Riassunto delle caratteristiche del prodotto eventi avversi di fratture ossee riportati da studi clinici randomizzati, controllati, in doppio ciecoin oltre 8.100 pazienti trattati con pioglitazone e 7.400 trattati con farmaco di confronto per unperiodo superiore ai 3,5 anni, è stata osservata un’aumentata incidenza di fratture ossee nelledonne. Sono state osservate fratture nel 2,6% delle
Gruporessonar.com.brCharacteristics Associated With Swallowing Changes
After Concurrent Chemotherapy and Radiotherapy
in Patients With Head and Neck Cancer
Joseph K. Salama, MD; Kerstin M. Stenson, MD; Marcy A. List, PhD; Loren K. Mell, MD; Ellen MacCracken, MS;Ezra E. Cohen, MD; Elizabeth Blair, MD; Everett E. Vokes, MD; Daniel J. Haraf, MD Objective: To define factors that acutely influenced swal-
to assess swallowing function prior to and within 1 to lowing function prior to and during concurrent chemo- 2 months after the completion of concurrent chemo- Design: A summary score from 1 to 7 (the swallowing
Main Outcome Measures: Factors associated with
performance status scale [SPS]) of oral and pharyngeal swallowing changes after chemoradiotherapy.
impairment, aspiration, and diet, was assigned to eachpatient study by a single senior speech and swallow pa- Results: The mean pretreatment and posttreatment OPM
thologist, with higher scores indicating worse swallow- scores were 3.09 and 3.77, respectively. Patients with T3 ing. Generalized linear regression models were formu- or T4 tumors (odds ratio [OR], 0.38; 95% confidence in- lated to asses the effects of patient factors (performance terval [CI], 0.15-0.95; P = .04) and a performance status status, smoking intensity, amount of alcohol ingestion, of 1 or 2 (OR, 0.37; 95% CI, 0.15-0.91; P = .03) were less and age), tumor factors (primary site, T stage, and N likely to have worsening of swallowing after chemora- stage), and treatment-related factors (radiation dose, useof intensity-modulated radiation therapy, response to in- diotherapy. There was a trend for worse swallowing with duction chemotherapy, postchemoradiotherapy neck dis- increasing age (OR, 1.04; 95% CI, 0.99-1.09; P=.08). Only section, and preprotocol surgery) on the differences be- T stage (T3 or T4) was associated with improved swal- tween SPS score before and after treatment.
lowing after treatment (OR, 8.96; 95% CI, 1.9-41.5;P Ͻ.001).
Setting: University hospital tertiary care referral
Conclusion: In patients undergoing concurrent chemo-
therapy and radiotherapy, improved swallowing func-
Patients: The study included 95 patients treated under
tion over baseline is associated with advanced T stage.
a multiple institution, phase 2 protocol who underwenta videofluorographic oropharyngeal motility (OPM) study Arch Otolaryngol Head Neck Surg. 2008;134(10):1060-1065 Author Affiliations:
nated timing of bolus propulsion, opening sure of the larynx, tongue base retraction, and vestibular penetration of barium have tients present with mild-moderate to mod- all been reported following concurrent che- addition, patients with hypopharyngeal and ally, increase from baseline in time to ve- to have worse swallowing at presentation.1 Section of Otolaryngology–Head and Neck Surgery mented severity of dysphagia after defini- tive or adjuvant radiation therapy or con- swallowing mechanism are important to aid comitant chemoradiotherapy,2,3 few studies in therapeutic intervention for patients un- changes from baseline in patients treated diotherapy, so is the identification of fac- in swallowing function. Therefore, in this Of the studies that have reported changes study, we sought to identify factors that in- in swallowing function from baseline, most (Drs Cohen and Vokes),University of Chicago, have focused on alterations occurring in the (REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 134 (NO. 10), OCT 2008 2008 American Medical Association. All rights reserved.
scores indicating worse swallowing, as outlined in Table 1.
