Overall, 127 patients were included in the research, categorized into the SF and HF groups, comprising of 63 and 64 patients, respectively. Average age (years) in SF was 63.9 ± 11.35, which was younger compared to 67.9 ± 10.4 in HF (p = 0.04). Other statistically significant differences (p < 0.05) were seen; SF patients had higher rates of COPD (29%) compared to HF patients (9%), higher rates of past smoking (90% vs 70%) and more active smoking (46% vs 19%). General characteristics and medical history comparison is depicted in Table 1.
Tumor subsites were glottic (49%), supraglottic (46%) and subglottic (5%) in the SF group, while there were exclusively glottic tumors (100%) in the HF group (p = 0.001). In the SF group, 29% of the patients and 71% of the patients had early (I/II) and advanced stage (III/IV) laryngeal tumors, respectively, compared to 98% and 2% in the HF group who presented with early and advanced-stage disease, respectively (p = < 0.001). Detailed tumor staging between the two groups, as well as recurrence rates and all-cause mortality are depicted in Table 1.
Prescription and usage of opioids during radiation treatments were evaluated and compared between the SF and HF groups. In SF 35% patients were prescribed Fentanyl patches, compared to 44% in HF group (p = 0.2). The mean dosage of Fentanyl patches in HF patients was 15 mg for every 72 hours, compared to 8.4 mg in SF patients (p = 0.002). Similarly, the mean SOS dosage of Oxycodone was also higher in HF patients, compared to SF patients (3.2 mg versus 2.1 mg, in HF and SF, respectively), although not statistically significant (p = 0.08); Moreover, higher rates of opioid use for longer periods (more than one month), was seen in HF (24%) compared to SF (14%), although not statistically significant (p = 0.2). Results are depicted in detail in Table 3. A sub-group comparison analyses based on smoking status and steroidal treatment during radiation therapy, failed to find any significant differences in Fentanyl and Oxycodone dosages for these factors in either the SF or HF groups (data not shown). A comparison within the HF group, between T1 patients treated with 63Gy and T2 patients treated with 65.5Gy also did not find any significant differences regarding Fentanyl or Oxycodone dosage (data not shown).
Weight loss rates (defined as loss of more than 1 kg) were comparable and seen in 51 (81%) and 48 (75%) patients in the SF and HF groups, respectively (N.S); with an average weight loss of 4.2 and 3.2 kg in SF and HF, accordingly (N.S). Steroids were given to 31% of patients, in both groups. Patients in HF group who received steroids demonstrated a mild weight gain (1.3kg, p = 0.001), compared to HF patients who did not receive steroids. Further details are depicted in Table 2 and Fig. 1.
Table 2
Treatment-related toxicity in SF and HF groups
|
Standard fractionation (SF), N = 63
|
Hypofractionation (HF), N = 64
|
Statistical significance
P-value
|
Hospitalization
|
19% (12)
|
13% (8)
|
0.3
|
Oral mucositis
|
13% (8)
|
14% (9)
|
0.8
|
Laryngeal mucositis
|
8% (5)
|
8% (5)
|
0.95
|
Treatment break
|
13% (8)
|
9% (6)
|
0.4
|
Dehydration
|
48% (30)
|
23% (15)
|
0.03
|
Steroids
|
31% (20)
|
31% (20)
|
0.95
|
Opioids during treatment
|
35% (22)
|
45% (29)
|
0.2
|
Opioids 1 month after end of treatment
|
14% (9)
|
24% (15)
|
0.2
|
Average Fentanyl patch dosage
|
8.4 ± 16.5
|
15.7 ± 22.8
|
0.002
|
Average SOS Oxycodone dosage
|
2.1 ± 3.1
|
2.9 ± 3.6
|
0.08
|
Average weight loss (Kg)
|
-4.2 ± 4.6
|
-3.2 ± 7.3
|
0.6
|
In a multivariate logistic regression analysis, comparing odds ratio in HF versus SF patients, the following variables were found significant: Male gender (OR = 2.4, p = 0.002), age over 60 (OR = 3.1, p = 0.003), Max Fentanyl dose (OR = 1.2, p = 0.03), average weight loss more than 1 kg (OR = 0.14, p = 0.002).
In subgroup analysis of SF patients, a trend of increased toxicity was seen in those who were given CT compared to RT alone. Rates of hospitalization, dehydration, laryngeal and oral mucositis were higher, although not significant, in patients undergoing concomitant chemotherapy with RT. Correspondingly, there was a significant increase in the use of steroids and opioids (both fentanyl patch and Oxycodone) in SF patients undergoing chemoradiotherapy compared with RT alone (Table 3 and Fig. 1).
Table 3
Chemotherapy related morbidity in SF patients
|
Standard fractionation RT (N = 13)
|
Standard fractionation RT + CT (N = 50)
|
Statistical significance
P-value
|
Average Fentanyl patch dosage
|
2.9 ± 4.3
|
9.8 ± 5.1
|
0.05
|
Average SOS Oxycodone dosage
|
0.9 ± 1.5
|
2.4 ± 0.9
|
0.002
|
Hospitalization
|
15% (2)
|
20% (10)
|
0.8
|
Oral mucositis
|
8% (1)
|
16% (8)
|
0.4
|
Laryngeal mucositis
|
8% (1)
|
8% (4)
|
0.6
|
Dehydration
|
33% (5)
|
54% (27)
|
0.1
|
Steroids
|
15% (2)
|
36% (18)
|
0.03
|
Average weight loss (Kg)
|
-2.8 ± 3.69
|
-4.6 ± 4.8
|
0.6
|