Table 3.
Characterization of the included studies
| References | Endpoints | Outcomes |
|---|---|---|
| Tian et al. [15] |
1. Incidence of mucositis 2. Severity of mucositis 3. Oral pain 4. Onset of mucositis 5. Toxicity 6. QoL |
1. No significant differences between the groups Gholizadeh et al. [19], Mansouri et al. [18], Rambod et al. [16]: RR = 0.52, 95% CI 0.17–1.64, p = 0.27, I2 = 92% 2. No significant differences between the groups moderate/heavy severity: Gholizadeh et al. [19], Mansouri et al. [18]: RR = 0.62, 95% CI 0.11–3.56, p = 0.60, I2 = 65% heavy severity: Gholizadeh et al. [19], Mansouri et al. [18], Arbabi-Kalati et al. [20]: RR = 0.70, 95% CI 0.29–1.71, p = 0.44, I2 = 0% Mehdipour et al. [17]: tendency of lower moderate severity in arm A (in two of four weeks significant, p = 0.025) 3. Arbabi-Kalati et al. [20]: less pain in arm A (week 3–10, p < 0.005) Gholizadeh et al. [19]: no differences in intensity, greater efficacy in relieving pain in arm B (at the end of week 4, p = 0.03) 4. Rambod et al. [16]: no significant differences (p = 0.34) 5. Mansouri et al. [18]: no side effects 6. Arbabi-Kalati et al. [20]: no significant differences between the groups (p = 0.15–0.91) |
| Arbabi-Kalati et al. [20] |
1. Mucositis 2. Xerostomia 3. Pain 4. QoL |
1. Significant differences in week 8, 12, 16 and 20 concerning severity Week 8: arm A: mean (95% CI) = 1.54 (1.29–1.79), arm B: 2.2 (1.99–2.4) Week 20: arm A: 1.16 (0.57–1.17), arm B: 2.33 (0.89–3.76), p < 0.005 No significant differences concerning duration (p = 0.13) 2. Significant differences from week 4 Week 4: arm A: mean (95% CI) = 2.44 (2.19–2.68), arm B: 3.32 (3.09–3.54), p < 0.005 Intensity remained lower Week 20: arm A: mean (95% CI) = 1.16 (0.73–1.59), arm B: 2.5 (2.05–2.94), p = 0.0049 No significant differences in duration of necessary treatment (p = 0.23) 3. Significant differences from 6 to 20th week Week 6: arm A: mean (95% CI) = 5.56 (5.097–6.02), arm B: 7.48 (7.04–7.91), p = 0.003 Week 20: arm A: 4.00 (3.12–4.87), arm B: 7.00 (6.40–7.59), p = 0.0049 4. No significant differences |
| Braga et al. [36] |
1. Antibody concentrations against serotypes 1, 5, 6B, 9 V, 14, and 18C 2. Seroconversion 3. Zinc plasma concentrations |
1. Higher antibody concentration against all polysaccharides in both arms before and 4 weeks after vaccination p < 0.01 16 weeks after vaccination significant higher concentrations of PS6- specific antibodies in arm A Arm A: mean (95% CI) = 2.96 (1.74–5.03), arm B: mean (95% CI) = 10.75 (5.37–21.54), p < 0.01 2. No significant differences 3. Higher zinc plasma concentration after zinc intake Arm A: before vaccination: mean (SD) = 86.0 (14.1), after 16 weeks: mean (SD) = 128.9 (33.4), p = 0.01 After 16 weeks: arm B: mean (SD) = 89.2 (19.0), p = 0.001 |
| Ertekin et al. [26] |
1. Oral mucositis: duration, severity, onset 2. Weight |
1. Significant differences in onset Arm A: median (range) week 3 (0–5), arm B: week 2 (2–3), p < 0.05 Significant differences in severity Arm A: median (range): 1 (0–2), arm B: 3 (2–3), p < 0.05 Significant differences in RT dose leading to mucositis Arm A: median (range): 3600 (2400–4400), arm B: 2000 (1800–2800), p < 0.01 6 weeks after RT, mucositis less frequently in arm A Arm A: 6.7%, arm B: 83.3%, p < 0.01 2. No significant differences (p = no information) |
| Gorgu et al. [23] |
1. Oral mucositis 2. Esophagitis 3. Serum zinc level |
1. No significant differences Grade 0, 1, 2, 3 in arm A: 12, 7, 5, 0, in arm B: 3, 6, 6, 1, X2 = 5.174, p = 0.159 2. No significant differences Grade 0, 1, 2, 3 in arm A: 6, 10, 6, 2 in arm B: 2, 6, 7, 1, p = 0.159 3. After the treatment in arm B significant lower Mean: no information, p = 0.05 |
| Halyard et al. [31] |
1. Onset of taste alteration 2. Incidence of taste alteration 3. QoL 4. Toxicity 5. Weight |
1. No significant differences Arm A: median interval = 2.3 weeks, arm B: median interval = 1.6 weeks, p = 0.09 2. No significant differences Arm A: 73%, arm B: 84%, p = 0.16 3. No significant differences 4. More often moderate or severe dysphagia in arm A; otherwise rare with comparable frequencies and severity dysphagia: arm A: 7%, arm B: 4%, p = 0.02 5. Better maintenance of weight in arm A Arm A: 99%, Arm B: 92%, p = 0.04 |
| Iovino et al. [37] | 1. Toxicity | 1. No significant differences |
| Lin et al. [25] |
1. Grade 2 and 3 mucositis 2. Grade 2 and 3 dermatitis 3. Toxicity |
1. Significant earlier appearance in arm B Grade 2: p = 0.017, grade 3: p = 0.0003 Less severity in Arm A, but 2 weeks after RT similar improvement p = 0.003 2. Significant earlier appearance in arm B Grade 2: p = 0.014, grade 3: p = 0.0092 Less severity in Arm A, but 2 weeks after RT similar improvement p = 0.003 3. No side effects |
