Time from Surgery to First Adjuvant Chemotherapy: Experiences at an Inner City Canadian Hospital C. Marchand1*, M. Hassan1, L. Sevick1, N. Baxter1, J. Ebrahim1, A. Bookwala1, A. Ansari1, A. Wong1, S. Hogeveen1, R. Nisenbaum2, D. Topic3, C. Brezden-Masley1.

1Medical Oncology, St. Michael’s Hospital, Toronto, Canada 2Centre for Research on Inner City Health, St. Michael’s Hospital, Toronto Canada

3Medical Oncology, Sindi Ahluwalia Hawkins Centre for the Southern Interior (BCCA), Kelowna, Canada

ABSTRACT Background: Cancer Care Ontario (CCO) guidelines advise that colorectal cancer (CRC) patients receive their first adjuvant chemotherapy (AC) no later than 8 weeks after surgical resection, with new data suggesting optimal treatment to commence between 4 and 6 weeks. This retrospective study was performed to determine treatment timelines and identify barriers at St. Michael’s Hospital (SMH). Methods: Of the 507 patients diagnosed with CRC between January 1, 2005 and May 1, 2012 at SMH, 304 patients had stage II or III CRC. Our sample population of 159 patients received both surgical resection and AC at SMH. Data collected included: time between surgery and first AC, patient demographics, systemic/clinical barriers and recurrence-free survival. Data was analyzed using SAS statistical software assuming p-values <0.05 as significant.

Results: Of our 159 patients, mean age was 61.3 years (range 28 – 91); 54% male and 70% had stage III disease; colon cancer (64%) and mean follow-up was 2.2 years (range 0.1 – 5.7). Mean time from surgery to first AC was 50.4 days (SD = 15.8) or 7.2 weeks (range 3-17). Medical complications affected 21.4% of patients. The presence of a complication was associated with delay in AC (9.5 days, p=0.001). Moreover, 11.1% of patients were excluded from sample, since complications exceeded treatment past 12 weeks, equating to no AC. Referral from surgeon averaged 21 days (SD=12.0), 10 days awaiting pathology. Medical Oncology consult to first AC averaged 19 days (SD=12.7), 12 days awaiting port-a-cath insertion. Each part of the referral process was correlated with delay to AC. Only 18.9% of patients recurred. While trends were identified, association between delay and recurrence was weak (p=0.146). Medical complication correlated strongly with recurrence (p=0.047). Patients with complications had a higher rate of recurrence (32.4% vs 15.2%). Conclusions: Compliance to current CCO guidelines can be optimized in CRC patients at SMH. Barriers to timely treatment include patient age, timely referral and presence of a medical complication. Quality improvement rapid cycling of confounding barriers will be used prospectively to lower variance and achieve greater consistency in treatment.

BACKGROUND • The initiation of systemic adjuvant chemotherapy (AC) in stage II and III colorectal cancer (CRC) patients has become a point of significant importance in the successful treatment of patients • A meta-analysis of previous studies, determined that optimal survival benefits come to patients who receive AC 4-6 weeks after surgery (Biagi et al, 2005) • In this study, the primary focus is whether a delay in the initiation of AC affects disease free survival (DFS) or overall survival (OS) (delay defined as > four weeks from surgical resection of primary tumour.)

METHODS • This study received REB approval from SMH

• Potentially eligible patients were reviewed retrospectively

• Eligible patients were identified through Medical Oncologist new patient records at SMH

• Table 1 shows the patient selection criteria

RESULTS

We would like to thank Rob Grandy and Sanofi Aventis Canada Inc for their unrestricted educational grant in support of this project. We would also like to acknowledge all the surgeons that operated on the included patients. Specifically we would like to thank: Dr. Ahmed, Dr. Baxter, Dr. Burnstein, Dr. George, Dr. Grantcharov, Dr. Lawless, Dr. Mustard, Dr. Nathans, and Dr. Rotstein.

