scholarly journals Superior Overall Survival in Patients with Colorectal Cancer, Regular Aspirin Use, and Combined Wild-Type PIK3CA and KRAS-Mutated Tumors

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4959
Author(s):  
Leonie Gebauer ◽  
Andrea Nist ◽  
Marco Mernberger ◽  
Thorsten Stiewe ◽  
Roland Moll ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Survival Data ◽  
Wild Type ◽  
Curative Intent ◽  
Mutational Status ◽  
Regular Aspirin ◽  
Overall Survival Benefit ◽  
The Impact ◽  
Prognostic Data

The impact of aspirin use after the diagnosis of colorectal cancer is unknown. Among others, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) mutational status was proposed as a molecular biomarker for the response to adjuvant aspirin therapy. However, prognostic data on aspirin use after a colorectal cancer diagnosis in relation to KRAS mutational status is limited. In a single-center retrospective study, we obtained KRAS and PIK3CA mutational status in a cohort of 153 patients with a first diagnosis of colorectal cancer receiving tumor surgery with curative intent. PIK3CA mutational status was determined by pyrosequencing, and KRAS mutational status was determined by next-generation sequencing. Clinicopathological data and survival data were assessed using patient records and reporting registers. We observed a significant 10-year overall survival benefit in patients with aspirin use and combined wild-type PIK3CA and mutated-KRAS tumors (HR = 0.38; 95% CI = 0.17–0.87; p = 0.02), but not in patients without aspirin use. Our data indicate a benefit of aspirin usage particularly for patients with combined wild-type PIK3CA and mutated-KRAS tumor characteristics.

Metastases resection in colorectal cancer patients with mutation in oncogene BRAF or tumors located on the right side: Experience at the HGUGM.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4041-4041
Author(s):  
Laura Ortega ◽  
Marianela Bringas Beranek ◽  
Natalia Gutiérrez Alonso ◽  
Javier Soto Alsar ◽  
Manuel Alva Bianchi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Disease ◽  
Positive Impact ◽  
Wild Type ◽  
Primary Tumors ◽  
Metastatic Lesions ◽  
Common Location ◽  
The Right ◽  
The Impact

4041 Background: Approximately 25% of patients with colorectal cancer (CRC) debut with metastatic disease. In addition, 25-35% of patients with localized disease at diagnosis develop metastatic lesions during the evolution of their disease. Consequently, approximately 50-60% of patients with CRC will present metastatic lesions at some point in their lives. Metastasis resection has improved the prognosis of these patients, achieving overall survival (OS) that exceed 40 months. However, there are doubts about the benefit of this approach in patients with mutations in oncogene BRAF or tumors located on the right-side, due their poor prognosis. The aim of the study is to analyze the impact of metastases resection on OS of these populations. Methods: We conducted a retrospective analysis of patients with mCRC attended in the Medical Oncology Department of the Hospital General Universitario Gregorio Marañón (Spain) between January 2010 and 2018. Results: 487 patients were identified and included in the analysis. Median age was 71 years (62-81). Most patients were males (62.4%). 55.2% had metastatic lesions at diagnosis. Most patients had ECOG 0-1 at diagnosis of metastatic disease (91.0%). 8.9% of patients had BRAF mutations (n = 21) and 31.8% of patients had primary tumors located on the right-side (n = 152). 474 patients received first-line chemotherapy (97.3%). OS of the entire cohort was 29.67 months; 30.69 months in BRAF mutated patients vs 35.89 in wild-type patients (p = 0.161); 25.29 months in right-side tumors vs 31.02 in left-side tumors (p = 0.044). 306 patients (62.8%) underwent metastases resection. Most common location was liver (51.4%). 147 patients (30.2%) underwent a second metastases resection. Mean number of metastases surgeries was 1.35 (+/-1.40). OS since metastases resection was 24.83 months in BRAF mutated patients vs 41.55 months in wild-type patients (p = 0.020). According to location, it was 35.49 months in right-side tumors vs 43.78 months in left-side tumors (p = 0.106). In BRAF mutated patients, OS was 38.19 months in patients underwent metastases resection vs 18.52 months in non-surgical patients (p = 0.043); 41.51 months vs 16.18 months respectively in patients with tumors located on the right-side (p < 0.001). Conclusions: Metastases resection has a positive impact on overall survival of patients with mutations in oncogene BRAF or right-side tumors, even though their prognosis is still poor compared to patients without these alterations.

