Trabectedin is used for the treatment of advanced soft tissue sarcomas (STSs). In this study, we evaluated if trabectedin could enhance the efficacy of irradiation (IR) by increasing the intrinsic ...cell radiosensitivity and modulating tumor micro-environment in fibrosarcoma (HS 93.T), leiomyosarcoma (HS5.T), liposarcoma (SW872), and rhabdomyosarcoma (RD) cell lines. A significant reduction in cell surviving fraction (SF) following trabectedin + IR compared to IR alone was observed in liposarcoma and leiomyosarcoma (enhancement ratio at 50%, ER50: 1.45 and 2.35, respectively), whereas an additive effect was shown in rhabdomyosarcoma and fibrosarcoma. Invasive cells' fraction significantly decreased following trabectedin ± IR compared to IR alone. Differences in cell cycle distribution were observed in leiomyosarcoma and rhabdomyosarcoma treated with trabectedin + IR. In all STS lines, trabectedin + IR resulted in a significantly higher number of γ-H2AX (histone H2AX) foci 30 min compared to the control, trabectedin, or IR alone. Expression of ATM, RAD50, Ang-2, VEGF, and PD-L1 was not significantly altered following trabectedin + IR. In conclusion, trabectedin radiosensitizes STS cells by affecting SF (particularly in leiomyosarcoma and liposarcoma), invasiveness, cell cycle distribution, and γ-H2AX foci formation. Conversely, no synergistic effect was observed on DNA damage repair, neoangiogenesis, and immune system.
Background and purpose
COVID-19 constitutes a worldwide threat, prompting Italian Government to implement specific measures on March 8, 2020, to protect patients and health workers from disease ...transmission. The impact of preventive measures on daily activity of a radiotherapy facility may hamper the ability to fulfill normal workload burden. Thus, we assessed the number of delivered treatments in a specific observation period after the adoption of preventive measures (since March 11 to April 24, 2020) and compared it with the corresponding period of the year 2019.
Materials and methods
Overall number of delivered fractions was related to actual time of platform daily activity and reported as a ratio between number of delivered fractions and activity hours (Fr/Hrs). Fr/Hrs were calculated and compared for two different periods of time, March 11–April 24, 2019 (Fr/Hrs1), and March 11–April 24, 2020 (Fr/Hrs2).
Results
Fr/Hrs1 and Fr/Hrs2 were 2.66 and 2.54 for year 2019 and 2020, respectively, for a Fr/Hrs
ratio
of 1.07 (95% CI 1.03–1.12,
p
= 0.0005). Fr/Hrs1 was significantly higher than Fr/Hrs2 for Sli
R
and Precise
R
, with Fr/Hrs
ratio
of 1.92 (95% CI 1.66–2.23,
p
< 0.0001) and 1.11 (95% CI 1.03–1.2,
p
= 0.003), respectively. No significant difference was reported for Synergy
R
and Cyberknife
R
with Fr/Hrs
ratio
of 0.99 (95% CI 0.91–1.08,
p
= 0.8) and 0.9 (95% CI 0.77–1.06,
p
= 0.2), respectively. Fr/Hrs1 was significantly lower than Fr/Hrs2 for Tomotherapy
R
, with Fr/Hrs
ratio
of 0.88 (95% CI 0.8–0.96,
p
= 0.007).
Conclusion
Preventive measures did not influence workload burden performed. Automation in treatment delivery seems to compensate effectively for health workers number reduction.
Background
ARTO trial was designed to evaluate the difference in terms of outcomes between patients affected by oligo metastatic castrate resistant prostate cancer (mCRPC) treated with Abiraterone ...acetate and randomized to receive or not SBRT on all sites of disease. Here, we present a preliminary analysis conducted on patients enrolled at promoting institution.
Objective
To present a preliminary overview about population features, clinical outcomes, adverse events, quality of life and explorative translational research.
Design, setting, and participants
ARTO (NCT03449719) is a phase II trial including patients affected by oligo mCRPC, randomized to receive standard of care (GnRH agonist or antagonist plus abiraterone acetate 1000 mg and oral prednisone 10 mg daily) with or without SBRT on all metastatic sites of disease. All subjects have < 3 bone or nodal metastases. All patients are treated in I line mCRPC setting, no previous lines of treatment for mCRPC are allowed.
