Neoadjuvant chemotherapy is considered a new treatment option for potentially resectable pancreatic cancer. However, data are not well established on overall survival and delaying surgery in ...resectable pancreatic cancer, as well as on those patients that ultimately cannot undergo surgery. We analyzed pancreatic cancer patients treated in a tertiary hospital from January 2016 to December 2020. Patients with resectable stage I and II pancreatic cancer were evaluated regarding surgery, neoadjuvant treatment, and other clinical demographics. The survival function was estimated using the Kaplan-Meier method, and the relationship between the variables of interest and the overall survival (OS) was assessed by adopting the proportional regression Cox models. A total of 216 patients were evaluated. 81 of them with resectable/borderline resectable disease and 135 with unresectable /metastatic disease at diagnosis. Median OS for stage I and II disease were 36 and 28 months, respectively. For resectable pancreatic cancer median OS was 28 months, for borderline resectable pancreatic cancer median OS was 11 months. Median OS for stage III (locally advanced) and stage IV (metastatic) were 10 and 7 months, respectively (p < 0.0001). Median OS of 9 months were obtained for patients with stage I and II that did not undergo surgery compared to 25 months in patients that underwent surgery in any time (p < 0.001). Comparing patients with localized disease, median OS for patients treated with upfront surgery was 28 months, compared to 15 months in patients treated with neoadjuvant approach (p = 0.04). Most patients that did not undergo surgery have decline of performance status or disease progression on neoadjuvant treatment. On multivariable analysis in pancreatic cancer stages I and II, including age, sex, borderline or resectable disease, CA 19-9, positive lymph nodes and neoadjuvant treatment, the surgery was the only factor associated with improved overall survival (p = 0.04). Upfront surgery should still be considered a standard of care approach for resectable pancreatic cancer. Biomarker driven studies and randomized trials with combination therapies are necessary to address neoadjuvant chemotherapy and delaying surgery in purely resectable pancreatic cancer.
In recent years, several drugs have been approved for the treatment of patients with metastatic cutaneous melanoma, completely reshaping the landscape of this aggressive disease. Immune therapy with ...cytotoxic T-lymphocyte antigen 4 and programmed cell death-1 inhibitors yielded significant and durable responses, achieving long-term disease control in up to 40% of the patients. BRAF inhibitors (BRAFi), in combination with MEK inhibitors, also resulted in improved overall survival compared with single-agent BRAFi in patients with BRAFV600-mutated metastatic melanoma. The optimized sequencing and duration of treatment, however, is yet to be found. In this article, we thoroughly review current data and discuss how to best sequence the various treatment modalities available at present, based on four distinct clinical presentations commonly seen in clinic. In addition, we review treatment options beyond checkpoint inhibitors and targeted therapy, which may be required by patients failing such effective treatments.
Yolk sac tumor (YST) is the second most common subtype of ovarian germ cell tumors. It usually occurs in the second and third decades of life and is rare in postmenopausal women. In postmenopausal ...women, YST is commonly an aggressive tumor and can present as a pure germ cell component or as a mixed component with other germ cell or epithelial components. The recognition of this histological subtype is important not only for differential diagnosis but also for determining prognosis and treatment decisions. In this case report, we describe a 61-year-old woman with YST coexisting with epithelial carcinoma focusing on the efficacy of systemic therapies.
•Yolk sac tumor (YST) is an aggressive common type of ovarian germ cell tumor.•YST commonly occurs in premenopausal women and is rare in postmenopausal women.•YST is commonly pure and rarely coexists with an epithelial component.•The coexistence of histologic subtypes is associated with an aggressive outcome.•Treatments are surgery and chemotherapy for the adjuvant and metastatic setting.
Palliative sedation (PS) is an intervention to treat refractory symptoms and to relieve suffering at the end of life. Its prevalence and practice patterns vary widely worldwide. The aim of our study ...was to evaluate the frequency, clinical indications and outcomes of PS in advanced cancer patients admitted to our tertiary comprehensive cancer center.
We retrospectively studied the use of PS in advanced cancer patients who died between March 1st, 2012 and December 31st, 2014. PS was defined as the use of continuous infusion of midazolam or neuroleptics for refractory symptoms in the end of life. This study was approved by the Research Ethics Committee of our institution (project number 2481-15).
