Raija Kallio - Academia.edu (original) (raw)

Papers by Raija Kallio

European Journal of Cancer, May 1, 2001

Reliable markers for identifying infections in cancer patients on admission are lacking. The util... more Reliable markers for identifying infections in cancer patients on admission are lacking. The utility of the balance between interleukin (IL)-10 and IL-12 was analysed in this respect. The infection group (n=56) had higher median serum levels of IL-10 (3.8 pg/ml; interquartile range (IQR) 1.7±11.4 pg/ml versus 1.8 pg/ml; IQR 0.6±4.6 pg/ml; P=0.005) and IL-10 to IL-12 ratio (0.4; IQR 0.06± 4.23pg/ml versus 0.05; IQR 0.02±0.31pg/ml; P<0.001) than the non-infection group (n=36). IL-10 and the ratio had the following ®gures of sensitivity (79%; 95% con®dence interval (CI) 66±88 versus 39%; 95% CI 27±53), speci®city (40%; 95% CI 12±74 versus 90%; 95% CI 56±100) and positive predictive value (88%; 95% CI 76±96 versus 96%; 95% CI 78±100) for identifying infections (56 cases with infection and 10 with neoplastic fever), and the corresponding area under curve (AUC) values for IL-10 and the ratio in identifying infections in general were 0.58; 95% CI 0.39±0.78 versus 0.64; 95% CI 0.46±0.82 and in bacteraemia 0.71; 95% CI 0.50± 0.92 versus 0.75; 95% CI 0.58±0.93, respectively. Thus, IL-10 can be used as a screening method for identifying infections in cancer patients and the ratio of IL-10 to IL-12 for con®rming the diagnosis.

Purpose: Limited data are available about the influence of KIT and PDGFRA mutations on overall su... more Purpose: Limited data are available about the influence of KIT and PDGFRA mutations on overall survival (OS) of patients with gastrointestinal stromal tumor (GIST) treated with adjuvant imatinib. Patients and Methods: The Scandinavian Sarcoma Group XVIII/AIO multicenter trial accrued 400 patients with a high risk for GIST recurrence after macroscopically complete surgery between February 4, 2004, and September 29, 2008. The patients received adjuvant imatinib 400 mg/day for either 1 year or 3 years based on random allocation. We analyzed using conventional sequencing KIT and PDGFRA mutations centrally from 341 (85%) patients who had localized, centrally confirmed GIST, and correlated the results with recurrence-free survival (RFS) and OS in exploratory analyses. Results: During a median follow-up time of 10 years, 164 RFS events and 76 deaths occurred. Most patients were retreated with imatinib when GIST recurred. Patients with KIT exon 11 deletion or indel mutation treated with 3 years of adjuvant imatinib survived longer than patients treated for 1 year [10-year OS 86% versus 64%, respectively; HR, 0.34; 95% confidence interval (CI), 0.15-0.72; P ¼ 0.007], and also had longer RFS (10-year RFS 47% versus 29%; HR, 0.48; 95% CI, 0.31-0.74; P < 0.001). Patients with KIT exon 9 mutation had unfavorable OS regardless of the duration of adjuvant imatinib. Conclusions: Compared with 1 year of imatinib, 3 years of adjuvant imatinib led to 66% reduction in the estimated risk of death and a high 10-year OS rate in the subset of patients with a KIT exon 11 deletion/indel mutation.

Supplementary Figure S3. Kaplan-Meier estimates of recurrence-free survival (A, C, E) and overall... more Supplementary Figure S3. Kaplan-Meier estimates of recurrence-free survival (A, C, E) and overall survival (B, D, F) of patients with KIT exon 11 insertion or duplication mutation (A, B), patients with PDGFRA exon 18 D842V mutation (C, D), and patients with no detected KIT or PDGFRA mutation (E, F). The 5-year and 10-year survival rates are shown. Censored patients are indicated with a bar.

