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Radiation Treatment of Head and Neck Cancers - Use, Types, and Side Effects

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 26262

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Prof. Dr. Stefan Rieken

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Department of Radiotherapy and Radiation Oncology, University Medicine Goettingen (UMG), Robert-Koch-Str. 40, 37075 Goettingen, Germany
Interests: precision radiotherapy; radioimmunotherapy; lung cancer; HNSCC; CNS malignancies
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Special Issue Information

Dear Colleagues,

Despite continuous efforts to increase oncological outcome and quality of life in head and neck squamous cell cancer patients, both difficult-to-treat local relapses and severe treatment-related toxicities still occur at considerable frequency and overshadow the progress that has been achieved through technical and conceptual modifications in recent decades. To assess the benefit of modern treatment techniques (such as dysphagia-adapted IMRT (Intensity-modulated Radiotherapy)) and the combination with novel agents (such as immunotherapy), to analyze treatment outcome in frail and elderly patients, and to investigate the quality of life in long-term survivors, this Special Issue invites experts from the field to share their findings and interpretations of their data.

Prof. Dr. Stefan Rieken
Guest Editor

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Keywords

HNSCC (Head and neck squamous cell carcinoma)
human papillomavirus
IMRT
de-escalation
combined radiochemotherapy
immunotherapy
dysphagia
quality of life

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Published Papers (8 papers)

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Research

23 pages, 8122 KiB

Open AccessArticle

Morphofunctional and Molecular Assessment of Nutritional Status in Head and Neck Cancer Patients Undergoing Systemic Treatment: Role of Inflammasome in Clinical Nutrition

by Soraya León-Idougourram, Jesús M. Pérez-Gómez, Concepción Muñoz Jiménez, Fernando L-López, Gregorio Manzano García, María José Molina Puertas, Natalia Herman-Sánchez, Rosario Alonso-Echague, Alfonso Calañas Continente, María Ángeles Gálvez Moreno, Raúl M. Luque, Manuel D. Gahete and Aura D. Herrera-Martínez

Cancers 2022, 14(3), 494; https://doi.org/10.3390/cancers14030494 - 19 Jan 2022

Cited by 13 | Viewed by 2287

Abstract

Malnutrition in patients with head and neck cancer is frequent, multifactorial and widely associated with clinical evolution and prognosis. Accurate nutritional assessments allow for early identification of patients at risk of malnutrition in order to start nutritional support and prevent sarcopenia. We aimed to perform a novel morphofunctional nutritional evaluation and explore changes in inflammasome-machinery components in 45 patients with head and neck cancer who are undergoing systemic treatment. To this aim, an epidemiological/clinical/anthropometric/biochemical evaluation was performed. Serum RCP, IL6 and molecular expression of inflammasome-components and inflammatory-associated factors (NOD-like-receptors, inflammasome-activation-components, cytokines and inflammation/apoptosis-related components, cell-cycle and DNA-damage regulators) were evaluated in peripheral-blood mononuclear-cells (PBMCs). Clinical-molecular correlations/associations were analyzed. Coherent and complementary information was obtained in the morphofunctional nutritional assessment of the patients when bioimpedance, anthropometric and ultrasound data were analyzed. These factors were also correlated with different biochemical and molecular parameters, revealing the complementary aspect of the whole evaluation. Serum reactive C protein (RCP) and IL6 were the most reliable parameters for determining patients with decreased standardized phase angle, which is associated with increased mortality in patients with solid malignancies. Several inflammasome-components were dysregulated in patients with malnutrition, decreased phase angle and dependency grade or increased circulating inflammation markers. A molecular fingerprint based on gene-expression of certain inflammasome factors (p27/CCL2/ASC) in PBMCs accurately differentiated patients with and without malnutrition. In conclusion, malnutrition induces a profound alteration in the gene-expression pattern of inflammasome-machinery components in PBMCs. A comprehensive nutritional assessment including novel morphofunctional techniques and molecular markers allows a broad characterization of the nutritional status in cancer patients. Profile of certain inflammasome-components should be further studied as potential targets for nutrition-focused treatment strategies in cancer patients. Full article

