https://rpubs.com/alex_istrate/534380

1 Pre-analysis

2 Abstract

We included 43 patients, of which 22 (51.2%) received neoadjuvant chemotherapy (NAC, 2 to 6 cycles, median=4). Patients’ stage ranged from IB to IVB with most common IIIB in NAC and IIB in controls (Mann-Whitney p=0.011). Stage was significantly correlated to the number of neoadjuvant chemotherapy cycles (RSpearman=0.58, p<0.001).

NAC patients received a statistically smaller median number of chemotherapy cycles (2, ranging from 1 to 5) as the controls (4, 1 to 5, p<0.001). NAC patients lost significalnty more of their planned cycles compared to controls (0 to 4, median=3 vs. 0 to 2, median=1, p<0.001). NAC patients received significantly less total chemotherapy (expresed as a fraction of the total planned number of cycles), compared to controls (20% to 100%, median=40%, vs 60% to 100%, median=80%, p<0.001). The total chemotherapy cycles received are significantly correlated with the number of neoadjuvant chemotherapy cycles (RSpearman=-0.610, p<0.001). However, NAC patients received a statisitcaly similar total chemotherapy (expresed as a fraction of the total planned dose) compared to controls (75% to 101%, median=92%, vs 63% to 100%, median=90%, p=0.402). The total chemotherapy received is not significantly correlated with the number of neoadjuvant chemotherapy cycles (RSpearman=-0.077, p=0.623).

Toxicity was measured by blood cell counts, hemoglobin and creatinin measurements and urinary and digestive toxicity.

2.1 Leucocytes

NAC patients showed insignifficant toxicity by leucocyte counts (median=2460, 850:6310 vs median=2610, 1500:5600, p=437), compared to cotrols, as well as grade of leucopenia (p=803).

Lowest leucocyte count is not significantly correlated with the number of neoadjuvant chemotherapy cycles (RSpearman=-0.223, p=0.150), even after adjusting for total chemotherapy received (RSpearman=-0.227, p=0.149), but showed an increased correlation after adjusting for stage (RSpearman=-0.499, p<0.001).

On average, every additional neadjuvant chemotherapy cycle decreased the neutrophile count by 81.90 ±84.52 cells/mL (non significant). After adjusting for total chemotherapy received the average WBC count decreased by 74.84 ±83.55 cells/mL (non significant) and after adjusting for stage, the average neutrophile count decreased by 260.96 ** ±94.59 cells/mL. When adjusting for both at the same time, the average neutrophile count decreased by 260.17 ** ±91.74 cells/mL.

2.2 Neutrophiles

NAC patients showed insignifficant toxicity by neutrophiles counts (median=1520, 720:5190 vs median=1960, 950:3970, p=0.087), compared to cotrols, as well as grade of neutropenia (p=0.194).

Lowest Neutrophile count was significantly correlated with the number of neoadjuvant chemotherapy cycles (RSpearman=-0.334, p=0.028), even after adjusting for total chemotherapy received (RSpearman=-0.329, p=0.033), and showed the strongest correlation after adjusting for stage (RSpearman=-0.589, p<0.001). Of special attention was the fact that Pearson’s correlation coefficient did not show significant corelations with the number of neoadjuvant chemotherapy cycles alone or adjusting for chemotherapy.

On average, every additional neadjuvant chemotherapy cycle decreased the neutrophile count by 96.74 ±71.68 cells/mL (non significant). After adjusting for total chemotherapy received the average neutrophile count decreased by 88.13 ±68.83 cells/mL (non significant) but after adjusting for stage, the average neutrophile count decreased by 272.49 *** ±76.64 cells/mL. When adjusting for both at the same time, the average neutrophile count increased by 271.54 *** ±70.34 cells/mL.

2.3 Lymphocytes

NAC patients showed insignifficant toxicity by lymphocyte counts (median=405, 70:950 vs median=390, 150:660, p=0.444), compared to cotrols, as well as grade of lymphopenia (p=0.693).

Lowest lymphocyte count is not significantly correlated with the number of neoadjuvant chemotherapy cycles (RSpearman=0.085, p=0.586), even after adjusting for total chemotherapy received (RSpearman=0.076, p=0.634) nor after adjusting for stage (RSpearman=0.140, p=0.377).

On average, every additional neadjuvant chemotherapy cycle increased the lymphocyte count by 2.16 ±11.51 cells/mL (non significant). After adjusting for total chemotherapy received the average lymphocyte count increased by 1.53 ±11.55 cells/mL (non significant) and after adjusting for stage, the average lymphocyte count increased by 10.22 ±14.28 cells/mL (non significant). When adjusting for both at the same time, the average lymphocyte count decreased by 10.15 ±14.28 cells/mL (non significant).

2.4 Platelets

NAC patients showed more toxicity by platelet counts with only a tendency to statistical significance (median=126.5, 29:271 vs median=150, 97:247, p=0.070), compared to cotrols, but not by grade of thrombocytopenia (p=0.264).

Lowest platelet count is significantly correlated with the number of neoadjuvant chemotherapy cycles (RSpearman=-0.333, p=0.029), even after adjusting for total chemotherapy received (RSpearman=-0.338, p=0.029) and after adjusting for stage (RSpearman=-0.376, p=0.014).

On average, every additional neadjuvant chemotherapy cycle insignificantly decreased the platelet count by 6.66 ±3.77 cells/mL. After adjusting for total chemotherapy received the average platelet count insignificantly decreased by 6.62 ±3.83 cells/mL and after adjusting for stage, the average platelet count insignificantly decreased by 9.06 ±4.69 cells/mL. When adjusting for both at the same time, the average platelet count insignificantly decreased by 9.06 ±4.75 cells/mL.

2.5 Hemoglobin

NAC patients showed signifficantly lower hemoglobin (median=10.15, 7.6:12.9 vs median=11.0, 9.0:12.4, p=0.004), compared to cotrols, but not a higher grade of anemia (p=0.146).

Lowest hemoglobin level is significantly correlated with the number of neoadjuvant chemotherapy cycles (RSpearman=-0.475, p=0.001), even after adjusting for total chemotherapy received (RSpearman=-0.471, p=0.002). After adjusting for stage, the partial correlation only showed a tendency towards statisatical significance (RSpearman=-0.288, p=0.065).

On average, every additional neadjuvant chemotherapy cycle decreased the hemoglobin level by 0.24** ±0.07 cells/mL. After adjusting for total chemotherapy received the average hemoglobin level decreased by 0.23** ±0.07 cells/mL and after adjusting for stage, the average hemoglobin level decreased by 0.16 ±0.09 cells/mL (not significant). When adjusting for both at the same time, the average hemoglobin level decreased by 0.16 ±0.09 cells/mL (not significant).

