Dysphagia, Speech, Voice, and Trismus following Radiotherapy and/or Chemotherapy in Patients with Head and Neck Carcinoma: Review of the Literature

Table 3

Overview of included observational and intervention studies ( = 60) that met eligibility criteria.

Reference	Subjects	Carcinoma	Staging	Topic	Evaluation technique	Treatment(s)	Follow-up	Key findings/author’s conclusions
Aaltonen et al. 2014 [21]		Glottic = 56 (100%)	T1a = 56 (100%)	V	Videolaryngostroboscopy; Expert rating (GRBAS); Patient self-rating (VAS) hoarseness and impact on everyday life	Group 1: laser surgery (); Group 2: RT ()	6, 24 months	Similar overall voice quality for both groups. Laser surgery yielded more breathiness compared to RT
Ackerstaff et al.; 2009 [22]		Oral cavity = 40 (19%); Oropharyngeal = 129 (62%); Hypopharyngeal = 38 (19%)	T3 = 65 (31%); T4 = 142 (69%)	V; D; QoL	EORTC QLQ-C30; EORTC QLQ-H&N35; Trial-specific questionnaires	Group 1: intra-arterial cisplatin 4 weekly () + RT; Group 2: intravenous cisplatin 3 weekly () + RT	7 weeks; 3 months; 1, 2, 5 years	Both groups showed improved oral intake and voice quality, at 1-year follow-up often better compared to baseline
Agarwal et al.; 2009 [23]		Glottic = 50 (100%)	T1 = 33 (66%); T2 = 17 (34%)	V	Voice analysis; Acoustic parameters: frequency, intensity, perturbation; Patient-reported improvement in voice quality	RT	3–6 months	A trend for improvement in voice quality following RT was found
Agarwal et al.; 2011 [45]		Oropharyngeal; Hypopharyngeal; Laryngeal; (No details provided)	T1; T2; T3; T4; (No details provided)	D	Videofluoroscopy; PSS-HN	CRT	2, 6, 12 months	Significant impairment of swallowing was found: most frequently residue and aspiration
Akst et al.; 2004 [46]		Oral cavity = 12 (6%); Base of tongue = 41 (21%); Tonsil = 41 (21%); Other oropharyngeal =; 15 (8%); Hypopharyngeal = 34 (17%); Laryngeal = 50 (26%); Unknown = 3 (1%)	T1 = 15 (8%); T2 = 42 (21%); T3 = 65 (33%); T4 = 70 (36%); Unknown = 4 (2%)	D	Presence of feeding tube; Presence of tracheotomy; Level of oral diet	CRT	3, 6, 12, 24 months	A majority of patients did not need a tracheotomy but need a feeding tube during treatment. At 1-year follow-up most patients had a (nearly) normal oral intake. Patients with tumor stage IV and age ≥ 60 had prolonged feeding tube use and slower recovery
Al-Mamgani et al.; 2012 [24]		Supraglottic = 121 (71%); Glottic = 49 (29%)	T3 = 170 (100%)	V; QoL	EORTC QLQ-C30; EORTC QLQ-H&N35; VHI	Group 1: CRT (); Group 2: RT ()	2, 4, 6 weeks; 3, 6, 12 months	Adding chemotherapy to RT did not diminish QoL or voice handicap
Al-Mamgani et al.; 2012 [47]		Hypopharyngeal = 176 (100%)	T1 = 18 (10%); T2 = 55 (31%); T3 = 56 (32%); T4a = 35 (20%); T4b = 12 (7%)	D; QoL	Tube dependency; EORTC QLQ-C30; EORTC QLQ-H&N35	Group 1: CRT (); Group 2: RT ()	2, 4, 6 weeks; 3, 6 months; 1, 2 years	CRT significantly improved functional outcome. Acute toxicity increased but late radiation side effects did not increase
Al-Mamgani et al.; 2013 [25]		Glottic = 1050 (100%)	T1a = 551 (52%); T1b = 168 (16%); T2a = 209 (20%); T2b = 122 (12%)	V; QoL	EORTC QLQ-C30; EORTC QLQ-H&N35; VHI	RT	4, 6 weeks; 3, 6, 12, 18, 24, 36, 48 months	Excellent outcome with good QoL and VHI scores
