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Keywords:

  • complications;
  • laryngectomy;
  • salvage surgery;
  • pharyngocutaneous fistula

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

BACKGROUND

The objectives of the current study were to report the incidence of postoperative complications for salvage total laryngectomy (STL) compared with primary total laryngectomy (PTL) and to identify patient and tumor-related factors predictive of postoperative complications.

METHODS

A sample of 183 patients who had received a total laryngectomy were identified from an existing database of 662 patients treated for squamous cell carcinoma of the larynx. PTL and STL were performed in 113 and 70 patients, respectively. Initial therapy in the patients who required salvage surgery included radiotherapy (RT) in 32 (46%) and chemoradiotherapy (CTRT) in 38 (54%). Postoperative complications were recorded for each group and categorized into local, swallowing, airway, and systemic complications. Postoperative complication rates for STL after RT and CTRT were compared with those after PTL by univariate analysis. Patient and tumor-related predictors of complications were identified by univariate and multivariate analyses.

RESULTS

The overall mortality rate was 0.5%. Forty percent of all patients developed a postoperative complication after total laryngectomy. Local complications, which were the most frequent, occurred in 52 (28%) patients. Pharyngocutaneous fistula occurred in 31 (17%) patients. Statistical analysis showed that there was a greater number of patients with local wound (45% vs. 25%, P = 0.02) and fistula complications (32% vs. 12%, P = 0.012) in the STL-CTRT group compared with the primary laryngectomy group. Multivariate analysis showed that primary CTRT was an independent predictor of local complications and pharyngocutaneous fistula.

CONCLUSIONS

Salvage laryngectomy was more frequently associated with postoperative complications after CTRT compared with PTL. Problems related to local wound healing, especially the development of pharyngocutaneous fistula, constituted the most common postoperative complication in these patients. Multivariate analysis showed that primary CTRT was an independent predictor of local wound complications and pharyngocutaneous fistula. Cancer 2005. © 2005 American Cancer Society.

Complications after laryngectomy such as pharyngocutaneous fistula, wound infection, chyle leak, swallowing, and airway problems have a significant impact on morbidity causing prolonged hospitalization and, inevitably, increased health care costs. Many factors have been implicated in the development of complications including previous radiotherapy (RT), preoperative tracheostomy, radical neck dissection, and extensive surgery and flap reconstruction. The objectives of the current study were to analyze a large database of patients with squamous cell carcinoma (SCC) of the larynx who were treated between 1984 and 1998 at a single institution and to report the incidence of postoperative complications for salvage total laryngectomy (STL) compared with primary total laryngectomy (PTL). Patients receiving total laryngectomy were comprised of three main groups: those receiving PTL, those receiving STL after chemoradiotherapy (STL-CTRT), and those receiving STL after radiotherapy (STL-RT). PTL was performed for locally advanced laryngeal tumors in the early part of the study period. After the publication by Wolf et al.1 concerning larynx preservation with CTRT, the policy of our department changed to using primary CTRT for locally advanced laryngeal tumors with surgery (total laryngectomy) reserved for salvage. For early-stage laryngeal tumors, our policy was to either employ conservation surgery or treat with primary RT, reserving surgery for salvage, either by partial or total laryngectomy. By examining patients who had total laryngectomy from these three groups, our goal was to identify patient and tumor-related variables predictive of postoperative complications using multivariate analysis.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

One hundred eighty-three patients who had undergone total laryngectomy were identified from an existing database of 662 patients treated for SCC of the larynx at Memorial Sloan-Kettering Cancer Center between 1984 and 1998. Patients who had laryngopharyngectomy for primary oropharyngeal or hypopharyngeal carcinoma were not included in the study.

Details regarding patient characteristics, tumor characteristics, previous treatment, surgical outcome, and postoperative complications were recorded. Of these, 113 patients had received PTL with 39 (34.5%) having surgery alone and 74 (65.5%) receiving surgery followed by postoperative RT. Of the remaining 549 patients, 70 underwent STL. We defined salvage laryngectomy as a total laryngectomy performed when patients either had biopsy-proven evidence of recurrent or persistent disease within the larynx after index therapy (RT or CTRT) or a nonfunctional larynx due to chondronecrosis or chronic aspiration. In our study, salvage laryngectomy was performed for persistent or local recurrent disease in 68 patients, RT necrosis in 1 patient, and chronic aspiration in 1 patient. Patients with RT necrosis and chronic aspiration received CTRT as initial therapy.

