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Survival benefit of statins in older patients with rectal cancer: A Swedish population-based cohort study
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Department of Medical and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.ORCID iD: 0000-0003-1253-1901
2019 (English)In: Journal of Geriatric Oncology, ISSN 1879-4068, E-ISSN 1879-4076, Vol. 10, no 5, p. 690-697Article in journal (Refereed) Published
Abstract [en]

Objectives

Increasing evidence suggests that statins may have antitumor effects but their rolein rectal cancer appears inconclusive. The aim of this study was to investigate whether statins may have an impact on survival of older and younger patients with rectal cancer.

Materials and Methods

This study included 238 patients ≥70 years and 227 patients <70 years old, from the Southeast Health Care Region of Sweden, who were diagnosed with rectal adenocarcinoma between 2004 and 2013.

Results

In the older group (n = 238), statin use at the time of diagnosis was related to better cancer-specific survival (CSS) and overall survival (OS), compared to non-use (CSS: Hazard Ratio (HR), 0.37; 95% CI, 0.19–0.72; P = .003; OS: HR, 0.62; 95% CI, 0.39–0.96; P = .032). In the older group with stages I-III disease (n = 199), statin use was associated with better disease-free survival (DFS) compared to non use (HR, 0.18; 95% CI, 0.06–0.59; P = .005). The improvement of CSS, OS and DFS remained significant after adjusting for potential confounders. In the older group with stage III disease, statin users had better CSS and DFS compared to non-users (log rank P = .043; log-rank P = .028, respectively). In the older group with short course radiotherapy, statin use was related to better CSS (log-rank P = .032). No such association was present in the younger group.

Conclusion

Statin use was related to improved survival in older patients with rectal cancer.

This observation is important given the low cost and safety of statins as a drug.

Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 10, no 5, p. 690-697
Keywords [en]
Statin;Rectal cancer;Survival;Older;Younger;Age;Stage;Radiotherapy;Outcome
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-157046DOI: 10.1016/j.jgo.2019.01.011ISI: 000485208300005PubMedID: 30692020Scopus ID: 2-s2.0-85060538794OAI: oai:DiVA.org:liu-157046DiVA, id: diva2:1317815
Note

Funding agencies: Swedish Cancer SocietySwedish Cancer Society; Foundation of Oncological Clinical Research in Linkoping; Swedish Research CouncilSwedish Research Council; Health Research Council in the Southeast of Sweden

Available from: 2019-05-24 Created: 2019-05-24 Last updated: 2024-02-09Bibliographically approved
In thesis
1. Clinical and Biological Factors Related to Survival in Patients with Rectal Cancer
Open this publication in new window or tab >>Clinical and Biological Factors Related to Survival in Patients with Rectal Cancer
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Rectal cancer is a common malignancy within the gastrointestinal tract. Despite the advances in diagnosis and treatment of rectal cancer patients during the last decades, there are still many patients who die from their disease. In order to personalise the therapy and optimise the clinical outcomes, it is important to identify factors that have an impact on survival of rectal cancer patients. Therefore, the overall aim of this thesis was to identify clinical and biological factors that were related to survival in patients with rectal cancer.  

Paper I aimed to evaluate the impact of statins on survival in older and younger patients with rectal cancer. The study included 238 older patients (≥70 years) and 227 younger patients (<70 years) from the southeast healthcare region of Sweden. The patients were classified as statin users if they used any type of statins at the time of the cancer diagnosis. In the older group, statin users had better cancer-specific survival, disease-free survival, and overall survival compared with non-users. No such association was present in the younger group.  

Paper II aimed to evaluate the impact of computed tomography (CT)-measured body composition on survival in rectal cancer patients. The study included 173 patients from the region Ostergotland of Sweden who underwent a CT colonography at the time of diagnosis. Skeletal muscle index (SMI) and visceral adipose tissue area (VAT) were quantified at the level of the third lumbar vertebral body, using the CT colonography acquired at the time of diagnosis. The patients were divided into a low or high SMI group, and a low or high VAT group. Low SMI was related to worse survival compared to high SMI in all the patients. High VAT was related to better survival in men with low or middle rectal cancer, while high VAT was related to worse survival in women with low or middle rectal cancer. 

Paper III aimed to evaluate the prognostic value of SPARCL1 expression in patients with rectal cancer with a focus on radiotherapy (RT). The study included 138 patients with rectal cancer who participated in the Swedish Rectal Cancer Trial. Of those, 63 patients underwent both preoperative RT and surgery, while 75 patients had surgery alone. SPARCL1 expression was determined by immunohistochemistry. Strong SPARCL1 expression was related to better overall survival compared to weak SPARCL1 expression in patients with stage III disease who received RT, but not in patients with stage III disease who did not receive RT. Moreover, SPARCL1 expression was increased in primary tumours with RT compared to tumours without RT.  

