Interstitial Photodynamic Therapy for Glioblastomas: A Standardized Procedure for Clinical Use.

Glioblastomas (GBMs) are high-grade malignancies with a poor prognosis. The current standard of care for GBM is maximal surgical resection followed by radiotherapy and chemotherapy. Despite all these treatments, the overall survival is still limited, with a median of 15 months. For patients harboring inoperable GBM, due to the anatomical location of the tumor or poor general condition of the patient, the life expectancy is even worse. The challenge of managing GBM is therefore to improve the local control especially for non-surgical patients. Interstitial photodynamic therapy (iPDT) is a minimally invasive treatment relying on the interaction of light, a photosensitizer and oxygen. In the case of brain tumors, iPDT consists of introducing one or several optical fibers in the tumor area, without large craniotomy, to illuminate the photosensitized tumor cells. It induces necrosis and/or apoptosis of the tumor cells, and it can destruct the tumor vasculature and produces an acute inflammatory response that attracts leukocytes. Interstitial PDT has already been applied in the treatment of brain tumors with very promising results. However, no standardized procedure has emerged from previous studies. Herein, we propose a standardized and reproducible workflow for the clinical application of iPDT to GBM. This workflow, which involves intraoperative imaging, a dedicated treatment planning system (TPS) and robotic assistance for the implantation of stereotactic optical fibers, represents a key step in the deployment of iPDT for the treatment of GBM. This end-to-end procedure has been validated on a phantom in real operating room conditions. The thorough description of a fully integrated iPDT workflow is an essential step forward to a clinical trial to evaluate iPDT in the treatment of GBM.

Is interstitial photodynamic therapy for brain tumors ready for clinical practice? A systematic review.

BACKGROUND: Interstitial photodynamic therapy (iPDT), inserting optical fibers inside brain tumors, has been proposed for more than 30 years. While a promising therapeutic option, it is still an experimental treatment, with different ways of application, depending on the team performing the technique. OBJECTIVE: In this systematic review, we reported the patient selection process, the treatment parameters, the potential adverse events and the oncological outcomes related to iPDT treatment applied to brain tumors. METHODS: We performed a search in PubMed, Embase and Medline based on the following Mesh terms: "interstitial" AND "photodynamic therapy" AND "brain tumor" OR "glioma" OR glioblastoma" from January 1990 to April 2020. We screened 350 studies. Twelve matched all selection criteria. RESULTS: 251 patients underwent iPDT. Tumors were mainly de novo or recurrent high-grade gliomas (171 (68%) of glioblastomas), located supratentorial, with a median volume of 12 cm3. Hematoporphyrin derive agent (HpD) or protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (5-ALA) was used as a photosensitizer. Up to 6 optical fibers were introduced inside the tumor, delivering 200 mW/cm at a wavelength of 630 nm. Overall mortality was 1%. Transient and persistent morbidity were both 5%. No permanent deficit occurred using 5-ALA PDT. Tumor response rate after iPDT was 92% (IQR, 67; 99). Regarding glioblastomas, progression-free-survival was respectively 14.5 months (IQR, 13.8; 15.3) for de novo lesions and 14 months (IQR, 7; 30) for recurrent lesions, while overall survival was respectively 19 months (IQR, 14; 20) and 8 months (IQR, 6.3; 8.5). In patients harboring high-grade gliomas, 33 (13%) were considered long-term survivors (> 2 years) after iPDT. CONCLUSION: Regardless of heterogeneity in its application, iPDT appears safe and efficient to treat brain tumors, especially high-grade gliomas. Stand-alone iPDT (i.e., without combined craniotomy and intracavitary PDT) using 5-ALA appears to be the best option in terms of controlling side effects: it avoids the occurrence of permanent neurological deficits while reducing the risks of hemorrhage and sepsis.

Investigating the limits of PET/CT imaging at very low true count rates and high random fractions in ion-beam therapy monitoring.

PURPOSE: External beam radiotherapy with protons and heavier ions enables a tighter conformation of the applied dose to arbitrarily shaped tumor volumes with respect to photons, but is more sensitive to uncertainties in the radiotherapeutic treatment chain. Consequently, an independent verification of the applied treatment is highly desirable. For this purpose, the irradiation-induced ß(+)-emitter distribution within the patient is detected shortly after irradiation by a commercial full-ring positron emission tomography/x-ray computed tomography (PET/CT) scanner installed next to the treatment rooms at the Heidelberg Ion-Beam Therapy Center (HIT). A major challenge to this approach is posed by the small number of detected coincidences. This contribution aims at characterizing the performance of the used PET/CT device and identifying the best-performing reconstruction algorithm under the particular statistical conditions of PET-based treatment monitoring. Moreover, this study addresses the impact of radiation background from the intrinsically radioactive lutetium-oxyorthosilicate (LSO)-based detectors at low counts. METHODS: The authors have acquired 30 subsequent PET scans of a cylindrical phantom emulating a patientlike activity pattern and spanning the entire patient counting regime in terms of true coincidences and random fractions (RFs). Accuracy and precision of activity quantification, image noise, and geometrical fidelity of the scanner have been investigated for various reconstruction algorithms and settings in order to identify a practical, well-suited reconstruction scheme for PET-based treatment verification. Truncated listmode data have been utilized for separating the effects of small true count numbers and high RFs on the reconstructed images. A corresponding simulation study enabled extending the results to an even wider range of counting statistics and to additionally investigate the impact of scatter coincidences. Eventually, the recommended reconstruction scheme has been applied to exemplary postirradiation patient data-sets. RESULTS: Among the investigated reconstruction options, the overall best results in terms of image noise, activity quantification, and accurate geometrical recovery were achieved using the ordered subset expectation maximization reconstruction algorithm with time-of-flight (TOF) and point-spread function (PSF) information. For this algorithm, reasonably accurate (better than 5%) and precise (uncertainty of the mean activity below 10%) imaging can be provided down to 80,000 true coincidences at 96% RF. Image noise and geometrical fidelity are generally improved for fewer iterations. The main limitation for PET-based treatment monitoring has been identified in the small number of true coincidences, rather than the high intrinsic random background. Application of the optimized reconstruction scheme to patient data-sets results in a 25% - 50% reduced image noise at a comparable activity quantification accuracy and an improved geometrical performance with respect to the formerly used reconstruction scheme at HIT, adopted from nuclear medicine applications. CONCLUSIONS: Under the poor statistical conditions in PET-based treatment monitoring, improved results can be achieved by considering PSF and TOF information during image reconstruction and by applying less iterations than in conventional nuclear medicine imaging. Geometrical fidelity and image noise are mainly limited by the low number of true coincidences, not the high LSO-related random background. The retrieved results might also impact other emerging PET applications at low counting statistics.

Negative-pressure wound therapy and external fixation for infection and hematoma after hallux abducto valgus surgery.

Hematoma refers to the collection or extravasation of blood, usually clotted, in a closed tissue space. It is caused by leakage from local vessels damaged by blunt trauma, local injury, or surgical dissection. In the postoperative phase, a hematoma often results in edema, pain, wound dehiscence, infection, and scarring of the surgical wound. We describe a 44-year-old woman who developed severe complications, including hematoma, abscess, failure of internal fixation, and loss of soft-tissue structures, after hallux abducto valgus surgery. Hospitalization was required for infection control, soft-tissue coverage through negative-pressure wound therapy, and first metatarsophalangeal joint stabilization through external fixation. Early recognition of the signs of infection and hematoma can help decrease the incidence of postoperative complications.