Acta Oncologica最新文献

Background and purpose: Many prostate cancer patients undergoing pelvic lymph node dissection (PLND) have no sign of lymph node invasion (LNI) during final pathological assessment. To improve preoperative staging accuracy, we developed the Oslo model, which estimates the risk of LNI based on clinical, histopathological, and magnetic resonance imaging (MRI) variables.

Patients/materials and methods: We utilized data from 903 prostate cancer patients treated at Oslo University Hospital (OUS) to develop the model using Bayesian logistic regression. The Oslo model was validated with data from 189 patients at IRCCS Ospedale San Raffaele (HRS), 157 from St. Olav's Hospital, and 231 from OUS. We assessed its performance against the Memorial Sloan Kettering Cancer Centre (MSKCC) and Briganti 2019 nomograms using metrics like AUC, R², decision curve analysis, and calibration plots.

Results: The Oslo model outperformed Briganti 2019, demonstrating a higher net benefit and a 10% reduction in interventions at a 7% cutoff. Key variables included clinical T stage on MRI, Prostate Specific Antigen (PSA), prostate volume, International Society of Urological Pathology grade group, and maximum lesion length on MRI. Validation showed strong reliability in the OUS and HRS cohorts but weaker performance in the St. Olav's cohort. The AUCs were 77% for the Oslo model, 74% for Briganti 2019, and 66% for MSKCC. Limitations include small and heterogeneous validation cohorts.

Interpretation: The Oslo model enhances predictive performance in intermediate- and high-risk patients using easily accessible clinical and MRI data, potentially reducing unnecessary PLND interventions and assisting clinicians in treatment decision-making.

Introduction: There is limited indication of how hyperthermia would influence the unique proposition of FLASH radiation - its ability to maintain comparable tumor response while offering protection to normal tissues. Hence, this study was designed to investigate the potential of combining FLASH radiation with hyperthermia.

Materials and methods: Experiments were performed using female CDF1 mice, where the tumor bearing or non-tumor bearing right hind legs were irradiated with either conventional dose rate (CONV) or FLASH radiation ± hyperthermia. Hyperthermia was applied 30 minutes after radiation at 42.5°C for 60 minutes. The tumor endpoint was growth delay to three times its initial treatment volume (TGT3) and the normal tissue endpoint was an acute skin toxicity of score 2.5 and above, characterized by moderate moist desquamation and partial leg deformity.

Results: In tumor studies, the thermal enhancement ratio (TER) was 1.68 for FLASH radiotherapy and 1.50 for conventional (CONV) radiation. In acute skin toxicity studies, the TER was slightly lower, at 1.37 for FLASH and 1.29 for CONV. The dose modifying factor (DMF) in tumor studies was 1.12 but decreased to 1.00 when hyperthermia was added. Similarly, in acute skin toxicity studies, the DMF was initially 1.53 and dropped to 1.45 with the addition of hyperthermia.

Interpretation: Hyperthermia significantly sensitized both the CONV and FLASH radiation, but the enhancement is comparable between the two different dose rate radiations in both tumors and normal tissues.

Background and purpose: Natural killer (NK) cells play an important role in defense against cancer. Low NK cell activity (NKA) has been linked to prostate cancer (PCa) detection, and effective NKA may be associated with better prognosis in metastatic PCa. Radiotherapy (RT) could affect the immune response, but data on NKA in patients with PCa receiving RT ± androgen deprivation therapy (ADT) remain limited. Hence, this study investigated NKA in such patients. Patient/material and methods: Peripheral blood from 150 patients with PCa receiving curatively intended RT was collected into NK Vue® tubes prior to RT (baseline, BL), after end of RT (EOT), and during follow-up. Patients received 0- (n = 15), 6- (n = 23), or 36-months of ADT (n = 112), starting 3 months before RT. Interferon-γ was a surrogate marker for NKA in NK Vue® tubes. Data were analyzed using descriptive statistics.

Results: Baseline characteristics were similar between patients with normal (≥ 250 pg/mL) (n = 46) and low (< 250 pg/mL) (n = 104) NKA; however, smoking was more prevalent in the low NKA group (28% vs. 11%). The distribution of NKA levels differed between groups and time points, notably showing a decreased interquartile range (IQR) for all groups at EOT (BL median 832 pg/mL, IQR 2901; EOT median 312 pg/mL, IQR 708). NKA fluctuated during follow-up and did not mirror prostate-specific antigen dynamics.

Interpretation: Patients with localized PCa treated with RT ± ADT displayed marked variation in NKA, including treatment-related dynamics. The overall complexity and heterogeneity of NKA raise questions about its clinical utility as a biomarker in this setting.

