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Cancers
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Chemoradiotherapy for Head and Neck Cancer
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Chemoradiotherapy for 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 (10 April 2022) | Viewed by 23900

Special Issue Editor

Prof. Dr. Salvatore Cappabianca

E-Mail Website
Guest Editor
Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy
Interests: abdominal radiology; thoracic imaging; interventional radiology; radiation oncology; radiobiology; contrast media; radiomics; artificial intelligence
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Head and Neck cancer accounts for 4 percent of malignancies, with more than 650,000 cases and 330,000 death worldwide.

These diseases are usually managed by a multidisciplinary team, that includes medical oncologists, radiation oncologists, surgical oncologists, dedicated radiologists, and other specialists involved in the clinical management of these patients.

Treatment options depend on several factors, including the type and stage of head and neck cancer, the potential side effects, and the preference of patients.

Chemoradiotherapy is the standard of care in locally advanced head and neck cancer and the concomitant approach has significantly increased the curability of this group of diseases.

Known risk factors are tobacco and alcohol use, human papillomaviruses (HPVs) infection. HPV-related head and neck cancers are known to have a better prognosis as compared to HPV-unrelated cancers, so that current treatment for HPV+ cancers might be more intensive than necessary.

At the same time, recent developments in radiotherapy with the incorporation of intensity-modulated radiotherapy, molecular imaging-guided radiotherapy, adaptive radiotherapy, and proton therapy has the potential to decrease the long-term toxicity of this technique.

Finally, the immune system is known to have a pivotal role in this group of diseases, so that the PD-1 blockade represents a concrete option for the treatment of recurrent or metastatic head and neck cancers.

For this Special Issue, we welcome basic translational and clinical research papers, cancer biomarkers, professional opinions, and reviews in the broad field of locally advanced head and neck cancers.

Prof. Dr. Salvatore Cappabianca
Guest Editor

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

  • HNSCC
  • chemoradiotherapy
  • immunotherapy
  • cancer biomarkers
  • radiomics

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Published Papers (8 papers)

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Editorial

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3 pages, 176 KiB  
Editorial
Chemoradiotherapy for Head and Neck Cancer
by Ida D’Onofrio, Valerio Nardone, Alfonso Reginelli and Salvatore Cappabianca
Cancers 2023, 15(10), 2820; https://doi.org/10.3390/cancers15102820 - 18 May 2023
Cited by 4 | Viewed by 1453
Abstract
Head and neck squamous cell carcinoma (HNSCC) is a highly challenging cancer [...] Full article
(This article belongs to the Special Issue Chemoradiotherapy for Head and Neck Cancer)

Research

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18 pages, 3344 KiB  
Article
Characterization of the Immune Response to PD-1 Blockade during Chemoradiotherapy for Head and Neck Squamous Cell Carcinoma
by Juan L. Callejas-Valera, Daniel W. Vermeer, Christopher T. Lucido, Caitlin Williamson, Marisela Killian, Paola D. Vermeer, William C. Spanos and Steven F. Powell
Cancers 2022, 14(10), 2499; https://doi.org/10.3390/cancers14102499 - 19 May 2022
Cited by 4 | Viewed by 2466
Abstract
Background: Chemoradiotherapy is a standard treatment for HNSCC. Blockade of the PD-1/L1-2 interaction may represent a target to overcome immune escape during this treatment. Methods: Utilizing a HNSCC mEERL C57BL/6 mouse model, we evaluated a PD-1 blockade alone or in combination with cisplatin-based [...] Read more.
Background: Chemoradiotherapy is a standard treatment for HNSCC. Blockade of the PD-1/L1-2 interaction may represent a target to overcome immune escape during this treatment. Methods: Utilizing a HNSCC mEERL C57BL/6 mouse model, we evaluated a PD-1 blockade alone or in combination with cisplatin-based chemoradiotherapy. Next, we evaluated peripheral blood mononuclear cells (PBMCs) with relative PD-1, TIM-3, and LAG-3 expression, and myeloid-derived suppressor-like (MDSC-like) populations from a clinical trial evaluating PD-1 blockade with chemoradiotherapy in HNSCC. Finally, we analyzed the effect of therapy on human T-cell clonality through T-cell Receptor (TCR) sequencing. Results: Anti-PD-1 monotherapy induced no response in the mEERL model; however, combination with chemoradiotherapy improved tumor clearance and survival. PBMCs from patients treated with this combination therapy demonstrate a decline in circulating T-cell populations with knockdown of PD-1 expressing CD3+CD4+ and CD3+CD8+ T cells during treatment. However, TIM-3, LAG-3 expressing T-cell and MDSC-like populations concordantly rose. During treatment, the TCR repertoire demonstrates overall clonal expansion, with both unique and previously reported T-cell clones. Conclusions: Our murine HNSCC model demonstrates efficacy of PD-1 blockade during chemoradiotherapy. However, while PD-1-expressing T cells decreased with this therapy, human PBMC findings also identified an increase in populations contributing to immune exhaustion. These findings further characterize PD-1 blockade during chemoradiotherapy for HNSCC and highlight potential competing mechanisms of immune evasion. Full article
(This article belongs to the Special Issue Chemoradiotherapy for Head and Neck Cancer)
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Graphical abstract

