Fieldable Muon Spectrometer Using Multi-Layer Pressurized Gas Cherenkov Radiators and Its Applications

Cosmic ray muons have been considered as a non-conventional radiation probe in various applications. To utilize cosmic ray muons in engineering applications, two important quantities, trajectory and momentum, must be known. The muon trajectories are easily reconstructed using two-fold detector arrays with a high spatial resolution. However, precise measurement of muon momentum is difficult to be achieved without deploying large and expensive spectrometers such as solenoid magnets. Here, we propose a new method to estimate muon momentum using multi-layer pressurized gas Cherenkov radiators. This is accurate, portable, compact (< 1m3), and easily coupled with existing muon detectors without the need of bulky magnetic or time-of-flight spectrometers. The results show that not only our new muon spectrometer can measure muon momentum with a resolution of ±0.5 GeV/c in a momentum range of 0.1 to 10.0 GeV/c, but also we can reconstruct cosmic muon spectrum with high accuracy (~90%).

RADT-23. RECURRENT OLIGODENDROGLIOMAS AFTER FIRST CHEMO-RADIATION THERAPY RESPONDED REMARKABLY TO RE-RADIATION

Oligodendrogliomas with 1p/19q-codeletion are relatively slow progressive tumors that show good response to chemo-radiation therapy after resection. The median survival is about 15 years regardless of WHO grade, although recurrences are mostly inevitable and there is no standard treatment for recurrence. We experienced 5 oligodendroglioma cases who underwent re-radiation for recurrent tumors after chemo-radiation treatment. We retrospectively investigated those for response to re-radiation, the duration from first radiation to second radiation, and Karnofsky Performance Status (KPS) before and after the re-radiation. Patients were all male; the median radiation dose for primary tumor was 60Gy (54-60Gy), the median age at first radiation was 46 years (35-59), the median duration from the first radiation to re-radiation was 65 months (range 18-116 months), and the median follow-up period after re-radiation was 15 months (1-39 months). In all 5 cases, tumors showed good response to re-radiation. In 3 of the 5 cases, tumor recurred in corpus callosum and/or lateral side of cerebral hemisphere or basal ganglia contiguous with primary tumor sites and were radiated by IMRT (50Gy/25fr) . In 2 cases, tumors recurred around the fourth ventricle and posterior fossa and underwent conventional radiation (54Gy/30fr and 30Gy/10fr). In 2 of the 5 cases, the tumors re-recurred 24 months later after re-radiation, but the KPS were maintained until re-recurrence. For oligodendrogliomas, re-radiation therapy appears to be very effective to recurrent tumors after first chemo-radiation. Although evaluation for longer-term side effects is to be examined, re-radiation appears to be a good option for recurrent oligodendrogliomas after first chemo-radiation therapy.

Proton Therapy and Gliomas: A Systematic Review

Background: Gliomas are primary cerebral tumors. Radiation therapy plays a key role in their treatment but with a risk of toxicity associated with the dose to and volume of normal tissue that is irradiated. With its precision properties allowing for the increased sparing of healthy tissue, proton therapy could be an interesting option for this pathology. Methods: Two reviewers performed a systematic review of original papers published between 2010 and July 2021 following PRISMA guidelines. We analyzed disease outcomes, toxicity outcomes, or dosimetry data in four separate groups: children/adults and individuals with low-/high-grade gliomas. Results: Among 15 studies, 11 concerned clinical and toxicity outcomes, and 4 reported dosimetry data. Proton therapy showed similar disease outcomes with greater tolerance than conventional radiation therapy, partly due to the better dosimetry plans. Conclusions: This review suggests that proton therapy is a promising technique for glioma treatment. However, studies with a high level of evidence are still needed to validate this finding.

