Clinical oncology最新文献

Aims: Variability in the target and organs at risk (OARs) in cervical cancer treatment presents challenges for precise radiotherapy. Adaptive radiotherapy (ART) offers the potential to enhance treatment precision and outcomes. However, the increased workload and a lack of consensus on the most suitable ART approach hinder its clinical adoption. This systematic review aims to assess the current use of adaptive strategies for cervical cancer and define the optimal approach.

Materials and methods: A systematic review of current literature published between January 2012 and May 2023 was conducted. Searches used PubMed/Medline, Cochrane Library, and Web of Science databases, supplemented with the University of Manchester, Google Scholar, and papers retrieved from reference lists. The review assessed workflows, compared dosimetric benefits, and examined resources for each identified strategy. Excluded were abstracts, conference abstracts, reviews, articles unrelated to ART management, proton therapy, brachytherapy, or qualitative studies. A narrative synthesis involved data tabulation, summarizing selected studies detailing workflow for cervical cancer and dosimetric outcomes for targets and OARs.

Results: Sixteen articles met the inclusion criteria; these were mostly retrospective simulation planning studies, except four studies that had been clinically implemented. We identified five approaches for ART radiotherapy for cervical cancer: reactive and scheduled adaptation, internal target volume (ITV)-based approach using library of plans (LOP), fixed-margin approach using LOP, and real-time adaptation, with each approach reducing irradiated volumes without compromising target coverage compared to the non-ART approach. The LOP-based ITV approach is the most used and clinically assessed.

Conclusion: Identifying the optimal strategy is challenging due to dosimetric assessment limitations. Implementing cervical cancer ART necessitates strategic optimization of clinical benefits and resources through research, including studies to identify the optimal frequency, and prospective evaluations of toxicity.

Aims: In the conventionally fractionated phase III FLAME prostate trial, focal boosts improved local control and biochemical disease-free survival (bDFS). We explored the toxicity and effectiveness of a moderately hypofractionated schedule with focal boosts.

Material and methods: BIOPROP20 is a phase II single-arm non-randomised trial for intermediate- to very high-risk localised prostate cancer patients with bulky tumour volumes. Multi-parametric magnetic resonance imaging (MRI) and 18F-choline positron emission tomography-computed tomography (PET-CT) scans were used for staging and boost volume definition. Patients were treated with 60Gy in 20 fractions with a boost dose up to 68Gy. Five patients with positive lymph nodes on the PET-CT scan received radiotherapy to pelvic lymph nodes (45Gy to elective nodes, boosted up to 50Gy to involved nodes). Primary outcomes were acute (≤18 weeks) and late urinary and gastrointestinal toxicity, prospectively recorded up to 5 years with Common Terminology Criteria for Adverse Events v4 (CTCAE). Secondary outcomes were biochemical or clinical progression, metastasis-free survival (MFS), and overall survival (OS).

Results: 61 patients completed radiotherapy with hormone therapy (range: 6-36 months). Cumulative acute and late gastrointestinal toxicity was low at 6.6% and 5.0%, respectively. Cumulative acute and late urinary toxicity was 49.2% and 30.1%, respectively; the prevalence reduced to 5.9% at 5 years. At 5 years: 6 patients had biochemical progression (bDFS: 88.5%; 95% CI: 80.2-97.6%), the MFS was 82.4% (95% CI: 73.0-92.9%), 5 patients died (OS: 91.2%; 95% CI: 84.1-98.9%), one with prostate cancer. The prostate, boost, nodal planning volumes, and the organs at risk (rectum, bowel, urethra, and bladder) met the optimal protocol dose constraints. There was a trend to increased urinary toxicity with increasing urethral (RR: 1.95, 95% CI: 0.73-5.22, p = 0.18), but not bladder dose.

Conclusion: Focal boosts with a 20 fraction hypofractionated prostate radiotherapy schedule are associated with an acceptable risk of gastrointestinal and urinary toxicity and achieve good cancer control.

Clinicaltrials:

Gov identifier: NCT02125175.

Aims: During the COVID-19 public health emergency, we previously identified decreased rates of radiotherapy (RT) peer review (PR) discussion and plan changes in virtual versus in-person PR conferences. To expand on these findings, we continued to prospectively collect data on all PR conferences from 2021 to 2023 and performed a follow-up analysis before and after the transition back to in-person PR.

