Acta Oncologica最新文献

Background and purpose: To review available data on toxicity during and/or after treatment of abdominal-pelvic lymph node oligometastases (A-P LN) with stereotactic body radiation therapy (SBRT) and to provide an overview of adverse events and its relation to dose or fractionation.

Material and methods: For this systematic review, we searched MEDLINE, Embase, Web of Science Core Collection, and CINAH for studies published between the database inception and October 3rd, 2023. Inclusion criteria were (1) patients with 1-5 A-P LN oligometastases, (2) treatment with SBRT to a median prescribed dose of ≥55 Gy BED10, and (3) description of acute and/or late toxicity. There were no language or date restrictions.

Results: A total of 35 studies, including 1,512 patients, were selected. Late grade 3 and 4 adverse events occurred in 0.6% and 0.1% of the patients treated for A-P LN oligometastases. All late adverse events grade ≥ 3 occurred after treatment of the tumor with a minimum BED10 of 72 Gy. Of the 11 patients with severe late toxicity, five patients were re-irradiated. Late grade 2 and 1 toxicity was reported in 3.4% and 8.3% of the patients. Acute toxicity grades 4, 3, 2, and 1 occurred in 0.1%, 0.2%, 4.4%, and 19.8% of the patients, respectively.

Interpretation: SBRT for A-P LN oligometastases show low toxicity rates. Nearly 50% of late adverse events ≥ grade 3 were associated with re-irradiation.

Background and purpose: Progression-free survival (PFS) remains to be validated as an outcome measure for diffuse WHO grade 2 gliomas, and knowledge about the relationships between PFS, post-progression survival (PPS), and overall survival (OS) in this subset of tumors is limited. We sought to assess correlations between PFS and OS, and identify factors associated with PFS, PPS, and OS in patients treated for diffuse supratentorial WHO grade 2 gliomas.

Material and methods: We included 319 patients from three independent observational cohorts. The correlation between PFS and OS was analyzed using independent exponential distributions for PFS and time from progression to death. Cox proportional hazards models were used to determine the effects of covariates on PFS, PPS, and OS.

Results: The overall correlation between PFS and OS was rs0.31. The correlation was rs 0.37 for astrocytomas and rs 0.19 for oligodendrogliomas. Longer PFS did not predict longer PPS. Patients with astrocytomas had shorter PFS, PPS, and OS. Larger preoperative tumor volume was a risk factor for shorter PFS, while older age was a risk factor for shorter PPS and OS. Patients who received early radio- and chemotherapy had longer PFS, but shorter PPS and OS.

Interpretation: We found a weak correlation between PFS and OS in WHO grade 2 gliomas, with the weakest correlation observed in oligodendrogliomas. Our analyses did not demonstrate any association between PFS and PPS. Critically, predictors of PFS are not necessarily predictors of OS. There is a need for validation of PFS as an endpoint in diffuse WHO grade 2 gliomas.

Purpose: Radiation pneumonitis (RP) is a dose-limiting toxicity associated with increased mortality for patients with non-small cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT). This study aims to assess the incidence of symptomatic RP (grade 2-5), rate of recovery and associated predictive factors.

Material and methods: We performed a retrospective population-based study including 602 patients with NSCLC who were treated with CRT between 2002 and 2016. RP and rate of recovery were analysed using Common Terminology Criteria for Adverse Events version 4.0. Stepwise logistic regression was performed to analyse potential predictive factors for the two endpoints RP grade ≥ 2 and RP grade ≥ 3.

Results: A total of 136 (23%) patients developed symptomatic RP and 37 (6%) developed RP grade ≥ 3. A total of 67 (71%) recovered, whereas the remaining 27 (29%), with the major proportion of patients belonging to the RP grade ≥ 3 group, suffered from prevailing sequelae. On multivariable analysis, the selected model for predicting RP grade ≥ 2 included the factors V20, smoking status, average fractions per week and chemotherapy agent. V20 and age were selected factors for RP grade ≥ 3.

Interpretation: The results suggest that regardless of all proposed factors predictive for RP, the most important influenceable significant factor still is dose to the lung. The main aim should be to avoid RP grade ≥ 3, where a substantial proportion of patients suffer from prevailing sequalae. Consequently, the technical improvement and precision of radiotherapy delivery should continue to focus on lung sparing techniques also in the ongoing immunotherapy-containing schedules where the risk of pneumonitis may be increased. e factor still is dose to the lung. Consequently, the technical improvement and precision of radiotherapy delivery should continue to focus on lung sparing techniques also in the ongoing immunotherapy-containing schedules where the risk of pneumonitis may be increased.

Background and purpose: Classic Kaposi sarcoma (CKS) is a rare vascular disease mainly found in populations of Mediterranean origin. The pathogenesis involves Human Herpes Virus 8 (HHV8) and genetic mutations such as SNP309 in the MDM2 gene. The recently discovered BPTF mutation in cells of CKS patients demonstrated higher latency-associated nuclear antigen (LANA) staining and altered vital transcriptomics, implicating a potential role in tumorigenesis. This review explores the genetic underpinnings and treatments for CKS.

