https://rpubs.com/alex_istrate/534380

1 Pre-analysis

2 Abstract

We included 58 patients, of which 22 (37.9%) 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<0.001). Stage is significantly correlated with the number of neoadjuvant chemotherapy cycles (RSpearman=0.50, p<0.001).

NAC patients received chemotherapy doses ranging from 30 to 40 (median=40) mg/mp, lower than controls (20 to 100, median=40, p=0.027). NAC patients received a statistically similar median number of chemotherapy cycles (2, ranging from 1 to 5) as the controls (3, 1 to 5, p=0.080). 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 50% 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=93%, vs 63% to 100%, median=93%, p=0.086). The total chemotherapy received is not significantly correlated with the number of neoadjuvant chemotherapy cycles (RSpearman=-0.045, p=0.739).

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=2565, 1080:5600, p=0.466) as well as grade of leucopenia (p=0.719).

Lowest leucocyte count is not significantly correlated with the number of neoadjuvant chemotherapy cycles (RSpearman=-0.157, p=0.238), even after adjuting for total chemotherapy received (RSpearman=-0.160, p=0.233), but showed an increased correlation after adjuting for stage (RSpearman=-0.300, p=0.023).

On average, every additional neadjuvant chemotherapy cycle decreased the neutrophile count by 59.68 ±75.04 cells/mL (non significant). After adjusting for total chemotherapy received the average WBC count decreased by 65.07 ±74.39 cells/mL (non significant) and after adjusting for stage, the average neutrophile count decreased by 163.97 ±83.22 cells/mL. When adjusting for both at the same time, the average neutrophile count decreased by 187.06 * ±81.65 cells/mL.

There is a high degree of similarity between the Lowest Neutrophile count and the Lowest Leucocyte count (R=0.93***, the same as Lin’s CCC on standardized data) which explains the similarity of the results involving these two measurements and suggests that leucocyte toxicity is primarly based on neutrophiles.

2.2 Neutrophiles

NAC patients showed insignifficant toxicity by neutrophiles counts (median=1520, 720:5190 vs median=1900, 610:3970, p=0.340) as well as grade of neutropenia (p=0.617).

Lowest Neutrophile count is not significantly correlated with the number of neoadjuvant chemotherapy cycles (RSpearman=-0.175, p=0.190), even after adjuting for total chemotherapy received (RSpearman=-0.182, p=0.176), but showed a stronger correlation after adjuting for stage (RSpearman=-0.316, p=0.017).

On average, every additional neadjuvant chemotherapy cycle decreased the neutrophile count by 57.84 ±65.97 cells/mL (non significant). After adjusting for total chemotherapy received the average neutrophile count decreased by 63.62 ±64.78 cells/mL (non significant) but after adjusting for stage, the average neutrophile count decreased by 162.4 * ±71.93 cells/mL. When adjusting for both at the same time, the average neutrophile count increased by 186.79 ** ±69.19 cells/mL.

2.3 Lymphocytes

NAC patients showed insignifficant toxicity by lymphocyte counts (median=405, 70:950 vs median=365, 150:660, p=0.251) as well as grade of lymphopenia (p=0.594).

Lowest lymphocyte count is not significantly correlated with the number of neoadjuvant chemotherapy cycles (RSpearman=0.132, p=0.323), even after adjuting for total chemotherapy received (RSpearman=0.131, p=0.331) nor after adjuting for stage (RSpearman=0.231, p=0.084).

On average, every additional neadjuvant chemotherapy cycle increased the lymphocyte count by 5.19 ±9.58 cells/mL (non significant). After adjusting for total chemotherapy received the average lymphocyte count increased by 5.36 ±9.67 cells/mL (non significant) and after adjusting for stage, the average lymphocyte count increased by 15.45 ±10.87 cells/mL (non significant). When adjusting for both at the same time, the average lymphocyte count decreased by 16.55 ±11.02 cells/mL (non significant).

2.4 Platelets

NAC patients showed signifficantly more toxicity by platelet counts (median=126.5, 29:271 vs median=153.5, 56:462, p=0.025) but not by grade of thrombocytopenia (p=0.685).

Lowest platelet count is significantly correlated with the number of neoadjuvant chemotherapy cycles (RSpearman=-0.423, p=0.003), even after adjuting for total chemotherapy received (RSpearman=-0.249, p=0.091) and after adjuting for stage (RSpearman=-0.419, p=0.003).

On average, every additional neadjuvant chemotherapy cycle decreased the platelet count by 14.11** ±5.1 cells/mL. After adjusting for total chemotherapy received the average platelet count decreased by 14.41* ±6.3 cells/mL and after adjusting for stage, the average platelet count decreased by 17.85** ±6.0 cells/mL. When adjusting for both at the same time, the average platelet count decreased by 18.79* ±7.3 cells/mL.

2.5 Hemoglobin

NAC patients showed signifficantly lower hemoglobin (median=10.15, 7.6:12.9 vs median=11.25, 8.2:13.4, p=0.004) but not a higher grade of anemia (p=0.128).

Lowest hemoglobin level is significantly correlated with the number of neoadjuvant chemotherapy cycles (RSpearman=-0.406, p=0.002), even after adjuting for total chemotherapy received (RSpearman=-0.415, p=0.001). After adjuting for stage, the partial correlation only showed a tendency towards statisatical significance (RSpearman=-0.257, p=0.054).

On average, every additional neadjuvant chemotherapy cycle decreased the hemoglobin level by 0.25 ** ±0.08 cells/mL. After adjusting for total chemotherapy received the average hemoglobin level decreased by 0.26 ** ±0.08 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 0.17 ±0.9 cells/mL (not significant).

2.6 Other toxicities

Elevated creatinin levels were found in 9.1% of the NAC patients and 11.1% of the control patients (OR=1.25 [0.21, 7.46. p=1.000). Among cases, 36.4% had registered urinary toxicity grade 1 (none with grade 2) while among controls 25.0% had toxicity grade 1 and another patient had grade 2 (OR=1.71 [0.54, 5.42], p=0.387).

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 58.3% (with 5 patients - 13.9% grade 2) of the control patients (p=0.439). RT was given to Lombo-aortics in 45.5% of the NAC patients and 13.9% of the control patinents (OR=5.17 [1.46, 18.28], p=0.013).

3 Results

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

Factor

Detalis

Total

NAC

Control

Statistics

Group

58

22 (37.9%)

36 (62.1%)

Neoadjuvant chemotherapy cycles

μ ±DS

1.45 ±1.95

3.82 ±0.907

0.00 ±0.0

MW: p<0.001

M (min:max)

0 (0:6)

4 (2:6)

0 (0:0)

Age at diagnosis (years)

μ ±DS

53.37 ±10.5

53.59 ±11.2

53.23 ±10.3

T-test: p=0.901

M (min:max)

53 (29:72)

53.5 (29:71)

51 (36:72)

Stage

IB