Pilot scale validation campaign of gel dosimetry for pre-treatment quality assurance in stereotactic radiotherapy

Purpose: Complex stereotactic radiotherapy treatment plans require prior verification. A gel dosimetry system was developed and tested to serve as a high-resolution 3D dosimeter for Quality Assurance (QA) purposes.Materials and Methods: A modified version of a polyacrylamide polymer gel dosimeter based on chemical response inhibition was employed. Different sample geometries (cuvettes and phantoms) were manufactured for calibration and QA acquisitions. Irradiations were performed with a Varian Trilogy linac, and analyses of irradiated gel dosimeters were performed via MRI with a 1.5 T Philips Achieva at 1 mm3 or 2 mm3 isotropic spatial resolution. To assess reliability of polymer gel data, 54 stereotactic clinical treatment plans were delivered both on dosimetric gel phantoms and on the Delta4 dosimeter. Results from the two devices were evaluated through a global gamma index over a range of acceptance criteria and compared with each other.Results: A quantitative and tunable control of dosimetric gel response sensitivity was achieved through chemical inhibition. An optimized MRI analysis protocol allowed to acquire high resolution phantom dose data in time -frames of approximate to 1 h. Conversion of gel dosimeter data into absorbed dose was achieved through internal calibration. Polymer gel dosimeters (2 mm3 resolution) and Delta4 presented an agreement within 4.8 % and 2.7 % at the 3 %/1 mm and 2 %/2 mm gamma criteria, respectively.Conclusions: Gel dosimeters appear as promising tools for high resolution 3D QA. Added complexity of the gel dosimetry protocol may be justifiable in case of small target volumes and steep dose gradients

Practical role of polymerization inhibitors in polymer gel dosimeters

The fundamental role of pre-treatment quality assurance in radiotherapy is to verify the radiation treatment with respect to the planned dose distribution by means of a devoted dosimeter. This step is necessary to achieve the full clinical potential of the treatment by guaranteeing sparing of healthy tissues. In this study, the dose response of a modified version of the PAGAT polymer gel dosimeter, a chemical dosimeter capable of direct 3D dose measurements, has been characterized. The physical response of the dosimeter is proportional to polymerization efficiency between its constituting monomers. The effect of several polymerization inhibitors in controlling the chemical response of the gel was investigated. The addition of these compounds allows a tailoring of the range of dose response of the gel to the dose range used in clinical practice. Obtained results from optical and magnetic resonance imaging analyses of irradiated gels indicate that an accurate control of inhibitor concentration can lead to a significant extension of the useful dose range, from approximately 4 Gy for the reference composition up to 40 Gy when inhibitors are added, with no significant detriment on fundamental dosimetric parameters such as accuracy, dose resolution and stability of the dose response

Analysis of the relation between adverse events and overall survival in patients treated with pembrolizumab as a first-line treatment for metastatic NSCLC

BACKGROUND: Many trials supported pembrolizumab as a first-line monotherapy to significantly improve overall survival (OS) in selected patients with previously untreated metastatic Non-Small Cell Lung Cancer (mNSCLC) and a PD-L1 TPS of ≥50% without EGFR/ALK mutations. The aim of this study was to reveal the correlation between OS and adverse events in real-world settings after 42 months. METHODS: This retrospective observational study involved 98 patients with mNSCLC, TPS ≥ 50%, and no EGFR/ALK aberrations. Patients were treated with pembrolizumab (200 mg q3w) as a first-line treatment. Clinical data, including PD-L1 expression, Performance Status (ECOG-PS), treatment duration, toxicity, and outcomes were retrieved from local electronic medical records and from the Italian Regulatory Agency Registry. RESULTS: The cohort's main characteristics were as follows: median age 73 [44-89] years, 64.3% were male and 35.7% were female, an ECOG-PS score of 0 (n = 73) and 1 or 2 (n = 25), and a PD-L1 > 90% in 29.6% of patients. The entire cohort had stage IV NSCLC at diagnosis. The median number of cycles was 8.5 at a median follow-up of 13 months. The median OS of 13.6 months (95% CI: 11.7-NA) was not influenced by sex and PD-L1, but was significantly associated with ECOG-PS (p = 0.02). Immune-Related Adverse Events (irAEs) occurred in 77.5% of patients (30.1% cutaneous, 27.5% gastrointestinal, and 20.4% endocrinological), but no grade 4 or 5 irAEs were identified. Patients experiencing any type of toxicity had a significantly longer median OS (20.39 months, 95% CI: 13.08-NA) than those with no toxicities (6.46 months, 95% CI: 1.41-NA, p = 0.006). CONCLUSION: The percentage of irAEs detected was comparable to that reported in KEYNOTE-024 and KEYNOTE-042. These real-world findings demonstrated the significant correlation between OS and cutaneous toxicities

Practical role of polymerization inhibitors in polymer gel dosimeters

The fundamental role of pre-treatment quality assurance in radiotherapy is to verify the radiation treatment with respect to the planned dose distribution by means of a devoted dosimeter. This step is necessary to achieve the full clinical potential of the treatment by guaranteeing sparing of healthy tissues. In this study, the dose response of a modified version of the PAGAT polymer gel dosimeter, a chemical dosimeter capable of direct 3D dose measurements, has been characterized. The physical response of the dosimeter is proportional to polymerization efficiency between its constituting monomers. The effect of several polymerization inhibitors in controlling the chemical response of the gel was investigated. The addition of these compounds allows a tailoring of the range of dose response of the gel to the dose range used in clinical practice. Obtained results from optical and magnetic resonance imaging analyses of irradiated gels indicate that an accurate control of inhibitor concentration can lead to a significant extension of the useful dose range, from approximately 4 Gy for the reference composition up to 40 Gy when inhibitors are added, with no significant detriment on fundamental dosimetric parameters such as accuracy, dose resolution and stability of the dose response