Background and purpose: The apparent diffusion coefficient (ADC), derived from diffusion-weighted MRI (DWI), is commonly calculated using a monoexponential model. However, there is no consensus on optimal b-value selection for ADC quantification in rectal cancer. This prospective observational study evaluated how varying b-value combinations influence ADC values. Patient/material and methods: DWI with seven b-values (b = 0, 25, 50, 100, 500, 1,000, and 1,300 s/mm2) was acquired from 23 rectal cancer patients in the OxyTarget study (NCT01816607) using a 1.5T Philips Achieva scanner. Two radiologists independently delineated whole-tumour volumes of interest. ADC values were calculated using 18 different b-value combinations and compared with a biexponential reference.

Results: Tumour ADCs varied significantly across b-value combinations. Excluding low b-values (b ≤ 100 s/mm²) led to reduced ADCs. Although b = 0 s/mm² is commonly included in ADC calculations, this study demonstrates that its inclusion leads to substantial overestimation. The use of two or three b-values from b = 500, 1,000, and 1,300 s/mm² yielded the smallest deviations from the biexponential reference.

Interpretation: In rectal cancer, tumour ADC calculated using the monoexponential model is strongly influenced by the choice of b-values. By eliminating the contribution from perfusion (b ≤ 100 s/mm2) the uncertainty in the calculations is significantly reduced. Our findings support the use of b-values exceeding 100 s/mm², ideally in combination with a high b-value of at least 1,000 s/mm², when assessing diffusion using the monoexponential model. Consistent b-value combinations across studies are recommended for reliable quantitative comparisons of ADC values.

Background and purpose: Anal cancer is treated with chemoradiotherapy and with salvage surgery in case of local failure. Curation rate depends on tumour stage but is overall high (80-90%). This study explored anal cancer survivors' perception of being cured and possible association with Quality of Life (QoL). Secondary aims were to explore fear of recurrence and if perception of cure changed over time or differed depending on tumour stage.

Patients/material and methods: The ANal CAncer study comprises a cohort of patients diagnosed with anal cancer in Sweden between 2011 and 2013 (n = 388). Participants filled out a study-specific questionnaire 3 and/or 6 years after diagnosis (n = 205). In this sub-study, only patients treated with curative intent were included. The association between perception of cure and QoL was analysed using logistic regression. Descriptive analyses were performed regarding secondary aims.

Results: A high proportion (80%) of the patients were either moderately or very sure of cure across all tumour stages, in both early and advanced tumour stages, and with no obvious improvement over time. Despite this 42% experienced fear of recurrence 6 years after diagnosis. A strong perception of cure was correlated with high QoL.

Interpretation: Even though most patients had a perception of being cured, several patients irrespective of tumour stage, felt unsure of cure and feared recurrence years after successful treatment. A strong perception of cure was also shown to be associated with a high QoL. We suggest that improved counselling could enhance the patient's perception of cure and to possibly improve QoL.

Background and purpose: Standard treatment for esophageal (EC) and gastroesophageal junction (GEJ) cancer includes neoadjuvant chemo-radiotherapy (nCRT), followed by surgery or definitive chemo-radiotherapy (dCRT) for inoperable patients. This study assessed real-world survival and morbidity in EC patients treated with radiotherapy (RT). Patient/material and methods: In this retrospective study, 417 patients with EC or GEJ cancer received nCRT or dCRT between 2012 and 2021 at a single center. We evaluated overall survival (OS), loco-regional control, progression-free survival, failure patterns, and toxicity. Data were sourced from clinical and treatment records. Patients were treated following national guidelines and received intensity-modulated radiotherapy and daily cone-beam Computed Tomography (CT) for setup. Radiotherapy doses were 41.4-66 Gy in 23-33 fractions.

Results: Of the patients, 250 received nCRT, and 167 received dCRT. Most (86%) had T3-T4 tumors, and 65% had node-positive disease. Histologies were adenocarcinoma (50%) and squamous cell carcinoma (45%). A total of 88% completed RT, and 92.4% of nCRT patients proceeded to surgery. Median OS was 31 months for nCRT and 24 months for dCRT; 3-year OS was 46% and 38%, respectively. Disease recurrence occurred in 46% with a median interval of 20 months. Multivariable analysis identified OS-associated factors for both nCRT and dCRT. Acute toxicity was common but generally mild; late side effects were not systematically recorded.

Interpretation: In clinical practice, OS after nCRT or dCRT was as expected. Most patients undergoing nCRT proceeded to surgery. Toxicity was frequent but manageable.

Background: The role and optimal sequencing of radium-223 in the treatment of metastatic castration-resistant prostate cancer (mCRPC) remain debated. In Europe, radium-223 is restricted to third line treatment or later for chemotherapy-eligible men, although studies suggest greater benefit with earlier use. In this nationwide, population-based study, we investigated radium-223 use in Sweden and analyzed the association between line of treatment and overall survival.

Methods: Men with mCRPC who started radium-223 in 2014-2020 were identified in national registers. The Kaplan-Meier method was used to estimate survival. The association between line of treatment and survival was analyzed with Cox regression and presented as adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). A subgroup with at least three mCRPC treatment lines was similarly analyzed.