(This article belongs to the Special Issue Radiation Treatment of Head and Neck Cancers - Use, Types, and Side Effects)

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14 pages, 1373 KiB

Open AccessArticle

Comparison of Clinical Outcomes of Definitive and Postoperative Radiotherapy for Adenoid Cystic Carcinoma of the Head and Neck: Can Definitive Radiotherapy Be a Treatment Option?

by Nobutaka Mizoguchi, Kio Kano, Satoshi Shima, Keisuke Tsuchida, Yosuke Takakusagi, Itsuko Serizawa, Keiko Akahane, Masahiro Kawahara, Manatsu Yoshida, Yuka Kitani, Kaori Hashimoto, Madoka Furukawa, Tadashi Kamada, Hiroyuki Katoh, Daisaku Yoshida and Katsuyuki Shirai

Cancers 2021, 13(21), 5507; https://doi.org/10.3390/cancers13215507 - 2 Nov 2021

Cited by 7 | Viewed by 2746

Abstract

Background: The standard treatment for adenoid cystic carcinoma of the head and neck is surgical resection followed by postoperative radiotherapy (PORT). Currently, definitive radiotherapy (defRT) is considered an inadequate treatment; however, its data are based on studies using classical radiotherapy techniques. Therefore, the therapeutic effects of current radiotherapy techniques have not been adequately evaluated, and it may have underestimated the efficacy of defRT. Methods: We retrospectively analyzed 44 adenoid cystic carcinoma patients treated with radiotherapy based on modern treatment techniques from 1993 to 2017. Results: Twenty-four patients underwent PORT and 20 patients underwent defRT. The 5-year overall survival rates for patients treated with PORT and defRT were 85.3% and 79.7%, respectively. The 5-year local control rates were 82.5% and 83.1%, respectively. There were no statistically significant differences in the overall survival and local control of patients treated with PORT and defRT (p = 0.4392 and p = 0.0904, respectively). Conclusion: Our results show that defRT is comparable to surgical resection followed by PORT with respect to overall survival and local control. The results suggest that defRT can be an effective treatment option for adenoid cystic carcinoma of the head and neck. Full article

(This article belongs to the Special Issue Radiation Treatment of Head and Neck Cancers - Use, Types, and Side Effects)

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12 pages, 866 KiB

Open AccessArticle

Report on Late Toxicity in Head-and-Neck Tumor Patients with Long Term Survival after Radiochemotherapy

by Anna Maria Stefanie Buchberger, Elmar Anton Strzelczyk, Barbara Wollenberg, Stephanie Elisabeth Combs, Anja Pickhard and Steffi Ulrike Pigorsch

Cancers 2021, 13(17), 4292; https://doi.org/10.3390/cancers13174292 - 26 Aug 2021