| Lin et al. [34] |
1. OS 2. LFS 3. MFS 4. DFS |
1. No significant differences Hazard ratio (95% CI) = no information, p = 0.19 2. Tendency towards shorter LFS in arm B but not significant Hazard ratio (95% CI) = 1.64 (0.92–2.93), p = 0.092 Subgroup: stage III–IV cancer with concurrent chemotherapy treatment: significantly poorer LFS in arm B Hazard ratio (95% CI) = 3.01 (1.1–8.23), p = 0.032 3. No significant differences p = 0.35 4. No significant differences p = 0.54 |
| Lin et al. [34] |
1. OS 2. DFS 3. LFS 4. MFS |
1. Significant better in arm A Death: arm A: n = 5 (29%), arm B: n = 11 (65%), p = 0.044 2. Significant better in arm A Recurrence: arm A: n = 7 (41%), arm B: n = 13 (76%), p = 0.033 3. Significant better in arm A Progression: arm A: n = 3 (18%), arm B: n = 10 (59%), p = 0.007 4. No significant differences Occurrence arm A: n = 6 (35%), arm B: n = 9 (53%), p = no information |
| Lin et al. [24] | 1. Grade 2 und 3 mucositis |
1. Earlier appearance in arm B Grade 2: p = 0.009, grade 3: p = 0.001 Shorter average duration in arm A Arm A: 3.55 weeks, arm B: 4.46 weeks, p = 0.033 Subgroup oral carcinoma: Earlier appearance in arm B (p < 0.001) Shorter average duration in arm A Arm A: 3.12 weeks, arm B: 5.14 weeks, p = 0.001 Subgroup nasopharyngeal carcinoma: No significant differences in onset and duration Arm A: 3.68 weeks, arm B: 4.10 weeks, p = 0.462 |
| Lyckholm et al. [30] | 1. Changes in taste and smell | 1. No significant differences: trend toward improvement over time in all groups but non-significant worsening in loss of smell in the zinc group |
| Moslemi et al. [27] | 1. Mucositis |
1. Highest severity in arm B (p < 0.0001) Significant differences in OMAS value (p < 0.05) Significant differences in the appearance in the first week prevalence arm A: 40%, arm B: 70.5%, p < 0.0001 Lower severity in arm A in week 2–7 and 8 (p < 0.003) |
| Najafizade et al. [29] | 1. Detection and recognition of the four taste qualities bitter, sour, sweet and salty |
1. Significant worsening in all four qualities in arm B at the end of RT (p’s ≤ 0.03) In arm A only change for sour (p = 0.038) Significant worsening in all four qualities in arm B 1 month after RT (p = 0.001) In arm A only higher threshold for perception of salty (p = 0.046) No group comparisons |
| Ribeiro et al. [32] |
1. Fatigue 2. QoL 3. BMI |
1. No significant differences 2. No significant differences 3. No significant differences Baseline: arm A: mean (SD) = 24.8 (5.9), arm B: 24.9 (5.1) 4th cycle of CTX: arm A: 23.9 (5.1), arm B: 24.2 (6.5), p = ns |
| Ripamonti et al. [28] |
1. Taste acuity: detection and recognition 2. Toxicity |
1. More deterioration in taste accuracy in arm B during RT Faster regeneration of taste accuracy in arm A one month after RT Significant differences in the perception of bitter and the detection of salty in arm A during RT Bitter: p = 0.015, salty: p = 0.001 Significant differences in the detection of salty, sweet and sour in arm A after RT Salty: p = 0.0241, sweet: p = 0.019, sour: p = 0.028 2. No significant differences |
| Sangthawan et al. [22] |
1. Development of oral mucositis und pharyngitis ≥ 2nd grades 2. Oral and throat pain 3. Toxicity 4. Weight |
1. No significant differences Grade 2: p = no information, grade 3: mucositis: p = 0.54, pharyngitis: p = 0.84 No differences in mean radiation doses until onset mucositis: p = 0.96, pharyngitis: p = 0.59 2. No significant differences (p = 0.77) No significant differences in using analgesics (p = 0.71) 3. Nausea and vomiting (in most cases mild, 1 patient from arm A with moderate severity) 4. No significant differences (p = no information) |
| Sangthawan et al. [33] |
1. OS 2. PFS 3. Toxicity |
1. No significant differences (p = 0.55) 2. No significant differences (p = 0.39) 3. No significant differences (p = 0.67) |
| Watanabe et al. [21] |
1. Oral mucositis 2. Pain 3. Xerostomia 4. Taste disturbance 5. Use of analgesics 6. Oral intake 7. Amount of daily meals |
1. Significant differences in occurrence of grade ≥ 2 Arm A: 40%, arm B: 86.7%, p = 0.009 2. Significant differences in grade ≥ 2 Arm A: 33.3%, arm B: 86.7%, p = 0.003 3. Significant differences in occurrence of grade ≥ 2 Arm A: 13.3%, arm B: 73.3%, p = 0.001 4. Significant differences Arm A: 19%, arm B: 87%, p = 0.0002 5. Reduced use of analgesics (p = 0.0025) 6. No significant differences Arm A: 40%, arm B: 12.5%, p = 0.113 7. Significant larger amount of meals in arm A Arm A: 78.8 (± 31.2%), arm B: 30.7 (± 37.9%), p = 0.002 |
CTX chemotherapy, DFS disease-free survival, LFS local-free survival, MFS metastases-free survival, ns not significant, OMAS Oral Mucositis Assessment Scale, OS overall survival, QoL quality of life