Dermoscopy of Chronic Radiation-Induced Dermatitis in Patients with Head and Neck Cancers Treated with Radiotherapy.

Radiotherapy (RT) is an integral part of many cancer treatment protocols. Chronic radiation-induced dermatitis (CRD) is a cutaneous toxicity that occurs in one-third of all patients treated with this method. CRD is usually observed several months after completion of treatment. Typical symptoms of CRD are telangiectasia, skin discoloration, atrophy, thickening, and cutaneous fibrosis. There are currently no data in the literature on the evaluation of the dermoscopic features of CRD. The aim of this prospective study was the identification of clinical and dermoscopic features in a group of 32 patients with head and neck cancer (HNC) in whom CRD developed after RT. CRD was assessed at 3, 6, and 12 months after RT in 16, 10, and 10 patients, respectively. CRD was assessed at one time point and two time points in 28 and 4 patients, respectively. The control included skin areas of the same patient not exposed to RT. The dataset consisted of 36 clinical and 216 dermoscopic photos. Clinical evaluation was performed according to the RTOG/EORTC radiation-induced dermatitis scale. The highest score was grade 2 observed in 21 patients. Clinical observations revealed the presence of slight and patchy atrophy, pigmentation change, moderate telangiectasias, and some and total hair loss. Dotted vessels, clustered vessel distribution, white patchy scale, perifollicular white color, white structureless areas, brown dots and globules, and white lines were the most frequently noted features in dermoscopy. Three independent risk factors for chronic toxicity, such as age, gender, and surgery before RT, were identified. The dermoscopic features that had been shown in our study reflect the biological reaction of the skin towards radiation and may be used for the parametrization of CRD regarding its intensity and any other clinical consequences in the future.

Metabolite Biomarkers of Prolonged and Intensified Pain and Distress in Head and Neck Cancer Patients Undergoing Radio- or Chemoradiotherapy by Means of NMR-Based Metabolomics-A Preliminary Study.

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.

Determinants of the level of circulating-tumor HPV16 DNA in patients with HPV-associated oropharyngeal cancer at the time of diagnosis.

Circulating tumor HPV DNA (ctHPV16) assessed in liquid biopsy may be used as a marker of cancer in patients with HPV-associated oropharyngeal cancer (HPV + OPC). Factors influencing the initial ctHPV16 quantity are not well recognized. In this study we aimed to establish what factors are related to the level of ctHPV16 at the time of diagnosis. 51 patients (37 men and 14 women, median age of 57 years old) with HPV + OPC prior to definitive treatment were included. ctHPV16 was measured by qPCR. Tumor and nodal staging were assessed according to AJCC8. Blood derived factors included squamous cell carcinoma antigen (SCC-Ag), serum soluble fragment of cytokeratin 19 (CYFRA 21-1), C-reactive protein (CRP), albumin level (Alb), neutrophils (Neut), thrombocytes (Plt) and lymphocyte (Lym) count, Neut/Lym ratio were assessed. The volumes of the primary tumor (TV) and involved lymph nodes (NV) were calculated using MRI, CT or PET-CT scans. Data were analysed using parametric and nonparametric methods. Variables for multivariable linear regression analysis were chosen based on the results from univariable analysis (correlation, univariable regression and difference). There were 9 (18%), 10 (19%) and 32 (63%) patients who had TV and NV assessed in MRI, CT or PET respectively. Primary tumor neither as T-stage nor TV was related to ctHPV16 level. Significant differences in the ctHPV16 between patients with high vs low pain (P = 0.038), NV (P = 0.023), TV + NV (P = 0.018), CYFRA 21-1 (P = 0.002), CRP (P = 0.019), and N1 vs N3 (P = 0.044) were observed. ctHPV16 was significantly associated with CYFRA 21-1 (P = 0.017), N stage (P = 0.005), NV (P = 0.009), TV + NV (P = 0.002), CRP (P = 0.019), and pain (P = 0.038). In univariable linear regression analysis the same variables predicted ctHPV16 level. In multivariable analyses, CYFRA 21-1 and CRP (both as categorical variables) were predictors of ctHPV16 level even above NV. ctHPV16 at presentation is driven by tumor volume measured mostly by N. CYFRA 21-1 and CRP are additional factors related to ctHPV16 prior to the treatment.