Cited by 7 | Viewed by 3029

Abstract

Regular tumor follow-up care provided by ear-nose-throat (ENT) specialists ends when patients reach 5-year survival, but radiotoxicity is a continuous lifelong process. In this study, long-term head-and-neck cancer (HNC) survivors undergoing tumor follow-up (FU) care exceeding five years in a certified HNC center of a German university hospital were analyzed for newly diagnosed late sequelae after radio-(chemo-)therapy. Patients diagnosed with squamous cell carcinoma (SCC) of the oral cavity, larynx or oro-/hypopharynx receiving treatment between 1990 and 2010 with a tumor FU care beyond five years were reviewed retrospectively for signs of late sequelae after radio-(chemo-)therapy (R(C)T) including carotid artery stenosis, stenosis of the cranial esophagus, dysphagia, osteoradionecrosis, and secondary malignancies. Long-term survivors that solely received surgical treatment served as control. Of 1143 analyzed patients we identified 407 patients with an overall survival beyond five years, 311 with R(C)T and 96 patients without R(C)T. Furthermore, 221/1143 patients were lost to FU and the mortality rate within the first 5-years was 45%. Moreover, 27.7% of the long-term survivors were diagnosed with new onset late sequelae within the following five years. RT was significantly associated with a two-fold risk increase for newly diagnosed symptoms, especially after RT of the lymphatic pathways (LP) which showed a hazard ratio of 23.3 to develop alterations on the carotid arteries. Additional chemotherapy had no statistical correlation with any late onset toxicity nor did the mode of R(C)T (adjuvant/definitive). Although the validity of this study might be limited due to its retrospective nature and the dependence on the voluntary participation in a prolonged tumor FU, the results nevertheless provide the need to offer and encourage a tumor FU by ENT specialists exceeding the common 5-year margin. This could prevent secondary morbidities and improve quality of life for long-term cancer survivors. Full article

(This article belongs to the Special Issue Radiation Treatment of Head and Neck Cancers - Use, Types, and Side Effects)

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14 pages, 1205 KiB

Open AccessArticle

Postoperative Radiochemotherapy Using Modern Radiotherapy Techniques in Elderly Patients with Head and Neck Squamous Cell Carcinoma: The Challenge of Weighing Up Benefits and Harms of Treatment Modalities in Clinical Practice

by Martin Leu, Christoph Patzer, Manuel Guhlich, Jacqueline Possiel, Yiannis Pilavakis, Markus Anton Schirmer, Stefan Rieken and Leif Hendrik Dröge

Cancers 2021, 13(14), 3384; https://doi.org/10.3390/cancers13143384 - 6 Jul 2021

Cited by 2 | Viewed by 2107

Abstract

Locally advanced head and neck squamous cell carcinomas (HNSCC) are often managed with surgery followed by postoperative radiochemotherapy (RCT). With the general increase in life expectancy, the proportion of elderly patients with HNSCC is expected to grow rapidly. Until now, a deeper understanding of specific management strategies for these patients in clinical routine was lacking. In the present study, we compared elderly patients (≥70 years, n = 52) and younger patients (n = 245) treated with postoperative RCT for HNSCC at our tertiary cancer center. All patients were irradiated with modern radiotherapy techniques (IMRT/VMAT). Patients ≥70 years of age had more comorbidities. Additionally, elderly patients less frequently received concomitant systemic treatment. The rates of mucositis and dermatitis were lower in patients ≥70 years. Elderly patients had significantly worse overall and progression-free survival. Locoregional and distant control were comparable in elderly and younger patients. In conclusion, postoperative RCT is a safe and effective treatment option in patients ≥70 years. In light of comorbidities and poor overall survival rates, benefits and harms of radiotherapy and concomitant systemic treatment should be weighed carefully. When exclusively applying up-to-date radiotherapy techniques with, at the same time, careful use of concomitant systemic therapy, favorable acute toxicity profiles are achieved. Full article

(This article belongs to the Special Issue Radiation Treatment of Head and Neck Cancers - Use, Types, and Side Effects)

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18 pages, 13695 KiB

Open AccessArticle

Re-Irradiation for Head and Neck Cancer: Cumulative Dose to Organs at Risk and Late Side Effects

by Anna Embring, Eva Onjukka, Claes Mercke, Ingmar Lax, Anders Berglund, Sara Bornedal, Berit Wennberg, Emmy Dalqvist and Signe Friesland

Cancers 2021, 13(13), 3173; https://doi.org/10.3390/cancers13133173 - 25 Jun 2021

