Acta Oncologica最新文献

Background and purpose: Venous thromboembolism (VTE) is a cause of increased morbidity and risk of death. Studies report VTE in up to 30% of glioma patients but the results vary. The VTE risk is relevant when evaluating prophylaxis to avoid unnecessary bleeding or overdiagnosis. This study examines the VTE incidence in patients with glioma WHO grade 2-4, and when VTE occurred, risk factors, and overall survival (OS) for patients with WHO grade 4.

Materials and methods: In total 3,630 patients with WHO grade 2 (n = 230), grade 3 (n = 317), and grade 4 (n = 3,083) gliomas from 2010 to 2018 were identified using the Danish Neuro-Oncology Registry. VTE diagnoses and time of death were obtained from Statistics Denmark.

Results and interpretation: The VTE incidence was 5.2, 6.3, and 6.8% in patients with WHO grade 2, 3, and 4 gliomas, respectively. The VTE incidence rate was highest during the first 3 months after the diagnosis with 53 events. Increasing age (HR 1.03, 95%CI 1.01-1.04), male sex (HR 1.47, 95%CI 1.09-1.99), poor performance status (HR 1.57, 95%CI 1.10-2.25), and post-operative long-course radiochemotherapy (HR 2.10, 95%CI 1.19-3.72) were predictors of VTE in patients with glioma WHO grade 4. There was no difference in OS comparing patients having VTE to those without (p = 0.068). In conclusion, patients with glioma WHO grade 2-4 were at high risk of VTE, especially the first 3 months after diagnosis. Increasing age, male sex, poor performance status, and long-course radiochemotherapy were associated with increased risk of VTE in patients with glioma WHO grade 4.

Background and purpose: Cancer may create problems and needs associated with impaired quality of life (QoL). The first health care encounter is important to enable patients to cope and may ultimately impact QoL. The aim of this study was to describe the patients' experiences of encounters with health care professionals. Another aim was to explore the possible impact that the encounters may have on QoL 1 year after a colon cancer diagnosis. We also wanted to investigate whether patients had received information about treatment related side-effects.

Patients and methods: This substudy within the QoLiCOL (Quality of Life in COLon cancer) study included 1687 patients (male n = 876, female n = 811, mean age 71) between 2015 and 2019. Questionnaires were answered at diagnosis and after 1 year. QoL was self-assessed with a seven-point Likert scale. Analyses were performed using descriptive statistics and ordinal logistic regression.

Results: A total of 1,550 patients (91.9%) reported feeling well received by health care professionals. We found no statistically significant association with QoL. Patients (87%) reported feeling well informed about their treatment, but few patients recalled having received information regarding potential side effects on bowel or sexual function.

Interpretation: Patients with colon cancer generally had a positive experience of the encounter with health care where they felt both well received and well informed. However, the amount of relevant information received was scarce. This indicates that it may be difficult to identify whether patients are properly informed prior to treatment for colon cancer only by asking if they feel well informed.

Background and purpose: We investigated the prognosis of breast cancer (BC) with low expression of human epidermal growth factor receptor 2 (HER2), as previous studies have found varying impacts on survival of HER2-low BC compared with HER2 0 BC (HER2 IHC score of 0). HER2-low is defined as a score of 1+ or 2+ in an immunohistochemical (IHC) assay without HER2 gene amplification.

Materials and methods: Patients with HER2 0 or HER2-low BC from the national Danish Breast Cancer Group database were examined by multivariable survival analysis in a retrospective noninterventional investigation. Patients were grouped as either HER2 0 or HER2-low. The primary endpoint was time to recurrence (TR), and the secondary endpoints were overall survival (OS) and distant recurrence-free interval (DRFI).

Results: 41,610 patients were included (12,981 with HER2 0 BC and 28,629 with HER2-low BC). HER2-low BC was associated with a lower risk of recurrence (hazard ratio [HR]: 0.92, p = 0.03). Regarding secondary endpoints, HER2-low disease was linked to improved overall OS (HR: 0.94, p = 0.02). No statistically significant effect of HER2-low was found for DRFI, along with no differential effect of HER2-low according to estrogen receptor (ER) status.

Interpretation: HER2-low BC was found to show an improved HR for OS and DRFI compared with HER2 0 BC; however, further studies are need to establish whether it represents a separate biological entity.

Background and purpose: In patients with metastatic melanoma who respond to anti-PD-1 therapy, the proliferation of intra-tumour CD8+ T cells is directly correlated with the clinical response, making tumour-infiltrating lymphocytes (TILs) a treatment of interest in combination with a PD-1 inhibitor, which is the undisputed gold standard in the management of metastatic melanoma. The aim of this trial was, therefore, to evaluate the safety and efficacy of sequential combination therapy consisting of nivolumab (a PD-1 inhibitor) and TILs adoptive T cells in patients with metastatic melanoma.