Al-Mamgani et al.; 2015 [26]		Glottic = 30 (100%)	T1a = 30 (100%)	V	Laryngoscopy; VHI	Single vocal cord RT	4, 6, 12 weeks; 6, 12, 18 months	Single vocal cord RT showed better voice quality compared to whole larynx RT
Bansal et al.; 2004 [27]		Base of tongue = 20 (44%); Tonsil = 10 (22%); Unknown = 15 (33%)	Stage III = 17 (38%); Stage IV = 23 (51%); Not reported = 5 (11%)	V; QoL	Acute and late morbidity scoring of skin, oropharyngeal mucosa, salivary glands, larynx, and oesophagus (LENT/SOMA); EORTC QLQ-C30	RT	1, 4 months	During RT a decline in all QoL domains was found. QoL improved after 1 month but did not reach pre-RT levels
Bibby et al.; 2008 [28]		Glottic = 30 (100%)	T1 = 21 (70%); T2 = 9 (30%)	V; QoL	Voice analysis; Patient self-rating voice quality; VR-QoL	RT	3, 6, 12 months	After RT expert-rated perceptual auditory outcomes, patient self-rated VAS and all subscales of VR-QoL showed significant improvement
Bottomley et al.; 2014 [78]		Laryngeal; Hypopharyngeal; (No details provided)	T2; T3; T4; (No details provided)	QoL	EORTC QLQ-C30; EORTC QLQ-H&N35	Group 1: sequential CRT (); Group 2: alternating CRT ()	6, 12, 18, 24, 36, 48 months	The HRQoL scores of the majority of patients returned to baseline after therapy. No group differences were found
Buchbinder et al.; 1993 [48]		No details provided	No details provided	D	MIO	Group 1: RT + unassisted exercise; Group 2: RT + stacked tongue depressors combined + unassisted exercise; Group 3: RT + TheraBite® system combined + unassisted exercise	2, 4, 6, 8, 10 weeks	The highest increase in MIO was reached in group 3
Caudell et al.; 2010 [49]		Nasal cavity = 3 (4%); Nasopharyngeal = 7 (8%); Oral cavity = 1 (1%); Oropharyngeal = 44 (53%); Hypopharyngeal = 6 (7%); Laryngeal = 17 (21%); Unknown = 5 (6%)	Tx-2 = 28 (34%); T3-T4 = 55 (66%)	D	Videofluoroscopy; PEG dependency	Group 1: CRT (); Group 2: RT ()	12 months	Mean dose to the larynx greater than 41 Gy and a receiving volume greater than 24% showed association with increased PEG dependency and aspiration
Christianen et al.; 2015 [50]		Nasopharyngeal = 8 (3%); Oral cavity = 11 (5%); Oropharyngeal = 71 (30%); Hypopharyngeal = 12 (5%); Laryngeal = 136 (57%)	T1-T2 = 161 (68%); T3-T4 = 77 (32%)	D	Grade of swallowing dysfunction according to the RTOG/EORTC Late Radiation Morbidity Scoring Criteria	Group 1: conventional RT (); Group 2: accelerated RT (); Group 3: CRT ()	6, 12, 18, 24 months	Patterns of swallowing dysfunction may be caused by radiobiological mechanisms of radiation induced damage and recovery. No group differences were found
Cohen et al.; 2006 [51]		Oral cavity = 14 (26%); Oropharyngeal = 11 (21%); Hypopharyngeal = 3 (6%); Laryngeal = 9 (17%); Supraglottic = 13 (24%); Unknown = 3 (6%)	T0 = 3 (6%); T1 = 3 (6%); T2 = 17 (32%); T3 = 30 (56%)	D; QoL	PSS-HN; Head and Neck RT Questionnaire (selected questions); FACT-H&N	CRT	3, 6, 12, 18, 24, 36, 48, 60 months	Most patients returned to pretreatment function (QoL and performance) by 12 months
Dornfeld et al.; 2007 [29]		Oral cavity = 1 (4%); Oropharyngeal = 16 (59%); Hypopharyngeal = 1 (4%); Laryngeal = 6 (22%); Unknown = 3 (11%)	Tx = 2 (7%); T1 = 6 (22%); T2 = 7 (26%); T3 = 5 (19%); T4 = 7 (26%)	V; D; QoL	Weight; Type of diet; Type of speech; Presence of PEG tube; HNCI	CRT	1 year	Speech, diet, and QoL outcomes showed an inverse relationship with the delivered radiation dose to the larynx