During the study period, 552 cancer patients died at the institution and 374 met the inclusion criteria for this study. Main reason for exclusion was death in the Intensive Care Unit. Among all included patients, 54.2% (n = 203) received PS. Patients who received PS as compared to those not sedated were younger (67.8 vs. 76.4 years-old, p < 0.001) and more likely to have a diagnosis of lung cancer (23% vs. 14%, p = 0.028). The most common indications for sedation were dyspnea (55%) and delirium (19.7%) and the most common drugs used were midazolam (52.7%) or midazolam and a neuroleptic (39.4%). Median initial midazolam infusion rate was 0.75 mg/h (interquartile range - IQR - 0.6-1.5) and final rate was 1.5 mg/h (IQR 0.9-3.0). Patient survival (length of hospital stay from admission to death) of those who had PS was more than the double of those who did not (33.6 days vs 16 days, p < 0.001). The palliative care team was involved in the care of 12% (n = 25) of sedated patients.
PS is a relatively common practice in the end-of-life of cancer patients at our hospital and it is not associated with shortening of hospital stay. Involvement of a dedicated palliative care team is strongly recommended if this procedure is being considered. Further research is needed to identify factors that may affect the frequency and outcomes associated with PS.
Exercise reduces sympathetic activity (SA), arterial pressure and heart rate in spontaneously hypertensive rats (SHR). Exercise increases oxidative stress (OS) and inflammation is implicated in the ...generation of reactive oxygen species (ROS) and progression of hypertension. To unravel these effects of exercise and considering that SA is driven by medullary areas, we hypothesized that swimming exercise (SW) affects the gene expression (g.e.) of proteins involved in inflammation and OS in the commissural Nucleus of the Solitary Tract (cNTS) and Rostral ventrolateral medulla (RVLM), which control the sympathetic outflow in SHR. We used male SHR and Wistar rats (14-16wks-old) which were maintained sedentary (SED) or submitted to SW (1 h/day, 5 days/wk./6wks). The g.e. of cycloxygenase-2 (COX-2), interleukin 6 (IL-6), interleukin 10 (IL-10), AT-1 receptor (AT-1r), neuroglobin (Ngb) and cytoglobin (Ctb) in cNTS and RVLM was carried out by qPCR. We observed that COX-2 g.e. increased in SW-SHR in cNTS and RVLM compared to SED-SHR. The IL-6 g.e. reduced in RVLM in SW-SHR, whereas IL-10 g.e. increased in SW-SHR in comparison to SED-SHR. The AT-1r g.e. decreased in SW-SHR in cNTS and RVLM compared to SED-SHR. The Ngb and Ctb g.e. in cNTS neurons increased in SHR and Wistar rats submitted to SW compared to SED, but only Ctb g.e. increased in RVLM in SW-SHR and Wistar in comparison to SED. Therefore, the SW altered the g.e. in cNTS and RVLM for reducing the inflammation and ROS formation, which is increased particularly in SHR, consequently decreasing the OS.
Introduction
Chemotherapy-induced nausea and vomiting (CINV) is a distressing side effect that affects many patients undergoing emetogenic chemotherapy, despite the use of antiemetic medications. The ...purpose of this trial was to evaluate the efficacy and safety of gabapentin for the prevention of CINV during the first cycle of treatment in patients receiving moderately or highly emetogenic chemotherapy.
Methods
Eighty chemotherapy-naive patients, scheduled to receive moderately and highly emetogenic chemotherapy, were enrolled in this randomised, double-blind, placebo-controlled clinical trial. All patients received intravenous ondansetron 8 mg, dexamethasone 10 mg and ranitidine 50 mg before chemotherapy on day 1 and oral dexamethasone 4 mg twice a day on days 2 and 3. Patients were randomly assigned to take gabapentin 300 mg or placebo on the following schedule: 5 and 4 days before chemotherapy once daily, 3 and 2 days before chemotherapy twice daily, 1 day before to 5 days after chemotherapy thrice daily. The primary endpoint was complete overall protection from both vomiting and nausea over the course of the entire study (day 1 through day 5), and complete protection during the delayed period (24–120 h after chemotherapy).
Results
The proportion of patients achieving complete response improved from 40% to 62.5%, (
p
= 0.04) when comparing the control group and the gabapentin group, respectively. In the subset of patients who achieved complete control in the acute phase, the percentage of patients who achieved delayed complete control was higher in the gabapentin group (89.3 × 60.7%,
p
= 0.01). Adverse events did not significantly differ between study arms.
