Age does not influence efficacy of ramucirumab in advanced gastric cancer: Subgroup analyses of REGARD and RAINBOW.

BACKGROUND AND AIM: REGARD and RAINBOW were global, phase 3, randomized, double-blind trials of second-line ramucirumab for metastatic gastric or gastroesophageal junction adenocarcinoma. Exploratory subgroup analyses were described to assess the efficacy and safety of ramucirumab in REGARD and RAINBOW in young (≤ 45 and < 65 years) and elderly (≥ 65, ≥ 70, and ≥ 75 years) patients. METHODS: Patients were randomized 2:1 to receive ramucirumab plus best supportive care or placebo plus best supportive care (REGARD) or 1:1 to ramucirumab plus paclitaxel or placebo plus paclitaxel (RAINBOW). Subpopulation Treatment Effect Pattern Plots assessed efficacy and adverse events by age groups for ramucirumab versus placebo. RESULTS: The hazard ratios (HRs) for overall survival favored treatment with ramucirumab: REGARD ≤ 45 years (HR: 0.59, 95% confidence interval: 0.27-1.26), < 65 years (0.80, 0.59-1.10), ≥ 65 years (0.72, 0.48-1.08), ≥ 70 years (0.73, 0.44-1.23), and ≥ 75 years (0.59, 0.25-1.37); and RAINBOW ≤ 45 years (0.56, 0.33-0.93), < 65 years (0.78, 0.63-0.97), ≥ 65 years (0.88, 0.66-1.18), and ≥ 70 years (0.88, 0.60-1.28). The exception was elderly patients aged ≥ 75 years in RAINBOW (0.97, 0.47-2.01); however, patient numbers were low in this subgroup (n = 36). Similar findings were observed for progression-free survival, for which HRs numerically favored ramucirumab-treated patients. Adverse events (including grade ≥ 3) were not associated with age. CONCLUSIONS: In comparison with placebo, ramucirumab conferred improvements in efficacy across age groups with a tolerable safety profile. Despite some limitations, these exploratory analyses support the use of ramucirumab in advanced gastric cancer, irrespective of age.

Oxygen therapy alternatives in COVID-19: From classical to nanomedicine.

Around 10-15% of COVID-19 patients affected by the Delta and the Omicron variants exhibit acute respiratory insufficiency and require intensive care unit admission to receive advanced respiratory support. However, the current ventilation methods display several limitations, including lung injury, dysphagia, respiratory muscle atrophy, and hemorrhage. Furthermore, most of the ventilatory techniques currently offered require highly trained professionals and oxygen cylinders, which may attain short supply owing to the high demand and misuse. Therefore, the search for new alternatives for oxygen therapeutics has become extremely important for maintaining gas exchange in patients affected by COVID-19. This review highlights and suggest new alternatives based on micro and nanostructures capable of supplying oxygen and/or enabling hematosis during moderate or acute COVID-19 cases.

Chemically crosslinked guar gum hydrogels: An investigation on the water transport and its relationship with hydrocortisone release.

In this work, we describe the synthesis, the characterization, and the potential application of a pH-responsive guar gum-based hydrogel. The polysaccharide produced permanent hydrogels with improved biocompatibility. In this work, we report the chemical modification of guar gum (with glycidyl methacrylate) and its use, as the main constituent, in obtaining chemically cross-linked hydrogels. The morphology, swelling properties, and cytotoxicity of the resulting materials were studied in-depth. The hydrogels showed to be pH-responsive, and non-toxic being safe to use it as a biomaterial. In addition, we tested the potential of this one as a drug carrier. Herein, we have chosen hydrocortisone (HCS) as a drug model. The mechanism of HCS release changed as a function of pH, owing to different responses in each medium. Our results indicate that the guar gum hydrogels have great potential to be used, with safety, as a drug carrier.

Overcoming Resistance to Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinomas.