The Scandinavian countries (Denmark, Finland, Iceland, Norway and Sweden) have a total population... more The Scandinavian countries (Denmark, Finland, Iceland, Norway and Sweden) have a total population of about 25 million. They possess similar social structures, a modern medical service covering all inhabitants, and an effective registration system for all cancer patients. This serves as a good base for cooperation. Accordingly, the Scandinavian Sarcoma Group (SSG) was founded in 1979. The aim of the Group was to improve the prognosis for sarcoma patients in the area. Guidelines for diagnosis, pathology, and treatment have been drawn which are now generally accepted by sarcoma centers in Scandinavia. Our first randomized adjuvant chemotherapy trial for high-grade soft tissue sarcoma was done during 1981-1986. A total of 240 patients where included also in the large metaanalysis, where adjuvant chemotherapy improved metastasis-free survival and local tumor control. In 2003 all Scandinavian Sarcoma Group members agreed on "Recommendations for the diagnosis and treatment of abdominal, pelvic and retroperitoneal sarcomas", see under www. ssg-org.net under ongoing trials. The present SSG XVIII protocol will be the third study of soft tissue sacoma with gastrointestinal stroma cell tumor (GIST) with a high risk for recurrence and this time a randomized adjuvant treatment with the tyrosine kinase inhibitor imatinib mesylate of operable GIST.

JAMA Oncology, May 1, 2017

IMPORTANCE Little is known about whether the duration of adjuvant imatinib influences the prognos... more IMPORTANCE Little is known about whether the duration of adjuvant imatinib influences the prognostic significance of KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor α (PDGFRA) mutations. OBJECTIVE To investigate the effect of KIT and PDGFRA mutations on recurrence-free survival (RFS) in patients with gastrointestinal stromal tumors (GISTs) treated with surgery and adjuvant imatinib. DESIGN, SETTING, AND PARTICIPANTS This exploratory study is based on the Scandinavian Sarcoma Group VIII/Arbeitsgemeinschaft Internistische Onkologie (SSGXVIII/AIO) multicenter clinical trial. Between February 4, 2004, and September 29, 2008, 400 patients who had undergone surgery for GISTs with a high risk of recurrence were randomized to receive adjuvant imatinib for 1 or 3 years. Of the 397 patients who provided consent, 341 (85.9%) had centrally confirmed, localized GISTs with mutation analysis for KIT and PDGFRA performed centrally using conventional sequencing. During a median follow-up of 88 months (completed December 31, 2013), 142 patients had GIST recurrence. Data of the evaluable population were analyzed February 4, 2004, through December 31, 2013. MAIN OUTCOMES AND MEASURES The main outcome was RFS. Mutations were grouped by the gene and exon. KIT exon 11 mutations were further grouped as deletion or insertion-deletion mutations, substitution mutations, insertion or duplication mutations, and mutations that involved codons 557 and/or 558. RESULTS Of the 341 patients (175 men and 166 women; median age at study entry, 62 years) in the 1-year group and 60 years in the 3-year group), 274 (80.4%) had GISTs with a KIT mutation, 43 (12.6%) had GISTs that harbored a PDGFRA mutation, and 24 (7.0%) had GISTs that were wild type for these genes. PDGFRA mutations and KIT exon 11 insertion or duplication mutations were associated with favorable RFS, whereas KIT exon 9 mutations were associated with unfavorable outcome. Patients with KIT exon 11 deletion or insertion-deletion mutation had better RFS when allocated to the 3-year group compared with the 1-year group (5-year RFS, 71.0% vs 41.3%; P < .001), whereas no significant benefit from the 3-year treatment was found in the other mutational subgroups examined. KIT exon 11 deletion mutations, deletions that involved codons 557 and/or 558, and deletions that led to pTrp557_Lys558del were associated with poor RFS in the 1-year group but not in the 3-year group. Similarly, in the subset with KIT exon 11 deletion mutations, higher-than-the-median mitotic counts were associated with unfavorable RFS in the 1-year group but not in the 3-year group. CONCLUSIONS AND RELEVANCE Patients with KIT exon 11 deletion mutations benefit most from the longer duration of adjuvant imatinib. The duration of adjuvant imatinib modifies the risk of GIST recurrence associated with some KIT mutations, including deletions that affect exon 11 codons 557 and/or 558. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00116935

Supplementary Figure S2. Kaplan-Meier estimates of recurrence-free survival of patients with KIT ... more Supplementary Figure S2. Kaplan-Meier estimates of recurrence-free survival of patients with KIT exon 11 substitution mutation (A) and patients with KIT exon 9 mutation (B). The 5-year and 10-year survival rates are shown. Censored patients are indicated with a bar.

Clinical Cancer Research, Apr 19, 2023

Kallio, Raija, Traditional and new markers of infection in adult cancer patients and the possible... more Kallio, Raija, Traditional and new markers of infection in adult cancer patients and the possible interfering effect of underlying malignancy on these markers.