Prognostic significance of SATB1 expression in metastatic colorectal cancer: A Nordic prospective cohort study.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 707-707
Author(s):  
Christina Siesing ◽  
Halfdan Sorbye ◽  
Anca Dragomir ◽  
Per Pfeiffer ◽  
Camilla Qvortrup ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prospective Cohort ◽  
Prognostic Value ◽  
Prognostic Significance ◽  
Hazard Ratio ◽  
Wild Type ◽  
Entire Cohort ◽  
Mutational Status ◽  
Satb1 Expression ◽  
The Impact

707 Background: Special AT-rich sequence binding protein 1 (SATB1) is a transcription factor involved in global gene regulation. SATB1 expression has been associated with poor prognosis in numerous cancer forms, including colorectal cancer (CRC). The value of SATB1 expression in metastatic CRC (mCRC) has, however, not yet been described. The aim was to evaluate the expression and prognostic significance of SATB1 in mCRC. Methods: SATB1 expression was analysed by immunohistochemistry in tissue microarrays with tumors from a prospective cohort with 454 mCRC patients from three Nordic countries. Cox regression proportional hazards models were applied to assess the impact of SATB1 expression on overall survival (OS); in the entire cohort, and in strata per chemotherapy and mutational status. Results: Among the 454 evaluable cases, 144 (32%) were positive and 310 (68%) were negative for SATB1 expression. Positive SATB1 expression was significantly more frequent in cases with lung metastases (41% vs 29%, p = 0.018), but did not correlate with other sites of distant metastasis. SATB1 expression (positive vs negative) was not prognostic in the entire cohort. The prognostic value of SATB1 did not differ between patients receiving palliative treatment (n = 281) and untreated patients (n = 178), and did not differ in relation to type of chemotherapy. In patients with BRAF wild type tumors, SATB1 expression was significantly associated with prolonged OS, whereas the opposite was seen in BRAF mutated tumors (hazard ratio = 0.77 vs 1.60, p for interaction = 0.005). SATB1 expression was significantly associated with prolonged OS in patients with KRAS mutated tumors (hazard ratio = 0.68), but not in KRAS wild type tumors, and there was no significant prognostic interaction between SATB1 expression and KRAS status. The prognostic value of SATB1 expression did not differ by tumor location. Conclusions: The prognostic value of SATB1 expression in mCRC appears to depend on the mutational status of the tumors, in particular BRAF. The potential value of SATB1 expression as a predictive biomarker for targeted therapies merits further investigation.

Association between timing and duration of adjuvant chemotherapy and survival for colorectal cancer in korea, 2011-2014: A nationwide study based on the database of quality assessment and the health insurance.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3605-3605 ◽  
Author(s):  
In Gyu Hwang ◽  
Ji Sung Lee ◽  
Sang-Cheol Lee ◽  
Sun Kyung Baek ◽  
Jong Gwang Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Health Insurance ◽  
Adjuvant Chemotherapy ◽  
Population Based ◽  
Stage Ii ◽  
Curative Intent ◽  
Nationwide Study ◽  
Time To Initiation ◽  
Overall Survival Benefit

3605 Background: Few population-based analyses on treatment outcomes of colorectal cancer (CRC) have been conducted in Asian countries. We conducted a nationwide study to assess relationship between timing and duration of adjuvant chemotherapy (AC) and survival for patients with CRC in South Korea. Methods: Data from the Health Insurance Review and Assessment Service Database (HIRA) were analyzed for demographics, tumor characteristics, adjuvant chemotherapy, and survival of patients who underwent curative-intent surgical resection for CRC from 2011 to 2014. Results: From the HIRA data, a total of 61315 patients were identified: 15620 (25.5%) in stage I, 20525 (33.5%) in Stage II, and 25170 (41.0%) in stage III. Chemotherapy regimens were consisted: 11332 (18.5%) in 5-fluorouracil and leucovorin/capecitabine (FL/CAP), 13183 (21.5%) in FL/CAP plus oxaliplatin (FOLFOX/CAPOX), 357 (0.6%) in uracil and tegafur/doxifluridine (UFT/D) and 36443 (59.4%) in surgery alone. For patients with stage II and III CRC, the initiation of AC ≥ 8 weeks after surgery was associated with a significant decrease in overall survival (OS) (FL/CAP: HR, 1.82; 95% CI, 1.53 to 2.17, and FOLFOX/CAPOX: HR, 2.92; 2.47 to 3.45, respectively), however UFT/D regimens were not statistically significant. For patients with stage II and III colon cancer, receiving AC < 3 months had lower OS (FL/CAP: HR, 3.72; 95% CI, 2.80 to 4.94, FOLFOX/CAPOX: HR, 2.15; 1.87 to 2.47, and UFT/D: HR, 1.74; 0.56 to 5.41, respectively). For patients with stage II and III rectal cancer, receiving AC < 3 months regardless of chemotherapy regimens had a significant lower survival (FL/CAP: HR, 1.91; 1.66 to 2.20, FOLFOX/CAPOX: HR, 2.20; 1.75 to 2.77, and UFT/D: HR, 3.71; 1.45 to 9.44, respectively). Conclusions: Time to initiation and duration of AC after surgery were associated with survival. Based on our results, starting within 8 weeks and receiving more than 3 months of AC are needed to have an overall survival benefit.