2.6 Other toxicities

Elevated creatinin levels were found in 9.1% of the NAC patients and 14.3% of the control patients (OR=1.67 [0.25, 11.13], p=0.664). Among cases, 36.4% had registered urinary toxicity compared to 33.3% among controls (OR=1.14 [0.33, 4.01, p>0.999). Digestive toxicity grade > 0 were found in 72.7% on the NAT patients (with 3 patients - 13.6% grade 2 and 1 patient - 4.5% grade 3) and 71.4% (with 5 patients - 11.6% grade 2) of the control patients (p=0.749). RT was given to Lombo-aortics in 45.5% of the NAC patients and only one of the control patinents (OR=16.67 [1.89, 146.95], p=0.004).

3 Results

Table 1: All recorded paramenters of the paticipants, for each treatment group.

Variable

Details

NAC

Control

Total

Statistics

Group

22 (51.2%)

21 (48.8%)

43

Neoadjuvant chemotherapy cycles

μ ±SD

3.82 ±0.907

0.00 ±0.0

1.95 ±2.03

MW: p<0.001

M (min:max)

4 (2:6)

0 (0:0)

2 (0:6)

Age at diagnosis (years)

μ ±SD

53.59 ±11.2

56.00 ±10.1

54.74 ±10.6

T-test: p=0.469

M (min:max)

53.5 (29:71)

55.5 (36:72)

54 (29:72)

Stage

IB

0

1 (4.8%)

1 (2.3%)

V=0.59 (p=0.011)

IIA

0

1 (4.8%)

1 (2.3%)

IIB

5 (22.7%)

14 (66.7%)

19 (44.2%)

IIIA

0

0

0

IIIB

10 (45.5%)

5 (23.8%)

15 (34.9%)

IVA

5 (22.7%)

0

5 (11.6%)

IVB

2 (9.1%)

0

2 (4.7%)

Stage (numeric)

μ ±SD

3.48 ±0.626

2.67 ±0.532

3.08 ±0.707

MW: p<0.001

M (min:max)

3.5 (2.5:4.5)

2.5 (1.5:3.5)

3.5 (1.5:4.5)

Dose used

Cis 30mg/m²

3 (13.6%)

3 (14.3%)

6 (14.0%)

OR=0.95 [0.17, 5.32] (p>0.999)

Cis 40mg/m²

19 (86.4%)

18 (85.7%)

37 (86.0%)

Cis dose (mg/m²)

μ ±SD

38.64 ±3.51

38.57 ±3.59

38.60 ±3.51

MW: p=0.968

M (min:max)

40 (30:40)

40 (30:40)

40 (30:40)

Concomitant chemotherapy cycles

μ ±SD

2.23 ±1.02

3.67 ±0.856

2.93 ±1.18

MW: p<0.001

M (min:max)

2 (1:5)

4 (2:5)

3 (1:5)

Lost cycles

μ ±SD

2.77 ±1.02

1.19 ±0.814

2.00 ±1.21

MW: p<0.001

M (min:max)

3 (0:4)

1 (0:2)

2 (0:4)

Concomitant chemotherapy
cycles received (%)

μ ±SD

0.445 ±0.204

0.762 ±0.163

0.60 ±0.243

MW: p<0.001

M (min:max)

0.4 (0.2:1)

0.8 (0.6:1)

0.6 (0.2:1)

Chemotherapy received (%)

μ ±SD

0.905 ±0.0734

0.889 ±0.0823

0.897 ±0.0773

MW: p=0.402

M (min:max)

0.92 (0.75:1.01)

0.9 (0.63:0.99)

0.91 (0.63:1.01)

Lowest Leucocyte count

μ ±SD

2670.45 ±1166.5

2891.90 ±1072.4

2778.60 ±1113.8

MW: p=0.437

M (min:max)

2460 (850:6310)

2610 (1500:5600)

2500 (850:6310)

Leucopenia grade

0

2 (9.1%)

3 (14.3%)

5 (11.6%)

V=0.19 (p=0.803)

1

4 (18.2%)

4 (19.0%)

8 (18.6%)

2

9 (40.9%)

10 (47.6%)

19 (44.2%)

3

6 (27.3%)

4 (19.0%)

10 (23.3%)

4

1 (4.5%)

0

1 (2.3%)

Lowest Neutrophile count

μ ±SD

1854.77 ±1056.2

2184.29 ±826.7

2015.70 ±954.5

MW: p=0.087

M (min:max)

1520 (720:5190)

1960 (950:3970)

1860 (720:5190)

Neutropenia grade

0

6 (27.3%)

10 (47.6%)

16 (37.2%)

V=0.33 (p=0.194)

1

5 (22.7%)

7 (33.3%)

12 (27.9%)

2

7 (31.8%)

3 (14.3%)

10 (23.3%)

3

4 (18.2%)

1 (4.8%)

5 (11.6%)

Lowest Lymphocyte count

μ ±SD

405.00 ±166.9

371.00 ±132.0

388.40 ±150.1

MW: p=0.444

M (min:max)

405 (70:950)

390 (150:660)

390 (70:950)

Lymphopenia grade

1

1 (4.5%)

0

1 (2.3%)

V=0.18 (p=0.693)

2

3 (13.6%)

4 (19.0%)

7 (16.3%)

3

16 (72.7%)

14 (66.7%)

30 (69.8%)

4

2 (9.1%)

3 (14.3%)

5 (11.6%)

Lowest Platelet count

μ ±SD

130.91 ±56.5

159.00 ±41.1

144.63 ±51.0

T-test: p=0.070

M (min:max)

126.5 (29:271)

150 (97:247)

142 (29:271)

Thrombocytopenia grade

0

18 (81.8%)

18 (85.7%)

36 (83.7%)

V=0.30 (p=0.264)

1

1 (4.5%)

3 (14.3%)

4 (9.3%)

2

1 (4.5%)

0

1 (2.3%)

3

2 (9.1%)

0

2 (4.7%)

Lowest Hemoglobin

μ ±SD

10.15 ±1.06

11.05 ±0.823

10.59 ±1.05

T-test: p=0.004

M (min:max)

10.15 (7.6:12.9)

11 (9:12.4)

10.6 (7.6:12.9)

Anemia grade

0

1 (4.5%)

2 (9.5%)

3 (7.0%)

V=0.35 (p=0.146)

1

14 (63.6%)

18 (85.7%)

32 (74.4%)

2

6 (27.3%)

1 (4.8%)

7 (16.3%)

3

1 (4.5%)

0

1 (2.3%)

Creatinine level

normal

20 (90.9%)

18 (85.7%)

38 (88.4%)

OR=1.67 [0.25, 11.13] (p=0.664)

elevated

2 (9.1%)

3 (14.3%)

5 (11.6%)

Urinary toxicity

8 (36.4%)

7 (33.3%)

15 (34.9%)

OR=1.14 [0.33, 4.01] (p>0.999)

Digestive toxicity

0

6 (27.3%)

6 (28.6%)

12 (27.9%)

V=0.17 (p=0.749)

1

12 (54.5%)

13 (61.9%)

25 (58.1%)

2

3 (13.6%)

2 (9.5%)

5 (11.6%)

3

1 (4.5%)

