Acta Oncologica最新文献

Background and purpose: Organised mammography screening reduces breast cancer mortality by 30-40% in women aged 50-69. Despite limited evidence for women aged 40-49, screening guidelines are trending toward younger ages. Iceland has offered biennial screening to women aged 40-69 since 1987. This study compares screening quality indicators and tumour characteristics between women aged 40-49 and 50-69 from 1990 to 2020. Patient/material and methods: Screening-related data were obtained from the Icelandic Breast Cancer Screening Program, and breast cancer diagnoses and tumour characteristics were sourced from the Icelandic Cancer Registry.

Results: In total, 84,677 women aged 40-69 years attended 455,532 organised screening sessions in Iceland over a 30-year period. Women aged 40-49 years demonstrated higher recall rates (4.9% vs. 3.5%) and lower participation rates (60.7% vs. 61.5%), lower breast cancer detection rates (2.1 vs. 6.0/1,000), and lower episode sensitivity (54.8% vs. 70.5%), compared to those aged 50-69 years. Among screen-detected cases, women aged 40-49 years exhibited a higher proportion of tumours larger than 20 mm (29.7% vs. 21.7%), more lymph node positivity (41.2% vs. 28.2%) and higher human epidermal growth factor receptor 2 (HER2) positivity (18.6% vs. 11.8%), compared to those aged 50-69 years.

Interpretation: The disparity in breast cancer screening performances between the age groups may reflect unmodifiable factors in younger women. The presence of advanced tumour characteristics among women aged 40-49 years who attended screening indicates the importance of early detection for improving prognosis.

Background and purpose: In the Netherlands, care for head and neck cancer (HNC) is centralised in head and neck oncology centres (HNOCs). Follow-up after treatment requires frequent visits that can burden patients and providers. Telemedicine, through remote evaluation of laryngopharyngoscopy videos recorded at local hospitals, may offer a feasible alternative. This study protocol describes the aim to assess patient satisfaction and safety with telemedicine follow-up after treatment of (pre-)malignant glottic lesions, including severe dysplasia, carcinoma-in-situ and T1 squamous cell carcinoma, conducted at one HNOC and participating general hospitals.

Methods and analysis: As a non-blinded, randomised controlled trial, 90 patients with a one-way travel time by car of over 45 min to the HNOC will be allocated to the intervention group (follow-up by an Ear, Nose and Throat surgeon at a nearby participating hospital) or the control group (standard follow-up at the HNOC). All patients undergo guideline-based care. In the intervention group, laryngopharyngoscopy recordings will be remotely reviewed by HNOC specialists on the same day. Surveys will be fulfilled at baseline, 6 and 12 months. The primary outcome is overall patient satisfaction using a 0-10 numeric rating scale at 12 months follow-up. Secondary outcomes are safety, quality of life, fear of recurrence, travel time and carbon-dioxide emission. Safety will be assessed through recurrence, complications, re-referral and survival. Between-group and within-group comparisons will be performed to evaluate differences in outcomes, using appropriate statistical methods based on data distribution.

Ethics and dissemination: This study explores regional collaboration and sustainable follow-up for HNC patients. The ethics board approved the protocol (M23.325004). The authors commit to publishing the findings.

Background and purpose: Rural-urban differences in head and neck cancer (HNC) incidence remain understudied, especially in Europe. Changes over time in risk factors, such as smoking and human papillomavirus status, may be reflected in alterations of HNC incidence by subsite, educational level, and urbanity.

Material and methods: Incidence rate ratios (IRR) - adjusted for age, calendar period, educational and urbanization level, and region - and age-standardized HNC incidence per 100,000 person-years were estimated by sex, subsite, levels of education and urbanization over 5-year periods from 1977 to 2021. We estimated the average annual percent change in incidence and IRRs between levels of urbanization and education using Poisson regression.