This rating scale is designed to summarize the clinical results
of the OPM study, and the score provides an overall clinical
From November 1998 to August 2002, 222 patients with stage picture of swallowing function. Because reliable SPS results de- III or IV advanced head and neck cancer were treated under a pend on skilled clinical interpretation, the score is not an ad- multiple institution, phase 2 protocol of concurrent chemotherapy ditive or formulaic summary. For each patient, the SPS score and radiotherapy. Organ preservation was the primary goal of prior to and following concurrent chemotherapy and radio- the treatment protocol. Resection of small tonsillar or oral cav- therapy was extracted from the OPM report.
ity primary tumors was allowed, as was pretherapy modified radi- Generalized linear modeling was used to model changes in the cal neck dissections. Two 21-day cycles of induction paclitaxel logSPSscore.Backwardstepwiselogisticregression(PϽ.10thresh- (135 mg/m2 over 3 hours) and carboplatin (area under the curve, old) was used to model improved or worsened swallowing. Co- 2; given after paclitaxel) were followed by 4 cycles (for resected variates included patient factors (performance status, smoking cases) or 5 cycles (for unresected cases) of concurrent chemo- intensity, amount of alcohol ingestion, and age), tumor factors therapy and radiotherapy. Each chemoradiotherapy cycle con- (primary site, T stage, and N stage), and treatment-related factors sisted of 1 weekly dose of paclitaxel (100 mg/m2 after the first (radiation dose, use of IMRT, response to induction chemotherapy, dose of radiation), continuous infusion fluorouracil (600 mg/ and preprotocol surgery). Statistical analysis was conducted using m2 for 5 days), oral hydroxyurea (500 mg every 12 hours for 6 Stata 7.0 software (StataCorp LP, College Station, Texas).
days), and twice daily radiation therapy (1.5 Gy per fraction witha minimum 6-hour interfraction interval) followed by a 9-day break. The total radiation dose to gross disease was initially 75Gy, but later decreased to 72 to 75 Gy based on the response toinduction chemotherapy. Initially patients were treated with Clinicopathologic characteristics are summarized in 3-dimensional conformal radiotherapy, but later some patients Table 2, while treatment-related characteristics are sum-
were treated with intensity-modulated radiotherapy (IMRT). Fol- marized in Table 3. Most of the patients had a good per-
lowing the completion of concurrent chemotherapy and radio- formance status (Eastern Cooperative Oncology Group therapy, patients with N2 or higher-stage neck disease under- [ECOG] score, 0-1), laryngeal (23%; n = 22) or oropha- went a planned neck dissection. Details of the protocol have been ryngeal primary tumors (52%; n = 49), advanced T stage (57% T3 or T4; n=54), and advanced nodal disease (75% Of the 222 patients enrolled, 132 eligible patients were treated N2 or N3; n = 54). Furthermore, 92% of patients did not at our institution. Our study population consisted of 95 of the132 who had swallowing function assessed both prior to the ini- have prior surgery (n = 87), and 80% had a response to tiation of concurrent chemotherapy and radiotherapy and within induction chemotherapy (n = 76). When compared with 1 to 2 months after the completion of chemoradiotherapy. Each patients treated on the same protocol but not included assessment consisted of an anterior and lateral videofluoro- in this analysis, our patients were more likely to have been graphic OPM study, as described previously.9,10 Briefly, a record- treated with IMRT (57% [n = 54] vs 34%) (P Ͻ.01) and ing was made by the speech pathologist while patients swal- to have an ECOG performance status of 0 (57% [n = 51] lowed small amounts of liquid barium, paste barium, and a vs 24%) (P Ͻ.01). Otherwise, there were no statistical barium-coated cookie. Slow motion, frame-by-frame analysis was differences among patients included and other patients.
used to evaluate oral, pharyngeal, laryngeal, and cricopharyn- In general, swallowing function decreased from base- geal function. In addition, attention was given to the presence line in patients after concurrent chemotherapy and ra- and cause of aspiration as well as laryngeal sensitivity, responseto therapeutic techniques, and percentage aspiration. Multiple diotherapy. Specifically, 59 patients had a worse SPS components of swallowing were summarized on the OPM rec- score after treatment (60%), 17 had no change in their ord and recorded in a computerized database storage and re- SPS score (17%), and 19 had an improvement in their porting system, as described previously.1 Using this standard- SPS score (19%). The mean pretreatment SPS score was ized format, interrater variability was low, and intrarater variability 3.09, and the mean posttreatment SPS score was 3.77 nonexistent because all studies were conducted at the Univer- (P Ͻ.01 by the Wilcoxon test). As listed in Table 4 and
sity of Chicago Speech and Swallowing Center by the senior illustrated in Figure 2, for 82% of patients whose swal-
speech pathologist (E.M.) for reliable and consistent reporting.
lowing changed, for worse or better (n = 78), the change A sample OPM report is provided as Figure 1.