13 pages, 646 KiB  
Article
Predictors of Outcome after (Chemo)Radiotherapy for Node-Positive Oropharyngeal Cancer: The Role of Functional MRI
by Pasqualina D’Urso, Alessia Farneti, Laura Marucci, Simona Marzi, Francesca Piludu, Antonello Vidiri and Giuseppe Sanguineti
Cancers 2022, 14(10), 2477; https://doi.org/10.3390/cancers14102477 - 18 May 2022
Cited by 7 | Viewed by 1823
Abstract
The prognosis of a subset of patients with locally advanced oropharyngeal cancer (LA-OPC) is still poor despite improvements in patient selection and treatment. Identifying specific patient- and tumor-related factors can help to select those patients who need intensified treatment. We aimed to assess [...] Read more.
The prognosis of a subset of patients with locally advanced oropharyngeal cancer (LA-OPC) is still poor despite improvements in patient selection and treatment. Identifying specific patient- and tumor-related factors can help to select those patients who need intensified treatment. We aimed to assess the role of historical risk factors and novel magnetic resonance imaging (MRI) biomarkers in predicting outcomes in these patients. Patients diagnosed with LA-OPC were studied with diffusion-weighted imaging (DWI) and dynamic-contrast enhanced MRI at baseline and at the 10th radiotherapy (RT) fraction. Clinical information was collected as well. The endpoint of the study was the development of disease progression, locally or distantly. Of the 97 patients enrolled, 68 were eligible for analysis. Disease progression was recorded in 21 patients (11 had loco-regional progression, 10 developed distant metastases). We found a correlation between N diameter and disease control (p = 0.02); features such as p16 status and extranodal extension only showed a trend towards statistical significance. Among perfusion MRI features, higher median values of Kep both in primary tumor (T, p = 0.016) and lymph node (N, p = 0.003) and lower median values of ve (p = 0.018 in T, p = 0.004 in N) correlated with better disease control. Kep P90 and N diameter were identified by MRMR algorithm as the best predictors of outcome. In conclusion, the association of non-invasive MRI biomarkers and patients and tumor characteristics may help in predicting disease behavior and patient outcomes in order to ensure a more customized treatment. Full article
(This article belongs to the Special Issue Chemoradiotherapy for Head and Neck Cancer)
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13 pages, 1107 KiB  
Article
Germline Variants in Angiogenesis-Related Genes Contribute to Clinical Outcome in Head and Neck Squamous Cell Carcinoma
by Dorota Butkiewicz, Agnieszka Gdowicz-Kłosok, Małgorzata Krześniak, Tomasz Rutkowski, Barbara Łasut-Szyszka and Krzysztof Składowski
Cancers 2022, 14(7), 1844; https://doi.org/10.3390/cancers14071844 - 6 Apr 2022
Cited by 5 | Viewed by 2302
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Chemoradiotherapy for Head and Neck Cancer)
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Review