Initial therapy in the salvage patients included RT in 32 (46%) and CTRT in 38 (54%) patients. We defined CTRT as the combined use of chemotherapy and RT for the primary treatment of laryngeal carcinoma. This was given either sequentially or concurrently. In our study, 23 patients had sequential CTRT and 15 patients had concurrent CTRT. This reflected the type of CTRT used during the period from 1988 to 1998, with patients receiving sequential (induction) CTRT between 1988 and 1995 and concurrent CTRT between 1995 and 1998. Between 1988 and 1990, sequential CTRT consisted of induction cisplatin followed by a definitive dose of RT (once-daily fractions, 66–70 gray [Gy] total) and concurrent cisplatin if there was a major response at the primary site and no progression in the neck. From 1991 to 1995, sequential CTRT consisted of induction cisplatin followed by concomitant boost RT (1.8 Gy per day, Weeks 1–4, and 1.8 Gy in the morning and 1.6 Gy in the evening during Weeks 5 and 6; 70 Gy total) with concurrent cisplatin. Between 1995 and 1998, patients were treated with concurrent CTRT consisting of cisplatin on Days 1, 22, and 43 and a definitive dose of RT (once-daily fractions, 66–70 Gy total).

One hundred thirty (71%) patients were men and 53 (29%) were women. Their mean age was 60 years (range, 22–86 years). Medical comorbidity was present in 91 (50%) patients. One hundred and seventy-three (94%) were smokers and 113 (62%) were active drinkers of alcohol. SCC of the glottic larynx was the most common subtype (94 [51%]) followed by the supraglottic (65 [36%]) and sub/transglottic (24 [13%]). Overall, 77% of patients presented with cT3T4 tumors and 35% were classified cN+ before initial therapy. Tables 1 and 2 show patient and tumor variables for each laryngectomy group, respectively. These variables were comparable in patients receiving PTL compared with those receiving STL-CTRT, although there was a trend for younger patients to receive CTRT (P = 0.01). Both patient and tumor variables were significantly different for those receiving STL-RT. In this group, there were more males as well as early-stage glottic tumors. RT was the initial definitive treatment for early-stage disease (AJCC Stage I/II) whereas PTL or CTRT was used for late-stage disease (Stage III/IV).

Table 1. Patient Characteristics
CharacteristicsAll patients (n = 183) (%)PTL (n = 113) (%)STL Post-RT (n = 32) (%)P valueaSTL Post-CTRT (n = 38) (%)P valueb
  • PTL; primary total larymgectomy; STL: salvage total laryngectomy; RT: radiotherapy; CTRT: chemoradiotherapy.

  • a

    Salvage total laryngectomy after radiotherapy compared with primary total laryngectomy.

  • b

    Salvage total laryngectomy after chemoradiotherapy compared with primary total laryngectomy.

Age group (yrs)      
 < 5030 (16.4)14 (12.4)4 (12.5) 12 (31.6) 
 > 50153 (83.6)99 (87.6)28 (87.5)126 (68.4)0.01
Gender      
 Male130 (71)77 (68.1)29 (90.6) 24 (63.2) 
 Female53 (29)36 (31.9)3 (9.4)0.01214 (36.8)0.69
Medical comorbidity      
 None92 (50.3)62 (54.9)12 (37.5) 18 (47.4) 
 Present91 (49.7)51 (45.1)20 (62.5)0.120 (52.6)0.46
Smoking      
 No10 (5.5)7 (6.2)3 (9.4) 0 (0) 
 Yes173 (94.5)106 (93.8)29 (90.6)0.6938 (100)0.19
Alcohol      
 No47 (25.7)32 (28.3)8 (25) 7 (18.4) 
 Former22 (12)13 (11.5)3 (9.4) 6 (15.8) 
 Yes114 (62.3)67 (59.2)21 (65.6)0.8325 (65.8)0.43
Table 2. Location and Extent of Primary Tumors
FeaturesAll patients (n = 183) (%)PTL (n = 113) (%)STL Post-RT (n = 32) (%)P valueaSTL Post-CTRT (n = 38) (%)P valueb
  • PTL: primary total laryrngectomy; STL: salvage total laryngectomy; RT: radiotherapy; CTRT: chemoradiotherapy.

