Upfront Chemotherapy Followed by Stereotactic Body Radiation Therapy with or without Surgery in Older Patients with Localized Pancreatic Cancer: A Single Institution Experience and Review of the Literature

Objective: To report on clinical outcomes and toxicity in older (age ≥ 70 years) patients with localized pancreatic cancer treated with upfront chemotherapy followed by stereotactic body radiation therapy (SBRT) with or without surgery. Methods: Endpoints included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and toxicity. Results: A total of 57 older patients were included in the study. Median OS was 19.6 months, with six-month, one-year, and two-year OS rates of 83.4, 66.5, and 42.4%. On MVA, resection status (HR: 0.30, 95% CI 0.12–0.91, p = 0.031) was associated with OS. Patients with surgically resected tumors had improved median OS (29.1 vs. 7.0 months, p < 0.001). On MVA, resection status (HR: 0.40, 95% CI 0.17–0.93, p = 0.034) was also associated with PFS. Patients with surgically resected tumors had improved median PFS (12.9 vs. 1.6 months, p < 0.001). There were 3/57 cases (5.3%) of late grade 3 radiation toxicity and 2/38 cases (5.3%) of Clavien-Dindo grade 3b toxicity in those who underwent resection. Conclusion: Multimodality therapy involving SBRT is safe and feasible in older patients with localized pancreatic cancer. Surgical resection was associated with improved clinical outcomes. As such, older patients who complete chemotherapy should not be excluded from aggressive local therapy when possible.

Intensification of radiation therapy for localized breast cancer in the settings of the COVID-19 pandemic: A literature review

Relevance: Since 2004, breast cancer steadily ranks first in the structure of the incidence of malignant neoplasms in the Republic of Kazakhstan in both sexes. In 2020, its share was 14.5% (vs. 15.2% in 2019). Breast cancer also constantly ranks first in the structure of female cancer incidence, with 44.3‰ in 2020 (vs. 51.6‰in 2019). In the early 1980s, radiation therapy was a standard specialized treatment for breast cancer. The current realities of the COVID-19 pandemic require a reorganization of healthcare facilities to determine the priorities. It is also important to balance the economic and clinical efficacy of radiotherapy methods applied. The study aimed to analyze the results of large randomized trials and compare breast cancer outcomes after hypofractionated and standard fractionation radiation treatment. Methods: We reviewed the results of large randomized trials of hypofractionated radiation therapy, emphasizing adequate patient selection according to the American Society of Therapeutic Radiology and Oncology (ASTRO) guidelines. Radiobiological aspects of hypofractionation were considered due to its implementation in clinical practice. The research materials were obtained from the “PubMed” database of evidence-based medicine by the keywords “radiotherapy,” “breast cancer,” “hypofractionation dose” for the period 2000-2021. Large randomized trials involving patients of any age diagnosed with stages T1-3, N0-1 breast cancer, who underwent beam therapy in standard or hypofractionated mode, met the criteria for inclusion in this study. Results: According to the results of large randomized trials, the hypofractionated regimen is similar to the standard regimen in terms of late effects on normal tissues and ensures good control over the oncological process. Conclusions: Hypofractionation has proven effectiveness and safety and has lower late and/or acute radiation toxicity when treating early breast cancer. Hypofractionation can become a new standard of radiation therapy at early stages after breast-conserving surgery.

Individual Radiosensitivity as a Risk Factor for the Radiation-Induced Acute Radiodermatitis

Background: Up to 95% of irradiated patients suffer from ionizing radiation (IR) induced early skin reaction, acute radiation dermatitis (ARD). Some experts think that additional skin hydration can reduce acute skin reactions. Individual radiosensitivity (IRS) determined from lymphocytes may help to predict acute radiation toxicity. The purpose of this study is to evaluate the clinical manifestation of ARD in different skincare groups during whole breast radiotherapy depending on IRS and other risk factors. Methods: A total of 108 early-stage breast cancer patients were randomized into best supportive care (BSC) and additional skincare (ASC) groups. IRS was evaluated using a G2 assay modified with caffeine-induced G2 checkpoint arrest. All patients received a 50 Gy dose to the breast planning target volume (PTV). Clinical assessment of ARD symptoms according to the CTCAE grading scale was performed once a week. Results: IRS was successfully determined for 91 out of 108 patients. A total of 10 patients (11%) had normal IRS, 47 patients (52%) were categorized as radiosensitive, and 34 (37%) as highly radiosensitive. There was no significant difference in the manifestation of ARD between patient groups by skincare or IRS. According to logistic regression, patients with bigger breasts were prone to more severe ARD (p = 0.002). Conclusions: The additional skincare did not improve skin condition during RT. A total of 89% of patients had increased radiosensitivity. IRS determined before RT did not show the predictive value for the manifestation of ARD. Logistic regression revealed that breast volume was the most significant risk factor for the manifestation of ARD.