Cited by 22 | Viewed by 6297

Abstract

Re-irradiation in head and neck cancer is challenging, and cumulative dose constraints and dose/volume data are scarce. In this study, we present dose/volume data for patients re-irradiated for head and neck cancer and explore the correlations of cumulative dose to organs at risk and severe side effects. We analyzed 54 patients re-irradiated for head and neck cancer between 2011 and 2017. Organs at risk were delineated and dose/volume data were collected from cumulative treatment plans of all included patients. Receiver–operator characteristics (ROC) analysis assessed the association between dose/volume parameters and the risk of toxicity. The ROC-curve for a logistic model of carotid blowout vs. maximum doses to the carotid arteries showed AUC = 0.92 (95% CI 0.83 to 1.00) and a cut-off value of 119 Gy (sensitivity 1.00/specificity 0.89). The near-maximum dose to bones showed an association with the risk of osteoradionecrosis: AUC = 0.74 (95% CI 0.52 to 0.95) and a cut-off value of 119 Gy (sensitivity 1.00/specificity 0.52). Our analysis showed an association between cumulative dose to organs at risk and the risk of developing osteoradionecrosis and carotid blowout, and our results support the existing dose constraint for the carotid arteries of 120 Gy. The confirmation of these dose–response relationships will contribute to further improvements of re-irradiation strategies. Full article

(This article belongs to the Special Issue Radiation Treatment of Head and Neck Cancers - Use, Types, and Side Effects)

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13 pages, 1332 KiB

Open AccessArticle

Nutritional Care in Patients with Head and Neck Cancer during Chemoradiotherapy (CRT) and Bioradiotherapy (BRT) Provides Better Compliance with the Treatment Plan

by Aleksandra Kapała, Agnieszka Surwiłło-Snarska, Magdalena Jodkiewicz and Andrzej Kawecki

Cancers 2021, 13(11), 2532; https://doi.org/10.3390/cancers13112532 - 21 May 2021

Cited by 11 | Viewed by 3233

Abstract

The treatment of locally advanced head and neck cancer (HNC) is based on extensive resections followed by concurrent chemoradiotherapy (CRT) with platinum derivatives or concurrent radiotherapy with cetuximab (bioradiotherapy; BRT). Malnutrition, which occurs in up to 60% of patients before treatment commencement, severely increases the risk of CRT/BRT drug dose reductions and the incidence of treatment-related adverse events. A prospective observational study was performed regarding the influence of nutritional care on nutritional status, compliance with the treatment’s planned regimen, and the incidence of treatment-related complications in patients with advanced HNC during CRT and BRT. The study population encompassed 153 patients compared with a retrospective control group of 72 patients treated before nutritional care was included in the standard of oncological care. Patients enrolled in the nutritional care programme received significantly higher doses of platinum derivatives or cetuximab than patients in the control group. A significant difference between the compared populations was observed in patients below 70 years of age (92.8% of the study population), after prior surgery, and with initial weight loss lower than 10%. Nutritional care reduced final weight loss and prevented a decline within the laboratory markers of nutritional status. Weight loss was comparable in both modes of treatment—CRT and BRT. The incidence of treatment-related complications was significantly higher in patients without nutritional support in the subgroups of patients under 70 years of age and after primary surgery. Nutritional care before and during CRT and BRT in patients with HNC is a determinant of therapeutic benefit, defined as preventing down-dosing, weight loss, and the incidence of complications. Platinum derivatives and cetuximab had comparable influence on weight loss. Full article

(This article belongs to the Special Issue Radiation Treatment of Head and Neck Cancers - Use, Types, and Side Effects)

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15 pages, 2547 KiB

Open AccessArticle

Radiooncological View on Therapy Outcome after Multidisciplinary Treatment of Sinonasal Tumors

by Olena Klymenko, Anna Maria Stefanie Buchberger, Barbara Wollenberg, Klaus-Dietrich Wolff, Victoria Kehl, Stephanie E. Combs, Anja Pickhard and Steffi U. Pigorsch

Cancers 2021, 13(10), 2364; https://doi.org/10.3390/cancers13102364 - 14 May 2021