Algorithms of follow-up in patients with head and neck cancer in relation to primary location and advancement. Consensus of Polish ENT Society Board and Head Neck Experts.

Summary: The algorithm of follow-up in patients with head and neck cancer (HNC) has been prepared by a board of Polish Head Neck and Oncology Experts. The aim of this research is to focus on the specificity of HNC monitoring, to review the current trends in follow-up, and to adapt the evidence-based medicine international standards to the capabilities of the local healthcare service. Materials and methods: The first methodological step was to categorize HNCs according to the estimated risk of failure after the adequate first-line treatment and according to the possibility of effective salvage treatment, resulting in improved overall survival. The final method used in this work was to prepare an authors' original monitoring algorithm for HNC groups with a high, moderate, and low risk of recurrence in combination with a high or low probability of using an effective salvage. Results: Four categories were established: Ia. low risk of recurrence + effective organ preservation feasible; Ib. low risk of recurrence + effective salvage feasible; II. moderate risk of recurrence + effective salvage feasible; III. high risk of recurrence + effective salvage feasible; and IV. high risk of recurrence + no effective salvage feasible. Follow-up visit consisting of 1. ENT examination + neck ultrasound, 2. imaging HN tests, 3. chest imaging, 4. blood tests, and 5. rehabilitation (speech and swallowing) was scheduled with a very different frequency, at the proposed monthly intervals, tailored to the needs of the group. The number of visits for individual groups varies from 1 to 8 in the first 2 years and from 1 to 17 in the entire 5-year monitoring period. Group IV has not been included in regular follow-up, visits on own initiative of the patient if symptomatic, or supportive care needs, having in mind that third-line therapy and immune checkpoint inhibitors are available. Conclusion: Universal monitoring algorithm for HNC four groups with a high, moderate, and low risk of recurrence after the adequate treatment in combination with a high or low probability of using an effective salvage is an innovative approach to redeploying system resources and ensuring maximum benefit for patients with HNC.

DNA Double-Strand Break Response and Repair Gene Polymorphisms May Influence Therapy Results and Prognosis in Head and Neck Cancer Patients.

Radiotherapy and cisplatin-based chemotherapy belong to the main treatment modalities for head and neck squamous cell carcinoma (HNSCC) and induce cancer cell death by generating DNA damage, including the most severe double-strand breaks (DSBs). Alterations in DSB response and repair genes may affect individual DNA repair capacity and treatment sensitivity, contributing to the therapy resistance and poor prognosis often observed in HNSCC. In this study, we investigated the association of a panel of single-nucleotide polymorphisms (SNPs) in 20 DSB signaling and repair genes with therapy results and prognosis in 505 HNSCC patients treated non-surgically with DNA damage-inducing therapies. In the multivariate analysis, there were a total of 14 variants associated with overall, locoregional recurrence-free or metastasis-free survival. Moreover, we identified 10 of these SNPs as independent predictors of therapy failure and unfavorable prognosis in the whole group or in two treatment subgroups. These were MRE11 rs2155209, XRCC5 rs828907, RAD51 rs1801321, rs12593359, LIG4 rs1805388, CHEK1 rs558351, TP53 rs1042522, ATM rs1801516, XRCC6 rs2267437 and NBN rs2735383. Only CHEK1 rs558351 remained statistically significant after correcting for multiple testing. These results suggest that specific germline variants related to DSB response and repair may be potential genetic modifiers of therapy effects and disease progression in HNSCC treated with radiotherapy and cisplatin-based chemoradiation.

Influence of nutritional counseling on treatment results in patients with head and neck cancers.