Outcome measurements and statistical analysis
Data about a mono-centric cohort of 42 patients enrolled are presented in the current analysis, with focus on baseline population features, PSA drop at 3 months, biochemical response, and quality of life outcomes. Descriptive statistics regarding translational research are also presented.
Results and limitation
Significant difference in terms of PSA drop at three months was not detected (
p
= 0.68). Biochemical response (PSA reduction > 50%) was reported in 73.7 versus 76.5% of patients in control vs SBRT arm, respectively (
p
= 0.84). All patients are alive. Progression occurred in 1 versus 0 patients in the control versus SBRT arm, respectively. After 3 months, an average decrease of 13 points in terms of Global Health Score was reported for the overall population. However, complete recovery was noticed at 6 months. Circulating tumor cells detection rate was 40%.
Conclusions
SBRT + Abiraterone treatment was safe and well tolerated, non-significant trend in terms of PSA drop and biochemical response at 3 months was detected in SBRT arm. Interestingly, CTCs detection in this selected cohort of oligo-mCRPC was lower if compared to historical data of unselected mCRPC patients.
Abstract
Background
tumor recurrence after NSCLC surgical resection is the most common cause of treatment failure that sharply reduces the patient’s life expectancy. The optimal treatment strategy ...for loco-regional recurrences developing after surgical resection in patients with non–small-cell lung cancer (NSCLC) is not established yet.
This report aims to describe the pattern of relapse, PFS, and OS in patients treated with radio-chemotherapy and durvalumab for loco-regional relapse after surgery.
Methods
We conducted a multicenter, retrospective study including subjects who underwent surgical resection for NSCLC and were treated with Pacific protocol after loco-regional relapse.
Results
Twenty-four patients met the inclusion criteria. At the time of diagnosis mean age was 65 years (range 47–78), the majority being male (58.3%). The 12-month progression-free survival rate was 68.7%, the 18-month progression-free survival rate was 45.8%, and the 24-month progression-free survival rate was 34.3%. There were three deaths: the 12-month survival rate was 91%, and the 18-month survival rate was 82.8%.
Conclusions
In this article, we propose a treatment strategy that might prolong post recurrence survival in patients with good performance status experiencing loco-regional relapse after surgery.
Artificial Intelligence (AI) is revolutionising many aspects of radiotherapy (RT), opening scenarios that were unimaginable just a few years ago. The aim of this study is to propose a Deep Leaning ...(DL) approach able to quickly generate synthetic Computed Tomography (CT) images from low-dose Cone Beam CT (CBCT) acquired on a modern linear accelerator integrating AI. Methods: A total of 53 patients treated in the pelvic region were enrolled and split into training (30), validation (9), and testing (14). A Generative Adversarial Network (GAN) was trained for 200 epochs. The image accuracy was evaluated by calculating the mean and mean absolute error (ME and ME) between sCT and CT. RT treatment plans were calculated on CT and sCT images, and dose accuracy was evaluated considering Dose Volume Histogram (DVH) and gamma analysis. Results: A total of 4507 images were selected for training. The MAE and ME values in the test set were 36 ± 6 HU and 7 ± 6 HU, respectively. Mean gamma passing rates for 1%/1 mm, 2%/2 mm, and 3%/3 mm tolerance criteria were respectively 93.5 ± 3.4%, 98.0 ± 1.3%, and 99.2 ± 0.7%, with no difference between curative and palliative cases. All the DVH parameters analysed were within 1 Gy of the difference between sCT and CT. Conclusion: This study demonstrated that sCT generation using the DL approach is feasible on low-dose CBCT images. The proposed approach can represent a valid tool to speed up the online adaptive procedure and remove CT simulation from the RT workflow.
Oligoprogression (OPD) is defined as a condition where limited progression (1-3 metastases) is observed in patients undergoing systemic cancer treatment. In this study we investigated the impact of ...stereotactic body radiotherapy (SBRT) in patients with OPD from metastatic lung cancer.
Data from a cohort of consecutive patients with SBRT treated between June 2015 and August 2021 were collected. All extracranial metastatic sites of OPD from lung cancer were included. Dose regimens consisted of mainly 24 in 2 fractions, 30-51 Gy in 3 fractions, 30-55 Gy in 5 fractions, 52.5 Gy in 7 fractions and 44-56 Gy in 8 fractions. Kaplan-Meier method was used to calculate Overall Survival (OS), Local Control (LC), and Disease-Free Survival (DFS) from the start date of SBRT to the event.
