Acta Oncologica最新文献

Background and purpose: Changes in treatment approaches, characterised by the shift from laryngectomy to a focus on organ-preserving methods may have potentially resulted in lower survival. We aim to identify differences in survival trends for laryngeal cancer (LC) in the Nordic countries over a period of 50 years, and discuss the potential impact of factors such as changes in treatment protocols.

Materials and methods: Five-year relative survival (RS) data from 1972 to 2021 were obtained from the NORDCAN database 2.0 which included 33,692 LC cases, of which 85% were diagnosed among men. In the NORDCAN database, the age-standardised RS is calculated using the Pohar Perme estimator with individual International Cancer Survival Standards weights. Joinpoint regression models were used to assess potential shifts in trend over the years in RS.

Results: While Denmark and Norway demonstrated an increasing trend in 5-year RS from 1972 to 2021, in Finland and Sweden, the 5-year RS among men remained static, without any discernible significant trend. Over the 30-year period from 1992-1996 to 2017-2021, RS improved by 9, 4, 13, and 2 percentage points in Denmark, Finland, Norway, and Sweden, respectively. Among women in Sweden, a linear negative trend was observed, noticeable as a 16 percentage-point decline in 5-year RS from the earliest to the latest period.

Interpretation: The underlying causes for the differences in survival trends remain unclear. Besides differences in treatment protocols, several other factors can affect RS making the interpretation of RS trends challenging.

Background: Tinzaparin, a low-molecular weight heparin (LMWH), has shown anti-neoplastic properties in animal models and in in vitro studies of human cancer cell lines. The reduction of CA-125 levels during neoadjuvant chemotherapy (NACT) in patients with epithelial ovarian cancer (EOC) co-varies with the prognosis; the larger the decrease in CA-125, the better the prognosis.

Purpose: This study aims to evaluate the potential anti-neoplastic effects of tinzaparin by investigating changes in serum CA-125 levels in advanced EOC patients who receive NACT.

Material and methods: This is an open randomized multicenter pilot trial. Forty patients with EOC selected to receive NACT will be randomized 1:1 to receive daily addition of tinzaparin or no tinzaparin. The processing and treatment of the patients will otherwise follow the recommendations in the Swedish National Guidelines for Ovarian Cancer. Before every cycle of chemotherapy, preoperatively, and 3 weeks after the last cycle of chemotherapy, a panel of biomarkers, including CA-125, will be measured.

Patients: Inclusion criteria are women aged 18 years or older, World Health Organization performance status 0-1, histologically confirmed high-grade serous, endometrioid or clear cell EOC, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV. In addition, a CA-125 level of ≥ 250 kIE/L at diagnosis. Exclusion criteria are contraindications to LMWH, ongoing or recent treatment with unfractionated heparin, LMWH, warfarin or non-vitamin K antagonist oral anticoagulants.

Interpretation: This study will make an important contribution to the knowledge of the anti-neoplastic effects of tinzaparin in EOC patients and may thus guide the planning of a future study on the impact of tinzaparin on survival in EOC.

Background and purpose: The aim of this study was to evaluate and compare the fear of cancer recurrence (FCR) in patients diagnosed with a small renal mass (SRM) and managed with either active surveillance (AS) or minimal invasive renal cryoablation (CA).

Patients/material and methods: A total of 398 patients with SRMs (263 AS and 135 CA patients) were retrospectively identified across three institutions and invited to complete the Fear of Cancer Recurrence-Short Form (FCRI-SF) questionnaire.

Results: No statistically significant differences in FCRI-SF score were observed between the AS (mean = 10.9, standard deviation [SD] = 6.9) and CA (mean = 10.2, SD = 7.2) (p = 0.559) patients, with the mean scores of both groups being below the suggested clinically significant cut-off of 16. A total of 25% of AS and 28% of CA patients reported sub-clinical or clinical levels of FCR (FCRI-SF score > 16). Within the AS group, a weak negative association between FCR severity and age was observed (r = -0.23, p = 0.006), and a statistically significant difference in FCRI-SF score between patients aged more or less than 73 years (p = 0.009).

Interpretation: FCR levels were comparable between AS and CA patients, suggesting that treatment decisions should prioritise clinical factors. Up to 28% of AS and CA patients report clinically significant FCR, highlighting the importance of considering the possibility of FCR, especially in younger patients.

Background: While soft tissue sarcomas affect younger patients, few studies have assessed the distribution of underlying pathogenic germline variants.

