Machine learning-based automated planning for hippocampal avoidance prophylactic cranial irradiation.

PURPOSE: Design and evaluate a knowledge-based model using commercially available artificial intelligence tools for automated treatment planning to efficiently generate clinically acceptable hippocampal avoidance prophylactic cranial irradiation (HA-PCI) plans in patients with small-cell lung cancer. MATERIALS AND METHODS: Data from 44 patients with different grades of head flexion (range 45°) were used as the training datasets. A Rapid Plan knowledge-based planning (KB) routine was applied for a prescription of 25 Gy in 10 fractions using two volumetric modulated arc therapy (VMAT) arcs. The 9 plans used to validate the initial model were added to generate a second version of the RP model (Hippo-MARv2). Automated plans (AP) were compared with manual plans (MP) according to the dose-volume objectives of the PREMER trial. Optimization time and model quality were assessed using 10 patients who were not included in the first 44 datasets. RESULTS: A 55% reduction in average optimization time was observed for AP compared to MP. (15 vs 33 min; p = 0.001).Statistically significant differences in favor of AP were found for D98% (22.6 vs 20.9 Gy), Homogeneity Index (17.6 vs 23.0) and Hippocampus D mean (11.0 vs 11.7 Gy). The AP met the proposed objectives without significant deviations, while in the case of the MP, significant deviations from the proposed target values were found in 2 cases. CONCLUSION: The KB model allows automated planning for HA-PCI. Automation of radiotherapy planning improves efficiency, safety, and quality and could facilitate access to new techniques.

Validation of 3D printing materials for high dose-rate brachytherapy using ionisation chamber and custom phantom.

Methods.Measurements were taken with the Exradin A20 (Standard Imaging) ionisation chamber, and the 'homemade' MARM phantom was made with the 3D Ultimaker 2+ printer using PLA material. The material used for validation was ABS Medical from Smart Materials 3D. The irradiation was undertaken with a192Ir source by means of Varian's GammaMed Plus iX HDR equipment. EBT3 films were used to run additional tests. We compared different measurements for PLA, ABS Medical, and water. Additional validation methods, described in the bibliography, were also compared.Results.The measurements with the ionisation chamber that we obtained using the MARM phantom with PLA and ABS within the clinically relevant range (0.5-1.5 cm) differ with respect to the measures in the water reference, by 2.3% and 0.94%, respectively.Discussion.The literature describes highly heterogeneous validation methods, complicating the performance of systematic reviews and comparisons between materials. Thus, creating a phantom represents a single effort that will quickly pay off. This system enables comparisons, ensuring that geometric conditions remain stable-something that is not always possible with radiochromic films. The use of a calibrated ionisation chamber in the corresponding energy range, combined with the 'homemade' MARM phantom applied according to the proposed methodology, allows a differentiation between the attenuation of the material itself and the drop in the dose due to distance.Conclusion.The validation method for 3D printing materials, using an ionisation chamber and the MARM PLA phantom, represents an accessible, standardisable solution for manufacturing brachytherapy applicators.

Outcomes after neoadjuvant treatment with gemcitabine and erlotinib followed by gemcitabine-erlotinib and radiotherapy for resectable pancreatic cancer (GEMCAD 10-03 trial).

BACKGROUND: Neoadjuvant therapy (NAT) for pancreatic adenocarcinoma (PDAC) patients has shown promising results in non-randomized trials. This is a multi-institutional phase II trial of NAT in resectable PDAC patients. METHODS: Patients with confirmed resectable PDAC after agreement by two expert radiologists were eligible. Patients received three cycles of GEM (1000 mg/m2/week) plus daily erlotinib (ERL) (100 mg/day). After re-staging, patients without progressive disease underwent 5 weeks of therapy with GEM (300 mg/m2/week), ERL 100 mg/day and concomitant radiotherapy (45 Gy). Efficacy was assessed using tumor regression grade (TRG) and resection margin status. Using a single-arm Simon's design, considering the therapy not useful if R0 < 40% and useful if the R0 > 70% (alpha 5%, beta 10%), 24 patients needed to be recruited. This trial was registered at ClinicalTrials.gov, number NCT01389440. RESULTS: Twenty-five patients were enrolled. Adverse effects of NAT were mainly mild gastrointestinal disorders. Resectability rate was 76%, with a R0 rate of 63.1% among the resected patients. Median overall survival (OS) and disease-free survival (DFS) were 23.8 (95% CI 11.4-36.2) and 12.8 months (95% CI 8.6-17.1), respectively. R0 resection patients had better median OS, compared with patients with R1 resection or not resected (65.5 months vs. 15.5 months, p = 0.01). N0 rate among the resected patients was 63.1%, and showed a longer median OS (65.5 vs. 15.2 months, p = 0.009). CONCLUSION: The results of this study confirm promising oncologic results with NAT for patients with resectable PDAC. Therefore, the present trial supports the development of phase II randomized trials comparing NAT vs. upfront surgery in resectable pancreatic cancer.

Once-Weekly Hypofractionated Radiotherapy for Breast Cancer in Elderly Patients: Efficacy and Tolerance in 486 Patients.