Materials and methods: We performed an exploratory, prospective, single-centre, open-label, non-randomised, uncontrolled phase I/II study. We enrolled 10 previously untreated patients with advanced melanoma. The treatment regimen was neoadjuvant anti-PD-1 therapy followed by 2 injections of TILs and a second sequence of anti-PD-1 therapy.

Results and interpretation: Among the four patients who received the autologous TILs + nivolumab combination, three (75%) achieved an objective response (two achieved a partial response [PR] at the end of the study, two achieved a complete response [CR]), and one achieved a CR at the end of the study. Among these three patients, one had a PR, and two had stable disease (SD) after the nivolumab course and before any TILs administration, reinforcing the importance of the tumour response after TILs injection. These responses were persistent, ranging from 9 months to 3.4 years.

Background: This study assessed the biochemical disease-free survival (bDFS), prostate cancer-specific survival (PCSS), overall survival (OS), and side effects in patients aged < 70 and ≥ 70 years following definitive radiotherapy (RT). It also analysed the correlation between age at diagnosis and clinicopathological characteristics of prostate cancer (PCa).

Methods: The prognostic factors for bDFS, PCSS, and OS were determined through univariable and multivariable analyses. Two age groups were also compared in terms of acute and late grade ≥ 2 genitourinary (GU) and gastrointestinal (GI) toxicities, the predictors of which were determined through logistic regression analysis.

Results: Of the 1,328 patients, 715 (53.8%) and 613 (46.2%) were aged < 70 and ≥ 70 years, respectively. Median follow-up time was 84.5 months. No significant differences in the 7-year bDFS (86.3% vs. 86.8%) and PCSS rates (92.9% vs. 93.3%) were found between the ≥ 70 and < 70 age groups. The multivariable analysis showed that advanced clinical T stage, high International Society of Urological Pathology (ISUP) grade, and high-risk disease independently predicted poor bDFS and PCSS. Metastatic lymph nodes were another bDFS prognostic factor. The multivariable analysis identified age ≥ 70 years, cardiac events at diagnosis, advanced stage, higher ISUP grade, and non-use of simultaneous integrated boost technique as negative factors for OS. Additionally, diabetes and transurethral resection of the prostate (TUR-P) independently predict late-grade ≥ 2 GU toxicity.

Interpretation: Definitive RT is a safe and effective treatment for patients with localised PCa no matter their age. Although patients over 70 years have higher risk factors and comorbidities, their bDFS, PCSS, and toxicities were comparable to those of patients aged < 70 years.

Background and purpose: Many non-neoplastic diseases have been established to be tumorigenic, and cancers are sometimes misdiagnosed as non-neoplastic diseases. We conducted a comprehensive registry-based study of site-specific cancer diagnosis risk following the diagnosis of any preceding medical condition (PMC) encoded by the International Classification of Diseases (ICD)-10 classification.

Material and methods: We analyzed healthcare data and cancer data for a random population-based sample of 2.5 million individuals living in Finland on January 1, 2000. Hazard ratios for each PMC and cancer pair were estimated using piecewise constant hazard regression models. P-values were corrected for multiple testing with the Bonferroni method.

Results: Several lifestyle-related PMCs were associated with the risk of cancer diagnosis, exemplified by chronic obstructive pulmonary disease and subsequent lung cancer diagnosis risk (female hazard ratio [HR] = 9.91, 95% confidence interval [CI]: 9.18-19.7, p-adj. < 0.0001; male HR = 5.69, 95% CI: 5.43-5.96, p-adj. < 0.0001). Diagnosis risk of ill-defined cancers appeared to increase following diagnosis of Alzheimer's disease (AD). We identified rare PMCs of potential interest.

Interpretation: A considerable proportion of the statistically significant associations were explainable by tobacco smoking and alcohol use. The enrichment of ill-defined cancer diagnoses in persons with AD, together with the overall inverse association between AD and cancer, may reflect underdiagnosis of cancer in this patient population. Our results provide a useful resource for research on the prevention and early detection of cancer.

Introduction: Nasopharyngeal carcinoma (NPC) is a rare disease and most studies have therefore been conducted in endemic areas. The aim of this study was to describe epidemiology and treatment outcomes of NPC in a population-based, non-endemic setting.

Material and methods: Patients with NPC diagnosed in Denmark from 2000 to 2018 were identified in the Danish Head and Neck Cancer Study Group (DAHANCA) database. Clinical records were reviewed to obtain missing data and confirm outcome, histological subtypes, Epstein-Barr virus (EBV)-status, prognostic factors, and treatment.

Results: NPC was identified in 394 patients corresponding to age-standardized incidence rates of 0.5 and 0.2 per 100,000 in men and women, respectively. The 5-year overall (OS) and disease-specific survival (DSS) were 56 and 66%. In multivariate analysis, stage, smoking, and histology affected both OS and DSS, as patients with undifferentiated carcinomas had superior outcomes. Tumor EBV-status was determined in 221 patients, of whom 160 (72%) tested positive. EBV-positivity was associated with an improved OS in univariate analysis, but not after adjustment for relevant clinical factors.