  • a

    Salvage total laryngectomy after radiotherapy compared with primary total laryngectomy.

  • b

    Salvage total laryngectomy after chemoradiotherapy compared with primary total laryngectomy.

Glottic94 (51.4)56 (49.5)25 (78.1) 13 (34.2) 
Supraglottic65 (35.5)41 (36.3)6 (18.8) 18 (47.4) 
Sub/transglottic24 (13.1)16 (14.1)1 (3.1)0.0147 (18.4)0.26
cT classification      
 18 (4.4)0 (0)8 (25) 0 (0) 
 234 (18.6)13 (11.5)20 (62.5) 1 (2.6) 
 395 (51.9)68 (60.2)4 (12.5) 23 (60.5) 
 446 (25.1)32 (28.3)0 (0)< 0.000114 (36.8)0.15
cN classification      
 0119 (65)64 (56.6)29 (90.6) 26 (68.5) 
 136 (19.7)31 (27.4)1 (3.1) 4 (10.5) 
 224 (13.1)15 (13.3)2 (6.3) 7 (18.4) 
 34 (2.2)3 (2.7)0 (0)0.00091 (2.6)0.15
cTNM classification      
 Stage I8 (4.4)0 (0)8 (25) 0 (0) 
 Stage II23 (12.6)3 (2.6)19 (59.4) 1 (2.6) 
 Stage III87 (47.5)66 (58.4)3 (9.4) 18 (47.4) 
 Stage IV65 (35.5)44 (39)2 (6.2)< 0.000119 (50)0.48

Table 3 gives details of surgery for each group. Reconstruction of the surgical defect was required in 5 (3%) patients and was comprised of a pectoralis myocutaneous flap in 3 patients, a free jejunum flap in 1 patient, and colon interposition in 1 patient. Classical radical neck dissection or type I modified radical neck dissection was performed in 90 (49%) patients. All three groups were comparable with regard to the technique of laryngectomy except for the STL-RT group, in which fewer patients received a neck dissection. This was correlated with the finding that a significantly higher proportion of patients had glottic tumors and early-stage disease in this group.

Table 3. Details of Laryngectomy
FeaturesAll patients (n = 183) (%)PTL (n = 113) (%)STL Post-RT (n = 32) (%)P valueaSTL Post-CTRT (n = 38) (%)P valueb
  • PTL: primary total laryrngectomy; STL: salvage total laryngectomy; RT: radiotherapy; CTRT: chemoradiotherapy; PMMF: pectoralis major myoautoneous; RND: radical neck dissection; MRND: modified radical neck dissection.

  • a

    Salvage total laryngectomy after radiotherapy compared with primary total laryngectomy.

  • b

    Salvage total laryngectomy after chemoradiotherapy compared with primary total laryngectomy.

Pharynx reconstruction      
 No178 (97.3)111 (98.2)31 (96.9) 36 (94.7) 
 Yes5 (2.7)2 (1.8)1 (3.1)0.532 (5.3)0.26
Type of reconstruction      
 None178 (97.3)111 (98.2)31 (96.9) 36 (94.7) 
 PMMF3 (1.7)1 (0.9)1 (3.1) 1 (2.6) 
 Colon interposition1 (0.5)0 (0)0 (0) 1 (2.6) 
 Free jejunum1 (0.5)1 (0.9)0 (0)0.550 (0)0.26
RND or type I MRND      
 No124 (67.8)71 (62.8)29 (90.6) 24 (63.2) 
 Yes59 (32.2)42 (37.2)3 (9.4%)0.00214 (36.8%)1

Complications were categorized into overall, local (wound infection, dehiscence, flap necrosis, fistula, carotid rupture, or chyle leak), swallowing (dysphagia or stricture), airway (lung, trachea, or stoma), and systemic (myocardial infarction, urinary tract infection, pulmonary, renal, or metabolic). A statistical comparison of frequencies of complications between groups was performed using the Fisher exact or chi-square tests. To identify patient and tumor factors predictive of complications, the following variables were analyzed by univariate analysis using the Fisher exact or chi-square tests: age, medical comorbidity, primary RT treatment, primary CTRT, pharyngeal reconstruction, and neck dissection (radical neck or modified radical type I neck dissection). Factors significant on univariate analysis were then assessed by multivariate analysis using a multinomial logistic regression method. Statistical analysis was performed using SPSS for Windows (version 11.01; SPSS Inc., Chicago, IL) and JMP (version 4.0; SASInstitute Inc., Cary, NC).