PURPOSE: Radiation therapy is a key treatment of breast cancer. Elderly patients with associated diseases that modify their performance status do not tolerate long periods of daily irradiation. The objective of this study is to analyze the results of weekly hypofractionated treatment in these patients. MATERIAL AND METHODS: Between 1992 and 2016, we included 486 elderly patients presenting concomitant pathology or sociofamilial problems in which it was not feasible to propose conventional treatment. They were treated with conservative surgery or mastectomy and then adjuvant hypofractionated irradiation, administering 5 Gy or 6.25 Gy in 6 fractions, once a week (total dose 30-37.5 Gy) over 6 weeks. RESULTS: Breast cancer overall survival according to the Kaplan-Meier method at 5 years was 74.2% ± 2.3%; breast cancer disease-free survival was 90% ± 1.6%; local relapse-free survival was 96.5% ± 1% showing that patients die more from other causes and not from their neoplasia. Acute dermatitis was mild (75.6% of the patients grades I-III) and 30.6% had moderate chronic fibrosis. CONCLUSIONS: The once-weekly hypofractionated radiotherapy is a feasible and convenient option for elderly patients with breast cancer. It is a safe treatment modality with similar survival and local control results compared to standard fractionation, while the side effects are acceptable.

Photo(geno)toxicity changes associated with hydroxylation of the aromatic chromophores during diclofenac metabolism.

Diclofenac (DCF) can cause adverse reactions such as gastrointestinal, renal and cardiovascular disorders; therefore, topical administration may be an attractive alternative to the management of local pain in order to avoid these side effects. However, previous studies have shown that DCF, in combination with sunlight, displays capability to induce photosensitivity disorders. In humans, DCF is biotransformed into hydroxylated metabolites at positions 4' and 5 (4'OH-DCF and 5OH-DCF), and this chemical change produces non negligible alterations of the drug chromophore, resulting in a significant modification of its light-absorbing properties. In the present work, 5OH-DCF exhibited higher photo(geno)toxic potential than the parent drug, as shown by several in vitro assays (3T3 NRU phototoxicity, DNA ssb gel electrophoresis and COMET), whereas 4'OH-DCF did not display significant photo(geno)toxicity. This could be associated, at least partially with their more efficient UV-light absorption by 5OH-DCF metabolite and with a higher photoreactivity. Interestingly, most of the cellular DNA damage photosensitized by DCF and 5OH-DCF was repaired by the cells after several hours, although this effect was not complete in the case of 5OH-DCF.

Extrahepatic malignancies in primary biliary cirrhosis: a comparative study at two European centers.

Limited information and divergent results are available on the prevalence/incidence, survival, and risk factors for developing extrahepatic malignancies (EMs) in primary biliary cirrhosis (PBC). The aim of the study was to analyze the epidemiology and survival rates for EM in PBC patients. The study was conducted on two series of patients followed up at two European centers (361 in Padova, Italy, and 397 in Barcelona, Spain) for a mean 7.7 ± 7 and 12.2 ± 7 years, respectively. The cancer incidence was compared with the standardized incidence ratios (SIRs) calculated using the Cancer Registry of the Veneto Region (Italy) and the Cancer Registry of Tarragona (Spain). Seventy-two patients developed EM. The prevalence of cases was similar in Padova (9.7 %) and Barcelona (9.4 %). The overall cancer incidence was similar to the expected incidence for the general population in the same geographical area (SIR = 1.2), and so was the crude EM rate (855.01 vs 652.86 per 100,000 patient-years, respectively, RR = 1.3). Logistic regression analysis showed that advanced histological stage and extrahepatic autoimmune diseases were significantly associated with the onset of EM. Survival was similar for PBC patients with and without EM (p = n.s.), and actual survival was similar to the one predicted by the Mayo model. The incidence of EM in PBC patients was found similar in Italy and Spain and no different from that of the general population. Advanced histological stage and extrahepatic autoimmune disease were risk factors significantly associated with EM developing in PBC. The onset of cancer in PBC patients does not influence the natural history of their liver disease.

Long-term results and prognostic factors of patients with cervical carcinoma treated with concurrent chemoradiotherapy.

AIMS AND BACKGROUND: To evaluate the predictive factors of recurrence in cervical cancer treated with radical radiochemotherapy. METHODS: A retrospective analysis of 56 women was performed. Response was assessed using the RECIST response. Overall survival and disease-free survival curves were estimated by the Kaplan-Meier method and the Cox proportional hazards model was used to analyse predictors of recurrence. RESULTS: Local recurrence was documented in 16 patients and distant metastases in 15. The Kaplan-Meier survival probabilities were 95.1 ± 6.4% at 3 years and 80.4 ± 13.1% at 5 years and the Kaplan-Meier curve values for disease-free survival were 60.3 ± 14.3% at 3 years and 53.0 ± 15.7% at 5 years. Thirty-five patients were alive and 21 patients died, 19 from metastatic disease and 2 from other causes. Complete response after chemoradiation therapy, squamous cell carcinoma and tumour size ≤ 4 cm were significantly associated with outcome. In the Cox regression model, tumour size > 4 cm (hazard ratio 7.48; 95% CI 2.71-20.6; p < 0.001) and partial response (hazard ratio 7.09; 95% CI 2.82-17.8; p < 0.001) were predictive factors for disease-free survival and partial response (hazard ratio 3.7; 95% CI 1.3-10.1; p < 0.001) and non-squamous cell carcinoma (hazard ratio 3.5; 95% CI 1.2-9.7; p < 0.001) were predictive factors for overall survival. CONCLUSIONS: Non-squamous histology and partial response were independent prognostic factors for overall survival and tumour size and partial response were independent prognostic variables for 5-year disease survival.