Patients and methods: We retrospectively identified all pediatric and young adult patients (0-22 years) at Haukeland University Hospital, Norway (1981-2019), through clinical and pathological records. We identified n = 46 eligible patients. From these 46 patients, adequate material representing normal tissue was available for n = 41 cases (n = 24 diagnosed with rhabdomyosarcoma, 9 with synovial sarcomas, 2 with Ewing sarcomas, and 6 without further classification), with matching tumor tissue for n = 40. Normal tissue samples were analyzed for germline pathogenic variants (PVs) by targeted sequencing of 360 cancer genes.

Results: Out of the 41 analyzed cases, we found PVs or likely PVs in 7 (17%). These variants were found in TP53, MUTYH, FANCC, DICER1, FANCA, MYO3A, and MYO5B. Supporting the causality of these PVs, four cases revealed loss of heterozygosity (LOH) of the wild-type allele in the tumor tissue, one patient with a PV in DICER1 had a second somatic variant in DICER1, and a patient with a PV in TP53 had the altered allele amplified in the tumor. For three out of five with available family history, a history of other cancers in relatives was recorded. Among genes with variants of uncertain significance, CHD1L was of particular interest, revealing a stop-gain and a missense variant.

Interpretation: A high fraction of young patients with soft tissue sarcoma harbor PVs. Among the genes affected, we substantiate a potential role of MYO5B and propose a potential role for MYO3A.

Background and purpose: Parenting concerns can be a major source of distress for patients with cancer who are parents of dependent children; however, these are often not addressed in health care. The Parenting Concerns Questionnaire (PCQ) is an instrument designed to assess parents' worries about the impact of cancer on their children and their ability to parent during this time. The Swedish version of the PCQ has, however, not been evaluated. This study therefore aimed to examine the psychometric properties of the PCQ in a sample of Swedish parents with cancer.

Material and methods: A sample of 336 patients with cancer having dependent children (≤18 years) were included in a cross-sectional web-based survey. Participants completed questionnaires assessing parenting concerns, depression, anxiety, and stress symptoms (DASS); self-efficacy, family functioning (FAD-GF); and sociodemographic and clinical characteristics. Descriptive analyses, as well as reliability and validity analyses, were conducted followed by a confirmatory factor analysis of the factor structure proposed by the authors of the original version of the PCQ.

Results: The majority were mothers (94.9%) with breast cancer (66.4%) aged 40-50 years (59.5%). The results showed evidence for convergent, criterion, and known group's validity, but the original three-factor structure of the PCQ was not fully supported by confirmatory factor analysis.

Interpretation: Evaluating parenting concerns may be an important step towards identifying patients who could benefit from targeted psychosocial interventions. However, the PCQ may require some further refinement to fully capture the breadth of parenting concerns in parents with cancer in different settings.

Background and purpose: The Swedish Lymphoma Register (SLR) was initiated in the year 2000 with the aim to monitor quality of care in diagnostics, treatment and outcome of all lymphomas diagnosed nationally among adults. Here, we present the first systematic validation of SLR records as a basis for improved register quality and patient care.

Patients and methods: We evaluated timeliness and completeness of register records among patients diagnosed with lymphoma in the SLR (n = 16,905) compared with the National Cancer Register for the period 2013-2020. Comparability was assessed through evaluation of coding routines against national and international guidelines. Accuracy of 42 variables was evaluated through re-abstraction of data from medical records among 600 randomly selected patients diagnosed in 2016-2017 and treated across all six Swedish healthcare regions.  Results: Completeness was high, >95% per year for the period 2013-2018, and >89% for 2019-2020 compared to the National Cancer Register. One in four patients was registered within 3 months, and 89.9% within 2 years of diagnosis. Registration instructions and coding procedures followed the prespecified guidelines. Missingness was generally low (<5%), but high for occasional variables, for example, those describing maintenance and consolidative treatment. Exact agreement of categorical variables was high overall (>80% for 24/34 variables), especially for treatment-related data (>80% for 17/19 variables).

Interpretation: Completeness and accuracy are high in the SLR, while timeliness could be improved. Finetuning of variable registration guided by this validation can further improve reliability of register reports and advance service to lymphoma patients and health care in the future.

Background and purpose: We have recently demonstrated that screen-detected invasive breast cancers had more favourable tumour characteristics than non-screen-detected. The objective of the study was to analyse differences in breast cancer treatment between screen-detected and non-screen-detected cases by age at diagnosis, with and without adjustment for tumour (T) and nodal (N) status, within a nationwide, population-based mammography screening programme utilising register data.

Material and methods: Data spanning 2008-2017 were collected from the National Quality Register for Breast Cancer. Multivariable logistic regression analysis was used to estimate odds ratios and 95% confidence intervals for treatment disparities between screen-detected and non-screen-detected breast cancer.

