Radiotherapy and Oncology最新文献

Background: To investigate changes of objective instrumental measures and correlate with patient reported outcomes (PROs) of radiation-induced dysphagia (RID) after swallowing organs at risk (SWOARs)-sparing IMRT.

Methods: Patients (pts) underwent Fiberoptic Endoscopic Evaluation of Swallowing (FEES), Videofluoroscopy (VFS) and M.D. Anderson Dysphagia Inventory (MDADI) questionnaire at baseline, 6 and 12 months after treatment. They were categorized in two groups: MDADI-C ≥ 80 and MDADI-C < 80. Pharyngeal residue (PR) and penetration (P) or aspiration (A) were considered as surrogate of RID.

Results: Between 2016 and 2022 we enrolled 75 pts, 40 (53 %) MDADI-C ≥ 80 and 35 (47 %) MDADI-C < 80 at baseline. Among MDADI-C ≥ 80 the mean baseline PR score at FEES was 0,42 rising to 1,36 at 6 months (p = 0,001) and stabilizing to 1,15 at 12 months (p = 0,21); indeed, the mean baseline PR score at VFS was 0,55 rising to 1 at 6 months (p = 0,069) and slightly dropping to 0,7 at 12 months (p = 0,069). Among MDADI-C < 80 the mean baseline PR score at FEES was 0,56 rising to 1,07 at 6 months (p = 0,012) and stabilizing to 1,07 at 12 months (p = 0,99); indeed the mean baseline PR score at VFS was 0,67 rising to 1,19 at 6 months (p = 0,04) and dropping to 0,78 at 12 months (p = 0,04). No correlation was found between PROs and objective measures.

Conclusion: Our results show optimal acceptable deglutition preservation from major complications after SWOARs-sparing IMRT by means of low objective scores in both MDADI-C groups. Lack of correlation between PROs and objective measures suggest that referred RID is likely associated to persistence of SWOARs inflammation rather than to a real impairment of function.

Background/purpose: The circadian clock governs the expression of genes related to immunity and DNA repair. We investigated whether the time of day of radiotherapy and/or systemic therapy infusions (chemotherapy or anti-PD-L1) are associated with disease control and survival in locally advanced non-small cell lung cancer (LA-NSCLC).

Materials/methods: 178 consecutive patients with inoperable LA-NSCLC who received definitive chemoradiotherapy followed by durvalumab between 5/2017-8/2022 were reviewed. Outcomes evaluated included progression-free survival (PFS), distant metastasis-free survival (DMFS), locoregional control (LRC), and overall survival (OS).

Results: At a median follow up of 48.0 mo from durvalumab initiation, median PFS and OS were 26.2 mo and 50.0 mo, respectively. Median LRC and DMFS were not reached and 41.0 mo, respectively. Receiving > 50 % (N = 23) versus ≤ 50 % (N = 155) of radiotherapy treatments within 3 h of sunset was associated with younger age; otherwise, there were no other differences between cohorts. There were no significant differences in characteristics between patients who received > 50 % (N = 23) versus ≤ 50 % (N = 155) of durvalumab infusions within 3 h of sunset. On multivariable analysis, receiving > 50 % of radiotherapy treatments within 3 h of sunset was independently associated with reduced risk for progression (HR 0.39, p = 0.017) and distant metastasis (HR 0.27, p = 0.007); conversely, receiving > 50 % of durvalumab infusions within 3 h of sunset was independently associated with increased risk for distant metastasis (HR 2.13, p = 0.025). The timing of chemotherapy was not associated with disease outcomes.

Conclusion: The time of day of radiotherapy and durvalumab infusion may be associated with disease control in LA-NSCLC, and the optimal time of treatment depends on the treatment modality.

Results from prospective randomized trial results are required to provide practice-changing level-1 evidence. However, if such a trial is not feasible, we should not accept that consequently practice could not change. We discuss hereby a pragmatically approach based on methodological alternatives.

