The overall survival results for both chemotherapy subgroups are consistent with the results in the overall intention-to-treat population with overlapping 95% CIs for the hazard ratio and point ...estimates less than 1. ...post-discontinuation anticancer therapy including both chemotherapy and immunotherapy or targeted therapy, was well balanced between the treatment groups. ...as we discuss in the Article, enrichment of PD-L1 expression is known to result in comparatively increased benefit for immunotherapies across a variety of tumour types,2,3 and this was observed in KEYNOTE-859, wherein the magnitude of benefit was greater for patients with increasing PD-L1 combined positive score (CPS) values.
The phase III POLO study demonstrated significant progression-free survival (PFS) benefit for active olaparib maintenance therapy versus placebo for patients with metastatic pancreatic adenocarcinoma ...and a germline BRCA mutation. Here, we report the final analysis of overall survival (OS) and other secondary end points.
Patients with a deleterious or suspected deleterious germline BRCA mutation whose disease had not progressed after ≥ 16 weeks of first-line platinum-based chemotherapy were randomly assigned 3:2 to active maintenance olaparib (300 mg twice daily) or placebo. The primary end point was PFS; secondary end points included OS, time to second disease progression or death, time to first and second subsequent cancer therapies or death, time to discontinuation of study treatment or death, and safety and tolerability.
In total, 154 patients were randomly assigned (olaparib, n = 92; placebo, n = 62). No statistically significant OS benefit was observed (median 19.0
19.2 months; hazard ratio HR, 0.83; 95% CI, 0.56 to 1.22;
= .3487). Kaplan-Meier OS curves separated at approximately 24 months, and the estimated 3-year survival after random assignment was 33.9% versus 17.8%, respectively. Median time to first subsequent cancer therapy or death (HR, 0.44; 95% CI, 0.30 to 0.66;
< .0001), time to second subsequent cancer therapy or death (HR, 0.61; 95% CI, 0.42 to 0.89;
= .0111), and time to discontinuation of study treatment or death (HR, 0.43; 95% CI, 0.29 to 0.63;
< .0001) significantly favored olaparib. The HR for second disease progression or death favored olaparib without reaching statistical significance (HR, 0.66; 95% CI, 0.43 to 1.02;
= .0613). Olaparib was well tolerated with no new safety signals.
Although no statistically significant OS benefit was observed, the HR numerically favored olaparib, which also conferred clinically meaningful benefits including increased time off chemotherapy and long-term survival in a subset of patients.
Prostate cancer is the second most common cause of cancer death in men in the United States. The most common sites of metastasis include the bone, lymph nodes, lung, liver, pleura, and adrenal ...glands, whereas metastatic prostate cancer involving the gastrointestinal tract has been rarely reported. A 64-year-old African-American man with a history of prostate cancer presented with anemia. He reported the passing of dark colored stools but denied hematemesis or hematochezia. Colonoscopy revealed circumferential nodularity, and histology demonstrated metastatic carcinoma of the prostate. Esophagogastroduodenoscopy showed hypertrophic folds in the gastric fundus, and microscopic examination revealed tumor cells positive for prostate-specific antigen. Bone scanning and computed tomography of the abdomen and pelvis did not show metastasis. It is crucial to distinguish primary gastrointestinal cancer from metastatic lesions, especially in patients with a history of cancer at another site, for appropriate management.