Materials and methods: A prospectively maintained database of weekly PR cases was queried for consecutive cases reviewed before and after the transition from virtual to in-person conferences. Rates of PR discussion and change recommendations were summarized and compared between the virtual and in-person groups. A survey was developed and administered to assess participants' perceived levels of engagement, opinions on optimal PR format, and preferences for future meetings before and 3 months after the transition back to in-person PR.

Results: In total, 2,103 RT plans were reviewed: 1,590 virtually and 513 after the transition back to in-person. There was no difference in faculty attendance between groups. The proportion of cases with PR discussion increased from virtual (9.8%) to in-person (25.5%) format (p < 0.001). In the virtual group, 8.1% of cases had 1 topic and 1.7% had 2+ topics discussed. This increased to 15.8% and 9.7% during in-person PR, respectively (p < 0.001). The rate of change recommendation also increased from 1.5% (virtual) to 3.3% (in-person, p = 0.016). Among cases with at least 1 topic discussed, there was no difference in changes. Survey-reported distraction significantly decreased from virtual to in-person PR (p < 0.001).

Conclusion: Upon returning to in-person PR conferences, peer discussion and plan change recommendations significantly increased and returned to pre-pandemic levels, and participants' perceived levels of distraction were reduced. In an increasingly virtual world, additional efforts to develop best practices that maximize PR discussion and minimize distraction outside virtual conferences are warranted.

Aims: Advanced gastroesophageal cancers are still associated with poor outcomes. We aim to study PD-1/PD-L1 inhibitors in phase III clinical trials that have compared them to chemotherapy in gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma.

Materials and methods: On March 28, 2024, we searched: PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov. We only included randomized clinical trials for PD-1/PD-L1 inhibitors alone or with chemo vs chemotherapy in advanced gastric, GEJ, or esophageal adenocarcinoma. The primary endpoints were overall survival and progression-free survival. A subgroup analysis was conducted for the following variables: treatment line, type of intervention, age group, gender, ECOG Performance Status, combined positive scores (CPS), microsatellite instability (MSI) status, liver metastasis, and primary tumor location.

Results: Only 10 out of 8,942 articles were included, involving 6,782 patients. PD-1/PD-L1 inhibitors showed a significant improvement in the overall survival compared to chemotherapy alone (hazard ratio (HR): 0.86, 95% CI: 0.80-0.93; p = 0.0002). Combining PD-1/PD-L1 inhibitors with chemotherapy significantly improved overall and progression-free survival compared to monotherapy (combined therapy HR 0.80; p < 0.00001 vs. monotherapy HR 0.98; p = 0.77). CPS ≥1 had an HR of 0.78 (95% CI: 0.73-0.84; p < 0.00001), CPS ≥10 had an HR of 0.67 (95% CI: 0.59-0.76; p < 0.00001), and MSI-high status had an HR of 0.35 (95% CI: 0.24-0.52; p < 0.00001). Esophageal adenocarcinoma, reported in three trials, did not show significant improvement in the overall survival (HR 0.89; 95% CI: 0.69-1.14; p = 0.37).

Conclusion: PD-1/PD-L1 inhibitors have significantly improved overall survival, and combining them with chemotherapy is more effective than monotherapy. Both CPS ≥10 and MSI-H showed an added benefit to overall survival and should be included in biomarker investigations. Clinical trials are needed for second-line treatments and esophageal adenocarcinoma.

Aims: In patients with locally advanced non-small cell lung cancer (LA-NSCLC), curative-intent radiotherapy (RT) or chemoradiotherapy (CRT) is associated with considerable toxicity, and approximately half of the patients die within two years. A better understanding of early mortality is needed to improve patient selection and guide supportive interventions. In this population-based, nationwide cohort study, we investigated the incidence, temporal distribution, and risk factors of early mortality.

Materials and methods: Patients with stage II-III NSCLC treated with curative-intent RT/CRT in Denmark from 2010-2017 were included. Patients treated with preoperative or postoperative RT/CRT or stereotactic body radiation therapy were excluded. Early mortality was defined as all-cause death within 180 days from RT/CRT initiation. Multiple logistic regression was used to assess the impact of clinical and demographic variables.