0

1 (2.3%)

Radiotherapy duration (days)

μ ±SD

41.91 ±10.0

36.48 ±1.83

39.26 ±7.7

MW: p=0.019

M (min:max)

38 (32:72)

37 (32:41)

37 (32:72)

Fractination used

50.4/28

16 (72.7%)

14 (66.7%)

30 (69.8%)

OR=1.33 [0.36, 4.92] (p=0.747)

45/25

6 (27.3%)

7 (33.3%)

13 (30.2%)

Radiotherapy to lombo-aortics

10 (45.5%)

1 (4.8%)

11 (25.6%)

OR=16.67 [1.89, 146.95] (p=0.004)

Simultaneous integrated boost (SIB)

13 (61.9%)

6 (28.6%)

19 (45.2%)

OR=4.06 [1.11, 14.80] (p=0.062)

Sequential Boost instead of SIB

6 (27.3%)

1 (4.8%)

7 (16.3%)

OR=7.50 [0.82, 68.83] (p=0.095)

Brachytherapy fractions

μ ±SD

2.57 ±1.6

2.71 ±1.45

2.64 ±1.51

MW: p=0.811

M (min:max)

3 (0:4)

3 (0:4)

3 (0:4)

μ ±SD = Mean (standard deviation); M (min:max) = Median (min:max); MW = Mann-Whitney Test; Welch = Welch T-Test (not assuming equal variances); OR/RR = odds-ratio / risk-ratio [95% CI] and p value from Fisher test); V = Cramér V (p value from Chi² test);

3.1 NAC ~ Stage

Figure 1: Correlation between Stage and the number of NaC cycles. Size reprezents number of patients. Boxplot by group. Control: no NAC cycles. In NAC cases, median and IQR are at the IIIB level.

3.2 NAC ~ Total chemotherapy received (fraction of planned total cycles)

Figure 2: Correlation between Total chemotherapy received (fraction of planned total cycles) and the number of NaC cycles. Size reprezents number of patients. Boxplot by group. Control: no NAC cycles.

3.3 NAC ~ Total chemotherapy received (fraction of planned total dose)

Figure 3: Correlation between DT Chimio Administrat / Recom (%) (fraction of planned total dose) and the number of NaC cycles. Size reprezents number of patients. Boxplot by group. Control: no NAC cycles.

3.4 NAC ~ Leucocytes

Figure 4: Correlation between Lowest Leucocyte count and the number of NaC cycles. Grade of Leucopenia highlighted. Boxplot by group. Control: no NAC cycles. Clinical Leucocyte tresholds marked by dotted blue line.

Table 2: Regression models of Lowest Leucocyte count by number of NaC cycles unadjusted and adjusted for chemotherapy receiced, stage and several other variables.
  simple chemo stage interaction full extended
Lowest Leucocyte count BY: Estimates Estimates Estimates Estimates Estimates Estimates
(intercept) 2938.59 *** (236.96) 5786.92 ** (1977.34) 597.75 (761.02) 1677.83 * (732.72) 3781.18 * (1849.87) 2055.31 (3989.14)
Neoadjuvant chemotherapy cycles -81.90 (84.52) -74.84 (83.55) -260.96 ** (94.59) -181.08 (98.79) -260.17 ** (91.74) -304.46 * (145.29)
Chemotherapy received (%) -3189.67 (2198.76) -3672.20 (1956.67) -3199.86 (2608.59)
Stage (numeric) 873.19 ** (272.42) 908.92 ** (264.90) 828.72 * (391.73)
(interaction) 525.12 (289.67)
Age at diagnosis (years) 1.67 (21.11)
Cis dose (mg/m²) 23.13 (56.78)
Concomitant chemotherapy cycles received (%) 220.18 (1077.57)
Radiotherapy duration (days) 15.70 (58.06)
Fractination used: 45/25 vs. 50.4/28 -661.02 (486.12)
Simultaneous integrated boost (SIB) 192.55 (431.20)
Radiotherapy to lombo-aortics 542.56 (530.66)
Sequential Boost instead of SIB 77.64 (844.23)
Brachytherapy fractions 56.50 (163.33)
Observations 43 43 43 43 43 40
R2 / R2 adjusted 0.022 / -0.001 0.071 / 0.025 0.222 / 0.183 0.097 / 0.051 0.287 / 0.232 0.375 / 0.098
AIC 729.378 729.173 721.548 727.983 719.830 685.135
  • p<0.05   ** p<0.01   *** p<0.001

R

Simple

Chemo

Stage

Interaction

Pearson

-0.150

-0.140

-0.400

-0.278

(p)

p=0.338

p=0.376

p=0.009

p=0.074

Spearman

-0.223

-0.227

-0.499

-0.440

(p)

p=0.150

p=0.149

p<0.001

p=0.004

Figure 5: Correlation between Lowest Leucocyte count and the number of NaC cycles by Stage (left) and Chemotherapy received as a fraction of planned total dose (right). Clinical tresholds marked by dotted blue line. Statistics depict the Pearson correlation coefficient (with p-value) for the raw relation, the partial corelation by each covariate (with p-value) and the adjusted R² of a regression model with each covariate (with model F-statistic’s p-value).

Error in optim(s0, fmin, gmin, method = “BFGS”, …) : initial value in ‘vmmin’ is not finite

Table 3: Ordinal logistic regression models of Leucopenia grade by number of NaC cycles unadjusted and adjusted for chemotherapy receiced, stage and several other variables.

Factor: OR

extended

full

interaction

chemo

stage

simple

0|1

0.23

0.083

0.007 ***

2.619

<0.001 ***

0.178 **

1|2

0.992

0.37

0.024 **

8.963

0.004 ***

0.593

2|3

12.951

4.676

0.224

63.96

0.042 *

4.213 **

3|4

286.116

90.346

4.133

956.386 ⁺

0.848

64.087 ***

Neoadjuvant chemotherapy cycles

2.04 ** [1.335, 3.257]

1.777 ** [1.23, 2.646]

1.516 * [1.081, 2.168]

1.19 [0.891, 1.603]

1.736 ** [1.21, 2.567]

1.203

Chemotherapy received (%)

484.978 [0.03, >1000]

257.486 [0.065, >1000]

20.297 [0.006, >1000]

Stage (numeric)

0.172 * [0.042, 0.642]

0.146 *** [0.045, 0.426]

0.165 ** [0.053, 0.472]

(interaction)

0.285 * [0.101, 0.763]

Age at diagnosis (years)

1.02 [0.951, 1.096]

Radiotherapy duration (days)

0.962 [0.801, 1.153]

Fractination used: 45/25 vs. 50.4/28

1.756 [0.81, 4.007]

Simultaneous integrated boost (SIB)

0.752 [0.363, 1.536]

Sequential Boost instead of SIB

0.555 [0.149, 1.981]

Brachytherapy fractions

0.807 [0.492, 1.309]

McFadden's pseudo-R²

0.208

0.129

0.068

0.018

0.113

0.014

AIC

118.0

115.2

120.3

126.0

115.0

124.6

3.5 NAC ~ Neutrophiles

Figure 6: Correlation between Lowest Neutrophile count and the number of NaC cycles. Grade of Neutropenia highlighted. Boxplot by group. Control: no NAC cycles. Clinical Neutrophile tresholds marked by dotted blue line.

