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      Open Partial Horizontal Laryngectomies for T3–T4 Laryngeal Cancer: Prognostic Impact of Anterior vs. Posterior Laryngeal Compartmentalization

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          Abstract

          Open partial horizontal laryngectomies (OPHLs) are well-established and oncologically safe procedures for intermediate–advanced laryngeal cancers (LC). T–N categories are well-known prognosticators: herein we tested if “anterior” vs. “posterior” tumor location (as defined in respect to the paraglottic space divided according to a plane passing through the arytenoid vocal process, perpendicular to the ipsilateral thyroid lamina) may represent an additional prognostic factor. We analyzed a retrospective cohort of 85 T3–4a glottic LCs, treated by Type II or III OPHL (according to the European Laryngological Society classification) from 2005 to 2017 at two academic institutions. Five-year overall survival (OS), disease-specific survivals (DSS), and recurrence-free survivals (RFS) were compared according to tumor location and pT category. Anterior and posterior tumors were 43.5% and 56.5%, respectively, 78.8% of lesions were T3 and 21.2% were T4a. Five-year OS, DSS, and RFS for T3 were 74.1%, 80.5%, and 63.4%, respectively, and for T4a 71.8%, 71.8%, and 43%, respectively ( p not significant). In relation to tumor location, the survival outcomes were 91%, 94.1%, and 72.6%, respectively, for anterior tumors, and 60.3%, 66.3%, and 49.1%, respectively, for posterior lesions (statistically significant differences). These data provide evidence that laryngeal compartmentalization is a valid prognosticator, even more powerful than the pT category.

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          Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group.

          We performed a prospective, randomized study in patients with previously untreated advanced (Stage III or IV) laryngeal squamous carcinoma to compare the results of induction chemotherapy followed by definitive radiation therapy with those of conventional laryngectomy and postoperative radiation. Three hundred thirty-two patients were randomly assigned to receive either three cycles of chemotherapy (cisplatin and fluorouracil) and radiation therapy or surgery and radiation therapy. The clinical tumor response was assessed after two cycles of chemotherapy, and patients with a response received a third cycle followed by definitive radiation therapy (6600 to 7600 cGy). Patients in whom ther was no tumor response or who had locally recurrent cancers after chemotherapy and radiation therapy underwent salvage laryngectomy. After two cycles of chemotherapy, the clinical tumor response was complete in 31 percent of the patients and partial in 54 percent. After a median follow-up of 33 months, the estimated 2-year survival was 68 percent (95 percent confidence interval, 60 to 76 percent) for both treatment groups (P = 0.9846). Patterns of recurrence differed significantly between the two groups, with more local recurrences (P = 0.0005) and fewer distant metastases (P = 0.016) in the chemotherapy group than in the surgery group. A total of 59 patients in the chemotherapy group (36 percent) required total laryngectomy. The larynx was preserved in 64 percent of the patients overall and 64 percent of the patients who were alive and free of disease. These preliminary results suggest a new role for chemotherapy in patients with advanced laryngeal cancer and indicate that a treatment strategy involving induction chemotherapy and definitive radiation therapy can be effective in preserving the larynx in a high percentage of patients, without compromising overall survival.
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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.

            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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              Perineural invasion in squamous cell carcinoma of the head and neck.

              To determine if perineural invasion (PNI) of small nerves affects the outcome of patients with squamous cell carcinoma (SCC) of the upper aerodigestive tract. Retrospective clinicopathological study of patients with at least 2 years of follow-up and with negative margins and no prior, synchronous, or metachronous SCC. Academic otolaryngology department. One hundred forty-two patients who had SCC of the oral cavity, oropharynx and hypopharynx, or larynx resected between 1981 and 1991. Surgery with or without adjuvant therapy. Local recurrence was examined with respect to PNI, nerve diameter, and microvascular or microlymphatic invasion. Perineural invasion was correlated with lymph node metastasis, extracapsular spread, and survival. Perineural invasion of nerves less than 1 mm in diameter was present in 74 patients, lymphatic invasion in 53, and vascular invasion in 9. Perineural invasion was significantly associated with local recurrence (23% for PNI vs 9% for no PNI; P=. 02), and disease-specific mortality (54% mortality for PNI vs 25% for no PNI; P<.001). With extralaryngeal tumors, PNI was associated with nodal metastasis (73% vs 46%; P=.03). Perineural invasion was not associated with extracapsular spread (P=.47). Microvascular invasion, lymphatic invasion, and nerve diameter were not significantly related to local recurrence. Perineural invasion of small nerves is associated with an increased risk of local recurrence and cervical metastasis and is, independent of extracapsular spread, a predictor of survival for patients with SCC of the upper aerodigestive tract.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                01 March 2019
                March 2019
                : 11
                : 3
                : 289
                Affiliations
                [1 ]Department of Otorhinolaryngology—Head and Neck Surgery, University of Brescia, Piazza Spedali Civili 1, 25123 Brescia, Italy; delbonfrancesca@ 123456gmail.com (F.D.B.), lancinidavide@ 123456gmail.com (D.L.); paolo.bosio92@ 123456gmail.com (P.B.); stefanotaboni@ 123456gmail.com (S.T.); dott.riccardomorello@ 123456gmail.com (R.M.); nausica.montalto@ 123456gmail.com (N.M.); adeganello@ 123456hotmail.com (A.D.); pieronicolai@ 123456virgilio.it (P.N.)
                [2 ]Department of Otorhinolaryngology, Maxillofacial and Thyroid Surgery, Fondazione IRCCS, National Cancer Institute of Milan, University of Milan, 20133 Milan, Italy; ceceplaza@ 123456libero.it (C.P.); Fabiola.Incandela@ 123456istitutotumori.mi.it (F.I.)
                [3 ]Department of Otorhinolaryngology, Head and Neck Surgery, University of Genoa—IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; missale.francesco@ 123456gmail.com (F.M.); filippomarchi@ 123456hotmail.it (F.M.); mfilauro@ 123456yahoo.com (M.F.); giorgioperetti18@ 123456gmail.com (G.P.)
                Author notes
                [* ]Correspondence: albpaderno@ 123456gmail.com
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-3525-3118
                https://orcid.org/0000-0002-5357-5348
                Article
                cancers-11-00289
                10.3390/cancers11030289
                6468624
                30832209
                06feed22-f44e-4d75-8de6-43adf2d14120
                © 2019 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
                : 22 January 2019
                : 24 February 2019
                Categories
                Article

                laryngeal cancer,open partial horizontal laryngectomy,conservative surgery,paraglottic space,prognosis

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