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      The Current Role of Salvage Surgery in Recurrent Head and Neck Squamous Cell Carcinoma

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          Abstract

          Chemoradiotherapy has emerged as a gold standard in advanced squamous cell carcinoma of the head and neck (SCCHN). Because 50% of advanced stage patients relapse after nonsurgical primary treatment, the role of salvage surgery (SS) is critical because surgery is generally regarded as the best treatment option in patients with recurrent resectable SCCHN. Surgeons are increasingly confronted with considering operation among patients with significant effects of failed non-surgical primary treatment. Wide local excision to achieve clear margins must be balanced with the morbidity of the procedure, the functional consequences of organ mutilation, and the likelihood of success. Accurate selection of patients suitable for surgery is a major issue. It is essential to establish objective criteria based on functional and oncologic outcomes to select the best candidates for SS. The authors propose first to understand preoperative prognostic factors influencing survival. Predictive modeling based on preoperative information is now available to better select patients having a good chance to be successfully treated with surgery. Patients with a high comorbidity index, advanced oropharyngeal or hypopharyngeal primary tumors, and both local and regional recurrence have a very limited likelihood of success with salvage surgery and should be strongly considered for other treatments. Following SS, identifying patients with postoperative prognostic factors predicting high risk of recurrence is essential because those patients could benefit of adjuvant treatment or be included in clinical trials. Finally, defining HPV tumor status is needed in future studies including recurrent oropharyngeal SCC patients.

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          Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer.

          Despite more than 70 randomised trials, the effect of chemotherapy on non-metastatic head and neck squamous-cell carcinoma remains uncertain. We did three meta-analyses of the impact of survival on chemotherapy added to locoregional treatment. We updated data on all patients in randomised trials between 1965 and 1993. We included patients with carcinoma of the oropharynx, oral cavity, larynx, or hypopharynx. The main meta-analysis of 63 trials (10,741 patients) of locoregional treatment with or without chemotherapy yielded a pooled hazard ratio of death of 0.90 (95% CI 0.85-0.94, p<0.0001), corresponding to an absolute survival benefit of 4% at 2 and 5 years in favour of chemotherapy. There was no significant benefit associated with adjuvant or neoadjuvant chemotherapy. Chemotherapy given concomitantly to radiotherapy gave significant benefits, but heterogeneity of the results prohibits firm conclusions. Meta-analysis of six trials (861 patients) comparing neoadjuvant chemotherapy plus radiotherapy with concomitant or alternating radiochemotherapy yielded a hazard ratio of 0.91 (0.79-1.06) in favour of concomitant or alternating radiochemotherapy. Three larynx-preservation trials (602 patients) compared radical surgery plus radiotherapy with neoadjuvant chemotherapy plus radiotherapy in responders or radical surgery and radiotherapy in non-responders. The hazard ratio of death in the chemotherapy arm as compared with the control arm was 1.19 (0.97-1.46). Because the main meta-analysis showed only a small significant survival benefit in favour of chemotherapy, the routine use of chemotherapy is debatable. For larynx preservation, the non-significant negative effect of chemotherapy in the organ-preservation strategy indicates that this procedure must remain investigational.
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            Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up.

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              Salvage surgery for patients with recurrent squamous cell carcinoma of the upper aerodigestive tract: when do the ends justify the means?