Material and methods: A comprehensive literature search was conducted from 2004 to 2024, yielding 70 relevant papers. Ongoing clinical trials investigating novel treatments such as talimogene and abemaciclib were included in the search and presented in the results.

Results: Clinical diagnosis and treatment can be challenging as the number of studies on CKS and treatment modalities is limited. Treatment strategies vary by disease stage, with local therapies like surgical intervention and radiation therapy recommended for early stages, while systemic therapies are considered in cases of systemic disease.

Interpretation: While advancements in CKS treatment offer hope, further studies on immunotherapy are warranted to broaden the therapeutic options, such as anti-bromodomain or BPTF-targeted therapy.

Background: Despite recent treatment advances in ovarian cancer (OC), more real-world evidence studies investigating patient outcomes are needed. OCRWE-Finland was an observational cohort study investigating OC outcomes in Finland during the pre-PARP inhibitor era.

Patients: Patients were diagnosed with OC between 2014 and 2019 in Finland. This analysis reports baseline characteristics of all patients, patients with high-grade serous OC (HGSOC), and overall survival (OS) for patients with HGSOC.

Results: Among 1,711 patients diagnosed with OC, 867 (51%) had HGSOC. The absence versus presence of visible residual disease post-debulking surgery was associated with improved OS for patients at stage III (n = 303; median: NR vs. 43 months; p = 0.005), but not stage IV (n = 118; median: 37 months vs. 40 months; p = 0.96). Bevacizumab treatment at any line at stages III/IV improved OS in the short-term only. Receiving versus not receiving bevacizumab at first-line for patients with visible residual disease post-debulking surgery was associated with improved OS at stage III (median: 48 months vs. 36 months; p = 0.003), but not stage IV (median: 42 months vs. 37 months; p = 0.26). Multivariate Cox regression analyses showed that stage IV at initial diagnosis and the presence of R2 classification post-debulking surgery resulted in poorer OS.

Interpretation: In the pre-PARP inhibitor era, the absence versus presence of visible residual disease post-debulking surgery was associated with improved OS in stage III, but not stage IV HGSOC. First-line bevacizumab seemed to be beneficial in patients with stage III HGSOC and visible residual disease.

Background: As the treatment landscape for advanced ovarian cancer (OC) evolves, it is important to understand patient outcomes in real-world clinical practice. OCRWE-Finland was an observational cohort study investigating OC outcomes, including treatment patterns, time to next treatment 1 (TTNT1), overall survival and healthcare resource utilisation, in Finland during the pre-PARPi era.

Materials and methods: Patients included in OCRWE-Finland were diagnosed with OC between 2014 and 2019. Here, we report treatment patterns and TTNT1 outcomes (as a surrogate for progression-free survival) for patients in the high-grade serous ovarian carcinoma (HGSOC) cohort.

Results: In OCRWE-Finland, there were 867 patients with HGSOC. Of the 811 patients who received first-line treatment, the most common regimen was surgery and adjuvant chemotherapy (53%), and 227 patients also received first-line bevacizumab. Median TTNT1 among 623 patients with stage III/IV disease was 19 months (95% confidence interval, 18-21 months), with no difference between patients with stage III or IV disease (p = 0.24). The presence versus absence of visible residual disease post-debulking surgery was associated with shorter TTNT1 among patients with stage III tumours (p = 0.031) but showed no impact for stage IV tumours (p = 0.55). First-line versus no first-line bevacizumab was associated with shorter TTNT1 among stages I-IV (p < 0.0001) but did not affect patients with stage III/IV tumours (p = 0.45).

Interpretation: In the pre-PARPi era, prognosis for advanced OC was poor, particularly for patients with stage III tumours and visible residual disease or stage IV tumours regardless of the presence of residual disease. The increasing use of PARPis will hopefully help address the need for effective treatments in advanced OC.

Background and purpose: Regional nodal irradiation (RNI) for breast cancer delivers radiation in proximity to the shoulder and torso, and radiation exposure may contribute to long-term upper extremity and postural morbidity. To date, no studies have assessed the differential dosimetric impact of proton versus photon radiation on shoulder and torso anatomy. This study examined clinically relevant musculoskeletal (MSK) structures and assessed the dose delivered with each modality.

Patients/material and methods: Ten MSK structures were contoured on IMPT (intensity-modulated proton therapy) and VMAT (volumetric modulated arc therapy) plans for 30 patients receiving RNI. Relevant dose metrics were compared for each of the structures. Intensity-modulated proton therapy dose was calculated using the relative biological effective value of 1.1. Hypo-fractionated plans were scaled to the equivalent dose in 2 Gy fractions (EQD2) using an alpha/beta ratio of four. Wilcoxon signed rank sum tests compared doses. Select three-dimensional and optimised VMAT plans were also informally compared.