Results: A lower incidence of oral cavity (IRR 0.82, 95% confidence interval [CI]: 0.73-0.93 for 2007-2021), oropharyngeal (0.75, 0.65-0.87), and nasopharyngeal cancer (0.43, 0.25-0.75) was noted among rural men when compared with urban men. Semi-urban men also showed lower incidences than urban men. Similarly, a lower incidence of oropharyngeal cancer (OPC) was observed among rural (IRR 0.62, 95% CI: 0.47-0.80) and semi-urban women (0.79, 0.63-0.99). Additionally, our study indicates that the rates of OPC and oral cavity cancer are increasing across all educational and urbanization levels. The rise in OPC is particularly notable since 1997-2001, especially among urban populations, in both men and women.

Interpretation: While a higher prevalence of risk factors among urban populations may explain the differences noted across the different urbanization levels, the reasons for the increasing trends across all strata remain unclear.

Background and purpose: Patients with metastatic melanoma live longer than a decade ago and have limited contact with the healthcare system. This requires a focus on their ability to manage their health. Patient involvement can contribute to this. The use of Patient-Reported Outcome (PRO) may facilitate patient involvement in clinical encounters, especially in the form of enhanced communication between patient and clinician. The purpose of the study was to investigate the association between active use of PRO and patient involvement for patients with metastatic melanoma. Patient/material and methods: This study was based on data from a non-randomized controlled study, in which Danish patients with metastatic melanoma were assigned to either an intervention (PRO actively used as a dialog tool in consultations throughout a year) or control group (standard treatment), based on geographic affiliation. The outcome in the present study was patient involvement, measured with five indicators of patient involvement. Linear regression models were used to estimate the crude and adjusted association between intervention and patient involvement at 3, 6, and 12 months.

Results: A total of 237 patients were included, 114 patients in the intervention group and 123 patients in the control group. Adjusted mean difference between intervention and control group was 1.54 (0.24; 2.83) at 6 months and 1.32 (0.06; 2.59) at 12 months (p < 0.05). Improvement was observed in just one indicator of patient involvement, specifically 'dialog between patient and physician'.

Interpretation: Using PRO actively as a dialog tool in consultations can contribute to improved patient involvement for patients with metastatic melanoma.

Background and purpose: The FLASH effect, where ultra-high dose rate elicits a favourable normal tissue-sparing, has been shown in several preclinical studies. Study setup differences, for example fixation methods that affect blood flow, can influence radiation response but are unexplored for FLASH. This study compared FLASH's acute skin-sparing effect with two fixation methods: a glued fixation (no blood flow restriction) and taped fixation (slight blood flow restriction). Patient/material and methods: Female CDF1 mice were irradiated on their hind foot using a glue-fixation or tape-fixation method. Glue-fixated mice were only taped during the glueing procedure and had a 10-min unrestricted period afterwards before irradiation, while tape-fixated mice were taped shortly before and throughout irradiation. Mice received single-dose irradiation (19-58 Gy) with either conventional dose rate (CONV, protons 0.06 Gy/s, electrons 0.16 Gy/s) or FLASH (electrons, 223-233 Gy/s). Differences in skin toxicity were analysed.

Results: CONV-treated tape-fixated mice required a 16-17% higher dose to induce skin toxicity relative to glued mice for both protons and electrons. Meanwhile, the fixation method did not affect FLASH-treated mice. The resulting electron FLASH-sparing effect was reduced by 18% due to the shift in radiosensitivity for CONV-treated mice.

Interpretation: CONV-treated tape-fixated mice were more radioresistant than the glue-fixated mice, consistent with the expected response to mild hypoxia. FLASH-treated mice were unaffected. These findings demonstrate the impact of fixation and, in turn, oxygen level on the differential CONV versus FLASH skin response. The results highlight the importance of minimal systemic influence on animals during FLASH studies.

