Organ Preservation with Concurrent Chemoradiation for Advanced Laryngeal Cancer
Purpose
To determine the rates of organ preservation and function in patients with advanced laryngeal and hypopharyngeal carcinomas treated with concurrent chemoradiotherapy (CRT).
Methods and Materials
Between April 1999 and September 2005, 82 patients with advanced laryngeal (67%) and hypopharyngeal carcinomas (33%) underwent conventional radiotherapy and concurrent platinum-based chemotherapy with curative intent. Sixty-two patients were male (75.6%). The median age was 59 years. Eighteen patients (22%) were in Stage III and 64 (78%) were in Stage IV. The median radiation dose was 70 Gy. The median potential follow-up was 3.9 years.
Results
Overall survival and disease-free survival were respectively 63% and 73% at 3 years. Complete response rate from CRT was 75%. Nineteen patients (23%) experienced significant long-term toxicity after CRT: 6 (7.3%) required a percutaneous endoscopic gastrostomy, 5 (6%) had persistent Grade 2 or 3 dysphagia, 2 (2.4%) had pharyngoesophageal stenosis requiring multiple dilations, 2 (2.4%) had chronic lung aspiration, and 7 (8.5%) required a permanent tracheostomy. Four patients (4.9%) underwent laryngectomy without pathologic evidence of disease. At last follow-up, 5 (6%) patients were still dependent on a gastrostomy. Overall, 42 patients (52%) were alive, in complete response, with a functional larynx and no other major complications.
Conclusions
In our institution, CRT for advanced hypopharyngeal and laryngeal carcinoma has provided good overall survival and locoregional control in the majority of patients, but a significant proportion did not benefit from this approach because of either locoregional failure or late complications. Better organ preservation approaches are necessary to improve locoregional control and to reduce long-term toxicities.
Larynx, Hypopharynx, Radiotherapy, Chemotherapy, Adverse effects, Late morbidity
Article Outline
• Abstract
• Introduction
• Methods and Materials
• Patient and tumor characteristics
• Radiotherapy
• Chemotherapy
• Surgery
• Toxicity assessment
• Statistical analysis
• Results
• Treatment outcome
• Late toxicities
• Discussion
• Conclusion
• Uncited reference
• References
• Copyright
Introduction
Larynx cancer is the most common cancer subsite in head and neck oncology. For patients with advanced tumors (Stage III or IV) of the larynx and hypopharynx, treatment options are concomitant chemoradiation (CRT) with surgery as salvage, or up-front surgery followed by adjuvant radiotherapy, with or without concurrent chemotherapy. These multimodal regimens are equivalent in terms of survival, but CRT offers the potential advantage of organ preservation 1, 2, 3, 4, 5, 6, 7.
Unfortunately, organ preservation treatment protocols are associated with significant acute and late adverse effects. Therefore, quality of life and morbidity should be considered when a treatment is proposed. Quality of life relates to overall well-being including the functional, emotional, mental, social, and economic components. The most common predictors of quality of life in surviving patients with advanced laryngeal cancer receiving CRT appear to be absence of pain and lower incidence of mood disorder rather than preservation of speech function (8).
Intensity-modulated radiotherapy (IMRT) is starting to be used in the larynx and hypopharynx substites (9). Although experience with this modality is accumulating, we wanted to review our current results with conventional radiotherapy. Our goal was to determine rates of functional organ preservation and late toxicities in patients treated for advanced laryngeal and hypopharyngeal cancer at our tertiary care health center.
Methods and Materials
Patient and tumor characteristics
Between August 1998 and September 2005, a total of 105 patients with histologically proven laryngeal and hypopharyngeal squamous cell cancer (SCC) were treated with concurrent CRT at the Centre Hospitalier de l'Université de Montréal. Pretreatment evaluations consisted of a complete history and physical examination including direct laryngoscopy using a flexible fiberoptic endoscope. Dental evaluation was mandatory in all except edentulous patients. All patients had a complete blood count and biochemical profile, chest X-ray, head-and-neck CT scan, and, in some cases, an MRI. All patients were presented to our multidisciplinary team, which includes head-and-neck surgeons, medical oncologists, radiation oncologists, nurses, nutritionists, speech and swallowing specialists, and pharmacists.