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15 pages, 572 KiB  
Review
Head and Neck Squamous Cell Carcinoma in Elderly Patients: Role of Radiotherapy and Chemotherapy
by Morena Fasano, Ida D’Onofrio, Maria Paola Belfiore, Antonio Angrisani, Valentina Caliendo, Carminia Maria Della Corte, Mario Pirozzi, Sergio Facchini, Marianna Caterino, Cesare Guida, Valerio Nardone, Alfonso Reginelli and Salvatore Cappabianca
Cancers 2022, 14(3), 472; https://doi.org/10.3390/cancers14030472 - 18 Jan 2022
Cited by 18 | Viewed by 3514
Abstract
Head and neck squamous cell carcinomas (HNSCC) constitute the sixth most common malignancy worldwide, with approximately 25–40% of the diagnosed patients older than 70 years. HNSCC patients are often frail and frequently have multiple comorbidities due to their unhealthy lifestyle, and evidence suggests [...] Read more.
Head and neck squamous cell carcinomas (HNSCC) constitute the sixth most common malignancy worldwide, with approximately 25–40% of the diagnosed patients older than 70 years. HNSCC patients are often frail and frequently have multiple comorbidities due to their unhealthy lifestyle, and evidence suggests that older patients may receive less aggressive and suboptimal treatment than younger patients with the same disease status. The aim of this review is to depict and summarize the evidence regarding the different strategies that can be used in the clinical management of elderly HNSCC patients. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. This paper contains a narrative report and a critical discussion of clinical approaches in the context of elderly HNSCC. Full article
(This article belongs to the Special Issue Chemoradiotherapy for Head and Neck Cancer)
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16 pages, 2055 KiB  
Review
Is There Still a Place for Brachytherapy in the Modern Treatment of Early-Stage Oral Cancer?
by Luboš Tuček, Milan Vošmik and Jiří Petera
Cancers 2022, 14(1), 222; https://doi.org/10.3390/cancers14010222 - 3 Jan 2022
Cited by 4 | Viewed by 5550
Abstract
Brachytherapy (BT) involves the direct application of radioactive sources to the tumour. This technique is characterised by a steep dose gradient, the delivery of high-dose radiation to the target volume centre, and the sparing of surrounding healthy tissues. Low-dose-rate (LDR) BT and manual [...] Read more.
Brachytherapy (BT) involves the direct application of radioactive sources to the tumour. This technique is characterised by a steep dose gradient, the delivery of high-dose radiation to the target volume centre, and the sparing of surrounding healthy tissues. Low-dose-rate (LDR) BT and manual afterloading played an important role in the treatment of early-stage oral cancer, with treatment outcomes that were comparable to surgery. Interest in BT as a primary treatment for oral cancer has declined in recent years due to the emergence of better surgical techniques, the switch from LDR BT to high-dose-rate (HDR) BT (which has a higher risk of complications), and to advances in external beam radiotherapy (EBRT). At present, the main indications for BT are in the postoperative setting due to the superior dose conformity and better quality of life offered by BT versus EBRT. Postoperative BT can be administered as monotherapy in early-stage (T1N0) cancers and in combination with elective neck dissection or EBRT to treat larger or deeper tumours. BT yields excellent results for lip carcinoma in older patients and in tumours with unfavourable localisations. BT is an effective salvage therapy for local recurrences in previously-irradiated areas. Despite its many advantages, brachytherapy is a complex treatment requiring meticulous technique and close cooperation between the radiation oncologist, physicist, and surgeon. Full article
(This article belongs to the Special Issue Chemoradiotherapy for Head and Neck Cancer)
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Other