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

The overall mortality rate was 0.5% (1 patient died after PTL). Table 4 shows the incidence of complications. Overall, approximately 40% of all patients developed a postoperative complication after total laryngectomy. Local complications, which were the most frequent, occurred in 52 (28%) patients. Pharyngocutaneous fistula occurred in 31 (17%) patients. Univariate analysis showed no significant difference in the frequency of complications for STL-RT compared with PTL. However, there was a statistically significant increase in local complications (45% vs. 25%, P = 0.02), pharyngocutaneous fistula (32% vs. 12%, P = 0.012), and a trend toward significance for overall complications (53% vs. 36%, P = 0.08) in the STL-CTRT compared with the PTL group.

Table 4. Postoperative Complications after Laryngectomy
Type of complicationAll patients (n = 183) (%)PTL (n = 113) (%)STLPost-RT (n = 32) (%)P valueaSTLPost-CTRT (n = 38) (%)P valueb
  • PTL: primary total laryrngectomy; STL: salvage total laryngectomy; RT: radiotherapy; CTRT: chemoradiotherapy; SD: standard deviation; NS: not significant.

  • a

    Salvage total laryngectomy after radiotherapy compared with primary total laryngectomy.

  • b

    Salvage total laryngectomy after chemoradiotherapy compared with primary total laryngectomy.

Overall complications      
 No111 (60.6)72 (63.7)21 (65.6) 18 (47.4) 
 Yes72 (39.4)41 (36.3)11 (34.4)120 (52.6)0.08
Local complications      
 No131 (71.6)85 (75.2)25 (78.1) 21 (55.3) 
 Yes52 (28.4)28 (24.8)7 (21.9)117 (44.7)0.02
Swallowing complications      
 No178 (97.3)110 (97.3)32 (100) 36 (94.7) 
 Yes5 (2.7)3 (2.7)0 (0)12 (5.3)0.6
Airway complications      
 No170 (92.9)106 (93.8)29 (90.6) 35 (92.1) 
 Yes13 (7.1)7 (6.2)3 (9.4)0.453 (7.9)0.71
Systemic/metabolic complications      
 No164 (89.6)101 (89.4)28 (87.5) 35 (92.1) 
 Yes19 (10.4)12 (10.6)4 (12.5)0.753 (7.9)0.76
Pharyngocutaneous fistula      
 No152 (83.1)99 (87.6)27 (81.8) 26 (68.4) 
 Yes31 (16.9)14 (12.4)5 (15.6)0.7612 (31.6)0.012
Carotid rupture      
 No179 (97.8)110 (97.3)32 (100) 37 (97.4) 
 Yes4 (2.2)3 (2.7)0 (0)11 (2.6)1
Chyle leak      
 No180 (98.4)111 (98.2)32 (100) 37 (97.4) 
 Yes3 (1.6)2 (1.8)0 (0)11 (2.6)1
Length of hospitalization      
 Mean (SD)20.2 (19)19.7 (14.4)20 (174)NS22 (29.7)NS
 Median (range)15 (6–174)15 (8–94)16 (6–104) 15 (8–74) 

We analyzed patient and tumor-related variables predictive of complications by univariate and multivariate analyses. The results for overall, local, and pharyngocutaneous fistula are shown in Tables 5–7, respectively. The results for swallowing, airway, systemic, carotid rupture, and chyle leak complications were not shown as no significant factors were identified. For overall complications (Table 5), univariate analysis showed a trend to significance for primary CTRT and clinical T classification as being predictive of complications but these were not found to be significant on multivariate analysis. Initial treatment with CTRT was the only significant predictor of local complications (Table 6) on multivariate analysis. Patients in the STL-CTRT group were nearly three times more likely to develop a local wound complication compared with those who had either PTL or STL-RT. Index treatment with CTRT was also the only independent predictor of pharyngocutaneous fistula development after total laryngectomy (Table 7). Patients in the STL-CTRT group were twice as likely to develop postlaryngectomy pharyngocutaneous fistula.

Table 5. Factors Predictive of Overall Complications
CharacteristicsComplications (%)Univariate analysisMultivariate analysis RR (95% CI), P value
  • 95%; CI: 95%; confidence interval; NS; not significant; RT: radiotherapy; CTRT: chemoradiotherapy; RND: radical neck dissection; MRND: modified radical neck dissection.

