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Multimodality and Sequential Therapy in Locally Advanced Head and Neck...
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Multimodality and Sequential Therapy in Locally Advanced Head and Neck Cancer

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

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 16744

Special Issue Editors

Prof. Dr. Giancarlo Pecorari

E-Mail Website
Guest Editor
Division of Otorhinolaryngology, Department of Surgical Sciences, University of Turin, 10126 Torino, Italy
Interests: head and neck cancer; head and neck surgery; skull base surgery; laryngeal surgery; organ preservation; flap reconstruction; oral cancer; laryngeal cancer
Special Issues, Collections and Topics in MDPI journals
Dr. Giuseppe Riva

E-Mail Website
Guest Editor
Department of Surgical Sciences, University of Turin, 10126 Torino, Italy
Interests: head and neck cancer; head and neck surgery; sinonasal cancer; laryngeal surgery; organ preservation; flap reconstruction; oral cancer; HPV-related head and neck cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The treatment of locally advanced head and neck cancer is often challenging. Despite the surgical and nonsurgical innovations in the last few decades, the oncologic and functional outcomes are not always improved. Multimodality and sequential therapy arose for locally advanced cancers and included induction chemotherapy, chemoradiation with organ-preservation protocols, immunotherapy, and targeted therapy. Surgery remains an important option, including after chemoradiotherapy failure. Moreover, treatment-related toxicity negatively affects patients’ quality of life and should be taken into account during treatment choice.

This Special Issue aims to highlight the current state of the art and to describe future perspectives for the multimodal management of locally advanced head and neck cancer. In particular, original research articles and reviews on sequential treatment, but also on the role of surgery after induction chemotherapy or as a salvage approach, are welcome.

We look forward to receiving your contributions.

Prof. Dr. Giancarlo Pecorari
Dr. Giuseppe Riva
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • head and neck cancer
  • chemotherapy
  • radiation therapy
  • head and neck surgery
  • immunotherapy
  • targeted therapy
  • biomarkers
  • human papillomavirus
  • organ preservation
  • nasopharyngeal cancer

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Published Papers (7 papers)

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Editorial

Jump to: Research, Review, Other

2 pages, 163 KiB  
Editorial
Editorial for the Special Issue on Multimodality and Sequential Therapy in Locally Advanced Head and Neck Cancer
by Giuseppe Riva and Giancarlo Pecorari
Cancers 2022, 14(17), 4247; https://doi.org/10.3390/cancers14174247 - 31 Aug 2022
Viewed by 1115
Abstract
Multimodal and sequential treatment for locally advanced head and neck cancer (HNC) included induction chemotherapy, chemoradiation organ preservation protocols, immunotherapy, and targeted therapy [...] Full article
(This article belongs to the Special Issue Multimodality and Sequential Therapy in Locally Advanced Head and Neck Cancer)
2 pages, 154 KiB  
Editorial
Multimodality and Sequential Therapy in Locally Advanced Head and Neck Cancer: A Preface to the Special Issue
by Giuseppe Riva and Giancarlo Pecorari
Cancers 2021, 13(11), 2609; https://doi.org/10.3390/cancers13112609 - 26 May 2021
Cited by 1 | Viewed by 2049
Abstract
Head and neck squamous cell carcinomas are heterogeneous in molecular pattern, clinical presentation and prognosis [...] Full article
(This article belongs to the Special Issue Multimodality and Sequential Therapy in Locally Advanced Head and Neck Cancer)