Of these patients, 23 were excluded from the analysis for the following reasons: retreatment (6 patients), use of IMRT (4 patients), follow-up less than 2 years (5 patients), or up-front laryngectomy (10 patients).
Of the remaining 82 eligible patients, 57 and 39 were Stage IVa and T3, respectively. All the data were reported according to the 1998 American Joint Committee on Cancer (AJCC). The distribution of the primary site was 55 larynx and 27 hypopharynx. Of the patients, 62 were male and 20 were female, with a median age of 59 years. Patient characteristics are shown in Table 1. Median potential follow-up was 3.9 years (10).
Table 1. Patient and tumor characteristics
Characteristic Value (%)
Total patients 82 (100)
Gender
Men 62 (76)
Women 20 (24)
Age (y)
Median 59
Range 42–77
Site
Larynx 55 (67)
Hypopharynx 27 (33)
Histological type (SCC) 82 (100)
T stage
T1–2 23 (28)
T3 39 (48)
T4a-b 20 (24)
N stage
N0 15 (18)
N1 12 (15)
N2 51 (62)
N3 4 (5)
Overall stage
III 18 (22)
IVA 57 (70)
IVB 7 (8)
Based on American Joint Committee on Cancer criteria.
Radiotherapy
Most patients were treated with conventional radiotherapy and standard fractionation, 2 Gy per day, five fractions per week for 7 weeks. Median dose was 70 Gy (16–72 Gy). Four patients received a concomitant boost to 72 Gy in 6 weeks. Nine patients did not receive the prescribed dose of radiotherapy (Table 2), including 4 patients who died during treatment, of which two deaths were from an unrelated cause. One of the 9 patients experienced recurrence in the treatment field.
Table 2. Treatment details
Treatment Value (%)
Radiation dose (Gy)
Median 70
Range 16–72
Chemotherapy
Cisplatin 46 (56)
Carboplatin 10 (12)
Carboplatin/5-fluorouracil 23 (28)
Unknown 3 (4)
A planning CT scan with a 5-mm slice thickness was performed in all patients. A thermoplastic head-to-shoulder mask was used for immobilization. Dosimetry was performed with Theraplan v3.8 (Nucletron, Veenendaal, the Netherlands); field arrangement consisted of half-beam blocked lateral opposed fields and supraclavicular field with 4-MV photons. Electrons fields were added as required to the spinal and tracheostomy regions. The target volumes and radiation doses were defined according to International Commission on Radiation Units (ICRU) 12, 13.
Chemotherapy
All patients underwent concurrent platinum-based chemotherapy. Most patients (56%) received cisplatin 100 mg/m2 every 3 weeks. A total of 23 (28%) had carboplatin-5FU given respectively 70 mg/m2/day and 600 mg/m2/day in continuous infusion, both for 4 days every 3 weeks (Table 2).
Surgery
A head-and-neck CT scan was performed 2 months after the completion of treatment. Neck dissection was performed in a patient with persistent clinical or radiographic evidence of residual nodal disease. A salvage total laryngectomy was performed if the primary tumor response was incomplete.
Toxicity assessment
Follow-up was done every 2 months for the first 2 years, then every 4 months up to 5 years, then annually. Patients with locoregional failure or death resulting from cancer were excluded from the assessment. Late toxicity was evaluated more then 3 months after the end of radiation treatment and defined as follow: Grade 2 or higher dysphagia according to the Common Terminology Criteria of Adverse Events (CTCAE) Version 3.0, requirement of a feeding tube/gastrostomy, pharyngoesophageal stenosis, chronic lung aspiration, and laryngectomy or tracheotomy without evidence of tumor recurrence.
Statistical analysis
Statistical analyses were performed with SAS version 8.2 (SAS Institute, Cary, NC). Disease-free survival and overall survival were calculated using the Kaplan-Meier method. Time variables were calculated from the start of radiotherapy. Freedom from local, regional, or distant progression was defined as the absence of demonstrable tumor on physical and radiographic examinations. Follow-up time was calculated using the method described by Schemper and Smith (10).