Preclinical data suggest that head and neck squamous cell carcinomas (HNSCC) may evade immune surveillance and induce immunosuppression. One mechanism of immune evasion involves the expression of programmed death ligand-1 (PD-L1) in tumor and immune cells, which is, to date, the only biomarker routinely used in clinical practice to select patients with advanced HNSCCs more likely to benefit from anti-PD-1 therapy. Nonetheless, PD-L1 expression alone incompletely captures the degree of sensitivity of HNSCCs to PD-1 inhibitors. Most patients exposed to anti-PD-1 antibodies do not respond to therapy, suggesting the existence of mechanisms of de novo resistance to immunotherapy. Furthermore, patients that initially respond to PD-1 inhibitors will eventually develop acquired resistance to immunotherapy through mechanisms that have not yet been completely elucidated. In this article, we will provide an overview of the immune landscape of HNSCCs. We will briefly describe the clinical activity of inhibitors of the PD-1/PD-L1 axis in this disease, as well as biomarkers of benefit from these agents that have been identified so far. We will review pre-clinical and clinical work in cancers in general, and in HNSCCs specifically, that have characterized the mechanisms of de novo and acquired resistance to immunotherapy. Lastly, we will provide insights into novel strategies under investigation to overcome resistance to immune checkpoint inhibitors.

Consensus on the Treatment and Follow-Up for Metastatic Castration-Resistant Prostate Cancer: A Report From the First Global Prostate Cancer Consensus Conference for Developing Countries (PCCCDC).

PURPOSE: To present a summary of the recommendations for the treatment and follow-up for metastatic castration-resistant prostate cancer (mCRPC) as acquired through a questionnaire administered to 99 physicians working in the field of prostate cancer in developing countries who attended the Prostate Cancer Consensus Conference for Developing Countries. METHODS: A total of 106 questions out of more than 300 questions addressed the use of imaging in staging mCRPC, treatment recommendations across availability and response to prior drug treatments, appropriate drug treatments, and follow-up, and those same scenarios when limited resources needed to be considered. Responses were compiled and the percentages were presented by clinicians to support each response. Most questions had five to seven relevant options for response including abstain and/or unqualified to answer, or in the case of yes or no questions, the option to abstain was offered. RESULTS: Most of the recommendations from this panel were in line with prior consensus, including the preference of a new antiandrogen for first-line therapy of mCRPC. Important aspects highlighted in the scenario of limited resources included the option of docetaxel as treatment preference as first-line treatment in several scenarios, docetaxel retreatment, consideration for reduced doses of abiraterone, and alternative schedules of an osteoclast-targeted therapy. CONCLUSION: There was wide-ranging consensus in the treatment for men with mCRPC in both optimal and limited resource settings.

Consensus on Treatment and Follow-Up for Biochemical Recurrence in Castration-Sensitive Prostate Cancer: A Report From the First Global Prostate Cancer Consensus Conference for Developing Countries.

PURPOSE: To present a summary of the treatment and follow-up recommendations for the biochemical recurrence in castration-sensitive prostate cancer (PCa) acquired through a questionnaire administered to 99 PCa experts from developing countries during the Prostate Cancer Consensus Conference for Developing Countries. METHODS: A total of 27 questions were identified as related to this topic from more than 300 questions. The clinician's responses were tallied and presented in a percentage format. Topics included the use of imaging for staging biochemical recurrence, treatment recommendations for three different clinical scenarios, the field of radiation recommended, and follow-up. Each question had 5-7 relevant response options, including "abstain" and/or "unqualified to answer," and investigated not only recommendations but also if a limitation in resources would change the recommendation. RESULTS: For most questions, a clear majority (> 50%) of clinicians agreed on a recommended treatment for imaging, treatment scenarios, and follow-up, although only a few topics reached a consensus > 75%. Limited resources did affect several areas of treatment, although in many cases, they reinforced more stringent criteria for treatment such as prostate-specific antigen values > 0.2 ng/mL and STAMPEDE inclusion criteria as a basis for recommending treatment. CONCLUSION: A majority of clinicians working in developing countries with limited resources use similar cutoff points and selection criteria to manage patients treated for biochemically recurrent castration-sensitive PCa.