Dijkstra et al.; 2007 [52]		Parotid = 4 (14%); Maxilla = 4 (14%); Gingiva = 2 (7%); Floor of mouth = 3 (10%); Trigonum retromolare = 4 (14%); Oropharyngeal = 8 (27%); Other localization = 4 (14%)	No details provided	D	MIO	RT	12–48 weeks	Increase in mouth opening was significantly less in the group of patients with trismus related to head and neck cancer and is difficult to treat with exercise therapy
Feng et al.; 2007 [53]		Base of tongue = 19 (53%); Tonsil = 12 (33%); Nasopharyngeal = 5 (14%)	T1 = 2 (5%); T2 = 11 (31%); T3 = 9 (25%); T4 = 14 (39%)	D; QoL	Videofluoroscopy; Esophagogram; HNQoL; UWQoL; EORTC Late Radiation Morbidity Scale	CRT	3 months	Statistically significant dose-volume effect relationships for dysphagia and aspiration were found. Reducing the doses to the swallowing structures may improve swallowing
Feng et al.; 2010 [54]		Base of tongue = 38 (52%); Tonsil = 35 (48%)	T1 = 9 (12%); T2 = 29 (40%); T3 = 17 (23%); T4 = 18 (25%)	D	Videofluoroscopy; UWQoL (swallowing question); HNQoL (eating domain); Observer rated dysphagia	CRT	3, 6, 12, 18, 24 months	Long-term measures of swallowing were slightly worse than pretherapy measures
Frowen et al.; 2010 [16]		Base of tongue = 19 (24%); Soft palate = 2 (2%); Tonsil = 26 (32%); Supraglottic = 8 (10%); Hypopharyngeal = 8 (10%); Laryngeal = 18 (22%)	T1 = 11 (14%); T2 = 27 (33%); T3 = 31 (38%); T4 = 12 (15%)	D	Videofluoroscopy	Group 1: CRT (); Group 2: CT ()	3, 6 months	Swallowing in both groups was best at baseline; a decline at 3 months and an improvement at 6 months after therapy were shown. Baseline levels were not reached. Predictors for swallowing outcome were intoxications, tumor size, RT technique, and baseline level of swallowing. Patients who received conformal RT had a very low risk of penetration and aspiration of liquids by 6 months after treatment
Haderlein et al.; 2014 [55]		Oropharyngeal = 3 (7%); Hypopharyngeal = 18 (40%); Laryngeal = 24 (53%)	T2 = 15 (33%); T3 = 17 (38%); T4 = 13 (29%)	D; QoL	PEG dependency; EORTC QLQ-C30	CRT	3–6- month intervals	Almost 50% of patients had deterioration of swallowing function after CRT
Hutcheson et al.; 2014 [56]		Nasopharyngeal = 1 (2%); Oral cavity = 1 (2%); Oropharyngeal = 41 (88%); Hypopharyngeal = 2 (4%); Supraglottic = 2 (4%)	T1 = 16 (34%); T2 = 14 (30%); T3 = 12 (25%); T4 = 5 (11%)	D	Videofluoroscopy; PSS-HN; MDADI	Group 1: RT (); Group 2: CRT (); Group 3: surgery ()	6, 12, 24 months	Two years after therapy, mild deterioration of swallowing without chronic aspiration was found
Jacobi et al.; 2016 [30]		Nasopharyngeal = 6 (18%); Oral cavity/oropharyngeal = 15 (44%); Hypopharyngeal = 13 (38%)	T1 = 6 (18%); T2 = 13 (38%); T3 = 11 (32%); T4 = 4 (12%)	V	Speech analysis	CRT	10 weeks; 1 year	Received dose to tongue and velopharynx were most relevant for speech and voice quality
Karlsson et al.; 2015 [31]		Laryngeal = 74 (100%)	T0 = 1 (1%); T1 = 44 (60%); T2 = 22 (30%); T3 = 6 (8%); T4 = 1 (1%)	V; QoL	EORTC QLQ-C30; EORTC QLQ-H&N35; S-SECEL	Group 1: CRT + voice rehabilitation (); Group 2: CRT only ()	1, 6 months	Patients treated with voice rehabilitation experienced benefits of therapy on communication and HRQoL