Conclusions
Gabapentin is a low-cost strategy to improve complete control of CINV, specially delayed CINV control.
HER2-Low is defined as low levels of HER2 expression, based on a score of 1+ on immunohistochemical (IHC) assay or as an IHC score of 2+ and negative results on in situ hybridization (ISH or FISH). ...They are a heterogeneous population of breast cancers that vary in prognosis and sensitivity to systemic treatments. The frequency and clinical characteristics of pathogenic germline variants (PGVs) in HER2-Low breast cancer (BC) patients is not defined. We analyzed results from patients with BC who underwent multi-gene panel testing (MGPT) (maximum 145 genes) between 2018–2019. We reclassified HER-2 status accordingly. Relationships between the variables of interest were assessed by adopting the proportional regression Cox models. Of a total of 167 BC patients who underwent MGPT, half were hormone-receptor-positive. The median age was 45 years. About two thirds of the patients were in the earlier stage of BC. A total of 57% of the cases were reclassified as HER-2-negative or -Low. PGVs were found in 19% of the patients overall, as follows: seven BRCA1, four BRCA2, two ATM, one ATR, two CFTR, three CHEK2, one FANCA, one MERTK, one MLH1, three MUTYH, one RAD50, three RAD51C, one RECQL4, and two TP53 mutations. In HER2-Low, 26.5% of the patients had PGVs, and in the overall cohort, this was 19.8%. In conclusion, differences in the prevalence of deleterious germline mutations in HER2-Low BC patients compared to non-HER2-Low BC patients were identified. Similar alterations in BRCA were observed in this group of patients compared to the overall cohort. Germline genetic tests should be evaluated in larger cohorts of patients with HER2-Low status to better address the findings.
Currently programmed cell death protein 1 (PD-1) inhibitors in combination with other therapies are being evaluated to determine their efficacy in cancer treatment. However, the effect of PD-ligand ...(L) 1 expression on disease outcomes in stage III (EC III) non-small cell lung cancer is not completely understood. Therefore, this study aimed to assess the influence of PD-L1 expression on the outcomes of EC III non-small cell lung cancer.OBJECTIVECurrently programmed cell death protein 1 (PD-1) inhibitors in combination with other therapies are being evaluated to determine their efficacy in cancer treatment. However, the effect of PD-ligand (L) 1 expression on disease outcomes in stage III (EC III) non-small cell lung cancer is not completely understood. Therefore, this study aimed to assess the influence of PD-L1 expression on the outcomes of EC III non-small cell lung cancer.This study was conducted on patients diagnosed with EC III non-small cell lung cancer who underwent treatment at a tertiary care hospital. PD-L1 expression was determined using immunohistochemical staining, all patients expressed PD-L1. Survival was estimated using the Kaplan-Meier method. Relationships between variables were assessed using Cox proportional regression models.METHODSThis study was conducted on patients diagnosed with EC III non-small cell lung cancer who underwent treatment at a tertiary care hospital. PD-L1 expression was determined using immunohistochemical staining, all patients expressed PD-L1. Survival was estimated using the Kaplan-Meier method. Relationships between variables were assessed using Cox proportional regression models.A total of 49 patients (median age=69 years) with EC III non-small cell lung cancer and PD-L1 expression were evaluated. More than half of the patients were men, and most were regular smokers. The patients were treated with neoadjuvant chemotherapy, surgery, or sequential or combined chemotherapy and radiotherapy. The median progression-free survival of the entire cohort was 14.2 months, and the median overall survival was 20 months. There was no significant association between PD-L1 expression and disease progression, clinical characteristics, or overall survival.RESULTSA total of 49 patients (median age=69 years) with EC III non-small cell lung cancer and PD-L1 expression were evaluated. More than half of the patients were men, and most were regular smokers. The patients were treated with neoadjuvant chemotherapy, surgery, or sequential or combined chemotherapy and radiotherapy. The median progression-free survival of the entire cohort was 14.2 months, and the median overall survival was 20 months. There was no significant association between PD-L1 expression and disease progression, clinical characteristics, or overall survival.PD-L1 expression was not correlated with EC III non-small cell lung cancer outcomes. Whether these findings differ from the association with immune checkpoint inhibitors remains to be addressed in future studies.CONCLUSIONSPD-L1 expression was not correlated with EC III non-small cell lung cancer outcomes. Whether these findings differ from the association with immune checkpoint inhibitors remains to be addressed in future studies.
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