OBJECTIVES: Nutritional intervention, including nutritional counseling (NC), plays a significant role in the comprehensive management of patients with head and neck cancer (HNC). The aim of this study was to investigate the effects of NC combined with oral nutritional supplements during radical treatment on weight loss and survival outcomes in patients with HNC. METHODS: The study included 310 patients who received radical treatment for HNC. Among these patients, 119 underwent NC along with oral nutritional supplements (NCONS); 191 were supported with oral nutritional supplements only (ONS). The study aimed to investigate the effects of sex, disease stage, treatment modality, and tumor site on weight loss. Additionally, the Kaplan-Meier method assessed the influence of NC on overall survival and disease-free survival. RESULTS: The present study suggested that the NC independently prevented weight loss, regardless of sex and disease stage (female: -1.6%, P = 0.001; male: -2.3 %, P = 0.003; T stage (0-2): -1.7%, P = 0.008; T stage (3-4): -2.7%, P = 0.003; N stage (0-1): 2.5%, P = 0,027; N stage (3-4): 2.9%, P < 0.001). The protective effect was most significant in patients with oral cancer and oropharyngeal cancer and in patients treated with chemotherapy (oral: -1.7%, P = 0.03; oropharynx: -3.3%, P < 0.001; radiochemotherapy: -3%, P = 0.028; induction chemotherapy preceded radiochemotherapy: -6%, P < 0.001). Furthermore, the 3-year overall survival rates were 93.4% and 85.4% in the NC along with oral nutritional supplements (NCONS) and oral nutritional supplement (ONS) groups, respectively (P = 0.031). CONCLUSIONS: Patients with HNC who received NC during radical treatment experienced reduced weight loss. This effect was particularly pronounced in patients with oral cavity or oropharyngeal cancer and those undergoing chemotherapy. Additionally, NC was associated with improved overall survival in this patient cohort. Nevertheless, further studies are required to validate and support these findings.

Dermoscopy of acute radiation-induced dermatitis in patients with head and neck cancers treated with radiotherapy.

Head and neck cancer (HNC) was the seventh most common cancer in the world in 2018. Treatment of a patient may include surgery, radiotherapy (RT), chemotherapy, targeted therapy, immunotherapy, or a combination of these methods. Ionizing radiation used during RT covers relatively large volumes of healthy tissue surrounding the tumor. The acute form of radiation-induced dermatitis (ARD) are skin lesions that appear usually within 90 days of the start of RT. This is a prospective study which compares 2244 dermoscopy images and 374 clinical photographs of irradiated skin and healthy skin of 26 patients at on average 15 time points. Dermoscopy pictures were evaluated independently by 2 blinded physicians. Vessels in reticular distribution, white, yellow or brown scale in a patchy distribution, perifollicular pigmentation and follicular plugs arranged in rosettes were most often observed. For these dermoscopic features, agreement with macroscopic features was observed. Two independent predictors of severe acute toxicity were identified: gender and concurrent chemotherapy. Knowledge of dermoscopic features could help in the early assessment of acute toxicity and the immediate implementation of appropriate therapeutic strategies. This may increase the tolerance of RT in these groups of patients.

Sacubitril/valsartan for cardioprotection in breast cancer (MAINSTREAM): design and rationale of the randomized trial.