Table 4: Regression models of Lowest Neutrophile count by number of NaC cycles unadjusted and adjusted for chemotherapy receiced, stage and several other variables.
  simple chemo stage interaction full extended
Lowest Neutrophile count BY: Estimates Estimates Estimates Estimates Estimates Estimates
(intercept) 2204.68 *** (200.97) 5680.54 ** (1629.04) -92.85 (616.64) 1031.59 (616.18) 3695.46 * (1418.45) 3995.15 (2944.10)
Neoadjuvant chemotherapy cycles -96.74 (71.68) -88.13 (68.83) -272.49 *** (76.64) -189.02 * (83.08) -271.54 *** (70.34) -295.57 * (107.23)
Chemotherapy received (%) -3892.40 * (1811.46) -4369.96 ** (1500.34) -4471.05 * (1925.22)
Stage (numeric) 857.03 *** (220.74) 899.55 *** (203.12) 835.87 ** (289.11)
(interaction) 488.60 (243.60)
Age at diagnosis (years) -13.99 (15.58)
Cis dose (mg/m²) 9.50 (41.91)
Concomitant chemotherapy cycles received (%) 365.32 (795.28)
Radiotherapy duration (days) 6.54 (42.85)
Fractination used: 45/25 vs. 50.4/28 -614.66 (358.77)
Simultaneous integrated boost (SIB) 171.63 (318.24)
Radiotherapy to lombo-aortics 362.66 (391.64)
Sequential Boost instead of SIB 184.44 (623.06)
Brachytherapy fractions 75.52 (120.54)
Observations 43 43 43 43 43 40
R2 / R2 adjusted 0.043 / 0.019 0.142 / 0.099 0.305 / 0.270 0.130 / 0.087 0.429 / 0.385 0.524 / 0.312
AIC 715.207 712.510 703.456 713.086 696.992 660.833
  • p<0.05   ** p<0.01   *** p<0.001

R

Simple

Chemo

Stage

Interaction

Pearson

-0.206

-0.198

-0.490

-0.339

(p)

p=0.185

p=0.208

p<0.001

p=0.028

Spearman

-0.334

-0.329

-0.589

-0.493

(p)

p=0.028

p=0.033

p<0.001

p<0.001

Figure 7: Correlation between Lowest Neutrophile count and the number of NaC cycles by Stage (left) and Chemotherapy received as a fraction of planned total dose (right). Clinical tresholds marked by dotted blue line. Statistics depict the Pearson correlation coefficient (with p-value) for the raw relation, the partial corelation by each covariate (with p-value) and the adjusted R² of a regression model with each covariate (with model F-statistic’s p-value).

0 1 2 3 16 12 10 5 Error in optim(s0, fmin, gmin, method = “BFGS”, …) : initial value in ‘vmmin’ is not finite

Table 5: Ordinal logistic regression models of Neutropenia grade by number of NaC cycles unadjusted and adjusted for chemotherapy receiced, stage and several other variables.

Factor: OR

extended

full

interaction

chemo

stage

simple

0|1

0.007

0.047

0.012 **

9.387

0.001 ***

1.057

1|2

0.047

0.298

0.057 *

34.005

0.007 **

3.77 **

2|3

0.456

2.083

0.369

160.911

0.054 ⁺

18.057 ***

Neoadjuvant chemotherapy cycles

3.332 *** [1.955, 6.343]

2.721 *** [1.732, 4.608]

2.198 *** [1.472, 3.476]

1.414 * [1.05, 1.933]

2.719 *** [1.733, 4.619]

1.43 *

Chemotherapy received (%)

85.677 [0.002, >1000]

74.516 [0.024, >1000]

11.482 [0.007, >1000]

Stage (numeric)

0.039 *** [0.005, 0.202]

0.073 *** [0.017, 0.25]

0.079 *** [0.019, 0.264]

(interaction)

0.154 ** [0.044, 0.461]

Age at diagnosis (years)

1.038 [0.96, 1.13]

Radiotherapy duration (days)

0.936 [0.758, 1.178]

Fractination used: 45/25 vs. 50.4/28

2.643 * [1.045, 7.366]

Simultaneous integrated boost (SIB)

1.346 [0.603, 3.106]

Sequential Boost instead of SIB

0.916 [0.155, 4.185]

Brachytherapy fractions

0.855 [0.492, 1.488]

McFadden's pseudo-R²

0.331

0.228

0.154

0.054

0.218

0.051

AIC

99.6

99.3

105.5

116.8

98.3

115.2

3.6 NAC ~ Lymphocytes

Figure 6: Correlation between Lowest Neutrophile count and the number of NaC cycles. Grade of Neutropenia highlighted. Boxplot by group. Control: no NAC cycles. Clinical Neutrophile tresholds marked by dotted blue line.

Table 6: Regression models of Lowest Lymphocyte count by number of NaC cycles unadjusted and adjusted for chemotherapy receiced, stage and several other variables.
  simple chemo stage interaction full extended
Lowest Lymphocyte count BY: Estimates Estimates Estimates Estimates Estimates Estimates
(intercept) 384.19 *** (32.28) 130.96 (273.36) 489.58 *** (114.90) 443.04 *** (103.35) 224.29 (287.94) -478.97 (568.13)
Neoadjuvant chemotherapy cycles 2.16 (11.51) 1.53 (11.55) 10.22 (14.28) 6.79 (13.94) 10.15 (14.28) 4.34 (20.69)
Chemotherapy received (%) 283.57 (303.97) 306.03 (304.56) 679.13 (371.51)
Stage (numeric) -39.32 (41.13) -42.29 (41.23) -1.15 (55.79)
(interaction) -24.51 (40.86)
Age at diagnosis (years) 4.06 (3.01)
Cis dose (mg/m²) -5.53 (8.09)
Concomitant chemotherapy cycles received (%) -64.24 (153.47)
Radiotherapy duration (days) 10.63 (8.27)
Fractination used: 45/25 vs. 50.4/28 -99.71 (69.23)
Simultaneous integrated boost (SIB) -6.72 (61.41)
Radiotherapy to lombo-aortics -50.72 (75.58)
Sequential Boost instead of SIB -122.86 (120.23)
Brachytherapy fractions -7.97 (23.26)
Observations 43 43 43 43 43 40
R2 / R2 adjusted 0.001 / -0.024 0.022 / -0.027 0.023 / -0.026 0.010 / -0.040 0.048 / -0.025 0.264 / -0.063
AIC 557.929 559.003 558.958 559.544 559.859 529.216
  • p<0.05   ** p<0.01   *** p<0.001

R

Simple

Chemo

Stage

Interaction

Pearson

0.029

0.021

0.112

0.077

(p)

p=0.852

p=0.895

p=0.478

p=0.629

Spearman

0.085

0.076

0.140

0.098

(p)

p=0.586

p=0.634

p=0.377

p=0.536

Figure 8: Correlation between Lowest Lymphocyte count and the number of NaC cycles by Stage (left) and Chemotherapy received as a fraction of planned total dose (right). Clinical tresholds marked by dotted blue line. Statistics depict the Pearson correlation coefficient (with p-value) for the raw relation, the partial corelation by each covariate (with p-value) and the adjusted R² of a regression model with each covariate (with model F-statistic’s p-value).