Karlsson et al.; 2016 [32]		Laryngeal = 40 (100%)	Tis = 2 (5%); T1 = 20 (50%); T2 = 13 (33%); T3 = 5 (12%)	V; QoL	EORTC QLQ-C30; EORTC QLQ-H&N35; S-SECEL; Perceptual and acoustic voice analysis	RT (1 subject received concomitant chemotherapy)	1, 6, 12 months	One year after treatment most outcomes showed no significant improvements compared to baseline measurements
Kazi et al.; 2008 [33]		Hypopharyngeal = 8 (38%); Laryngeal = 10 (48%); Supraglottic = 3 (14%)	Stage III; Stage IV; No details provided	V	Voice analysis; Electroglottography	CRT	1, 6, 12 months	Patients treated with CRT had a better voice quality compared to patients after total laryngectomy
Kerr et al.; 2015 [34]		Tongue base = 77 (38%); Tonsil/soft palate = 123 (62%)	T0-T1 = 42 (21%); T2 = 72 (36%); T3 = 48 (24%); T4 = 38 (19%)	V; D	KPS; ECOG toxicity and response criteria scale; PSS-HN; RBHOMS; VHI-10; Edmonton Self-Assessment Scale (Self-rated Xerostomia)	Group 1: 3DCRT (); Group 2: IMRT ()	3, 6, 12, 24 months	IMRT showed better functional outcomes compared to 3DCRT, both 3–6 and 12–24 months after treatment
Kotz et al.; 2012 [57]		Nasopharyngeal = 1 (4%); Tongue base = 11 (42%); Tonsil = 11 (42%); Oropharyngeal = 1 (4%); Glottic = 1 (4%); Unknown = 1 (4%)	T2 = 1 (4%); T3 = 5 (19%); T4 = 20 (77%)	D	PSS-HN (eating in public and normalcy of diet); FOIS	Group 1: CRT + prophylactic swallowing therapy (); Group 2: CRT ()	3, 6, 9, 12 months	Prophylactic swallowing therapy improves swallowing at 3 and 6 months; later there were no group differences
Kraaijenga et al.; 2014 [35]		Nasopharyngeal = 4 (18%); Oral cavity/; oropharyngeal = 10 (46%); Hypopharyngeal/; laryngeal = 8 (36%)	T1 = 5 (23%); T2 = 9 (41%); T3 = 7 (32%); T4 = 1 (4%)	V; D; QoL	Videofluoroscopy; Acoustic analysis; Presence of feeding tube; FOIS; Pain (VAS); Trismus; QoL aspects (based on EORTC QLQ-C30 and EORTC QLQ-H&N35); SWAL-QoL; VHI	CRT	2, 6 years	Functional swallowing and voice problems at 6 years after treatment were minimal, possibly due to preventive swallowing rehabilitation programs
Kumar et al.; 2014 [58]		Tonsil = 19 (41%); Base of tongue = 22 (47%); Pharyngeal wall = 3 (7%); Unknown = 2 (5%)	T0 = 2 (4%); T1 = 15 (33%); T2 = 14 (30%); T3 = 12 (26%); T4 = 3 (7%)	D	Videofluoroscopy	CRT	From <6 to >18 months	Aspiration and penetration were associated with dose and volume delivered to the floor of mouth muscles
Lazarus et al.; 2014 [36]		Nasopharyngeal = 3 (10%); Oropharyngeal = 18 (63%); Pharyngeal = 1 (3%); Hypopharyngeal = 1 (3%); Laryngeal = 5 (18%); Unknown primary = 1 (3%)	Stage I = 2 (7%); Stage II = 1 (4%); Stage III = 5 (17%); Stage IVa = 21 (72%)	D; V; QoL	Tongue strength, jaw ROM, and tongue ROM; Saliva weight; Eating Assessment Tool; MDADI; Speech Handicap Index; EORTC QLQ-H&N35; PSS-HN (normalcy of diet, eating in public, and understandability of speech); KPS	CRT	3, 6 months	Patients performed worse in oral outcomes, performance status, and QoL after treatment
List et al.; 1999 [59]		Nasopharyngeal = 1 (2%); Oral cavity = 6 (9%); Oropharyngeal = 34 (53%); Hypopharyngeal = 10 (16%); Laryngeal = 9 (14%); Other = 4 (6%)	Stage III = 4 (6%); Stage IV = 60 (94%)	D; QoL	KPS; PSS-HN; McMaster University Head and Neck RT Questionnaire (selected questions); FACT-H&N	CRT	1, 3, 6, 9, 12 months	Decline of QoL and functional aspects resolved 1 year after treatment; however, oral intake stayed restricted
