Efficacy and Safety of Trans-Arterial Yttrium-90 Radioembolization in Patients with Unresectable Liver-Dominant Metastatic or Primary Hepatic Soft Tissue Sarcomas

Patients with liver-dominant metastatic or primary hepatic soft tissue sarcomas (STS) have poor prognosis. Surgery can prolong survival, but most patients are not surgical candidates, and treatment response is limited with systemic chemotherapy. Liver-directed therapies have been increasingly employed in this setting, and Yttrium-90 trans-arterial radioembolization (TARE) is an understudied yet promising treatment option. This is a retrospective analysis of 35 patients with metastatic or primary hepatic STS who underwent TARE at a single institution between 2006 and 2020. The primary outcomes that were measured were overall survival (OS), liver progression-free survival (LPFS), and radiologic tumor response. Clinical and biochemical toxicities were assessed 3 months after the procedure. Median OS was 20 months (95% CI: 13.9–26.1 months), while median LPFS was 9 months (95% CI: 6.2–11.8 months). The objective response rate was 56.7%, and the disease control rate was 80.0% by mRECIST at 3 months. The following correlated with better OS post-TARE: liver disease control (DC) at 6 months (median OS: 40 vs. 17 months, p = 0.007); LPFS ≥ 9 months (median OS: 50 vs. 8 months, p < 0.0001); ECOG status 0–1 vs. 2 (median OS: 22 vs. 6 months, p = 0.042); CTP class A vs. B (median OS: 22 vs. 6 months, p = 0.018); and TACE post-progression (median OS: 99 vs. 16 months, p = 0.003). The absence of metastases at diagnosis was correlated with higher median LPFS (7 vs. 1 months, p = 0.036). Two grade 4 (5.7%) and ten grade 3 (28.6%) laboratory toxicities were identified at 3 months. There was one case of radioembolization-induced liver disease and two cases of radiation-induced peptic ulcer disease. We concluded that TARE could be an effective and safe treatment option for patients with metastatic or primary hepatic STS with good tumor response rates, low incidence of severe toxicity, and longer survival in patients with liver disease control post-TARE.

Systemic lupus erythematosus reactivation after chemoimmunotherapy in preexisting autoimmune disease

The use of immune checkpoint inhibitors (ICIs) offers new possibilities in modern treatment of many types of cancers. Few data regarding safety and efficacy of ICIs are available, and are mainly from retrospective studies and case reports rather than from clinical trials, in the context of preexisting autoimmune disease, mainly due to the risk of severe toxicity. We present an unexpected life-threatening reactivation of systemic lupus erythematosus after one dose of chemo-immunotherapy with pembrolizumab for oligometastatic non-small-cell lung cancer. We analyze data coming from the published literature in this setting and discuss the risk–benefit balance of immunotherapy in patients with preexisting severe autoimmune disease.

Selenium Biofortification of Lettuce Plants (Lactuca sativa L.) as Affected by Se Species, Se Rate, and a Biochar Co-Application in a Calcareous Soil

Selenium biofortification of lettuce plants was studied for two rates (5 and 10 mg kg−1 soil) of either selenate or selenite and for the effect of 5% w/w biochar addition. Lettuce seedlings were grown in pots containing 1 kg of a calcareous soil. Twelve weeks later, the plants were harvested and selenium (Se), phosphorus (P), and sulfur (S) concentrations were determined in heads and roots. Plant growth characteristics were measured and plant biometrics were assessed by NDVI, NDRE, and SPAD measurements. The highest Se concentration of 315.19 mg kg−1 D.W. and the highest amount of Se taken up by plants (950.5 μg/pot) were observed for the low selenate rate with biochar. The corresponding values for selenite treatments were an order of magnitude lower. Although in general, minor to severe toxicity symptoms occurred with selenium application in no biochar treatments (except selenite low rate), the addition of biochar secured plant growth and increased S and P concentrations in plants, regulating Se uptake by plants at high selenite rate and allowing maximum plant uptake at the low selenate rate. To propose an appropriate Se fertilization rate, the fate of excess selenates in the soil environment should be examined and experimentation under soil conditions is necessary.

