high-performing cancer networks and a methodology for evaluating their quality and effectiveness. This article describes methods and standards/indicators for network evaluation found in literature, gives a comparative overview of the new OECI European Cancer Network Quality standards, and proposes principles for evaluating the performance of Comprehensive Cancer Networks as a basis for continuous improvement. MATERIALS AND METHODS: We performed a scoping literature review on methods and standards/indicators for care-network evaluation. We then compared the OECI set with literature findings, categorised standards that were similar, reflected on standards that were different, and deduced principles for quality standards for cancer networks. RESULTS: Of 1002 articles identified, 17 reported on evaluation methods and/or (mostly) qualitative indicators. Sixteen studies described indicators/standards for evaluating care networks, critical success factors or desirable outcomes. Of the 54 present OECI standards, 32 had a literature equivalent. No literature equivalent was found for 22 standards, especially on those related to the combination of care and research. The proposed OECI evaluation methods (survey, document review, and interviews) were all reported in the literature. From the conformity of these results, we deduced 8 principles for standards evaluating the effectiveness of Comprehensive Cancer Networks. CONCLUSIONS: Research on the evaluation of the effectiveness of care networks is scarce. Evaluation methods vary and are often single time-point assessments. The OECI set contributes to establishing clear principles and standards to evaluate the effectiveness of Comprehensive Cancer Networks.

Long-term nutrition in patients candidate to neoadjuvant and adjuvant treatments.

To improve outcomes, to decrease the rate of local recurrence and development of distant metastases neoadjuvant and adjuvant therapies are employed in cancer patients in forms of radiation, chemo-, endocrine-, targeted-, and immunotherapy or their combination. Nutrition therapy plays important role in all phases of the cancer journey. From neoadjuvant therapy to prehabilitation, early postoperative nutrition, and long-term nutrition care during the adjuvant phase and survivorship determines the survival and quality of life of cancer patients. During the neoadjuvant phase patients may be in poor nutritional condition which can be aggravated by the applied oncological treatment. Beside this apparent threat this period also gives an excellent opportunity to maintain or even improve the nutritional status of the patients by nutrition therapy. After surgery the burdening effects of the operation may jeopardize the execution of adjuvant therapy. After early postoperative feeding a long-term nutrition strategy should be developed for cancer patients in order to avoid nutritional deterioration during the usually lengthy postoperative therapy. In this narrative review we discuss how preoperative nutritional status and medical nutrition therapy influence the results of surgery and after the operation what is the available evidence about nutritional status and outcome and the potentials to influence them by nutrition therapy.

Case Report: A Novel Pathomechanism in PEComa by the Loss of Heterozygosity of TP53.

Since the introduction of next-generation sequencing, the frequency of germline pathogenic TP53 variants and the number of cases with unusual clinical presentations have been increasing. This has led to the expansion of the classical Li-Fraumeni syndrome concept to a wider cancer predisposition syndrome designated as the Li-Fraumeni spectrum. Here, we present a case with a malignant, metastatic perivascular epithelioid cell tumor (PEComa) of the thigh muscle and a sinonasal carcinoma harboring a novel TP53 germline splice mutation (NM_000546.5:c.97-2A>C). The classical presentation of LFS in the long-since deceased mother and the presence of a germline TP53 variant in the proband suggested a possible familial TP53-related condition. Complex pathological, molecular, and clinical genetic analyses (whole exome sequencing of germline variants, multigene panel sequencing of tumor DNA, Sanger validation, an in vitro functional test on splicing effect, 3D protein modeling, p53 immunohistochemistry, and pedigree analysis) were performed. The in vitro characterization of the splice mutation supported the pathogenic effect that resulted in exon skipping. A locus-specific loss of heterozygosity in the PEComa but not in the sinonasal carcinoma was identified, suggesting the causative role of the splice mutation in the PEComa pathogenesis, because we excluded known pathogenetic pathways characteristic to PEComas (TSC1/2, TFE3, RAD51B). However, the second hit affecting TP53 in the molecular pathogenesis of the sinonasal carcinoma was not identified. Although PEComa has been reported previously in two patients with Li-Fraumeni syndrome, to the best of our knowledge, this is the first report suggesting a relationship between the aberrant TP53 variant and PEComa.

