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      Salvage surgery in post-chemoradiation laryngeal and hypopharyngeal carcinoma: outcome and review Translated title: Chirurgia di salvataggio nel carcinoma della laringe o dell'ipofaringe post-chemioradioterapia: risultati e revisione della letteratura

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          SUMMARY

          Our objective was to evaluate recurrence patterns of hypopharyngeal and laryngeal carcinoma after chemoradiation and options for salvage surgery, with special emphasis on elderly patients. In a retrospective study all patients who underwent chemoradiation for hypopharyngeal and laryngeal carcinoma in a tertiary care academic center from 1990 through 2010 were evaluated. Primary outcome measures were the survival and complication rates of patients undergoing salvage surgery, especially in elderly patients. Secondary outcome measures were the predictors for salvage surgery for patients with locoregional recurrence after failed chemoradiotherapy. A review of the literature was performed. Of the 136 included patients, 60 patients had recurrent locoregional disease, of whom 22 underwent salvage surgery. Fifteen patients underwent a total laryngectomy with neck dissection(s) and 7 neck dissection without primary tumour surgery. Independent predictors for salvage surgery within the group of 60 patients with recurrent disease, were age under the median of 59 years (p = 0.036) and larynx vs. hypopharynx (p = 0.002) in multivariate analyses. The complication rate was 68% (14% major and 54% minor), with fistulas in 23% of the patients. Significantly more wound related complications occurred in patients with current excessive alcohol use (p = 0.04). Five-year disease free control rate of 35%, overall survival rate of 27% and disease specific survival rate of 35% were found. For the 38 patients who were not suitable for salvage surgery, median survival was 12 months. Patients in whom the tumour was controlled had a 5-year overall survival of 70%. In patients selected for salvage surgery age was not predictive for complications and survival. In conclusion, at two years follow-up after chemoradiation 40% of the patients were diagnosed with recurrent locoregional disease. One third underwent salvage surgery with 35% 5-year disease specific survival and 14% major complications. Older patients selected for salvage surgery had a similar complication rate and survival as younger patients.

          RIASSUNTO

          Il nostro obiettivo è stato quello di valutare i pattern di recidiva dei carcinomi della laringe e dell'ipofaringe dopo chemioradioterapia, e le opzioni chirurgiche per un trattamento di salvataggio, con particolare attenzione ai pazienti anziani. Sono stati valutati retrospettivamente tutti i pazienti sottoposti a chemioradioterapia per carcinoma dell'ipofaringe e della laringe dal 1990 al 2010, trattati presso un policlinico universitario. Le principali misure dell'outcome sono state la sopravvivenza e il tasso di complicanze dei pazienti sottoposti a chirurgia di salvataggio. Sono stati valutati i fattori predittivi per la chirurgia di salvataggio nei pazienti con recidiva locoregionale dopo fallimento radiochemioterapico. È stata infine eseguita una revisione della letteratura. Dei 136 pazienti inclusi nello studio, 60 hanno avuto una recidiva locoregionale e 22 di questi sono stati sottoposti a chirurgia di salvataggio. 15 pazienti sono stati sottoposti a una laringectomia totale con svuotamento e 7 pazienti sono stati sottoposti solo a svuotamento laterocervicale. Nel gruppo dei 60 pazienti con recidiva di malattia, i fattori predittivi per la chirurgia di salvataggio emersi all'analisi multivariata sono stati l'età inferiore a 59 anni (p = 0,036) e la localizzazione laringea rispetto a quella ipofaringea (p = 0,002). La percentuale di complicanze registrata è stata del 68% (14% maggiori e 54% minori), con il 23% di fistole. Nei pazienti soggetti ad abuso di sostanze alcoliche si è registrata una maggiore quantità di complicanze relative alla ferita chirurgica (p = 0,04). Il controllo di malattia a 5 anni è stato del 35%, la sopravvivenza è stata del 27% e la sopravvivenza cancro specifica è stata del 35%. La sopravvivenza mediana per i 38 pazienti non sottoponibili a chirurgia di salvataggio è stata di 12 mesi. Per i pazienti nei quali si è ottenuto un controllo di malattia la sopravvivenza a 5 anni è stata del 70%. Per i pazienti sottoposti a chirurgia di salvataggio l'età non ha rappresentato un fattore predittivo né della sopravvivenza né del tasso di complicanze. In conclusione dopo due anni di followup dalla chemioradioterapia è stata diagnosticata una recidiva locoregionale nel 40% dei pazienti. Un terzo è stato sottoposto a chirurgia di salvataggio con una sopravvivenza cancro specifica a 5 anni del 35% e un 14% di complicanze maggiori. I pazienti anziani, selezionati per la chirurgia di salvataggio, hanno avuto un tasso di sopravvivenza e di complicanze maggiori sovrapponibili a quelli dei pazienti più giovani.

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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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            Larynx preservation in pyriform sinus cancer: preliminary results of a European Organization for Research and Treatment of Cancer phase III trial. EORTC Head and Neck Cancer Cooperative Group.