Results and interpretation: Each of the 10 structures received a statistically significantly lower dose with the use of IMPT compared with VMAT. Differences were greatest for posterior structures, including the trapezius, latissimus dorsi and glenohumeral joint. Mean absolute differences were as great as 23 Gy (supraspinatus D5cc) and up to 30-fold dose reductions were observed (deltoid D50cc). An average 3.7-fold relative dose reduction existed across all structures. Measures of low/intermediate dose (V15Gy and D50cc) showed the largest differences. Intensity-modulated proton therapy results in statistically lower radiation exposure to relevant shoulder and torso anatomy compared to photon radiation for patients requiring RNI. Prospective study is needed to correlate functional outcomes with radiation dose.

Background and purpose: Data on real-world prevalence and outcomes in patients diagnosed with pathogenic germline variants in BRCA1 or BRCA2 (gBRCAm) breast cancer is sparse.

Material and methods: An observational cohort study including all patients diagnosed with incident early-stage breast cancer and recorded in Helsinki University Hospital data lake 2012-2022, accounting for one-third of the Finnish breast cancer patient population.

Results: Among 14,696 incident early-stage breast cancer patients, 11.2% (n = 1,644) were tested for gBRCAm. Of the tested population, 7.4% (n = 122) carried gBRCAm. Of the 122 gBRCAm patients, 95.1% (n = 116) were women, with a median age at diagnosis of 46.4 years. Among the same patient group, HER2 status was available for 87.7% (n = 107) of the patients. Among these, 49.5% (n = 53) had hormone receptor-positive (HR+), HER2-negative breast cancer, 13.1% were (n = 14) HER2-positive, and 37.3% (n = 40) of patients had triple-negative breast cancer. The tested patients were significantly younger compared with non-tested patients. No significant differences in overall survival or healthcare resource utilization between the tested patients with gBRCAm and gBRCA wild-type (gBRCAwt) were observed.

Interpretation: This comprehensive observational study supports previous findings of gBRCAm prevalence in the Western early-stage breast cancer population. While no differences in survival were observed between patients with gBRCAm and gBRCAwt, it is important to consider the potential influence of selection bias, particularly due to the younger gBRCAm testing target population and the overall low frequency of testing. Therefore, a substantial proportion of the patients carrying gBRCAm likely remained undiagnosed, and wider screening criteria are warranted.

Background and purpose: Bladder cancer (BC) is a common malignancy in the Western World with men being diagnosed almost four times as often as women. The etiology of bladder cancer may involve sex hormones. Prostate cancer (PCa) patients treated with chemical castration, such as androgen deprivation therapy, or surgical castration, may therefore have a lower risk of developing bladder cancer.

Patients/material and methods: In a nation-wide population-based cohort study using national Danish registry data, we included a cohort of men with a first-time PCa diagnosis between 2002 and 2018 divided according to antihormonal treatment in the first year after PCa diagnosis and a comparison cohort consisting of 10 age-matched persons for each PCa patient. Each individual was followed from 1 year after PCa diagnosis until death or end of follow-up. We computed cumulative incidences (risk) and hazard ratios (HRs) for BC. In a second cohort analysis, we determined overall survival and BC-specific mortality, determined from date of BC diagnosis until death.

Results and interpretation: We included 48,776 PCa patients of whom 13,592 were treated with chemical castration, 2,261 with surgical castration, and 32,923 received no antihormonal treatment. The 5-year risk of BC for each PCa group was 1.1%, 0.7%, and 1.3%, respectively, corresponding to an adjusted HR of 1.13 (95% CI 0.98; 1.31), 0.95 (95% CI 0.62; 1.47), and 1.18 (95% CI 1.09; 1.28) compared to individuals without PCa. Patients receiving antihormonal treatment had a slightly lower incidence of BC compared to individuals without PCa, however, this was not supported by the HRs. The treatment, however, was not associated with overall survival.

Background: Patients with advanced ovarian cancer (AOC) undergoing surgery are often subjected to red blood cell (RBC) transfusions. Both anemia and RBC transfusion are associated with increased morbidity. The aim was to evaluate patient recovery after the implementation of patient blood management (PBM) strategies.

Methods: This retrospective cohort study included 354 patients with AOC undergoing surgery at Skane University Hospital Lund, Sweden, between January 2016 and December 2021. The gradual implementation of PBM strategies included restrictive RBC transfusion, tranexamic acid as standard medication before laparotomies and intravenous iron administered to patients with iron deficiency. Severe complications were defined as Clavien-Dindo (CD) grade ≥ 3a. Logistic and linear regression analyses were used to evaluate the differences between three consecutive periods.

Results: After the implementation of new strategies, 52% of the patients had at least one transfusion compared to 83% at baseline (p < 0.001). There was no difference in the rate of severe complications (CD ≥ 3a) between the groups, adjusted odds ratio 0.55 (95% CI 0.26-1.17). The mean difference in hemoglobin before chemotherapy was -1.32 g/L (95% CI -3.04 to -0.22) when adjusted for blood loss and days from surgery to chemotherapy. The length of stay (LOS) decreased from 8.5 days to 7.5 days (p 0.002).

Interpretation: The number of patients transfused were reduced by 31%. Despite a slight increase in anemia rate, severe complications (CD ≥ 3a) remained stable. The LOS was reduced, and chemotherapy was given without delay, indicating that PBM is feasible and without causing major severe effects on short-term recovery.