Az alacsony testtömegindex és testtömegcsökkenés vizsgálata magyar tüdodaganatos betegek adatainak felhasználásával.

During oncological treatments, body mass index (BMI) and weight loss (WL) are important prognostic factors, but can be influenced by nutrition therapy. The aim of the study was to collect data on BMI and WL of patients with lung cancer and on the nutritional therapy influencing malnutrition. In our multicenter, retrospective study involving 1616 patients, data were collected using a questionnaire with 51 questions, and statistical analysis was performed with descriptive, and multivariate analysis methods with IBM SPSS 20 software. According to the method of Martin, based on BMI and WL, patients were ranked on a scale of 0 to 4 (grade 0 24.9%; grade 1 20.7%; grade 2 14.9%; grade 3 22.4%; grade 4 17.0%). Based on this data low BMI and WL may affect survival in 75.1%. In contrast, only 37.6% of patients received nutritional therapy, based on 47 different strategies. The data substituted into the prognostic matrix highlights that weight loss may shorten patients' survival. The 47 strategies indicate that the use of nutritional therapy is inconsistent throughout this patient cohort.

COVID-19 Vaccinations: Summary Guidance for Cancer Patients in 28 Languages: Breaking Barriers to Cancer Patient Information.

BACKGROUND: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations' delivery and their application in the world's population and generates information inequalities across the different populations. METHODS: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries. RESULTS: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population. CONCLUSION: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level.

[Radiotherapy of pancreatic cancer]. / A hasnyálmirigyrák sugárterápiája.

The therapy of pancreatic cancer is fundamentally based on surgical removal and chemotherapy. The available evidence and results of publications concerning the application of radiotherapy are controversial. Accordingly, the international guidelines formulated by radiation oncology organizations have paramount interest in this particular pathology. Answers are eagerly awaited in several unclear questions from ongoing, or recently closed, yet unpublished trials. Modern radiotherapy techniques, like stereotactic radiotherapy, or actually less available modalities, like particle therapy or magnetic resonance imaging guided radiotherapy show promising results, as well as combination of radiation with immunotherapy.

Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial.

BACKGROUND: Chemoradiotherapy is the standard of care for unresected locally advanced squamous cell carcinoma of the head and neck. We aimed to assess if addition of avelumab (anti-PD-L1) to chemoradiotherapy could improve treatment outcomes for this patient population. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 study, patients were recruited from 196 hospitals and cancer treatment centres in 22 countries. Patients aged 18 years or older, with histologically confirmed, previously untreated, locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, larynx, or oral cavity (unselected for PD-L1 status), an Eastern Cooperative Oncology Group performance status score of 0 or 1, and who could receive chemoradiotherapy were eligible. Patients were randomly assigned (1:1) centrally by means of stratified block randomisation with block size four (stratified by human papillomavirus status, tumour stage, and nodal stage, and done by an interactive response technology system) to receive 10 mg/kg avelumab intravenously every 2 weeks plus chemoradiotherapy (100 mg/m2 cisplatin every 3 weeks plus intensity-modulated radiotherapy with standard fractionation of 70 Gy [35 fractions during 7 weeks]; avelumab group) or placebo plus chemoradiotherapy (placebo group). This was preceded by a single 10 mg/kg avelumab or placebo lead-in dose given 7 days previously and followed by 10 mg/kg avelumab or placebo every 2 weeks maintenance therapy for up to 12 months. The primary endpoint was progression-free survival by investigator assessment per modified Response Evaluation Criteria in Solid Tumors, version 1.1, in all randomly assigned patients. Adverse events were assessed in patients who received at least one dose of avelumab or placebo. This trial is registered with ClinicalTrials.gov, NCT02952586. Enrolment is no longer ongoing, and the trial has been discontinued. FINDINGS: Between Dec 12, 2016, and Jan 29, 2019, from 907 patients screened, 697 patients were randomly assigned to the avelumab group (n=350) or the placebo group (n=347). Median follow-up for progression-free survival was 14·6 months (IQR 8·5-19·6) in the avelumab group and 14·8 months (11·6-18·8) in the placebo group. Median progression-free survival was not reached (95% CI 16·9 months-not estimable) in the avelumab group and not reached (23·0 months-not estimable) in the placebo group (stratified hazard ratio 1·21 [95% CI 0·93-1·57] favouring the placebo group; one-sided p=0·92). The most common grade 3 or worse treatment-related adverse events were neutropenia (57 [16%] of 348 patients in the avelumab group vs 52 [15%] of 344 patients in the placebo group), mucosal inflammation (50 [14%] vs 45 [13%]), dysphagia (49 [14%] vs 47 [14%]), and anaemia (41 [12%] vs 44 [13%]). Serious treatment-related adverse events occurred in 124 (36%) patients in the avelumab group and in 109 (32%) patients in the placebo group. Treatment-related deaths occurred in two (1%) patients in the avelumab group (due to general disorders and site conditions, and vascular rupture) and one (<1%) in the placebo group (due to acute respiratory failure). INTERPRETATION: The primary objective of prolonging progression-free survival with avelumab plus chemoradiotherapy followed by avelumab maintenance in patients with locally advanced squamous cell carcinoma of the head and neck was not met. These findings may help inform the design of future trials investigating the combination of immune checkpoint inhibitors plus CRT. FUNDING: Pfizer and Merck KGaA, Darmstadt, Germany.

