Search

Eetu Heervä,1 Vesa Väliaho,1 Heidi Nurmi,1 Elina Lietzen,2 Annika Ålgars,1 Saila Kauhanen2 1Department of Oncology, Turku University Hospital and University of Turku, Turku, Finland; 2Department of Digestive Surgery, Turku University Hospital and University of Turku, Turku, FinlandCorrespondence: Eetu Heervä, Department of Oncology, Turku University Hospital, Hämeentie 11, Turku, 20521, Finland, Tel +35823130000, Fax +35823131316, Email eetu.heerva@utu.fiBackground: Pancreatic ductal adenocarcinoma (PDAC) remains a lethal and rarely resectable malignancy. Here we explore the outcomes of surgery, as compared to definitive radiotherapy (dRT) or systemic therapy only in PDAC.Methods: Pancreatic surgery and radiotherapy in Southwest Finland have been centralized to Turku University Hospital. Previously validated population-based electronic health records database was searched for all unselected PDAC patients from the years 2009– 2019. Main outcome was median overall survival (mOS). Demographics, pathology, surgery, and oncological treatment data were collected.Results: We identified 1006 patients with PDAC, 49% male, median age 71 years and 77% presenting with metastatic disease. In total, 405 patients were treated; 92 resected, 26 dRT without resection and 287 systemic therapy only. mOS was 34.6 months for resected, 26.7 months for dRT, and 7.5 months for systemic therapy patients. Among the 88 patients with locally advanced inoperable PDAC, dRT was independently associated with longer mOS (26.7 months) as compared to systemic therapy only (mOS 10.6 months). Among the 287 patients treated with systemic therapy only, combination chemotherapy was independently associated with longer mOS (11.6 months) as compared to gemcitabine-monotherapy (6.8 months). In patients progressing to second-line systemic treatment after gemcitabine failure, mOS was the same (5.0 months) with single or combination regimens.Conclusion: Surgery remains the only curative approach for PDAC. In locally advanced PDAC, dRT was associated with longer survival as compared to systemic therapy only. Concerning first-line systemic therapy, our results support the use of combination chemotherapy over single-agent therapy.Keywords: pancreatic cancer, pancreas, pancreatectomy, nab-paclitaxel, chemoradiotherapy

Background and purpose: The CardioSwitch-study demonstrated that patients with solid tumors who develop cardiotoxicity on capecitabine or 5-fluorouracil (5-FU) treatment can be safely switched to S-1, an alternative fluoropyrimidine (FP). In light of the European Medicines Agency approval of S-1 in metastatic colorectal cancer (mCRC), this analysis provides more detailed safety and efficacy information, and data regarding metastasectomy and/or local ablative therapy (LAT), on the mCRC patients from the original study. Materials and methods: This retrospective cohort study was conducted at 12 European centers. The primary endpoint was recurrence of cardiotoxicity after switch. For this analysis, safety data are reported for 78 mCRC patients from the CardioSwitch cohort (N = 200). Detailed efficacy and outcomes data were available for 66 mCRC patients. Results: Data for the safety of S-1 in mCRC patients were similar to the original CardioSwitch cohort and that expected for FP-based treatment, with no new concerns. Recurrent cardiotoxicity (all grade 1) with S-1-based treatment occurred in 4/78 (5%) mCRC patients; all were able to complete FP treatment. Median progression-free survival from initiation of S-1-based treatment was 9.0 months and median overall survival 26.7 months. Metastasectomy and/or LAT was performed in 33/66 (50%) patients, and S-1 was successfully used in recommended neoadjuvant/conversion or adjuvant-like combination regimens and schedules as for standard FPs. Interpretation: S-1 is a safe and effective FP alternative when mCRC patients are forced to discontinue 5-FU or capecitabine due to cardiotoxicity and can be safely used in the standard recommended regimens, settings, and schedules.

Abstract Background Family therapy for adolescent anorexia nervosa (AN) has stronger evidence of efficacy in comparison with individual therapy, and family-based treatment (FBT) is the most evaluated in numerous randomized clinical trials. However, few studies have focused on how FBT performs outside of research settings. The current study is the first to assess clinical outcomes of FBT for adolescent AN in Finland, in a specialized outpatient clinic. Aim The naturalistic outcome of outpatient FBT for adolescent AN was investigated. Methods Fifty-two female patients and their families who received FBT at a tertiary eating disorders unit participated in the study. Data on their pre-treatment parameters, treatment details, and condition at the end of treatment (EOT) was collected from their medical records. Results At EOT, a majority (61.5%) had achieved a full weight restoration [percentage of expected body weight (%EBW) ≥ 95%]. Participants with an %EBW ≥ 95 at EOT had a significantly higher pre-treatment %EBW than those with an EBW

