Tumorigenic Responses of Cancer-Associated Stromal Fibroblasts after Ablative Radiotherapy: A Transcriptome-Profiling Study

Cancer-associated fibroblasts (CAFs) are key elements in the progression of cancer and thereby represent important targets for cancer therapies. Increased attention has been given to ablative radiotherapy in the clinics. Therefore, in this study we have aimed at identifying the transcriptional responses occurring in primary CAFs exposed to high-dose irradiation. Established primary CAFs obtained from non-small-cell lung cancer (NSCLC) patient material were irradiated with a single dose of 18 Gy and total RNA was isolated 24 hrs after treatment. Radiation-induced transcriptional alterations were investigated by gene expression analysis using genome-wide microarrays. Obtained results were verified by qRT-PCR of relevant genes. Confirmation of gene expression outcomes was achieved by diverse functional and expression assays including DNA damage response, measurements of reactive oxygen species (ROS) by flow cytometry and senescence-associated β-galactosidase. Irradiation resulted in differential expression of 680 genes of which 557 were up- and 127 down-regulated. Of those, 153 genes were differentially expressed with a fold-change greater than 1.0 and an adjusted p-value less than 0.05 across different comparisons (non-irradiated vs. irradiated). Expression patterns revealed profound changes in biological functions and processes involved in DNA repair, apoptosis, p53 pathway, autophagy, senescence, ROS production and immune response. CAFs display pro- and anti-tumorigenic effects after having received a single high-dose radiation. The measured effects will have an impact on the tumor microenvironment in respect to tumor growth and metastasis.

Stereotactic body radiotherapy in pancreatic adenocarcinoma

Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue.This review aimed at the SBRT application in the treatment of pancreatic cancer.Data sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to December 2022.Keywords used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were included.All articles were assessed for validity and relevant content.Results:Optimal doses and fractionation have not yet been defined.However,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to CRT.Furthermore,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic adenocarcinoma.Conclusions:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease control.SBRT opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.

Precision radiotherapy for brain tumors A 10-year bibliometric analysis

OBJECTIVE： Precision radiotherapy plays an important role in the management of brain tumors. This study aimed to identify global research trends in precision radiotherapy for brain tumors using a bibliometric analysis of the Web of Science. DATA RETRIEVAL： We performed a bibliometric analysis of data retrievals for precision radiotherapy for brain tumors containing the key words cerebral tumor, brain tumor, intensity-modulated radiotherapy, stereotactic body radiation therapy, stereotactic ablative radiotherapy, imaging-guided radiotherapy, dose-guided radiotherapy, stereotactic brachytherapy, and stereotactic radiotherapy using the Web of Science. SELECTION CRITERIA： Inclusion criteria： （a） peer-reviewed articles on precision radiotherapy for brain tumors which were published and indexed in the Web of Science; （b） type of articles： original research articles and reviews; （c） year of publication： 2002-2011. Exclusion criteria： （a） articles that required manual searching or telephone access; （b） Corrected papers or book chapters. MAIN OUTCOME MEASURES： （1） Annual publication output; （2） distribution according to country; （3） distribution according to institution; （4） top cited publications; （5） distribution according to journals; and （6） comparison of study results on precision radiotherapy for brain tumors. RESULTS： The stereotactic radiotherapy, intensity-modulated radiotherapy, and imaging-guided radiotherapy are three major methods of precision radiotherapy for brain tumors. There were 260 research articles addressing precision radiotherapy for brain tumors found within the Web of Science. The USA published the most papers on precision radiotherapy for brain tumors, followed by Germany and France. European Synchrotron Radiation Facility, German Cancer Research Center and Heidelberg University were the most prolific research institutes for publications on precision radiotherapy for brain tumors. Among the top 13 research institutes publishing in this field, seven are in the USA, three are in Germany, two are in France, and there is one institute in India. Research interests including urology and nephrology, clinical neurology, as well as rehabilitation are involved in precision radiotherapy for brain tumors studies. CONCLUSION： Precision radiotherapy for brain tumors remains a highly active area of research and development.

Stereotactic radiotherapy for intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma(iCCA)is an aggressive malignancy with an increasing incidence worldwide and poor prognosis,despite several advances and continuous efforts to develop effective treatments.Complete surgical resection is the mainstay of treatment and offers a potentially curative option,but is only possible in less than a third of patients,owing to advanced disease.Chemotherapy is a well-established treatment in the adjuvant and palliative setting,however,confers limited benefit.Conventional radiotherapy is challenging due to local toxicity.With recent advances in stereotactic ablative radiotherapy(SABR),it is now possible to focus ablative beams of radiotherapy precisely aimed at tumours to minimise damage to surrounding viscera.This review details the history,technical background and application of SABR to iCCA,with directions for future research suggested.

Radiotherapy of Oligoprogressive Lesions in Castration-Resistant Prostate Cancer: Impact on Second-Generation Hormone Therapy

Background: The therapeutic standard for oligoprogressive prostate cancer resistant to castration is second-generation hormone therapy. This systemic treatment is expensive. There are oligoprogressive lesions accessible to radiotherapy. Objectives: To study the impact of radiotherapy of oligoprogressive lesions on the implementation of second generation hormone therapy. Patients and Methods: A retrospective study from 2012 to 2020 was carried out. All patients with oligoprogressive prostate cancer who had received radiotherapy on one or more lesions in progression were collated. Survival was calculated using the Kaplan-Meier method. Results: 8 patients were treated with stereotactic and conformational radiotherapy between August 2012 and August 2020 in the context of oligoprogressive prostate cancer resistant to castration. The median age at diagnosis of oligoprogression was 73 years with a median PSA level of 3.11 ng/ml. Nine lesions were diagnosed with PET scan PSMA. All the lesions were treated by radiotherapy with different regimens. After a median follow-up of 12.5 months, 7 patients showed a biochemical response to treatment with a median decrease in PSA of 67%. The median survival without clinical or biochemical progression was 7 months. The median survival without the need for further systemic treatment was 9 months. During the follow-up period, six patients received second-generation hormone therapy to treat their relapse, and the other two showed no clinical or biochemical relapse. Conclusion: Radiotherapy may be an alternative to delay the introduction of difficult-to-access second-generation hormone therapy in developing countries. A prospective study could validate this therapeutic approach.

Single-fraction stereotactic ablative body radiation therapy for primary and metastasic lung tumor:A new paradigm?

Stereotactic ablative body radiotherapy(SABR)is an effective technique comparable to surgery in terms of local control and efficacy in early stages of non-small cell lung cancer(NSCLC)and pulmonary metastasis.Several fractionation schemes have proven to be safe and effective,including the single fraction(SF)scheme.SF is an option costeffectiveness,more convenience and comfortable for the patient and flexible in terms of its management combined with systemic treatments.The outbreak of the severe acute respiratory syndrome coronavirus 2 pandemic has driven this not new but underutilized paradigm,recommending this option to minimize patients’visits to hospital.SF SABR already has a long experience,strong evidence and sufficient maturity to reliably evaluate outcomes in peripheral primary NSCLC and there are promising outcomes in pulmonary metastases,making it a valid treatment option;although its use in central locations,synchronous and recurrencies tumors requires more prospective safety and efficacy studies.The SABR radiobiology study,together with the combination with systemic therapies,(targeted therapies and immunotherapy)is a direction of research in both advanced disease and early stages whose future includes SF.