Nanowell-enhanced Raman spectroscopy enables the visualization and quantification of nanoplastics in the environment

Nanoplastics are persistent pollutants that can cause severe toxicity to mammals. To date, no technology could simultaneously capture nanoplastic chemical and morphological information while conducting quantitative detection. Surface-enhanced Raman spectroscopy...

Effect of D-mannose on Philadelphia chromosome-positive leukemia cells

BACKGROUND: Although Abelson (ABL) tyrosine kinase inhibitors (TKIs) have demonstrated potency against chronic myeloid leukemia (CML), resistance to ABL TKIs can develop in CML patients after discontinuation of therapy. OBJECTIVE: Glucose metabolism may be altered in CML cells because glucose is a key metabolite used by tumor cells. We investigated whether D-mannose treatment induced metabolic changes in CML cells and reduced CML growth in the presence of ABL TKIs. METHODS: We investigated whether D-mannose treatment induced metabolic changes in CML cells and reduced CML growth in the presence of ABL TKIs. RESULTS: Treatment with D-mannose for 72 h inhibited the growth of K562 cells. Combined treatment using ABL TKIs and D-mannose induced a significantly higher level of cytotoxicity in Philadelphia chromosome (Ph)-positive leukemia cells than in control cells. In the mouse model, severe toxicity was observed as evidenced by body weight loss in the ponatinib and D-mannose combination treatment groups. CONCLUSION: Our results indicate that metabolic reprogramming may be a useful strategy against Ph-positive leukemia cells. However, caution should be exercised during clinical applications.

Comparison of Anticancer Drug Toxicities: Paradigm Shift in Adverse Effect Profile

The inception of cancer treatment with chemotherapeutics began in the 1940s with nitrogen mustards that were initially employed as weapons in World War II. Since then, treatment options for different malignancies have evolved over the period of last seventy years. Until the late 1990s, all the chemotherapeutic agents were small molecule chemicals with a highly nonspecific and severe toxicity spectrum. With the landmark approval of rituximab in 1997, a new horizon has opened up for numerous therapeutic antibodies in solid and hematological cancers. Although this transition to large molecules improved the survival and quality of life of cancer patients, this has also coincided with the change in adverse effect patterns. Typically, the anticancer agents are fraught with multifarious adverse effects that negatively impact different organs of cancer patients, which ultimately aggravate their sufferings. In contrast to the small molecules, anticancer antibodies are more targeted toward cancer signaling pathways and exhibit fewer side effects than traditional small molecule chemotherapy treatments. Nevertheless, the interference with the immune system triggers serious inflammation- and infection-related adverse effects. The differences in drug disposition and interaction with human basal pathways contribute to this paradigm shift in adverse effect profile. It is critical that healthcare team members gain a thorough insight of the adverse effect differences between the agents discovered during the last twenty-five years and before. In this review, we summarized the general mechanisms and adverse effects of small and large molecule anticancer drugs that would further our understanding on the toxicity patterns of chemotherapeutic regimens.

Prediction of Chemotoxicity, Unplanned Hospitalizations and Early Death in Older Patients with Colorectal Cancer Treated with Chemotherapy

Purpose: To identify risk factors for toxicity, unplanned hospitalization (UH) and early death (ED) in older patients with colorectal carcinoma (CRC) initiating chemotherapy. Methods: 215 patients over 70 years were prospectively included. Geriatric assessment was performed before treatment, and tumor and treatment variables were collected. The association between these factors and grade 3–5 toxicity, UH and ED (<6 months) was examined by using multivariable logistic regression. Score points were assigned to each risk factor. Results: During the first 6 months of treatment, 33% of patients developed grade 3–5 toxicity, 31% had UH and 23% died. Risk factors were, for toxicity, instrumental activities of daily living, creatinine clearance, weight loss and MAX2 index; for UH, Charlson Comorbidity Score, creatinine clearance, weight loss, serum albumin, and metastatic disease; and for ED, basic activities in daily living, weight loss, metastatic disease, and hemoglobin levels. Predictive scores were built with these variables. The areas under receiver operation characteristic (ROC) curves for toxicity, UH and ED were 0.70 (95% CI: 0.64–0.766), 0.726 (95% IC: 0.661–0.799) and 0.74 (95% IC: 0.678–0.809), respectively. Conclusion: Simple scores based on geriatric, tumor and laboratory characteristics predict severe toxicity, UH and ED, and may help in treatment planning.