  • a

    Fisher exact test, two tailed.

  • b

    Pearson chi-square test.

Age group (yrs)   
 < 5015/30 (50%)  
 > 5057/153 (37.9)0.22aNS
Medical comorbidity   
 None31/92 (33.7)  
 Present41/91 (45.1)0.17aNS
Smoking   
 No5/11 (45.4)  
 Yes67/171 (47.5)0.52aNS
Alcohol use   
 No25/47 (53.2)  
 Former8/22 (36.4)  
 Yes39/122 (32)0.09bNS
Primary RT   
 No61/152 (40.1)  
 Yes11/31 (35.5)0.69aNS
Primary CTRT   
 No52/145 (35.9)  
 Yes20/38 (52.6)0.09aNS
cT classification   
 11/8 (12.5)  
 215/34 (44.1)  
 332/95 (33.7)  
 424/46 (52.2)0.086bNS
cN classification   
 043/119 (36.1)  
 113/36 (36.1)  
 213/24 (54.2)  
 33/4 (75)0.18bNS
Pharynx reconstruction   
 No69/178 (38.8)  
 Yes3/5 (60)0.38aNS
Neck dissection (RND or type I MRND)   
 No48/124 (38.7)  
 Yes24/59 (40.7)0.87aNS
Table 6. Factors Predictive of Local Complications
CharacteristicsComplications (%)Univariate analysisMultivariate analysis RR (95% CI) P value
  1. 95% CI; 95%; confidence interval; RT: radiotherapy; CTRT: chemoradiotherapy; RR: relative risk; NS: not significant; RND: radical neck dissection; MRND: modified radical neck dissection

  2. a Fisher's exact test, two tailed.

  3. b Pearson chi-square test.

Age group (yrs)   
 < 5012/30 (40)  
 > 5040/153 (26.1)0.18a
Medical comorbidity   
 None22/92 (23.9)  
 Present30/91 (33)0.25a
Smoking   
 No4/11 (36.4)  
 Yes48/171 (28.1)0.48a
Alcohol use   
 No16/48 (33.3)  
 Former7/22 (31.8)  
 Yes29/112 (25.9)0.55b
Primary RT   
 No45/152 (29.6)  
 Yes7/31 (22.6)0.52a
Primary CTRT   
 No35/145 (24.1) Reference RR = 2.7 (1.1–6.4), P = 0.025
 Yes17/38 (44.7)0.016a
cT classification   
 10/8 (0)  
 213/34 (38.2)  
 321/95 (22.1)  
 418/46 (39.1)0.032bNS
cN classification   
 030/119 (25.2)  
 19/36 (25)  
 210/24 (41.7)  
 33/4 (75)0.071b
Pharynx reconstruction   
 No50/178 (28.1)  
 Yes2/5 (40)0.62a
Neck dissection (RND or type I MRND)   
 No31/124 (25)  
 Yes21/59 (35.6)0.16a
Table 7. Factors Predictive of Fistula Complications
CharacteristicsComplications (%)Univariate analysisMultivariate analysis RR (95% CI) P value
  1. 95% CI: 95%; confidence interval; RT: radiotherapy; CTRT: chemoradiotherapy; RR: relative risk; NS: not significant; RND: radical neck dissection; MRND: modified radical neck-dissection.

  2. a Fisher's exact test, two tailed.

  3. b Pearson chi-square test.

Age group (yrs)   
 < 508/30 (26.7)  
 > 5023/153 (15)0.18a
Medical comorbidity   
 None13/92 (14.1)  
 Present18/91 (19.8)0.33a
Smoking   
 No1/11 (9.1)  
 Yes30/172 (17.4)1a
Alcohol use   
 No9/48 (18.8)  
 Former3/22 (13.6)  
 Yes19/113 (16.8)0.85b
Primary RT   
 No26/151 (17.2)  
 Yes5/32 (15.6)1a
Primary CTRT   
 No19/145 (13.1) Reference
 Yes12/38 (31.6)0.013aRR = 2.4 (1.1–5.1), P = 0.027
cT classification   
 10/9 (0)  
 27/34 (20.6)  
 311/95 (11.6)  
 413/46 (28.3)0.044bNS
cN classification   
 020/120 (16.6)  
 14/36 (11/1)  
 26/24 (25)  
 31/4 (25)0.54b
Pharynx reconstruction   
 No30/178 (16.8)  
 Yes1/5 (20)1a
Neck dissection (RND or type 1 MRND)   
 No20/124 (16.1)  
 Yes11/59 (18.6)0.68a

