Radiodermatitis and Fibrosis in the Context of Breast Radiation Therapy: A Critical Review

Background: Radiation therapy has been progressively improved in order to maintain a satisfactory tumour response, while reducing toxicity. We will review the incidence of radiodermatitis and fibrosis according to the various radiation and fractionation techniques. We will then focus on the various methods used to manage, prevent, and quantify this toxicity. Method: More than 1753 articles were identified using the various search terms. We selected 53 articles to answer the questions addressed in this study according to criteria set in advance. Result: The literature reports lower acute toxicity with IMRT compared to 3DCRT, but no significant differences in terms of late toxicities. Partial breast irradiation appears to be less effective in terms of local control with a higher rate of late toxicity. Intra operative radiation therapy appears to provide good results in terms of both local control and late toxicity. The hypofractionation has equivalent efficacy and safety to the normofractionated regimen, but with lower rates of radiodermatitis and fibrosis. The adddition of a boost, particularly a sequential boost, increases the risk of fibrosis and radiodermatitis during treatment. Conclusion: The development of IMRT has significantly reduced acute toxicity and has improved tolerability during treatment. Modified fractionation has reduced treatment time, as well as adverse effects.

HLA Does Not Impact on Short-Medium-Term Antibody Response to Preventive Anti-SARS-Cov-2 Vaccine

The response to anti-SARS-Cov-2 preventive vaccine shows high interpersonal variability at short and medium term. One of the explanations might be the individual HLA allelic variants. Indeed, B cell response is stimulated and sustained by CD4+ T helper cells activated by antigens presented by HLA-class II alleles on antigen-presenting cells (APCs). The impact of the number of antigens binding to HLA class-II alleles on the antibody response to the COVID vaccine has been assessed in a cohort of 56 healthcare workers who received the full schedule of the Pfizer-BioNTech BNT162b2 vaccine. Such vaccine is based on the entire spike protein of the SARS-CoV-2. Ab titers have been evaluated 2 weeks after the first dose as well as 2 weeks and 4 months after the boosting dose. HLA-DRB1 and DBQ1 for each of the vaccinees have been assessed, and strong binders have been predicted. The analysis showed no significant correlation between the short-medium-term Ab titers and the number of strong binders (SB) for each individual. These results indicate that levels of Ab response to the spike glycoprotein is not dependent on HLA class II allele, suggesting an equivalent efficacy at global level of the currently used vaccines. Furthermore, the pattern of persistence in Ab titer does not correlate with specific alleles or with the number of SBs.

Use of SGLT-2 Inhibitors in Patients with Chronic Kidney Disease

KEY TAKEAWAYS • Chronic kidney disease (CKD) is common, occurring in 1 of 7 adults in the United States. • 9 out of 10 adults with CKD are unaware of it. • People with CKD have the same risk for cardiovascular (CV) death as people with known atherosclerotic heart disease. • The risk for CV events and death increases with worsening albuminuria and estimated glomerular filtration rate (eGFR). • Patients with risk factors for CKD (hypertension, diabetes, family history of CKD, or advancing age) should be screened by measuring both eGFR and urinary albuminto-creatinine ratio. • Sodium-glucose cotransporter-2 inhibitors are first-line agents for treatment of patients with type 2 diabetes mellitus and CKD or a history of atherosclerotic CV disease. • Dapagliflozin has demonstrated equivalent efficacy for reducing kidney events in patients with CKD irrespective of diabetes status, and a similar, ongoing trial with empaglifloz

Equivalent Efficacy but Different Safety Profiles of Gemcitabine Plus Nab-Paclitaxel and FOLFIRINOX in Metastatic Pancreatic Cancer

FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GN) are the most common chemotherapy regimens in first-line treatment of metastatic pancreatic cancer (PC). They have not been compared each other in a prospective trial, but only in retrospective studies, which can thus be affected by several biases. In order to overcome these biases, we took advantage of matching-adjusted indirect comparison (MAIC), that allows an indirect comparison by reducing cross-trial differences, and compared data from 268 patients treated with GN in a real-world setting with data from the 171 patients included in the FFX arm of the PRODIGE trial. Survival outcomes did not differ between the two populations. Overall survival was 11.1 months for both treatments (hazard ratio (HR) of FFX 1.10, 95% confidence interval (CI) 0.81–1.49; p = 0.527). Progression-free survival was 6.0 months with GN and 6.4 months with FFX (HR of FFX 1.11, 95% CI 0.82–1.50; p = 0.520). On the other hand, we observed a difference in the toxicity profiles: grade 3/4 anemia was more frequent with GN, whereas a higher occurrence of grade 3/4 vomiting and diarrhea was reported with FFX. FFX and GN show an equivalent efficacy but different safety profiles in the first-line therapy of metastatic pancreatic cancer. Searching for reliable predictive biomarkers is advised in order to improve therapeutic strategy in metastatic PC.

Efficacy and safety of biosimilar CT-P17 versus reference adalimumab in subjects with rheumatoid arthritis: 24-week results from a randomized study

Background To demonstrate equivalent efficacy of the proposed high-concentration (100 mg/ml), citrate-free adalimumab biosimilar CT-P17 to European Union-approved adalimumab (EU-adalimumab) in subjects with active rheumatoid arthritis (RA). Methods This randomized, double-blind phase III study (ClinicalTrials.gov, NCT03789292) randomized (1:1) subjects with active RA at 52 centers to receive CT-P17 or EU-adalimumab 40 mg subcutaneously every 2 weeks until week 52. Results to week 24 are reported here. The primary endpoint was 20% improvement by American College of Rheumatology criteria (ACR20) response rate at week 24. Equivalence was concluded if the corresponding confidence intervals (CIs) for the estimate of treatment difference were within predefined equivalence margins: − 15 to 15% (95% CI; European Medicines Agency assumption); − 12 to 15% (90% CI; Food and Drug Administration assumption). Additional efficacy, pharmacokinetic, usability, safety, and immunogenicity endpoints were evaluated. Results 648 subjects were randomized (324 CT-P17; 324 EU-adalimumab). The ACR20 response rate at week 24 was 82.7% (n = 268/324) in both groups (intention-to-treat population). The 95% CI (− 5.94 to 5.94) and 90% CI (− 4.98 to 4.98) were within predefined equivalence margins for both assumptions and equivalent efficacy was concluded. Additional endpoints and overall safety were comparable between groups. Mean trough serum concentrations of CT-P17 were slightly higher than those of EU-adalimumab. Immunogenicity was slightly lower numerically for the CT-P17 group than for the EU-adalimumab group. Conclusions CT-P17 and EU-adalimumab have equivalent efficacy and comparable safety and immunogenicity in subjects with active RA. Overall safety of CT-P17 is consistent with the known safety profile of reference adalimumab. Trial registration ClinicalTrials.gov, NCT03789292. Registered 28 December 2018—retrospectively registered.

Estimation of Radionuclide Concentration in Medical Waste

Almost all hospitals use radioisotopes for different purposes, as their applications grow, so their concentration in the waste of those hospitals does. To address this issue, twenty-nine samples were collected from (9) sites, these samples were collected from the incinerators of medical areas and the waste collection chambers. After collecting the samples, they were prepared for the examination, where a high-purity Germanium detector (HPGe) was used to detect radioactive elements. The lead element (Pb-214) of the uranium chain (U-238) and the actinium element (Ac-228), the lead element (Pb-212) of the thorium chain (Th-246) and the potassium element (K-40) appeared in some medical areas Iodine (I-131). Some regions showed high concentrations of these elements compared to some sites, Iodine (I-131) appeared in high rates in some hospitals specialized in treating cancerous diseases. The equivalent efficacy of radium, the annual equivalent internal and external dose, and the internal and external risk factors were calculated and the results obtained were compared with the global limits.

Treatment of Disseminated Germ Cell Tumors With Cisplatin, Bleomycin, and Either Vinblastine or Etoposide

This chapter reviews a landmark trial that randomized patients with disseminated testicular cancer to treatment with cisplatin, etoposide, and bleomycin (BEP) versus treatment with cisplatin, vinblastine, and bleomycin (PVB). This study demonstrated BEP to be superior to PVB in terms of adverse effects in this trial, with at least equivalent efficacy if not superiority in the setting of advanced disease. This study established BEP as the standard induction chemotherapy regimen used for the majority of patients with metastatic testicular cancer.