Carol Beeke

South Australian clinical registry for metastatic colorectal cancer.

Introduction:  The aims of the South Australian Clinical Registry for Metastatic Colorectal Cancer are to record case outcomes according to site of recurrence and mode of clinical practice and to utilize the accumulated information for quality assurance activities.

Does the primary site of colorectal cancer impact outcomes for patients with metastatic disease

Previous reports have described differences in biology and outcome for colorectal cancer based on whether the primary is right or left sided. Further division by right, left, and rectum or even exact primary site has also been explored. Possible differences in response to biological agents have also been reported based on side of primary lesion.

Survival Differences in Patients With Metastatic Colorectal Cancer and With Single Site Metastatic Disease at Initial Presentation: Results From South Australian Clinical Registry for Advanced Colorectal Cancer

BACKGROUND Colorectal cancer is the third most common cancer in Australia. The median overall survival for metastatic colorectal cancer is nearly 2 years. However, there may be survival differences based on site of metastatic disease. METHODS Data was collected from the South Australian Registry for Advanced Colorectal Cancer. A total of 1207 patients with single site metastatic disease at initial diagnosis were subclassified into 6 subgroups: liver only (n = 780), pelvic only (n = 148), lung only (n = 142), lymph node only (n = 95), bone only (n = 32), and brain only (n = 10). Univariate and multivariate parametric survival analyses were performed. RESULTS Median overall survival was 20.3 months for the whole group. The overall survival for lung-only metastases group was 41.1 months followed by liver- and pelvic-only disease groups (22.8 and 23.8 months, respectively). Patients with isolated bone-only and brain-only metastases had poor overall survival (5.1 and 5.7 months, respectively). On multivariate analysis, prognosis was superior for the lung-only group. CONCLUSIONS Lung only group had the longest median overall survival. Bone and brain sites had a poor outlook. Site of metastatic disease at initial presentation may be prognostic.

Colorectal Cancer Survival: An Analysis of Patients With Metastatic Disease Synchronous and Metachronous With the Primary Tumor

BACKGROUND Whether metastatic colorectal cancer (mCRC) that presents synchronously with the primary lesion behaves differently from mCRC that appears metachronously to the primary disease is not clear. PATIENTS AND METHODS The South Australian Clinical Registry for mCRC collects data for patients diagnosed after February 2006. Data from 2502 patients, available on October 22, 2012, were analyzed according to stage at initial diagnosis (SAID) to compare outcomes between metachronous tumors (MTs) (stages I, II, III) and synchronous tumors (STs) (stage IV). Overall survival (OS) was calculated from the date of mCRC diagnosis. RESULTS Patients with ST had more liver-only metastases, and patients with MT had more lung-only, non-lung and non-liver, and non-lung metastases. The median time to recurrence differed significantly according to SAID: stage I, 49.3 mo (n = 29), stage II, 25.2 mo (n = 346) and stage III, 18.4 mo (n = 497). The median OS was longer for patients with MT than for those with ST (19.0 vs.14.9 mo, P = .003). For patients who received any treatment for mCRC, the OS was longer for patients with MT than for those with ST (19.2 vs. 15.3 mo, P = .005). In patients who received only chemotherapy for mCRC, the median OS was longer for patients with MT than for those with ST (15.2 vs. 9.9 mo, P < .0001). No difference in OS between the MT and ST groups for patients who did not receive treatment for mCRC (1.6 vs. 2.6 mo; P = .95). CONCLUSION Patients with MT have a longer OS than those with ST, independent of treatment. Classification of patients according to whether they have metachronous or synchronous presentation of mCRC is prognostic. These results may add further support for population screening with the aim to reduce de novo metastatic disease.

A population-based study of metastatic colorectal cancer in individuals aged ≥ 80 years: findings from the South Australian Clinical Registry for Metastatic Colorectal Cancer

Life expectancy is increasing, and more patients are presenting with cancer at an advanced age (≥80 years). Optimal management for this group of patients has not been well defined.

Impact of age on choice of chemotherapy and outcome in advanced colorectal cancer

BACKGROUND Age is a major risk factor for development of sporadic colorectal cancer but elderly patients are underrepresented in clinical trials and are potentially offered chemotherapy less often. METHODS Data were obtained from South Australian Clinical Registry for advanced colorectal cancer between 1st February 2006 and 9th September 2010. Patients who received chemotherapy were analysed to assess the impact of single versus combination chemotherapy and to assess the outcome in two age cohorts, age < 70 years and ≥ 70 years. RESULTS Out of a total of 1745 patients in the database during this time period, 951 (54.5%) received systemic chemotherapy. 286 (30%) received first line therapy (median age 74 years) with single agent fluoropyrimidine and 643 patients (68%) received first line combination chemotherapy (median age 64 years). The median overall survival of patients receiving first line combination chemotherapy was 23.9 months compared to 17.2 months for those who received single agent fluoropyrimidine (p<0.001). Combination chemotherapy was given to 81% of patients aged < 70 years compared to 53% of those ≥ 70 years. There was no significant difference in median overall survival of patients receiving chemotherapy by age cohort, 21.3 months for age <70 years and 21.1 months for age ≥ 70 years (p = 0.4). CONCLUSION Treatment outcomes are comparable in both the elderly and younger patients. Patients who received initial combination chemotherapy were younger and had a longer median overall survival. In our study, age appeared to influence the treatment choices but not necessarily outcome.

