Time interval between neoadjuvant radiation therapy and surgery and overall survival of rectal cancer patients

Figures & data

Figure 1. Flow chart of the selection criteria.

pCR: Pathological complete response; RT: Radiation therapy.

Table 1. Baseline characteristics and factors associated with the probability of achieving pathological complete response of patients diagnosed with rectal and rectosigmoid cancer between 2004–2019 (n = 28,656) and reported to the National Cancer Database.

Variable		pCR n = 4,455 (15.6%)	No pCR n = 24,201 (84.4%)	Total n = 28,656	Multivariable analysis OR (95% CI)	p-value
	Continuous (median and ranges)	59 (21–90)	58 (18–90)	58 (18–90)	1.01 (1.00–1.01)	0.01
Year of diagnosis	2004–2013	1,980 (44.4)	12,148 (50.2)	14,128 (49.3)	Ref
	2014–2019	2,475 (55.6)	12,053 (49.8)	14,528 (50.7)	1.21 (1.13–1.31)	0.001
Sex	Male	2,728 (61.2)	15,110 (62.4)	17,838 (62.3)	Ref
	Female	1,727 (38.8)	9,091 (37.6)	10,818 (37.7)	1.07 (0.99–1.16)	0.06
Race	White	3,860 (87.1)	20,767 (86.3)	24,627 (86.4)	Ref
	Black	296 (6.7)	1,951 (8.1)	2,247 (7.9)	0.90 (0.78–1.04)	0.16
	Non-White non-Black	276 (6.2)	1,338 (5.6)	1,614 (5.7)	1.08 (0.93–1.26)	0.31
	Unknown	23	145	168
Time between RT completion and surgery	≤4 weeks	78 (1.8)	793 (3.3)	871 (3.0)	Ref
	5–8 weeks	1,793 (40.3)	11,079 (45.8)	12,872 (44.9)	1.63 (1.24–2.14)	0.001
	9–12 weeks	2,134 (47.9)	9,882 (40.8)	12,016 (41.9)	2.16 (1.64–2.84)	0.001
	13–16 weeks	328 (7.3)	1755 (7.2)	2,083 (7.3)	1.82 (1.35–2.46)	0.001
	17–20 weeks	84 (1.9)	472 (2.0)	556 (2.0)	1.73 (1.19–2.52)	0.004
	21–24 weeks	38 (0.9)	220 (0.9)	258 (0.9)	1.75 (1.08–2.82)	0.02
T Stage	I and II	395 (8.9)	1,304 (5.4)	1,699 (5.9)	Ref
	III and IV	40,601 (91.1)	22,895 (94.6)	26,957 (94.1)	0.57 (0.50–0.66)	0.001
N stage	0	1,891 (42.4)	9,994 (41.3)	11,885 (41.5)	Ref
	I	2,111 (47.4)	11,202 (46.3)	13,313 (46.5)	0.91 (0.84–0.98)	0.001
	III	453 (10.2)	3,005 (12.4)	3,458 (12.0)	0.71 (0.62–0.81)	0.001
Chemotherapy sequence	Neoadjuvant and adjuvant chemotherapy within 7 days of RT	3,694 (82.9)	19,856 (82.1)	23,550 (82.2)	Ref
	Neoadjuvant and adjuvant chemotherapy but >7 days after RT	137 (3.1)	879 (3.6)	1,016 (3.5)	0.77 (0.62–0.96)	0.02
	Neoadjuvant and adjuvant chemotherapy but >days before RT	545 (12.2)	2,836 (11.7)	3,381 (11.8)	0.98 (0.88–1.10)	0.74
	Adjuvant chemotherapy	79 (1.8)	630 (2.6)	709 (2.5)	0.78 (0.60–1.02)	0.07
RT dose	25 Fr with 50 Gy or 28 Fr with 50.4 Gy	2,734 (61.4)	15,413 (63.7)	18,147 (63.3)	Ref
	30 Fr with 54 Gy	1,570 (35.2)	7,939 (32.8)	9,509 (33.2)	0.91 (0.84–0.98)	0.01
	All other doses	151 (3.4)	849 (3.5)	1,000 (3.5)	0.99 (0.81–1.23)	0.98
Charlson/Deyo comorbidity score	0	3,589 (80.6)	19,309 (79.8)	22,898 (79.9)	Ref
	1	639 (14.3)	3,787 (15.7)	4,426 (15.5)	0.90 (0.82–1.00)	0.06
	≥2	227 (5.1)	1,105 (4.6)	1,332 (4.6)	1.04 (0.88–1.23)	0.64
Neighborhood education level	≥10.9% NHD	1,687 (43.8)	9,714 (46.5)	11,401 (46.0)	1.02 (0.94–1.12)	0.63
	<10.9% NHD	2,164 (56.2)	1,1201 (53.5)	13,365 (54.0)	Ref
	Unknown	604	3,286	3,890
Household income	<$50,353	1,419 (37.0)	8,593 (41.2)	10,012 (40.5)	0.86 (0.79–0.94)	0.001
	≥$50,353	2,421 (63.0)	12,287 (58.8)	14,708 (59.5)	Ref
	Unknown	615	3,321	3,936
Insurance	No	134 (3.0)	1,150 (4.8)	1,284 (4.5)	0.71 (0.58–0.87)	0.001
	Yes	4,273 (97.0)	22,746 (95.2)	27,019 (95.5)	Ref
	Unknown	48	305	353
Treatment facility type	Academic	1,460 (34.6)	7,374 (32.20)	8,834 (32.6)	Ref
	Community	2,766 (65.4)	15,528 (67.8)	18,294 (67.4)	0.90 (0.83–0.97)	0.008
	Unknown	229	1,299	1,528
Place of living	Urban	4,222 (97.9)	22,866 (97.6)	27,088 (97.6)	Ref
	Rural	90 (2.1)	573 (2.4)	663 (2.4)	0.94 (0.73–1.21)	0.62
	Unknown	143	762	905

Multivariable analysis was adjusted for age at diagnosis, sex, race, income, education, health insurance, treatment hospital type, place of residence, T stage, N stage, comorbidity score, chemotherapy sequence with surgery, and year of diagnosis.

