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      Routine restaging after primary non-surgical treatment of laryngeal squamous cell carcinoma—a review

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          Abstract

          Purpose

          Treatment of patients with laryngeal squamous cell carcinoma with radiotherapy or chemoradiation is an established alternative to laryngeal surgery in many cases, but particularly for advanced tumors without cartilage invasion. Imaging modalities face the challenge of distinguishing between posttherapeutic changes and residual disease in the complex anatomic subsite of the larynx. Guidelines concerning restaging of head and neck squamous cell carcinomas (HNSCC) are presented by the National Comprehensive Cancer Network (NCCN) and other national guidelines, but clearly defined recommendations for routine restaging particularly for laryngeal cancer are lacking.

          Methods

          A systematic search was carried out in PubMed to identify studies evaluating routine restaging methods after primary non-surgical treatment of laryngeal squamous cell carcinoma from 2009 to 2020.

          Results

          Only three studies were deemed eligible, as they included at least ≥50% patients with laryngeal squamous cell carcinoma and evaluated imaging modalities to detect residual cancer. The small number of studies in our review suggest restaging with fluoro-deoxy-glucose positron-emission tomography/computed tomography (FDG PET/CT) 3 months after initial treatment, followed by direct laryngoscopy with biopsy of the lesions identified by FDG PET/CT.

          Conclusion

          Studies evaluating restaging methods after organ-preserving non-surgical treatment of laryngeal carcinoma are limited. As radiotherapy (RT), chemoradiotherapy (CRT), systemic therapy followed by RT and radioimmunotherapy are established alternatives to surgical treatment, particularly in advanced laryngeal cancers, further studies are needed to assess and compare different imaging modalities (e.g. PET/CT, MRI, CT, ultrasound) and clinical diagnostic tools (e.g., video laryngoscopy, direct laryngoscopy) to offer patients safe and efficient restaging strategies. PET or PET/CT 3 months after initial treatment followed by direct laryngoscopy with biopsy of the identified lesions has the potential to reduce the number of unnecessary laryngoscopies.

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          Most cited references48

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          Cancer statistics, 2019

          Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2019)
          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2016, were collected by the National Center for Health Statistics. In 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2006-2015) was stable in women and declined by approximately 2% per year in men, whereas the cancer death rate (2007-2016) declined annually by 1.4% and 1.8%, respectively. The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the racial gap in cancer mortality is slowly narrowing, socioeconomic inequalities are widening, with the most notable gaps for the most preventable cancers. For example, compared with the most affluent counties, mortality rates in the poorest counties were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during 2012-2016. Some states are home to both the wealthiest and the poorest counties, suggesting the opportunity for more equitable dissemination of effective cancer prevention, early detection, and treatment strategies. A broader application of existing cancer control knowledge with an emphasis on disadvantaged groups would undoubtedly accelerate progress against cancer.
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            Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer.

            Arlene Forastiere, Qiang Zhang, Randal Weber … (2013)
            To report the long-term results of the Intergroup Radiation Therapy Oncology Group 91-11 study evaluating the contribution of chemotherapy added to radiation therapy (RT) for larynx preservation. Patients with stage III or IV glottic or supraglottic squamous cell cancer were randomly assigned to induction cisplatin/fluorouracil (PF) followed by RT (control arm), concomitant cisplatin/RT, or RT alone. The composite end point of laryngectomy-free survival (LFS) was the primary end point. Five hundred twenty patients were analyzed. Median follow-up for surviving patients is 10.8 years. Both chemotherapy regimens significantly improved LFS compared with RT alone (induction chemotherapy v RT alone: hazard ratio [HR], 0.75; 95% CI, 0.59 to 0.95; P = .02; concomitant chemotherapy v RT alone: HR, 0.78; 95% CI, 0.78 to 0.98; P = .03). Overall survival did not differ significantly, although there was a possibility of worse outcome with concomitant relative to induction chemotherapy (HR, 1.25; 95% CI, 0.98 to 1.61; P = .08). Concomitant cisplatin/RT significantly improved the larynx preservation rate over induction PF followed by RT (HR, 0.58; 95% CI, 0.37 to 0.89; P = .0050) and over RT alone (P < .001), whereas induction PF followed by RT was not better than treatment with RT alone (HR, 1.26; 95% CI, 0.88 to 1.82; P = .35). No difference in late effects was detected, but deaths not attributed to larynx cancer or treatment were higher with concomitant chemotherapy (30.8% v 20.8% with induction chemotherapy and 16.9% with RT alone). These 10-year results show that induction PF followed by RT and concomitant cisplatin/RT show similar efficacy for the composite end point of LFS. Locoregional control and larynx preservation were significantly improved with concomitant cisplatin/RT compared with the induction arm or RT alone. New strategies that improve organ preservation and function with less morbidity are needed.
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              Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer.