            As a general rule, surgery whenever possible, followed by irradiation is considered to be the standard treatment for cancer of the hypopharynx, thus sacrificing natural speech. In most patients, surgery includes removal of the larynx. A prospective, randomized phase III study was conducted by the European Organization for Research and Treatment of Cancer (EORTC) starting in 1990 to compare a larynx-preserving treatment (induction chemotherapy plus definitive, radiation therapy in patients who showed a complete response or surgery in those who did not respond) with conventional treatment (total laryngectomy with partial pharyngectomy, radical neck dissection, and postoperative irradiation) in previously untreated and operable patients with histologically proven squamous cell carcinomas of the pyriform sinus or aryepiglottic fold, but free of other cancers. Patients were randomly assigned to one of two treatment arms: 1) immediate surgery with postoperative radiotherapy (50-70 Gy) or 2) induction chemotherapy (cisplatin [100 mg/m2] given as a bolus intravenous injection on day 1, followed by infusion of fluorouracil [1000 mg/m2 per day] on days 1-5). An endoscopic evaluation was performed after each cycle of chemotherapy. After two cycles, only partial and complete responders received a third cycle. Patients with a complete response after two or three cycles of chemotherapy were treated thereafter by irradiation (70 Gy); nonresponding patients underwent conventional surgery with postoperative radiation (50-70 Gy). Salvage surgery was also performed when patients relapsed after chemotherapy and irradiation. The trial was designed to test the equivalence of the two treatment arms; i.e., the induction chemotherapy treatment would be judged equivalent to immediate surgery if the relative risk of death for induction chemotherapy compared with immediate surgery was significantly less than 1.43 using a one-sided hypothesis test at the .05 level of significance. Two hundred two patients entered the trial and were randomly assigned; only 194 were eligible for treatment (94 in the immediate-surgery arm and 100 in the induction-chemotherapy arm). In the induction-chemotherapy arm, complete response was seen in 52 (54%) of 97 patients with local disease (primary tumor) and in 31 (51%) of 61 patients with regional disease (involvement of the neck). Treatment failures at local, regional, and second primary sites occurred at approximately the same frequencies in the immediate-surgery arm (12%, 19%, and 16%, respectively) and in the induction-chemotherapy arm (17%, 23%, and 13%, respectively). In contrast, there were fewer failures at distant sites in the induction-chemotherapy arm than in the immediate-surgery arm (25% versus 36%, respectively; P = .041). The median duration of survival was 25 months in the immediate-surgery arm and 44 months in the induction-chemotherapy arm and, since the observed hazard ratio was 0.86 (logrank test, P = .006), which was significantly less than 1.43, the two treatments were judged to be equivalent. The 3- and 5-year estimates of retaining a functional larynx in patients treated in the induction-chemotherapy arm were 42% (95% confidence interval = 31%-53%) and 35% (95% confidence interval = 22%-48%), respectively. Larynx preservation without jeopardizing survival appears feasible in patients with cancer of the hypopharynx. On the basis of these observations, the EORTC has now accepted the use of induction chemotherapy followed by radiation as the new standard treatment in its future phase III larynx preservation trials.
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              Complications in head and neck surgery: a meta-analysis of postlaryngectomy pharyngocutaneous fistula.

              To summarize the potential risk factors for postlaryngectomy pharyngocutaneous fistula. Observational studies in the English-language literature about postlaryngectomy pharyngocutaneous fistula from January 1, 1970, to March 31, 2003. Studies were identified through a MEDLINE search with relevant key words; additional studies were identified through references. We included studies about the site of primary malignancy, type of procedure, and type of closure; studies had to have been based on individual-level data, with a comparison group for each risk factor evaluated. Data required to calculate the relative risk of fistula associated with commonly reported risk factors were abstracted from the studies, and a meta-analysis using a random-effects approach was performed to estimate a summary relative risk of fistula for each risk factor. The statistical significance of heterogeneity of effects among studies was assessed. Of 65 studies identified, 26 met the inclusion criteria. Significant risk factors identified in the pooled analysis included postoperative hemoglobin level less than 12.5 g/dL, prior tracheotomy, preoperative radiotherapy, and preoperative radiotherapy and concurrent neck dissection. The degree of heterogeneity of effects among studies was significant for postoperative hemoglobin level, preoperative radiotherapy, concurrent neck dissection, and comorbid illness. The severity of fistula was greater in patients with a history of radiotherapy. This meta-analysis identified several significant risk factors for postlaryngectomy pharyngocutaneous fistula. The clinical implications of these findings and the potential sources of heterogeneity of effects among studies are discussed.
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                Author and article information

                Journal
                Acta Otorhinolaryngol Ital
                Acta Otorhinolaryngol Ital
                Pacini
                Acta Otorhinolaryngologica Italica
                Pacini Editore SpA
                0392-100X
                1827-675X
                June 2015
                : 35
                : 3
                : 162-172
                Affiliations
                [1 ] Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands;
                [2 ] Department of Otolaryngology, Medical Center Alkmaar, Alkmaar, The Netherlands;
                [3 ] Department of Head and Neck Surgical Oncology, UMC Utrecht Cancer Center, UMCU Utrecht, Utrecht, The Netherlands;
                [4 ] Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands;
                [5 ] Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands;
                [6 ] Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
                Author notes
                Address for correspondence: R. de Bree, Department of Otolaryngology, Head and Neck Surgery, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Tel. 0031 204443689. Fax 0031 204443688. E-mail: r.bree@ 123456vumc.nl
                Article
                Pacini
                4510934
                26246660
                bf9b51ed-7ebd-48d4-a778-93ab510caf11
                © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License, which permits for noncommercial use, distribution, and reproduction in any digital medium, provided the original work is properly cited and is not altered in any way. For details, please refer to http://creativecommons.org/licenses/by-nc-nd/3.0/

                History
                : 02 December 2014
                : 15 April 2015
                Categories
                Head and Neck

                Otolaryngology
                laryngeal cancer,hypopharyngeal cancer,salvage surgery,chemoradiation,complications,survival,elderly,review

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