Abstract Background Approximately 20–30% of people with anorexia nervosa develop an enduring form of the disorder. In the present study a newly developed outpatient treatment unit for patients with severe and enduring anorexia nervosa was described. The treatment model is flexible, patient-centered, and aims at enhancing quality of life, maintaining medical stability, and minimizing harm. Treatment contents, patient characteristics, treatment goals, and course of treatment from the first five years of operation were described and analyzed. Methods The participants (N = 22) consisted of all referrals resulting in an assessment or treatment period at the unit between May 2017 and May 2022. All participants were women. The study was a registry study. Information regarding patient characteristics, treatment goals, and the course of treatment was gathered from medical records. Results On average, the participants had had a diagnosed eating disorder for 12.80 years, and self-reported eating disorder symptoms for 19 years. Their symptomatology included severe eating disorder symptoms, psychiatric comorbidities, extreme underweight, and co-occurring medical conditions. Their treatment goals commonly concerned improving physical health, reducing eating disorder symptoms, improving psychological well-being, and improving quality of life. The majority of participants for whom this information was available benefited from the treatment (60%) and their treatment goals were met or partly met (66.6%), as measured by evaluations made by the patient or the treatment team. More than two thirds (69.2%) of the participants for whom this information was available remained weight stable or showed an increase in BMI. Conclusions This observational study suggests that many individuals with severe and enduring anorexia nervosa may benefit from flexible treatment, aiming at supporting quality of life. The results highlight the importance of coordinating and integrating the treatment of severe and enduring anorexia nervosa and co-occurring psychiatric disorders as well as medical complications. Further research and international dialogue about the how treatment for this vulnerable patient group should best be organized is called for. Trial registration Trial registration number: NCT05708404. Date of registration: 01/23/2023 (retrospectively registered).

Introduction: Pelvic insufficiency fractures (PIFs) are adverse events associated with chemoradiotherapy (CRT) administered preoperatively in rectal cancer, with incidences of 0–33.6% reported in the literature. Data on PIFs after 5 × 5 Gy fractionated short-course radiotherapy (SCRT) using highly conformal radiotherapy techniques such as volumetric modulated arc therapy (VMAT) is limited. Methods: The Turku University Hospital colorectal cancer database was searched for patients operated on for stage I–III rectal cancer during the years 2014–2018. The hospital’s routine follow-up includes a 2-year computed tomography (CT) scan, which was systemically re-evaluated to detect PIFs. Only radiotherapy delivered using VMAT and image-guided approaches was included. Baseline demographics, tumor data, and dose-volume data were collected to identify risk factors for PIFs. Results: Median time to CT scan was 24 months. Among the 164 patients analyzed, the 2-year PIF incidence was 22.2% for SCRT (n = 12/54, OR 9.1 (CI95% 1.9–42.9), p = 0.004), 9.1% for CRT (n = 4/44, OR 3.2 (CI95% 0.6–18.3), p = 0.13) and 3.0% (n = 2/66, reference) for those operated on without radiotherapy. The PIF incidence was not explained by differences in dose-volume data in either the SCRT or CRT groups. Fracture risk was higher in women, up to 50% after SCRT. Conclusions: Every fifth patient treated with SCRT and rectal surgery presented with a PIF. Critical bony structures to be avoided during radiotherapy contouring could not be identified. Clinicians, especially those involved with the follow-up of rectal cancer, should be aware of this potentially debilitating and surprisingly common adverse event.

Emma Saure,1,2 Monica Ålgars,1,3,4 Marja Laasonen,5 Anu Raevuori6,7 1Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 2BABA Center and Department of Clinical Neurophysiology, Children’s Hospital, Helsinki, Finland; 3Department of Psychiatry, Helsinki University Hospital, Helsinki, Finland; 4Department of Psychology, Åbo Akademi University, Turku, Finland; 5Logopedics, School of Humanities, Philosophical Faculty, University of Eastern Finland, Joensuu, Finland; 6Department Psychiatry, Division of Adolescent Psychiatry, Helsinki University Hospital, Helsinki, Finland; 7Clinicum, Department of Public Health, University of Helsinki, Helsinki, FinlandCorrespondence: Emma Saure, Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, P.O. Box 21, Helsinki, FI-00014, Finland, Tel +358443035828, Email emma.saure@helsinki.fiAbstract: Anorexia nervosa (AN) is a potentially severe eating disorder whose core characteristics include energy intake restriction leading to low body weight. Autism spectrum disorder (ASD) is a developmental disorder characterized by deficits in social interaction and communication as well as repetitive, stereotyped behavior and interests. Both high ASD traits and diagnosed ASD are overrepresented among individuals with AN, and AN and ASD appear to share certain neurocognitive features. These features are associated with the severity of eating disorder symptoms and prolongation of AN. Thus, individuals with AN and high ASD traits or ASD may benefit less from traditional treatment when compared to those with low ASD traits. No previous reviews have summarized what is known about treatment adaptations for individuals with AN and high ASD traits or ASD. The purpose of this narrative review was to investigate the feasibility of cognitive remediation therapy (CRT), cognitive remediation and emotional skill training (CREST), and cognitive behavioral therapy (CBT), and give an overview of treatment modifications for individuals with AN and co-occurring ASD or high ASD traits. We found nine studies that fulfilled our inclusion criteria. The combined results suggest that individuals with AN and high ASD traits or ASD benefit less from CRT, CREST, and CBT than those with AN and low ASD traits. However, CRT and CREST administered in individual format may be associated with improved cognitive flexibility, motivation for change, and decreased alexithymia among adults with AN and high ASD traits or ASD. Individuals with comorbid AN and ASD themselves highlight the importance of treatment adaptations that take the characteristics of ASD into account. In the future, controlled studies of the treatment strategies for individuals with AN and ASD/high ASD traits are needed in order to improve the outcome of individuals with this challenging comorbidity.Keywords: anorexia nervosa, feeding and eating disorders, autism spectrum disorder, treatment, cognitive remediation, cognitive behavioral therapy