Kaplan-Meier estimates of recurrence-free survival (A, C) and overall survival (B, D) of patients... more Kaplan-Meier estimates of recurrence-free survival (A, C) and overall survival (B, D) of patients with KIT exon 11 deletion mutation (A, B) and patients with KIT exon 11 indel mutation (C, D)

European Journal of Cancer, May 1, 2000

The diagnostic utility of C-reactive protein (CRP), procalcitonin (PCT) and interleukin-8 (IL-8) ... more The diagnostic utility of C-reactive protein (CRP), procalcitonin (PCT) and interleukin-8 (IL-8) were studied in 66 cancer patients with suspected infection (39 with de®nite foci of infection, 17 with antibiotic responses without foci and 10 with neoplastic fever without infection) and 26 patients scheduled for chemotherapy. The infection group (n=56) had higher median CRP (91 versus 19 mg/l, P<0.001), PCT (0.28 versus 0.12 ng/ml, P<0.001) and IL-8 values (27.7 versus 16.9 pg/ml, P=0.032) than the noninfection group (n=36). In patients with suspected infection, only PCT was a good marker to discriminate bacteraemia with an area under the receiver operating characteristics curve of 0.92 (95% con®dence interval (CI), 0.77±1.0), but even PCT was less well able to dierentiate between non-bacteraemic infections and neoplastic fever (0.56; 95% CI, 0.35±0.77). In conclusion, PCT was a good indicator for bacteraemia, but none of the three markers were reliable indicators for minor infections in non-neutropenic cancer patients.

Acta Oncologica, Apr 23, 2018

Background: In Finland, selective internal radiation therapy (SIRT) is at present the preferred f... more Background: In Finland, selective internal radiation therapy (SIRT) is at present the preferred first-line loco-regional therapy for uveal melanoma patients with hepatic metastases not suitable for surgery. We retrospectively evaluate the outcome and safety of SIRT in this group of patients. Material and methods: Yttrium-90 microspheres were delivered via the hepatic artery into the circulation of metastases from uveal melanoma in 18 patients with a predicted life expectancy of more than three months in three Finnish tertiary referral centers between November 2010 and December 2015. Progression-free survival (PFS), toxicity and overall survival (OS) were evaluated. Patients with historical uveal melanoma without extrahepatic metastases, who had received systemic chemotherapy as firstline treatment for their hepatic metastases at the Helsinki University Hospital between January 2006 and May 2010, were used as a historical control group. Results: Partial response and stable disease were observed in three (17%) and eight (44%) patients, respectively; one patient was not evaluable for response. Median PFS after SIRT was 5.6 (range, 1.3-40.8) months. Median OS after SIRT was 13.5 (range, 3.6-44.8) months compared with 10.5 (range, 3.0-16.5; p ¼ .047) months for the historical chemotherapy group. Among patients who received SIRT as first-line treatment, the median OS was 18.7 (range, 8.2-44.8) months, significantly longer than that of the chemotherapy group (10.5 months, p ¼ .017). There were no treatment-related deaths. Toxicity was mainly WHO grade 1-2 and self-limited. Conclusion: SIRT is a feasible and safe treatment for liver metastases in patients with uveal melanoma.

Supportive Care in Cancer, Mar 1, 2001

Objective: To test the hypothesis that high levels of pre-operative C-reactive protein (CRP) and ... more Objective: To test the hypothesis that high levels of pre-operative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are associated with an increased risk of systemic inflammatory response syndrome (SIRS) following percutaneous nephrolithotomy (PCNL). Materials and Methods: Retrospective study of patients who underwent PCNL at our institution between October 2012 and October 2013 when ESR and CRP levels were part of our standard preoperative order set. The primary endpoint was development of SIRS. Receiver operating characteristics curves were used to evaluate the discriminative ability of the test. Results: Among the 107 PCNLs performed during the study period, 35 (33%) of patients had evidence of SIRS during the post-operative stay. Patients who experienced SIRS had a longer operative time (99 min vs. 85 min, p = 0.016), were more likely to have been transferred to the intensive care unit (ICU) (15% vs. 0%, p = 0.002) and experienced a longer length of stay (2 days vs. 1 day, p < 0.001). On multivariable analysis controlling for operative time and positive urine culture, ESR (odds ratio [OR] 1.32, 95% confidence interval [CI], 1.01-1.72, p = 0.04) and CRP (OR 1.59; 95% CI, 1.07-2.37, p = 0.02) were associated with development of SIRS. Among patients without a positive urine culture, an ESR >6.5 mm/hr (AUC 0.62; 95% CI, 0.52-0.78) had sensitivity, specificity, and negative predictive value (NPV) of 70.4%, 61.5%, and 80.0% respectively, for development of SIRS. Among all patients, a CRP >0.65 mg/dL (AUC 0.63; 95% CI, 0.51 to 0.74) had sensitivity, specificity, and NPV of 51.4%, 69.4%, 74.6%. Conclusions: A preoperative blood test for ESR and CRP was predictive for the development of SIRS after PCNL. This knowledge could be used to risk-stratify patients and guide duration of antibiotic prophylaxis prior to PCNL, particularly among those without a positive urine culture.