Technologies to reduce radiation toxicity in prostate cancer patients: spacers - a simple and effective solution

The basic principles of the treatment of prostate cancer patients have underwent significant revisions in recent years. Modern radiotherapy techniques, which have demonstrated high efficacy and safety in long-term randomized trials, are beginning to take a leading position in the treatment of prostate cancer in an overwhelming number of clinical scenarios (National Comprehensive Cancer Network, 2021). Despite the obvious successes of radiation oncology, a number of important problems remain unresolved, first of all - the need to reduce the rates of radiation complications. The topographical anatomy of the prostate gland determines the main profiles of post-radiation damage: rectal and genitourinary radiation toxicity. The previous five years have been marked by a significant intensification of research work abroad aimed at clinical testing of a number of biopolymer compositions and products for use as spacers between irradiated structures and normal tissues. The experience has made it possible for the first time to consider the possibility of using spacers in radiotherapy treatment of prostate cancer in the modern recommendations of the European Association of Urology (2021). The analysis of the national literature shows a complete lack of publications on the possibilities of optimizing the radiation treatment of prostate cancer through the use of specers. The purpose of this work was the need to highlight this important and perspective clinical problem.

Tolerance of Normal Rabbit Facial Bones and Teeth to Synchrotron X-Ray Microbeam Irradiation

Microbeam radiation therapy, an alternative radiosurgical treatment under preclinical investigation, aims to safely treat muzzle tumors in pet animals. This will require data on the largely unknown radiation toxicity of microbeam arrays for bones and teeth. To this end, the muzzle of six young adult New Zealand rabbits was irradiated by a lateral array of microplanar beamlets with peak entrance doses of 200, 330 or 500 Gy. The muzzles were examined 431 days postirradiation by computed microtomographic imaging (micro-CT) ex vivo, and extensive histopathology. The boundaries of the radiation field were identified histologically by microbeam tracks in cartilage and other tissues. There was no radionecrosis of facial bones in any rabbit. Conversely, normal incisor teeth exposed to peak entrance doses of 330 Gy or 500 Gy developed marked caries-like damage, whereas the incisors of the two rabbits exposed to 200 Gy remained unscathed. A single, unidirectional array of microbeams with a peak entrance dose ≤200 Gy (valley dose14 Gy) did not damage normal bone, teeth and soft tissues of the muzzle of normal rabbits longer than one year after irradiation. Because of that, Microbeam radiation therapy of muzzle tumors in pet animals is unlikely to cause sizeable damage to normal teeth, bone and soft tissues, if a single array as used here delivers a limited entrance dose of 200 Gy and a valley dose of ≤14 Gy.

Identification of Risk Loci for Radiotoxicity in Prostate Cancer by Comprehensive Genotyping of TGFB1 and TGFBR1

Genetic variability in transforming growth factor beta pathway (TGFB) was suggested to affect adverse events of radiotherapy. We investigated comprehensive variability in TGFB1 (gene coding for TGFβ1 ligand) and TGFBR1 (TGFβ receptor-1) in relation to radiotoxicity. Prostate cancer patients treated with primary radiotherapy (n = 240) were surveyed for acute and late toxicity. Germline polymorphisms (n = 40) selected to cover the common genetic variability in TGFB1 and TGFBR1 were analyzed in peripheral blood cells. Human lymphoblastoid cell lines (LCLs) were used to evaluate a possible impact of TGFB1 and TGFBR1 genetic polymorphisms to DNA repair capacity following single irradiation with 3 Gy. Upon adjustment for multiplicity testing, rs10512263 in TGFBR1 showed a statistically significant association with acute radiation toxicity. Carriers of the Cytosine (C)-variant allele (n = 35) featured a risk ratio of 2.17 (95%-CI 1.41–3.31) for acute toxicity ≥ °2 compared to Thymine/Thymine (TT)-wild type individuals (n = 205). Reduced DNA repair capacity in the presence of the C-allele of rs10512263 might be a mechanistic explanation as demonstrated in LCLs following irradiation. The risk for late radiotoxicity was increased by carrying at least two risk genotypes at three polymorphic sites, including Leu10Pro in TGFB1. Via comprehensive genotyping of TGFB1 and TGFBR1, promising biomarkers for radiotoxicity in prostate cancer were identified.