Analysing the attributes of Comprehensive Cancer Centres and Cancer Centres across Europe to identify key hallmarks.

There is a persistent variation in cancer outcomes among and within European countries suggesting (among other causes) inequalities in access to or delivery of high-quality cancer care. European policy (EU Cancer Mission and Europe's Beating Cancer Plan) is currently moving towards a mission-oriented approach addressing these inequalities. In this study, we used the quantitative and qualitative data of the Organisation of European Cancer Institutes' Accreditation and Designation Programme, relating to 40 large European cancer centres, to describe their current compliance with quality standards, to identify the hallmarks common to all centres and to show the distinctive features of Comprehensive Cancer Centres. All Comprehensive Cancer Centres and Cancer Centres accredited by the Organisation of European Cancer Institutes show good compliance with quality standards related to care, multidisciplinarity and patient centredness. However, Comprehensive Cancer Centres on average showed significantly better scores on indicators related to the volume, quality and integration of translational research, such as high-impact publications, clinical trial activity (especially in phase I and phase IIa trials) and filing more patents as early indicators of innovation. However, irrespective of their size, centres show significant variability regarding effective governance when functioning as entities within larger hospitals.

Chromosomal Aberrations in Blood Lymphocytes as Predictors of Respiratory Function After Stereotactic Lung Irradiation.

Due to the profound difference in radiosensitivity of patients and various side effects caused by this phenomenon, a radiosensitivity marker is needed. Prediction by a marker may help personalise the treatment. In this study, we tested chromosomal aberrations (CA) of in vitro irradiated blood as predictor of pulmonary function decrease of nonsmall cell lung cancer (NSCLC) patients and also compared it with the CAs in the blood of irradiated patients. Peripheral blood samples were taken from 45 lung cancer patients before stereotactic radiotherapy (SBRT) and immediately after the last fraction and 3, 6, 9, 12, 15, 18, 21, and 24 months later. Respiratory function measurements were performed at the same time. Diffusing capacity of lung for carbon monoxide (DLCO), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1s), and FEV1s/FVC (FEV1%) were monitored. Metaphase preparations of lymphocytes were made with standard procedures, and chromosome aberrations were analysed. In our cohort, the 36-month local relapse-free survival was 97.4%, and the distant metastasis-free survival was 71.5% at 36 months. There was no change in the mean of the pulmonary function tests (PFTs) after the therapy. However, there was a considerable variability between the patients. Therefore, we subtracted the baseline and normalised the PFT values. There were significant decreases at 12-24 months in relative FEV1s and relative FEV1%. The tendentious decrease of the PFTs could be predicted by the in vitro chromosome aberration data. We also found connections between the in vitro and in vivo CA values (i.e., dicentrics plus rings after 3 Gy irradiation predicts dicentric-plus-ring value directly after the radiotherapy/V54 Gy (p = 0.001 24.2%)). We found that-after further validation-chromosome aberrations resulted from in vitro irradiation before radiotherapy can be a predictive marker of pulmonary function decrease after lung irradiation.

