Radiotherapy for the treatment of pituitary adenomas: A dosimetric comparison of three planning techniques.

AIM: Our goal was to compare conformal 3D (C3D) radiotherapy (RT), modulated intensity RT (IMRT), and volumetric modulated arc therapy (VMAT) planning techniques in treating pituitary adenomas. BACKGROUND: RT is important for managing pituitary adenomas. Treatment planning advances allow for higher radiation dosing with less risk of affecting organs at risk (OAR). MATERIALS AND METHODS: We conducted a 5-year retrospective review of patients with pituitary adenoma treated with external beam radiation therapy (C3D with flattening filter, flattening filter-free [FFF], IMRT, and VMAT). We compared dose-volume histogram data. For OARs, we recorded D2%, maximum, and mean doses. For planning target volume (PTV), we registered V95%, V107%, D95%, D98%, D50%, D2%, minimum dose, conformity index (CI), and homogeneity index (HI). RESULTS: Fifty-eight patients with pituitary adenoma were included. Target-volume coverage was acceptable for all techniques. The HI values were 0.06, IMRT; 0.07, VMAT; 0.08, C3D; and 0.09, C3D FFF (p < 0.0001). VMAT and IMRT provided the best target volume conformity (CI, 0.64 and 0.74, respectively; p < 0.0001). VMAT yielded the lowest doses to the optic pathway, lens, and cochlea. The position of the neck in extreme flexion showed that it helps in planning mainly with VMAT by allowing only one arc to be used and achieving the desired conformity, decreasing the treatment time, while allowing greater protection to the organs of risk using C3D, C3DFFF. CONCLUSIONS: Our results confirmed that EBRT in pituitary adenomas using IMRT, VMAT, C3D, C3FFF provide adequate coverage to the target. VMAT with a single arc or incomplete arc had a better compliance with desired dosimetric goals, such as target coverage and normal structures dose constraints, as well as shorter treatment time. Neck extreme flexion may have benefits in treatment planning for better preservation of organs at risk. C3D with extreme neck flexion is an appropriate treatment option when other treatment techniques are not available.

Pelvic radiation therapy with volumetric modulated arc therapy and intensity-modulated radiotherapy after renal transplant: A report of 3 cases.

AIM: Describe characteristics and outcomes of three patients treated with pelvic radiation therapy after kidney transplant. BACKGROUND: The incidence of pelvic cancers in kidney transplant (KT) recipients is rising. Currently it is the leading cause of death. Moreover, treatment is challenging because anatomical variants, comorbidities, and associated treatments, which raises the concern of using radiotherapy (RT). RT has been discouraged due to the increased risk of urethral/ureteral stricture and KT dysfunction. MATERIALS AND METHODS: We reviewed the electronic health records and digital planning system of patients treated with pelvic RT between December 2013 and December 2018 to identify patients with previous KT. CASES DESCRIPTION: We describe three successful cases of KT patients in which modern techniques allowed full standard RT for pelvic malignances (2 prostate and 1 vaginal cancer) with or without elective pelvic nodal RT, without allograft toxicity at short and long follow-up (up to 60 months). CONCLUSION: When needed, RT modern techniques remain a valid option with excellent oncologic results and acceptable toxicity. Physicians should give special considerations to accomplish all OAR dose constraints in the patient's specific setting. Recent publications recommend KT mean dose <4 Gy, but graft proximity to CTV makes this unfeasible. We present 2 cases where dose constraint was not achieved, and to a short follow-up of 20 months renal toxicity has not been documented. We recommend the lowest possible mean dose to the KT, but never compromising the CTV coverage, since morbimortality from recurrent or progressive cancer disease outweighs the risk of graft injury.

Complement activation in acute myocardial infarction: An early marker of inflammation and tissue injury?