HER2 Status in Gastric and Gastroesophageal Junction Cancer: Results of the Large, Multinational HER-EAGLE Study.

Human epidermal growth factor receptor 2 (HER2) dysregulation is associated with tumorigenesis in gastric/gastroesophageal junction cancer; however, the number of patients with HER2-positive disease is unclear, possibly due to differing scoring criteria/assays. Data are also lacking for early disease. We aimed to assess the HER2-positivity rate using approved testing criteria in a large, real-life multinational population. HER2-positivity was defined as an immunohistochemistry staining score of 3+, or immunohistochemistry 2+ and HER2 amplification detected by in situ hybridization. A total of 4949 patients were enrolled and results showed that 14.2% of 4920 samples with immunohistochemistry results were HER2-positive. HER2-positivity was significantly higher in males (16.1% vs. 9.6% in females), in gastroesophageal versus stomach tumors (22.1% vs. 12.9%), in biopsy versus surgical samples (18.3% vs. 13.0%), in intestinal tumor subtypes versus diffuse (21.5% vs. 4.8%) and mixed types (21.5% vs. 8.5%) (P<0.001), in mixed versus diffuse types (8.5% vs. 4.8%), and in "other" versus diffuse types (11.7% vs. 4.8%; P=0.002). There were no significant differences between stages. Patients in the youngest age percentile had significantly lower HER2-positivity rates than patients in the remaining percentiles (9.2% vs. 15.9%, 15.7%, and 15.1%; P<0.001). HER2-positivity was highest in France (20.2%) and lowest in Hong Kong (10.4%). In conclusion, HER-EAGLE, the first study of its kind to be conducted in a large, multinational population of almost 5000 patients, gives valuable insights into the real-world HER2-positivity rate in a gastric/gastroesophageal junction cancer patient population not selected for disease stage or histology.

Curative-Intent Surgery for Pancreatic Tumors: A Review of Procedures From the Brazilian National Health System.

PURPOSE: In Brazil, a country with major health access disparities, resource limitations make management of pancreatic cancer (PC) challenging. This study evaluated curative-intent surgery for PC in the Brazilian public health care system. METHODS: We collected data for PC surgical procedures with curative intent in Brazil's public health care system (DATASUS) and from the demographic database. Costs, lengths of stay, number of perioperative deaths, and PC deaths were analyzed for each state and then associated with population, gross domestic product (GDP) per capita, and number of procedures. RESULTS: A total of 37,142 patients died as a result of PC in Brazil between 2008 and 2012. The number of deaths (per 100,000 person-years) was highest in the south and southeast regions. Mortality from PC had a positive association with the number of procedures and GDP per capita. Between January 2008 and July 2014, 3,386 procedures were performed, the majority (51.2%) in the southeast region. Four hundred ninety-three patients died, which translates to an inpatient mortality rate of 14.6%. The northern states had the highest perioperative mortality (mean, 25%). The number of procedures per 100,000 residents was higher in the southeast and south. Overall, cost tended to increase as the number of procedures or population increased. For fixed GDP per capita and population, cost tended to increase as the number of procedures increased, whereas for a fixed number of procedures and GDP per capita, cost tended to decrease as population increased. The mean length of hospital stay was 16.9 days, which was higher than in major international centers. CONCLUSION: This study is the first to our knowledge to evaluate regional disparities in PC care in Brazil. Perioperative mortality was high in the public health care system. Regionalized policies that improve care are needed.

Bcl-2 targeted-therapy for the treatment of head and neck squamous cell carcinoma.

Despite recent advances in treatment of head and neck cancer, survival has not improved as expected. Bcl-2 family proteins play important role in regulating apoptosis. Recently, newer molecules have been developed for inhibition of Bcl-2 related proteins. We, herein aim to discuss the importance of Bcl-2 family proteins to the development of head and neck cancer and how the targeted-therapy for inhibition of Bcl-2 and related proteins, based on new drugs and recent patents, could improve the efficacy of the systemic therapy.