Outpatient parenteral antibiotic therapy for bone and joint infections: an italian multicenter study

In the early eighties, the advantages of outpatient parenteral antibiotic therapy (OPAT) (reduced costs, no hospitalization trauma in children, no immobilization syndrome in elderly, reduction in nosocomial infections by multiresistant organisms) were identified in the United States, and suitable therapeutic programs were established. Currently, more than 250,000 patients per year are treated according to an OPAT program. In order to understand the different ways of managing OPAT and its results, a National OPAT Registry was set up in 2003 in Italy. Analysis of data concerning osteomyelitis, septic arthritis, prosthetic joint infection and spondylodiskitis, allowed information to be acquired about 239 cases of bone and joint infections, with particular concern to demographics, therapeutic management, clinical response, and possible side effects. Combination therapy was the first-line choice in 66.9% of cases and frequently intravenous antibiotics were combined with oral ones. Teicoplanin (38%) and ceftriaxone (14.7%), whose pharmacokinetic/pharmacodynamic properties permit once-a-day administration, were the two top antibiotics chosen; fluoroquinolones (ciprofloxacin and levofloxacin) were the most frequently utilized oral drugs. Clinical success, as well as patients' and doctors' satisfaction with the OPAT regimen was high. Side-effects were mild and occurred in 11% of cases. These data confirm that the management of bone and joint infections in an outpatient setting is suitable, effective and safe

Outpatient parenteral antibiotic therapy in the elderly: an Italian observational multicenter study.

Bacterial infections are the most frequent cause of hospitalization in elderly patients. In the early eighties, the advantages of Outpatient parenteral Antibiotic therapy (OPAT) were identified in the United States, and suitable therapeutic programs were established. In order to understand the different ways of managing OPAT, a National OPAT Registry was set up in 2003 in Italy. This study analyzes data concerning bacterial infections in 176 elderly patients including demographics, therapeutic management, clinical response, and side-effects. Bone and joint infections (48.9%) and skin and soft tissue infections (27.8%) were the most common infections treated with OPAT. Teicoplanin (28.9%) and ceftriaxone (22.1%) were the top two antibiotics chosen. OPAT was mainly performed at a hospital infusion center (52.8%). The clinical success rate was high and side-effects were low (12.6% of cases). Management of bacterial infections in the elderly with an outpatient program is effective and safe

Outpatient parenteral antibiotic therapy for bone and joint infections: an italian multicenter study

In the early eighties, the advantages of outpatient parenteral antibiotic therapy (OPAT) (reduced costs, no hospitalization trauma in children, no immobilization syndrome in elderly, reduction in nosocomial infections by multiresistant organisms) were identified in the United States, and suitable therapeutic programs were established. Currently, more than 250,000 patients per year are treated according to an OPAT program. In order to understand the different ways of managing OPAT and its results, a National OPAT Registry was set up in 2003 in Italy. Analysis of data concerning osteomyelitis, septic arthritis, prosthetic joint infection and spondylodiskitis, allowed information to be acquired about 239 cases of bone and joint infections, with particular concern to demographics, therapeutic management, clinical response, and possible side effects. Combination therapy was the first-line choice in 66.9% of cases and frequently intravenous antibiotics were combined with oral ones. Teicoplanin (38%) and ceftriaxone (14.7%), whose pharmacokinetic/pharmacodynamic properties permit once-a-day administration, were the two top antibiotics chosen; fluoroquinolones (ciprofloxacin and levofloxacin) were the most frequently utilized oral drugs. Clinical success, as well as patients' and doctors' satisfaction with the OPAT regimen was high. Side-effects were mild and occurred in 11% of cases. These data confirm that the management of bone and joint infections in an outpatient setting is suitable, effective and safe

Outpatient parenteral antibiotic therapy for bone and joint infections: an italian multicenter study

In the early eighties, the advantages of outpatient parenteral antibiotic therapy (OPAT) (reduced costs, no hospitalization trauma in children, no immobilization syndrome in elderly, reduction in nosocomial infections by multiresistant organisms) were identified in the United States, and suitable therapeutic programs were established. Currently, more than 250,000 patients per year are treated according to an OPAT program. In order to understand the different ways of managing OPAT and its results, a National OPAT Registry was set up in 2003 in Italy. Analysis of data concerning osteomyelitis, septic arthritis, prosthetic joint infection and spondylodiskitis, allowed information to be acquired about 239 cases of bone and joint infections, with particular concern to demographics, therapeutic management, clinical response, and possible side effects. Combination therapy was the first-line choice in 66.9% of cases and frequently intravenous antibiotics were combined with oral ones. Teicoplanin (38%) and ceftriaxone (14.7%), whose pharmacokinetic/pharmacodynamic properties permit once-a-day administration, were the two top antibiotics chosen; fluoroquinolones (ciprofloxacin and levofloxacin) were the most frequently utilized oral drugs. Clinical success, as well as patients' and doctors' satisfaction with the OPAT regimen was high. Side-effects were mild and occurred in 11% of cases. These data confirm that the management of bone and joint infections in an outpatient setting is suitable, effective and safe