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      Treatment and Outcomes of Colorectal Cancer in Armenia: A Real-World Experience From a Developing Country

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          Abstract

          PURPOSE

          In Armenia, colorectal cancer (CRC) is one of the most frequently diagnosed cancers. It is in the third place by incidence. The aim of this study was to evaluate treatment and outcomes of CRC in Armenia during the last 9 years.

          MATERIALS AND METHODS

          For this retrospective hospital-based study, we have collected data from two main oncology centers in Armenia: National Oncology Center and “Muratsan” Hospital of Yerevan State Medical University. The information about patients with CRC who were treated at these two centers between January 1, 2010 and July 1, 2018 was collected from the medical records. Log-rank test and Kaplan-Meier curves were used for survival analysis. Prognostic factors were identified by Cox regression.

          RESULTS

          A total of 602 patients with CRC were involved in the final analysis. Median follow-up time was 37 months (range, 3-207 months). A total of 8.6% of patients had stage I, 32.9% stage II, 38.0% stage III, and 17.6% stage IV cancer; for 2.7% patients, the stage was unknown. The main independent prognostic factors for overall survival (OS) were tumor stage, grade, and histology. Adjuvant chemotherapy has been shown to improve survival in stage II colon cancer and stage III rectal but not in stage II rectal cancer. Radiotherapy did not yield survival improvement in stage II or III rectal cancer. Three- and 5-year OS rates were 62.9% and 51.8% for all stages combined and 79.7% and 68.5% for stages I-II, 62.5% and 48.4% for stage III, and 24.4% and 17% for stage IV respectively.

          CONCLUSION

          As seen from our results, our survival rates are lower than those of the developed world. Additional research is needed to identify the underlying reasons and to improve patients’ treatment and outcomes in Armenia.

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          Most cited references29

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          Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer.

          Christine Ribic, Daniel Sargent, Malcolm J Moore … (2003)
          Colon cancers with high-frequency microsatellite instability have clinical and pathological features that distinguish them from microsatellite-stable tumors. We investigated the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II and stage III colon cancer. Tumor specimens were collected from patients with colon cancer who were enrolled in randomized trials of fluorouracil-based adjuvant chemotherapy. Microsatellite instability was assessed with the use of mononucleotide and dinucleotide markers. Of 570 tissue specimens, 95 (16.7 percent) exhibited high-frequency microsatellite instability. Among 287 patients who did not receive adjuvant therapy, those with tumors displaying high-frequency microsatellite instability had a better five-year rate of overall survival than patients with tumors exhibiting microsatellite stability or low-frequency instability (hazard ratio for death, 0.31 [95 percent confidence interval, 0.14 to 0.72]; P=0.004). Among patients who received adjuvant chemotherapy, high-frequency microsatellite instability was not correlated with increased overall survival (hazard ratio for death, 1.07 [95 percent confidence interval, 0.62 to 1.86]; P=0.80). The benefit of treatment differed significantly according to the microsatellite-instability status (P=0.01). Adjuvant chemotherapy improved overall survival among patients with microsatellite-stable tumors or tumors exhibiting low-frequency microsatellite instability, according to a multivariate analysis adjusted for stage and grade (hazard ratio for death, 0.72 [95 percent confidence interval, 0.53 to 0.99]; P=0.04). By contrast, there was no benefit of adjuvant chemotherapy in the group with high-frequency microsatellite instability. Fluorouracil-based adjuvant chemotherapy benefited patients with stage II or stage III colon cancer with microsatellite-stable tumors or tumors exhibiting low-frequency microsatellite instability but not those with tumors exhibiting high-frequency microsatellite instability. Copyright 2003 Massachusetts Medical Society
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            Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer.

