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True progression or pseudoprogression in glioblastoma patients?

MIAMI, FLORIDA (STRICTLY EMBARGOED UNTIL SEPT. 29, 2023 AT 5PM ET) – Is it true progression or pseudoprogression in tumor growth? Credit: Photo by Sylvester…



MIAMI, FLORIDA (STRICTLY EMBARGOED UNTIL SEPT. 29, 2023 AT 5PM ET) – Is it true progression or pseudoprogression in tumor growth?

Credit: Photo by Sylvester

MIAMI, FLORIDA (STRICTLY EMBARGOED UNTIL SEPT. 29, 2023 AT 5PM ET) – Is it true progression or pseudoprogression in tumor growth?

That’s the critical question for radiation and medical oncologists treating patients with glioblastoma, the most common and aggressive form of brain cancer. Distinguishing between these types of progression is vitally important for treatment management.

“Knowing if it’s true progression, indicative of a poor response to treatment, or pseudoprogression, a favorable response that may look worse due to swelling or tumor necrosis, is essential for clinicians,” said Eric Mellon, MD, PhD, a radiation oncologist and researcher with Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine. “That knowledge can guide us in adjusting current treatment in real time.”

He and his research colleagues are presenting results from two recent studies on this topic at ASTRO 2023, the annual meeting of the American Society for Radiation Oncology, Oct. 1-4, in San Diego.

One study was designed to determine if daily monitoring of tumor changes during a course of radiation therapy could result in early prediction of treatment response. The MRI-guided linear accelerator systems, known as MR-linac, that deliver radiation therapy allow for this type of monitoring and detection of patterns within these volume changes. 

Sylvester researchers used sophisticated analytical and machine learning tools, including a linear fitting model to test their prediction theory on a prospective cohort of glioblastoma patients undergoing chemoradiation for their cancers.

“The model was trained to predict between no progression, pseudoprogression and true progression, and the results were cross-validated,” explained Kaylie Cullison, an MD/PhD student who is conducting her PhD research in Mellon’s Sylvester laboratory, is the study’s first author, and will present the data at ASTRO 2023. 

Of the 28 patients analyzed in the study, 11 had no tumor growth on first diagnostic MRI after treatment (no progression), five were found to have pseudoprogression based on long-term stability of MRI findings, and 12 had true progression determined by continuing tumor growth beyond six months, tissue sampling showing active malignancy or rapid death.

The model achieved an overall accuracy of 86%, when predicting three outcome classes (no progression, true progression and pseudoprogression), and an accuracy of 93% when predicting between no progression versus any kind of progression.

“We identified patterns of tumor behavior during therapy that were indicative of differences in growth patterns between true progression and pseudoprogression,” said Mellon, co-leader of Sylvester’s Neuro-Oncology Site Disease Group who leads numerous clinical trials for brain tumors. “These volume changes during treatment may be early markers of treatment response.”

Next steps, according to Mellon and Cullison, include automating real-time tumor monitoring by using a deep-learning solution for volume delineation on daily treatment scans.

Their other study, conducted simultaneously with the above one, sought to determine the predictive value of weekly delta-radiomic features extracted from MR-linac systems used for treating glioblastoma patients.

Whereas radiomics focus on quantitative features extracted from medical images to correlate with various biological features and clinical endpoints for cancer diagnosis, prognosis and clinical decisions, delta radiomics extend that analysis by examining feature variation at different time points, usually before and after therapy.

In this case, however, the acquisition time points were during therapy. Sylvester researchers deployed supervised machine learning with a sophisticated classification model to predict true progression or pseudoprogression outcomes. Their model included 41 variables – 39 tumor texture features plus lesion volume and mean lesion intensity – per time point to generate the predictions.

Of the 10 most prognostic features, 90% happened during an early time point, suggesting that prognostic changes in the underlying tumor microenvironment occur within the first 15 treatment sessions (or first half of treatment).

“Our findings support the theory that delta-radiomic features from MR-linac radiotherapy can predict treatment response during therapy, which is earlier than current methods,” concluded Mellon. “And doing so would allow physicians to intensify current treatment for poorly responding patients.”       

Mellon and Cullison say future research should include a larger patient cohort and the use of MR-linac systems with multiparametric MRI to further test the model’s prognostic value.

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Essential retailer files for bankruptcy, stores will close

A retail store chain relied on by millions of shoppers will close stores after filing for Chapter 11 bankruptcy.



Retail store chains that file for Chapter 11 bankruptcy can suffer from damaged vendor relationships that cause empty shelves, limited access to capital needed to pay landlords and wages, and a damaged reputation that keeps shoppers away. It can also cause store closures, leaving customers in the lurch.