was only 1 to 2 points on the SPS scale. The median and Individualized therapy was provided based on the results mean change values during chemoradiotherapy were 1 of the OPM study and directed to specific disorders docu-mented during the videofluorographic procedure. In addi- and 1.7 points (range, 1-5 points), respectively. Most pa- tion, therapeutic techniques were applied during the OPM study tients with laryngeal primary tumors had T3 (14%; n=3) to assess response to maneuvers and change in swallow physi- or T4 (82%; n = 18) tumors. When patients with laryn- ology and aspiration. Patients were provided with base-of-the- geal cancer were analyzed separately, the mean pretreat- tongue and laryngeal motility exercises, which they were en- ment SPS score was 4.3 (range, 1-7), and the mean post- couraged to perform during treatment. A safe oral diet with a treatment SPS score was 4.2 (range, 2-7). While 4 patients variety of food textures based on OPM results was encouraged had no change in their swallowing after chemoradio- with the goal of maintaining optimal flexibility and range of therapy, 10 had a decrement, and 8 had improvement in their swallowing. The median and mean changes in swal- Changes in patient swallowing were defined in 2 ways: lowing scores were 0 and 0.1 (range, 0-5), respectively.
(1) worsening of swallowing was defined as a posttherapy swal-lowing performance scale (SPS) score higher than the pre- When factors associated with worsening of swallow- therapy SPS score; (2) improvement in swallowing was de- ing were analyzed, only a trend for worse swallowing with fined as a posttherapy SPS score lower than the pretherapy score.
increasing age was found (odds ratio [OR], 1.04; 95% con- The SPS score is a summary score from 1 to 7 of oral impair- fidence interval [CI], 0.99-1.09) (P = .08). Surprisingly, ment, pharyngeal impairment, aspiration, and diet, with higher patients with T3 or T4 tumors (OR, 0.38; 95% CI, (REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 134 (NO. 10), OCT 2008 2008 American Medical Association. All rights reserved.
THE UNIVERSITY OF CHICAGO
Center for Speech and Swallowing Disorders Oropharyngeal Motility (OPM) Study Data Entry Form 1. Rationale for the Study, Brief History Notes 2. WFL - abnormal oral or pharyngeal stage but able to eat regular diet without modifications or swallowing precautions.
3. Mild impairment - mild dysfunction in oral or pharyngeal stage. Requires modified diet or therapeutic swallowing precautions.
4. Mild-moderate impairment - need for therapeutic precautions - mild dysfunction in oral or pharyngeal stage, requires modified diet andtherapeutic precautions to minimize aspiration risk.
5. Moderate impairment - moderate dysfunction in oral or pharyngeal stage, aspiration noted on exam, requires modified diet and swallowing precautions to minimize risk of aspiration.
6. Moderate-severe dysfunction - requires supplemental central feeding support - moderate dsyfunction is oral or pharyngeal stage, Aspiration noted on exam, requires modified diet and swallowing precaution to minimize risk of aspiration, needs supplemental enteral 7. Severe impairment - severe dysfunction with significant aspiration or inadequate oropharyngeal transit to esophagus, NPO, requires primary Figure 1. Oropharyngeal motility study data entry form.
(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 134 (NO. 10), OCT 2008 2008 American Medical Association. All rights reserved.
Table 1. Swallowing Performance Status Scale
Table 2. Clinicopathologic Characteristicsa
Patients, No. (%)
examination; requires modifieddiet and swallowing precautions a The median (range) patient age was 58 (35-77) years.
to minimize risk of aspiration;needs supplemental feedingsupport Table 3. Treatment-Related Factorsa
aspiration or inadequateoropharyngeal transit to Characteristic
Patients, No. (%)
0.15-0.95) (P = .04) and an ECOG performance status of 1 to 2 (OR, 0.37; 95% CI, 0.15-0.91) (P = .03) were less likely to have worse swallowing after a course of con- current chemotherapy and radiotherapy. Only ad- vanced T stage (T3 or T4 tumors) was associated with improved swallowing after chemoradiotherapy (OR, 8.96; Abbreviations: CR, complete response; CTX, chemotherapy; 95% CI, 1.6-41.6) (P Ͻ.001).
IMRT, intensity-modulated radiation therapy; PR, partial response; A total of 51 patients had gastrostomy tubes placed before, during, or within 6 months of the completion of a The mean (range) radiation dose was 72.5 (59.0-75.0) Gy.
concurrent chemotherapy and radiotherapy (54%). Thisincluded 11 patients with gastrostomy tube placementprior to the initiation of protocol treatment (12%), 36 Table 4. Absolute Change in SPS Score
patients with gastrostomy tubes placed during the course Absolute Difference
of concurrent chemotherapy and radiotherapy (38%), and in SPS Score
Patients, No. (%)
4 had gastrostomy tube placement within 6 months ofcompleting concurrent chemotherapy and radiotherapy (4.2%). At final follow-up, 12 patients had gastrostomy tubes in place (13%), and 77 patients were free of gas- trostomy tubes (81%). In the remaining 6 patients, in- formation on gastrostomy tube status was not available.