              Bonnie Glisson, Jen-Ai Lee, Arlene Forastiere … (2003)
              Induction chemotherapy with cisplatin plus fluorouracil followed by radiotherapy is the standard alternative to total laryngectomy for patients with locally advanced laryngeal cancer. The value of adding chemotherapy to radiotherapy and the optimal timing of chemotherapy are unknown. We randomly assigned patients with locally advanced cancer of the larynx to one of three treatments: induction cisplatin plus fluorouracil followed by radiotherapy, radiotherapy with concurrent administration of cisplatin, or radiotherapy alone. The primary end point was preservation of the larynx. A total of 547 patients were randomly assigned to one of the three study groups. The median follow-up period was 3.8 years. At two years, the proportion of patients who had an intact larynx after radiotherapy with concurrent cisplatin (88 percent) differed significantly from the proportions in the groups given induction chemotherapy followed by radiotherapy (75 percent, P=0.005) or radiotherapy alone (70 percent, P<0.001). The rate of locoregional control was also significantly better with radiotherapy and concurrent cisplatin (78 percent, vs. 61 percent with induction cisplatin plus fluorouracil followed by radiotherapy and 56 percent with radiotherapy alone). Both of the chemotherapy-based regimens suppressed distant metastases and resulted in better disease-free survival than radiotherapy alone. However, overall survival rates were similar in all three groups. The rate of high-grade toxic effects was greater with the chemotherapy-based regimens (81 percent with induction cisplatin plus fluorouracil followed by radiotherapy and 82 percent with radiotherapy with concurrent cisplatin, vs. 61 percent with radiotherapy alone). The mucosal toxicity of concurrent radiotherapy and cisplatin was nearly twice as frequent as the mucosal toxicity of the other two treatments during radiotherapy. In patients with laryngeal cancer, radiotherapy with concurrent administration of cisplatin is superior to induction chemotherapy followed by radiotherapy or radiotherapy alone for laryngeal preservation and locoregional control. Copyright 2003 Massachusetts Medical Society
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                Author and article information

                Contributors
                Caroline Theresa Seebauer: caroline.seebauer@ukr.de
                Berit Hackenberg: berit.hackenberg@unimedizin-mainz.de
                Jirka Grosse: jirka.grosse@ukr.de
                Janine Rennert: janine.rennert@ukr.de
                Ernst-Michael Jung: Ernst-Michael.Jung@ukr.de
                Ines Ugele: ines.ugele@ukr.de
                Ioannis Michaelides: ioannis.michaelides@ukr.de
                Hisham Mehanna: H.Mehanna@bham.ac.uk
                Matthias G. Hautmann: matthias.hautmann@ukr.de
                Christopher Bohr: Christopher.bohr@ukr.de
                Julian Künzel:
                ORCID: http://orcid.org/0000-0001-9785-1386
                julian.kuenzel@ukr.de
                Journal
                Journal ID (nlm-ta): Strahlenther Onkol
                Journal ID (iso-abbrev): Strahlenther Onkol
                Title: Strahlentherapie Und Onkologie
                Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )
                ISSN (Print): 0179-7158
                ISSN (Electronic): 1439-099X
                Publication date (Electronic): 20 November 2020
                Publication date PMC-release: 20 November 2020
                Publication date (Print): 2021
                Volume: 197
                Issue: 3
                Pages: 167-176
                Affiliations
                [1 ]GRID grid.411941.8, ISNI 0000 0000 9194 7179, Department of Otorhinolaryngology, Head and Neck Surgery, , University Hospital of Regensburg, ; Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
                [2 ]GRID grid.410607.4, Department of Otorhinolaryngology, Head and Neck Surgery, , University Medical Center of Mainz, ; 55131 Mainz, Germany
                [3 ]GRID grid.411941.8, ISNI 0000 0000 9194 7179, Department of Nuclear Medicine, , University Hospital of Regensburg, ; 93053 Regensburg, Germany
                [4 ]GRID grid.411941.8, ISNI 0000 0000 9194 7179, Institute of Radiology, , University Hospital of Regensburg, ; 93053 Regensburg, Germany
                [5 ]GRID grid.6572.6, ISNI 0000 0004 1936 7486, Department of Head and Neck Surgery, , University of Birmingham, ; B15 2TT Birmingham, UK
                [6 ]GRID grid.411941.8, ISNI 0000 0000 9194 7179, Department of Radiotherapy, , University Hospital of Regensburg, ; 93053 Regensburg, Germany
                Author information
                http://orcid.org/0000-0001-9785-1386
                Article
                Publisher ID: 1706
                DOI: 10.1007/s00066-020-01706-9
                PMC ID: 7892687
                PubMed ID: 33216194
                SO-VID: c78fb7d7-7cb4-4e0f-95dc-5196592d88f5
                Copyright © © The Author(s) 2020
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 1 April 2020
                Date accepted : 23 October 2020
                Funding
                Funded by: Universitätsklinikum Regensburg (8921)
                Open Access :

                Open Access funding enabled and organized by Projekt DEAL.

                Categories
                Subject: Review Article
                Custom metadata
                issue-copyright-statement © Springer-Verlag GmbH Germany, part of Springer Nature 2021

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: therapy control,imaging,larynx cancer,organ-preserving treatment,radiotherapy,chemoradiotherapy
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: therapy control, imaging, larynx cancer, organ-preserving treatment, radiotherapy, chemoradiotherapy

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