Results
Treatment outcome
Overall survival, disease-free survival, and the laryngectomy-free survival were respectively 63%, 73%, and 53% at 3 years (Fig 1, Fig 2). Complete response rate with CRT was 75%. The primary tumor response rate was higher, with 88% complete response vs. 79% for nodal complete response.
Fig 1. Kaplan-Meier estimate of overall survival.
Fig 2. Kaplan-Meier estimate of disease-free survival.
Late toxicities
Nineteen patients (23%) experienced significant complications after CRT corresponding to Grade 2, 3, or 4 on the CTCAE scale. Six (7%) required a percutaneous gastrostomy (PEG), 5 (6%) had persistent Grade 2 or 3 dysphagia, 2 (2%) had pharyngoesophageal stenosis requiring multiple dilations, 2 (2%) had chronic lung aspiration, and 7 (8.5%) required a permanent tracheostomy. Four patients (4.9%) underwent laryngectomy because of poor pain control or dysfunctional larynx, without pathologic evidence of disease (Table 3).
Table 3. Late complications
Complications and treatment n
Percutaneous endoscopic gastrostomy 6
Dysphagia Grade 2–3 5
Pharyngoesophageal stenosis 2
Chronic lung aspirations 2
Tracheostomy 7
Laryngectomy 4
At last follow-up, 5 (6%) patients were still dependent on their PEG for adequate intake for a mean duration of 43 months (range, 18–61 months) after radiation. Overall, 42 (52%) patients obtained a complete response and had a functional larynx with no other major complications.
Discussion
Few studies have addressed functional outcomes of larynx preservation protocols. The main goal of our study was to review the toxicity of laryngeal preservation treatments in our center for patient with advanced larynx or hypopharynx squamous cell carcinoma. Both subjective and objective swallowing problems are frequent and severe long-term side effects after radiotherapy for pharyngeal cancer. Swallowing dysfunction has been correlated with dose and volume parameters of the upper aerodigestive tract 14, 15, 16. Organ preservation treatment impairs movement of structures that are essential for effective swallowing 17, 18, 19.
With a median potential follow-up of 3.9 years, our 3-year laryngectomy-free survival, progression-free survival and overall survival are comparable four Phase III laryngectomy preservation trials 1, 2, 3, 7. Toxicity remains significant with this treatment option, as only half of surviving patients are able to return to pretreatment function. These findings are corroborated by Guadagnolo et al. (20) In a recent meta-analyses of 230 patients receiving CRT for SCC of the head and neck, the laryngeal and hypopharyngeal primary site was the strongest independent risk factor on multivariate analysis for severe late toxicity (21).
The successful management of swallowing dysfunction after chemoradiation is complex and difficult to achieve, requiring a multidisciplinary approach. Collaboration among different specialists (physicians, speech pathologists, dietitians, and psychologists) remains the key to a desirable outcome (22). Prophylactic swallowing exercises may benefit these patients and we reinforce this with our patients 23, 24. Moreover, Mekhail et al. reported more pharyngeal stenosis and duration of nutritional support with PEG vs. nasogastric tube at their institution when patients underwent concurrent chemoradiation for advanced head-and-neck carcinoma (25).
In our center, to decrease the incidence of pharyngeal stenosis and to prevent PEG dependency, we tend not to install PEG up front. We hypothesize that encouraging patients to use their swallowing mechanisms during treatment for the longest period of time might decrease those patients' likelihood of developing a PEG dependency as well as requiring pharyngeal dilation in the long run. Even with this approach, 15% of our patients experienced one of these late toxicities.
The present study has several limitations. First, it is a retrospective single-institution study on the long-term toxicities of concomitant chemotherapy and conventional radiotherapy in the treatment of advanced laryngeal and hypopharyngeal tumors. Toxicities were retrospectively determined from a review of the patient charts and thus possibly underreported for the lower grades. Nevertheless, severe complications were likely to be reported, as patient with Grade 2 or greater toxicities are closely followed weekly after treatment by our multidisciplinary team.