Interpretation: NPC is a rare malignancy in Denmark, and three in four patients have EBV-associated tumors. Tumor histology, smoking status, and stage, but not EBV-status, had independent prognostic impact on survival.

Introduction: In recent decades, attendance to organized breast cancer screening has been decreasing in European countries. This could be partly due to an increase in the use of opportunistic screening. The aim of this study was to assess the coverage of imaging in and outside the screening program in Finland during the period of 1999-2018. We also compared the usage of imaging services across sociodemographic groups in the more recent years (2017-2018).

Methods: Our initial data consisted of 1,159,000 screening-target-aged women (50-69 years) in 1999-2018 and 1,849,000 women aged 30-89 years in 2017-2018. Data on organized breast cancer screening program was drawn from the Finnish Cancer Registry and supplemented with comprehensive individual data on mammograms and ultrasounds performed outside the program.

Results: Among the screening-aged women (50-69), a clear decline in the overall imaging coverage was observed during the study period (from 89 to 85%). The use of outside imaging increased slightly but not enough to compensate for the overall decrease. There were large differences in coverages between sociodemographic groups. Compared to manual workers and the unemployed, upper-level employees were around two times more active in using outside imaging (8.2% vs. 3.6% and 4.3%, respectively).

Interpretation: Overall breast imaging coverage has slowly decreased during the 2000s, while outside imaging has increased slightly. The coverage of imaging in and outside the program largely followed the same trends, with the highest usage concentrating on higher socioeconomical groups, native speakers and highly educated women.

Background and purpose: Intensity Modulated Proton Therapy (IMPT) faces challenges in lung cancer treatment, like maintaining plan robustness for moving tumors against setup, range errors, and interplay effects. Proton Arc Therapy (PAT) is an alternative to maintain target coverage, potentially improving organ at risk (OAR) sparing, reducing beam delivery time (BDT), and enhancing patient experience. We aim to perform a systematic plan comparison study between IMPT and energy layer (EL) and spot assignment algorithm - Proton Arc Therapy (ELSA-PAT) to assess its potential for lung cancer treatment.

Material and methods: A total of 14 Lung ELSA-PAT plans were compared retrospectively with IMPT plans. 4D worst-case minimax robust optimization was performed, including 84 scenarios (3%, 3 mm). Dosimetry assessment included target (clinical tumor volume [CTV]) and important OARs, on nominal and worst-case scenarios. Most relevant normal tissue complication probabilities (NTCP), target coverage robustness against interplay effect, and BDT were evaluated.

Results: CTV D95% and D98% showed no significant difference in comparison. PAT demonstrated better conformality by 66% (p = 0.00012) but delivered a higher heart mean dose (HMD, 23%). There was a 2% increase in NTCP 2-year mortality risk with PAT. Total BDT was comparable among techniques. IMPT was more robust than PAT against interplay effect, considering both D1% (1.0 ± 0.8 Gy vs 1.1 ± 1.4 Gy) and D98% bandwidths (0.9 ± 0.9 Gy vs 1.1 ± 1.3 Gy).

Interpretation: Both techniques provide a similar level of dose coverage to the target volume. Although PAT improved dose conformality, higher HMD translated into increased heart toxicity, presumably due to chosen planning methodology and OAR proximity to target. Increased ELs and spots raised PAT BDT, although it could improve daily treatment workflow.

Objectives: To evaluate the feasibility of AI-assisted reading of prostate magnetic resonance imaging (MRI) in Organized Prostate cancer Testing (OPT).

Methods: Retrospective cohort study including 57 men with elevated prostate-specific antigen (PSA) levels ≥3 µg/L that performed bi-parametric MRI in OPT. The results of a CE-marked deep learning (DL) algorithm for prostate MRI lesion detection were compared with assessments performed by on-site radiologists and reference radiologists. Per patient PI-RADS (Prostate Imaging-Reporting and Data System)/Likert scores were cross-tabulated and compared with biopsy outcomes, if performed. Positive MRI was defined as PI-RADS/Likert ≥4. Reader variability was assessed with weighted kappa scores.

Results: The number of positive MRIs was 13 (23%), 8 (14%), and 29 (51%) for the local radiologists, expert consensus, and DL, respectively. Kappa scores were moderate for local radiologists versus expert consensus 0.55 (95% confidence interval [CI]: 0.37-0.74), slight for local radiologists versus DL 0.12 (95% CI: -0.07 to 0.32), and slight for expert consensus versus DL 0.17 (95% CI: -0.01 to 0.35). Out of 10 cases with biopsy proven prostate cancer with Gleason ≥3+4 the DL scored 7 as Likert ≥4.

Interpretation: The Dl-algorithm showed low agreement with both local and expert radiologists. Training and validation of DL-algorithms in specific screening cohorts is essential before introduction in organized testing.