CI: Confidence interval; NHD: No high school degree; OR: Odds ratio; pCR: Pathological complete response; RT: Radiation therapy.

Table 2. Factors associated with overall survival of patients diagnosed with rectal and rectosigmoid cancer between 2004 and 2019 and reported to the National Cancer Database.

Variable		Multivariable analysis HR (95% CI)	p-value
	Continuous (median and ranges)	1.04 (1.04–1.04)	0.001
Year of diagnosis	2004–2013	Ref
	2014–2019	1.00 (0.94–1.07)	0.95
Sex	Male	Ref
	Female	0.82 (0.77–0.87)	0.001
Race	White	Ref
	Black	1.19 (1.08–1.31)	0.001
	Non-White, non-Black	0.85 (0.74–0.97)	0.02
Time between RT completion and surgery	≤4 weeks	Ref
	5–8 weeks	0.90 (0.78–1.04)	0.16
	9–12 weeks	1.01 (0.87–1.17)	0.90
	13–16 weeks	1.27 (1.07–1.50)	0.007
	17–20 weeks	1.63 (1.31–2.02)	0.001
	21–24 weeks	1.73 (1.31–2.28)	0.001
pCR	Yes	Ref
	No	2.10 (1.90–2.32)	0.001
T Stage	I and II	Ref
	III and IV	1.32 (1.15–1.52)	0.001
N stage	0	Ref
	I	1.05 (0.99–1.11)	0.12
	III	1.29 (1.17–1.41)	0.001
Chemotherapy sequence	Neoadjuvant and adjuvant chemotherapy within 7 days of RT	Ref
	Neoadjuvant and adjuvant chemotherapy but >7 days after RT	1.02 (0.89–1.17)	0.79
	Neoadjuvant and adjuvant chemotherapy but >days before RT	1.05 (0.96–1.15)	0.28
	Adjuvant chemotherapy	0.91 (0.76–1.093)	0.31
RT dose	25 Fr with 50 Gy or 28 Fr with 50.4 Gy	Ref
	30 Fr with 50 Gy	0.95 (0.90–1.01)	0.12
	All other doses	1.19 (1.03–1.37)	0.02
Charlson/Deyo comorbidity score	0	Ref
	1	1.27 (1.18–1.36)	0.001
	≥2	1.78 (1.60–1.98)	0.001
Neighborhood education level	≥10.9% NHD	1.06 (0.99–1.13)	0.11
	<10.9% NHD	Ref
Household income	<$50,353	1.12 (1.04–1.19)	0.001
	≥$50,353	Ref
Insurance	No	1.28 (1.13–1.45)	0.001
	Yes	Ref
Treatment facility type	Academic	Ref
	Community	1.31 (1.23–1.39)	0.001
Place of living	Urban	Ref
	Rural	1.02 (0.86–1.21)	0.85

Multivariable analysis was adjusted for age at diagnosis, sex, race, income, education, health insurance, treatment hospital type, place of residence, T stage, N stage, comorbidity score, chemotherapy sequence with surgery, and year of diagnosis.

CI: Confidence interval; HR: Hazard ratio; NHD: No high school degree; pCR: Pathological complete response; RT: Radiation therapy.

Figure 2. Hazard ratio [no pCR vs. pCR] as a function of the time interval between RT completion and surgery.

CI: Confidence interval; pCR: Pathological complete response; RT: Radiation therapy.

Table 3. Overall survival of patients diagnosed with rectal and rectosigmoid cancer stratified by pathological complete response status.

Variable		Multivariable analysis HR (95% CI)	p-value
Patients who achieved pCR
Time between RT completion and surgery	≤4 weeks	Ref
	5–8 weeks	0.71 (0.37–1.36)	0.30
	9–12 weeks	0.75 (0.39–1.43)	0.39
	13–16 weeks	0.70 (0.34–1.45)	0.33
	17–20 weeks	1.05 (0.44–2.56)	0.91
	21–24 weeks	1.06 (0.33–3.44)	0.92
Patients who did not achieve pCR
Time between RT completion and surgery	≤4 weeks	Ref
	5–8 weeks	0.90 (0.78–1.05)	0.19
	9–12 weeks	1.02 (0.88–1.19)	0.78
	13–16 weeks	1.32 (1.10–1.57)	0.002
	17–20 weeks	1.67 (1.33–2.08)	0.001
	21–24 weeks	1.79 (1.343–2.379)	0.001

Multivariable analysis was adjusted for age at diagnosis, sex, race, income, education, health insurance, treatment hospital type, place of residence, T stage, N stage, comorbidity score, chemotherapy sequence with surgery, and year of diagnosis.

CI: Confidence interval; HR: Hazard ratio; pCR: Pathological complete response.