23 pages, 2500 KiB  
Systematic Review
Adding Concomitant Chemotherapy to Postoperative Radiotherapy in Oral Cavity Carcinoma with Minor Risk Factors: Systematic Review of the Literature and Meta-Analysis
by Alessia Di Rito, Francesco Fiorica, Roberta Carbonara, Francesca Di Pressa, Federica Bertolini, Francesco Mannavola, Frank Lohr, Angela Sardaro and Elisa D’Angelo
Cancers 2022, 14(15), 3704; https://doi.org/10.3390/cancers14153704 - 29 Jul 2022
Cited by 4 | Viewed by 2581
Abstract
When presenting with major pathological risk factors, adjuvant radio-chemotherapy for oral cavity cancers (OCC) is recommended, but the addition of chemotherapy to radiotherapy (POCRT) when only minor pathological risk factors are present is controversial. A systematic review following the PICO-PRISMA methodology (PROSPERO registration [...] Read more.
When presenting with major pathological risk factors, adjuvant radio-chemotherapy for oral cavity cancers (OCC) is recommended, but the addition of chemotherapy to radiotherapy (POCRT) when only minor pathological risk factors are present is controversial. A systematic review following the PICO-PRISMA methodology (PROSPERO registration ID: CRD42021267498) was conducted using the PubMed, Embase, and Cochrane libraries. Studies assessing outcomes of POCRT in patients with solely minor risk factors (perineural invasion or lymph vascular invasion; pN1 single; DOI ≥ 5 mm; close margin < 2–5 mm; node-positive level IV or V; pT3 or pT4; multiple lymph nodes without ENE) were evaluated. A meta-analysis technique with a single-arm study was performed. Radiotherapy was combined with chemotherapy in all studies. One study only included patients treated with POCRT. In the other 12 studies, patients were treated with only PORT (12,883 patients) and with POCRT (10,663 patients). Among the patients treated with POCRT, the pooled 3 year OS rate was 72.9% (95%CI: 65.5–79.2%); the pooled 3 year DFS was 70.9% (95%CI: 48.8–86.2%); and the pooled LRFS was 69.8% (95%CI: 46.1–86.1%). Results are in favor of POCRT in terms of OS but not significant for DFS and LRFS, probably due to the heterogeneity of the included studies and a combination of different prognostic factors. Full article
(This article belongs to the Special Issue Chemoradiotherapy for Head and Neck Cancer)
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14 pages, 1113 KiB  
Systematic Review
Prognostic Biomarkers for Survival in Nasopharyngeal Carcinoma: A Systematic Review of the Literature
by Kazi Anisha Islam, Larry Ka-Yue Chow, Ngar Woon Kam, Ying Wang, Chi Leung Chiang, Horace Cheuk-Wai Choi, Yun-Fei Xia, Anne Wing-Mui Lee, Wai Tong Ng and Wei Dai
Cancers 2022, 14(9), 2122; https://doi.org/10.3390/cancers14092122 - 24 Apr 2022
Cited by 9 | Viewed by 2807
Abstract
This systematic review aims to identify prognostic molecular biomarkers which demonstrate strong evidence and a low risk of bias in predicting the survival of nasopharyngeal carcinoma (NPC) patients. The literature was searched for on PubMed to identify original clinical studies and meta-analyses which [...] Read more.
This systematic review aims to identify prognostic molecular biomarkers which demonstrate strong evidence and a low risk of bias in predicting the survival of nasopharyngeal carcinoma (NPC) patients. The literature was searched for on PubMed to identify original clinical studies and meta-analyses which reported associations between molecular biomarkers and survival, including ≥150 patients with a survival analysis, and the results were validated in at least one independent cohort, while meta-analyses must include ≥1000 patients with a survival analysis. Seventeen studies fulfilled these criteria—two studies on single nucleotide polymorphisms (SNPs), three studies on methylation biomarkers, two studies on microRNA biomarkers, one study on mutational signature, six studies on gene expression panels, and three meta-analyses on gene expressions. The comparison between the hazard ratios of high-risk and low-risk patients along with a multivariate analysis are used to indicate that these biomarkers have significant independent prognostic values for survival. The biomarkers also indicate a response to certain treatments and whether they could be used as therapeutic targets. This review highlights that patients’ genetics, epigenetics, and signatures of cancer and immune cells in the tumor microenvironment (TME) play a vital role in determining their survival. Full article
(This article belongs to the Special Issue Chemoradiotherapy for Head and Neck Cancer)
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