Research

Jump to: Editorial, Review, Other

16 pages, 7283 KiB  
Article
Dual PI3K/mTOR Inhibitor NVP-BEZ235 Leads to a Synergistic Enhancement of Cisplatin and Radiation in Both HPV-Negative and -Positive HNSCC Cell Lines
by Florentine S. B. Subtil, Carolin Gröbner, Niklas Recknagel, Ann Christin Parplys, Sibylla Kohl, Andrea Arenz, Fabian Eberle, Ekkehard Dikomey, Rita Engenhart-Cabillic and Ulrike Schötz
Cancers 2022, 14(13), 3160; https://doi.org/10.3390/cancers14133160 - 28 Jun 2022
Cited by 5 | Viewed by 2159
Abstract
The standard of care for advanced head and neck cancers (HNSCCs) is radiochemotherapy, including cisplatin. This treatment results in a cure rate of approximately 85% for oropharyngeal HPV-positive HNSCCs, in contrast to only 50% for HPV-negative HNSCCs, and is accompanied by severe side [...] Read more.
The standard of care for advanced head and neck cancers (HNSCCs) is radiochemotherapy, including cisplatin. This treatment results in a cure rate of approximately 85% for oropharyngeal HPV-positive HNSCCs, in contrast to only 50% for HPV-negative HNSCCs, and is accompanied by severe side effects for both entities. Therefore, innovative treatment modalities are required, resulting in a better outcome for HPV-negative HNSCCs, and lowering the adverse effects for both entities. The effect of the dual PI3K/mTOR inhibitor NVP-BEZ235 on a combined treatment with cisplatin and radiation was studied in six HPV-negative and six HPV-positive HNSCC cell lines. Cisplatin alone was slightly more effective in HPV-positive cells. This could be attributed to a defect in homologous recombination, as demonstrated by depleting RAD51. Solely for HPV-positive cells, pretreatment with BEZ235 resulted in enhanced cisplatin sensitivity. For the combination of cisplatin and radiation, additive effects were observed. However, when pretreated with BEZ235, this combination changed into a synergistic interaction, with a slightly stronger enhancement for HPV-positive cells. This increase could be attributed to a diminished degree of DSB repair in G1, as visualized via the detection of γH2AX/53BP1 foci. BEZ235 can be used to enhance the effect of combined treatment with cisplatin and radiation in both HPV-negative and -positive HNSCCs. Full article
(This article belongs to the Special Issue Multimodality and Sequential Therapy in Locally Advanced Head and Neck Cancer)
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16 pages, 2182 KiB  
Article
Early Response Prediction of Multiparametric Functional MRI and 18F-FDG-PET in Patients with Head and Neck Squamous Cell Carcinoma Treated with (Chemo)Radiation
by Roland M. Martens, Thomas Koopman, Cristina Lavini, Tim van de Brug, Gerben J. C. Zwezerijnen, J. Tim Marcus, Marije R. Vergeer, C. René Leemans, Remco de Bree, Pim de Graaf, Ronald Boellaard and Jonas A. Castelijns
Cancers 2022, 14(1), 216; https://doi.org/10.3390/cancers14010216 - 3 Jan 2022
Cited by 15 | Viewed by 2821
Abstract
Background: Patients with locally-advanced head and neck squamous cell carcinoma (HNSCC) have variable responses to (chemo)radiotherapy. A reliable prediction of outcomes allows for enhancing treatment efficacy and follow-up monitoring. Methods: Fifty-seven histopathologically-proven HNSCC patients with curative (chemo)radiotherapy were prospectively included. All patients had [...] Read more.
Background: Patients with locally-advanced head and neck squamous cell carcinoma (HNSCC) have variable responses to (chemo)radiotherapy. A reliable prediction of outcomes allows for enhancing treatment efficacy and follow-up monitoring. Methods: Fifty-seven histopathologically-proven HNSCC patients with curative (chemo)radiotherapy were prospectively included. All patients had an MRI (DW,-IVIM, DCE-MRI) and 18F-FDG-PET/CT before and 10 days after start-treatment (intratreatment). Primary tumor functional imaging parameters were extracted. Univariate and multivariate analysis were performed to construct prognostic models and risk stratification for 2 year locoregional recurrence-free survival (LRFFS), distant metastasis-free survival (DMFS) and overall survival (OS). Model performance was measured by the cross-validated area under the receiver operating characteristic curve (AUC). Results: The best LRFFS model contained the pretreatment imaging parameters ADC_kurtosis, Kep and SUV_peak, and intratreatment imaging parameters change (Δ) Δ-ADC_skewness, Δ-f, Δ-SUV_peak and Δ-total lesion glycolysis (TLG) (AUC = 0.81). Clinical parameters did not enhance LRFFS prediction. The best DMFS model contained pretreatment ADC_kurtosis and SUV_peak (AUC = 0.88). The best OS model contained gender, HPV-status, N-stage, pretreatment ADC_skewness, D, f, metabolic-active tumor volume (MATV), SUV_mean and SUV_peak (AUC = 0.82). Risk stratification in high/medium/low risk was significantly prognostic for LRFFS (p = 0.002), DMFS (p < 0.001) and OS (p = 0.003). Conclusions: Intratreatment functional imaging parameters capture early tumoral changes that only provide prognostic information regarding LRFFS. The best LRFFS model consisted of pretreatment, intratreatment and Δ functional imaging parameters; the DMFS model consisted of only pretreatment functional imaging parameters, and the OS model consisted ofHPV-status, gender and only pretreatment functional imaging parameters. Accurate clinically applicable risk stratification calculators can enable personalized treatment (adaptation) management, early on during treatment, improve counseling and enhance patient-specific post-therapy monitoring. Full article
(This article belongs to the Special Issue Multimodality and Sequential Therapy in Locally Advanced Head and Neck Cancer)
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Review