Summary Background PD-1 inhibitors combined with chemotherapy have shown efficacy in gastric or gastro-esophageal junction cancer. We compared the efficacy and safety of pembrolizumab plus ...chemotherapy with placebo plus chemotherapy in participants with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma. Methods KEYNOTE-859 is a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial, done at 207 medical centres across 33 countries. Eligible participants were aged 18 years and older with previously untreated histologically or cytologically confirmed locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive pembrolizumab or placebo 200 mg, administered intravenously every 3 weeks for up to 35 cycles. All participants received investigator's choice of fluorouracil (intravenous, 800 mg/m2 per day) administered continuously on days 1–5 of each 3-week cycle plus cisplatin (intravenous, 80 mg/m2) administered on day 1 of each 3-week cycle or capecitabine (oral, 1000 mg/m2) administered twice daily on days 1–14 of each 3-week cycle plus oxaliplatin (intravenous, 130 mg/m2) administered on day 1 of each 3-week cycle. Randomisation was done using a central interactive voice-response system and stratified by geographical region, PD-L1 status, and chemotherapy in permuted block sizes of four. The primary endpoint was overall survival, assessed in the intention-to-treat (ITT) population, and the populations with a PD-L1 combined positive score (CPS) of 1 or higher, and PD-L1 CPS of 10 or higher. Safety was assessed in the as-treated population, which included all randomly assigned participants who received at least one dose of study intervention. Here, we report the results of the interim analysis. This study is registered with ClinicalTrials.gov, NCT03675737, and recruitment is complete. Findings Between Nov 8, 2018, and June 11, 2021, 1579 (66%) of 2409 screened participants were randomly assigned to receive pembrolizumab plus chemotherapy (pembrolizumab group; n=790) or placebo plus chemotherapy (placebo group; n=789). Most participants were male (527 67% of 790 participants in the pembrolizumab plus chemotherapy group; 544 69% of 789 participants in the placebo plus chemotherapy group) and White (426 54%; 435 55%). Median follow-up at the data cutoff was 31·0 months (IQR 23·0–38·3). Median overall survival was longer in the pembrolizumab group than in the placebo group in the ITT population (12·9 months 95% CI 11·9–14·0 vs 11·5 months 10·6–12·1; hazard ratio HR 0·78 95% CI 0·70–0·87; p<0·0001), in participants with a PD-L1 CPS of 1 or higher (13·0 months 11·6–14·2 vs 11·4 months 10·5–12·0; 0·74 0·65–0·84; p<0·0001), and in participants with a PD-L1 CPS of 10 or higher (15·7 months 13·8–19·3 vs 11·8 months 10·3–12·7; 0·65 0·53–0·79; p<0·0001). The most common grade 3–5 adverse events of any cause were anaemia (95 12% of 785 participants in the pembrolizumab group vs 76 10% of 787 participants in the placebo group) and decreased neutrophil count (77 10% vs 64 8%). Serious treatment-related adverse events occurred in 184 (23%) participants in the pembrolizumab group and 146 (19%) participants in the placebo group. Treatment-related deaths occurred in eight (1%) participants in the pembrolizumab group and 16 (2%) participants in the placebo group. No new safety signals were identified. Interpretation Participants in the pembrolizumab plus chemotherapy group had a significant and clinically meaningful improvement in overall survival with manageable toxicity compared with participants in the placebo plus chemotherapy group. Therefore, pembrolizumab with chemotherapy might be a first-line treatment option for patients with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma. Funding Merck Sharp and Dohme.
Despite curative-intent treatment, most patients with locally advanced esophageal cancer will experience disease recurrence or locoregional progression, highlighting the need for new therapies. ...Current guidelines recommend definitive chemoradiotherapy in patients ineligible for surgical resection, but survival outcomes are poor. Pembrolizumab is well tolerated and provides promising antitumor activity in patients with previously treated, advanced, unresectable esophageal/esophagogastric junction cancer. Combining pembrolizumab with chemoradiotherapy may further improve outcomes in the first-line setting. Here, we describe the design and rationale for the double-blind, Phase III, placebo-controlled, randomized KEYNOTE-975 trial investigating pembrolizumab in combination with definitive chemoradiotherapy as first-line treatment in patients with locally advanced, unresectable esophageal/gastroesophageal junction cancer. Overall survival and event-free survival are the dual primary end points.
Our objective was to assess the gender-related effects of alcohol consumption on blood pressure (BP) in a representative sample of the adult US population.
We examined data from the National Health ...and Nutrition Examination Survey 1999-2000. The effects of various risk factors for hypertension on BP were examined with analysis of covariance statistics.