            Daniel Sargent, Silvia Marsoni, Geneviève Monges … (2010)
            Prior reports have indicated that patients with colon cancer who demonstrate high-level microsatellite instability (MSI-H) or defective DNA mismatch repair (dMMR) have improved survival and receive no benefit from fluorouracil (FU) -based adjuvant therapy compared with patients who have microsatellite-stable or proficient mismatch repair (pMMR) tumors. We examined MMR status as a predictor of adjuvant therapy benefit in patients with stages II and III colon cancer. MSI assay or immunohistochemistry for MMR proteins were performed on 457 patients who were previously randomly assigned to FU-based therapy (either FU + levamisole or FU + leucovorin; n = 229) versus no postsurgical treatment (n = 228). Data were subsequently pooled with data from a previous analysis. The primary end point was disease-free survival (DFS). Overall, 70 (15%) of 457 patients exhibited dMMR. Adjuvant therapy significantly improved DFS (hazard ratio [HR], 0.67; 95% CI, 0.48 to 0.93; P = .02) in patients with pMMR tumors. Patients with dMMR tumors receiving FU had no improvement in DFS (HR, 1.10; 95% CI, 0.42 to 2.91; P = .85) compared with those randomly assigned to surgery alone. In the pooled data set of 1,027 patients (n = 165 with dMMR), these findings were maintained; in patients with stage II disease and with dMMR tumors, treatment was associated with reduced overall survival (HR, 2.95; 95% CI, 1.02 to 8.54; P = .04). Patient stratification by MMR status may provide a more tailored approach to colon cancer adjuvant therapy. These data support MMR status assessment for patients being considered for FU therapy alone and consideration of MMR status in treatment decision making.
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              Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials†

              D. Arnold, B Lueza, J-Y Douillard … (2017)
              There is increasing evidence that metastatic colorectal cancer (mCRC) is a genetically heterogeneous disease and that tumours arising from different sides of the colon (left versus right) have different clinical outcomes. Furthermore, previous analyses comparing the activity of different classes of targeted agents in patients with KRAS wild-type (wt) or RAS wt mCRC suggest that primary tumour location (side), might be both prognostic and predictive for clinical outcome.
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                Author and article information

                Journal
                Journal ID (nlm-ta): JCO Glob Oncol
                Journal ID (iso-abbrev): JCO Glob Oncol
                Journal ID (hwp): go
                Journal ID (pmc): go
                Journal ID (publisher-id): GO
                Title: JCO Global Oncology
                Publisher: American Society of Clinical Oncology
                ISSN (Electronic): 2687-8941
                Publication date Collection: 2020
                Publication date (Electronic): 12 August 2020
                Volume: 6
                Electronic Location Identifier: GO.20.00251
                Affiliations
                [ 1 ]Department of Oncology, Yerevan State Medical University, Yerevan, Armenia
                [ 2 ]Adult Solid Tumors Chemotherapy Department, Haematology Center Yerevan State Medical University, Yerevan, Armenia
                [ 3 ]Berd Military Hospital, Tavush, Armenia
                [ 4 ]Department of Chemotherapy, Mikaelyan Institute of Surgery, Yerevan, Armenia
                [ 5 ]Pediatric Cancer and Blood Disorders Center of Armenia, Hematology Center, Yerevan State Medical University, Yerevan, Armenia
                [ 6 ]Department of Pediatric Oncology and Hematology, Yerevan State Medical University, Yerevan, Armenia
                Author notes
                Samvel Bardakhchyan, MD, Adult Solid Tumors Chemotherapy Department, Haematology Center after R. Yeolyan, 0014, Yerevan, Armenia; e-mail: bardakchyan-5samvel@ 123456yandex.ru .
                Article
                Publisher ID: 2000251
                DOI: 10.1200/GO.20.00251
                PMC ID: 7456313
                PubMed ID: 32783650
                SO-VID: ec5e661a-dd96-4991-b701-f55b0e2fcba4
                Copyright © © 2020 by American Society of Clinical Oncology
                License:

                Licensed under the Creative Commons Attribution 4.0 License: https://creativecommons.org/licenses/by/4.0/

                History
                Date accepted : 10 July 2020
                Page count
                Figures: 5, Tables: 2, Equations: 0, References: 55, Pages: 12
                Categories
                Compound subject: 00, Gastrointestinal: Colorectal & Anal Cancer
                Compound subject: 00, Gastrointestinal: Colorectal & Anal Cancer
                Compound subject: LIS, Low income settings
                Compound subject: MIS, Middle incoming settings
                Compound subject: LIS, Low income settings
                Compound subject: MIS, Middle incoming settings
                Compound subject: 00, Radiation Oncology
                Compound subject: 00, Targeted Therapy
                Subject: Original Reports
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