For these reasons, filing for bankruptcy reorganization is a retailer’s last option. Nevertheless, bankruptcy has become increasingly common because of fierce competition from e-commerce stores like Amazon  (AMZN) - Get Free Report and big-box retailers like Walmart  (WMT) - Get Free Report and Costco Wholesale  (COST) - Get Free Report.

Shoppers can usually find the items they buy at those stores when retailers close because of bankruptcy. However, that task is more challenging when the retailer filing for Chapter 11 bankruptcy sells essential items not readily available elsewhere.

Store closing sale announcement at a Bed Bath & Beyond indoor mall in northern Idaho. (Photo by: Don & Melinda Crawford/UCG/Universal Images Group via Getty Images)

UCG/Getty Images

Brick-and-mortar retailers face stiff competition.

Sears had 700 stores when it filed for bankruptcy in 2018. Nowadays, it operates fewer than 20 stores after reemerging from Chapter 11 bankruptcy in 2022.

Bed Bath & Beyond had over 1,500 stores in 2018, but less than 300 when it went bankrupt earlier this year.

Related: Bankruptcy could force this popular retailer to close 500 stores

The success of large brick-and-mortar stores like Walmart and Costco and e-commerce alternatives like Amazon are a big reason behind those failures.

Walmart’s annual revenue surged from over $450 billion to $611 billion over the past decade. Costco’s revenue has more than doubled to $242 billion, and Amazon’s sales have increased from $74 billion to over $500 billion.

Those sales have come at the expense of other retailers less able to compete on price and convenience due to impaired balance sheets, buying power, or both.

A mountain of debt takes its toll

Rite Aid  (RAD) - Get Free Report is the latest retailer to declare bankruptcy. It has similarly lost sales because of increasing competition from these larger competitors. 

Walmart is the fifth largest company, and Costco Wholesale is the 11th largest company ranked by prescription market share. Meanwhile, Amazon is pushing more deeply into pharmacy by offering online prescriptions.

Competition isn't the only reason why Rite Aid sought bankruptcy protection from creditors on Oct 15.

Rite Aid also filed for bankruptcy to insulate itself against a lawsuit that could cost it over one billion dollars to settle.

More bankruptcy:

The Department of Justice filed a civil suit against Rite Aid in March, alleging pharmacists “repeatedly filled prescriptions for controlled substances with obvious red flags" and that it "intentionally deleted internal notes about suspicious prescribers.”

The company was already struggling before the Department of Justice alleged it inappropriately filled opioid prescriptions, contributing to the opioid epidemic.

Revenue at the 2,300-store retail pharmacy chain slumped 6% from one year ago during the June quarter, despite millions of shoppers relying on it to fill prescriptions or buy everyday items, like aspirin, vitamins, and toothpaste, every week.

Slumping sales couldn't have happened at a worse time for the company. Its interest expense on over $3.3 billion in debt has soared 35% to $65 million per quarter because of rising interest rates. 

That extra burden, plus higher costs, increased theft, and goodwill write-downs on past acquisitions led to staggering losses exceeding $300 million in the quarter and full-year guidance for losses eclipsing $4.78 per share.

Those losses left Rite Aid with little wiggle room to negotiate a settlement with the Justice Department, given Walgreens Boots  (WBA) - Get Free Report and CVS Health  (CVS) - Get Free Report settled similar suits for $5.7 billion and $4.9 billion in the past year.

Rite Aid's decision to file for bankruptcy protection is based on restructuring plan negotiated with creditors that includes store closures.

“In connection with the court-supervised process, the Company will continue assessing its footprint and close additional underperforming stores. These efforts will further reduce the Company’s rent expense and are expected to strengthen its overall financial performance,” said Rite Aid in a statement announcing the bankruptcy news.

Rite Aid hasn't said which stores will close yet, but the Wall Street Journal previously reported the company could shutter up to 500 locations. 

Stores that don't close will remain in operation via a $3.45 billion debtor-in-possession financing agreement with lenders.

“Rite Aid has received a commitment for $3.45 billion in new financing from certain of its lenders. This financing is expected to provide sufficient liquidity to support the Company throughout this process,” according to the statement.

The bankruptcy filing follows the receipt of a non-compliance letter from the New York Stock Exchange on Oct. 4 due to its shares trading below $1 and its market cap being below $50 million. The company was given a short window of time to get shares back above those thresholds before being delisted, further pressuring management into its decision.

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Apple’s iPhone can help you understand risk level of two common health issues

New improvements and updates to Apple’s hallmark product come with strides in the health and wellness field.



Each year, Apple  (AAPL) - Get Free Report releases a new iPhone that promises to be higher-powered, broadly better, and oftentimes bigger, than previous models. 

The 2023 iteration of the coveted tech comes as no exception. 