Abbreviation: SPS, swallowing performance status scale (a summary Multiple studies have demonstrated improved locore- control and survival continue to improve in patients with gional control and in some cases survival with definitive advanced head and neck cancer, functional, cosmetic, and or adjuvant chemoradiotherapy over radiotherapy.11-14 As quality-of-life issues become more important. While con- (REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 134 (NO. 10), OCT 2008 2008 American Medical Association. All rights reserved.
therapy and radiotherapy. To our knowledge, this has not been reported in the literature. Our group’s prior investi-gations with pretherapy swallowing studies revealed no as- sociation between T stage and aspiration status, cervical esophageal impairment, pharyngeal impairment, oral im- pairment, and SPS score.1 Other investigators have not foundan association between T stage and dysphagia, but the popu- lation studied was heterogeneous and included patients treated with definitive and adjuvant radiation and chemo-radiation.2,17 Our finding that patients with advanced T stages were less likely to have worsening of their swal- lowing and more likely to have improved swallowing will aid practitioners in counseling patients as to expectationsduring treatment. However, it must be noted that patients Figure 2. Frequency of change in swallowing performance status scale
were strongly encouraged to maintain oral intake as long (SPS) score (SPS score before treatment minus SPS score after treatment).
as possible during treatment and did not undergo routine Improvement in swallowing is indicated by a positive value, worsening by percutaneous endoscopic gastrostomy tube placement. This strategy was used to encourage patients to exercise the swal-lowing mechanism throughout treatment.
trol is improved with concurrent chemotherapy and ra- Our investigation found no correlation between the diotherapy, rates of dysphagia are also higher, as seen in use of IMRT and swallowing dysfunction. However, this the report of Radiation Therapy Oncology Group (RTOG) is not surprising, since our main goal of IMRT was to de- 91-1111 in which 23% of patients treated with concomi- crease the dose to the parotid glands, skin, larynx, and tant cisplatin and radiotherapy were able to swallow only oral cavity, while no attempt was made to spare the pha- soft foods compared with 9% of patients receiving sequen- ryngeal constrictors owing to their close proximity to the tial cisplatin/fluorouracil irradiation and 15% of patients retropharyngeal nodal region. Other investigators have found that radiation dose to the upper, middle, and lower Quality-of-life studies demonstrate that for patients pharyngeal constrictors and the supraglottic and glottic with advanced head and neck cancer, difficulties and em- larynx have been associated with swallowing dysfunc- barrassment caused by eating in public, distorted speech, tion.18 Preliminary results from patients treated prospec- hoarseness, and mouth pain are important predictors of tively with IMRT to spare these structures demon- overall quality of life.15 Furthermore, after “being cured strated statistically significant correlations between of my cancer” and “living as long as possible,” patients aspiration risk and partial volumes of the pharyngeal con- prioritize “being able to swallow all foods and liquids” strictors and glottic and supraglottic larynx receiving ra- only behind “having no pain,” “returning to regular ac- diation doses between 50 and 65 Gy. Furthermore, dose tivities,” and “having a normal amount of energy.” Given to the pharyngeal constrictors was associated with stric- the high level of importance that patients place on swal- ture risk and worsening of liquid and solid swallow- lowing, we sought to determine in this study the factors ing.19 We are currently investigating the interactions of that could predict detrimental or improved swallowing chemotherapy and IMRT in regard to swallowing func- outcomes following a course of chemoradiotherapy.