scholarly journals Evidence-Based Second-Line Treatment in RAS Wild-Type/Mutated Metastatic Colorectal Cancer in the Precision Medicine Era

2021 ◽  
Vol 22 (14) ◽  
pp. 7717
Author(s):  
Guido Giordano ◽  
Pietro Parcesepe ◽  
Giuseppina Bruno ◽  
Annamaria Piscazzi ◽  
Vincenzo Lizzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Braf Mutations ◽  
Mutational Status ◽  
First Line Treatment

Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such a context, antiangiogenic and anti-Epidermal Growth Factor Receptor (EGFR) agents as well as immune checkpoint inhibitors have been approved as second-line options, and RAS and BRAF mutations and microsatellite status represent the molecular drivers that guide therapeutic choices. Patients harboring K- and N-RAS mutations are not eligible for anti-EGFR treatments, and bevacizumab is the only antiangiogenic agent that improves survival in combination with chemotherapy in first-line, regardless of RAS mutational status. Thus, the choice of an appropriate therapy after the progression to a bevacizumab or an EGFR-based first-line treatment should be evaluated according to the patient and disease characteristics and treatment aims. The continuation of bevacizumab beyond progression or its substitution with another anti-angiogenic agents has been shown to increase survival, whereas anti-EGFR monoclonals represent an option in RAS wild-type patients. In addition, specific molecular subgroups, such as BRAF-mutated and Microsatellite Instability-High (MSI-H) mCRCs represent aggressive malignancies that are poorly responsive to standard therapies and deserve targeted approaches. This review provides a critical overview about the state of the art in mCRC second-line treatment and discusses sequential strategies according to key molecular biomarkers.

scholarly journals Actual survival after resection of primary colorectal cancer: results from a prospective multicenter study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Inge van den Berg ◽  
Robert R. J. Coebergh van den Braak ◽  
Jeroen L. A. van Vugt ◽  
Jan N. M. Ijzermans ◽  
Stefan Buettner
Keyword(s):  
Colorectal Cancer ◽  
Postoperative Complications ◽  
Multicenter Study ◽  
Survival Data ◽  
Standard Therapy ◽  
Tumor Grade ◽  
National Registry ◽  
Stage I ◽  
Stage Iii ◽  
Curative Intent

Abstract Background Colorectal cancer is the third most common type of cancer in the world. We characterize a cohort of patients who survived up to 5 years without recurrence and identify factors predicting the probability of cure. Methods We analyzed data of patients who underwent curative intent surgery for stage I–III CRC between 2007 and 2012 and who had had been included in a large multicenter study in the Netherlands. Cure was defined as 5-year survival without recurrence. Survival data were retrieved from a national registry. Results Analysis of data of 754 patients revealed a cure rate of 65% (n = 490). Patients with stage I disease and T1- and N0-tumor had the highest probability of cure (94%, 95% and 90%, respectively). Those with a T4-tumor or N2-tumor had the lowest probability of cure (62% and 50%, respectively). A peak in the mortality rate for older patients early in follow-up suggests early excess mortality as an explanation. A similar trend was observed for stage III disease, poor tumor grade, postoperative complications, sarcopenia, and R1 resections. Patients with stage III disease, poor tumor grade, postoperative complications, sarcopenia, and R1 resections show a similar trend for decrease in CSS deaths over time. Conclusion In the studied cohort, the probability of cure for patients with stage I–III CRC ranged from 50 to 95%. Even though most patients will be cured from CRC with standard therapy, standard therapy is insufficient for those with poor prognostic factors, such as high T- and N-stage and poor differentiation grade.