Cited by 1 | Viewed by 2585

Abstract

Purpose: We report the outcome of a mono-institutional retrospective study of sinonasal carcinoma with the primary focus on GTV (gross tumor volume) and the effect of radiotherapy. Methods: 53 patients with sinonasal carcinoma and that of the nasal cavity, paranasal sinus or both except lymphoma were included. All patients were treated between 1999 and 2017. For tumor volume delineation, all pre-therapeutic images were fused to the planning CT (computed tomography). Results: The median follow-up was 17 months [0.3–60], the median age 60 years, 35 males and 18 females were included. Squamous cell carcinoma (SCC) (60.4%) was the predominant histology, followed by adenocarcinoma (15.1%). The mean composite OS (overall survival) time was 33.3 ± 3.5 months. There was no significant difference in the 5 y composite OS between tumor localization or radiotherapy setting. The simultaneous integrated boost concept showed a trend towards improving five-year composite OS compared to the sequential boost concept. The only factor with a significant impact on the 5 y composite OS rate was the pre-therapeutic GTV (cutoff 75 cm³; p = 0.033). The GTV ≥ 100 cm³ has no effect on the 5 y composite OS rate for SCC. Conclusions: The pre-therapeutic GTV is a prognostic factor for five-year composite OS for the entire group of patients with sinonasal tumors, influencing the outcome after completion of all treatment strategies. The GTV seems to not influence five-year composite OS in SCC. For this rare tumor entity, an intensive, multidisciplinary discussion is essential to finding the best treatment option for the patient. Full article

(This article belongs to the Special Issue Radiation Treatment of Head and Neck Cancers - Use, Types, and Side Effects)

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13 pages, 1540 KiB

Open AccessArticle

Pulsed Dose Rate Brachytherapy of Lip Carcinoma: Clinical Outcome and Quality of Life Analysis

by Radouane El Ayachy, Roger Sun, Kanta Ka, Adrien Laville, Anne-Sophie Duhamel, Anne Tailleur, Isabelle Dumas, Sophie Bockel, Sophie Espenel, Pierre Blanchard, Yungan Tao, Stéphane Temam, Antoine Moya-Plana, Christine Haie-Meder and Cyrus Chargari

Cancers 2021, 13(6), 1387; https://doi.org/10.3390/cancers13061387 - 19 Mar 2021

Cited by 6 | Viewed by 2694

Abstract

Purpose: Lip carcinoma represents one of the most common types of head and neck cancer. Brachytherapy is a highly effective therapeutic option for all stages of lip cancers. We report our experience of pulsed dose rate brachytherapy (PDR) as treatment of lip carcinoma. Methods and Materials: this retrospective single center study included all consecutive patients treated for a lip PDR brachytherapy in our institution from 2010 to 2019. The toxicities and outcomes of the patients were reported, and a retrospective quality of life assessment was conducted by phone interviews (FACT H&N). Results: From October 2010 to December 2019, 38 patients were treated in our institution for a lip carcinoma by PDR brachytherapy. The median age was 73, and the majority of patients presented T1-T2 tumors (79%). The median total dose was 70.14 Gy (range: 60–85 Gy). With a mean follow-up of 35.4 months, two patients (5.6%) presented local failure, and seven patients (19%) had lymph node progression. The Kaplan–Meier estimated probability of local failure was 7.2% (95% CI: 0.84–1) at two and four years. All patients encountered radiomucitis grade II or higher. The rate of late toxicities was low: three patients (8.3%) had grade II fibrosis, and one patient had grade II chronic pain. All patients would highly recommend the treatment. The median FACT H&N total score was 127 out of 148, and the median FACT H&N Trial Outcome Index was 84. Conclusions: This study confirms that an excellent local control rate is achieved with PDR brachytherapy as treatment of lip carcinoma, with very limited late side effects and satisfactory functional outcomes. A multimodal approach should help to improve regional control. Full article

(This article belongs to the Special Issue Radiation Treatment of Head and Neck Cancers - Use, Types, and Side Effects)

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