In summary, statin use was related to improved survival in older patients with rectal cancer. CT-measured body composition parameters provided useful information for determining the prognosis of rectal cancer patients. SPARCL1 was identified as a potential prognostic biomarker in rectal cancer patients who received preoperative RT. Conclusively, the results of this thesis indicate that statin drugs, CT-measured body composition and SPARCL1 are factors related to survival in patients with rectal cancer. The evidence may benefit patients by more accurate estimating of their prognosis, personalised treatment and improved clinical outcomes.  

Abstract [sv]

Varje år diagnostiseras cirka 1 200 män och 800 kvinnor med ändtarmscancer i Sverige. De flesta patienter är över 65 år när diagnosen ställs. Trots utvecklingen av cancerdiagnostik och behandling dör fortfarande en del ändtarmscancerpatienter i sin sjukdom, medan andra får besvärliga biverkningar av given behandling. Detta understryker vikten av att hitta faktorer som har betydelse för överlevnad av patienter med ändtarmscancer och som kan leda till förbättrade behandlingsstrategier. Därför var det övergripande målet med avhandlingen att undersöka kliniskt användbara faktorer som kan påverka överlevnad av patienter med ändtarmscancer.   

I delarbete I undersökte vi om statiner, en grupp av blodfettsänkande läkemedel, kunde påverka överlevnad hos äldre och yngre patienter med ändtarmscancer. Vi fann att de äldre patienter som tog statiner när de fick sin cancerdiagnos levde längre jämfört med de äldre som inte tog statiner. Bland de yngre patienterna hittade vi inget samband mellan användning av statiner och överlevnad.      

I delarbete II undersökte vi om det finns någon relation mellan kroppssammansättning i form av muskelmassa och fettmängd i magen och överlevnad hos patienter med ändtarmscancer.  Vi beräknade muskelmassan och fettmängden med hjälp av skiktröntgenundersökningen av magen som gjordes när patienterna fick sin cancerdiagnos. Patienter som hade liten muskelmassa hade sämre överlevnad jämfört med patienter med större muskelmassa. Bland män levde de som hade mycket bukfett längre, medan hos kvinnor hade de med mycket bukfett kortare överlevnad.   

I delarbete III undersökte vi om ett protein som kallas SPARCL1 påverkade överlevnad hos patienter med ändtarmscancer. Hälften av patienterna fick strålbehandling och opererades, medan den andra hälften opererades utan föregående strålbehandling. Bland patienter som fick strålbehandling visade vi att högt SPARCL1 uttryck i tumörvävnad var kopplat till bättre överlevnad jämfört med lågt SPARCL1 uttryck. I gruppen som inte fick strålbehandling sågs ingen skillnad i överlevnad mellan patienter med högt SPARCL1 uttryck och patienter med lågt SPARCL1 uttryck.  

Sammanfattningsvis visade vi att statiner, kroppsammansättning och proteinet SPARCL1 är faktorer kopplade till överlevnad hos patienter med ändtarmscancer. Våra resultat talar för att statiner, som är ett av de mest förskrivna läkemedlen mot hjärt-kärlproblem och inte har några större biverkningar, möjligen kan ges till äldre patienter med ändtarmscancer för att förlänga deras överlevnad. Den skiktröntgen av magen som patienter genomgår under utredning för cancer kan även användas för att beräkna muskelmassa och fettmängd. Dessa kroppsmått ger oss information om patienternas prognos som kan användas i kliniken vid planering av cancerbehandling och uppföljning. Slutligen, skulle proteinet SPARCL1 kunna användas som markör för att förutsäga överlevnad hos ändtarmscancerpatienter som fått strålbehandling innan operation. Vår förhoppning är att dessa tre faktorer ska kunna användas i framtiden för att förbättra överlevnaden hos ändtarmscancerpatienter.     

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2022. p. 76
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1807
Keywords
Age, Radiotherapy, Rectal cancer, Skeletal muscle, SPARCL1, Statins, Survival, Visceral adipose tissue
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-184312 (URN)10.3384/9789179292669 (DOI)9789179292652 (ISBN)9789179292669 (ISBN)
Public defence
2022-05-12, Berzeliussalen, Building 463, Campus US, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Note

Funding agencies: This work was supported by grants from the Swedish Cancer Society, the Swedish Research Council, the Foundation of Oncological Clinical Research in Linköping, Linköping’s Lions Research Fund, as well as the Health Research Council in the Southeast of Sweden and Linköping’s University Hospital.

Available from: 2022-04-12 Created: 2022-04-12 Last updated: 2024-01-10Bibliographically approved

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