The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern

<p><b>Background:</b> Pattern of spread in patients with metastatic colorectal cancer (mCRC) is variable and may reflect different biology in subsets of patients. This is a retrospective study to explore the outcome of patients with mCRC based on their site of metastasis at diagnosis and to explore the association between tumor characteristics [KRAS/RAS, BRAF, mismatch repair (MMR) status, site of primary] and the site of metastasis.</p> <p><b>Methods:</b> Patients from two Australian databases were divided into six groups based on site of metastasis at time of diagnosis of metastatic disease; lung-only, liver-only, lymph node-only or any patients with brain, bone or peritoneal metastases. Primary endpoint was overall survival (OS) of each cohort compared with the rest of the population. A Mantel–Haenszel chi-squared test used to explore the association between site of metastasis and selected tumor characteristics.</p> <p><b>Results:</b> Five thousand nine hundred and sixty-seven patients were included. In a univariate analysis, median OS was significantly higher when metastases were limited to lung or liver and shorter for those with brain, bone or peritoneal metastases (<i>p</i> < .001) in both datasets. BRAF mutation was strongly associated with peritoneal metastases (relative risk = 1.8, <i>p</i> < .001) with lower incidence of lung (RR = 0.3, <i>p</i> = .004) and liver (RR = 0.7, <i>p</i> = .005) limited metastases. Lung-only metastases were more frequent with KRAS/RAS mutation (RR = 1.4, <i>p</i> = .007). Left colon tumors were associated with bone (RR = 1.6, <i>p</i> < .001) and lung-only metastases (RR = 2.3, <i>p</i> = .001) while peritoneal spread was less frequent compared with right colon tumors (RR = 0.6, <i>p</i> < .001). Rectal cancer was associated with brain, bone and lung metastases (RR = 1.7; <i>p</i> = .002, 1.7; <i>p</i> < .001, 2.0; <i>p</i> < .001). Liver-only metastases were less frequent in deficient MMR tumors (RR = 0.7, <i>p</i> = .01).</p> <p><b>Conclusion:</b> Survival duration with mCRC is related to the site of metastases with lung limited disease showing a more favorable survival outcome compared to other single metastatic site disease. The BRAF mutation and primary rectal cancer were associated with poor prognostic metastatic sites.</p

Comorbidity and cervical cancer survival of Indigenous and non-Indigenous Australian women: A semi-national registry-based cohort study (2003-2012)

<div><p>Background</p><p>Little is known about the impact of comorbidity on cervical cancer survival in Australian women, including whether Indigenous women’s higher prevalence of comorbidity contributes to their lower survival compared to non-Indigenous women.</p><p>Methods</p><p>Data for cervical cancers diagnosed in 2003–2012 were extracted from six Australian state-based cancer registries and linked to hospital inpatient records to identify comorbidity diagnoses. Five-year cause-specific and all-cause survival probabilities were estimated using the Kaplan-Meier method. Flexible parametric models were used to estimate excess cause-specific mortality by Charlson comorbidity index score (0,1,2+), for Indigenous women compared to non-Indigenous women.</p><p>Results</p><p>Of 4,467 women, Indigenous women (4.4%) compared to non-Indigenous women had more comorbidity at diagnosis (score ≥1: 24.2% vs. 10.0%) and lower five-year cause-specific survival (60.2% vs. 76.6%). Comorbidity was associated with increased cervical cancer mortality for non-Indigenous women, but there was no evidence of such a relationship for Indigenous women. There was an 18% reduction in the Indigenous: non-Indigenous hazard ratio (excess mortality) when comorbidity was included in the model, yet this reduction was not statistically significant. The excess mortality for Indigenous women was only evident among those without comorbidity (Indigenous: non-Indigenous HR 2.5, 95%CI 1.9–3.4), indicating that factors other than those measured in this study are contributing to the differential. In a subgroup of New South Wales women, comorbidity was associated with advanced-stage cancer, which in turn was associated with elevated cervical cancer mortality.</p><p>Conclusions</p><p>Survival was lowest for women with comorbidity. However, there wasn’t a clear comorbidity-survival gradient for Indigenous women. Further investigation of potential drivers of the cervical cancer survival differentials is warranted.</p><p>Impact</p><p>The results highlight the need for cancer care guidelines and multidisciplinary care that can meet the needs of complex patients. Also, primary and acute care services may need to pay more attention to Indigenous Australian women who may not obviously need it (i.e. those without comorbidity).</p></div

Cause-specific survival for NSW women (n = 1,069) by Charlson Comorbidity Index score, stratified by cancer stage, adjusted for age at diagnosis and Indigenous status.

<p>Cause-specific survival for NSW women (n = 1,069) by Charlson Comorbidity Index score, stratified by cancer stage, adjusted for age at diagnosis and Indigenous status.</p

Demographic characteristics of Indigenous and non-Indigenous women’s Pap smears by abnormality, 2000–2011.

<p>Demographic characteristics of Indigenous and non-Indigenous women’s Pap smears by abnormality, 2000–2011.</p

Adjusted hazard ratios for five-year cause-specific mortality for Australian women, 22–89 years, diagnosed with cervical cancer, 2003–2012 ^{a, b}.

<p>Adjusted hazard ratios for five-year cause-specific mortality for Australian women, 22–89 years, diagnosed with cervical cancer, 2003–2012 ^{a, b}.</p

Crude five-year Kaplan-Meier survival estimates for 4,467 Australian women (22–89 years)^a diagnosed with cervical cancer, 2003–2012, stratified by Charlson comorbidity score (0,1,2+).

<p>Crude five-year Kaplan-Meier survival estimates for 4,467 Australian women (22–89 years)^a diagnosed with cervical cancer, 2003–2012, stratified by Charlson comorbidity score (0,1,2+).</p

Cause-specific mortality rates for Indigenous and non-Indigenous women stratified by Charlson Comorbidity Index score, adjusted for age at diagnosis, area-level socioeconomic status, and histology type.

<p>Cause-specific mortality rates for Indigenous and non-Indigenous women stratified by Charlson Comorbidity Index score, adjusted for age at diagnosis, area-level socioeconomic status, and histology type.</p

Demographic and clinical characteristics of 4,467 Australian women diagnosed with cervical cancer 2003–2012, by Indigenous status.

<p>Demographic and clinical characteristics of 4,467 Australian women diagnosed with cervical cancer 2003–2012, by Indigenous status.</p

Characteristics of Indigenous and non-Indigenous women at their first recorded Pap smear.

<p>Characteristics of Indigenous and non-Indigenous women at their first recorded Pap smear.</p

Time trends in prevalence of cytology low-grade and histologically confirmed high-grade abnormalities by age-group, 2000–2011.

<p>Time trends in prevalence of cytology low-grade and histologically confirmed high-grade abnormalities by age-group, 2000–2011.</p