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.

Integration of functional MRI and white matter tractography in stereotactic radiosurgery clinical practice.

PURPOSE: To study the efficacy of the integration of functional magnetic resonance imaging (fMRI) and diffusion tensor imaging tractography data into stereotactic radiosurgery clinical practice. METHODS AND MATERIALS: fMRI and tractography data sets were acquired and fused with corresponding anatomical MR and computed tomography images of patients with arteriovenous malformation (AVM), astrocytoma, brain metastasis, or hemangioma and referred for stereotactic radiosurgery. The acquired data sets were imported into a CyberKnife stereotactic radiosurgery system and used to delineate the target, organs at risk, and nearby functional structures and fiber tracts. Treatment plans with and without the incorporation of the functional structures and the fiber tracts into the optimization process were developed and compared. RESULTS: The nearby functional structures and fiber tracts could receive doses of >50% of the maximum dose if they were excluded from the planning process. In the AVM case, the doses received by the Broadmann-17 structure and the optic tract were reduced to 700 cGy from 1,400 cGy and to 1,200 cGy from 2,000 cGy, respectively, upon inclusion into the optimization process. In the metastasis case, the motor cortex received 850 cGy instead of 1,400 cGy; and in the hemangioma case, the pyramidal tracts received 780 cGy instead of 990 cGy. In the astrocytoma case, the dose to the motor cortex bordering the lesion was reduced to 1,900 cGy from 2,100 cGy, and therefore, the biologically equivalent dose in three fractions was delivered instead. CONCLUSIONS: Functional structures and fiber tracts could receive high doses if they were not considered during treatment planning. With the aid of fMRI and tractography images, they can be delineated and spared.

CT-guided fiducial placement for cyberknife stereotactic radiosurgery: an initial experience.

CyberKnife frameless image-guided radiosurgery has become a widely used system for parenchymal extracranial lesions. Gold fiducials are required for the planning and aiming of CyberKnife therapy. We report our initial experience and describe the technique of positioning tumor markers, under CT guidance. We conducted a retrospective review of 105 patients who were referred for CyberKnife stereotactic radiosurgery at Iatropolis CyberKnife Center in Athens. All patients underwent percutaneous fiducial placement via CT guidance. At the desired location, the 18-G needle was advanced into or near the tumor. Data collected included number and locations of fiducials placed and complications experienced to date. One hundred five patients underwent fiducial placement under CT guidance and a total number of 319 gold seeds were implanted. We experienced one episode of pneumothorax that required drainage, one mild pneumothorax, and three episodes of perifocal pulmonary hemorrhage. In conclusion, fiducial implantation under CT guidance appears to be a safe and efficient procedure, as long as it is performed by an experienced interventional radiologist.

Updated results of a phase I trial of motexafin lutetium-mediated interstitial photodynamic therapy in patients with locally recurrent prostate cancer.

Locally recurrent prostate cancer after treatment with radiation therapy is a clinical problem with few acceptable treatments. One potential treatment, photodynamic therapy (PDT), is a modality that uses laser light, drug photosensitizer, and oxygen to kill tumor cells through direct cellular cytotoxicity and/or through destruction of tumor vasculature. A Phase I trial of interstitial PDT with the photosensitizer Motexafin lutetium was initiated in men with locally recurrent prostate cancer. In this ongoing trial, the primary objective is to determine the maximally tolerated dose of Motexafin lutetium-mediated PDT. Other objectives include evaluation of Motexafin lutetium uptake from prostate tissue using a spectrofluorometric assay and evaluation of optical properties in the human prostate. Fifteen men with biopsy-proven locally recurrent prostate cancer and no evidence of distant metastatic disease have been enrolled and 14 have been treated. Treatment plans were developed using transrectal ultrasound images. The PDT dose was escalated by increasing the Motexafin lutetium dose, increasing the 732 ran light dose, and decreasing the drug-light interval. Motexafin lutetium doses ranged from 0.5 to 2 mg/kg administered IV 24, 6, or 3 hr prior to 732 ran light delivery. The light dose, measured in real time with in situ spherical detectors was 25-100 J/cm2. Light was delivered via optical fibers inserted through a transperineal brachytherapy template in the operating room. Optical property measurements were made before and after light therapy. Prostate biopsies were obtained before and after light delivery for spectrofluorometric measurements of photosensitizer uptake. Fourteen patients have completed protocol treatment on eight dose levels without dose-limiting toxicity. Grade I genitourinary symptoms that are PDT related have been observed. One patient had Grade II urinary urgency that was urinary catheter related. No rectal or other gastrointestinal PDT-related tox-icities have been observed to date. Measurements of Motexafin lutetium demonstrated the presence of photosensitizer in prostate tissue from all patients. Optical property measurements demonstrated substantial heterogeneity in the optical properties of the human prostate gland which supports the use of individualized treatment planning for prostate PDT.