Coastal communities are flooding more than we realize. Here's why.
'I view it as a harbinger of what's to come,' said Katherine Anarde, an assistant professor of coastal engineering at North Carolina State University and one of the lead authors of the study, published Monday in the journal Communications Earth & Environment.
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Medscape
16 minutes ago
- Medscape
ASCO 2025: Melanoma TILs, Toxicity, and Diet Insights
This transcript has been edited for clarity. Welcome, everybody. My name is Teresa Amaral. Today I'm here with you to follow up on my presentation on the best of ASCO 2025. Today, we'll have two different sections. The first one is dedicated to the rapid oral communications, and the second one is dedicated to the oral communications that took place on the last day of the congress. For the rapid oral communications, we'll focus on one topic that came through three presentations, tumor-infiltrating lymphocyte (TIL) therapy. Then we will look into a very interesting aspect: the reduction in toxicity associated with immunotherapy that we know is an important aspect for patients that need to receive immunotherapy. And finally, we'll look into a potential modifiable factor that might be associated with better outcomes in patients receiving immunotherapy, which is a diet rich in fiber. In the oral communications, we'll focus on the adjuvant trials — two of them that were quite important to be presented in this session. Then [I'll discuss] a trial that dealt with an unanswered question, which is how long should we treat patients in the metastatic setting. And finally, we will look into two different trials. The first one was on sequencing therapy, which was the DREAMseq trial on the final analysis, and then [there was] a specific analysis for patients that have symptomatic brain metastases, which are still a population of patients that unfortunately are excluded from the majority of clinical trials despite the fact that they do not a very good outcome. Starting with the TIL therapy, the first trial or the first presentation that I want to show you is a new way of applying TIL therapy. Basically, this is a new engineered TIL cell therapy that is intended to be given to patients that already received immune checkpoint inhibitors — so [patients] that are resistant to this therapy. But the interesting part of this type of therapy is that it doesn't require giving interleukin-2, and it also is possible to be given with a low dose of lymphodepletion. This is one of the reasons why I decided to bring this study because we know that TIL therapy might have a good outcome in the long run and these are the results that we are going to discuss in the next presentation. One of the problems is the toxicity that is associated with the pre-therapy and the after-therapy that we need to give to these patients, which includes this lymphodepleting chemotherapy and then the interleukin-2. What these very preliminary data showed is that it is indeed feasible to do this type of therapy by not giving interleukin-2 and reducing the lymphodepleting chemotherapy, and that the overall response rate was quite reassuring because we have an overall response rate that is around 67%. The median duration of response was not reached. Of course, we will need to wait for further data because this phase 1/2 trial is recruiting and we will need to confirm this data further in a broader population with more patients. But I think these results are quite reassuring and will maybe allow us to give this type of therapy to a broader spectrum of patients, as we don't need to have fitter patients to receive this therapy because we have low toxicity. The next discussion, or the next work, that was presented was indeed quite interesting because it looked into the 5-year-old outcome of another TIL product that is called lifileucel. Basically, what the authors showed was that this one-time therapy that was given was able to demonstrate durable and deepening responses in patients with advanced melanoma. It was also interesting to see the long-term toxicity is not more than what we saw before, because the toxicity is mostly associated with the interleukin-2 and lymphodepleting chemotherapy that is necessary to give with this product. So in line with what we discussed in the previous work, this is one of the reasons why most patients, or some patients, cannot receive this type of therapy. What we saw was that after 5 years, approximately 20% of the patients remained alive. Obviously, the best outcomes are seen in the patients that do respond. If the patient responds, the chances that they have a long-term outcome are significant, which is expected. So, the other side shows that this might be feasible, at least for approximately one fifth of the population. Another point that I would like to go through with you is that we saw two works looking into TILs that are definitely a potential therapeutic option for patients that received therapy in the first line, or patients that did not benefit from immunotherapy in the first line. The third work that I would like to discuss with you is the fact — and it was also presented in these rapid oral communications — that indeed not all TILs that we give to patients are the same. What the authors from this work looked into are the infusion product characteristics that are able to predict the response of patients that are treated with TILs. What they showed is the TIL persistence and also the distinctive TIL population in terms of immunophenotypic features, in terms of the proportion of CD8+ T cells, and the high surface expression of LAG3+. All of these characteristics are associated with improved TIL outcomes in patients with metastatic melanoma, meaning that not everything that we infuse that are called TILs work exactly the same and have the same influence, let's say, on the patient's response. This is obviously important because in the future, we might need to concentrate on some strategies, or on other strategies, that modulate ex vivoTIL expansion, so that we have the optimal TIL phenotype associated with better outcomes and we make sure the TILs that we are giving to our patients are the ones that will most likely produce a better outcome — a longer response, but a more durable response. I found this work quite interesting because it's always nice and important to look into these details and understand exactly what we are treating our patients with and how these treatment characteristics influence the patient's outcomes. The second point I would like to discuss with you is the toxicity that I mentioned in the very beginning. We treat a significant amount of patients with immunotherapy, but we know that one of the problems of immunotherapy is the toxicity associated with the therapy. Several