Results: Among 46,481 women diagnosed with invasive breast cancer aged 40-74 and invited for mammography screening, significant differences in treatment were observed. Screen-detected cases showed higher likelihoods of partial mastectomy compared to mastectomy, endocrine therapy, and radiotherapy, whereas chemotherapy and antibody therapy were less likely compared to non-screen-detected cases. However, when adjusting for surgery type, screen-detected cases showed lower likelihoods of radiotherapy. Age at diagnosis significantly influenced treatment odds ratios, with interactions observed for all treatments except radiotherapy adjusted for surgery. Differences increased with age, except for endocrine therapy. Radiotherapy adjusted for surgery type showed no age-related interaction. Adjusting for T and N did not alter these patterns.

Interpretation: In general, screen-detected cases received less aggressive treatment, such as mastectomy, chemotherapy, and antibody therapy, compared to non-screen-detected cases. Disparities increased with age, except for endocrine therapy and radiotherapy adjusted for surgery. Differences persisted after adjusting for T and N, suggesting that these factors cannot solely explain the results.

Background: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers. Using the Auria Biobank in Finland, we aimed to identify and characterize patients with these gene fusions, and describe their clinical and tumor characteristics, treatments received, and outcomes.

Material and methods: We evaluated pediatrics with any solid tumor type and adults with colorectal cancer (CRC), non-small cell lung cancer (NSCLC), sarcoma, or salivary gland cancer. We determined tropomyosin receptor kinase (TRK) protein expression by pan-TRK immunohistochemistry (IHC) staining of tumor samples from the Auria Biobank, scored by a certified pathologist. NTRK gene fusion was confirmed by next generation sequencing (NGS). All 2,059 patients were followed-up starting 1 year before their cancer diagnosis.

Results: Frequency of NTRK gene fusion tumors was 3.1% (4/127) in pediatrics, 0.7% (8/1,151) for CRC, 0.3% (1/288) for NSCLC, 0.9% (1/114) for salivary gland cancer, and 0% (0/379) for sarcoma. Among pediatrics there was one case each of fibrosarcoma (TPM3::NTRK1), Ewing's sarcoma (LPPR1::NTRK2), primitive neuroectodermal tumor (DAB2IP::NTRK2), and papillary thyroid carcinoma (RAD51B::NTRK3). Among CRC patients, six harbored tumors with NTRK1 fusions (three fused with TPM3), one harbored a NTRK3::GABRG1 fusion, and the other a NTRK2::FXN/LPPR1 fusion. Microsatellite instability was higher in CRC patients with NTRK gene fusion tumors versus wild-type tumors (50.0% vs. 4.4%). Other detected fusions were SGCZ::NTRK3 (NSCLC) and ETV6::NTRK3 (salivary gland cancer). Four patients (three CRC, one NSCLC) received chemotherapy; one patient (with CRC) received radiotherapy.

Conclusion: NTRK gene fusions are rare in adult CRC, NSCLC, salivary tumors, sarcoma, and pediatric solid tumors.

Background: Hormone receptor positivity predicts benefit from endocrine therapy but the knowledge about the long-term survival of patients with different tumor receptor levels is limited. In this study, we describe the 25 years outcome of tamoxifen (TAM) treated patients.

Patients and methods: Between 1983 and 1992, a total of 4,610 postmenopausal patients with early-stage breast cancer were randomized to receive totally 2 or 5 years of TAM therapy. After 2 years, 4,124 were alive and free of breast cancer recurrence. Among these, 2,481 had demonstrated estrogen receptor positive (ER+) disease. From 1988, the Abbot enzyme immunoassay became available and provided quantitative receptor levels for 1,210 patients, for which our analyses were done.

Results: After 5 years of follow-up, when all TAM treatment was finished, until 15 years of follow-up, breast cancer mortality for patients with ER+ disease was significantly reduced in the 5-year group as compared with the 2-year group (hazard ratios [HR] 0.67, 95% confidence intervals [CI] 0.55-0.83, p < 0.001). After 15 years, the difference between the groups remained but did not increase further. A substantial benefit from prolonged TAM therapy was only observed for the subgroup of patients with ER levels below the median (HR = 0.62, 95% CI 0.46-0.84, p = 0.002). Similarly, patients with progesterone receptor negative (PR-) disease did benefit from prolonged TAM treatment. For patients with progesterone receptor positive (PR+) disease, there was no statistically significant benefit from more than 2 years of TAM.  Interpretation: As compared with 2 years of adjuvant TAM, 5 years significantly prolonged breast cancer-specific survival. The benefit from prolonged TAM therapy was statistically significant for patients with ER levels below median or PR-negative disease. There was no evident benefit from prolonged TAM for patients with high ER levels or with PR+ tumors.