Efficient combination of radiotherapy and CAR-T - A systematic review.

Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking immunotherapy. However, it faces formidable challenges in treating solid tumors, grappling with issues like poor trafficking, limited penetration, and insufficient persistence within the tumor microenvironment (TME). CAR-T cells are engineered to express receptors that target specific cancer antigens, enhancing their ability to recognize and eliminate cancer cells. This review paper explores the intricate interplay between CAR-T therapy and radiotherapy (RT), investigating their synergistic potential. Radiotherapy, a standard cancer treatment, involves using high doses of radiation to target and damage cancer cells, disrupting their ability to grow and divide. We highlight that RT modulates the TME, augments antigen presentation, and promotes immune cell infiltration, bolstering CAR-T cell-mediated tumor eradication. Molecular insights shed light on RT-induced alterations in tumor stroma, T cell recruitment promotion, and induction of immunogenic cell death. Noteworthy, strategies, such as combining hypofractionated radiotherapy with myeloid-derived suppressor cell blockade, underscore innovative approaches to enhance CAR-T cell therapy in solid tumors. Bridging indications for RT and CAR-T cells in hematological malignancies are discussed, emphasizing scenarios where RT strategically enhances CAR-T cell efficacy. The paper critically evaluates the RT as a bridge compared to traditional chemotherapy, highlighting timing and dosage considerations crucial for optimizing CAR-T therapy outcomes. In summary, the paper provides valuable insights into the intricate molecular mechanisms activated by RT and innovative strategies to improve CAR-T cell therapy, fostering a deeper understanding of their combined potential in cancer treatment.

The pilot project of the National Cancer Network in Poland: Assessment of the functioning of the National Cancer Network and results from quality indicators for lung cancer (2019-2021).

BACKGROUND: This analysis presents the outcomes of the operations of the National Cancer Network (NCN) pilot project in Lower Silesian Voivodeship, Poland, for lung cancer for the period of 2019-2021. The results concerning measures of the quality of medical processes were analysed. METHODS: Twenty-one measures used to gauge the quality of oncological care for lung cancer were assessed. Data collection and processing for the purpose of calculating the measures were carried out as part of the NCN pilot project based on the Regulation of the Ministry of Health enacted on 13 December 2018. The measures were calculated at the Voivodeship Coordination Center, and the data were derived from the centres included in the network in the area of the analysed voivodeship. RESULTS: A total of 3,638 patients diagnosed with lung cancer were enrolled in the NCN pilot program during the analysed period. For 3 measures, out of 21, target values were obtained. For 2 measures, the values differed significantly from the assumed target value. CONCLUSION: In our opinion, the NCN pilot study, as a test of the network's functioning, meets the assumed goal. The NCN assessment is based on, inter alia, analysis of the outcomes of oncological quality of care measures for lung cancer, and facilitates monitoring of the quality of medical services provided and the identification of areas for improvement. In addition, the pilot program, which will last until the end of 2022, will allow for further in-depth analysis regarding the network's limitations before implementing the system on a national scale in Poland. This will be the subject of further investigation.

Analysis of lung cancer measures of the National Cancer Network pilot study in Poland for potential improvement in the quality of advanced-stage lung cancer therapy.

BACKGROUND: This study aimed to present the performance of the National Cancer Network's (NCN) pilot program in the Lower Silesian Voivodeship (southwestern province of Poland with a population of 2,9 million in 2019), to analyse measures describing lung cancer patients and to determine whether those measures can be used to improve the treatment outcomes of stage III and IV patients with lung cancer in Poland. METHODS: Three measures of the NCN pilot programme were analysed: "Percentage of patients with genetic and molecular testing for predictive factors", "Assessment of the completeness of a pathological examination", and "Percentage of stage III and IV cancer patients". As many as 2,218 patients with ICD-10-CM Diagnosis Code C34 were included in the NCN pilot program from 1 to 2019 to 31 December 2020, in the Lower Silesian Voivodeship. The scores of each measure were calculated quarterly by the Regional Coordinating Centre, Wroclaw Comprehensive Cancer Center, Wroclaw, Poland. RESULTS: Genetic and molecular testing among stage III and IV patients was performed in only 40% and 60% of patients, respectively. The incompleteness of histopathological examinations did not exceed 0.5%. Stage III and stage IV patients accounted for 37% and 35% of the analysed patients, respectively. CONCLUSIONS: The NCN pilot program measures presented in this study appear to be highly sensitive, simple, and transparent tools to monitor the quality of lung cancer diagnosis and assess clinical staging in patients within a specific region. An increase in the proportion of stage III and IV patients who will undergo genetic and molecular testing in the era of modern drug therapies should result in improved treatment outcomes in this patient group. In the present analysis, the values of the main analysed measure, which evaluates the number of genetic and molecular tests for predictive factors for lung cancer, were subject to significant fluctuations during the pilot project. Both upwards and downwards trends were observed. Further analysis in the future is warranted to eliminate the unfavourable factors influencing the obtained values of the measure.