AIMS: In recent years, survival in patients with breast cancer has increased. Despite the improvement in outcomes of those patients, the risk of treatment-related cardiotoxicity remains high, and its presence has been associated with a higher risk of treatment termination and thus lower therapeutic efficacy. Prior trials demonstrated that a preventive initiation of heart failure drugs, including the renin-angiotensin-aldosterone inhibitors, might reduce the risk of treatment-related cardiotoxicity. However, to date, no study investigated the efficacy of sacubitril/valsartan, a novel antineurohormonal drug shown to be superior to the previous therapies, in the prevention of cardiotoxicity in patients with early-stage breast cancer, which is the aim of the trial. METHODS AND RESULTS: MAINSTREAM is a randomized, placebo-controlled, double-blind, multicentre, clinical trial. After the run-in period, a total of 480 patients with early breast cancer undergoing treatment with anthracyclines and/or anti-human epidermal growth factor receptor 2 drugs will be randomized to the highest tolerated dose of sacubitril/valsartan, being preferably 97/103 mg twice daily or placebo in 1:1 ratio. The patients will be monitored, including routine transthoracic echocardiography (TTE) and laboratory biomarker monitoring, for 24 months. The primary endpoint of the trial will be the occurrence of a decrease in left ventricular ejection fraction by ≥5% in TTE within 24 months. The key secondary endpoints will be the composite endpoint of death from any cause or hospitalization for heart failure, as well as other imaging, laboratory, and clinical outcomes, including the occurrence of the cancer therapy-related cardiac dysfunction resulting in the necessity to initiate treatment. The first patients are expected to be recruited in the coming months, and the estimated completion of the study and publication of the results are expected in December 2027, pending recruitment. CONCLUSIONS: The MAINSTREAM trial will determine the efficacy and safety of treatment with sacubitril/valsartan as a prevention of cardiotoxicity in patients with early breast cancer (ClinicalTrials.gov number: NCT05465031).

Stereotactic Radiotherapy in Combination with Immunotherapy in Treatment of Advanced Recurrent Squamous Cell Carcinoma of the Larynx.

Squamous cell carcinoma (SCC) of the larynx in advanced stages is a challenging malignancy to treat with a high recurrence and death rate. An individualized approach to treatment is crucial in such patients. We present a 58-year-old male patient with SCC of the larynx in the T3N0M0 stage who was treated with concurrent radiochemotherapy. A total of 17 months after the radical treatment, the patient underwent a laryngectomy due to recurrence. A total of 11 months after the operation, local failure was diagnosed. In the next order, the patient received six cycles of palliative chemotherapy according to cisplatin 100 mg/m2 and 5-fluorouracil 1000 mg/m2. After three months, due to progression, Nivolumab-based immunotherapy was administered, ensuring disease stabilization. After the 56th cycle of Nivolumab, another progression was documented. The addition of stereotactic radiotherapy (18 Gy in three fractions) to immunotherapy led to significant regression of the disease and enabled the continuation of Nivolumab to the 70th cycle. The presented case demonstrates the usefulness of the combination of stereotactic radiotherapy with immunotherapy in prolonging the local control.

Stereotactic Radiotherapy Boost in Treatment of Persistent Periocular Sebaceous Carcinoma after Surgery.

Sebaceous carcinoma is a rare malignancy that should be treated with surgical resection. Nonetheless, a dynamic and aggressive course of the disease may disqualify a patient from this treatment. Applying radiotherapy with the escalation dose using a stereotactic boost is worthy of consideration as a radical treatment. In this paper, we present the case study of a young patient with a tumor localized in the periocular area. The patient was treated with operation two times without a satisfactory effect. Conventional radiotherapy, 60 Gy in 30 fractions, combined with chemotherapy based on cisplatin 40 mg/m2 and the addition of a stereotactic radiosurgery boost were administered. The tolerance of this treatment was acceptable. During the 2-year follow-up, local and distant recurrences were not diagnosed. The presented case shows the usefulness of an individualized approach in the radical treatment of sebaceous carcinoma with the use of the stereotactic radiotherapy boost. This is a subsequent example of the implementation of the boost in head and neck carcinoma, which yields a positive result.

Walking through the valley of the shadow of death-The psychotherapy of the head and neck cancer patient expressing suicidal ideations and impulses.

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.

Low-Dose Radiotherapy for Patients with Pneumonia Due to COVID-19: A Single-Institution Prospective Study.

PURPOSE: Results of the low-dose radiation therapy (LDRT) in patients with pneumonia due to COVID-19 has been presented. METHODS: Fifteen patients received a single-fraction radiation dose of 1 Gy to the bilateral lungs due to pre-ARDS pneumonia in the course of COVID-19. Follow-up was performed on days 1, 3, 5, 7, 14 after LDRT. RESULTS: Eleven patients (73%) were released up until day 28. Median hospitalization was 20 days; 28-day mortality was 13%. Median O2 saturation improved within 24 h after LDRT in 14/15, with median SpO2 values of 84.5% vs. 87.5% p = 0.016, respectively. At day 14 of hospitalization, 46% did not require oxygen supplementation. Significant decline in CRP and IL-6 was observed within 24 h post LDRT. No organ toxicities were noted. CONCLUSION: LDRT is feasible, well tolerated and may translate to early clinical recovery in patients with severe pneumonia. Further studies are needed to determine optimal candidate, time and dose of LDRT for COVID-19 patients with pneumonia.