Background and purpose: The association between the tumor size and the risk of lymph node metastasis (LNM) is well known. The purpose of this study is to describe a new model for predicting the occurrence of LNM at an earlier time for breast cancer patients where at a given time this association is known. Patient/material and methods: The subjects studied were 59,400 breast cancer patients treated in the period 1995-2012 and registered in the Danish Breast Cancer Group (DBCG) database. Data included age, year of treatment, menopausal status, tumor size, lymph node status, localization, focality, histological type, grade, estrogen receptor (ER), HER2 status, lympho-vascular invasion (LVI), and type of surgery. Univariate and multivariate analyses were made.

Results: 46% of patients presented with LNM. The occurrence increased with increasing tumor size. HER2 positive tumors had more LNM 56.9% versus 44.7% (p < 0.001) (odds ratio [OR] 1.17 [95% confidence interval, CI 1.09-1.26]) and mostly pronounced in relation to ER negative tumors (p < 0.001). ER negative/HER2 negative tumors had lower risk of LNM (OR 0.57 [95% CI 0.52-0.63]). Central tumors and tumors in the lower lateral quadrant were more often node positive. LVI showed increased odds for LNM (OR 5.16 [95% CI 4.84-5.52]).

Interpretation: Increasing tumor size is the only time-dependent risk of LNM. HER2 positive tumors had an increased risk of LNM, and ER negative/HER2 negative tumors had a decreased risk of LNM. LVI was associated with substantial increased risk of LNM. The knowledge of breast cancer patient and tumor characteristics at a given time may predict stage of cancer at an earlier time.

Background and purpose: Esophageal cancer (EC) histological subtypes have contrasting incidence trends according to previous studies. In high-income countries, the incidence of esophageal squamous cell carcinoma (SCC) has decreased, while the incidence of esophageal adenocarcinoma (AC) has increased. This descriptive registry-based study evaluates incidence trends by EC subtype in Finland during 2000-2021.

Material and methods: Data on all EC cases by histological subtype, sex and 10-year age group diagnosed over the period 2000-2021 was obtained from the Finnish Cancer Registry. In total, 6,482 cases (2,604 AC, 2,979 SCC) were observed. Time trends by histology, sex and age group were evaluated with Poisson regression and joinpoint regression.

Results: EC incidence in men increased by an annual percentage change (APC) of 1.3 (95% confidence intervals [CI] 0.8-1.8) while no significant increase was observed in women with APC of -0.1, 95% CI -0.8-0.6). Incidence of AC in men increased with APC of 3.5 (95% CI 2.7-4.2) and by 2.0 (95% CI 0.4-3.6) in women. No consistent trends were observed in SCC incidence although in joinpoint regression, from 2000 to 2006 SCC incidence decreased in men by APC of -6.5 (95% CI -20.3 to -1.1). From 2006 to 2021, rates plateaued with APC of 0.9 (95% CI -0.4 to 7.2). No other joinpoints were identified.

Interpretation: EC incidence increased in Finland during 2000-2021 due to an increase in AC. Incidence of AC increased more than threefold in men, with a lesser increase in women. SCC incidence declined until 2006 and plateaued thereafter.

Background and purpose: Optimal treatment duration is unknown in metastatic renal cell carcinoma (mRCC) responding to immune checkpoint inhibitors (ICPIs). Prolonged treatment can lead to late toxicity, burden for day clinics and financial impact.

Patients and methods: This multicenter retrospective study included mRCC patients responding to ipilimumab/nivolumab in first-line or nivolumab in later lines, who were treated for at least 21 months and did not stop for toxicity. Progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS) were modeled non- and semi-parametrically. The effect of elective ICPI discontinuation (i.e. treatment interruption at the clinician's discretion) between 21 and 25 months on PFS was assessed by a causal inference approach using artificial censoring along with inverse probability of censoring weighting.

