The present study compares two groups of locally advanced patients with head and neck squamous cell carcinoma (LA-HNSCC) undergoing concurrent chemoradiotherapy (cCHRT), specifically those for whom ...it is a first-line treatment and those who have previously received induction chemotherapy (iCHT). The crucial question is whether iCHT is a serious burden during subsequent treatment for LA-HNSCC and how iCHT affects the tolerance to cCHRT. Of the 107 LA-HNSCC patients, 54 received cisplatin-based iCHT prior to cCHRT. The patients were clinically monitored at weekly intervals from the day before until the completion of the cCHRT. The 843 blood samples were collected and divided into two aliquots: for laboratory blood tests and for nuclear magnetic resonance (NMR) spectroscopy (a Bruker 400 MHz spectrometer). The NMR metabolites and the clinical parameters from the laboratory blood tests were analyzed using orthogonal partial least squares analysis (OPLS) and the Mann-Whitney U test (MWU). After iCHT, the patients begin cCHRT with significantly (MWU
-value < 0.05) elevated blood serum lipids, betaine, glycine, phosphocholine, and reticulocyte count, as well as significantly lowered NMR inflammatory markers, serine, hematocrit, neutrophile, monocyte, red blood cells, hemoglobin, and CRP. During cCHRT, a significant increase in albumin and psychological distress was observed, as well as a significant decrease in platelet, N-acetyl-cysteine, tyrosine, and phenylalanine, in patients who received iCHT. Importantly, all clinical symptoms (except the decreased platelets) and most metabolic alterations (except for betaine, serine, tyrosine, glucose, and phosphocholine) resolve until the completion of cCHRT. In conclusion, iCHT results in hematological toxicity, altered lipids, and one-carbon metabolism, as well as downregulated inflammation, as observed at the beginning and during cCHRT. However, these complications are temporary, and most of them resolve at the end of the treatment. This suggests that iCHT prior to cCHRT does not pose a significant burden and should be considered as a safe treatment option for LA-HNSCC.
The aim of this prospective study is to identify the biomarkers associated with the effects of induction chemotherapy (iCHT) in terms of the favorable/weaker response to the treatment in locally ...advanced head and neck squamous cells carcinomas (LA-HNSCC).
The studied group consisted of 53 LA-HNSCC patients treated with iCHT. The treatment tolerance was measured by the Common Terminology Criteria for Adverse Events (CTCAE). The response to the treatment was evaluated by the clinical, fiberoptic and radiological examinations made before and after iCHT (the TNM Classification of Malignant Tumors was used for classifying the extent of cancer spread). Proton nuclear magnetic resonance (
H NMR) serum spectra of the samples collected before and after iCHT were acquired with a 400 MHz spectrometer and analyzed using the multivariate and univariate statistical methods.
The molecular response to iCHT involves an increase of the serum lipids which is accompanied by the simultaneous decrease of alanine, glucose and N-acetyl-glycoprotein (NAG). Furthermore, in males, the iCHT induced changes in the lipid signals and NAG significantly correlate with the regression of the primary tumor. The OPLS-DA multivariate model identified two subgroups of the patients with a weaker metabolic and clinical response. The first one consisted of the patients with a significantly lower initial nodal stage, the second one showed no differences in the initial clinical and metabolic statuses.
The NMR-based metabolomic study of the serum spectra revealed that iCHT induces the marked changes in the LA-HNSCC patients' metabolic profiles and makes it possible to stratify the patients according to their response to iCHT. These effects are sex dependent. Further studies on a larger scale accounting for sex and the clinical and metabolic factors are warranted.
In the present study, we analyze the nuclear magnetic resonance (NMR) blood serum metabolic profiles of 106 head and neck squamous cell carcinoma (HNSCC) patients during radio (RT) and concurrent ...radio-chemotherapy (CHRT). Four different fractionation schemes were compared. The blood samples were collected weekly, from the day before the treatment until the last week of CHRT/RT. The NMR spectra were acquired on A Bruker 400 MHz spectrometer at 310 K and analyzed using multivariate methods. Seven metabolites were found significantly to be altered solely by radiotherapy: N-acetyl-glycoprotein (NAG), N-acetylcysteine, glycerol, glycolate and the lipids at 0.9, 1.3 and 3.2 ppm. The NMR results were correlated with the tissue volumes receiving a particular dose of radiation. The influence of the irradiated volume on the metabolic profile is weak and mainly limited to sparse correlations with the inflammatory markers, creatinine and the lymphocyte count in RT and the branched-chain amino-acids in CHRT. This is probably due to the optimal planning and delivery of radiotherapy improving sparing of the surrounding normal tissues and minimizing the differences between the patients (caused by the tumor location and size).
Treatment of head and neck squamous cell carcinoma (HNSCC) has a detrimental impact on patient quality of life. The rate of recognized distress/depression among HNSCC patients ranges from 9.8% to ...83.8%, and the estimated prevalence of depression among patients receiving radiotherapy is 63%. Shorter overall survival also occurs in preexisting depression or depressive conditions. The present study analyzes the nuclear magnetic resonance (NMR) blood serum metabolic profiles during radio-/chemoradiotherapy and correlates the detected alterations with pain and/or distress accumulated with the disease and its treatment. NMR spectra were acquired on a Bruker 400 MHz spectrometer and analyzed using multivariate methods. The results indicate that distress and/or pain primarily affect the serum lipids and metabolites of energy (glutamine, glucose, lactate, acetate) and one-carbon (glycine, choline, betaine, methanol, threonine, serine, histidine, formate) metabolism. Sparse disturbances in the branched-chain amino acids (BCAA) and in the metabolites involved in protein metabolism (lysine, tyrosine, phenylalanine) are also observed. Depending on the treatment modality-radiotherapy or concurrent chemoradiotherapy-there are some differences in the altered metabolites.