Background and purpose: In proton therapy, a relative biological effectiveness (RBE) of 1.1 is used toreach an isoeffective biological response between photon and proton doses. However, the RBE varies with biological endpoints and linear energy transfer (LET), two key parameters in radiotherapy. Few in vivo studies have investigated the increasing RBE with increasing LET. This study aims to test the hypothesis that the RBE varies between endpoints and has a distal edge effect in vivo.

Materials and methods: Unanesthetized micewere restrainedin jigs where their right hind legs were irradiated with a single dose of protons at the center (LET, _all = 5.3 keV/μm) and distal edge (LET, _all = 7.6 keV/μm) of a spread-out Bragg peak (SOBP). 6 MV photons were used as reference. The acute damage and skin toxicity were scored daily until day 30, and the late damage was evaluated using a joint contracture assay for one year after treatment.

Results: An acute damage RBE of 1.06 ± 0.02(1.02-1.10) and late damage RBE of 1.16 ± 0.08(1.00-1.32) were found, displaying an enhanced RBE for late damage in the center SOBP. The distal edge RBE for acute and late damage was 1.15 ± 0.02(1.10-1.19) and 1.26 ± 0.09(1.07-1.43), showing a similar center-to-distal edge RBE enhancement of 8 % and 9 % for acute and late damage.

Conclusion: The findings demonstrate an increased RBE for late damage than acute damage and the distal edge effect is evident with increased RBE at the distal end of the proton SOBP in vivo.

Background: Radiation oncologists closely monitor patients during weekly on-treatment visits (OTVs). This study examines whether routine patient-reported outcome measures (PROMs) during OTVs change physicians' perceptions of treatment-toxicity and inform symptom-management.

Patient and methods: IMPROVE is a single-arm prospective multicenter trial, conducted from 2020 to 2023. Patients with locally-advanced or oligometastatic thoracic or gastrointestinal cancers receiving definitive-intent radiation, with or without chemotherapy, and their physicians enrolled. Patients completed a 14-question disease-specific PROM in clinic prior to OTVs. Physicians rated their patient's global toxicity-burden based on clinical data/assessments, then re-rated their patient's toxicity-burden and reported management-changes after PROM review. At radiotherapy end, physicians completed a Feedback Form. PROMs and outcome-data collection used electronic or paper forms. We report any change in physician-assessed burden-score and symptom-management due to PROMs.

Results: The 100 patients enrolled (49 academic, 51 community-based) were 70 years old (median), 51% female, 81% Caucasian, 95% ECOG 0-1, and 94% received concurrent chemotherapy. The median radiation dose was 60 Gy, delivered over 6 weeks. PROMs were available for review for 607/629 (97%) OTVs: full 433/629 (69%), partial 174/629 (28%). For 75/100 patients (75%; 95% CI:65%-83%), PROM review resulted in any change in physician-reported burden-score, and for 50/100 patients (50%; 95% CI:40%-60%) any change in patients' on-treatment management. Rates of burden-score and management-changes were similar between academic and community-based practices (78% vs. 73%; 53% vs. 47%, respectively). For 78/100 patients with Feedback Forms, physicians agreed/strongly agreed that PROMs improved patients' quality-of-care (91%).

Conclusions: PROM review changes radiation oncologists' on-treatment toxicity assessment in 75% and care delivery in 50% of their patients.

Aim: We aimed to examine the influence of various prognostic factors on the outcome of external auditory canal (EAC) cancer and create a graphical prediction tool, marking a first in this field, premised on these determinants.

Methods: We retrospectively analysed 173 patients with EAC cancer, making this the largest patient cohort in the literature. Survival analysis was performed using the Kaplan-Meier method, and the log-rank test was used to assess the differences between established prognostic variables. The risk factors for overall survival (OS) rates were analysed by univariate and multivariable Cox regression analyses.