Results: We included 1742 patients. The early mortality rate was 10%. The temporal distribution of deaths was uniform across the first year following RT/CRT, indicating the absence of a high-risk period. In multivariable analysis, increasing age and performance status, male sex, and unspecified histology (NSCLC not otherwise specified) were associated with an increased risk. By contrast, the Charlson Comorbidity Index (CCI), TNM stage, and treatment period did not significantly alter the risk of early mortality. Overall survival rates improved throughout the inclusion period but early mortality rates did not.

Conclusion: No high-risk period for early mortality could be identified. Early mortality was not associated with CCI and other tools should be explored to quantify comorbidity for risk stratification in this setting.

Aims: A significant proportion of locally advanced cervical cancer (LACC) patients experience disease progression post chemoradiotherapy (CRT). Currently existing clinical variables are suboptimal predictors of treatment response. This study reported a radiomics-based model leveraging information extracted from magnetic resonance (MR) T2-weighted image (T2WI) to predict the progression-free survival (PFS) for LACC following CRT.

Materials and methods: Radiomics features were extracted from pre-treatment MR T2WI in 105 LACC patients. Following pre-feature selection and a step forward feature selection method, an optimal feature set was determined with a Cox proportional hazard (CPH) model. The PFS predictions were generated through a radiomics-clinical combined model utilized five repeated nested 5-fold cross-validation (5-fold CV). Disease progression risk was stratified into high- and low-risk groups based on the predicted PFS and assessed by Kaplan-Meier analysis.

Results: The radiomics texture feature extracted from MR T2WI significantly predict PFS in LACC after CRT. In comparison with the model using clinical variables alone, the radiomics-clinical combined model achieves significantly improved performance in testing patient cohort, achieving higher C-index (0.748 vs 0.655) and area under the curve (0.798 vs 0.660 for 2-year PFS). Meanwhile, the proposed method significantly differentiated the high- and low-risk patients groups for disease progression (P < 0.001).

Conclusion: An MR T2WI-based radiomics and clinical combined model provided improved prognostic capabilities in predicting the PFS for LACC patients treated with CRT, outperforming a model using clinical variables alone. The incorporation of MR T2WI-based radiomics is promising in assisting in personalized management in LACC, indicating the potential of MR T2WI radiomics as imaging biomarker.

Aims: Breath holding can reduce the cardiac dose in radiotherapy for left-sided breast cancer. We evaluated whether any of the existing commonly used breath-hold techniques was superior in maintaining a more reproducible mean heart dose (MHD) during treatment.

Materials and methods: This was a single-institution, interventional, nonrandomised, three-armed prospective trial, comparing the reproducibility of MHD in breath-hold radiotherapy using voluntary deep inspiration breath hold (vDIBH), active breathing control (ABC), and surface-guided radiotherapy (SGRT). The MHDs were determined based on the anatomy in planning computed tomography (CT) and each weekly cone beam computed tomography (CBCT) during radiotherapy. The reproducibility of MHD was measured by calculating the interfractional variation of MHD (represented by the standard deviation) across the CBCT and the difference between the cumulative MHD at CBCT and at planning CT. These two measures of reproducibility were then compared among vDIBH, ABC, and SGRT.

Results: Of the 55 patients recruited, 19 had ABC, 20 had SGRT, and 16 had vDIBH. SGRT was associated with a slightly greater interfractional variation of the MHD than vDIBH (least squares mean (LSM): 28.8 cGy (SGRT) vs 10.5 cGy (vDIBH), P = 0.0052) and ABC (LSM: 28.8 cGy (SGRT) vs 15.1 cGy (ABC), P = 0.026). In the SGRT group, the cumulative MHD at CBCT was lower than that at planning CT (mean difference: -22.1 cGy, P = 0.013). No such difference existed in vDIBH and ABC. In terms of the reproducibility of cumulative MHD at CBCT as compared to that in planning CT, there was no significant difference between vDIBH (mean: -12.1 cGy), ABC (mean: -4.8 cGy), and SGRT (mean: -22.1 cGy) (P value for pairwise comparison: all >0.1).

Conclusions: SGRT was associated with a slightly greater interfractional variation of MHD than vDIBH and ABC, but the difference may not be clinically significant. All three breath-hold techniques were broadly comparable in their reproducibility of MHD at CBCT relative to the planning CT.