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27 pages, 726 KiB  
Review
Sinonasal Side Effects of Chemotherapy and/or Radiation Therapy for Head and Neck Cancer: A Literature Review
by Giuseppe Riva, Ester Cravero, Claudia Pizzo, Marco Briguglio, Giuseppe Carlo Iorio, Chiara Cavallin, Oliviero Ostellino, Mario Airoldi, Umberto Ricardi and Giancarlo Pecorari
Cancers 2022, 14(9), 2324; https://doi.org/10.3390/cancers14092324 - 7 May 2022
Cited by 18 | Viewed by 3428
Abstract
Radiotherapy and chemotherapy represent important treatment modalities for head and neck cancer. Rhinosinusitis and smell alterations are common side effects in the sinonasal region. This review will summarize and analyze our current knowledge of the sinonasal side effects of chemotherapy and/or radiation therapy [...] Read more.
Radiotherapy and chemotherapy represent important treatment modalities for head and neck cancer. Rhinosinusitis and smell alterations are common side effects in the sinonasal region. This review will summarize and analyze our current knowledge of the sinonasal side effects of chemotherapy and/or radiation therapy for head and neck cancer (HNC), with a specific focus on mucosal and olfactory disorders. A review of the English literature was performed using several databases (PubMed, Embase, Cochrane, Scopus). Fifty-six articles were included in qualitative synthesis: 28 assessed mucosal disorders (rhinitis or rhinosinusitis), 26 evaluated olfactory alterations, and 2 articles addressed both topics. The incidence and severity of olfactory dysfunction and chronic rhinosinusitis were highest at the end of radiotherapy and at three months after treatment and decreased gradually over time. Smell acuity deterioration and chronic rhinosinusitis seemed to be related to radiation dose on olfactory area and nasal cavities, but different degrees of recovery were observed. In conclusion, it is important to establish the severity of chronic rhinosinusitis and olfactory dysfunction in order to find strategies to support patients and improve their quality of life. Full article
(This article belongs to the Special Issue Multimodality and Sequential Therapy in Locally Advanced Head and Neck Cancer)
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Other