Error in optim(s0, fmin, gmin, method = “BFGS”, …) : initial value in ‘vmmin’ is not finite

Table 7: Ordinal logistic regression models of Lymphopenia grade by number of NaC cycles unadjusted and adjusted for chemotherapy receiced, stage and several other variables.

Factor: OR

extended

full

interaction

chemo

stage

simple

1|2

<0.001 *

<0.001 *

0.011 *

<0.001 *

0.02 *

0.025 ***

2|3

<0.001 *

<0.001 ⁺

0.105

<0.001 ⁺

0.191

0.238 **

3|4

<0.001 *

0.027

3.588

0.026

6.37

7.93 ***

Neoadjuvant chemotherapy cycles

1.004 [0.626, 1.598]

1.038 [0.704, 1.527]

1.082 [0.748, 1.572]

1.039 [0.756, 1.433]

1.037 [0.709, 1.522]

1.021

Chemotherapy received (%)

<0.001 * [<0.001, 0.065]

0.001 [<0.001, 6.305]

0.001 [<0.001, 6.08]

Stage (numeric)

0.46 [0.081, 2.382]

1.008 [0.314, 3.197]

0.922 [0.296, 2.849]

(interaction)

0.716 [0.231, 2.142]

Age at diagnosis (years)

0.927 ⁺ [0.846, 1.009]

Radiotherapy duration (days)

0.897 [0.698, 1.125]

Fractination used: 45/25 vs. 50.4/28

2.006 [0.768, 5.674]

Simultaneous integrated boost (SIB)

1.011 [0.424, 2.339]

Sequential Boost instead of SIB

2.696 [0.529, 17.821]

Brachytherapy fractions

1.252 [0.691, 2.303]

McFadden's pseudo-R²

0.241

0.031

0.005

0.031

0

0

AIC

81.7

85.7

85.7

83.7

86.0

84.0

3.7 NAC ~ Platelets

Figure 6: Correlation between Lowest Neutrophile count and the number of NaC cycles. Grade of Neutropenia highlighted. Boxplot by group. Control: no NAC cycles. Clinical Neutrophile tresholds marked by dotted blue line.

Table 8: Regression models of Lowest Platelet count by number of NaC cycles unadjusted and adjusted for chemotherapy receiced, stage and several other variables.
  simple chemo stage interaction full extended
Lowest Platelet count BY: Estimates Estimates Estimates Estimates Estimates Estimates
(intercept) 157.63 *** (10.58) 172.91 (90.54) 126.17 ** (37.74) 138.54 *** (33.88) 146.51 (95.72) 35.78 (185.64)
Neoadjuvant chemotherapy cycles -6.66 (3.77) -6.62 (3.83) -9.06 (4.69) -8.16 (4.57) -9.06 (4.75) -4.34 (6.76)
Chemotherapy received (%) -17.11 (100.68) -23.46 (101.25) 30.01 (121.40)
Stage (numeric) 11.74 (13.51) 11.96 (13.71) -1.52 (18.23)
(interaction) 7.95 (13.40)
Age at diagnosis (years) -0.93 (0.98)
Cis dose (mg/m²) 3.69 (2.64)
Concomitant chemotherapy cycles received (%) 58.66 (50.15)
Radiotherapy duration (days) 0.12 (2.70)
Fractination used: 45/25 vs. 50.4/28 -24.44 (22.62)
Simultaneous integrated boost (SIB) -19.88 (20.07)
Radiotherapy to lombo-aortics 36.51 (24.70)
Sequential Boost instead of SIB -4.02 (39.29)
Brachytherapy fractions -7.12 (7.60)
Observations 43 43 43 43 43 40
R2 / R2 adjusted 0.071 / 0.048 0.071 / 0.025 0.088 / 0.042 0.079 / 0.033 0.089 / 0.019 0.342 / 0.049
AIC 462.009 463.978 463.206 463.632 465.147 439.735
  • p<0.05   ** p<0.01   *** p<0.001

R

Simple

Chemo

Stage

Interaction

Pearson

-0.266

-0.264

-0.292

-0.272

(p)

p=0.085

p=0.091

p=0.060

p=0.082

Spearman

-0.333

-0.338

-0.376

-0.392

(p)

p=0.029

p=0.029

p=0.014

p=0.010

Figure 9: Correlation between Lowest Platelet count and the number of NaC cycles by Stage (left) and Chemotherapy received as a fraction of planned total dose (right). Clinical tresholds marked by dotted blue line. Statistics depict the Pearson correlation coefficient (with p-value) for the raw relation, the partial corelation by each covariate (with p-value) and the adjusted R² of a regression model with each covariate (with model F-statistic’s p-value).

Error in optim(s0, fmin, gmin, method = “BFGS”, …) : initial value in ‘vmmin’ is not finite

Table 9: Ordinal logistic regression models of Thrombocytopenia grade by number of NaC cycles unadjusted and adjusted for chemotherapy receiced, stage and several other variables.

Factor: OR

extended

full

interaction

chemo

stage

simple

0|1

>1000

310.485

8.394

465.078

3.932

6.104 **

1|2

>1000

818.258

21.79

>1000

10.239

15.854 ***

2|3

>1000

>1000

33.642 ⁺

>1000

15.807

24.47 ***

Neoadjuvant chemotherapy cycles

1.277 [0.75, 2.258]

1.134 [0.683, 1.906]

1.065 [0.652, 1.724]

1.086 [0.714, 1.643]

1.128 [0.683, 1.869]

1.091

Chemotherapy received (%)

>1000 [<0.001, >1000]

147.122 [0.002, >1000]

121.334 [0.002, >1000]

Stage (numeric)

0.476 [0.036, 4.311]

0.805 [0.171, 3.482]

0.848 [0.186, 3.548]

(interaction)

1.141 [0.264, 4.91]

Age at diagnosis (years)

1.166 * [1.033, 1.399]

Radiotherapy duration (days)

0.902 [0.658, 1.196]

Fractination used: 45/25 vs. 50.4/28

1.537 [0.446, 7.188]

Simultaneous integrated boost (SIB)

1.542 [0.41, 7.527]

Sequential Boost instead of SIB

1.633 [0.168, 12.326]

McFadden's pseudo-R²

0.188

0.017

0.004

0.015

0.005

0.004

AIC

63.9

62.7

61.4

60.8

61.4

59.4

3.8 NAC ~ Hemoglobin

Figure 6: Correlation between Lowest Neutrophile count and the number of NaC cycles. Grade of Neutropenia highlighted. Boxplot by group. Control: no NAC cycles. Clinical Neutrophile tresholds marked by dotted blue line.