Long Term Arm and Shoulder Toxicities in Breast Cancer Patients Receiving Hypofractionated Radiation Therapy

Aim: The purpose of this study is to evaluate the late toxicities in hypo fractionated radiation schedule in breast cancer patients with regional nodal irradiation (RNI), limited to axilla and supraclavicular regions. Late effects on arm and shoulder were noted as follows: skin edema (lymphedema), restricted shoulder movements (brachial plexus injury) and localised pain.Material and Methods: In this study we randomly enrolled 100 breast cancer post mastectomy cases in the year 2018. All cases were previously asymptomatic after surgery. They were prospectively treated with hypo fractionated local and regional nodal irradiation by 2.67 gray / fraction dose, total 15 fractions (total dose-40 gray). Evaluation was done at 12 months after completion of radiation therapy. Assessment was done by RTOG, LENT- SOMA scales. Results: Significant lymphedema was observed in 17 (17%) cases. Restricted arm mobility was seen in 14 (14%) of patients. Pain (moderate/severe) in arm and shoulder was most commonly seen, in 25 (25%) cases. Conclusions: As hypo fractionated regimes in breast cancer treatment have become new standard; its late term effects are significant and comparable to other conventional radiation therapy regimes. These studies need further and longer duration of evaluation.

Effect of Microwave and Conventional Modes of Heating on Sintering Behavior, Microstructural Evolution and Mechanical Properties of Al-Cu-Mn Alloys

In this research, we intended to examine the effect of heating mode on the densification, microstructure, mechanical properties, and corrosion resistance of sintered aluminum alloys. The compacts were sintered in conventional (radiation-heated) and microwave (2.45 GHz, multimode) sintering furnaces followed by aging. Detailed analysis of the final sintered aluminum alloys was done using optical and scanning electron microscopes. The observations revealed that the microwave sintered sample has a relatively finer microstructure compared to its conventionally sintered counterparts. The experimental results also show that microwave sintered alloy has the best mechanical properties over conventionally sintered compacts. Similarly, the microwave sintered samples showed better corrosion resistance than conventionally sintered ones.

Molecular Mechanisms of Drug Resistance in Glioblastoma

Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and is not amenable to effective surgical resection. The present review summarizes recent advances in our understanding of the molecular mechanisms of therapeutic resistance of GBM to already known drugs, the molecular characteristics of glioblastoma cells, and the barriers in the brain that underlie drug resistance. We also discuss the progress that has been made in the development of new targeted drugs for glioblastoma, as well as advances in drug delivery across the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB).

IMMU-04. FIRST-IN-CHILDREN PHASE 1B STUDY USING THE IDO PATHWAY INHIBITOR INDOXIMOD IN COMBINATION WITH RADIATION AND CHEMOTHERAPY FOR CHILDREN WITH NEWLY DIAGNOSED DIPG (NCT02502708, NLG2105)

Background Diffuse intrinsic pontine glioma (DIPG) is a uniformly fatal brain tumor with no available cure. Indoximod blocks the IDO (indoleamine 2,3-dioxygenase) pathway, thereby reversing IDO-mediated immune suppression in the tumor microenvironment. Methods Patients aged 3 to 21 years with treatment-naive DIPG were eligible for this phase 1b dose-confirmation study of indoximod. The treatment regimen comprised continuous oral indoximod (38.4 mg/kg/day divided twice daily) with conformal photon radiation (54 Gy in 30 fractions), followed by cycles of indoximod with temozolomide (200 mg/m2/day, days 1–5 in 28-day cycles). Results Thirteen patients (median age 9 years, range 5 to 20 years) with DIPG were treated. Median OS was 14.5 months (follow-up ranged 4.8 to 29.3 months), 12-month OS was 61.5% (8/13), and 18-month OS was 30.8% (4/13), with 1 patient remaining in follow-up at the data cutoff. This compared favorably to expected median OS of approximately 10.8 months, 12-month OS of 45.3%, and 18-month OS of 16.2% taken from published historical data from the Pediatric Brain Tumor Consortium. Two patients showed near-complete responses lasting until relapsing after 7.6 months and 13.3 months of study therapy, respectively. Many patients had increased circulating non-classical monocytes (nc-Monos, CD16+, CD14neg, CD33+, HLA-DR+) within the first 3 treatment cycles, and elevation of this early pharmacodynamic marker was predictive of subsequent OS. Patients with nc-Monos &gt;10% (n=7) had median OS of 19 months, whereas patients with nc-Monos below 10% (n=5) had median OS of 7 months (p=0.0047). No patients stopped therapy for toxicity. The most common indoximod-attributed adverse events were thrombocytopenia, neutropenia, nausea, vomiting, dizziness, and fatigue. Conclusions Adding indoximod immunotherapy to conventional radiation and chemotherapy for front-line treatment of pediatric patients with DIPG was well-tolerated. Improved outcomes were observed in patients having evidence of pharmacodynamic response. A follow-on phase 2 study is in progress (NCT04049669).