e13040 Background: Cancer stem-like cells (CSLCs) can resist certain chemotherapies, thereby causing relapse of the disease. Thus, development of a test that identifies the most effective chemotherapy management offers great promise for individualized anticancer treatments. Methods: We have developed ChemoID, an in vitro chemotherapy assay, designed to predict the sensitivity and resistance of a given patient’s CSLCs and bulk of tumor cells to a variety of chemotherapy agents. Results: A 5-month female (Patient A), and a 21-year old male (Patient B), both affected by anaplastic WHO grade 3 ependymoma were screened using the ChemoID assay. A range of concentrations flanking the clinical doses for vincristine, carboplatin, cyclophosphamide, etoposide, cisplatin, methotrexate, cytosine arabinoside, oxaliplatin, irinotecan, avastin, procarbazine, lomustine, and busulfan were tested. The CSLCs and bulk of tumor ependymoma cells of Patient A were found moderately sensitive (30% cell kill) to only cisplatin and procarbazine, both as single agents and in combination. Following 6 cycles of vincristine, carboplatin, cyclophosphamide, etoposide, and cisplatin in various combinations, Patient A rapidly progressed and proton beam therapy was recommended. The CSLCs and bulk of tumor ependymoma cells of Patient B were found highly sensitive (80% cell kill) to the combination of irinotecan and avastin, which resulted in 18 months free of disease progression. After recurrence, chemotherapies were tested in combination with benzyl-isothiocyanate (BITC), a bioactive natural food component contained in extracts from cruciferous vegetables. BITC greatly increased the chemosensitivity in Patient B to the combination of irinotecan and avastin, resulting in average 90% CSLCs and bulk of tumor ependymoma cell eradication. MRI scan of Patient B showed over 50% tumor regression after two months of treatment with a combination of irinotecan, avastin, and supplements containing BITC. Conclusions: Our findings suggest that no patients are alike in their chemotherapy response. ChemoID assay that measures cell death of CSLCs and bulk of tumor cells from patient biopsies to standard chemotherapy agents in vitro is a feasible approach to personalized anticancer treatments.

Background and Objectives: Photodynamic therapy (PDT) with porfimer sodium, FDA approved to treat premalignant lesions in Barrett's esophagus, causes photosensitivity for 6-8 weeks. HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a) shows minimal photosensitization of short duration and promising efficacy in preclinical studies. Here we explore toxicity and optimal drug and light dose with endoscopic HPPH-PDT. We also want to know the efficacy of one time treatment with HPPH-PDT.Study Design/Materials and Methods: Two nonrandomized dose escalation studies were performed (18 patients each) with biopsy-proven high grade dysplasia or early intramucosal adenocarcinoma of esophagus. HPPH doses ranged from 3 to 6 mg/m(2). At 24 or 48 hours after HPPH administration the lesions received one endoscopic exposure to 150, 175, or 200 J/cm of 665 nm light.Results: Most patients experienced mild to moderate chest pain requiring symptomatic treatment only. Six patients experienced grade 3 and 4 adverse events (16.6%). Three esophageal strictures were treated with dilatation. No clear pattern of dose dependence of toxicities emerged. In the drug dose ranging study (light dose of 150 J/cm at 48 hours), 3 and 4 mg/m(2) of HPPH emerged as most effective. In the light dose ranging study (3 or 4 mg/m(2) HPPH, light at 24 hours), complete response rates (disappearance of high grade dysplasia and early carcinoma) of 72% were achieved at 1 year, with all patients treated with 3 mg/m(2) HPPH plus 175 J/cm and 4 mg/m(2) HPPH plus 150 J/cm showing complete responses at 1 year.Conclusions: HPPH-PDT for precancerous lesions in Barrett's esophagus appears to be safe and showing promising efficacy. Further clinical studies are required to establish the use of HPPH-PDT. Lasers Surg. Med. 43: 705-712, 2011. (C) 2011 Wiley-Liss, Inc.

4161 Background: FDA approved PDT with porfimer sodium has been explored to treat lesions associated with Barrett's esophagus. Porfimer sodium PDT has the drawback of skin photosensitivity for 6-8 weeks. The photosensitizer HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a) showed minimal photosensitization of short duration and promising efficacy in preclinical studies. Here we explore toxicity and optimal drug and light dose with endoscopic HPPH-PDT. Methods: Two phase I/II nonrandomized dose escalation studies involving 36 patients with biopsy-proven High grade dysplasia, carcinoma in situ or early intramucosal adenocarcinoma of esophagus were performed between 2000 and 2004. The studies were approved by IRB. HPPH doses ranged from 3 to 6 mg/m2. At 24 to 48 hours after HPPH administration the lesion was exposed to 665 nm light for a light dose of 150, 175 or 200 J/cm from a cylindrical diffuser fiber. Endoscopy and 4-quadrant biopsies every 2 cm were done during the procedure and on follow-up at 2, 4 and 6 months, and every 6 months thereafter up to 5 years. Results: A total of 32 men and 4 women, age range 50-86 yrs, were treated. Most patients experienced mild to moderate chest pain requiring symptomatic treatment only. Ten expected serious adverse events, mainly related to respiratory and cardiac system, were treated uneventfully. Three esophageal strictures were treated with dilatation. No clear pattern of dose dependence of toxicities emerged. In the first dose ranging study with 18 patients 3 and 4 mg/m2 of HPPH showed initial complete responses, while HPPH doses of 5 and 6 mg/m2 achieved no complete responses. In the second dose ranging study of 18 patients with HPPH doses of 3 and 4 mg/m2 and light doses of 150, 175 and 200 J/cm achieved an initial complete response rate (best response) of 72.22%, with 100% initial complete responses with the combinations of 3 mg/m2-175 J/cm and 4 mg/m2-150 J/cm. Conclusions: We established that 3 or 4 mg/m2 HPPH with 150 or 175 J/cm appears to be effective. The best initial response results are comparable to published results of porfimer sodium-PDT. No significant financial relationships to disclose.

In this book you will find chapters describing the most up-to-date information concerning the important clinical applications and methodology of photodynamic therapy. This introduction will provide some background on general mechanisms, cellular targets, and note a few significant new findings relevant to photodynamic action in clinical practice. A short description of the development of photodynamic therapy at Roswell Park Cancer Institute is included.