Table 10: Regression models of Lowest Hemoglobin by number of NaC cycles unadjusted and adjusted for chemotherapy receiced, stage and several other variables.
  simple chemo stage interaction full extended
Lowest Hemoglobin BY: Estimates Estimates Estimates Estimates Estimates Estimates
(intercept) 11.06 *** (0.20) 13.79 *** (1.65) 12.09 *** (0.70) 12.29 *** (0.61) 14.58 *** (1.72) 10.03 ** (3.18)
Neoadjuvant chemotherapy cycles -0.24 ** (0.07) -0.23 ** (0.07) -0.16 (0.09) -0.14 (0.08) -0.16 (0.09) -0.15 (0.12)
Chemotherapy received (%) -3.06 (1.84) -2.87 (1.82) -1.37 (2.08)
Stage (numeric) -0.38 (0.25) -0.36 (0.25) -0.10 (0.31)
(interaction) -0.51 * (0.24)
Age at diagnosis (years) -0.03 (0.02)
Cis dose (mg/m²) 0.06 (0.05)
Concomitant chemotherapy cycles received (%) 0.40 (0.86)
Radiotherapy duration (days) 0.07 (0.05)
Fractination used: 45/25 vs. 50.4/28 -0.85 * (0.39)
Simultaneous integrated boost (SIB) -0.19 (0.34)
Radiotherapy to lombo-aortics 0.02 (0.42)
Sequential Boost instead of SIB -1.26 (0.67)
Brachytherapy fractions -0.04 (0.13)
Observations 43 43 43 43 43 40
R2 / R2 adjusted 0.216 / 0.197 0.267 / 0.231 0.260 / 0.223 0.296 / 0.261 0.305 / 0.251 0.516 / 0.301
AIC 120.448 119.563 119.978 117.856 119.308 114.431
  • p<0.05   ** p<0.01   *** p<0.001

R

Simple

Chemo

Stage

Interaction

Pearson

-0.465

-0.466

-0.281

-0.266

(p)

p=0.002

p=0.002

p=0.071

p=0.089

Spearman

-0.475

-0.471

-0.288

-0.312

(p)

p=0.001

p=0.002

p=0.065

p=0.044

Figure 10: Correlation between Lowest Hemoglobin and the number of NaC cycles by Stage (left) and Chemotherapy received as a fraction of planned total dose (right). Clinical tresholds marked by dotted blue line. Statistics depict the Pearson correlation coefficient (with p-value) for the raw relation, the partial corelation by each covariate (with p-value) and the adjusted R² of a regression model with each covariate (with model F-statistic’s p-value).

Error in optim(s0, fmin, gmin, method = “BFGS”, …) : initial value in ‘vmmin’ is not finite

Table 11: Ordinal logistic regression models of Anemia grade by number of NaC cycles unadjusted and adjusted for chemotherapy receiced, stage and several other variables.

Factor: OR

extended

full

interaction

chemo

stage

simple

0|1

0.01

0.893

0.356

0.36

0.395

0.131 **

1|2

15.841

97.34

38.656 *

37.236

42.715 ⁺

13.425 ***

2|3

326.939

>1000

424.36 **

405.805

468.581 **

146.231 ***

Neoadjuvant chemotherapy cycles

1.847 * [1.081, 3.506]

1.454 [0.942, 2.389]

1.464 ⁺ [0.963, 2.375]

1.566 * [1.085, 2.456]

1.452 [0.941, 2.379]

1.564 *

Chemotherapy received (%)

0.17 [<0.001, >1000]

2.545 [<0.001, >1000]

3.108 [<0.001, >1000]

Stage (numeric)

0.732 [0.092, 5.671]

1.505 [0.438, 5.403]

1.514 [0.444, 5.405]

(interaction)

1.523 [0.448, 5.48]

Age at diagnosis (years)

1.206 ** [1.072, 1.43]

Radiotherapy duration (days)

0.796 ⁺ [0.602, 1.018]

Fractination used: 45/25 vs. 50.4/28

2.657 ⁺ [0.867, 9.492]

Simultaneous integrated boost (SIB)

1.822 [0.628, 5.727]

Sequential Boost instead of SIB

5.607 ⁺ [0.831, 46.592]

Brachytherapy fractions

1.2 [0.573, 2.535]

McFadden's pseudo-R²

0.389

0.094

0.093

0.087

0.093

0.087

AIC

65.4

73.5

71.5

71.9

71.5

70.0

3.9 NAC ~ Creatinin, Urinary, Digestive, RT to lombo-aortics

Figure 11: Creatinin toxicity, Urinary and Digestive Toxicity, RT to lombo-aortics by Neoadjuvant chemotherapy groups.

Error in optim(s0, fmin, gmin, method = “BFGS”, …) : initial value in ‘vmmin’ is not finite

Table 12: Ordinal logistic regression models of Digestive toxicity by number of NaC cycles unadjusted and adjusted for chemotherapy receiced, stage and several other variables.

Factor: OR

extended

full

interaction

chemo

stage

simple

0|1

0.015

0.132

0.501

0.077

0.786

0.422 *

1|2

0.353

2.15

8.005

1.24

12.64

6.744 ***

2|3

2.863

15.008

54.813 *

8.541

87.283 *

46.098 ***

Neoadjuvant chemotherapy cycles

0.919 [0.616, 1.376]

1.002 [0.703, 1.435]

1.036 [0.738, 1.467]

1.049 [0.783, 1.417]

1.004 [0.706, 1.437]

1.048

Chemotherapy received (%)

0.211 [<0.001, >1000]

0.13 [<0.001, 471.189]

0.151 [<0.001, 546.959]

Stage (numeric)

1.361 [0.412, 4.546]

1.287 [0.436, 3.788]

1.261 [0.426, 3.734]

(interaction)

1.073 [0.371, 3.125]

Age at diagnosis (years)

0.947 [0.88, 1.015]

Radiotherapy duration (days)

1.023 [0.892, 1.175]

Fractination used: 45/25 vs. 50.4/28

0.632 [0.282, 1.399]

Simultaneous integrated boost (SIB)

1.365 [0.659, 2.892]

McFadden's pseudo-R²

0.112

0.006

0.001

0.003

0.003

0.001

AIC

97.1

98.3

96.7

96.5

96.5

94.7

4 RT given to LomboAortics

Table 13: Summary table for RT given to Lombo-aortics in NAC patients by several predictors.