tion, neck fibrosis, and saliva flow. Patients analyzed in One of the interesting findings from our study popula- the present study were more likely to have been treated tionwasthepreservationoffunctioninpatientswithadvanced with IMRT, which may enhance the applicability of these laryngeal cancer. Recent reports demonstrate that patients results because 76% to 82% of practitioners are cur- with larynx cancer treated with concurrent chemotherapy rently using IMRT to treat patients with head and neck and radiotherapy had improved quality of life over surgically treated patients and that patients with an intact larynx were These data indicate that 54% of patients required gas- more likely to obtain nutrition orally without supplements.16 trostomy tube nutritional assistance during the course Furthermore, patients with advanced larynx cancer treated of or shortly after concurrent chemotherapy and radio- withconcurrentchemotherapyandradiotherapywerefound therapy (n = 51). These numbers are consistent with the to have intelligible communication and efficient swallow- entire protocol cohort from which these patients were ing.6 Our analysis demonstrated that patients with laryngeal drawn in which 62% of patients had gastrostomy tubes cancer had a worse mean baseline swallowing score than the placed prior to (26%) or during (36%) the course of che- entire study population. However, after treatment, these pa- moradiotherapy. However, at final follow-up, only 13% tients had little change in their swallowing score compared had gastrostomy tubes in place (n = 12). This is prob- with a mean decrement of 0.78 in the population as a whole.
ably owing to many causes, the first of which is that pa- These results indicate that patients with advanced laryngeal tients with gastrostomy tubes in place are more likely to cancer treated with concurrent chemotherapy and radio- have multiple swallowing assessments and therefore therapy may be able to preserve swallowing function.
would have data making them eligible for this analysis.
Perhaps the most interesting finding from this analysis Furthermore, mucosal healing and swallowing therapy is that patients with more advanced T stages were less likely enable patients to regain swallowing function.
to have worsened swallowing and more likely to have im- Our study is limited by the retrospective nature of the proved swallowing after a course of concurrent chemo- analysis as well as the short follow-up period. The goal of (REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 134 (NO. 10), OCT 2008 2008 American Medical Association. All rights reserved.
this study was only to assess what factors were associated vision of the manuscript for important intellectual content: with swallowing changes during a course of chemoradio- Salama, Stenson, List, Mell, MacCracken, Cohen, Blair, therapy. Swallowing function for these patients will con- Vokes, and Haraf. Statistical analysis: Mell. Administra- tinue to evolve with longer follow-up. Furthermore, the tive, technical, and material support: Stenson, List, tools used to assess swallowing limit the analysis. The SPS MacCracken, Cohen, Blair, Vokes, and Haraf. Study super- itself has not been validated by statistical analysis; rather, vision: Salama, Stenson, List, Cohen, and Haraf.
it is a quick, clinically relevant scoring system for patients Financial Disclosure: None reported.
with head and neck cancer and a simple, single-step tech- Previous Presentation: This article was presented at the 2006
nique for classifying swallowing functional status. While AmericanHeadandNeckSocietyAnnualMeeting&Research other more specific measures are available to score vid- Workshop; August 18, 2006; Chicago, Illinois.
eofluorographic swallowing test results (eg, oropharyn-geal swallow efficiency), these methods are extremely la-bor intensive and are best suited for the laboratory setting.
By design, our study was only intended to assess acute swal-lowing changes of concurrent chemotherapy and radio- 1. Stenson KM, MacCracken E, List M, et al. Swallowing function in patients with head and neck cancer prior to treatment. Arch Otolaryngol Head Neck Surg. 2000; therapy. Further investigation will be needed to determine long-term swallowing changes. However, all the patient 2. Nguyen NP, Moltz CC, Frank C, et al. Dysphagia severity following chemoradia- data was collected prospectively by a single senior speech tion and postoperative radiation for head and neck cancer. Eur J Radiol. 2006; pathologist (E.M.). Furthermore, all patients described in 3. Smith RV, Goldman SY, Beitler JJ, Wadler SS. Decreased short- and long-term this study were managed uniformly with organ-preserving swallowing problems with altered radiotherapy dosing used in an organ- intent by an experienced multidisciplinary team of head sparing protocol for advanced pharyngeal carcinoma. Arch Otolaryngol Head Neck and neck surgeons, medical oncologists, and a single ra- diation oncologist (D.J.H.). The value of the SPS might have 4. Graner DE, Foote RL, Kasperbauer JL, et al. Swallow function in patients before been more limited if it had been administered by multiple and after intra-arterial chemoradiation. Laryngoscope. 2003;113(3):573-579.