TABLE 2: Patient Demographics Patient Demographic Results/Data Collected Age Mean age : 61.3 years Range: 28-91 years

Gender Male: 54% Female: 46%

Stage of Disease Stage II: 30% Stage III: 70%

Type of Cancer Colon cancer: 64% LARC: 36%

Medical Complications With: 21% Without: 79%

Recurrence Yes: 18.9% No: 81.1%

TIMELINE

• The following figure (Figure 1) shows the frequency distribution of time from surgery to AC for all included patients (n=159), patients without complication (n=125), and patients with complications (n=34)

CONCLUSIONS • SMH treats 37.1% of patients between 4 and 6 weeks.

• Patients are treated as per recommended Cancer Care Ontario guidelines.

• Clinical barriers were identified. • The presence of a medical complication is known to increase wait times between surgery and first AC. Areas of improvement may be considered in earlier identification and treatment of surgical complications.

• Systemic barriers were identified. • Time to availability of pathological diagnosis (formal report) was recognized as a barrier to timely medical oncology referral and initiation of systemic therapy. Recognizing this significant barrier and working together with service providers may improve these barriers moving forward.

TABLE 1: Patient Selection Criteria

Inclusion Criteria: i.  Patients with stage II and III colorectal cancer. ii.  Patients surgically resected at SMH. iii.  Patients treated with systemic AC (Xeloda or

FOLFOX) at SMH. iv.  Patients with date of surgery between 29-

August-2005 – 1-May-2012

Exclusion Criteria: i.  Stage I or IV colorectal cancer. ii.  Patients who have surgery and/or AC at an

institution other than SMH.

• Figure 3 shows a breakdown of the mean number of days between surgery and AC. The average number of days between surgery and AC was 50.4 days with a SD of 15.8.

FIGURE 3: Timeline showing the mean number of days between surgery and AC

Waiting for

pathology report post

surgery

From Surgeon to

Medical Oncologist

First Consult with Medical

Oncologist Awaiting

CVAD insertion First treatment

with AC Surgery Pathology Referral 1st Consult Port-a-cath Chemotherapy

10 days 12 days 21 days (sd: 12.0) 19 days (SD: 12.7)

50.4 days (SD: 15.8)

Resources: Biagi, J.J., Raphael, M.J., Mackillop, et al. Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer. JAMA 2005 305(22):2335-2342.

FUTURE DIRECTIONS

• Rapid Cycling Quality Improvement will be used to ensure that the identified barriers can be improved to achieve the recommended timeline of AC in adjuvant colorectal cancer patients.

0

10

20

30

40

50

60

21-34 35-46 47-58 59-70 71-82 83-94 95-106 107-118

Num

ber

of P

atie

nts

Number of Days

FIGURE 1: Histogram of time from surgery to AC for all patients (n=159)

With Complications

Without Complications

ACKNOWLEDGEMENTS

• The search strategy yielded 507 patients diagnosed with colorectal cancer in the last 7 years at SMH • Of the 507 identified patients, data extraction was completed for 159 patients • Table 2 highlights the patient demographics for the 159 included patients

• For patients who experienced no surgical complications, the mean number of days between surgery and AC was 47.5 with a standard deviation (SD) of 13.7. In contrast, patients who had surgical complications had a mean time of 60.9 with a SD of 18.4. This difference proved to be statistically significant, supporting the hypothesis that patients with surgical complications will require a longer recovery time than patients without complications. Consequently, these patients also experienced a longer wait time between surgery and first treatment with AC.

5%

26%

38%

31%

FIGURE 2: Percentage of patients treated following the

older guidelines versus the new recommendations

<4 weeks

4-6 weeks

6-8 weeks

>8 weeks

• Figure 2 depicts the number of patients treated at less than four weeks, between 4 and 6 weeks (new recommendations, between 6 and 8 weeks (old recommendations), and greater than 8 weeks.

• Finally, only 18.9% of patients recurred. While trends were identified, association between delay and recurrence was weak (p=0.146). Medical complications correlated strongly with recurrence (p=0.047). Patients with complications had a higher rate of recurrence (32.4% vs 15.2%).