Supplemental Table 1. Distribution of Covariates by hCG Quartiles: Finnish Maternity Cohort

Journal of Clinical Medicine

Older adults are underrepresented in metastatic colorectal cancer (mCRC) studies and thus may not... more Older adults are underrepresented in metastatic colorectal cancer (mCRC) studies and thus may not receive optimal treatment, especially not metastasectomies. The prospective Finnish real-life RAXO-study included 1086 any organ mCRC patients. We assessed repeated centralized resectability, overall survival (OS), and quality of life (QoL) using 15D and EORTC QLQ-C30/CR29. Older adults (>75 years; n = 181, 17%) had worse ECOG performance status than adults (<75 years, n = 905, 83%), and their metastases were less likely upfront resectable. The local hospitals underestimated resectability in 48% of older adults and in 34% of adults compared with the centralized multidisciplinary team (MDT) evaluation (p < 0.001). The older adults compared with adults were less likely to undergo curative-intent R0/1-resection (19% vs. 32%), but when resection was achieved, OS was not significantly different (HR 1.54 [CI 95% 0.9–2.6]; 5-year OS-rate 58% vs. 67%). ‘Systemic therapy only’ patients ...

Representativeness of Study Participants

Kaplan-Meier estimates of recurrence-free survival of patients with KIT exon 11 substitution muta... more Kaplan-Meier estimates of recurrence-free survival of patients with KIT exon 11 substitution mutation (A) and patients with KIT exon 9 mutation (B). The 5-year and 10-year survival rates are shown. Censored patients are indicated with a bar

Kaplan-Meier estimates of recurrence-free survival (A, C, E) and overall survival (B, D, F) of pa... more Kaplan-Meier estimates of recurrence-free survival (A, C, E) and overall survival (B, D, F) of patients with KIT exon 11 insertion or duplication mutation (A, B), patients with PDGFRA exon 18 D842V mutation (C, D), and patients with no detected KIT or PDGFRA mutation (E, F). The 5-year and 10-year survival rates are shown. Censored patients are indicated with a bar.

Journal of Gastrointestinal Surgery

Background Preoperative esophageal stenting is proposed to have a negative effect on outcomes. Th... more Background Preoperative esophageal stenting is proposed to have a negative effect on outcomes. The aim was to compare a 5-year survival in patients undergoing esophagectomy for esophageal cancer with and without preoperative esophageal stent in a population-based nationwide cohort from Finland. The secondary outcome was 90-day mortality. Methods This study included curatively intended esophagectomies for esophageal cancer in Finland between 1999 and 2016, with follow-up until December 31, 2019. Cox proportional hazards models provided hazard ratios (HRs) with 95% confidence intervals (CIs) of overall 5-year and 90-day mortality. Model 1 was adjusted for age, sex, year of the surgery, comorbidities, histology, pathological stage, and neoadjuvant therapy. Model 2 included also albumin level and BMI. Result Of 1064 patients, a total of 134 patients underwent preoperative stenting and 930 did not. In both adjusted models 1 and 2, higher 5-year mortality was seen in patients with preoper...

Human chorionic gonadotropin (hCG) is necessary for the maintenance of early pregnancy and promot... more Human chorionic gonadotropin (hCG) is necessary for the maintenance of early pregnancy and promotes normal breast cell differentiation. Administered hCG reduces risk of carcinogen-induced breast cancer in animal models, and higher circulating hCG concentrations were associated with significantly lower long-term risk of breast cancer in a prior nested case–control study. In this study, we investigated early-pregnancy hCG concentrations and subsequent breast cancer risk. We conducted a nested case–control study with 1,191 cases and 2,257 controls (matched on age and date at blood collection) in the Finnish Maternity Cohort, a cohort with serum samples from 98% of pregnancies registered in Finland since 1983. This study included women with a serum sample collected early (<140 days gestation) in their first pregnancy resulting in a live, term birth. Breast cancer cases were identified via the Finnish Cancer Registry. Age at breast cancer diagnosis ranged from 22 to 58 years (mean: 41...