INtraoperative photoDYnamic Therapy for GliOblastomas (INDYGO): Study Protocol for a Phase I Clinical Trial.

BACKGROUND: Glioblastoma (GBM) is characterized by marked proliferation, major infiltration, and poor prognosis. Despite current treatments, including surgery, radiation oncology, and chemotherapy, the overall median survival is 15 mo and the progression-free survival is 7 to 8 mo. Because of systematic relapse of the tumor, the improvement of local control remains an issue. In this context, photodynamic therapy (PDT) may offer a new treatment modality for GBM. OBJECTIVE: To assess the feasibility of intraoperative PDT early after surgical resection of GBM without unacceptable and unexpected toxicities. METHODS: The INDYGO clinical trial (INtraoperative photoDYnamic Therapy for GliOblastomas) treatment will be carried out in addition to the current standard of care (SOC) of glioblastoma: maximum resection surgery followed by concomitant radio-chemotherapy and adjuvant chemotherapy. PDT treatment will be delivered during surgery early, after the fluorescence-guided resection. Immunological responses and biomarkers will also be investigated during the follow-up. A total of 10 patients will be recruited during this study. EXPECTED OUTCOMES: Clinical follow-up after the SOC with PDT is expected to be similar (no significant difference) to the SOC alone. DISCUSSION: This INDYGO trial assesses the feasibility of intraoperative 5-aminolevulinic acid PDT, a novel seamless approach to treat GBM. The technology is easily embeddable within the reference treatment at a low-incremental cost. The safety of this new treatment modality is a preliminary requirement before a multicenter randomized clinical trial can be further conducted to assess local control improvement by treating infiltrating and nonresected GBM cells.

Comparison of different treatment schemes in 5-ALA interstitial photodynamic therapy for high-grade glioma in a preclinical model: An MRI study.

BACKGROUND: There is currently no therapy that prevents high-grade glioma recurrence. Thus, these primary brain tumors have unfavorable outcomes. Recently, 5-ALA photodynamic therapy (PDT) has been proposed to delay relapse and is highly expected to have potential synergistic effects with the current standard of care. However, PDT treatment delivery needs to be optimized by evaluating the impact of both the number of fractions and the light power used. OBJECTIVES: Previous studies have reported MRI examination-based outcomes for PDT in glioblastoma. Our study aimed to compare MRI markers across different treatment schemes that use interstitial PDT in high-grade glioma in a preclinical model. MATERIALS AND METHODS: Forty-eight "nude" rats were grafted with human U87 cells into the right putamen and subsequently submitted to interstitial PDT. The rats were randomized into six groups, including two different sham groups and four different treated groups (5 fractions at 5 mW or 30 mW and 2 fractions at 5 mW or 30 mW). After photosensitizer (PS) precursor (5-ALA) intake, an optical fiber was introduced into the tumor. Treatment effects were assessed with early high-field MRI to acquire T1 and T2 diffusion and perfusion images. RESULTS: There was no difference in the variation of the diffusion coefficient among the six groups (p = 0.0549, Kruskal-Wallis test). However, a significant difference was identified among the six groups in terms of variation in perfusion (p = 0.048, Kruskal-Wallis test), supporting a lesional effect in the treated groups. Additionally, the sham groups had significantly smaller edema volumes than were observed in the treated groups. Moreover, the 5-fraction group treated with 30 mW was associated with edema volumes that were significantly greater than those in the 5-fraction group treated with 5 mW (p = 0.019). CONCLUSION: Based on observations of MRI data and considering treatment effects, the 5-fraction group treated at 5 mW was not significantly different from the other treated groups in terms of cell deaths, characterized by diffusion imaging, or necrosis level. However, the significantly lower level of edema observed in this group indicated that this treatment scheme had limited toxicity.

Evaluation of the Relevance of Surgery in Patients with Multiple Myeloma Harboring Symptomatic Spinal Involvement: A Retrospective Case Series.