Variabila

Detalii

yes

no

Total

Teste statistice

Radiotherapy to lombo-aortics

10 (45.5%)

12 (54.5%)

22

Group

NAC

10 (100%)

12 (100%)

22 (100%)

OR=0.84 [0.02, 46.09] (p>0.999)

Control

0

0

0

Neoadjuvant chemotherapy cycles

M (min:max)

4 (3:6)

4 (2:6)

4 (2:6)

MW: p=0.793

μ ±DS

3.90 ±0.876

3.75 ±0.965

3.82 ±0.907

Age at diagnosis (years)

M (min:max)

53 (29:67)

57 (35:71)

53.5 (29:71)

T-test: p=0.313

μ ±DS

50.90 ±11.2

55.83 ±11.1

53.59 ±11.2

Stage

IB

0

0

0

V=0.57 (p=0.069)

IIA

0

0

0

IIB

1 (10.0%)

4 (33.3%)

5 (22.7%)

IIIA

0

0

0

IIIB

3 (30.0%)

7 (58.3%)

10 (45.5%)

IVA

4 (40.0%)

1 (8.3%)

5 (22.7%)

IVB

2 (20.0%)

0

2 (9.1%)

Stage (numeric)

M (min:max)

4 (2.5:4.5)

3.5 (2.5:4)

3.5 (2.5:4.5)

MW: p=0.017

μ ±DS

3.80 ±0.587

3.21 ±0.542

3.48 ±0.626

Dose used

Cis 30mg/m²

1 (10.0%)

2 (16.7%)

3 (13.6%)

OR=0.56 [0.04, 7.21] (p>0.999)

Cis 40mg/m²

9 (90.0%)

10 (83.3%)

19 (86.4%)

Cis dose (mg/m²)

M (min:max)

40 (30:40)

40 (30:40)

40 (30:40)

MW: p=0.698

μ ±DS

39.00 ±3.16

38.33 ±3.89

38.64 ±3.51

Concomitant chemotherapy cycles

M (min:max)

2 (1:5)

2 (1:4)

2 (1:5)

MW: p=0.700

μ ±DS

2.20 ±1.23

2.25 ±0.866

2.23 ±1.02

Lost cycles

M (min:max)

3 (0:4)

3 (1:4)

3 (0:4)

MW: p=0.700

μ ±DS

2.80 ±1.23

2.75 ±0.866

2.77 ±1.02

Concomitant chemotherapy
cycles received (%)

M (min:max)

0.4 (0.2:1)

0.4 (0.2:0.8)

0.4 (0.2:1)

MW: p=0.700

μ ±DS

0.44 ±0.246

0.45 ±0.173

0.445 ±0.204

Chemotherapy received (%)

M (min:max)

0.92 (0.75:1.01)

0.93 (0.78:0.99)

0.92 (0.75:1.01)

T-test: p=0.835

μ ±DS

0.901 ±0.0813

0.908 ±0.0697

0.905 ±0.0734

Lowest Leucocyte count

M (min:max)

2610 (850:6310)

2375 (1640:3700)

2460 (850:6310)

MW: p=0.381

μ ±DS

2921.00 ±1541.3

2461.67 ±741.3

2670.45 ±1166.5

Leucopenia grade

0

2 (20.0%)

0

2 (9.1%)

V=0.55 (p=0.156)

1

1 (10.0%)

3 (25.0%)

4 (18.2%)

2

5 (50.0%)

4 (33.3%)

9 (40.9%)

3

1 (10.0%)

5 (41.7%)

6 (27.3%)

4

1 (10.0%)

0

1 (4.5%)

Lowest Neutrophile count

M (min:max)

1842.5 (720:5190)

1445 (910:2810)

1520 (720:5190)

MW: p=0.381

μ ±DS

2174.50 ±1375.9

1588.33 ±640.6

1854.77 ±1056.2

Neutropenia grade

0

4 (40.0%)

2 (16.7%)

6 (27.3%)

V=0.30 (p=0.575)

1

2 (20.0%)

3 (25.0%)

5 (22.7%)

2

2 (20.0%)

5 (41.7%)

7 (31.8%)

3

2 (20.0%)

2 (16.7%)

4 (18.2%)

Lowest Lymphocyte count

M (min:max)

355 (70:430)

450 (380:950)

405 (70:950)

MW: p<0.001

μ ±DS

301.00 ±116.9

491.67 ±154.9

405.00 ±166.9

Lymphopenia grade

1

0

1 (8.3%)

1 (4.5%)

V=0.52 (p=0.118)

2

0

3 (25.0%)

3 (13.6%)

3

8 (80.0%)

8 (66.7%)

16 (72.7%)

4

2 (20.0%)

0

2 (9.1%)

Lowest Platelet count

M (min:max)

151.5 (29:271)

106.5 (68:198)

126.5 (29:271)

Welch: p=0.423

μ ±DS

142.60 ±75.1

121.17 ±35.3

130.91 ±56.5

Thrombocytopenia grade

0

8 (80.0%)

10 (83.3%)

18 (81.8%)

V=0.43 (p=0.254)

1

0

1 (8.3%)

1 (4.5%)

2

0

1 (8.3%)

1 (4.5%)

3

2 (20.0%)

0

2 (9.1%)

Lowest Hemoglobin

M (min:max)

10.1 (7.6:11.2)

10.35 (8.8:12.9)

10.15 (7.6:12.9)

T-test: p=0.171

μ ±DS

9.81 ±1.07

10.44 ±1.02

10.15 ±1.06

Anemia grade

0

0

1 (8.3%)

1 (4.5%)

V=0.34 (p=0.474)

1

7 (70.0%)

7 (58.3%)

14 (63.6%)

2

2 (20.0%)

4 (33.3%)

6 (27.3%)

3

1 (10.0%)

0

1 (4.5%)

Creatinine level

normal

8 (80.0%)

12 (100%)

20 (90.9%)

OR=0.14 [0.01, 3.20] (p=0.195)

elevated

2 (20.0%)

0

2 (9.1%)

Urinary toxicity

2 (20.0%)

6 (50.0%)

8 (36.4%)

OR=0.25 [0.04, 1.70] (p=0.204)

Digestive toxicity

0

2 (20.0%)

4 (33.3%)

6 (27.3%)

V=0.52 (p=0.118)

1

4 (40.0%)

8 (66.7%)

12 (54.5%)

2

3 (30.0%)

0

3 (13.6%)

3

1 (10.0%)

0

1 (4.5%)

Radiotherapy duration (days)

M (min:max)

39 (35:72)

37.5 (32:58)

38 (32:72)

MW: p=0.219

μ ±DS

44.10 ±11.5

40.08 ±8.69

41.91 ±10.0

Fractination used

50.4/28

8 (80.0%)

8 (66.7%)

16 (72.7%)

OR=2.00 [0.28, 14.20] (p=0.646)

45/25

2 (20.0%)

4 (33.3%)

6 (27.3%)

Simultaneous integrated boost (SIB)

7 (77.8%)

6 (50.0%)

13 (61.9%)

OR=3.50 [0.50, 24.27] (p=0.367)

Sequential Boost instead of SIB

4 (40.0%)

2 (16.7%)

6 (27.3%)

OR=3.33 [0.46, 24.05] (p=0.348)

Brachytherapy fractions

M (min:max)