McLaughlin et al.; 2010 [60]		Nasopharyngeal = 9 (10%); Oral cavity = 19 (21%); Oropharyngeal = 32 (35%); Hypopharyngeal = 7 (8%); Laryngeal = 12 (13%); Unknown = 4 (4%); Other = 8 (9%)	Stage II = 1 (1%); Stage III = 21 (23%); Stage IV = 69 (76%)	D	Weight loss; Aspiration; Overall nutritional status; Duration G-tube placement; Treatment-related complications	CRT	6, 12 months	Patients treated with CRT could be managed without nutritional support via G-tube. Dysphagia at baseline and advanced tumor stage are associated with increased risk of longer G-tube dependency
Mittal et al.; 2001 [37]		Nasopharyngeal = 4 (10%); Oropharyngeal = 17 (44%); Hypopharyngeal = 7 (18%); Laryngeal = 5 (13%); Unknown = 6 (15%)	Stage III = 5 (13%); Stage IV = 34 (87%)	D; V	Videofluoroscopy; Saliva production; PSS-HN; FACT-H&N; Fisher-Logemann Test of Articulation Competence	Group 1: CRT with TDC (); Group 2: CRT without TDC ()	3 months	Patients treated with TDC had better oral intake, swallowing function, and articulation
Murry et al. 1998 [61]		Oropharyngeal = 19 (52%); Hypopharyngeal = 6 (16%); Laryngeal = 12 (32%)	T3; T4; (No details provided)	D	HNRQ; Questionnaire on swallowing	CRT	6 months	During treatment QoL and swallowing function decreased acutely and significantly. Six months after therapy QoL exceeded pretreatment level. Recovery was site-specific: oropharyngeal tumor patients had poorest outcome, whereas hypopharyngeal tumor patients showed most rapid recovery. Physical recovery followed psychosocial recovery. Organ preservation treatment may improve swallowing after treatment
Niedzielska et al.; 2010 [38]		Laryngeal = 45 (100%)	T1 = 24 (53%); T2 = 21 (47%)	V	Videolaryngostroboscopy; Acoustic analysis	RT	1–3 years	All irradiated patients showed reduced vibration of the vocal cords. Except for some of the acoustic parameters, most data were comparable to a healthy control group ()
Nourissat et al.; 2010 [62]		Oral cavity = 63 (12%); Oropharyngeal = 17 (3%); Hypopharyngeal = 8 (1%); Supraglottic = 100 (19%); Glottic = 347 (65%)	T1 = 329 (61%); T2 = 206 (39%)	D; QoL	Weight; KPS; EORTC QLQ-C30; Structured general questionnaire	RT	Direct posttherapy	The occurrence of adverse effects of RT appeared to be one of the main reasons for weight loss. Correlations were found between genetic factors associated with the adverse effects of cancer treatments
Ottoson et al.; 2014 [63]		Oral cavity = 20 (20%); Oropharyngeal = 62 (61%); Hypopharyngeal = 8 (8%); Laryngeal = 11 (11%)	T1 = 11 (10%); T2 = 16 (16%); T3 = 28 (28%); T4 = 46 (46%)	D	Videofluoroscopy; BMI	RT	5 years	Dysphagia with aspiration was related to unintentional weight loss and a lower BMI
Pauli et al.; 2013 [64]		Sinus, nose = 6 (8%); Salivary gland = 10 (13%); Gingiva, buccal = 6 (8%); Tongue, floor of mouth = 15 (20%); Tonsil = 24 (32%); Base of tongue, oropharyngeal = 11 (15%); Other = 3 (4%)	T0 = 5 (7%); T1 = 13 (17%); T2 = 29 (39%); T3 = 9 (12%); T4 = 18 (24%); Unknown = 1 (1%)	D; QoL	MIO; Patient-reported outcome; Gothenburg Trismus Questionnaire; EORTC QLQ-C30; EORTC QLQ-H&N35; HADS	Group 1: surgery (); Group 2: surgery + RT (); Group 3: surgery + CRT (); Group 4: RT (); Group 5: CRT (); Group 6: no treatment ()	3, 6, 12 months	Trismus was a major side effect of the treatment of head and neck cancer and deteriorates HRQoL