Results of Primary Treatment and Salvage Treatment in the Management of Patients with Non-Squamous Cell Malignant Tumors of the Sinonasal Region: Single Institution Experience.

Non-squamous cell carcinoma-related malignant sinonasal tract tumors (non-SCC MSTT) are rare and diverse malignancies. In this study, we report our experience in the management of this group of patients. The treatment outcome has been presented, involving both primary treatment and salvage approaches. Data from 61 patients treated radically due to non-SCC MSTT between 2000 and 2016 at the National Cancer Research Institute, Gliwice branch, were analyzed. The group consisted of the following pathological subtypes of MSTT: adenoid cystic carcinoma (ACC), undifferentiated sinonasal carcinoma (USC), sarcoma, olfactory neuroblastoma (ONB), adenocarcinoma, small cell neuroendocrine carcinoma (SNC), mucoepidermic carcinoma (MEC), and acinic cell carcinoma, which were found in nineteen (31%), seventeen (28%), seven (11.5%), seven (11.5%), five (8%), three (5%), two (3%) and one (2%) of patients, respectively. There were 28 (46%) males and 33 (54%) females at the median age of 51 years. Maxilla was the primary tumor localization followed by the nasal cavity and ethmoid sinus in thirty-one (51%), twenty (32.5%), and seven (11.5%) patients, respectively. In 46 (74%) patients, an advanced tumor stage (T3 or T4) was diagnosed. Primary nodal involvement (N) was found in three (5%) cases, and all patients underwent radical treatment. The combined treatment consisted of surgery and radiotherapy (RT) and was given to 52 (85%) patients. The probabilities of overall survival (OS), locoregional control (LRC), metastases-free survival (MFS), and disease-free survival (DFS) were assessed in pathological subtypes and grouped together, along with the ratio and effectiveness of salvage. Locoregional treatment failure was seen in 21 (34%) patients. Salvage treatment was performed in fifteen (71%) patients and was effective in nine (60%) cases. There was a significant difference in OS between patients who underwent salvage and those who did not (median: 40 months vs. 7 months, p = 0.01). In the group of patients who underwent salvage, OS was significantly longer when the procedure was effective (median: 80.5 months) than if it failed (median: 20.5 months), p < 0.0001. OS in patients after effective salvage was the same as in patients who were primary cured (median: 80.5 months vs. 88 months, p = 0.8). Distant metastases developed in ten (16%) patients. Five and ten year LRC, MFS, DFS, and OS were 69%, 83%, 60%, 70%, and 58%, 83%, 47%, 49%, respectively. The best treatment results were observed for patients with adenocarcinoma and sarcoma, while USC gave the poorest results in our set of patients. In this study, we indicate that salvage is possible in most patients with non-SCC MSTT with locoregional failure and that it may significantly prolong their overall survival.

Metabolomic Insight into Implications of Induction Chemotherapy Followed by Concomitant Chemoradiotherapy in Locally Advanced Head and Neck Cancer.

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 p-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.

Low Post-Treatment Quality of Life and the High Incidence of Pain Are Common and Significantly Exacerbated in Depressed Head and Neck Patients Treated with Definitive Accelerated Radiotherapy.

