The Predictive Value of 8-Hydroxy-Deoxyguanosine (8-OHdG) Serum Concentrations in Irradiated Non-Small Cell Lung Carcinoma (NSCLC) Patients.

Ionizing radiation is strongly linked to direct or indirect DNA damage, as with the production of reactive oxygen species (ROS), which in turn produce DNA damage products, such as 8-hydroxy-2-deoxyguanosine (8-OHdG). In this study, we aimed to investigate the formation of 8-OHdG after irradiation in patients with non-small cell cancer (NSCLC) and its use as a biomarker. Sixteen patients with squamous and thirty-six patients with non-squamous pathology were included. An enzyme-linked-immunosorbent assay (ELISA) was performed before and after radiation. A dose-dependent relationship was confirmed: 8-OHdG plasma concentrations, increased in the total of NSCLC patients and specifically with a linear correlation in non-squamous pathology; in squamous histology, after an initial increase, a significant decrease followed after 20 Gy dose of irradiation. The pretreatment total irradiated tumor volume (cm3) was positively correlated with 8-OHdG levels in patients with squamous histology. When plotting the 8-OHdG plasma concentration at a 10 Gy irradiation dose to the baseline, the AUC was 0.873 (95% CI 0.614-0.984), p < 0.0001, with an associated criterion value of >1378 as a cutoff (sensitivity 72.7%, specificity 100%). When normalizing this ratio to BSA, the associated criterion cutoff value was >708 (sensitivity of 100%, specificity 80%). Lastly, 8-OHdG levels were closely related with the development of radiation-induced toxicities.

8-Hydroxy-2'-Deoxyguanosine and 8-Nitroguanine Production and Detection in Blood Serum of Breast Cancer Patients in Response to Postoperative Complementary External Ionizing Irradiation of Normal Tissues.

It is widely known that ionizing irradiation is strongly linked to the production of reactive oxygen (ROS) and nitrative species (RNS) through which DNA damage products like 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-nitroguanine (8-NG) are generated, respectively. In the present study, we aimed to investigate the formation of 8-OHdG and 8-NG upon irradiation and to further explore whether alterations in their concentration levels are related to the administered radiation doses and exposure time. Our research work was conducted in blood serum samples collected from 33 breast cancer patients who received adjuvant radiotherapy. The detection of 8-OHdG and 8-NG was assessed by enzyme-linked immunosorbent assay. Our results suggest that both, 8-OHdG and 8-NG, were formed during the radiation regimen. Significant correlations with radiation dose were also demonstrated by the dose-response curves of 8-OHdG and 8-NG, fitted by logarithmic distribution and polynomial regression, respectively. More precisely, 8-OHdG and 8-NG concentrations (ng/mL) were considerably increased when patients received ionizing radiation up to 30 Gy whereas irradiation over 30 Gy did not induce any further increases. The current study supports a) the production of 8-OHdG and 8-NG during radiotherapy and b) significant correlations between either 8-OHdG or 8-NG levels and radiation doses, indicating a radiation-dose-dependent relationship.

Evidence for Efficacy of Treatment With the Anti-PD-1 Mab Nivolumab in Radiation and Multichemorefractory Advanced Penile Squamous Cell Carcinoma.

Penile squamous cell carcinoma (PeSCC) is a rare tumor and advanced PeSCC is associated with poor survival due to the aggressiveness of the disease and lack of effective systemic therapies. We describe for the first time a case with advanced chemoradiation refractory PeSCC who had documented response to active immunotherapy with the immune checkpoint inhibitor, anti-programmed death-1 monoclonal antibody Nivolumab. The patient suffered from a poor prognosis human papillomavirus-negative PeSCC, with a somatic inactivation mutation of cyclin-dependent kinase inhibitor 2A (CDKN2A) gene in tumor cells, and treatment with Nivolumab resulted in a partial response to therapy and significant tumor shrinkage. Histology transitions and alterations in tumor-infiltrating cytotoxic CD8 T-cell lymphocytes, programmed death ligand-1 expression on tumor cells and immune cells in tumor lesion biopsies pretreatment and posttreatment with Nivolumab were observed and described. In conclusion, in patients with metastatic PeSCC active immunotherapy combinations with an anti-programmed death-1/programmed death ligand-1 agent may be beneficial and further relative clinical studies are required.

Local recurrence of pancreatic cancer after primary surgical intervention: how to deal with this devastating scenario?

The dismal prognosis of pancreatic cancer reflects into the increased recurrence rate, even after R0 pancreaticoduodenectomy. Although, conventional radiation-, chemo- or surgical therapy in much selected cases, seem to work out favorably long term, less invasive and non-toxic methods with more immediate results are always preferred, concerning the already aggravated status of this group of patients. We present hereby a comprehensive review of the literature concerning the treatment of recurrent pancreatic cancer based on the case of a patient who 20 months after a pancreaticoduodenectomy developed portal hypertension and symptomatic first degree esophageal, gastric and mesenteric varices, caused by the nearly complete splenic vein obstruction at the portal vein confluence. The varices were revascularized by a percutaneous transhepatic placement of an endovascular stent into the splenic vein, along with a sequent stereotactic body radiation therapy for the local tumor control. Thanks to the accuracy and safety of the present combined treatment, the patient one year later presents control of the disease and its complications. Our paper is the first in the international literature that tries to review all the treatment modalities available (surgical, adjuvant, neoadjuvant and palliative therapy) and their efficacy, concerning the locally recurrent pancreatic cancer; furthermore, we tried to analyze the application of the above mentioned combined therapeutic approach in similar cases, elucidating simultaneously all the questions that arise. The limited existing data in the international literature and the lack of randomized controlled trials make this effort difficult, but the physician should be aware after all of all the available and innovative treatment modalities, before he chooses one. Finally, we would like to emphasize the fact that not only the local control but also the management of the complications are important for a prolonged median survival and a better quality of life after all.