13 pages, 2333 KiB  
Systematic Review
Does Tumor Volume Have a Prognostic Role in Oropharyngeal Squamous Cell Carcinoma? A Systematic Review and Meta-Analysis
by Elena Russo, Remo Accorona, Oreste Iocca, Andrea Costantino, Luca Malvezzi, Fabio Ferreli, Ciro Franzese, Marta Scorsetti, Pasquale Capaccio, Giuseppe Mercante, Giuseppe Spriano and Armando De Virgilio
Cancers 2022, 14(10), 2465; https://doi.org/10.3390/cancers14102465 - 17 May 2022
Cited by 5 | Viewed by 1818
Abstract
The aim of this study was to assess the prognostic value of tumor volume in oropharyngeal squamous cell carcinoma (OPSCC). The study was performed according to the PRISMA guidelines. A total of 1417 patients with a median age of 59.3 years (IQR 57.5–60) [...] Read more.
The aim of this study was to assess the prognostic value of tumor volume in oropharyngeal squamous cell carcinoma (OPSCC). The study was performed according to the PRISMA guidelines. A total of 1417 patients with a median age of 59.3 years (IQR 57.5–60) were included. The combined Hazard Ratios (HRs) for overall survival (OS) were 1.02 (95% CI, 0.99–1.05; p = 0.21) for primary tumor volume (pTV) and 1.01 (95% CI, 1.00–1.02; p = 0.15) for nodal tumor volume (nTV). Regarding locoregional control (LRC), the pooled HRs were 1.07 (95% CI, 0.99–1.17; p = 0.10) for pTV and 1.02 (95% CI, 1.01–1.03; p < 0.05) for nTV. Finally, the pooled HRs for disease-free survival (DFS) were 1.01 (95% CI, 1.00–1.03; p < 0.05) for pTV and 1.02 (95% CI, 1.01–1.03; p < 0.05) for nTV. In conclusion, pTV and nTV seem not to behave as reliable prognostic factors in OPSCC. Full article
(This article belongs to the Special Issue Multimodality and Sequential Therapy in Locally Advanced Head and Neck Cancer)
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12 pages, 434 KiB  
Systematic Review
Free Periosteal Flaps with Scaffold: An Overlooked Armamentarium for Maxillary and Mandibular Reconstruction
by Remo Accorona, Luca Gazzini, Roberto Grigolato, Enrico Fazio, Letizia Nitro, Monir Abousiam, Giovanni Giorgetti, Lorenzo Pignataro, Pasquale Capaccio and Luca Calabrese
Cancers 2021, 13(17), 4373; https://doi.org/10.3390/cancers13174373 - 30 Aug 2021
Cited by 4 | Viewed by 2245
Abstract
Introduction: Head and neck bone reconstruction is a challenging surgical scenario. Although several strategies have been described in the literature, bone free flaps (BFFs) have become the preferred technique for large defects. Revascularized free periosteal flaps (FPFs) with support scaffold represents a possible [...] Read more.
Introduction: Head and neck bone reconstruction is a challenging surgical scenario. Although several strategies have been described in the literature, bone free flaps (BFFs) have become the preferred technique for large defects. Revascularized free periosteal flaps (FPFs) with support scaffold represents a possible alternative in compromised patient, BFF failure, or relapsing cancers as salvage treatment. However, only few clinical applications in head and neck are reported in literature. Purpose of the study was to systematically analyse the results of functional and oncologic maxillary and mandibular reconstruction with FPF with scaffold. Materials and Methods: A comprehensive review of the dedicated literature was performed according to the PRISMA guidelines searching on Scopus, PubMed/MEDLINE, Cochrane Library, Embase, Researchgate and Google Scholar databases using relevant keywords, phrases and medical subject headings (MeSH) terms. An excursus on the most valuable FPF’ harvesting sites was also carried out. Results: A total of 7 studies with 55 patients were included. Overall, the majority of the patients (n = 54, 98.1%) underwent an FPF reconstruction of the mandibular site. The most used technique was the radial forearm FPF with autologous frozen bone as scaffold (n = 40, 72.7%). The overall rate of complications was 43.7%. The success rate intended as scaffold integration resulted to be 74.5%. Conclusions: Maxillary and mandibular reconstruction with FPF and scaffold is a possible alternative in patient unfit for complex BFF reconstruction and it should be considered as a valid alternative in the sequential salvage surgery for locally advanced cancer. Moreover, it opens future scenarios in head and neck reconstructive surgery, as a promising tool that can be modelled to tailor complex 3D defects, with less morbidities to the donor site. Full article
(This article belongs to the Special Issue Multimodality and Sequential Therapy in Locally Advanced Head and Neck Cancer)
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