Prognostic factors for 60-day mortality in first-line treatment of metastatic colorectal cancer (mCRC): individual patient analysis of four randomised, controlled trials by the AIO colorectal cancer study group

Gießen, Clemens; Graeven, Ullrich; Laubender, Rüdiger P.; Modest, Dominik Paul; Schulz, Christoph; Porschen, Rainer; Schmiegel, Wolff; Reinacher‐Schick, Anke; Hegewisch-Becker, S.; Stintzing, Sebastian

doi:10.1093/annonc/mdt402

Cited by 12 publications

(9 citation statements)

References 18 publications

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“…Leukocytosis, a well-known marker of inflammation, has been associated with worse outcomes in many cancers (20). In colorectal cancer, a meta-analysis of four large randomized clinical trials of firstline chemotherapy for metastatic colorectal cancer showed that 60-day mortality was higher, with a baseline leukocyte count higher than 8000/mm 3 (21). A previous meta-analysis of clinical trials of 5-fluouracil in metastatic colorectal cancer showed similar results—survival was poorer in patients with a baseline leukocyte count higher than 10 000/mm 3 (22).…”

Section: Discussionmentioning

confidence: 99%

Clinical Predictors of Early Mortality in Colorectal Cancer Patients Undergoing Chemotherapy: Results From a Global Prospective Cohort Study

Sohal

Kuderer

Shepherd

et al. 2017

JNCI Cancer Spectrum

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Background Early mortality is a major problem in colorectal cancer (CRC). We have shown that Khorana Score is predictive of early mortality in other cancers. Here, we evaluated the value of this score and other prognostic variables in predicting early mortality in CRC. Methods CANTARISK was a prospective, noninterventional, global cohort study in patients with CRC initiating a new chemotherapy regimen. Data were collected at zero, two, four, and six months. Early mortality was defined as death within six months of enrollment. All data were compiled centrally and analyzed after the study closed. Statistically significant univariate associations were tested in multivariable models; adjusted odds ratios (ORs) are presented. Statistical tests were two-sided. Results From 2011 to 2012, 1789 CRC patients were enrolled. The median age was 62 years; 71% were Caucasian. One-third (35%) had a rectal primary, and 65% had metastatic disease. There were 184 (10.3%) patients who died during their first six months in the study. For low, intermediate, and high Khorana Score, there were 8.1%, 11.2% and 32.5% deaths, respectively. In multivariable analyses, Khorana Score was an independent predictor of early death (OR for high/intermediate vs low score = 1.70, P = .0027), in addition to age (OR for each incremental year = 1.03, P = .0014), presence of metastatic disease (OR = 3.28, P < .0001), and Easter Cooperative Oncology Group Performance Status Score of 2 or higher (OR = 3.85, P < .0001). Conclusions This study demonstrates that Khorana Score is predictive of early mortality in CRC patients. Intermediate- or high-risk patients, as defined by this score, may benefit from additional interventions aimed at reducing early mortality.

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Section: Discussionmentioning

confidence: 99%

Clinical Predictors of Early Mortality in Colorectal Cancer Patients Undergoing Chemotherapy: Results From a Global Prospective Cohort Study

Sohal

Kuderer

Shepherd

et al. 2017

JNCI Cancer Spectrum

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“…Although the analyses were adjusted for ECOG performance status and line of therapy these findings could be influenced by disease burden and aggressiveness. Thus, future studies should focus on single tumour types in prior untreated patients including established scores determining biology of disease and co-morbidity [ 11 – 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, these factors were among the main issues of relevance for cancer patients in a recent survey [ 26 ]. The impact of SYB before chemotherapy on treatment efficacy is well known and reflected by the prognostic value of performance status on survival, which has therefore been integrated in different scores in the last decades [ 11 – 14 , 27 – 29 ]. Moreover, physical symptoms at baseline significantly predicted treatment efficacy in metastatic gastrointestinal cancer [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