5. Eisbruch A, Lyden T, Bradford CR, et al. Objective assessment of swallowing dys- raters, with subjective scoring changes leading to inter- function and aspiration after radiation concurrent with chemotherapy for head- observer variability. However, because all of the OPM and-neck cancer. Int J Radiat Oncol Biol Phys. 2002;53(1):23-28.
findings were interpreted by a single senior speech 6. Carrara-de Angelis E, Feher O, Barros AP, Nishimoto IN, Kowalski LP. Voice and pathologist, our data were obtained without interobserver swallowing in patients enrolled in a larynx preservation trial. Arch OtolaryngolHead Neck Surg. 2003;129(7):733-738.
variability. To validate these conclusions, we plan on ex- 7. Logemann JA, Rademaker AW, Pauloski BR, et al. Site of disease and treatment panding our data set with patients treated at our institu- protocol as correlates of swallowing function in patients with head and neck can- tion with similar chemoradiotherapy regimens. In addi- cer treated with chemoradiation. Head Neck. 2006;28(1):64-73.
tion, swallowing function continues to change over time 8. Haraf DJ, Rosen FR, Stenson K, et al. Induction chemotherapy followed by con- in patients treated with chemoradiotherapy for head and comitant TFHX chemoradiotherapy with reduced dose radiation in advanced headand neck cancer. Clin Cancer Res. 2003;9(16, pt 1):5936-5943.
neck cancer. Therefore, we plan to determine which fac- 9. Logemann JA, Bytell DE. Swallowing disorders in three types of head and neck tors are associated with chronic swallowing function surgical patients. Cancer. 1979;44(3):1095-1105.
10. Lazarus C, Logemann JA, Gibbons P. Effects of maneuvers on swallowing func- In conclusion, we found that patients with advanced T tion in a dysphagic oral cancer patient. Head Neck. 1993;15(5):419-424.
11. Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radio- stages (T3 and T4) and worse performance status (ECOG therapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003; 1 and 2) were less likely to have worsening of swallowing during a course of concurrent chemotherapy and radio- 12. Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy therapy. Additionally, patients with T3 or T4 tumors were and chemotherapy for high-risk squamous-cell carcinoma of the head and neck.
more likely to have an improvement in swallowing func- N Engl J Med. 2004;350(19):1937-1944.
13. Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or with- tion after the completion of their treatment. Patients with out concomitant chemotherapy for locally advanced head and neck cancer.
advanced laryngeal tumors, while initially presenting with N Engl J Med. 2004;350(19):1945-1952.
worse swallowing function, had less of a decrement in swal- 14. Adelstein DJ, Li Y, Adams GL, et al. An intergroup phase III comparison of stan- lowing function after chemoradiotherapy.
dard radiation therapy and two schedules of concurrent chemoradiotherapy inpatients with unresectable squamous cell head and neck cancer. J Clin Oncol.
Submitted for Publication: October 15, 2006; final re-
15. List MA, Siston A, Haraf D, et al. Quality of life and performance in advanced vision received October 24, 2007; accepted October 30, head and neck cancer patients on concomitant chemoradiotherapy: a prospec- tive examination. J Clin Oncol. 1999;17(3):1020-1028.
Correspondence: Joseph K. Salama, MD, Department of
16. Fung K, Lyden TH, Lee J, et al. Voice and swallowing outcomes of an organ- preservation trial for advanced laryngeal cancer. Int J Radiat Oncol Biol Phys.
Radiation and Cellular Oncology, 5758 S Maryland Ave, MC 9006, Chicago, IL 60637 ([email protected] 17. Nguyen NP, Frank C, Moltz CC, et al. Impact of dysphagia on quality of life after treatment of head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2005;61(3): Author Contributions: Dr Salama had full access to all the
18. Eisbruch A, Schwartz M, Rasch C, et al. Dysphagia and aspiration after chemoradio- data in the study and takes responsibility for the integrity therapy for head-and-neck cancer: which anatomic structures are affected and can of the data and the accuracy of the data analysis. Study con- they be spared by IMRT? Int J Radiat Oncol Biol Phys. 2004;60(5):1425-1439.
cept and design: Salama, List, Mell, Blair, Vokes, and Haraf.
19. Eisbruch A. Intensity-modulated radiotherapy (IMRT) aiming to reduce dyspha- Acquisition of data: Salama, Stenson, Mell, MacCracken, gia: early dose-effect correlations. Paper presented at: American Head and Neck Cohen, Blair, and Vokes. Analysis and interpretation of data: Society 2006 Annual Meeting & Research Workshop on the Biology, Preven-tion, & Treatment of Head & Neck Cancer; August 18, 2006; Chicago, IL.
Salama, Stenson, List, Mell, Cohen, and Haraf. Drafting of 20. Mell LK, Mehrotra AK, Mundt AJ. Intensity-modulated radiation therapy use in the manuscript: Salama, Mell, Vokes, and Haraf. Critical re- the U.S., 2004. Cancer. 2005;104(6):1296-1303.
(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 134 (NO. 10), OCT 2008 2008 American Medical Association. All rights reserved.
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