Pauloski et al.; 2006 [65]		Nasopharyngeal = 8 (5%); Oral cavity = 15 (9%); Oropharyngeal = 80 (47%); Hypopharyngeal = 14 (8%); Laryngeal = 42 (25%); Unknown = 11 (6%)	Stage IV = 122 (72%); Other = 48 (28%)	D	Videofluoroscopy; Oral intake	Group 1: CRT (); Group 2: RT (); Unknown ()	1, 3, 6, 12 months	In both groups limitations in oral intake and diet after cancer treatment were significantly related to reduced laryngeal elevation and reduced cricopharyngeal opening due to treatment
Rademaker et al.; 2003 [66]		Nasopharyngeal = 13 (5%); Oral cavity = 25 (10%); Oropharyngeal = 118 (46%) Hypopharyngeal = 22 (9%); Laryngeal = 59 (23%); Unknown = 18 (7%)	Stage II = 16 (6%); Stage III = 48 (19%); Stage IV = 187 (73%); Unknown = 4 (2%)	D	Percentage of oral intake; Food consistencies	CRT	1, 3, 6, 12 months	Eating ability decreased during treatment and improved 12 months after treatment to near pretreatment levels
Remmelts et al.; 2013 [39]		Glottic = 248 (100%)	Tis = 26 (10%); T1a = 103 (42%); T1b = 42 (17%); T2 = 77 (31%)	V	VHI (physical subscale); 5-item questionnaire	Group 1: RT (); Group 2: laser surgery ()	12 months	VHI scores were comparable for both groups. Regarding laryngeal preservation surgery is the treatment of first choice
Salama et al.; 2008 [67]		Nasopharyngeal = 4 (4%); Oral cavity = 8 (9%); Oropharyngeal = 49 (52%); Hypopharyngeal = 5 (5%); Laryngeal = 22 (23%); Other = 7 (7%)	Tx = 7 (7%); T1 = 15 (16%); T2 = 19 (20%); T3 = 16 (17%); T4 = 38 (40%)	D	Videofluoroscopy; SPS	CRT	1-2 months	Improvement of swallowing ability compared to baseline was associated with advanced tumor stage
Sanguineti et al.; 2014 [40]		Base of tongue = 54 (43%); Soft palate = 2 (2%); Tonsil = 59 (48%); Pharyngeal wall = 1 (1%); Unknown = 8 (6%)	T0 = 8 (6%); T1 = 37 (30%); T2 = 49 (40%); T3 = 14 (11%); T4 = 16 (13%)	V	CTCAE; FACT-HN (items HN4 and HN10)	Group 1: CRT (); Group 2: RT ()	3, 6, 12, 18, 24, 36, 48, 60 months	Mild voice changes were common and strictly correlated to mean dose to larynx and should be kept under 50 Gy
Scrimger et al.; 2007 [68]		Nasopharyngeal = 10 (21%); Oral cavity = 20 (43%); Oropharyngeal = 9 (19%); Hypopharyngeal/; laryngeal = 6 (13%); Unknown primary = 2 (4%)	T0 = 2 (4%); T1 = 7 (15%); T2 = 20 (42%); T3 = 12 (26%); T4 = 6 (13%)	D; QoL	Mouth saliva flow; UW-QoL; RTOG late-toxicity scale; XQoL	Group 1: RT (); Group 2: CRT (); Group 3: surgery + RT ()	3, 6, 12 months	Nonsurgery resulted in better QoL questionnaire scores compared to surgery. Patients with good saliva production did not exhibit better QoL after RT than patients with less saliva production
Spector et al.; 1999 [41]		Glottic = 659 (100%)	T1 = 659 (100%)	V	Voice preservation	Group 1: low-dose RT (); Group 2: high-dose RT (); Group 3: conservation surgery (); Group 4: endoscopic resection ()	5 years	Groups 2–4 had similar unaided laryngeal voice preservation rates; however group 1 had significant lower unaided laryngeal voice preservation
Starmer et al.; 2014 [69]		Oropharyngeal = 71 (100%)	T1 = 24 (34%); T2 = 19 (27%); T3 = 13 (18%); T4 = 12 (17%); Unknown = 3 (4%)	D	Videofluoroscopy; FOIS	Group 1: CRT (); Group 2: RT ()	1–18 months	Patients undergoing nonsurgical treatment for oropharyngeal tumors were at risk for posttreatment dysphagia