Does Gender Difference Effect Radiation-Induced Lung Toxicity? An Experimental Study by Genetic and Histopathological Predictors

Several studies have reported differences in radiation toxicity between the sexes, but these differences have not been tested with respect to histopathology and genes. This animal study aimed to show an association between histopathological findings of radiation-induced lung toxicity and the genes ATM, SOD2, TGF-β1, XRCC1, XRCC3 and HHR2. In all, 120 animals were randomly divided into 2 control groups (male and female) and experimental groups comprising fifteen rats stratified by sex, radiotherapy (0 Gy vs. 10 Gy), and time to sacrifice (6, 12, and 24 weeks postirradiation). Histopathological evaluations for lung injury, namely, intra-alveolar edema, alveolar neutrophils, intra-alveolar erythrocytes, activated macrophages, intra-alveolar fibrosis, hyaline arteriosclerosis, and collapse were performed under a light microscope using a grid system; the evaluations were semi quantitatively scored. Then, the alveolar wall thickness was measured. Real-time quantitative reverse transcription PCR (RT-qPCR) was used to determine gene expression differences in ATM, TGF-β1, XRCC1, XRCC3, SOD2 and HHR2L among the groups. Histopathological data showed that radiation-induced acute, subacute, and chronic lung toxicity were worse in male rats. The expression levels of the evaluated genes were significantly higher in females than males in the control group, but this difference was lost over time after radiotherapy. Less toxicity in females may be attributable to the fact that the expression of the evaluated genes was higher in normal lung tissue in females than in males and the changes in gene expression patterns in the postradiotherapy period played a protective role in females. Additional data related to pulmonary function, lung weights, imaging, or outcomes are needed to support this data that is based on histopathology alone.

Reasonable Timing of Radiotherapy for Stage IV Non-Small-Cell Lung Cancer During Targeted Therapy Based on Tumour Volume Change

PurposeThe aim of this study was to investigate the reasonable timing of radiotherapy for stage IV non-small-cell lung cancer (NSCLC) with EGFR-positive mutations during targeted therapy based on tumour volume change (TVC).Patients and MethodsSimulation Computed Tomography Scan (SCTS) measurements were taken to test TVC in patients with stage IV NSCLC during targeted therapy at intervals of 10 days. The SCTS measurement was terminated when the tumour volume shrinkage rate in the latter simulation compared with the previous simulation was ≤5% or when the time after treatment was 90 days. Then, primary tumour radiotherapy was performed. Related parameters of the radiotherapy plan were compared between the implementation and simulation plans.ResultsTwenty-seven patients were enrolled in the analysis. After treatment, shrinkage of the primary tumour was observed in all patients, but the rate and speed were inconsistent. The average tumour volume decreased obviously within 40 days and was significantly different every 10 days (P ≤ 0.001). The average volume decreased slowly and tended to be stable (P&gt;0.05) after 40 days. After the termination of SCTSs, 21 patients accepted primary tumour radiotherapy. No patients experienced grade 3+ acute radiation toxicity. The implementation radiotherapy plan was significantly better than that before treatment (all P&lt;0.05) but not better than that on the 40th day after treatment (all P&gt;0.05).ConclusionsTo obtain a high radiation dose and control radiation toxicity, the 40th day after targeted therapy may be a reasonable time to start radiotherapy for stage IV NSCLC with EGFR-positive mutations.Clinical Trial Registrationhttps://www.clinicaltrials.gov/ct2/show/NCT03258671, identifier, NCT03258671.