Results: The cohort demonstrated 2-, 5-, and 10-year progression-free survival (PFS) rates of 86.9%, 72.7%, and 60.1%, respectively. The overall survival (OS) rates for the cohort at 2, 5, and 10-years were 93.6%, 80.6%, and 65.8%, respectively. The key predictors of both OS and PFS were squamous cell carcinoma, T stage, margin status, and radiotherapy. The nomogram showed good predictive accuracy and discriminative ability. Post-radiotherapy follow-up data indicated that the incidence rates of allotriogeustia, saprodontia, xerostomia, difficulty in opening the mouth, and facioplegia were 1.3%, 6.5%, 22.7%, 8.4%, and 3.2%, respectively.

Conclusion: Our findings highlight the significance of squamous cell carcinoma, T stage, margin status, and radiotherapy as predictors of OS and PFS. Validation analysis confirmed the applicability of the developed nomogram in predicting individual survival probabilities for patients with EAC cancers, signifying a notable progression in the diagnosis and treatment of EAC cancers.

Background: To evaluate the efficacy of local-regional radiotherapy (LRRT) in de novo metastatic nasopharyngeal carcinoma (dm NPC) patients receiving chemo-immunotherapy as first-line treatment and select the beneficiaries from LRRT.

Methods and materials: M1-NPC patients receiving platinum-based chemo-immunotherapy with or without LRRT from four centers were included in this study. The propensity score matching (PSM) analysis was employed to balance the baseline characteristics between the LRRT and non-LRRT groups.

Results: 546 dm NPC patients (140 patients in the non-LRRT group and 406 patients in the LRRT group) were incorporated. Patients receiving LRRT demonstrated significantly improved progression-free survival (3-year PFS rate, 53.2 % vs 31.2 %, p < 0.001). After PSM analysis, there were 244 patients in the LRRT group and 122 patients in the non-LRRT group. Multivariable analysis indicated that LRRT was not an independent prognostic factor in the matched cohort (HR, 1.25, 95 % CI, 0.92-1.69, p = 0.156). Subgroup analysis among the matched cohort showed a significant increase in PFS for patients with oligo metastatic disease (OMD) who received LRRT (3-year PFS rate, 70.6 % vs 49.3 %, p = 0.043). In contrast, no such benefit was observed in patients with poly metastatic disease (PMD, 3-year PFS rate, 35.8 % vs 27.8 %, p = 0.17). Furthermore, LRRT significantly enhanced survival in patients with undetectable EBV DNA_{2-6 cycles} (3-year PFS rate, 57.9 % vs. 43.4 %, p = 0.043), whereas no survival improvement was noted in patients with detectable EBV DNA_{2-6 cycles} (16.2 % vs. 20.3 %, p = 0.21).

Conclusion: LRRT could prolong PFS in M1-NPC patients. OMD and undetectable EBV DNA_{2-6 cycles} are potential indicators for selecting beneficiaries from LRRT.

Purpose: Radiotherapy presents a curative approach for nasopharyngeal carcinoma (NPC); however, the cellular radiosensitivity heterogeneity limits its efficacy. Thus, investigating the specific mechanisms of radioresistance in NPC is crucial for identifying and employing effective radiosensitizing agents to enhance treatment success.

Methods and materials: Radioresistant NPC cell lines HONE1-RR and SUNE1-RR were established. Quantitative reverse transcription-PCR (qRT-PCR), western blot, and enzyme-linked immuno sorbent assay (ELISA) were employed to detect the activation of the angiotensinogen (AGT) and local angiotensin II (Ang II). Transmission electron microscopy, ferrous ion detection, and lipid oxidation levels were utilized to detect radiation-induced ferroptosis in NPC. Bioinformatics analysis, along with qRT-PCR, western blotting, co-immunoprecipitation, and dual-luciferase assays were employed to explore downstream mechanisms. Colony formation assay, Cell Counting Kit-8 (CCK-8) assay, and a nude mouse xenograft model were utilized to assess NPC radiosensitivity. The expression of AGT, hypoxia-inducible factor-1 alpha (HIF-1α), hypoxia-inducible lipid droplet-associated protein (HILPDA), and glutathione peroxidase 4 (GPX4) in NPC tissues was detected through immunohistochemistry.