The paper aims to show the multilevel and complex cooperation and the inclusion of the psychotherapist leading the psychotherapy in the medical team at the radiotherapy and clinical oncology clinic. ...We illustrate these interventions with the case of Stan. This 43‐year‐old firefighter was diagnosed with advanced head and neck cancer and pre‐existing mental health problems meeting the criteria of ICD‐10: obsessive‐compulsive disorder, post‐traumatic stress disorder and psychoactive substance abuse. During the treatment, suicidal thoughts and impulses emerged, triggered at the hospital by electronic noises and the feeling of entrapment without a way out. This situation put the patient at high risk and the whole healthcare team needed an urgent effective response. The patient agreed to stay in the secured room, where he was cared for by doctors, nurses, a dietitian, and a psychotherapist. He actively attended daily sessions with noticeable engagement. Psychotherapy sessions focused on alleviating posttraumatic stress disorder and OCD. Mindfulness and breathwork‐based exercises were implemented to increase non‐judgemental self‐awareness and regulate the over‐aroused nervous system. As a result, the patient's mental health has improved and the completion of the cancer treatment was possible. Psychotherapy, good therapeutic alliance, and attentive teamwork effectively managed his mental health and treatment‐related symptoms.
Supported by the National Science Centre, Poland, 2020/39/O/NZ5/02625.
Induction chemotherapy (iCH) although is not a standard approach, is often used in clinical practice for patients with advanced ...head and neck cancer (HNSCC). Tumor regression is a potential goal of induction treatment to reduce target volume in the second stage of treatment - radiochemotherapy or radiotherapy.
In this study the most common iCH, TPF (docetaxel, cisplatin, and 5-fluoruracil) has been replaced with two-drugs regimen combined with low-dose radiation. Complementary mechanisms of action and excellent radiation sensitization of drugs together with hyperradiosensitivity (HRS) phenomenon of low-dose fractionated radiation therapy may be beneficial for patients with bulky disease. Additionally, lower toxicity could be expected for two-drugs modality. Preliminary results on effectiveness and toxicity has been presented.
The group consisted of 27 patients treated due to advanced HNSCC in National Research Institute of Oncology, Gliwice branch between 2020 and 2023. There were 23 (85%) men and 4 (15%) women in the median age of 60 years. In most cases primary tumor site was oropharynx followed by hypopharynx and CUP in 17 (63%), 7 (26%) and 3 (11%) cases respectively. All patients presented advanced stage - III stage in 16 cases (59%) and IV stage in 11 cases (41%). HPV- positive tumors were found in 13 (48%) patients. There were 2 cycles of iCHT consisting of carboplatin (AUC 6) and paclitaxel (75 mg/m2) combined with low-dose radiotherapy 2 x 0.5 Gy on days 1, 8 and 15. Additionally, two doses of 0.5 Gy was given on day 2. CT, MRI and PET-CT scans were performed to estimate the staging of the cancer, all according to the 8th edition of the TNM classification for malignant tumors.
The volume of the primary tumor and metastatic lymph nodes were estimated in cm3 before and after induction radiochemotherapy with low dose fractionation radiotherapy to analyze the potential value of tumor volume regression. After ICHRTL, all patients were qualified for the second stage of treatment - radiochemotherapy in 24 cases and radiotherapy in 3 cases, respectively. To investigate the presence of HRS effect, fibroblasts were irradiated in vitro with doses ranging from 0.1 to 4 Gy (6-MV X-ray beam) and cell radiosensitivity was estimated by flow cytometry-based clonogenic survival assay and RIANS test (pATM and H2AX foci assays). Display omitted
Clinical and experimental data will be presented.The mean volumes of tumor and metastatic lymph nodes among 27 patients before ICHRTL were 32.5 cm3 (Vt) and 45.1 cm3 (Vn), respectively. After ICHRTL, these mean values were 17.2 cm3 (Vt) and 22.2 cm3 (Vn). Wilcoxon test analize showed significant decrease in T volume (Vt) and N volume (Vn) before and after iCHRTL (p=0.003) and p=0.00008) respectively. Due to complications 16 patients (60%) did not receive the full dose of chemotherapy and radiotherapy (ICHRTL). Leukopenia and neutropenia occurred in 12 (44%) and 11 (40%) patients respectively. Poor drug tolerance (vomiting, nausea, abdominal pain) was observed in 3 (11%) patients, and renal failure in 1 (4%) patient. Among normal skin fibroblasts assessed from 21 patients two demonstrated HRS effect.
The use of ICHRTL in patients with advanced HNSCC is a low-toxicity and effective method. The obtained regression of tumor volume (Vt) and metastatic lymph nodes (Vn) in most patients managed to reduce the high dose area in the second stage of treatment (radiotherapy/radiochemotherapy). Further observations are needed to estimate the potential role of decrease in T volume (Vt) and N volume (Vn) after ICHRTL on the expected survival of patients.
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