Sixty-three patients, 34 female and 29 males were included. Median age was 75 years (range 25-83). All patients received concurrent systemic treatment before the start of the SBRT: 19 chemotherapy (CT), 26 CT plus immunotherapy (IT) or Tyrosin kinase inhibitors (TKI) and 18 IT/TKI. SBRT was delivered to the lung (n = 29), mediastinal node (n = 9), bone (n = 7), adrenal gland (n = 19), other visceral metastases (1) and other node metastases (n = 4). After a median follow-up of 17 months, median OS was 23 months. LC was 93% at 1 year and 87% at 2 years. DFS was 7 months. According to our results, there was no statistically significant correlation between prognostic factors and OS after SBRT in OPD patients.
Median DFS was 7 months, translating into the continuation of effective systemic treatment as other metastases grow slowly. In patients with oligoprogression disease, SBRT is a valid and efficient treatment that may enable postponing the switch of systemic line.
Purpose
This systematic review and meta-analysis aimed to evaluate the efficacy of barrier films and dressings in preventing acute radiation dermatitis (RD).
Methods
OVID Medline, Embase, and ...Cochrane databases were searched from 1946 to September 2020 to identify randomized controlled trials on the use of barrier films or dressings to prevent RD. For comparable outcomes between studies, pooled effect sizes and 95% confidence intervals (CI) were calculated using the random effects analysis in RevMan 5.4.
Results
Fourteen and 11 studies were included in the qualitative and quantitative analyses, respectively. Five types of barrier films used for RD were identified: Hydrofilm, StrataXRT®, Mepitel® Film, 3 M™ Cavilon™ No-Sting Barrier Film, and silver leaf nylon dressing. Hydrofilm and Mepitel Film significantly reduced the development of RD grade ≥ 2 in breast and head and neck cancer patients (RR 0.32, 95%CI 0.19, 0.56, p < 0.0001; RR 0.21, 95%CI 0.05, 0.89, p = 0.03, resp.). Moreover, Hydrofilm had a beneficial effect on patient-reported outcomes (PROs) (SMD -0.75, 95%CI -1.2, -0.29, p = 0.001). The meta-analyses on the other barrier films did not show any significant effect.
Conclusion
This review and meta-analysis demonstrated that Hydrofilm and Mepitel Film could effectively reduce RD severity and improve PROs. The evidence is generally weak for all the studies on barrier films and dressings due to a limited study number, high risk of bias, small sample sizes, and minimal comparable outcome measures. It’s potential has been proven, but future research in this field is recommended to confirm the efficacy of these products and assess real-world feasibility.
The cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the standard treatment for hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer. Data ...about the balance between efficacy and toxicity of combined palliative radiotherapy (RT) and CDK4/6 inhibition are lacking.
We undertook a review of 46 patients with metastatic breast cancer on systemic treatment with CDK4/6i who underwent 62 metastases-directed RT. Clinical, laboratory, and RT treatment planning data were collected. Statistical analyses included Student t test, paired sample t test, and logistic regression modeling.
Thirty patients (65.2%) received palbociclib, 15 (32.6%) received ribociclib, and one patient received abemaciclib (2.2%). Median total prescribed RT dose was 20 Gy (range, 8-63 Gy). Sites of RT were bone (n = 50; 80.7%), visceral (n = 7; 11.3%), or brain metastases (n = 3; 4.8%), as well as primary tumor of the breast (n = 2; 3.2%). Overall, the rates of grade 3 or higher adverse events (AEs) were 6.5%, 4.3%, 15.2%, and 23.9% before the start of RT, during RT, 2 and 6 weeks after RT completion, respectively. We found no correlation between dose distribution to organs at risk and the development of AEs. The local control rates for the entire cohort were 98% at 6 months and 90% at 12 months. Overall, pain relief (complete or partial) was experienced by 80% (24/30) of patients who initially reported pain at the treated metastatic site.
We observed a modest increase in the rates of grade 3 or higher AEs after combined RT and CDK4/6i, with maintained efficacy of concomitant RT.
We present a real-world experience of adverse events (AEs) associated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) provided concomitantly with metastasis-directed radiotherapy (n = 62) in patients with advanced breast cancer (n = 46). We observed a modest increase in the rates of grade 3 or higher AEs after irradiation with maintained efficacy of concomitant treatment.
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