BackgroundKRAS mutations, present in over 40% of metastatic colorectal cancer (mCRC), are negative predictive factors for anti-EGFR therapy. Mutations in KRAS-G12C have a cysteine residue for which drugs have been developed. Published data on this specific mutation are conflicting; thus, we studied the frequency and clinical characteristics in a real-world and population-based setting.MethodsPatients from three Nordic population-based cohorts and the real-life RAXO-study were combined. RAS and BRAF tests were performed in routine healthcare, except for one cohort. The dataset consisted of 2,559 patients, of which 1,871 could be accurately classified as KRAS, NRAS, and BRAF-V600E. Demographics, treatments, and outcomes were compared using logistic regression. Overall survival (OS) was estimated with Kaplan–Meier, and differences were compared using Cox regression, adjusted for baseline factors.ResultsThe KRAS-G12C frequency was 2%–4% of all tested in the seven cohorts (mean 3%) and 4%–8% of KRAS mutated tumors in the cohorts (mean 7%). Metastasectomies and ablations were performed more often (38% vs. 28%, p = 0.040), and bevacizumab was added more often (any line 74% vs. 59%, p = 0.007) for patients with KRAS-G12C- vs. other KRAS-mutated tumors, whereas chemotherapy was given to similar proportions. OS did not differ according to KRAS mutation, neither overall (adjusted hazard ratio (HR) 1.03; 95% CI 0.74–1.42, reference KRAS-G12C) nor within treatment groups defined as “systemic chemotherapy, alone or with biologics”, “metastasectomy and/or ablations”, or “best supportive care”, RAS and BRAF wild-type tumors (n = 548) differed similarly to KRAS-G12C, as to other KRAS- or NRAS-mutated (n = 66) tumors.ConclusionsIn these real-life and population-based cohorts, there were no significant differences in patient characteristics and outcomes between patients with KRAS-G12C tumors and those with other KRAS mutations. This contrasts with the results of most previous studies claiming differences in many aspects, often with worse outcomes for those with a KRAS-G12C mutation, although not consistent. When specific drugs are developed, as for this mutation, differences in outcome will hopefully emerge.

Background: Resection of colorectal cancer (CRC) metastases provides good survival but is probably underused in real-world practice. Methods: A prospective Finnish nationwide study enrolled treatable metastatic CRC patients. The intervention was the assessment of resectability upfront and twice during first-line therapy by the multidisciplinary team (MDT) at Helsinki tertiary referral centre. The primary outcome was resection rates and survival. Findings: In 2012–2018, 1086 patients were included. Median follow-up was 58 months. Multiple metastatic sites were present in 500 (46%) patients at baseline and in 820 (76%) during disease trajectory. In MDT assessments, 447 (41%) were classified as resectable, 310 (29%) upfront and 137 (18%) after conversion therapy. Six-hundred and ninety curative intent resections or local ablative therapies (LAT) were performed in 399 patients (89% of 447 resectable). Multiple metastasectomies for multisite or later developing metastases were performed in 148 (37%) patients. Overall, 414 liver, 112 lung, 57 peritoneal, and 107 other metastasectomies were performed. Median OS was 80·4 months in R0/1-resected (HR 0·15; CI95% 0·12–0·19), 39·1 months in R2-resected/LAT (0·39; 0·29–0·53) patients, and 20·8 months in patients treated with “systemic therapy alone” (reference), with 5-year OS rates of 66%, 40%, and 6%, respectively. Interpretation: Repeated centralized MDT assessment in real-world metastatic CRC patients generates high resectability (41%) and resection rates (37%) with impressive survival, even when multisite metastases are present or develop later. Funding: The funders had no role in the study design, analysis, and interpretation of the data or writing of this report.