Results: 1,133 men were included. Median overall survival was 13.9 months (95% CI 13.0-14.5). Later line of radium-223 treatment was associated with shorter survival; with first line as reference, aHR for death for second line was 1.34 (95% CI 1.12-1.59) and for third line 1.55 (1.29-1.87). The opposite was observed for 596 men with at least three lines of mCRPC treatment: aHR for second line was 0.80 (0.59-1.08) and for third line 0.78 (0.59-1.03).

Interpretation: Survival after start of radium-223 in Sweden was comparable to pivotal trials, suggesting effective use. Our overall results do not suggest a better effect of radium-223 in first versus later mCRPC treatment lines but rather emphasize the value of a randomized controlled trial to more definitely determine the optimal timing of radium-223 treatment.

Background and purpose: We evaluated the impact of the coronavirus disease 2019 (COVID-19) pandemic on health-related quality of life (HRQoL) in early-stage breast cancer patients receiving adjuvant chemotherapy.

Patients and methods: The study involved 180 patients with stage I-III breast cancer who initiated adjuvant chemotherapy between June 2020 and May 2021. The pre-pandemic comparison data included 113 early breast cancer patients who began adjuvant chemotherapy between November 2018 and August 2019. HRQoL was assessed using the EORTC QLQ-C30 at baseline and again after 3 and 6 months. The subscales were compared between the COVID-19 pandemic and the pre-pandemic eras.

Results: We observed deterioration on almost all HRQoL subscales of the patients treated during the pandemic from baseline to 3 months. After the chemotherapy at 6 months, the scales remained deteriorated, whereas only appetite loss and emotional functioning improved. A comparison between the pandemic and the pre-pandemic eras revealed that several HRQoL subscales showed better results during chemotherapy in the pandemic era. Global health and role functioning at 6 months presented declined levels during the pandemic.

Interpretation: The well-being of breast cancer patients during the chemotherapy treatment in the pandemic era was moderately better than in the pre-pandemic era. Patients in the pandemic era might have reported fewer symptoms during the treatment, as the focus was on the COVID-19 pandemic and its restrictions.

Background and purpose: Treatment of cancer with immune checkpoint inhibitors (ICIs) entails a risk of immune-related adverse events (irAEs). Data on the treatment of immune-related enterocolitis (irEC) in patients with inadequate symptom control after treatment with standard therapy including corticosteroids, infliximab, and vedolizumab are scarce. Based on limited data, recommendations include treatment with the pan-Janus kinase (JAK) inhibitor tofacitinib. Filgotinib is a more recently developed JAK inhibitor with preferential inhibition of JAK1, which might imply a more favorable safety profile. Filgotinib is approved for the treatment of ulcerative colitis and might thus be an option in refractory irEC.

Patients and methods: We present two cases of metastatic melanoma treated with ICIs who developed corticosteroid and infliximab-refractory irEC. Given non-conventional pharmaceutical management, literature review was performed regarding mechanisms of action and safety profiles of JAK inhibitors.

Results: Both patients were treated with filgotinib, which resulted in rapid remission of symptoms in both cases. One of the patients was treated with off-label high-dose filgotinib, which has not been described previously. The rationale and safety regarding the use of JAK1 inhibitors in irAEs are discussed, including the seemingly diverging existing data on potential effects of JAK inhibition on ICI-induced anti-tumoral immune-responses. In addition, the rationale for the high-dose treatment is scrutinized.

Interpretation: This report suggests that filgotinib may be considered for treating irEC refractory to standard therapy.

Background: Several studies have reported associations between statin treatment and a more favourable prognosis in prostate cancer (PC) patients. The underlying biology, however, has not been fully investigated.

Objective: To perform whole-transcriptome profiling of prostate tumour samples from PC patients to identify gene expression patterns and molecular pathways that may be associated with statin treatment. Furthermore, to investigate correlations between statin-associated gene expression changes and clinical outcomes.

Material and methods: We performed messenger Ribonucleic Acid (mRNA) sequencing on radical prostatectomy specimens from 186 patients with clinically-localised PC. The final dataset included 93 statin-users (93 PC and 43 adjacent normal [AN] samples) and 93 non-users (93 PC and 43 AN samples). We performed Differential Expression Analysis and Gene Set Enrichment Analysis (GSEA) between statin-users and non-users. Genes of interest were included in uni- and multivariate analyses exploring time to Biochemical Recurrence (BCR).

Results: Comparing statin-users and non-users, there were zero significantly differentially expressed genes (DEGs) in AN samples and 163 DEGs in PC samples. In statin-users, GSEA revealed downregulation of pathways known to drive PC aggressiveness, most significantly epithelial-mesenchymal transition. Low-density Lipoprotein Receptor (LDLR) was among the top-upregulated genes and expressed higher in atorvastatin than in simvastatin users. The LDLR upregulation was associated with prolonged BCR-free survival.

Interpretation: We identified several genes and pathways in PC tissue potentially associated with the reported beneficial effects of statin treatment in PC. Specifically, we identified an association between statin treatment and intra-tumour LDLR upregulation. This study contributes to the understanding of statin-mediated effects on PC.