Results: Ninety-five patients were included with a median follow-up of 62.1 (95% confidence interval [CI]: 57.3-67.5) months. Fifty-four received ipilimumab/nivolumab, whereas 41 patients received nivolumab, for a median treatment duration of 33.8 (95% CI: 28.5-39.6) months. Fifty-seven patients discontinued ICPIs electively. Three-year PFS after discontinuation was 57.1% (95% CI: 34.3-95.1), 3-year OS 67.5% (95% CI: 37.0-100.0), and 3-year CSS 90.0% (95% CI: 73.2-100.0). Fifteen (15.8%) patients discontinued ICPIs between 21 and 25 months. Compared to 80 patients who were treated longer, they had more often a metachronous metastatic pattern (p = 0.048) and a complete response (p = 0.045). Elective ICPI stop between 21 and 25 months did not significantly impact the hazard for progression/death (adjusted HR 1.08, 95% CI: 0.64-1.84, p = 0.766).

Interpretation: Among mRCC patients responding to ICPI, elective therapy discontinuation approximately 24 months after initiation does not appear to compromise outcomes compared to continuing therapy.

Background and purpose: Chemoradiotherapy (CRT) for squamous cell carcinoma of the anus (SCCA) results in favorable survival. However, treatment intensity must be balanced against late side effects. The aim of this current study was to prospectively investigate patient-reported outcomes (PROs) before CRT and up to 5 years after completed CRT for SCCA. Patient/material and methods: This prospective study included 120 patients with SCCA receiving CRT to total doses of 54-58 Gy with concomitant mitomycin and 5-fluorouracil. Patients completed PRO questionnaires before CRT, and at 3 months, 1-, 3-, and 5 years after completed CRT. The questionnaires were the EORTC QLQ-C30 and QLQ-CR29, St. Marks incontinence score, Fatigue Questionnaire, the Hospital Anxiety and Depression Scale, and a scoring for neuroticism.

Results: Patients reported a high burden of symptoms and impaired functional outcomes prior to treatment. Tumor-related symptoms, such as buttock pain, improved (difference 11.1, p = 0.002) at a clinically relevant level 3 months after CRT, consistent with tumor response. Other functional outcomes and symptoms, such as body image (difference 11.5, p < 0.001), worsened. While some outcomes, such as anxiety (difference 10.4, p = 0.001), improved over time, several were persistently impaired, in particular anorectal and sexual function, where symptom burden remained high 5 years after CRT. Chronic fatigue (CF) was reported by 28% of patients at 5-year follow-up.

Interpretation: Five years after CRT for SCCA, patients report a persistently high symptom burden regarding anorectal and sexual function, and one-third report CF, demonstrating the long-term impact of treatment.

Background and purpose: To study incidence changes, tumor characteristics, and relative survival (RS) among patients with early- (18-49 years) and late-onset (≥50 years) colorectal cancer (CRC). Patient/material and methods: In this retrospective registry study, all patients diagnosed with CRC in Finland between 1991 and 2015 were included and followed until death or the end of 2022. Data were extracted from the Finnish Cancer Registry. Changes in incidence as an average annual percentage change as well as age- and sex-standardized RS for CRC were estimated for 5-year periods between 1991-1995 and 2011-2015.

Results: The annual increase in incidence was higher for early-onset CRC versus late-onset CRC (1.2% vs. 0.44%), primarily due to an increase in left-sided colon cancer (2.0%) and rectal cancer (1.5%). Among 59,631 CRC patients, 3,988 (6.7%) had early-onset CRC, of whom 2,073 (52%) were female. Among 55,643 late-onset CRC patients, 27,796 (50%) were female. Among early-onset CRCs, 44% were right-sided, 19% left-sided, and 34% rectal compared with late-onset CRCs, of which 33% were right-sided, 23% left-sided, and 38% rectal. The 5-year RS for early-onset male patients improved from 64% to 72% and for female patients from 69% to 77%, whereas in late-onset patients, survival improved from 51% to 64% among males and from 52% to 67% among females.

Interpretation: The incidence of early-onset CRC is increasing more rapidly than for late-onset CRC. Overall, 5-year RS has improved and is higher in early-onset CRC patients compared with late-onset CRC.