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Integrating patient reported measures as predictive parameters into decisionmaking about palliative chemotherapy: a pilot study

et al. 2016

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BackgroundSystemic treatment has proven to improve physical symptoms in patients with advanced cancer. Relationship between quality of life (QoL) or symptom burden (SYB) and treatment efficacy (tumour response and survival) is poorly described. Therefore, we evaluated the predictive value of pretreatment QoL and SYB on treatment outcomes.MethodsEligible patients had metastatic gastrointestinal cancers and were about to receive 1st/2nd line palliative chemotherapy. 47 patients were consecutively enrolled. QoL and SYB were assessed by EORTC QLQ-C30 and MSKCC MSAS questionnaires before treatment and after first response evaluation after 8–12 weeks. Logistic regression analysis of QoL and SYB for prediction of objective treatment efficacy was performed. Patients were categorized according to response rate (RR) based on RECIST1.1 and progression free survival (PFS). PFS was categorized by a ratio (individual PFS/expected PFS) in above median (ratio ≥ 1) or below median PFS (ratio < 1). QoL and SYB were analysed for RR groups (partial response, stable or progressive disease) and PFS ratio (PFSR).ResultsObjective response to chemotherapy and increase in PFS were associated with better pretreatment QoL and less SYB. Patients with future objective treatment efficacy (PFSR ≥ 1) evidenced clinically relevant better role/emotional/cognitive/social functioning and less fatigue and appetite loss at baseline in comparison to PFSR < 1 (>10 points difference). Lowest scores in all functioning scales at treatment start were seen in patients with future PFSR < 1. Global health status (EORTC), PSYCH subscale and global distress index (MSAS) predicted PFSR, even if adjusted for gender, age, cancer type, ECOG and line of treatment (p < 0.05). Interestingly, improved QoL and SYB (subjective benefit) were noted even in patients with worse pretreatment status and no objective tumour response.ConclusionFuture non-responders seem to show distinct QoL patterns before chemotherapy. This may facilitate early detection of patients deriving less or even no benefit from treatment regarding prolongation of survival. Even in patients with primarily progressive disease QoL and SYB may improve during treatment. Integration of QoL and SYB assessment into decision-making about palliative chemotherapy seem to be an important approach to improve patient outcome and should be further evaluated.

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“…A variety of clinical prognostic factors have been evaluated and combined in scores in the treatment of mCRC, showing the high relevance of performance status, number of metastatic sites, age, and tumor stage [13,14,15]. In addition, elevated serum carcinoembryonic antigen (CEA) is a poor prognostic factor for both localized and metastatic disease [16,17,18].…”

Section: Introductionmentioning

confidence: 99%

Baseline and On-Treatment Markers Determining Prognosis of First-Line Chemotherapy in Combination with Bevacizumab in Patients with Metastatic Colorectal Cancer

Quidde¹,

Denne²,

Kutscheidt³

et al. 2017

Oncol Res Treat

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Background: In metastatic colorectal cancer, no upfront or on-treatment markers are available to determine the prognosis or efficacy for chemotherapy in combination with bevacizumab. Patients and Methods: The current analysis was performed to evaluate the prognostic value of disease and patient characteristics (age, number of metastatic sites, stage of primary tumor, performance status, carcinoembryonic antigen (CEA)) and on-treatment changes of CEA (response after 8-12 weeks of treatment and specific patterns of CEA kinetics) in patients from an observational cohort study of chemotherapy with bevacizumab. Results: Baseline factors were available from 1,438 patients. Patients with baseline CEA levels > 20 ng/ml, more than 1 metastatic site, and age > 75 years showed significantly lower progression-free (PFS) and overall survival in multivariate analysis. A CEA response of > 30% during treatment was associated with increased PFS. In addition, the pattern of CEA kinetics predicts survival and response to treatment. Conclusion: In summary, baseline CEA, number of metastatic sites, and age are strong independent prognostic factors for survival. By monitoring CEA, clear patterns with distinct prognostic value can be determined. CEA kinetics and/or response after 8-12 weeks might be a useful and simple tool to stratify the post-induction treatment approach based on individual prognosis in the future.

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Prognostic factors for 60-day mortality in first-line treatment of metastatic colorectal cancer (mCRC): individual patient analysis of four randomised, controlled trials by the AIO colorectal cancer study group

Cited by 12 publications

References 18 publications

Clinical Predictors of Early Mortality in Colorectal Cancer Patients Undergoing Chemotherapy: Results From a Global Prospective Cohort Study

Clinical Predictors of Early Mortality in Colorectal Cancer Patients Undergoing Chemotherapy: Results From a Global Prospective Cohort Study

Integrating patient reported measures as predictive parameters into decisionmaking about palliative chemotherapy: a pilot study

Baseline and On-Treatment Markers Determining Prognosis of First-Line Chemotherapy in Combination with Bevacizumab in Patients with Metastatic Colorectal Cancer

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