Pain response

Summary of pain response outcomes from individual studies is listed in Table 2. The arms treated with SBRT report pain response of 70 % immediately after treatment (Sakr et al. 2020);

After one month of SBRT Pichon et al. (2016) report a significant decrease in VAS score from 2,40 to 1,35. After one month pain response rates varied from 44 % to 85 % (Nguyen et al. 2019, Jin et al. 2007); Three months after SBRT pain response varied from 33% to 95 % (Nguyen et al. 2019, Wardak et al. 2019); Six months after SBRT pain response rates varied from 69% to 83 % (Ito et al. 2019, van de Ven et al. 2020).

Overall pain response rate after SBRT reported by Van de Ven et al. (2020) was 84 % with a median duration of six months (range 0 – 12.5). The difference was not statistically significant compared to conventional RT with overall pain response rate of 81% and a median duration of

5.75 months (range 0.25 – 14.5) (van de Ven et al. 2020). From the systematic review by Spencer et al. (2019) the range of pain response outcomes of SBRT treatment varied from 27 % to 98 % (Spencer et al. 2019). In a study by Sprave et al. (2018b), no significant differences were reported at three months, but significant lower VAS scores were found at six months in SBRT group

compared with conventional RT (Sprave et al. 2018b).

Table 2. Pain response outcome summary

N/A At four weeks after SBRT overall pain relief was seen in 85 % of the patients treated. Complete pain relief was achieved in 38 % of patients. Partial pain relief was achieved in 47 % of patients.

Nguyen et al. 2019

160 Multiple Lesions >4cm 12 Gy / 1Fx Lesions <4cm 16 Gy / 1 Fx

30 Gy / 10 The response rates (CR + PR) at one month were 44 % for the SBRT group vs 30 % for the conventional RT group (P = .18), and the corresponding rates at three months were 38 % vs 21 % (P = .05)

Pichon et al. 2016

30 Spine 9 Gy / 3 Fx N/A The mean pain scores diminished significantly in one month (1.35; P=.0125) and 3 months (0.77; P<.0001) after treatment compared with pain scores at study entry (2.49).

Author year

N Site Mean SBRT

Dose/Fractionation (range)

Mean Conv-RT Dose/Fractionation (range)

Outcome pain response

Redmond et al. 2020

35 Spine 30 Gy / 5 Fx N/A In comparison to the baseline, VAS score at the time of last recorded follow-up was reduced in 54.2 %, stable in 12.5 %, increased by one point in 8.3 % and

increased by two or more points in 25 %; 20.8 % of patients reported no pain in any part of their body at the time of last follow-up.

Sakr et al.

2020

22 Multiple 27 Gy / 3 Fx 20 Gy / 5 Fx Complete pain relief was not documented in any patient in both groups. Partial pain relief after three months was comparable with a p-value of 0.6.

Immediate partial pain relief was seen in seven patients (70 %) of 27Gy/3fr schedule versus only one patient (8 %) in 20Gy/5fr schedule with a p-value of 0.06. The increase in immediate pain relief in the 27Gy arm was numerically but not statistically significant.

Author

N/A Studies included report higher rates of pain response following SBRT than have previously been reported following conventional RT. However, these outcomes may very well be the result of study methodology and, most importantly selection bias.

Sprave et al. 2018b

55 Spine 24 Gy / 1 Fx 30 Gy / 10 Fx At three months after SBRT no significant differences for VAS score between groups (p = 0.13). At six months significantly lower VAS values were reported in the SBRT group (p = 0.002). There were no differences in OMED consumption at three (p = 0.761) and six months (p = 0.174). There was a trend toward improved pain response in the SBRT arm at three months (p = 0.057), but significantly so after six months (p = 0.003).

Author

At a median follow-up of 23 weeks (range 1-58) and 24 weeks (range 0-50), pain response was achieved in 81% and 84% among the patients treated with conventional RT and SBRT, respectively.

Wardak et al. 2019

35 Spine 20 Gy / 1 GTV and 14 Gy / 1 Fx for bone marrow

Historical control The three-month pain response was significantly improved compared to RTOG 9714: 95 % versus 51 % (P < .0001). The local control with a median follow-up of 9.6 months was 92 %.

Meta-analysis outcome for pain response

Five studies fulfilled the criteria for meta-analysis for pain response. See Table 5. Pain response categorization was based on patient reported VAS or NRS ranged (0-10) and analgesic

consumption (MEDs or OMED) (Sprave et al. 2018b, Nguyen et al. 2019, Wardak et al. 2019, Sakr et al. 2020, van de Ven et al. 2020). Definition was as follow:

• Complete response (CR): was defined as VAS = 0 without an increase in analgesic use.

• Partial response (PR): Reduction of two or more in pain score from baseline site without increasing analgesic intake, or analgesic reduction of 25 % or more from baseline without an increase in pain.

• Pain progression (PP): Increase in pain score of two or more above baseline or an increase of 25 % or more in analgesic intake compared with baseline.

• Indeterminate response (IR): Any response that is not categorized as CR, PR, or PP.

• Responders (CR + PR)

• No responders (PP + IR)

Scores provided by the authors had equivalency and were all assessed by the patients.

Categorization and analgesic used were also comparable allowing to perform a second

categorization into dichotomous data as responders and no responders. Using the “Per-protocol analysis data” instead of “Intent to treat data” form the studies the results from the

meta-analysis for month three and month six are presented in figures 6 and 7, respectively. Results present a significant improvement of 38 % in pain response in SBRT treatment compared to conventional RT after three months with a 95 % confidence interval of [1.08, 1.71]. See figure 6.

Heterogeneity among studies is moderated. At six months the was difference towards

improvement of 27 % in SBRT treatment compared to conventional RT but not significant with a 95 % confidence interval [0.92, 1.76].

Figure 6. SBRT vs. Conventional RT pain response at three moths forest plot.

Figure 7. SBRT vs. Conventional RT pain response at six months forest plot.