Radiotherapy in the Management of Pediatric and Adult Osteosarcomas: A Multi-Institutional Cohort Analysis.

BACKGROUND: Due to the rarity of osteosarcoma and limited indications for radiotherapy (RT), data on RT for this tumor are scarce. This study aimed to investigate the utilization of RT for osteosarcomas in the recent 20 years and to identify factors related to patients' response to radiation. METHODS: We performed a retrospective analysis of patients irradiated for osteosarcoma treatment. We planned to assess differences in the utilization of RT between the periods of 2000-2010 and 2011-2020, identify the risk factors associated with local progression (LP), determine whether RT-related parameters are associated with LP, and calculate patients' survival. RESULTS: A total of 126 patients with osteosarcoma who received 181 RT treatments were identified. We found a difference in RT techniques between RT performed in the years 2000-2010 and that performed in the years 2011-2020. LP was observed after 37 (20.4%) RT treatments. Intent of RT, distant metastases, and concomitant systemic treatment affected the risk of LP. Five-year overall survival was 33% (95% confidence interval (26%-43%)). CONCLUSIONS: RT for osteosarcoma treatment has evolved from simple two-dimensional palliative irradiation into more conformal RT applied for new indications including oligometastatic and oligoprogressive disease. RT may be a valuable treatment modality for selected patients with osteosarcoma.

Dosimetric comparison of conformal technique (3D) with volumetric modulated arc therapy with respect to doses obtained in the temporal lobe area in patients irradiated for brain meningioma.

AIM: The aim of the analysis was to compare doses obtained for temporal lobes in patients being irradiated for meningiomas of the brain using the conformal technique and volumetric modulated arc therapy (VMAT). We try to answer the question whether the application of VMAT would lead to higher doses within temporal lobes. BACKGROUND: In recent years a significant increase in the detection of meningiomas and effectiveness of treatment has been observed. Hence quality of life should be considered as an important aspect after a treatment course. MATERIALS AND METHODS: Treatment plans of 27 patients were evaluated retrospectively. Radiotherapy procedures were carried out from 2007 until 2016 at the Department of Radiation Oncology in Wroclaw, Poland. For individual patients, alternative treatment plans were generated in relation to the ones originally used, wherein from dynamic techniques, volumetric modulated arc therapy was selected for analysis. Evaluated dosimetric parameters for temporal lobes were: mean dose, V10 Gy, V20 Gy, V45 Gy. RESULTS: Statistically significant differences were observed for V45 Gy for both temporal lobes (p = 0.023) and for V45 Gy for the right (p = 0.001) and the left temporal lobe (p = 0.016) considered for VMAT. The mean values of the V45 Gy for both temporal lobes, for the right temporal lobe and for the left temporal lobe were lower for VMAT than for 3D, respectively: 7.54% and 7.90%, 6.82% and 9.47%, 5.67% and 7.14%.Analysis of the remaining results found no statistical differences. CONCLUSION: Application of VMAT in patients treated for meningioma of the brain is not related to higher doses of radiation in the temporal lobe area, compared with the conformal technique.

Tolerance of combined radiochemotherapy in cervical cancer patients.

BACKGROUND: Radiochemotherapy in cervical cancer was implemented to clinical practice based on 5 randomized clinical trials, published at the end of the 20th century, which showed improvement in the total and symptomless survivals by about 10-18%. The increase of therapeutic index of such treatment can take place only when the efficiency of the treatment outweighs the increase of its toxicity. Thus, it is necessary to monitor treatment reaction during radiochemotherapy. OBJECTIVES: The aim of this study was to assess the acute post-radiation reaction during radiochemotherapy for cervical cancer and the to analyze the reasons of the unplanned course of combined treatment. MATERIAL AND METHODS: A group of consecutive 176 cervical cancer patients in the clinical stage from IB to IIIB acc. to FIGO classification who underwent radiochemotherapy were taken under prospective observation in Clinical Gynecologic Radiotherapy Ward of the Lower Silesian Cancer Center in Wroclaw between April 2010 and September 2012. Early post-radiation reaction was assessed in RTOG/EORTC scale once a week. RESULTS: During the treatment early post-radiation reaction of upper part of alimentary duct was observed in 74.4% of the patients, the reaction of lower part of gastrointestinal tract in 51.2%, and in bladder 44.8%. The most frequent symptoms of post-radiation reaction are: nausea (73.3% of the patients), diarrhea (51.2%) and vomiting (20.9%). Leucopenia was observed in 97.1% of the patients, granulocytopenia in 70.4%, anemia in 69.2%, and thrombocytopenia in 25.5%. The planned dose of radiotherapy was administered completely in 90.1% of the patients. A break in radiotherapy was necessary in 15.7% of the patients. In total, 44.8% of the patients did not receive radiochemotherapy according to the plan, because of the side effects of the treatment (most often leucopenia, thrombocytopenia and gastrointestinal reaction). CONCLUSIONS: The presented data shows that radiochemotherapy causes the intensification of acute side effects of treatment and may cause unplanned course of treatment and prolongation of the total treatment time.