Of the 5448 adults over 20 years of age, 2650 (48.7%) reported the intake of one or more drinks per day over the past year. In this population, the mean +/- SEM age was 46.9 +/- 0.34 years, the body mass index was 24.8 kg/m, 1257 (47.4%) were women, systolic BP was 124.3 +/- 0.44 mmHg and diastolic BP was 72.7 +/- 0.27 mmHg. Hypertension was reported in 21.1%, diabetes in 5.1% and cigarette smoking in 39.7%. A significant effect on systolic BP was shown with age (P < 0.01), body mass index (P < 0.01), race (P = 0.01), gender (P < 0.01) and diabetes (P < 0.01). The interaction with gender and alcohol drinking level was significant (P = 0.02). Post-hoc analysis localized the source of this effect. There was a significant increase in systolic BP between one and three and between one and four, but not between one and two, drinks per day in men. This effect was not observed in women.
Consistent with previous reports, our study suggests that alcohol intake up to two drinks per day has no effect on BP. There was a gender-related effect of alcohol intake in excess of two drinks per day on BP, with increased BP observed only in men but not in women.
Neurorehabilitation is an important part of getting better for people who have nerve illnesses or accidents. Brain-computer interfaces (BCIs) and robotic exoskeletons have shown promise in better ...recovery results by allowing focused therapy and making neurons more flexible. This paper gives an outline of the current study on closed-loop control systems that combine robotic exoskeletons and brain-computer interfaces (BCIs) for neurorehabilitation. It also talks about the pros and cons of these systems. Closed-loop control systems try to make two-way communication possible between the user's brain activity (measured by BCIs) and the robotic suit. This way, treatments can be changed in real time based on the user's neurological signs. This method makes it possible for more personalized and flexible therapy plans, which can help people recover their movement skills and become more useful. When BCIs are combined with artificial exoskeletons, they offer many benefits, such as exact control over movement parameters, increased involvement and motivation through immersive feedback, and the chance to induce learning by coordinating brain activity and physical output. To make these systems work better, though, problems like signal processing delay, calibration issues, and the need for user training must be fixed. Recent research has shown that closed-loop control systems can be used and might be helpful in a number of neurorehabilitation situations, such as helping people who have had a stroke or spinal cord injury get their movement skills back and helping people with neurological conditions regain their independence. In the future, researchers should work on improving these systems' algorithms and hardware, running large-scale clinical studies to show that they work, and finding new ways to improve neurorehabilitation results by combining modern technology.
It is well-known that malignancies, particularly pancreatic and brain cancers, often present as venous thromboembolism. However, stroke and angina attributable to arterial occlusion are relatively ...common presentations as well. We are reporting a patient, with treatment-naïve hepatitis C and multiple liver nodules, was admitted for deep vein thrombosis (DVT) and pulmonary embolism (PE). Subsequently, she developed an ascending paralysis due to spinal cord infarct (SCI) despite adequate anticoagulation. She also had an enlargement of left supraclavicular lymph node, which was confirmed histologically metastatic cholangiocarcinoma. To our best knowledge, this is the first literature report showing the association linking SCI to metastatic cholangiocarcinoma as a consequence of hypercoagulable state of malignancy.
Prostate cancer is the second most common cause of cancer death in men in the United States. The most common sites of metastasis include the bone, lymph nodes, lung, liver, pleura, and adrenal ...glands, whereas metastatic prostate cancer involving the gastrointestinal tract has been rarely reported. A 64-year-old African-American man with a history of prostate cancer presented with anemia. He reported the passing of dark colored stools but denied hematemesis or hematochezia. Colonoscopy revealed circumferential nodularity, and histology demonstrated metastatic carcinoma of the prostate. Esophagogastroduodenoscopy showed hypertrophic folds in the gastric fundus, and microscopic examination revealed tumor cells positive for prostate-specific antigen. Bone scanning and computed tomography of the abdomen and pelvis did not show metastasis. It is crucial to distinguish primary gastrointestinal cancer from metastatic lesions, especially in patients with a history of cancer at another site, for appropriate management.
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