Comparison of Treatment, Cost, and Survival in Patients With Metastatic Colorectal Cancer in Western Washington, United States, and British Columbia, Canada

2020 ◽  
Vol 16 (5) ◽  
pp. e425-e432 ◽  
Author(s):  
Todd A. Yezefski ◽  
Dan Le ◽  
Leo Chen ◽  
Caroline H. Speers ◽  
Shasank Chennupati ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
British Columbia ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Systemic Therapy ◽  
Survival Data ◽  
De Novo ◽  
Tumor Resection ◽  
Care Utilization ◽  
Western Washington

PURPOSE: Few studies have directly compared health care utilization, costs, and outcomes between patients treated in the US multipayer health system and Canada’s single-payer system. Using cancer registry and claims data, we assessed treatment types, costs, and survival for patients with metastatic colorectal cancer (mCRC) in Western Washington State (WW) and British Columbia (BC). MATERIALS AND METHODS: Patients age ≥ 18 years diagnosed with mCRC in 2010 and later were identified from the BC Cancer database and a regional database linking WW SEER to claims from Medicare and two large commercial insurers. Demographics, treatment characteristics, costs of systemic therapy, and survival data were obtained from these databases and compared between the two regions. RESULTS: A total of 1,592 patients from BC and 901 from WW were included in the study. Median age was similar (BC, 66 years; WW, 63 years), but patients in BC were more likely to be male (57.1% v 51.2%; P ≤ .01) and to have de novo metastatic disease (61.0% v 38.3%; P ≤ .01). The use of radiation therapy was similar between regions (BC, 31.2%; WW, 33.9%; P = .18), but primary tumor resection was more common in BC (74.1% v 66.3%; P ≤ .01) as was hepatic metastasectomy (12.4% v 2.3%; P ≤ .01). Similar percentages of patients received systemic therapy (BC, 68.8%; WW, 67.1%; P = .40), but costs were significantly higher for first-line systemic therapy in WW ($6,226 v $15,792 per patient per month; P ≤ .01). Median overall survival was similar (BC, 16.9 months; WW, 18 months). CONCLUSION: Cost of systemic therapy for mCRC was significantly higher for patients in WW than in BC, but this did not translate to a difference in overall survival.

scholarly journals Primary and Secondary Kinase Genotypes Correlate With the Biological and Clinical Activity of Sunitinib in Imatinib-Resistant Gastrointestinal Stromal Tumor

2008 ◽  
Vol 26 (33) ◽  
pp. 5352-5359 ◽  
Author(s):  
Michael C. Heinrich ◽  
Robert G. Maki ◽  
Christopher L. Corless ◽  
Cristina R. Antonescu ◽  
Amy Harlow ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Clinical Results ◽  
Clinical Activity ◽  
Wild Type ◽  
Mutational Status ◽  
Imatinib Resistant ◽  
Exon 9 ◽  
Exon 11 ◽  
The Impact

PurposeMost gastrointestinal stromal tumors (GISTs) harbor mutant KIT or platelet-derived growth factor receptor α (PDGFRA) kinases, which are imatinib targets. Sunitinib, which targets KIT, PDGFRs, and several other kinases, has demonstrated efficacy in patients with GIST after they experience imatinib failure. We evaluated the impact of primary and secondary kinase genotype on sunitinib activity.Patients and MethodsTumor responses were assessed radiologically in a phase I/II trial of sunitinib in 97 patients with metastatic, imatinib-resistant/intolerant GIST. KIT/PDGFRA mutational status was determined for 78 patients by using tumor specimens obtained before and after prior imatinib therapy. Kinase mutants were biochemically profiled for sunitinib and imatinib sensitivity.ResultsClinical benefit (partial response or stable disease for ≥ 6 months) with sunitinib was observed for the three most common primary GIST genotypes: KIT exon 9 (58%), KIT exon 11 (34%), and wild-type KIT/PDGFRA (56%). Progression-free survival (PFS) was significantly longer for patients with primary KIT exon 9 mutations (P = .0005) or with a wild-type genotype (P = .0356) than for those with KIT exon 11 mutations. The same pattern was observed for overall survival (OS). PFS and OS were longer for patients with secondary KIT exon 13 or 14 mutations (which involve the KIT-adenosine triphosphate binding pocket) than for those with exon 17 or 18 mutations (which involve the KIT activation loop). Biochemical profiling studies confirmed the clinical results.ConclusionThe clinical activity of sunitinib after imatinib failure is significantly influenced by both primary and secondary mutations in the predominant pathogenic kinases, which has implications for optimization of the treatment of patients with GIST.

Sign in / Sign up

Export Citation Format

Share Document