Preliminary studies have shown that IMRT can achieve encouraging locoregional control rates for advanced laryngeal and hypopharyngeal carcinomas (9). Xerostomia improves over time but pharyngoesophageal stricture with PEG dependency remains a problem, particularly for patients with hypopharyngeal carcinoma and, to a lesser extent, those with laryngeal cancer. Strategies using IMRT to limit the dose delivered to the esophagus/inferior constrictor musculature without compromising target coverage might be useful to further minimize these late complications (16). Moreover, the grade of laryngeal edema is correlated with mean dose to the larynx, which should ideally be kept to less than 43 to 45 Gy 26, 27. This dose constraint is difficult to achieve when one considers that the larynx is part of the radiation therapy target volume and that the tumoricidal dose usually is approximately 70 Gy.
One has to remember that total laryngectomy has psychological and social consequences, and the choice of the optimal treatment modality is largely dependent on the expertise and experience of the multidisciplinary team 28, 29. Given that survival appears equivalent between the two modalities, post-treatment quality of life becomes a decisive factor. Only a few studies compared qualilty of life between CRT for laryngeal preservation with total laryngectomy and postoperative radiation. Although some trials have shown an improvement in some components of quality of life 8, 30 many others have described equivalent results 31, 32, 33, 34. Furthermore, cost consideration may be an important factor in decision making for the treatment of advanced laryngeal cancer 35, 36.
Conclusion
In this study, half of all patients with advanced laryngeal or hypopharyngeal carcinomas treated with CRT, experienced either significant complications of laryngeal failure or locoregional relapse. For patients treated with the objective of preserving a functional larynx, PEG dependency and laryngectomy are frequent negative outcomes. More efforts and studies are necessary to further improve locoregional control, improve quality of life, and reduce late complications.
Given that survival appears equivalent between the two modalities, patient preference may be an important factor in decision making for the treatment of advanced laryngeal cancer, and clear and informed consent should be obtained. The incorporation of targeted biological therapies and IMRT may reduce long-term toxicities. Prospective Phase III studies are needed with quality of life assessment.
To determine the rates of organ preservation and function in patients with advanced laryngeal and hypopharyngeal carcinomas treated with concurrent chemoradiotherapy (CRT).
Methods and Materials
Between April 1999 and September 2005, 82 patients with advanced laryngeal (67%) and hypopharyngeal carcinomas (33%) underwent conventional radiotherapy and concurrent platinum-based chemotherapy with curative intent. Sixty-two patients were male (75.6%). The median age was 59 years. Eighteen patients (22%) were in Stage III and 64 (78%) were in Stage IV. The median radiation dose was 70 Gy. The median potential follow-up was 3.9 years.
Results
Overall survival and disease-free survival were respectively 63% and 73% at 3 years. Complete response rate from CRT was 75%. Nineteen patients (23%) experienced significant long-term toxicity after CRT: 6 (7.3%) required a percutaneous endoscopic gastrostomy, 5 (6%) had persistent Grade 2 or 3 dysphagia, 2 (2.4%) had pharyngoesophageal stenosis requiring multiple dilations, 2 (2.4%) had chronic lung aspiration, and 7 (8.5%) required a permanent tracheostomy. Four patients (4.9%) underwent laryngectomy without pathologic evidence of disease. At last follow-up, 5 (6%) patients were still dependent on a gastrostomy. Overall, 42 patients (52%) were alive, in complete response, with a functional larynx and no other major complications.
Conclusions
In our institution, CRT for advanced hypopharyngeal and laryngeal carcinoma has provided good overall survival and locoregional control in the majority of patients, but a significant proportion did not benefit from this approach because of either locoregional failure or late complications. Better organ preservation approaches are necessary to improve locoregional control and to reduce long-term toxicities.