Results: Activation of local Ang II was revealed to play a critical role in driving radioresistance in NPC cells modulating ferroptosis. This local Ang II established a positive feedback loop with HIF-1α through two parallel pathways; Ang II stabilizes HIF-1α by activating the MAPK pathway, and AGT directly binds HIF-1α to prevent its degradation. This AGT-HIF-1α loop regulated NPC cell ferroptosis via transcriptional regulation of HILPDA expression. Moreover, the co-administration of Ang II receptor antagonist (ARB) and ferroptosis inducers markedly increased NPC radiosensitivity.Additionally, the expression of AGT, HIF-1α, and HILPDA was closely correlated with the intensity of ferroptosis, radiosensitivity, and prognosis in NPC.

Conclusions: Our findings suggest that the AGT-HIF-1α-HILPDA pathway promotes radioresistance in NPC by enhancing lipid droplet accumulation, thereby suppressing ferroptosis. Targeting local Ang II alongside ferroptosis induction offers a promising strategy to improve radiosensitivity in NPC.

Purpose: To evaluate the impact of hypofractionated radiotherapy (Hypo-RT) with different interfraction intervals on tumor growth, immune response, and synergistic effects with anti-PD-1 immunotherapy.

Methods: The mouse MC38 colon cancer model was utilized. Various radiation regimens were designed to investigate the effects of fraction interval and fraction size on tumor growth, immune mobilization, and combination effects with anti-PD-1 immunotherapy.

Results: For a fixed-dose experiment, the 6 × 5 Gy for every other day (qod) regimen demonstrated an equivalent effect on tumor growth compared to the 6 × 5 Gy once daily (qd) regimen, while the 6 × 5 Gy for twice weekly (biw) regimen failed to inhibit tumor growth. Both qod and biw regimens induced an enhanced immune response, unlike the qd regimen. For a fixed biologically equivalent dose experiment, 6 × 5 Gy qod, 4 × 7 Gy biw, and 2 × 11 Gy once weekly (qw) regimens exhibited similar tumor suppression to the 12 × 3 Gy qd regimen. The long-interval Hypo-RT regimens significantly mobilized host immunity, whereas 12 × 3 Gy qd did not. The peripheral and intratumoral T cells increased as the fraction interval and size increased. All Hypo-RT regimens combined with anti-PD-1 immunotherapy demonstrated higher intratumoral CD8 + T cells and more effective tumor growth delay compared to the 12 × 3 Gy qd regime.

Conclusions: The current study suggested that a prolonged inter-fraction interval with an increased fraction size in Hypo-RT may be a promising option to balance the therapeutic effect on tumor and immune activation.

Sarcopenia describes the degenerative loss of muscle mass and strength, and is emerging as a pan-cancer prognostic biomarker. It is linked with increased treatment toxicity, decreased survival and significant healthcare financial burden. Systematic analyses of sarcopenia studies have focused on outcomes in patients treated surgically or with systemic therapies. There are few publications concerning patients treated with radiotherapy. This manuscript presents a pan-cancer systematic review of the association between sarcopenia and survival outcomes in patients treated with definitive (chemo-)radiotherapy. A literature search was performed, with 26 studies identified, including a total of 5,784 patients. The prognostic significance of sarcopenia was mixed. This may reflect lack of consensus in methods used to measure skeletal muscle mass and define sarcopenia. Many papers analyse small samples and present sarcopenia cutoffs optimised on the local population, which may not generalise to external populations. Recent advances in artificial intelligence allow for automatic measurement of body composition by segmenting the muscle compartment on routinely collected imaging. This provides opportunity for standardisation of measurement methods and definitions across populations. Adopting sarcopenia diagnosis into clinical workflows could reduce futile treatments and associated financial burden, by reducing treatment toxicities, and improving treatment completion, patient survival, and quality-of-life after cancer.