Single-Valued Integration and Superstring Amplitudes in Genus Zero.

We study open and closed string amplitudes at tree-level in string perturbation theory using the methods of single-valued integration which were developed in the prequel to this paper (Brown and Dupont in Single-valued integration and double copy, 2020). Using dihedral coordinates on the moduli spaces of curves of genus zero with marked points, we define a canonical regularisation of both open and closed string perturbation amplitudes at tree level, and deduce that they admit a Laurent expansion in Mandelstam variables whose coefficients are multiple zeta values (resp. single-valued multiple zeta values). Furthermore, we prove the existence of a motivic Laurent expansion whose image under the period map is the open string expansion, and whose image under the single-valued period map is the closed string expansion. This proves the recent conjecture of Stieberger that closed string amplitudes are the single-valued projections of (motivic lifts of) open string amplitudes. Finally, applying a variant of the single-valued formalism for cohomology with coefficients yields the KLT formula expressing closed string amplitudes as quadratic expressions in open string amplitudes.

Standardized intraoperative 5-ALA photodynamic therapy for newly diagnosed glioblastoma patients: a preliminary analysis of the INDYGO clinical trial.

PURPOSE: Glioblastoma (GBM) is the most aggressive malignant primary brain tumor. The unfavorable prognosis despite maximal therapy relates to high propensity for recurrence. Thus, overall survival (OS) is quite limited and local failure remains the fundamental problem. Here, we present a safety and feasibility trial after treating GBM intraoperatively by photodynamic therapy (PDT) after 5-aminolevulinic acid (5-ALA) administration and maximal resection. METHODS: Ten patients with newly diagnosed GBM were enrolled and treated between May 2017 and June 2018. The standardized therapeutic approach included maximal resection (near total or gross total tumor resection (GTR)) guided by 5-ALA fluorescence-guided surgery (FGS), followed by intraoperative PDT. Postoperatively, patients underwent adjuvant therapy (Stupp protocol). Follow-up included clinical examinations and brain MR imaging was performed every 3 months until tumor progression and/or death. RESULTS: There were no unacceptable or unexpected toxicities or serious adverse effects. At the time of the interim analysis, the actuarial 12-months progression-free survival (PFS) rate was 60% (median 17.1 months), and the actuarial 12-months OS rate was 80% (median 23.1 months). CONCLUSIONS: This trial assessed the feasibility and the safety of intraoperative 5-ALA PDT as a novel approach for treating GBM after maximal tumor resection. The current standard of care remains microsurgical resection whenever feasible, followed by adjuvant therapy (Stupp protocol). We postulate that PDT delivered immediately after resection as an add-on therapy of this primary brain cancer is safe and may help to decrease the recurrence risk by targeting residual tumor cells in the resection cavity. Trial registration NCT number: NCT03048240. EudraCT number: 2016-002706-39.

Parallelized Monte-Carlo dosimetry using graphics processing units to model cylindrical diffusers used in photodynamic therapy: From implementation to validation.

The Monte-Carlo method is the standard method for computing the dosimetry of both ionizing and non-ionizing radiation. Because this technique is highly time-consuming in conventional implementations, several improvements have recently been developed to speed-up simulations. Among the improvements, the use of graphics processing units (GPU) to parallelize algorithms provides a cost-efficient solution to accelerate the Monte-Carlo method. Parallel implementation of Monte-Carlo using GPU technology is described in the context of photodynamic therapy (PDT) dosimetry. This algorithm has been optimized to compute light emitted from optical fibers with cylindrical diffusers that are used in interstitial PDT applications. A comparison of the experimental measurements used to assess the results of the Monte-Carlo method is detailed. Illumination profiles of several commercially available diffusers are measured using an optical phantom that mimics the optical properties of the brain. Additionally, this Monte-Carlo method is compared to ex-vivo measurements made by a device dedicated to intraoperative PDT treatment of brain tumors. The results of the GPU Monte-Carlo validation are in accordance with the recommendations of the American Association of Physicists in Medicine. The acceleration obtained with the GPU implementation is in accordance with the literature and is sufficiently fast to be integrated in a treatment planning system dedicated to planning routine clinical interstitial PDT treatments.

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.

Photodynamic therapy for glioblastoma: A preliminary approach for practical application of light propagation models.

PURPOSE: Photodynamic therapy (PDT) is a promising treatment modality to be added in the management of glioblastoma multiforme (GBM). Light distribution modeling is required for planning and optimizing PDT. Several models have been developed to predict the light propagation inside biological tissues. In the present study, two analytical methods of light propagation emitted from a cylindrical fiber source were evaluated: a discrete and a continuous method. METHODS: The two analytical approaches were compared according to their fluence rate results. Several cylindrical diffuse lengths were evaluated, and the relative deviation in the fluence rates was estimated. Moreover, a sensitivity analysis was conducted to compute the variance of each analytical model. RESULTS: The discrete method provided fluence rate estimations closer to the Monte-Carlo simulations than the continuous method. The sensitivity study results did not reveal significant differences between the variance of the two analytical models. CONCLUSIONS: Although the discrete model provides relevant light distribution, the heterogeneity of GBM tissues was not considered. With the improvement in parallel computing that drastically decreased the computing time, replacing the analytical model by a Monte-Carlo GPU-accelerated code appeared relevant to the GBM case. Nonetheless, the analytical modeling may still function in the optimization algorithms, which might be used in the Photodynamic treatment planning system. Lasers Surg. Med. 50:523-534, 2018. © 2017 Wiley Periodicals, Inc.

A novel device for intraoperative photodynamic therapy dedicated to glioblastoma treatment.

AIM: Photodynamic therapy (PDT) appears to be a valuable new treatment modality for cancer therapy. Studies have reported successful application of PDT for glioblastoma. Here, we introduce a new device dedicated to intraoperative PDT delivered early after fluoro-guided resection combined with a transfer function that determines the treatment time based on the size of the surgical resection cavity. MATERIALS & METHODS: First, we describe the device, which is composed of a trocar, a balloon filled with a diffusing solution, and a fiber guide in which a cylindrical light diffuser is inserted. Ex vivo experiments were performed to measure the fluence rate inside biological tissues. A calibration factor was defined to convert power measurements into fluence rate values. Calf brains were used to simulate light propagation in human brain tissue, and the photosensitizer administration effect on optical properties was discussed. The temperature elevation during illumination was evaluated. RESULTS: Light power was measured in tissues surrounding the device during ex vivo experiments. Using the previously characterized calibration factor, power measurements were converted to fluence rate values to obtain the transfer function. No thermal elevation was observed during a 2-h temperature test, and the impact of protoporphyrin IX on brain optical properties was considered negligible. CONCLUSION: A discussion of experimental precision is presented. The light duration determined by the abacus had a standard deviation of <1 min. This value is weak compared with the total illumination time necessary to treat one patient. The main advantage of our device lies in its straightforward implementation of intraoperative PDT for neurosurgery with acceptable dosimetry and easy treatment time.