Radiation-Induced Oral Mucositis in Head and Neck Cancer Patients. Five Years Literature Review.

Backround: Radiation-induced oral mucositis consists of a series of relatively frequent side effects after head and neck cancer radiotherapy and has an adverse impact on both regular treatment process and the quality of life of patients. OBJECTIVE: The purpose of the present review is to optimize the current management of radiation-induced oral mucositis in head and neck cancer patients. METHODS: PubMed database research was performed on articles published since 2015 that demonstrated efficacy in the management of radiation-induced oral mucositis in head and neck cancer patients. The study selection included observational, prospective, comparative, randomized, double- blind, placebo-controlled or uncontrolled, and retrospective studies, as well as systematic reviews and metanalyses. RESULTS: From the 931 citations obtained from the search, only 94 articles met the inclusion criteria, including mucosal protectants, anti-inflammatory agents, growth factors, and various miscellaneous and natural agents. Several methods, including both pharmacological and natural agents, have been proposed for the management of oral mucositis. In addition to the already known interventions with strong evidence, according to the Multinational Association of Supportive Care in Cancer and he International Society of Oral Oncology guidelines, further agents have been used. However, a great number of them lack clear evidence, which surely requires the design of more controlled clinical trials for a better assessment of the ideal methods. CONCLUSION: The management of oral mucositis constitutes an active area of research. In light of these results, it is aimed to illustrate those treatment strategies that are most effective regarding the treatment approach of oral mucositis.

European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCC): Lung cancer.

European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCC) are written by experts representing all disciplines involved in cancer care in Europe. They give patients, health professionals, managers and policymakers a guide to essential care throughout the patient journey. Lung cancer is the leading cause of cancer mortality and has a wide variation in treatment and outcomes in Europe. It is a major healthcare burden and has complex diagnosis and treatment challenges. Care must only be carried out in lung cancer units or centres that have a core multidisciplinary team (MDT) and an extended team of health professionals detailed here. Such units are far from universal in European countries. To meet European aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship.

ECCO Essential Requirements for Quality Cancer Care: Prostate cancer.

BACKGROUND: ECCO Essential Requirements for Quality Cancer Care (ERQCC) are written by experts representing all disciplines involved in cancer care in Europe. They give oncology teams, patients, policymakers and managers an overview of essential care throughout the patient journey. PROSTATE CANCER: Prostate cancer is the second most common male cancer and has a wide variation in outcomes in Europe. It has complex diagnosis and treatment challenges, and is a major healthcare burden. Care must only be a carried out in prostate/urology cancer units or centres that have a core multidisciplinary team (MDT) and an extended team of health professionals. Such units are far from universal in European countries. To meet European aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship.

[Combination of radiation and immunotherapy in cancer treatment]. / A sugárkezelés és immunterápia együttes alkalmazásának lehetõségei a daganatok kezelésében.

It is known since the beginning of the 20th century that ionizing radiation has an effect on the immune system. The abscopal effect was well known but extremely rare. However, many study groups performed intensive preclinical research in the field. One of the most prominent recent developments of medical science is the introduction of modern immunotherapy to the treatment of cancer. The widespread use of immunotherapy drew again the attention to the possible role of radiation in conjunction with immunotherapy. There is growing evidence that ionizing radiation may potentiate the effect of immunotherapy. Prospective trials have been launched and the results are very much awaited. But research is booming and new targets of immunotherapy are identified, while we have insufficient knowledge about the underlying biological mechanisms. Therefore, it is highly important that intensive basic and translation research be done and its results should provide sound knowledge to design new clinical trials which, we believe, will lead to better treatment of our patients. In this short review we try to give a snapshot about the current state of the combined clinical use of radiation and immunotherapy.