BACKGROUND: Multiple myeloma spinal involvement can lead to bone fractures and neurologic impairment that can severely alter quality of life. The role of surgery is controversial, given its high morbidity, and the lack of evidence. We hereby aim to evaluate efficacy and safety of surgery in the management of symptomatic spinal lesions in patients with multiple myeloma. METHODS: We included all patients operated on for a myeloma-related spinal lesion in our institution between 2007 and 2015. Demographic, clinical, and surgical data were collected as well as hematologic profiles. We retrospectively assessed the surgical success of the procedures, if at 3 months the patient fulfilled the following 4 criteria: pain relief, ability to walk, spinal stability, and no relevant morbidity. RESULTS: Thirty-six men and 19 women, with a median age of 62 years, were included. Seventeen patients underwent an emergency intervention, whereas 38 patients underwent elective surgery. At 3 months, 88.2% and 96.1%, respectively, of patients experienced pain relief and were able to walk. Spinal stability was considered satisfactory for 94.1% of patients. We reported 8 major complications in 8 patients. Altogether, 34 patients (61.8%) fulfilled all criteria for surgical success. An International Staging System score of 1 and the absence of previous chemotherapy were significantly associated with surgical success. CONCLUSIONS: Management of myeloma-related spine lesions requires a multidisciplinary approach. Surgery rapidly provides both decompression and stabilization. Using a strict patient-specific evaluation, we reported rewarding functional results, with acceptable morbidity. Surgery for multiple myeloma vertebral lesions seems to be a valuable option for carefully selected patients.

Reappearance of arteriovenous malformations after complete resection of ruptured arteriovenous malformations: true recurrence or false-negative early postoperative imaging result?

OBJECTIVE Ruptured arteriovenous malformations (AVMs) are often obliterated after emergency microsurgical treatment. However, some studies have reported AVM recurrence after the obliteration of ruptured AVMs. The authors report their experience with AVM recurrence after successful microsurgical treatment of ruptured AVMs. METHODS The authors reviewed the medical data of 139 consecutive patients who underwent microsurgery at the authors' institution for ruptured AVM between 2002 and 2012. Each patient underwent a conventional cerebral angiography examination immediately after the surgery. Subsequent follow-ups were performed with MR angiography after 6 months, and, if there was no indication of AVM recurrence, patients were followed up with conventional cerebral angiography between 1 and 2 years after the treatment; pediatric patients were followed up until age 18 years. Recurrence was defined as new radiological evidence of an AVM at the site of a ruptured AVM or a new hemorrhage in patients with angiographically documented AVM obliteration on postoperative angiograms. RESULTS The mean age of the patients at the time of ruptured AVM diagnosis was 30.8 years (SD ± 5, range 4-69 years), and 44 of the patients were younger than 18 years (the mean age at diagnosis in this pediatric subgroup was 11.4 years [range 4-17.9 years]). Complete AVM obliteration after the initial microsurgery was observed in 123 patients (89.5%). Reappearance of an AVM was noted in 7 patients between 12 and 42 months after the treatment, and all of these patients were younger than 18 years. The recurrent AVM was located in an eloquent zone in 4 patients, and deep venous drainage was noted in 3 patients. Radiosurgery was performed in 6 of these patients, and 1 patient underwent another microsurgical procedure. The authors noted only one rebleeding due to an AVM recurrence during the latency period after radiosurgery. CONCLUSIONS The recurrence of an AVM is fairly rare and affects mostly pediatric patients. Therefore, especially in children, long-term angiographic follow-up is required to detect AVM recurrence or an AVM remnant. The authors stress the need for discussion involving a multidisciplinary neurosurgical team to decide on treatment in cases of any AVM recurrence or remnant.

Stacking denoising auto-encoders in a deep network to segment the brainstem on MRI in brain cancer patients: A clinical study.

Delineation of organs at risk (OARs) is a crucial step in surgical and treatment planning in brain cancer, where precise OARs volume delineation is required. However, this task is still often manually performed, which is time-consuming and prone to observer variability. To tackle these issues a deep learning approach based on stacking denoising auto-encoders has been proposed to segment the brainstem on magnetic resonance images in brain cancer context. Additionally to classical features used in machine learning to segment brain structures, two new features are suggested. Four experts participated in this study by segmenting the brainstem on 9 patients who underwent radiosurgery. Analysis of variance on shape and volume similarity metrics indicated that there were significant differences (p<0.05) between the groups of manual annotations and automatic segmentations. Experimental evaluation also showed an overlapping higher than 90% with respect to the ground truth. These results are comparable, and often higher, to those of the state of the art segmentation methods but with a considerably reduction of the segmentation time.