              Salvage surgery is widely viewed as a "double-edged sword." It is the best option for many patients with recurrent cancer of the upper aerodigestive tract, especially when original therapy included irradiation, yet it may provide only modest benefit at high personal cost to the patient. The stakes are high because alternatives are of limited value. The primary objective of this study was to fully assess the value of salvage surgical procedures in the treatment of local and regional recurrence. The following hypotheses were developed to focus the study design and data analysis. 1) The efficacy of salvage surgery correlates recurrent stage, recurrent site, and time to presalvage recurrence. 2) The economic and noneconomic costs of salvage surgery increase with higher recurrent stage. 3) Information relating the value of salvage surgery to recurrent stage and recurrent site will be useful to these patients and the physicians who treat them. Two complimentary methods of investigation were used: a meta-analysis of the published literature and a prospective observational study of patients undergoing salvage surgery for recurrent cancer of the upper aerodigestive tract. The meta-analysis combined 32 published reports to obtain an estimate of average treatment effect for salvage surgery with regard to survival, disease-free survival, surgical complications, and operative mortality. The prospective observational study included detailed data in 109 patients who underwent salvage surgery. In addition to parameters studied in the meta-analysis, we obtained baseline and interval quality of life data (Functional Living Index for Cancer [FLIC] scores), baseline and interval performance status evaluations (Performance Status Scale for Head and Neck Cancer Patients [PSS head and neck scores]), length of hospital stay, and hospital and physician charges, and related this data primarily to recurrent stage, recurrent site, and time to presalvage recurrence. The weighted average of 5-year survival in the meta-analysis was 39% in 1,080 patients from 28 different institutions. In the prospective study, median disease-free survival was 17.9 months in 109 patients, and this correlated strongly with recurrent stage, weakly with recurrent site, and not at all with time to presalvage recurrence. Noneconomic costs for patients and economic costs correlated with recurrent stage, but not with site. Baseline FLIC and PSS head and neck scores correlated with recurrent stage, but not with site. After salvage surgery the percentage of patients reaching or exceeding baseline was 51% for FLIC scores, and this differed significantly with recurrent stage. Postoperative interval "success" in PSS head and neck subscale scores for diet and eating in public also correlated with recurrent stage. Overall, the expected efficacy for salvage surgery in patients with recurrent head and neck cancer was surprisingly good, but success was limited and costs were great in stage III and, especially, in stage IV recurrences. A strong correlation of efficacy and noneconomic costs with recurrent stage allowed the creation of expectation profiles that may be useful to patients. Additional systematic clinical research is needed to improve results. In the end, the decision to undergo salvage surgery should be a personal choice made by the patient after honest and compassionate discussion with his or her surgeon.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                10 August 2018
                August 2018
                : 10
                : 8
                : 267
                Affiliations
                [1 ]Department of Head and Neck Surgery, King Albert II Cancer Institute, St Luc University Hospital, 1200 Brussels, Belgium; sandra.schmitz@ 123456uclouvain.be
                [2 ]Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
                [3 ]Instituto de Investigación Sanitaria del Principado de Asturias and CIBERONC, ISCIII, Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, 33011 Oviedo, Spain; csuareznieto@ 123456gmail.com
                [4 ]Department of Radiation Oncology, Institute of Oncology, Ljubljana SI-1000, Slovenia; pstrojan@ 123456onko-i.si
                [5 ]Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77006, USA; KArnold@ 123456mdanderson.org
                [6 ]Department of Otolaryngology, Hospital Universitario Central de Asturias, IUOPA, University of Oviedo, CIBERONC, 33011 Oviedo, Spain; jprodrigo@ 123456uniovi.es
                [7 ]Department of Radiation Oncology, University of Florida, Gainesville, FL 32610-0385, USA; mendwm@ 123456shands.ufl.edu
                [8 ]Head and Neck Cancer Unit, Guy’s and St Thomas’ Hospital NHS Foundation Trust, London SE1 9RT, UK; Ricard.Simo@ 123456gstt.nhs.uk
                [9 ]Department of Hematology and Medical Oncology, The Winship Cancer Institute of Emory University, Atlanta, GA 30305, USA; nfsaba@ 123456emory.edu
                [10 ]Head Neck Services, Tata Memorial Hospital, Parel Mumbai 400012, India; docdcruz@ 123456gmail.com
                [11 ]Division of Hematology/Oncology, Department of Medicine, Morristown Medical Center/Atlantic Health System, Morristown, NJ 07960, USA; Missak.Haigentz@ 123456atlantichealth.org
                [12 ]Department of Otolaryngology—Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109, USA; cbradfor@ 123456med.umich.edu
                [13 ]Department of Otolaryngology—Head and Neck Surgery, Mount Sinai Medical Center, New York, NY 10029, USA; Eric.Genden@ 123456mountsinai.org
                [14 ]University of Udine School of Medicine, 33100 Udine, Italy; alessandra.rinaldo@ 123456uniud.it
                [15 ]International Head and Neck Scientific Group, 35030 Padua, Italy; alfio.ferlito@ 123456uniud.it
                Author notes
                [* ]Correspondence: marc.hamoir@ 123456uclouvain.be ; Tel.: +1-3227641974; Fax: +1-3227648935
                Author information
                https://orcid.org/0000-0001-8547-2768
                https://orcid.org/0000-0002-0445-112X
                https://orcid.org/0000-0003-3063-0890
                https://orcid.org/0000-0002-3610-2266
                Article
                cancers-10-00267
                10.3390/cancers10080267
                6115801
                30103407
                7f898ab8-ebf6-4649-909b-e5ff7a44d65d
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 July 2018
                : 07 August 2018
                Categories
                Review

                cancer recurrence,head and neck cancer,squamous cell carcinoma,treatment failure,salvage surgery

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