Combination of pentoxifylline and α-galactosylceramide with radiotherapy promotes necro-apoptosis and leukocyte infiltration and reduces the mitosis rate in murine melanoma.

Despite the success for the treatment of melanoma such as targeted molecular therapy, the use of such treatments are expensive For this reason, this study was carried out to explore the anti-cancer properties of available drugs that are able to modify the melanoma prognosis. The study was conducted in two phases: Evaluation of pharmacological effects of pentoxifylline (PTX) administered above (60 mg/kg) which is the therapeutic dose that is aimed at reducing the side-effect of radiotherapy, and of α- galactosylceramide (GalCer) administered at 100 µg/kg, as well as their combination using a murine model (BDF1 mice) of melanoma cell line (B16-F1, ATCC). For the radiotherapy phase, 9 Gy was applied in the tumor area, before (3 days), during (30 min) and after (3 days) the PTX + GalCer treatment. In both study phases, the mitosis rate, leukocyte infiltration and necro-apoptosis were assessed using histological and immunohistochemical approach and tumor volume evaluation as biomarkers. All treatments showed good prognosis results estimated as reduction of mitosis rate (PTX + GalCer after radiotherapy and GalCer), increased leukocyte infiltrate (PTX + GalCer after radiotherapy and GalCer) and necro-apoptosis augmentation (PTX + GalCer after radiotherapy and radiotherapy control). Nevertheless, a lower development of tumor volume was found in GalCer treatment. In this way, it is possible to suggest that the integrated treatment with immuno-stimulators such as GalCer, plus drug used for peripheral vascular disease (PTX) after radiotherapy is probably an alternative for controlling aggressive melanoma in murine model.

Local immune parameters as potential predictive markers in head and neck squamous cell carcinoma patients receiving induction chemotherapy and cetuximab.

BACKGROUND: The aim of this study was to determine whether tumor-associated immune cells may predict response to therapy and disease outcome in head and neck squamous cell carcinoma (HNSCC) patients receiving induction chemotherapy and cetuximab. METHODS: Paraffin-embedded pretreatment biopsy samples from 45 patients with stage III-IV resectable HNSCC were investigated retrospectively by immunohistochemistry for density of different immune cell types based on expression of CD8, FOXP3, CD134, CD137, PD-1, CD20, NKp46, dendritic cell lysosomal-associated membrane protein (DC-LAMP), CD16, CD68, and myeloperoxidase. Results were analyzed for possible correlations with clinicopathologic parameters, response to therapy, and survival. RESULTS: Of the immune cell types studied, we found significant association with response to induction chemotherapy only in the case of DC-LAMP+ mature dendritic cells and PD-1+ lymphocytes; density of DC-LAMP+ cells also correlated with progression-free survival. CONCLUSION: DC-LAMP+ mature dendritic cells and PD-1+ cells may be implicated in response to induction chemotherapy and cetuximab in HNSCC patients.

[Stereotactic body radiotherapy of liver metastasis: early experience]. / Májáttétes betegek sztereotaxiás ablatív sugárkezelésével (SABRT) elért elsõ eredményeink.

Recently the prevalence of oligometastatic patients is increasing. A common site of distant spread is the liver. The standard of care is curative surgical resection, however, the resecability rate is only 10-20%. Alternatively, radiofrequency ablation (RFA) or transarterial chemoembolization (TACE) may be used. Stereotactic ablative body radiotherapy (SABRT) makes it possible to deliver curative radiation dose without radiation injury to the healthy liver tissue. We delivered SABRT to three patients with inoperable hepatic metastases. The primary tumors were rectal (2) and lung (1). The dose was 3x20 Gy every other day. We observed one grade 1 side effect. All the metastases showed complete remission and no local recurrence or late side effect occurred during the one year of follow-up. One patient is tumor-free, one has stable disease, in one patient two new hepatic metastases appeared and receives chemo-biological therapy. SABRT of liver metastases is safe and highly effective. It can be expected that in the near future it will become one of the standard treatments of hepatic tumors.