Related: Apple addresses iPhone radiation allegations with a swift update (here's what to do)

Cupertino's Sept. 12 Wonderlust event unveiled the latest lineup of iPhones, an upgraded Apple Watch 9, new operating systems, updated software for popular accessories, and more.

The iPhone 15 lineup offers a slick new set of features including an improved camera. And with the top-of-the-line iPhone 15 Pro Max selling for $1,199 in the U.S., many users expect it to be just that: the very best.

While plenty of us continue to fawn over its zoom capabilities and crisp video quality, other users are finding more utilitarian ways to leverage the new iOS 17 and improve their lives markedly. 

A particularly useful new iPhone feature

Apple's latest operating system, iOS 17, features a new tool to help users better understand their mental well being. If you've got the latest operating system downloaded onto your phone, you can fill out a preloaded mental-health questionnaire to probe how you're doing. 

Here's how to do it: 

  1. Open the health app
  2. Click browse -> mental wellbeing
  3. Choose your age range and begin
  4. Answer all 16 questions to the best of your ability
  5. Complete questionnaire
  6. View your results and complete
  7. (Optional) export as a PDF and share with your doctor or trusted mental health expert. 

Sample questions include: "Over the last two weeks, how often have you been bothered by the following problems?" and lists factors like "feeling nervous, anxious or on edge." Users are prompted to select from a sliding scale of multiple-choice answers ranging from "not at all" to "nearly every day."

Based on your answers, Apple will give you a range of risks and markers to determine things like anxiety and depression levels. The scale ranges from none (little to no risk) to severe. 

AliveCor President and CEO Vic Gundotra rests his thumb on a wristband sensor to check his heart rate in Mountain View, Calif. on Thursday, Dec. 7, 2017. AliveCor just received FDA approval for its Kardia Band EKG-monitoring wristband for the Apple Watch. (Photo By Paul Chinn.

San Francisco Chronicle/Hearst Newspapers via Getty Images/Getty Images

This move marks yet another concerted effort by Apple to seamlessly integrate current users in its push toward wellness. 

Other features in the Health app include medication reminders and trackers, emotional mood logging, and mindful minute tracking.

Apple has long said it wants to get a strong foothold in the health-and-wellness space. What had initially been met by surprise and skepticism is now largely accepted as the tech giant's next frontier; Chief Executive Tim Cook predicts the company's health strides will be its "greatest contribution to mankind." 

Apple notes to TheStreet, "These assessments are not to diagnose anxiety or depression. These assessments can help users determine their risk level, connect to resources available in their region, and create a PDF to share with their doctor."

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Why Invest in Diamonds?

Investors Alley
Why Invest in Diamonds?
Diamonds are a $1.2 trillion natural resource, uncorrelated to stocks and negatively correlated to gold and silver…



Investors Alley
Why Invest in Diamonds?

Diamonds are a $1.2 trillion natural resource, uncorrelated to stocks and negatively correlated to gold and silver with significantly less volatility than these asset classes.

Diversification is essential for asset preservation, risk management, and consistent returns. Investors seek to combine uncorrelated assets, and for this reason, diamonds are an extremely attractive asset. They often produce returns when other assets fall.

Uncorrelated Stability & Opportunity

Historically, diamonds had a negative correlation to other commodities including gold and silver, and no correlation to stocks or bonds. Now that diamonds can be priced via Diamond Standard’s technology, and traded with lower friction, the diamond commodity provides effective diversification for any portfolio.

Interestingly, diamonds have a mild negative correlation against those assets whereas gold has a mild positive correlation with the USD Index, commodities overall, and non-US equities. So diamonds are an effective diversification in portfolios that already hold gold.

Diamonds provide exceptional and essential protection against inflation. Since the advent of fiat money, inflation has been a constant tax on investments. The supply of money grows over time, reducing its purchasing power. Since 1913, that decline is 96% for the U.S. Dollar.

Precious metals have intrinsic value. They cannot be printed like fiat currencies, issued like stock certificates or bonds, and they are not a liability on another entity’s balance sheet, subject to an insolvency crisis. There are drawbacks, such as storage costs, and the lack of investment income.

Diamonds at Multi-Year Low

Diamonds are at a multi-year low price, vs. gold and silver near multi-year highs—while investors increasingly seek hard assets, due to the macro environment.

However, the negative correlation to gold may not be long lived, once diamonds are available as a liquid commodity and via securities. Previously, during past economic downturns, investors were less likely to demand more gold, while consumers might demand less jewelry.

But for the next five to fifteen years, as investors build positions in diamonds for the first time, the one-way demand is likely to outweigh short-term economic trends.

Want to Know More?

Find out more about investing in diamonds for long term grown, asset diversification, and wealth protection. Join Tim Plaehn and Jay Soloff as they host a live informational webinar with Diamond Standard on October 26th. Click here for details and registration.

Why Invest in Diamonds?
Investors Alley Staff

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