strategies are being investigated to reduce the toxicity associated with immunotherapy. One of the strategies that was presented this year is looking into interleukin-6 receptor blocking with an antibody called sarilumab. This was tested in patients that received a combination of ipilimumab, nivolumab, and relatlimab — patients with resectable stage III or stage IV melanoma. Basically, what the author showed was that indeed it was possible to reduce the toxicity associated with this triple combination. Not only did this reduce the grade 3 to grade 5 immune-related adverse events to 12% when we use this interleukin-6 receptor inhibitor, but it also resulted in the best overall response rate being more than 60% — 64%, approximately. This means that it might not only be able to reduce the severe toxicity, so grade 3 and grade 4 adverse events, but also allow patients to have a long-term benefit — especially because this is one of the highest overall response rates that we saw recently in terms of combination of immunotherapy. Obviously, these data need to be confirmed by a larger trial looking into whether this triple combination with, or without, this interleukin-6 receptor inhibitor allows lower toxicity and the high response rate we saw in this smaller trial. Finally, for the rapid oral communications, I would like to show you a trial that looks into acting on some potential modulated factors, including the diet of the patients that we treat with immune checkpoint inhibitors. This was a randomized phase 2 trial that looked into a high-fiber diet intervention in patients who received immune checkpoint inhibitors. What they showed is that it is feasible to do these kinds of studies, but it's quite challenging, especially because some patients progressed earlier or abandoned the study due to other aspects that did not really have to do with the diet itself. Giving this high-fiber diet is safe and it's also well tolerated, and it seems that this high-fiber diet might lead to improved responses in patients receiving immune checkpoint inhibitors. I must say that it might lead [to these responses], only because these are very preliminary data and they need some kind of confirmation before we start prescribing high fiber diets to all patients that are receiving immune checkpoint inhibitors. I think it's very interesting that these types of factors are being analyzed and are being discussed and investigated because these might be, I would say, simple changes that we can make in order to improve the patient's outcomes to the current therapies that we offer them anyhow. Moving into oral communications, I will start by looking into the adjuvant trials. Two important adjuvant trials were discussed. The first one was RELATIVITY-098. This was a trial that investigated programmed cell death protein 1 (PD-1) monotherapy vs PD-1 plus a LAG-3 inhibitor in the adjuvant setting. Unfortunately, the trial was negative, but I think it's very important that we show these negative trials because it allows us to understand what happened and prevents other companies or other groups from looking at the same question exactly the same way, because the reasons, or the potential reasons, for the failure of the trial were not known or were not published. I think it's very important that these negative data are presented so that we can all learn and avoid repetition of the same issues. Basically, the combination did not improve relapse-free survival compared to the monotherapy, although there were no new safety data. Interestingly enough, from the biomarker analysis and the preliminary analysis that was presented, the message came out that for this combination to work, it may be necessary for some tumor cells to be present and not completely excised, as was [the case] in this setting. These comparisons were made with the same combination in the metastatic setting, where the combination was better than immunotherapy. This kind of analysis is always interesting to look into because it might give us some hints on where we can move with this combination in the future.
Associated Press
18 minutes ago
- Associated Press
Leaping sturgeon provide a show for nature lovers on Maine rivers
AUGUSTA, Maine (AP) — The Kennebec River in Maine's capital city of Augusta is known for its population of Atlantic and shortnose sturgeon. The fish sometimes leap completely from the water, as at least one did on Wednesday. The shortnose population on the river nearly doubled from about 5,100 in the late 1970s to more than 9,400 around 2000, and it has likely grown since, state biologists have said. The ancient fish have also shown signs of recovering elsewhere in Maine, such as the Saco River further south. Scientists have proposed a number of reasons why sturgeon jump out of the water, including regulating their swim bladder, communicating with other sturgeon, shedding parasites and avoiding predators. Shortnose sturgeon can weigh up to 60 pounds (27 kilograms), while Atlantic sturgeon can be much larger, with some weighing as much as 800 pounds (363 kilograms). The fish thrill nature lovers who are fortunate to catch their sudden leaps along Maine rivers. Catching a glimpse of them is often a matter of luck.
CBS News
18 minutes ago
- CBS News
Map shows where Philadelphia parents can get free backpacks, immunizations ahead of school year
Is it too soon to talk back-to-school? Not for the School District of Philadelphia. The district is gearing up for its annual "Ring the Bell" bus tour, designed to connect families with essential school resources ahead of the upcoming academic year. Over the next few weeks, families can spot a colorful "Ring the Bell" school bus making stops in neighborhoods across the city. The goal: to bring support directly to where families live, work and shop. All stops run from 10 a.m. to 2 p.m. At each stop, parents and guardians can: Parents don't need to bring their student to the tour — only their student ID. Philadelphia public schools reopen Monday, Aug. 25, 2025. Check out the map above for locations where you can get a free backpack for your child, or get them their required immunizations and physicals for the upcoming school year. Monday, July 28, 2025*School of the Future – 4021 Parkside Ave, Phila., PA 19104 Friday, Aug. 1, 2025Fashion District Philadelphia – 901 Market St, Phila., PA 19107 Monday, Aug. 4, 2025*Martin Luther King High School – 6100 Stenton Ave, Phila., PA 19138 Wednesday, Aug. 6, 2025*George Washington High School Football Field – 10175 Bustleton Ave, Phila., PA 19116 Saturday, Aug. 9, 2025Citizens Bank Park – 1 Citizens Bank Way, Phila., PA 19148 Tuesday, Aug. 12, 2025Marcus Foster Memorial Stadium (Gratz Supersite) – 1627 W. Hunting Park Ave, Phila., PA 19140 Friday, Aug. 15, 2025Roosevelt Mall – 2329 Cottman Ave, Phila., PA 19152