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Organ-preserving RT and CTRT for laryngeal carcinoma produce comparable survival outcomes to primary laryngectomy and postoperative RT with the benefit of preserving voice and swallowing in a significant number of patients.1–4 However, not all patients respond and some have disease recurrence after successful therapy. Surgical salvage for these patients requires total laryngectomy. The morbidity for STL-RT and particularly CTRT is not well documented in the literature. More importantly, patient and treatment-related variables that might help to predict the development of postlaryngectomy complications have not been systematically analyzed. In an ideal situation, the question of whether STL is associated with a higher postoperative complication rate will need a prospective randomized comparison with patients undergoing PTL. Currently, however, CTRT is accepted as standard therapy for locally advanced-stage laryngeal carcinoma that would otherwise require total laryngectomy if surgical treatment were to be pursued. Therefore, any randomized comparison of these groups is unlikely to happen. Within the limitations of our study design, we have compared the frequency of postlaryngectomy complications in three groups of patients. We recognize that the retrospective nature of the current study makes comparisons prone to the ill effects of selection bias. An example is the heterogeneity that might be introduced due to lack of comparative details of radiation therapy technique for the two salvage groups considering the differences in the site and stage distribution in these two groups. Conversely, the strength of the study is that we have a relatively large sample size that included all patients who underwent a total laryngectomy extracted from a database of patients managed with a uniform, multidisciplinary treatment philosophy at a single institution.

Previous studies have reported an increased incidence of wound and systemic complications for STL-RT.5–11 A recent study by Schwartz et al.11 comprising > 2000 patients from multiple institutions from 1989 to 1999 reported an increased incidence of wound complications in patients with a history of previous RT. The incidence of pharyngocutaneous fistula has also been reported to be increased for STL-RT. Sarker et al.9 reported a fistula rate of 34.7% of which 65% had received previous RT. Johansen et al.7 reported an overall fistula rate of 32% with an increase in fistula rate with RT dose (a fistula rate of 25% for patients who had received 57 Gy compared with 92% for those receiving a dose of 72 Gy). They also reported an increase in fistula rate with RT field sizes > 50 cm2. However, more recent studies by Stoeckli et al.12 and Weber et al.3 reported lower fistula rates of 14% and 15%, respectively. In our study, the incidence of fistula for STL-RT was 15.6%, which is similar to these 2 studies and is comparable to that of PTL alone (12.4%). From our report and those of Weber et al.3 and Stoeckli et al.,12 it appears that the fistula rate has decreased in recent years. This may be due to advances in surgical technique, liberal use of regional or free flaps for reconstruction, antibiotics, and better postoperative care. However, it may also be due to advances in RT with more accurate dosing and delivery, better tissue sparing, and smaller RT portals.