(1) Background: The goal of this study is to evaluate psychological tolerance and health-related quality of life (QOL) in head and neck (HN) cancer patients treated with definitive accelerated radiotherapy (DART). (2) Methods: 76 recurrence-free patients eligible for the study, who were treated with DART in the CAIR-2 phase III clinical study (median of follow-up = 47 months), completed EORTC QLQ-C30 with the H&N35 module, Hospital Anxiety and Depression Scale (HADS) and Visual-Analog Scales (VAS) of pain in HN and the neck/arm areas. (3) Results: The most dominant symptoms measured with QLQ-C30 were as follows: fatigue (44/100), sleeplessness (39/100), financial problems (38/100) and pain (32/100). Within the H&N35, the highest scores were reported on the subscales of sticky saliva (60/100), mouth dryness (65/100) and increased intake of painkillers (50/100). Pain (VAS) was reported by 87% (HN area) and 78% (shoulder area) of the patients, with a mean score of 3/10. One-third of the patients reported depressive moods (HADS ≥ 15 points) with an average score of 12.5/42 p. The depressed group, who smoked more as compared to the non-depressed group before DART (96% vs. 78%) and required steroids treatment (85% vs. 58%) during DART, also scored significantly worse on 23 of the 35 subscales of QLQ-C30 and H&N35 and experienced more intense pain (VAS). Women and less-advanced patients scored better in several aspects of quality of life. (4) Conclusions: Patients treated with DART struggle with low quality of life and persistent treatment-related symptoms including constant pain. HNC survivors, especially those who are depressed, may require additional psychosocial, rehabilitation and medical intervention programmes.

Escalating a Biological Dose of Radiation in the Target Volume Applying Stereotactic Radiosurgery in Patients with Head and Neck Region Tumours.

Background: The treatment of head and neck tumours is a complicated process usually involving surgery, radiation therapy, and systemic treatment. Despite the multidisciplinary approach, treatment outcomes are still unsatisfactory, especially considering malignant tumours such as squamous cell carcinoma or sarcoma, where the frequency of recurrence has reached 50% of cases. The implementation of modern and precise methods of radiotherapy, such as a radiosurgery boost, may allow for the escalation of the biologically effective dose in the gross tumour volume and improve the results of treatment. Methods: The administration of a stereotactic radiotherapy boost can be done in two ways: an upfront boost followed by conventional radio(chemo)therapy or a direct boost after conventional radio(chemo)therapy. The boost dose depends on the primary or nodal tumour volume and localization regarding the organs at risk. It falls within the range of 10-18 Gy. Discussion: The collection of detailed data on the response of the disease to the radiosurgery boost combined with conventional radiotherapy as well as an assessment of early and late toxicities will contribute crucial information to the prospective modification of fractionated radiotherapy. In the case of beneficial findings, the stereotactic radiosurgery boost in the course of radio(chemo)therapy in patients with head and neck tumours will be able to replace traditional techniques of radiation, and radical schemes of treatment will be possible for future development.

High-dose stereotactic radiotherapy boost in the treatment of squamous cell carcinoma of the head and neck region.

BACKGROUND: Surgical resection with adjuvant concurrent radiochemotherapy is the standard of care for stage III-IV oral cavity cancer. In some cases, the dynamic course of the disease is out of the prepared schedule of treatment. In that event, a stereotactic radiosurgery boost might be the only chance for disease control. CASE PRESENTATION: Here, we present a case study of a patient with oral cancer who underwent surgery. During adjuvant radiotherapy, a metastatic cervical lymph node was diagnosed based on fine-needle aspiration biopsy. To increase the total dose to the metastatic tumor, a stereotactic radiosurgery boost of 1 × 18 Gy was performed two days after the last fraction of conventional radiotherapy. The early and late tolerance of this treatment were positive. During the 18-month follow-up, locoregional recurrence was not detected. The patient died due to secondary malignancy. CONCLUSIONS: This paper shows that a stereotactic radiosurgery boost added to adjuvant conventional radiotherapy is an effective approach permitting the maintenance of good local control in well-selected patients.

Analysis of Selected Nutritional Parameters in Patients with HPV-Related and Non-HPV-Related Oropharyngeal Cancer before and after Radiotherapy Alone or Combined with Chemotherapy.

