Objectives: The use of parotid gland (PG) sparing intensity-modulated radiotherapy (IMRT) significantly reduces high grade xerostomia. Data on saliva composition analysis post radiotherapy (RT) is limited pre-IMRT due to poor residual salivary flow. Chemotherapy (Ch) is suggested to worsen toxicity from RT. Ch-IMRT improves 5 year overall survival vs. IMRT alone by ~6%, however use of induction Ch prior to Ch-IMRT is controversial. We present interim analysis of PG saliva flow rate and composition for patients treated with IMRT+/- Ch within five trials at RMH.
Methods: Stimulated and unstimulated PG salivas were collected from right and left glands using Lashley cups (2% citric acid). Samples were collected at baseline, 3, 6, 12 and 24 months (m) post-RT. Salivas were analysed for protein and ionic components using ELISA, BCA assay and ICP-mass spectrometry. Two groups of stimulated PG salivas, A (IMRT alone) and B (Induction-Ch and Ch-IMRT) were compared. Samples were analysed for early (3-6m) and late (12-24m) changes.
Results: Baseline parameters were similar for groups A and B, except total protein concentration (TP) and age (table 1). Sequential results (table 2) showed significant changes in several parameters in group A: a persistent (early and late) decrease in TP and calcium concentration (Ca2+), a transient (early) increase in lactoferrin and sodium concentration (Na+) and a decrease in flow rate, returning to normal in late samples, also a late reduction in beta-2-microglobulin. Group B showed no significant early or late changes except a late reduction in Na+.
Table 1-Baseline parameters (95% CI) Stimulated PG saliva (*= p<0.05)
|
|
Group A |
Group B |
| Patient (n) |
8 |
8 |
| Samples (n) |
14 |
14 |
| Mean age (Yr) |
65.2 (57.1-73.2) |
52.6* (46.2-59.0) |
| Gender (M,F) |
7, 1 |
6, 2 |
| Mean PG dose (Gy) |
29.1 (21.1-37.1) |
27.2 (24.6-29.8) |
| TP (mg/ml) |
2.41 (1.71-3.1) |
1.54* (1.1-1.99) |
| PG Flow (ml/min) |
0.22 (0.11-0.33) |
0.32 (0.18-0.45) |
| IgA Conc (µg/ml) |
337.2 (210.3-464.2) |
265.6 (96.7-434.5) |
| B2M Conc (µg/ml) |
1.19 (0.78-1.6) |
0.98 (0.66-1.29) |
| LF Conc (µg/ml) |
47.85 (24.3-71.38) |
50.72 (5.61-95.82) |
| Ca2+Conc (mmol/l) |
1.78 (1.31-2.24) |
2.05 (1.67-2.42) |
| Na+Conc (mmol/l) |
1.57 (0.87-2.28) |
3.5 (1.87-5.13) |
|
Table 2 - % of Baseline (100%) (+/-95% CI) Stimulated PG saliva (*= p<0.05)
|
|
Group A |
Group B |
|
3-6m (n=14) |
12-24m (n=4) |
3-6m (n=6) |
12-24m (n=9) |
| T. Protein |
64.6%* +/-9.4
|
64.2%* +/-24
|
98.7% +/-41.3
|
108% +/-42
|
| PG Flow |
41.6%* +/-17
|
241% +/-241
|
80.7% +/- 80.5
|
139% +/-134
|
| IgA Conc |
99.8% +/-29.2
|
76.5% +/-66.5
|
173.3% +/-173
|
128.5% +/-59.1
|
| B2M Conc |
124.9% +/-53.9
|
59.7%* +/-33
|
172.7% +/-96.2
|
208.8% +/-168
|
| LF Conc |
335.6%* +/-205
|
170.3% +/-163 |
375.7% +/-375 |
202.3% +/-136 |
| Ca2+Conc |
70.1%* +/-4.7
|
70.7%* +/-18
|
96% +/-20.5
|
100.1% +/-27.6
|
| Na+Conc |
206.9%* +/-89.5
|
142.5% +/-142
|
156.8% +/-92.5
|
79.6%*+/-19.7
|
|
Conclusions: These results indicate that induction Ch then Ch-IMRT does not worsen PG acinar or ductal dysfunction vs. IMRT alone. Increased Na+ with decreased Ca2+ and TP indicate transient ductal and persistent acinar dysfunction in group A. A persistent decrease in stimulated and unstimulated Ca2+ to 24m may have implications for dental health.