Early Onset Is a Negative Prognostic Factor in High-Risk Stage III CRC, Hinting to Aggressive Nature of the Disease

PURPOSE Early-onset (EO) colorectal cancer (CRC, age < 50 years) incidence is increasing. Decisions on optimal adjuvant therapy should consider treatment adherence, adverse events, and expected outcomes in a population with life expectancy longer than later-onset (LO) CRC (age ≥ 50 years). MATERIALS AND METHODS Individual patient data from six trials in the International Duration Evaluation of Adjuvant Chemotherapy database were analyzed. Characteristics, treatment adherence, and adverse events in stage II or III EO-CRC and LO-CRC were compared. To reduce confounders of non–cancer-related deaths because of age or comorbidities, time to recurrence (3-year relapse-free rate) and cancer-specific survival (5-year cancer-specific mortality rate) were considered. RESULTS Out of 16,349 patients, 1,564 (9.6%) had EO-CRC. Compared with LO-CRC, EO-CRC had better performance status (86% v 80%, P < .01), similar T stage (% T1-3/T4: 76/24 v 77/23, P = .97), higher N2 disease rate (24% v 22%, P < .01), more likely to complete the planned treatment duration (83.2% v 78.2%, P < .01), and received a higher treatment dose intensity, especially with 6-month regimens. Gastrointestinal toxicity was more common in EO-CRC; hematologic toxicity was more frequent in LO-CRC. Compared with LO-CRC, significantly worse cancer-specific outcomes were demonstrated especially in high-risk stage III EO-CRC: lower 3-year relapse-free rate (54% v 65%; hazard ratio [HR] 1.33; 95% CI, 1.14 to 1.55; P value < .001) and higher 5-year cancer-specific mortality rate (24% v 20%; HR 1.21; 95% CI, 1.00 to 1.47; P value < .06). In this subgroup, no difference was observed with 3 or 6 months of therapy, with equally poor disease-free survival rates (57% v 56%; HR 0.97; 95% CI, 0.73 to 1.29; P value = .85). CONCLUSION Young age is negatively prognostic in high-risk stage III CRC and associated with significantly higher relapse rate; this is despite better treatment adherence and higher administered treatment intensity, suggesting more aggressive disease biology.

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Mutated KRAS Is an Independent Negative Prognostic Factor for Survival in NSCLC Stage III Disease Treated with High-Dose Radiotherapy

Lung Cancer International ◽

10.1155/2012/587424 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

A. Hallqvist ◽

F. Enlund ◽

C. Andersson ◽

H. Sjögren ◽

A. Hussein ◽

...

Keyword(s):

Prognostic Factor ◽

Induction Chemotherapy ◽

Phase Ii Study ◽

Stage Iii ◽

Egfr Mutations ◽

High Dose ◽

Kras Mutations ◽

Negative Prognostic Factor ◽

Combined Radiochemotherapy ◽

Independent Negative Prognostic Factor

Background. The main attention regarding prognostic and predictive markers in NSCLC directs towards the EGFR-targeted pathway, where the most studied genetic alterations include EGFR mutations, EGFR copy number, and KRAS mutations. We wanted to explore the prognostic impact of mutated KRAS in the stage III setting treated with high-dose radiochemotherapy. Methods. Samples were obtained from patients participating in two prospective studies of locally advanced NSCLC receiving combined radiochemotherapy: the RAKET study, a randomized phase II study where patients were treated with induction chemotherapy (carboplatin/paclitaxel) followed by concurrent radiochemotherapy, and the Satellite trial, a phase II study with induction chemotherapy (cisplatin/docetaxel) followed by radiotherapy concurrent cetuximab. The samples were analysed regarding KRAS mutations, EGFR mutations, and EGFR FISH positivity. Results. Patients with mutated KRAS had a significantly inferior survival, which maintained its significance in a multivariate analysis when other possible prognostic factors were taken into account. The prevalence of KRAS mutations, EGFR mutations, and EGFR FISH positivity were 28.8%, 7.5%, and 19.7%, respectively. Conclusion. Mutated KRAS is an independent negative prognostic factor for survival in NSCLC stage III disease treated with combined radiochemotherapy. The prevalence of KRAS mutations and EGFR mutations are as expected in this Scandinavian population.