Larynx, Hypopharynx, Radiotherapy, Chemotherapy, Adverse effects, Late morbidity
Article Outline
• Abstract
• Introduction
• Methods and Materials
• Patient and tumor characteristics
• Radiotherapy
• Chemotherapy
• Surgery
• Toxicity assessment
• Statistical analysis
• Results
• Treatment outcome
• Late toxicities
• Discussion
• Conclusion
• Uncited reference
• References
• Copyright
Introduction
Larynx cancer is the most common cancer subsite in head and neck oncology. For patients with advanced tumors (Stage III or IV) of the larynx and hypopharynx, treatment options are concomitant chemoradiation (CRT) with surgery as salvage, or up-front surgery followed by adjuvant radiotherapy, with or without concurrent chemotherapy. These multimodal regimens are equivalent in terms of survival, but CRT offers the potential advantage of organ preservation 1, 2, 3, 4, 5, 6, 7.
Unfortunately, organ preservation treatment protocols are associated with significant acute and late adverse effects. Therefore, quality of life and morbidity should be considered when a treatment is proposed. Quality of life relates to overall well-being including the functional, emotional, mental, social, and economic components. The most common predictors of quality of life in surviving patients with advanced laryngeal cancer receiving CRT appear to be absence of pain and lower incidence of mood disorder rather than preservation of speech function (8).
Intensity-modulated radiotherapy (IMRT) is starting to be used in the larynx and hypopharynx substites (9). Although experience with this modality is accumulating, we wanted to review our current results with conventional radiotherapy. Our goal was to determine rates of functional organ preservation and late toxicities in patients treated for advanced laryngeal and hypopharyngeal cancer at our tertiary care health center.
Methods and Materials
Patient and tumor characteristics
Between August 1998 and September 2005, a total of 105 patients with histologically proven laryngeal and hypopharyngeal squamous cell cancer (SCC) were treated with concurrent CRT at the Centre Hospitalier de l'Université de Montréal. Pretreatment evaluations consisted of a complete history and physical examination including direct laryngoscopy using a flexible fiberoptic endoscope. Dental evaluation was mandatory in all except edentulous patients. All patients had a complete blood count and biochemical profile, chest X-ray, head-and-neck CT scan, and, in some cases, an MRI. All patients were presented to our multidisciplinary team, which includes head-and-neck surgeons, medical oncologists, radiation oncologists, nurses, nutritionists, speech and swallowing specialists, and pharmacists.
Of these patients, 23 were excluded from the analysis for the following reasons: retreatment (6 patients), use of IMRT (4 patients), follow-up less than 2 years (5 patients), or up-front laryngectomy (10 patients).
Of the remaining 82 eligible patients, 57 and 39 were Stage IVa and T3, respectively. All the data were reported according to the 1998 American Joint Committee on Cancer (AJCC). The distribution of the primary site was 55 larynx and 27 hypopharynx. Of the patients, 62 were male and 20 were female, with a median age of 59 years. Patient characteristics are shown in Table 1. Median potential follow-up was 3.9 years (10).
Table 1. Patient and tumor characteristics
Characteristic Value (%)
Total patients 82 (100)
Gender
Men 62 (76)
Women 20 (24)
Age (y)
Median 59
Range 42–77
Site
Larynx 55 (67)
Hypopharynx 27 (33)
Histological type (SCC) 82 (100)
T stage
T1–2 23 (28)
T3 39 (48)
T4a-b 20 (24)
N stage
N0 15 (18)
N1 12 (15)
N2 51 (62)
N3 4 (5)
Overall stage
III 18 (22)
IVA 57 (70)
IVB 7 (8)
Based on American Joint Committee on Cancer criteria.
Radiotherapy
Most patients were treated with conventional radiotherapy and standard fractionation, 2 Gy per day, five fractions per week for 7 weeks. Median dose was 70 Gy (16–72 Gy). Four patients received a concomitant boost to 72 Gy in 6 weeks. Nine patients did not receive the prescribed dose of radiotherapy (Table 2), including 4 patients who died during treatment, of which two deaths were from an unrelated cause. One of the 9 patients experienced recurrence in the treatment field.
Table 2. Treatment details
Treatment Value (%)
Radiation dose (Gy)
Median 70
Range 16–72
Chemotherapy
Cisplatin 46 (56)
Carboplatin 10 (12)
Carboplatin/5-fluorouracil 23 (28)
Unknown 3 (4)
A planning CT scan with a 5-mm slice thickness was performed in all patients. A thermoplastic head-to-shoulder mask was used for immobilization. Dosimetry was performed with Theraplan v3.8 (Nucletron, Veenendaal, the Netherlands); field arrangement consisted of half-beam blocked lateral opposed fields and supraclavicular field with 4-MV photons. Electrons fields were added as required to the spinal and tracheostomy regions. The target volumes and radiation doses were defined according to International Commission on Radiation Units (ICRU) 12, 13.
Chemotherapy
All patients underwent concurrent platinum-based chemotherapy. Most patients (56%) received cisplatin 100 mg/m2 every 3 weeks. A total of 23 (28%) had carboplatin-5FU given respectively 70 mg/m2/day and 600 mg/m2/day in continuous infusion, both for 4 days every 3 weeks (Table 2).
Surgery
A head-and-neck CT scan was performed 2 months after the completion of treatment. Neck dissection was performed in a patient with persistent clinical or radiographic evidence of residual nodal disease. A salvage total laryngectomy was performed if the primary tumor response was incomplete.
Toxicity assessment
Follow-up was done every 2 months for the first 2 years, then every 4 months up to 5 years, then annually. Patients with locoregional failure or death resulting from cancer were excluded from the assessment. Late toxicity was evaluated more then 3 months after the end of radiation treatment and defined as follow: Grade 2 or higher dysphagia according to the Common Terminology Criteria of Adverse Events (CTCAE) Version 3.0, requirement of a feeding tube/gastrostomy, pharyngoesophageal stenosis, chronic lung aspiration, and laryngectomy or tracheotomy without evidence of tumor recurrence.
Statistical analysis
Statistical analyses were performed with SAS version 8.2 (SAS Institute, Cary, NC). Disease-free survival and overall survival were calculated using the Kaplan-Meier method. Time variables were calculated from the start of radiotherapy. Freedom from local, regional, or distant progression was defined as the absence of demonstrable tumor on physical and radiographic examinations. Follow-up time was calculated using the method described by Schemper and Smith (10).
Results
Treatment outcome
Overall survival, disease-free survival, and the laryngectomy-free survival were respectively 63%, 73%, and 53% at 3 years (Fig 1, Fig 2). Complete response rate with CRT was 75%. The primary tumor response rate was higher, with 88% complete response vs. 79% for nodal complete response.
Fig 1. Kaplan-Meier estimate of overall survival.
Fig 2. Kaplan-Meier estimate of disease-free survival.
Late toxicities
Nineteen patients (23%) experienced significant complications after CRT corresponding to Grade 2, 3, or 4 on the CTCAE scale. Six (7%) required a percutaneous gastrostomy (PEG), 5 (6%) had persistent Grade 2 or 3 dysphagia, 2 (2%) had pharyngoesophageal stenosis requiring multiple dilations, 2 (2%) had chronic lung aspiration, and 7 (8.5%) required a permanent tracheostomy. Four patients (4.9%) underwent laryngectomy because of poor pain control or dysfunctional larynx, without pathologic evidence of disease (Table 3).
Table 3. Late complications
Complications and treatment n
Percutaneous endoscopic gastrostomy 6
Dysphagia Grade 2–3 5
Pharyngoesophageal stenosis 2
Chronic lung aspirations 2
Tracheostomy 7
Laryngectomy 4
At last follow-up, 5 (6%) patients were still dependent on their PEG for adequate intake for a mean duration of 43 months (range, 18–61 months) after radiation. Overall, 42 (52%) patients obtained a complete response and had a functional larynx with no other major complications.
Discussion
Few studies have addressed functional outcomes of larynx preservation protocols. The main goal of our study was to review the toxicity of laryngeal preservation treatments in our center for patient with advanced larynx or hypopharynx squamous cell carcinoma. Both subjective and objective swallowing problems are frequent and severe long-term side effects after radiotherapy for pharyngeal cancer. Swallowing dysfunction has been correlated with dose and volume parameters of the upper aerodigestive tract 14, 15, 16. Organ preservation treatment impairs movement of structures that are essential for effective swallowing 17, 18, 19.