Stenson et al. 2010 [70]		Buccal = 4 (3%); Alveolus/gingivae = 7 (6%); Floor of mouth = 32 (29%); Tongue = 50 (45%); Palate/oral cavity NOS = 4 (4%); Trigonum retromolare = 13 (12%); Unknown = 1 (1%)	T1 = 9 (8%); T2 = 15 (14%); T3 = 20 (18%); T4 = 67 (60%)	D	Videofluoroscopy; SPS	Group 1: CRT (); Group 2: surgery + CRT ()	2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36 months	Ninety-two percent of all patients were able to maintain weight via oral route.; Both groups showed comparable overall survival. Ninety-two percent of all patients had a sufficient oral intake
Strigari et al.; 2010 [71]		Nasopharyngeal = 44 (70%); Floor of mouth/oral cavity = 2 (3%); Oropharyngeal = 11 (17%); Hypopharyngeal = 4 (7%); Unknown primary = 2 (3%)	T1-T2 = 17 (23%); T3-T4 = 46 (73%)	D	Saliva flow; Xerostomia related questionnaires; RTOG late-toxicity scale	RT	3, 6, 12, 18, 24 months	The mean score on the xerostomia related questionnaire increased (worsened) after RT and decreased (improved) over time in all patients
Tuomi et al.; 2015 [42]		Supraglottic = 13 (19%); Glottic = 54 (81%)	Tis = 2 (3%); T1 = 41 (61%); T2 = 17 (25%); T3 = 6 (9%); T4 = 1 (2%)	V; D; QoL	Acoustic analysis; EORTC QLQ-C30; EORTC QLQ-H&N35; S-SECEL	RT	1 month	Patients treated for supraglottic tumors experienced more problems in eating and swallowing prior to therapy compared to glottic tumors and demonstrated significant HRQoL reduction after treatment. In contrast, glottic tumors presented with inferior voice quality
Urdaniz et al.; 2005 [77]		Paranasal sinuses = 3 (5%); Nasopharyngeal = 3 (5%); Oral cavity = 2 (3%); Oropharyngeal = 25 (42%); Hypopharyngeal = 9 (15%); Laryngeal = 18 (30%)	T2 = 2 (3%); T3 = 20 (33%); T4 = 38 (64%)	QoL	EORTC QLQ-C30; EORTC QLQ-H&N35	Group 1: hyperfractionated concomitant boost RT + cisplatin (); Group 2: hyperfractionated conventional RT + cisplatin ()	1 month	QoL in both groups was relatively good. QoL improved in the follow-up period
Vainshtein et al.; 2015 [72]		Base of tongue = 18 (45%); Tonsil = 22 (55%)	T1 = 8 (20%); T2 = 20 (50%); T3 = 8 (20%); T4 = 4 (10%)	D; QoL	HNQoL; UWQoL; XQoL	CRT	1, 3, 6, 12, 18, 24 months	At 6.5 years after therapy patients showed a stable or improved HRQoL in most domains comparable with baseline and 2 years after therapy
van der Molen et al.; 2011 [73]		Nasopharyngeal = 7 (14%); Oral cavity/; oropharyngeal = 24 (49%); Hypopharyngeal/; laryngeal = 18 (37%)	T1 = 8 (16%); T2 = 15 (31%); T3 = 19 (39%); T4 = 7 (14%)	D	Videofluoroscopy; MIO; BMI; FOIS; VAS pain	Group 1: standard rehabilitation (); Group 2: experimental rehabilitation ()	10 weeks	(Preventive) rehabilitation; in head and neck cancer patients was feasible and improved functional outcomes after therapy
van der Molen et al.; 2012 [44]		Nonlaryngeal = 36 (65%); Laryngeal = 19 (35%)	T1 = 8 (15%); T2 = 15 (27%); T3 = 21 (38%); T4 = 11 (20%)	V; QoL	Acoustic analysis; Study-specific QoL questionnaire	CRT	10 weeks; 1 year	CRT effects 10 weeks after therapy were worse than 1 year after therapy, and both were worse than baseline