Background: Radiotherapy plays an essential role in the treatment of oropharyngeal carcinoma (OPC). The aim of this study was to assess and compare the nutritional status (NS) of patients with HPV-related (HPV+) and non-HPV-related (HPV-) OPC before and after radiotherapy (RT) or chemoradiotherapy (CRT). Methods: The analysis included 127 patients with OPC who underwent radiotherapy (RT) alone, or in combination with chemotherapy (CRT), in the I Radiation and Clinical Oncology Department of Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Poland. Patients were divided according to HPV status. Confirmation of HPV etiology was obtained from FFPE (formalin-fixed, paraffin-embedded) tissue material and/or extracellular circulating HPV DNA. Basic anthropometric and biochemical parameters before and after RT/CRT were compared between the HPV- and HPV+ groups. The effect of NS on survival was also analyzed. Results: In both groups, a significant decrease in all analyzed nutritional parameters was noted after RT/CRT (p < 0.01). CRT caused significant weight loss and decreases in BMI, albumin, total lymphocyte count (TLC), and hemoglobin concentration, as well as an increase in the Nutritional Risk Score (NRS) 2002, in HPV- and HPV+ patients. A significant decrease in prealbumin levels after CRT was noted only in HPV+ patients. RT caused a significant decrease in hemoglobin concentration and TLC in HPV- patients. There were no significant differences regarding other nutritional parameters after RT in either group. RT did not have negative impact on body mass index (BMI), weight, NRS, CRP, Alb, Prealb, or PNI. Overall survival (OS) and disease-free survival (DFS) were significantly better in patients with a higher BMI in the HPV- group (OS, p = 0.011; DFS, p = 0.028); DFS was significantly better in patients with C-reactive protein (CRP) < 3.5 g/dL in the HPV- (p = 0.021) and HPV+ (p = 0.018) groups, and with total lymphocyte count (TLC) >1.28/mm3 in the HPV+ group (p = 0.014). Higher NRS 2002 was an independent adverse prognostic factor for OS and DFS in HPV-, but not in the HPV+ group. Kaplan−Meier analysis showed that both OS and DFS were significantly better in HPV- patients with lower NRS 2002 scores. However, this relationship was not observed in the HPV+ group. Conclusions: Regardless of HPV status, patients with OPC can develop malnutrition during RT/CRT. Therefore, nutritional support during RT/CRT is required in patients with HPV- and HPV+ OPC.

Germline Variants in Angiogenesis-Related Genes Contribute to Clinical Outcome in Head and Neck Squamous Cell Carcinoma.

Fibroblast growth factor (FGF)/FGF receptor (FGFR), and platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR) systems, as well as some matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), are involved in various steps of angiogenesis. Data indicate that common germline variations in angiogenesis-regulating genes may modulate therapy results and cancer progression. However, whether these variants affect clinical outcome in head and neck squamous cell carcinoma (HNSCC) is unclear. Hence, we assessed the relationship between FGF/FGFR, PDGF/PDGFR, MMP, and TIMP genetic variants and treatment outcomes in HNSCC patients receiving radiotherapy (RT) alone or combined with cisplatin-based chemotherapy. In multivariate analysis, FGF2 rs1048201 CC homozygotes showed a higher risk of death (p = 0.039), while PDGFRA rs2228230 T was strongly associated with an increased risk of locoregional relapse (HR 2.49, p = 0.001) in the combination treatment subgroup. In the RT alone subset, MMP2 rs243865 TT carriers had a higher risk of locoregional recurrence (HR 2.92, p = 0.019), whereas PDGFRB rs246395 CC homozygotes were at increased risk of metastasis (HR 3.06, p = 0.041). The MMP2 rs7201 C and TIMP2 rs7501477 T were associated with a risk of locoregional failure in the entire cohort (p = 0.032 and 0.045, respectively). Furthermore, rs1048201, rs2228230, rs246395, rs243865, rs7201, and rs7201/rs7501477 were independent indicators of an unfavorable outcome. This study demonstrates that the FGF2, PDGFRA, PDGFRB, MMP2, and TIMP2 variants may contribute to treatment failure and poor prognosis in HNSCC.