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Analysis of p53/BAX in primary colorectal carcinoma: Low BAX protein expression is a negative prognostic factor in UICC stage III tumors

International Journal of Cancer ◽

10.1002/ijc.10380 ◽

2002 ◽

Vol 99 (4) ◽

pp. 589-596 ◽

Cited By ~ 44

Author(s):

Katharina Schelwies ◽

Isrid Sturm ◽

Patricia Grabowski ◽

Hans Scherübl ◽

Isabell Schindler ◽

...

Keyword(s):

Prognostic Factor ◽

Colorectal Carcinoma ◽

Protein Expression ◽

Stage Iii ◽

Uicc Stage ◽

Bax Protein ◽

Negative Prognostic Factor

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Early-onset stage II/III colorectal adenocarcinoma in the IDEA database: Treatment adherence, toxicities, and outcomes from adjuvant fluoropyrimidine and oxaliplatin.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.3517 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 3517-3517

Author(s):

Elisa Fontana ◽

Jeffrey P. Meyers ◽

Alberto F. Sobrero ◽

Timothy Iveson ◽

Anthony Frank Shields ◽

...

Keyword(s):

High Risk ◽

Early Onset ◽

Late Onset ◽

Performance Status ◽

Dose Intensity ◽

Stage Ii ◽

Stage Iii ◽

Cancer Specific Survival ◽

T Stage ◽

N2 Disease

3517 Background: Incidence of early-onset colorectal cancer (eoCRC, age < 50) is steadily increasing. Decisions on adjuvant treatment (adjTx) regimen and duration should consider tx adherence, toxicity (tox) and expected outcomes in a population with life-expectancy longer than late onset CRC (loCRC, age ≥ 50). Methods: Individual patient data from stage II/III patients (pts) from 6 randomised trials in the IDEA database were used to compare characteristics, tx adherence, and adverse events of eoCRC to loCRC. To reduce the confounder of non-cancer-related deaths due to age/co-morbidities, time-to-recurrence (TTR) and cancer-specific survival (CSS) were compared by stratified Gay k-sample test. 5-year cancer-specific mortality (CSM) rate were estimated by adjusted cumulative incidence function. 3-year relapse-free survival (RFS) rate were compared by stratified and adjusted COX models. Results: Out of 16,349 pts included, 1564 (9.6%) were eoCRC. Compared to loCRC, eoCRC had lower percent of male pts (51% vs 57%, p < 0.01) better performance status (PS0 86% vs 80%, p < 0.01), similar T stage distribution (% T1-3/T4: 76/24 vs 77/23, p = 0.97), higher rate of N2 disease (24% vs 22%, p < 0.01), more likely to complete pre-planned duration of adjTx (83.2% vs 78.2%, p < 0.01) and received a higher tx intensity especially with 6 month tx (mean oxaliplatin dose intensity 75% vs 72%, p < 0.01; capecitabine 85% vs 78%, p < 0.01; 5FU 85% vs 82% p < 0.01). Gastrointestinal tox was more common in eoCRC (any grade nausea 58% vs 45%, p < 0.01; any grade vomiting 22% vs 16%, p < 0.01); haematological tox was more frequent in loCRC (62% vs, 69%, p = < 0.01); any grade neuropathy rate was similar (75%). Significant interaction was found between age and T stage for TTR (p = 0.04). Clinical outcome estimates and comparisons are shown in Table. Notably, high risk stage III (T4/N2) eoCRC had significantly lower 3-y RFS rate (54% vs 64%, HRadj 0.74, p < 0.01). Conclusions: eoCRC have better tx adherence than loCRC, as expected. While in high risk stage II and low risk stage III, cancer-specific outcomes are not different, in high risk stage III young age is negatively prognostic and associated with significantly higher relapse rate and risk of CRC death; this is despite a higher administered adjTx-intensity, suggesting a more aggressive disease biology. Clinical trial information: NCT00749450 (SCOT); NCT00646607 (TOSCA); NCT01150045 (CALGB/SWOG 80702); NCT00958737 (IDEA France) [Table: see text]

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