Rechallenge with oxaliplatin and fluoropyrimidine for metastatic colorectal carcinoma after prior therapy

Objectives:Patients with advanced colorectal cancer (CRC) who have received oxaliplatin, 5-fluoropyrimidine, and irinotecan chemotherapy (with or without bevacizumab) and antiepidermal growth factor receptor therapy (if KRAS is wild type) have no further standard treatment options. Although repeating a prior chemotherapy [in particular, oxaliplatin and fluoropyrimidine (FOX)] is an option, there is very little evidence in the literature for this approach; thus, we reviewed our registry to assess the frequency and outcome of rechallenging with FOX. Methods:Patients who had been rechallenged with FOX were identified from the South Australian metastatic CRC database. Patient characteristics were analyzed, and tumor response was retrospectively assessed using Response Evaluation Criteria in Solid Tumors criteria. Results:Twenty patients were eligible for inclusion in this analysis. The number of prior lines of therapy received for metastatic CRC was 4 lines for 2 patients, 3 lines for 6 patients, 2 lines for 7 patients, and 1 line for 3 patients, with 3 patients having received oxaliplatin as adjuvant therapy. Four patients had received bevacizumab previously, 7 patients had undergone antiepidermal growth factor receptor treatment, and 4 patients had undergone liver resection earlier. Response rate was 18%, and 47% had stable disease. The median progression-free survival was 3.7 months, median overall survival was 7.8 months, and 1-year survival was 37%. Conclusions:In this selected population, there is evidence of modest activity of rechallenge with FOX chemotherapy, although radiologic response is uncommon.

Do metastatic colorectal cancer patients who present with late relapse after curative surgery have a better survival

Background:Patients who relapse after potentially curative surgery for colorectal cancer tend to relapse within 5 years. There is, however, a group of patients who relapse beyond 5 years after resection and this late relapsing group may have a different behaviour and prognosis.Methods:We analysed data from a prospective population-based registry to compare the characteristics and survival of relapsed patients with metachronous mCRC. Patients were categorised into relapse at <2, 2–5 and >5 years following their initial surgery. Univariate log-rank tests and multivariate Cox regression was performed to determine whether time to relapse (TTR) and other factors were associated with overall survival (OS).Results:A total of 750 metachronous mCRC patients were identified. In all, 56% relapsed ⩽2 years, 32.4% at 2–5 years and 11.6% >5 years. Median survival time from the time of diagnosis of mCRC for the three groups was 17.6, 26.1 and 27.5 months, respectively. Short TTR (<2 years) was significantly associated with survival (HR=0.75, 95% confidence interval (CI)=0.60–0.93 and HR=0.73, 95% CI=0.53–1.01, respectively, for 2–5 and >5 years vs <2 years, P<0.05). However, there was no significant difference in survival between patients who relapsed at 5 years or later compared with those who relapsed between 2 and 5 years (HR=0.98, 95% CI=0.69–1.38, P=0.90).Conclusion:TTR within 2 years is an independent predictor of shorter survival time for mCRC patients who experience a relapse. These data do not support the hypothesis that patients who have late relapse late (>5 years) have a ‘better’ biology or survival compared with patients with a TTR of 2–5 years.

“Watchful waiting” for metastatic colorectal cancer, antediluvian or an option to be considered again?

Aim:  The role of chemotherapy in metastatic colorectal cancer (mCRC) is firmly established and the option of watchful waiting (WW) has become an alternative rarely considered. However, there may be a group of patients who are diagnosed with low volume and asymptomatic disease and who may be suitable for a WW plan.

Association of BMI with overall survival in patients with mCRC who received chemotherapy versus EGFR and VEGF-targeted therapies

Although a raised body mass index (BMI) is associated with increased risk of colorectal cancer (CRC) and recurrence after adjuvant treatment, data in the metastatic setting is limited. We compared overall survival (OS) across BMI groups for metastatic CRC, and specifically examined the effect of BMI within the group of patients treated with targeted therapies (TT). Retrospective data were obtained from the South Australian Registry for mCRC from February 2006 to October 2012. The BMI at first treatment was grouped as underweight <18.5 kg/m2, Normal = 18.5 to <25 kg/m2, Overweight = 25 to <30 kg/m2, Obese I = 30 to <35 kg/m2, Obese II ≥35 kg/m2. Of 1174 patients, 42 were underweight, 462 overweight, 175 Obese I, and 77 Obese II. The OS was shorter for patients who were underweight and overweight compared to normal (OS 13.7 and 22.3 vs. 24.1 months, respectively, hazard ratio [HR] 2.21 and 1.23). The adjusted median OS was longer for normal versus overweight or obese I patients receiving chemotherapy + targeted therapy (35.7 vs 25.1 or 22.8 months, HR 1.59 and 1.63, respectively) with no difference in OS for chemotherapy alone. On breakdown by type of targeted therapy, overweight and obese I patients had a poorer outcome with Bevacizumab. The BMI is predictive of a poorer outcome for underweight and overweight patients in the whole population. Of those receiving chemotherapy and targeted therapy, BMI is an independent predictor for OS for overweight and obese I patients, specifically for those treated with Bevacizumab. Patients who are overweight or obese (group I) may be a target group for lifestyle and nutrition advice to improve OS with TT.