More recently, patients with Stage III/IV laryngeal carcinoma have been treated by organ-preserving CTRT. This was initially performed with induction chemotherapy followed by RT1 but, more recently, by concurrent CTRT.3, 4 These studies have reported larynx preservation rates of approximately 60–88% with an overall survival rate similar to that for conventional surgical treatment. Although these studies have reported the complications of CTRT, to our knowledge there is little in the literature regarding the morbidity of STL when CTRT fails. Both RT13 and chemotherapy14 produce adverse effects on wound healing with a synergistic interaction when used together.15 Chemotherapy alone has been reported to increase wound complications in patients with advanced-stage resectable head and neck carcinoma. Schuller et al.16 reported a wound complication rate of 46% after 3 cycles of chemotherapy whereas Cory et al.17 reported a wound complication rate of 56% after induction methotrexate. When chemotherapy is combined with RT, wound complications increased in some studies.17–19 In the current study, we report that the incidence of overall and local complications, particularly pharyngocutaneous fistula, was greater in patients undergoing STL-CTRT compared with PTL. The overall incidence of complications after CTRT was 53%, which is similar to the 59% reported by Weber et al.3 The incidence of pharyngocutaneous fistula (32%) was also similar to that reported by Weber et al.3 after CTRT (25–30%). This increased incidence of pharyngocutaneous fistula has also been reported by Kraus et al.20 Our multivariate analysis showed that primary CTRT was an independent predictor of both local and fistula complications. This suggests that the addition of chemotherapy enhances the damaging effects of RT on normal tissues, leading to impaired wound healing and increased wound infection, dehiscence, and fistula formation. Further evidence for this can be derived from the time to salvage surgery. In our study, the median time from index therapy to STL was 4.2 months (range, 1–77.2 months) for STL-CTRT compared with 8.8 months (range, 2.6–47.5 months) for STL-RT. Figure 1 shows that there was a statistically significant difference between the timing of salvage surgery between the two groups, with salvage surgery being performed earlier in the CTRT group (Wilcoxon test: P = 0.02). For RT alone, wound complications from salvage surgery increase as the time interval from RT to salvage surgery increases. This is believed to be due to increased fibrosis and poorer blood supply to the irradiated tissues. However, in our study, we found that patients who received STL-CTRT had an increased incidence of major wound complications compared with STL-RT, yet had salvage surgery earlier than patients who received STL-RT. This suggests that the increased incidence of complications is a consequence of the addition of chemotherapy. This observation has been reported before by Sassler et al.18 and Lavertu et al.21 In the study by Sassler et al.,18 patients who had surgery in a time period < 12 months after CTRT had a significantly increased incidence of major wound complications compared with patients who had surgery after 12 months (P = 0.047). The most likely explanation for this is related to the nutritional and immune status of patients. In CTRT, patients have poor nutritional and immune status in the initial months and this may take several months to return to normality. Thus, our observation that wound complications are increased in the patients who received STL-CTRT can be best explained in terms of the poorer nutritional and immune status of patients receiving CTRT during the period of salvage surgery.

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Figure 1. Time from index therapy to salvage laryngectomy. STL-CTRT: salvage total laryngectomy after chemoradiotherapy; STL-RT: salvage total laryngectomy after radiotherapy.

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In addition to primary RT and primary CTRT, we chose to analyze the effects of age, medical comorbidity, smoking, alcohol use, T classification, N classification, pharyngeal reconstruction, and neck dissection (radical neck or modified radical type I neck dissection) by multivariate analyses to assess the interplay of these factors for the development of local and fistula complications. Herranz et al.22 reported an increase in the complication rate when simultaneous neck dissection was carried out with laryngectomy (35% vs. 14%, P = 0.001). A study by Lavelle and Maw23 had also reported an association with neck dissection and fistula formation. However, we were unable to demonstrate a significant relation. Shemen and Spiro24 and Herranz et al.22 also reported that complication rates were increased when flap reconstruction was required. In our study, there was no significant correlation albeit flap reconstruction was only required in five patients. A recent study by Schwartz et al.11 has also reported no association between wound complications and neck dissection or flap reconstruction. Herranz et al.22 has reported an increase in the complication rate with increasing age and more advanced T classification. Although our univariate analysis showed an association with more advanced T classification and complication rate, this was not significant when the influence of other factors was accounted for on multivariate analysis.

Because this was a retrospective study, we were unable to assess the impact of nutritional status in our multivariate analysis. This is best measured by the prognostic nutritional index, which is a combination of biochemical factors (serum albumin, transferrin), immune competence (total lymphocyte count, hypersensitivity skin tests), and anthropometric measurements (body mass index, arm muscle circumference, and skin fold thickness). In head and neck carcinoma, nutritional status deteriorates during CTRT or hyperfractionated RT25, 26 and this has been shown to have a negative effect on morbidity, mortality, and also survival.27 It is likely that the increased morbidity of surgery in patients receiving STL-CTRT compared with patients of comparable T classification receiving PTL is due to impaired nutritional status as well as the direct toxic effects of CTRT on tissue healing. Indeed, Schwartz et al.11 have recently reported that a history of weight loss 6 months before surgery, preoperative hypoalbuminemia, and anemia were independent predictors of wound complications after laryngectomy. This suggests that the morbidity of CTRT may be limited by the use of prophylactic gastrostomy tubes as reported by Lee et al.28

STL is associated with an increased incidence of overall, local, and fistula complications when the surgery is performed after CTRT treatment failure. Multivariate analysis shows that primary CTRT is an independent predictor of both local and fistula complications. However, these complications can be successfully managed and rarely result in postoperative mortality.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES