1 Radiation Oncology, 2 Audiology and Speech Pathology, 4 Radiology and 7 Dietetics Services, VA North Texas Health Care System, Dallas, TX; Departments of 3 Biostatistics and 5 Radiation Oncology, East Carolina University, Greenville, NC; 6 Department of Radiation Oncology, Plano Cancer Center, Plano, TX; 8 Division of Hematology/Oncology, Louisiana State University, Shreveport, LA, USA
Received 29 May 2003; revised 3 November 2003; accepted 17 December 2003
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ABSTRACT |
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To assess the prevalence, severity and morbidity of dysphagia following concurrent chemoradiation for head and neck cancer.
Patients and methods:
Patients who underwent chemotherapy and radiation for head and neck malignancies were evaluated for their ability to resume oral feeding following treatment. Modified barium swallow (MBS) studies were performed if the patients complained of dysphagia or if there was clinical suspicion of aspiration. The severity of dysphagia was graded on a scale of 17. If significant abnormalities were found, swallowing studies were repeated until resolution of dysphagia.
Results:
Between March 1999 and May 2002, 55 patients with locally advanced head and neck cancer underwent concurrent chemotherapy and radiation. Aspiration pneumonia was observed in eight patients, three during treatment and five following treatment. Five patients died from pneumonia. Two patients developed respiratory failure requiring intubation as a complication of pneumonia. At a median follow-up of 17 months (range 648 months), 25 patients (45%) developed severe dysphagia requiring prolonged tube feedings for more than 3 months (22 patients) or repeated dilatations (three patients). Among 33 patients who underwent MBS following treatment, 12 patients (36%) had silent aspiration (grade 67 dysphagia). Thirteen patients (39%) developed grade 45 dysphagia which required prolonged enteral nutritional support to supplement their oral intake. Most patients had severe weight loss (021 kg) during treatment, likely due in part to mucositis in the orodigestive tube.
Conclusions:
Dysphagia is a common, debilitating and potentially life-threatening sequela of concurrent chemoradiation for head and neck malignancy. Physicians should be aware that the clinical manifestations of aspiration may be unreliable and insidious, because of the depressed cough reflex. Modified and traditional barium swallows should be performed following treatment to assess the safety of oral feeding and the structural integrity of the pharynx and esophagus. Patients with severe dysphagia may benefit from rehabilitation. Tube feeding should be continued for those with aspiration.
Key words: aspiration, chemoradiation, dysphagia, head and neck cancer
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Introduction |
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Critical structures necessary for normal deglutition, such as tongue, larynx and pharyngeal muscles, may be treated to a high radiation dose. The increased radiation dose may lead to hyperactivation of transforming growth factor ß1 (TGFß1), a peptide involved in collagen deposition and degradation [4]. Excessive fibrosis may be responsible for abnormal motility of the deglutition muscles and may lead to the aspiration, dysphagia and stenosis observed following head and neck chemoradiation [5]. The patients quality of life may be adversely affected [6]. For proper patient management, it is therefore important for the clinician to assess the prevalence and severity of dysphagia following the combined regimen.
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Patients and methods |
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Prior to treatment, the patients underwent dental extraction, nutritional assessment and placement of a gastrostomy tube for enteral feeding during treatment. Following enrolment, the patients received 5-fluorouracil (5-FU) 1000 mg/m2 intravenously (i.v.) by continuous infusion on days 14 and 2124, and cisplatin 100 mg/m2 i.v. on days 1 and 21 of radiation. Patients with nasopharyngeal carcinoma received cisplatin 100 mg/m2 i.v. on days 1, 22 and 43 of radiation.
Radiation therapy was delivered on a Cobalt Unit or a 6 mV linear accelerator using standard technique (two lateral and one supraclavicular field, off cord at 39604000 cGy, 180200 cGy/fraction). The dose to the gross tumor was 66007200 cGy; lymph nodes at risk of subclinical metastasis received 50005400 cGy. Patients were evaluated weekly during treatment or more frequently if clinically indicated. Toxicity during treatment was assessed according to the Radiation Therapy Oncology Group (RTOG) toxicity scale. Degree of weight loss and any treatment delays were recorded at the end of treatment.
After completion of treatment, patients were followed monthly with repeated endoscopy by the Ear, Nose, and Throat service at each visit. Patients were instructed to continue with tube feeding until resolution of the acute mucositis enabled them to resume a normal diet. Modified barium swallow (MBS) studies were performed if the dysphagia persisted 3 months after treatment or if there was clinical suspicion of aspiration [7].
During the MBS procedure, the patients were either sitting or standing and viewed in frontal and lateral planes. The fluoroscopy tube was positioned to view the oral cavity anteriorly, the soft palate superiorly, the posterior pharyngeal wall posteriorly, and the seventh cervical vertebra inferiorly. In this way, the oral preparatory, oral, pharyngeal and cervical esophageal phases of deglutition could be assessed and viewed simultaneously. Seven consistencies of food and liquid were introduced by teaspoon to the patient. Water, liquid barium, applesauce, mashed potatoes, green beans, ground meat and sliced meat mixed with barium paste were used in the assessment. With each swallow, the patient was instructed to hold the material in his mouth until told to swallow. The fluoroscope remained focused on the oral cavity and pharynx during and after each swallow. A number of observations were made during each swallow. Residue on the tongue or in the pharynx after the swallow, laryngeal penetration or aspiration during or after the swallow, backflow, esophageal-pharyngeal reflux, and disordered peristalsis in the pharynx or esophagus were noted. The patient was then repositioned in the anteriorposterior position and presented with at least two additional consistencies, usually liquid barium and mashed potatoes introduced by teaspoon. Finally, at the completion of swallowing, the patient was instructed to vocalize on a and count to five while being videotaped with fluoroscopy.
Each patient was scored using the Swallowing Performance Scale [8]. Grade 1: normal. Grade 2: within functional limitsabnormal oral or pharyngeal stage but able to eat a regular diet without modifications or swallowing precautions. Grade 3: mild impairmentmild dysfunction in oral or pharyngeal stage, requires a modified diet without need for therapeutic swallowing precautions. Grade 4: mild-to-moderate impairment with need for therapeutic precautionsmild dysfunction in oral or pharyngeal stage, requires a modified diet and therapeutic precautions to minimize aspiration risk. Grade 5: moderate impairmentmoderate dysfunction in oral or pharyngeal stage, aspiration noted on exam, requires a modified diet, and swallowing precautions to minimize aspiration risk. Grade 6: moderatesevere dysfunctionmoderate dysfunction of oral or pharyngeal stage, aspiration noted on exam; requires a modified diet and swallowing precautions to minimize aspiration risk; needs supplemental enteral feeding support. Grade 7: severe impairmentsevere dysfunction with significant aspiration or inadequate oropharyngeal transit to esophagus; nothing by mouth; requires primary enteral feeding support.
In addition to a modified diet, patients were instructed about safe eating techniques, and the swallowing maneuvers designed to facilitate the safest swallow. The rehabilitation technique was individualized for each patient who was then followed at regular intervals by the speech pathologist. Modified barium swallow was repeated if deemed necessary by the team. Traditional barium swallow was also obtained to complement the MBS if abnormal structural integrity of pharynx and esophagus were suspected by the team. The patients weight and nutritional status were also monitored by a dietitian who provided enteral nutritional support recommendations as needed.
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Results |
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Acute toxicity was primarily grade 34 mucositis (45 patients) and hematological. Grade 34 neutropenia, anemia and thrombocytopenia occurred in 27, 12 and three patients, respectively. Three patients developed aspiration pneumonia during treatment requiring artificial ventilation (one patient) or resulting in death (two patients). One patient had severe cellulitis which resolved with antibiotics. Six patients developed transient abnormal renal function (four patients), requiring replacement of cisplatin by carboplatin during the second cycle of chemotherapy (one patient) or discontinuation of chemotherapy (one patient). The amount of weight loss ranged from 0 to 21 kg (median 8 kg).
At a median follow-up of 17 months (range 648 months), 43 (78%) patients were alive. Late aspiration pneumonia developed in five patients and contributed to the death of three patients. Two patients required intubation because of respiratory failure resulting from the pneumonia, but they recovered. The causes of death in other patients were tumor recurrence (four patients), liver cirrhosis (one patient) and cardiovascular (two patients).
Twenty-five patients (45%) developed severe dysphagia requiring prolonged (>3 months) tube feeding (22 patients) or repeated dilatation because of pharyngeal or esophageal stenosis (three patients). The time dependence for tube feeding for these patients ranged from 4 to 21 months (median 9 months). Thirty-three patients underwent MBS studies. Twelve patients (36%) had grade 67 dysphagia. Three of them improved on repeated studies (grade 3, 4 and 5, respectively). The other nine patients still required tube feeding as the severity of the dysphagia did not improve on subsequent studies. Thirteen patients (39%) had grade 45 dysphagia that required prolonged tube feeding to supplement their oral intake, as they developed severe weight loss during treatment. The remaining eight patients had grade 2 (two patients) or grade 3 (six patients) dysphagia. Table 2 summarizes the degree of dysphagia for these patients.
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Discussion |
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To monitor the treatment effects objectively, videofluoroscopic swallowing studies following chemoradiation were performed. There was severe dysfunction of the base of the tongue, larynx and pharyngeal muscles, leading to stasis of the bolus, vallecular residue, epiglottic dysmotility, and in severe cases, aspiration [5, 13]. If aspiration occurred during treatment, its combination with neutropenia resulting from the chemotherapy may lead to aspiration pneumonia, sepsis and respiratory failure. Eight of our patients (14%) developed aspiration pneumonia requiring artificial ventilation (three patients) or resulting in death during or shortly following treatment (four patients). The eighth patient recovered with conservative management.
Another factor that may have contributed to the high morbidity of the aspiration pneumonia was the severe weight loss that compromised the immune system, leading to a poor outcome. The median weight loss was 8 kg in our study (range 021 kg). This was consistent with other studies where the mean weight loss during chemoradiation was reported to be 1012% of the initial body weight [10, 14, 15].
The high rate of aspiration pneumonia has also been observed in other studies with different chemotherapy regimen for organ preservation. In Machtay et al.s [16] study, patients had induction chemotherapy with carboplatin and paclitaxel followed by concurrent chemoradiation. Two of the 53 patients (4%) died from respiratory failure during chemotherapy and radiation. Following treatment, 12% of their patients developed chronic severe dysphagia that persisted for >9 months. Eisbruch et al. [17] performed videofluoroscopic swallow studies following treatment for advanced head and neck cancer patients who had concurrent gemcitabine and radiation. One to three months post therapy, 65% of the patients showed evidence of aspiration which persisted for up to 1 year. Six patients developed aspiration pneumonia and two died. It was noteworthy that the aspiration was often unrecognized, dysphagia being the only complaint. The patients had suppressed cough reflex when they aspirated. Pauloski et al. [18] also corroborated the silent nature of the aspiration with videofluoroscopic swallow studies. Patients who complained of dysphagia during radiation treatment had larger residue and a higher rate of aspiration (22%) during the swallowing study compared to the ones with no dysphagia (3%). They subconsciously reduced their oral intake and lost weight. Wu et al. [19] also noticed that following radiation for nasopharyngeal tumors, 41% of their patients who complained of dysphagia revealed silent aspiration during the endoscopic swallowing exam. We therefore believe that aspiration is under-reported in chemoradiation series, because it is often silent. Twelve of our patients with grade 67 dysphagia also had aspiration, discovered serendipitously following treatment, as we performed swallowing studies for all patients who complained of dysphagia and as a safety precaution, prior to the removal of their G-tube. Table 3 summarizes the aspiration rate and dysphagia described in the literature following chemoradiation for head and neck cancer.
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The long-term need for a G-tube following concurrent chemotherapy and radiation is also documented in other series. Staton et al. [23] treated locally advanced laryngeal carcinoma with intra-arterial cisplatin and radiation. Six months following treatment, 16 of 45 patients (36%) still required a G-tube because of an inability to swallow. Kies et al. [24] combined hyperfractionated radiation and chemotherapy for stage III and IV tumors of different sites. At 1 year, 17% of the patients were still unable to swallow adequately. Nineteen and 30% of the surviving patients in studies by Ackerstaff et al. [25] and Samant et al. [26], respectively, required tube feeding >12 months following concurrent intra-arterial cisplatin and radiation. Even at 18 months following completion of chemotherapy and radiation, 13% of the patients in the Newman et al. [27] study were still fed by G-tube. However, it is difficult to assess the prevalence of aspiration in these studies, as MBS studies were not performed. Table 4 summarizes the need for prolonged tube feeding described in the literature.
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The limitations of our study include short follow-up, lack of baseline swallowing study, prior to treatment, and the retrospective nature of the study, as only patients who complained of dysphagia underwent swallowing studies. Patients with locally advanced carcinoma, particularly larynx and hypopharynx, may experience high-grade dysphagia because of the tumor extent and the destruction of normal tissue [29]. Some patients who complained of dysphagia did not undergo swallowing studies because of refusal, loss to follow-up, or physician reluctance to order the study. Nevertheless, we believe that physicians should be aware of the insidious nature of the aspiration complication and the debilitating effect of prolonged tube feeding that often result from effective therapy for advanced head and neck tumors.
The long-term toxicity of our study may be related to the chemotherapy regimen and the radiation therapy fractionation. Our chemotherapy regimen is similar to the intergroup study which reported 77% grade 3 or worse toxicity in patients with concurrent chemoradiation despite a split course of radiotherapy [30]. High dose of chemotherapy and conventional radiotherapy fractionation may explain high-grade toxicity as compared to the Brizel et al. study [31], where hyperfractionation and low-dose chemotherapy apparently did not lead to long-term dysphagia. Further studies should be carried out to investigate the toxicity and efficacy of different chemoradiation regimens. It is our current policy that all patients with locally advanced head and neck cancer undergo a MBS study before and following treatment to assess the safety of oral feeding. A traditional barium swallow may be obtained if deemed necessary (if structural damage of the pharynx and esophagus is suspected). If high-grade dysphagia is found, the patients are prescribed counseling and teaching of compensatory swallowing maneuvers to enhance the safety of oral feeding, while tube feeding continues to supplement their caloric intake based on nutritional assessment. We also use amifostine during chemoradiation to reduce the acute toxicity of the treatment and possibly lessen its long-term sequelae.
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Conclusion |
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Acknowledgements |
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FOOTNOTES |
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