BACKGROUND: Acute myocardial infarction (AMI) is a potentially fatal condition, being a major cause of death worldwide. Ischemia suffered during AMI causes tissue damage, leading to an inflammatory process. Moreover, myocardial injury can generate damage-associated molecular patterns that activate pattern recognition molecules including some complement proteins. METHODS: Here we investigated products of complement activation, C3d and soluble C5b9 (sC5b9), as potential biomarkers for myocardial injury and inflammation, as well as serum cytokines (IL-6 and TNF-alpha), alpha-1-acid glycoprotein (AGP), and classical markers of myocardial necrosis (creatine kinase, creatine kinase-MB isoform, myoglobin and troponin-I) in a longitudinal study of patients with AMI (from admission, 6 h and 12 h post admission, and at discharge from hospital). Individuals undergoing cardiac catheterization (CC) with normal coronary arteries and asymptomatics with no history of cardiovascular disease or invasive procedures were included as controls. RESULTS: Plasma C3d was higher in AMI at admission, 6 h, 12 h, and discharge vs CC (p < 0.0001; p = 0.0061; p = 0.0081; p = 0.044) and asymptomatic (p = 0.0001 for admission, 6 h and 12 h; p = 0.0002 for discharge). Moreover, sC5b9 was higher only at admission and 6 h vs asymptomatic (p = 0.0031 and p = 0.0019). Additionally, AGP levels were elevated at admission, 6 h, 12 h, and discharge vs asymptomatic (p = 0.0003; p = 0.0289; p = 0.0009, p = 0.0017). IL-6 concentration was low at admission and 6 h and reached a peak at 12 h (p < 0.0001 for all groups). All classical markers of myocardial necrosis presented higher concentration at 6 h. CONCLUSIONS: Our results showed that complement activation is an early event in AMI occurring before the elevation of classical markers of myocardial necrosis such as creatine kinase, creatine kinase-MB isoform, myoglobin and troponin-I. These findings indicated C3d and sC5b9 as possible biomarkers for inflammation and tissue damage in AMI.

Addition of C3d-P28 adjuvant to a rabies DNA vaccine encoding the G5 linear epitope enhances the humoral immune response and confers protection.

Rabies DNA vaccines based on full-length glycoprotein (G) induce virus neutralizing antibody (VNA) responses and protect against the virus challenge. Although conformational epitopes of G are the main target of VNAs, some studies have shown that a polypeptide linear epitope G5 is also able to induce VNAs. However, a G5 DNA vaccine has not been explored. While multiple doses of DNA vaccines are required in order to confer a protective immune response, this could be overcome by the inclusion of C3d-P28, a molecular adjuvant is know to improve the antibody response in several anti-viral vaccine models. To induce and enhance the immune response against rabies in mice, we evaluated two DNA vaccines based on the linear epitope G5 of Rabies Virus (RABV) glycoprotein (pVaxG5 vaccine) and another vaccine consisting of G5 fused to the molecular adjuvant C3d-P28 (pVaxF1 vaccine). VNA responses were measured in mice immunized with both vaccines. The VNA levels from the group immunized with pVaxG5 decreased gradually, while those from the group vaccinated with pVaxF1 remained high throughout the experimental study. After challenge with 22 LD50 of the Challenge Virus Strain (CVS), the survival rate of mice immunized with pVaxG5 and pVaxF1 was increased by 27% and 50% respectively, in comparison to the PBS group. Furthermore, the in vitro proliferation of anti-rabies specific spleen CD4+ and CD8+ T cells from mice immunized with pVaxF1 was observed. Collectively, these results suggest that the linear G5 epitope is a potential candidate vaccine. Furthermore, the addition of a C3d-P28 adjuvant contributed to enhanced protection, the sustained production of VNAs, and a specific T-cell proliferative response.

Delivery route determines the presence of immune complexes on umbilical cord erythrocytes.

OBJECTIVE: Umbilical cord blood offers a unique opportunity to study the basal level of immunoglobulin complexes. This study aims to determine the presence of immune complexes and complement deposition on erythrocytes from umbilical cord blood from normal, full-term pregnancies. METHODS: In vitro pre-formed IgA, IgG, and IgM complexes were used as positive control for flow cytometry detection, and for C3d deposition. Blood samples (34) of umbilical cord blood taken from vaginal and cesarean deliveries were tested for the presence of immunoglobulin complexes. RESULTS: Fourteen samples from vaginal deliveries and 20 samples from cesarean deliveries were assessed. IgG and IgM complexes were detected on erythrocytes, whereas no IgA complexes or complement deposition was observed. Interestingly, the percentage of IgG complexes was higher on erythrocytes from vaginal delivery samples compared to those from cesarean deliveries. No other associations between immune complexes and other maternal or newborn variables were found. CONCLUSIONS: IgG and IgM complexes seem to be normally present on umbilical cord erythrocytes. Erythrocytes from vaginal deliveries have a higher percentage of IgG complexes present compared to that from cesarean deliveries. Since no C3d activity was detected, these complexes are non-pathological and should be part of the newborn's initial innate immune response.