With a median potential follow-up of 3.9 years, our 3-year laryngectomy-free survival, progression-free survival and overall survival are comparable four Phase III laryngectomy preservation trials 1, 2, 3, 7. Toxicity remains significant with this treatment option, as only half of surviving patients are able to return to pretreatment function. These findings are corroborated by Guadagnolo et al. (20) In a recent meta-analyses of 230 patients receiving CRT for SCC of the head and neck, the laryngeal and hypopharyngeal primary site was the strongest independent risk factor on multivariate analysis for severe late toxicity (21).
The successful management of swallowing dysfunction after chemoradiation is complex and difficult to achieve, requiring a multidisciplinary approach. Collaboration among different specialists (physicians, speech pathologists, dietitians, and psychologists) remains the key to a desirable outcome (22). Prophylactic swallowing exercises may benefit these patients and we reinforce this with our patients 23, 24. Moreover, Mekhail et al. reported more pharyngeal stenosis and duration of nutritional support with PEG vs. nasogastric tube at their institution when patients underwent concurrent chemoradiation for advanced head-and-neck carcinoma (25).
In our center, to decrease the incidence of pharyngeal stenosis and to prevent PEG dependency, we tend not to install PEG up front. We hypothesize that encouraging patients to use their swallowing mechanisms during treatment for the longest period of time might decrease those patients' likelihood of developing a PEG dependency as well as requiring pharyngeal dilation in the long run. Even with this approach, 15% of our patients experienced one of these late toxicities.
The present study has several limitations. First, it is a retrospective single-institution study on the long-term toxicities of concomitant chemotherapy and conventional radiotherapy in the treatment of advanced laryngeal and hypopharyngeal tumors. Toxicities were retrospectively determined from a review of the patient charts and thus possibly underreported for the lower grades. Nevertheless, severe complications were likely to be reported, as patient with Grade 2 or greater toxicities are closely followed weekly after treatment by our multidisciplinary team.
Preliminary studies have shown that IMRT can achieve encouraging locoregional control rates for advanced laryngeal and hypopharyngeal carcinomas (9). Xerostomia improves over time but pharyngoesophageal stricture with PEG dependency remains a problem, particularly for patients with hypopharyngeal carcinoma and, to a lesser extent, those with laryngeal cancer. Strategies using IMRT to limit the dose delivered to the esophagus/inferior constrictor musculature without compromising target coverage might be useful to further minimize these late complications (16). Moreover, the grade of laryngeal edema is correlated with mean dose to the larynx, which should ideally be kept to less than 43 to 45 Gy 26, 27. This dose constraint is difficult to achieve when one considers that the larynx is part of the radiation therapy target volume and that the tumoricidal dose usually is approximately 70 Gy.
One has to remember that total laryngectomy has psychological and social consequences, and the choice of the optimal treatment modality is largely dependent on the expertise and experience of the multidisciplinary team 28, 29. Given that survival appears equivalent between the two modalities, post-treatment quality of life becomes a decisive factor. Only a few studies compared qualilty of life between CRT for laryngeal preservation with total laryngectomy and postoperative radiation. Although some trials have shown an improvement in some components of quality of life 8, 30 many others have described equivalent results 31, 32, 33, 34. Furthermore, cost consideration may be an important factor in decision making for the treatment of advanced laryngeal cancer 35, 36.
Conclusion
In this study, half of all patients with advanced laryngeal or hypopharyngeal carcinomas treated with CRT, experienced either significant complications of laryngeal failure or locoregional relapse. For patients treated with the objective of preserving a functional larynx, PEG dependency and laryngectomy are frequent negative outcomes. More efforts and studies are necessary to further improve locoregional control, improve quality of life, and reduce late complications.
Given that survival appears equivalent between the two modalities, patient preference may be an important factor in decision making for the treatment of advanced laryngeal cancer, and clear and informed consent should be obtained. The incorporation of targeted biological therapies and IMRT may reduce long-term toxicities. Prospective Phase III studies are needed with quality of life assessment.
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