The POLO (Partially Omitted Lobe) approach to safely treat in-breast recurrence after intraoperative radiotherapy with electrons

Objectives: The aim of this study is to evaluate feasibility of salvage 4-week hypofractionated whole breast radiotherapy (WBRT) in patients with in-breast recurrence after receiving intraoperative radiotherapy with electrons (IOERT) for primary breast cancer (BC). Methods: BC patients who had repeated quadrantectomy underwent modified WBRT with intensity-modulated radiotherapy using Helical Tomotherapy to underdose the IOERT region. This approach, called POLO (Partially Omitted Lobe), excluded the IOERT volume from receiving the full prescription dose. Results: Nine patients were treated with this approach, receiving 45 Gy in 20 fractions. A simultaneous integrated boost of 2.5 Gy in 20 fractions was delivered in 6/9 patients. Dose constraints and planning objectives were reported. No severe toxicity was reported while local control and overall survival were 100%. Conclusion: The POLO approach is technically feasible and capable to achieve a significant reduction of radiation dose delivered to the previous treated IOERT area. Advances in knowledge: The study demonstrates the technical and dosimetric feasibility of conservative salvage whole breast radiotherapy, while sparing the area already treated with IORT, in patients with in-breast recurrence.

3D-Printed Coaxial Hydrogel Patches with Mussel-Inspired Elements for Prolonged Release of Gemcitabine

With the aim of fabricating drug-loaded implantable patches, a 3D printing technique was employed to produce novel coaxial hydrogel patches. The core-section of these patches contained a dopamine-modified methacrylated alginate hydrogel loaded with a chemotherapeutic drug (Gemcitabine), while their shell section was solely comprised of a methacrylated alginate hydrogel. Subsequently, these patches were further modified with CaCO3 cross linker and a polylactic acid (PLA) coating to facilitate prolonged release of the drug. Consequently, the results showed that addition of CaCO3 to the formula enhanced the mechanical properties of the patches and significantly reduced their swelling ratio as compared to that for patches without CaCO3. Furthermore, addition of PLA coating to CaCO3-containing patches has further reduced their swelling ratio, which then significantly slowed down the release of Gemcitabine, to a point where 4-layered patches could release the drug over a period of 7 days in vitro. Remarkably, it was shown that 3-layered and 4-layered Gemcitabine loaded patches were successful in inhibiting pancreatic cancer cell growth for a period of 14 days when tested in vitro. Lastly, in vivo experiments showed that gemcitabine-loaded 4-layered patches were capable of reducing the tumor growth rate and caused no severe toxicity when tested in mice. Altogether, 3D printed hydrogel patches might be used as biocompatible implants for local delivery of drugs to diseased site, to either shrink the tumor or to prevent the tumor recurrence after resection.

Рembrolizumab as second line therapy for hepatocellular patient

The optimal hepatocellular cancer (HCC) therapy remains a challenge. Due to checkpoint inhibitors patients with intolerance to the targeted therapy and or those with the impaired liver function can get an appropriate drug therapy. This clinical observation illustrates the long-term effect of pembrolizumab as the 2-line therapy in a patient diagnosed with. Sorafenib in standard doses as first line therapy led to severe toxicity and necessitated the withdrawal of therapy. Although subsequently the doses were reduced and concomitant medications used, sorafenib therapy was discontinued due to pronounced side effects typical of kinase inhibitors. From August 2017 to September 2019, as a part of a clinical study, the patient received 35 courses of immunotherapy with pembrolizumab 200 mg i.v. every 3 weeks, with satisfactory tolerance. The best response - partial tumor regression – was achieved at 84 weeks of therapy and continues to this day. Favorable toxicity profile makes checkpoints inhibitors a good treatment option in patients with impaired liver function (Child-Pugh 7–8 points) or with intolerable toxicity of kinase inhibitors.