van der Molen et al.; 2013 [74]		Nasopharyngeal = 7 (13%); Oral cavity/; oropharyngeal = 29 (53%); Hypopharyngeal/; laryngeal = 19 (34%)	T1 = 8 (15%); T2 = 15 (27%); T3 = 21 (38%); T4 = 11 (20%)	D	Videofluoroscopy; MIO; Study-specific structured questionnaire	CRT	10 weeks; 1 year	A correlation between doses and structures was found for dysphagia and trismus
Verdonck-de Leeuw et al.; 1999 [43]		Glottic = 60 (100%)	T1 = 60 (100%)	V	Videolaryngostroboscopy Voice quality rating; Self-rating of vocal performance and quality	RT	0.5–10 years	Voice and its characteristics improved after treatment but did not reach pretreatment levels in half of the patients
Verdonck-de Leeuw et al.; 2014 [79]		Oral/oropharyngeal = 95 (58%); Hypopharyngeal/; laryngeal = 69 (42%)	No details provided	QoL	EORTC QLQ-C30; EORTC QLQ-H&N35	CRT	6 weeks; 6, 12, 18, 24 months	Significant difference in HRQoL between survivors and nonsurvivors in favor of survivors was found
Vlacich et al.; 2014 [75]		Sinus/nasal cavity = 2 (1%); Nasopharyngeal = 12 (9%); Oral cavity = 5 (4%); Oropharyngeal = 82 (58%); Hypopharyngeal = 6 (4%); Laryngeal = 30 (21%); Unknown = 4 (3%)	Stage III = 42 (30%); Stage IVa = 81 (57%); Stage IVb = 18 (13%)	D	PEG requirement	CRT	12 months	IMRT dose to the inferior constrictor correlated with persistent dysphagia requiring prolonged PEG use
Wilson et al.; 2011 [76]		Nasopharyngeal = 5 (3%); Oropharyngeal = 66 (39%); Hypopharyngeal = 21 (13%); Laryngeal = 63 (38%); Unknown primary = 12 (7%)	T1 = 37 (22%); T2 = 37 (22%); T3 = 37 (22%); T4 = 44 (27%); Unknown = 12 (7%)	D; QoL	MDADI; UWQoL	Group 1: CRT (); Group 2: RT ()	3, 6, 12 months	HRQoL deteriorated significantly after treatment. Little improvement may be expected 3 to 12 months after treatment

3DCRT: 3D conformal radiotherapy; BMI: body mass index; CRT: chemoradiotherapy; CTCAE: common terminology criteria for adverse events; D: digestive tract; ECOG: Eastern Cooperative Oncology Group; EORTC QLQ-C30: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ-H&N35: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Module Head and Neck Cancer; FACT-HN: functional assessment of cancer therapy-head and neck; FOIS: functional oral intake scale; GRBAS: grade, roughness, breathiness, asthenia, strain scale; HADS: hospital anxiety and depression scale; HNCI: head and neck cancer inventory; HNQoL: head and neck quality of life; HNRQ: head and neck radiotherapy questionnaire; HRQoL: health-related quality of life; IMRT: intensity-modulated radiation therapy; KPS: Karnofsky performance status scale; LENT/SOMA: late effects normal tissue-subjective, objective, management, analytic scales; MDADI: MD Anderson dysphagia inventory; MIO: maximum incisal opening; NOS: not otherwise specified; PEG: percutaneous endoscopic gastrostomy; PSS-HN: performance status scale for head and neck cancer patients; QoL: quality of life; RBHOMS: Royal Brisbane Hospital outcome measure for swallowing; ROM: range of motion; RT: radiotherapy; RTOG: Radiation Therapy Oncology Group; S-SECEL: Swedish version of the self-evaluation of communication experiences after laryngeal cancer; SPS: swallowing performance status scale; TDC: tissue/dose compensation; UWQoL: University of Washington Quality of Life Questionnaire; V: voice and/or speech; VAS: visual analog scale; VHI: voice handicap index; VHI-10: voice handicap index-10; VR-QoL: voice-related quality of life; XQoL: xerostomia questionnaire.