3 (0:4)

3 (0:4)

3 (0:4)

MW: p=0.709

μ ±DS

2.78 ±1.48

2.42 ±1.73

2.57 ±1.6

μ ±DS = Media (deviația standard); M (min:max) = Mediana (min:max); MW = Test Mann-Whitney; KW = Test Kruskal-Wallis; Welch = Test T Welch (fără presupunerea de varianțe egale); OR/RR = odds-ratio / risc relativ [cu IC 95%] și p calculat prin testul Fisher); V = Cramér V (p calculat prin testul Chi²);

5 extra

names(canva_palettes) %>% sort(decreasing = T)
  [1] "Wintery reds"                              
  [2] "Watery blue-greens"                        
  [3] "Warm tones"                                
  [4] "Warm naturals"                             
  [5] "Warm and wonderful"                        
  [6] "Warm and rustic"                           
  [7] "Warm and cool"                             
  [8] "Warm and bold"                             
  [9] "Violet sunset"                             
 [10] "Vintage charm 2"                           
 [11] "Vintage charm"                             
 [12] "Vineyard neutrals"                         
 [13] "Urban oasis"                               
 [14] "Urban living"                              
 [15] "Unique and striking"                       
 [16] "Unexpected color combinations"             
 [17] "Understated and versatile"                 
 [18] "Tropical tones"                            
 [19] "Trendy and metropolitan"                   
 [20] "Tints and tones"                           
 [21] "Timeless and nautical"                     
 [22] "Technology meets nature"                   
 [23] "Surf and turf"                             
 [24] "Sunset to dusk"                            
 [25] "Sunny citrus"                              
 [26] "Sunny and calm"                            
 [27] "Sunkissed village"                         
 [28] "Sun and sky"                               
 [29] "Summer sunflower"                          
 [30] "Summer inspired"                           
 [31] "Summer fiesta"                             
 [32] "Summer barbeque"                           
 [33] "Subtle and versatile"                      
 [34] "Subdued and proffesional"                  
 [35] "Stylish and retro"                         
 [36] "Striking and energetic"                    
 [37] "Strawberries and cream"                    
 [38] "Stormy hues"                               
 [39] "Splash of color"                           
 [40] "Spicy neutrals"                            
 [41] "Smoky purples"                             
 [42] "Sleek and modern"                          
 [43] "Simple but bold"                           
 [44] "Simple and fresh"                          
 [45] "Sharp and modern"                          
 [46] "Shadowy and dramatic"                      
 [47] "Shades of citrus"                          
 [48] "Shabby chic neutrals"                      
 [49] "Serene and spa like"                       
 [50] "Retro inspired"                            
 [51] "Retro and relaxing"                        
 [52] "Refreshing and pretty"                     
 [53] "Professional and traditional"              
 [54] "Professional and modern"                   
 [55] "Primary colors with a vibrant twist"       
 [56] "Pretty pastels"                            
 [57] "Pop art"                                   
 [58] "Pool party"                                
 [59] "Polished and inviting"                     
 [60] "Playful greens and blues"                  
 [61] "Pastels"                                   
 [62] "Outdoorsy and Natural"                     
 [63] "Orange accent"                             
 [64] "Nightlife"                                 
 [65] "Neutral and versatile"                     
 [66] "Neon tones and sharp contrast"             
 [67] "Neon night"                                
 [68] "Neon and bold"                             
 [69] "Naturally elegant"                         
 [70] "Muted tones"                               
 [71] "Muted and minimal"                         
 [72] "Muted and antique"                         
 [73] "Modern and urban"                          
 [74] "Modern and muted"                          
 [75] "Modern and minimal"                        
 [76] "Modern and crisp"                          
 [77] "Modern and clean"                          
 [78] "Misty greens"                              
 [79] "Mediterranean afternoon"                   
 [80] "Maritime brights"                          
 [81] "Luxurious and modern"                      
 [82] "Light and natural"                         
 [83] "Lemonade stand"                            
 [84] "Jewel tones"                               
 [85] "Industrial and in control"                 
 [86] "Icy blues and grays"                       
 [87] "High saturation and high energy"           
 [88] "Hazy grays"                                
 [89] "Green fields"                              
 [90] "Grecian holiday"                           
 [91] "Golden afternoon"                          
 [92] "Garden fresh"                              
 [93] "Fun and tropical"                          
 [94] "Fun and professional"                      
 [95] "Fun and cheerful"                          
 [96] "Fresh greens"                              
 [97] "Fresh and lively"                          
 [98] "Fresh and energetic"                       
 [99] "Fresh and bright"                          
[100] "Exotic and high impact"                    
[101] "Elegant and sophisticated"                 
[102] "Earthy and fresh"                          
[103] "Distintive and unexpected"                 
[104] "Day and night"                             
[105] "Dark and handsome"                         
[106] "Dark and earthy"                           
[107] "Crisp complementary colors"                
[108] "Crisp and dramatic"                        
[109] "Cozy and warm"                             
[110] "Cosmopolitan"                              
[111] "Corporate and sleek"                       
[112] "Cool vs warm"                              
[113] "Cool jewel tones"                          
[114] "Cool blues"                                
[115] "Cool and calm"                             
[116] "Colorful without clashing"                 
[117] "Coastal"                                   
[118] "Clean gradient and fresh blues"            
[119] "Clean and highlighted"                     
[120] "Clean and crisp"                           
[121] "Clean and collegiate"                      
[122] "Classy and timeless"                       
[123] "Classic metallics"                         
[124] "City sights"                               
[125] "Chocolaty browns"                          
[126] "Cheerful brights"                          
[127] "Cheerful blues and pink"                   
[128] "Cheerful and sleek"                        
[129] "Cheerful and friendly"                     
[130] "Candy coated brights"                      
[131] "Bright and tropical"                       
[132] "Bright and painterly"                      
[133] "Bold feature colors"                       
[134] "Bold blacks and vibrand highlights"        
[135] "Bold berries"                              
[136] "Bold and punchy"                           
[137] "Bold and cultured"                         
[138] "Bold and basic"                            
[139] "Birds and berries"                         
[140] "Beyond black and white"                    
[141] "Berry blues"                               
[142] "Back to school"                            
[143] "Autumn oranges and complemtentary neutrals"
[144] "Autumn in vermont"                         
[145] "Artic sunrise"                             
[146] "Art history inspired"                      
[147] "Aqua blues"                                
[148] "Antique tones"                             
[149] "Antique and clean"                         
[150] "1950s kitchen"                             
canva_df <- purrr::map2_df(canva_palettes, names(canva_palettes) ,
                    ~ tibble(colors = .x, .id = seq_along(colors),
                             palette = .y))

ggplot(canva_df, aes(y = palette, x = .id, fill = colors)) +
       geom_raster() +
       scale_fill_identity(guide = FALSE) +
       theme_minimal() +
       theme(panel.grid = element_blank(),
             axis.text.x = element_blank()) +
       labs(x = "", y = "")