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.

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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.

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.

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