Improvement in colorectal cancer outcomes over time is limited to patients with left-sided disease

Rumpold, Holger; Hackl, Monika; Petzer, Andreas; Wolf, Dominik

doi:10.1007/s00432-021-03868-0

Cited by 3 publications

(2 citation statements)

References 60 publications

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“…These new treatment options have improved overall survival (OS) of patients with mCRC from approximately 1 year in the era of single agent 5-fluorouracil (5-FU) to more than 3 years with currently available options ( 2 ). This remarkable increase in survival appears to be largely based on the outcome data of left-sided mCRC ( 4 ). Left-sided mCRC has a more favourable predictive biological profile with a lower incidence of RAS mutations ( RAS -MT) ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Current concepts of anti-EGFR targeting in metastatic colorectal cancer

Doleschal¹,

Petzer²,

Rumpold³

2022

Front. Oncol.

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Anti-EGFR targeting is one of the key strategies in the treatment of metastatic colorectal cancer (mCRC). For almost two decades oncologists have struggled to implement EGFR antibodies in the mCRC continuum of care. Both sidedness and RAS mutational status rank high among the predictive factors for the clinical efficacy of EGFR inhibitors. A prospective phase III trial has recently confirmed that anti-EGFR targeting confers an overall survival benefit only in left sided RAS-wildtype tumors when given in first line. It is a matter of discussion if more clinical benefit can be reached by considering putative primary resistance mechanisms (e.g., HER2, BRAF, PIK3CA, etc.) at this early stage of treatment. The value of this procedure in daily routine clinical utility has not yet been clearly delineated. Re-exposure to EGFR antibodies becomes increasingly crucial in the disease journey of mCRC. Yet re- induction or re-challenge strategies have been problematic as they relied on mathematical models that described the timely decay of EGFR antibody resistant clones. The advent of liquid biopsy and the implementation of more accurate next-generation sequencing (NGS) based high throughput methods allows for tracing of EGFR resistant clones in real time. These displays the spatiotemporal heterogeneity of metastatic disease compared to the former standard radiographic assessment and re-biopsy. These techniques may move EGFR inhibition in mCRC into the area of precision medicine in order to apply EGFR antibodies with the increase or decrease of EGFR resistant clones. This review critically discusses established concepts of tackling the EGFR pathway in mCRC and provides insight into the growing field of liquid biopsy guided personalized approaches of EGFR inhibition in mCRC.

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Section: Introductionmentioning

confidence: 99%

Current concepts of anti-EGFR targeting in metastatic colorectal cancer

Doleschal¹,

Petzer²,

Rumpold³

2022

Front. Oncol.

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“…Some clinicopathological characteristics have been associated with CC prognosis, such as age, race, and tumor site (3)(4)(5). Patients with proximal CC (right-sided CC) were shown to have a worse prognosis than those with distal CC (left-sided CC) (6). Several prediction models have been developed to predict the survival of CC patients.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a survival prediction model for 113,239 patients with colon cancer: a retrospective cohort study

Liu¹,

Lai²,

Yang³

et al. 2022

J Gastrointest Oncol

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Background: Colon cancer (CC) is the third most commonly diagnosed malignant tumor and remains the second leading cause of cancer-related deaths worldwide. However, the risk assessment of poor prognosis of CC is limited in previous studies. This study aimed to develop a predictive nomogram for the survival of CC patients. Methods:In this retrospective cohort study, 113,239 CC patients from the Surveillance, Epidemiology, and End Results (SEER) database were randomly divided into training (n=56,619) and testing (n=56,620) sets with a ratio of 1:1. Demographic, clinical data and survival status of patients were extracted. The outcomes were 3-and 5-year survival of CC. Univariate and multivariate Cox regression analyses were used to screen the predictors to develop the predictive nomogram. Internal validation and stratified analyses were further assessed the nomogram. The C-index and area under the curve (AUC) were calculated to estimate the model's predictive capacity, and calibration curves were adopted to estimate the model fit.Results: Totally 38,522 (34.02%) patients died during the 5-year follow-up. The nomogram incorporated variables associated with the prognosis of CC patients, including age, gender, marital status, insurance status, tumor grade, stage (T/N/M), surgery, and number of nodes examined, with a C-index of 0.775 in the training set and 0.774 in the testing set. The AUCs of the nomogram for the 3-and 5-year survival prediction in the training set were 0.817 and 0.808, with the sensitivity of 0.688 and 0.716, and the specificity of 0.785 and 0.740, respectively. Similar results were found in the testing set. The C-index of the predictive nomogram for male, female, White, Black, and other races was 0.769, 0.779, 0.773, 0.770, and 0.770, respectively. The calibration curves for the nomogram in the above five cohorts showed a good agreement between actual and predicted values. Conclusions:The nomogram may exhibit a certain predictive performance based on the SEER database, which may provide individual survival predictions for CC patients.

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