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After 40 years of smoking, she survived lung cancer thanks to new treatments

Yuki Noguchi

Denise Lee on her last day of chemo. In addition to chemo and surgery, she was treated with immunotherapy. She's currently in remission. Denise Lee hide caption

Denise Lee on her last day of chemo. In addition to chemo and surgery, she was treated with immunotherapy. She's currently in remission.

Denise Lee grew up in Detroit in the mid-1970s and went to an all-girls Catholic high school. She smoked her first cigarette at age 14 at school, where cigarettes were a popular way of trying to lose weight.

Instead, her nicotine addiction lasted four decades until she quit in her mid-50s.

"At some point it got up as high as 2.5 packs a day," Lee, 62, recalls.

Yet she didn't think about lung cancer risk — until she saw a billboard urging former smokers to get screened. Lee, a retired lawyer living in Fremont, Calif., used to drive past it on her way to work.

"The thing that caught my attention was the fact that it was an African American female on the front," she recalls.

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The american cancer society says more people should get screened for lung cancer.

She eventually got the low-dose CT scan recommended for current and former smokers. When doctors found an early, but dangerous, tumor, Lee cried and panicked. Her mother had cared for her father, who'd died of prostate cancer. "My biggest concern was telling my mom," she says.

But that was six years ago, and Lee is cancer free today. Surgery removed the 2-inch tumor in her lung, then new treatments also boosted her immune system, fighting off any recurrence.

Lung cancer remains the most lethal form of the disease, killing about 135,000 Americans a year – more than breast, prostate and colon cancer combined – which is why many people still think of a diagnosis as synonymous with a death sentence. But with new treatments and technology, the survival rates from lung cancer are dramatically improving, allowing some patients with relatively late-stage cancers to live for years longer.

"If you're gonna have lung cancer, now is a good time," Lee says of the advances that saved her.

Denise Lee has been cancer-free for six years. She says she's grateful she got screened and caught her lung cancer early enough that treatment has been effective. Denise Lee hide caption

Denise Lee has been cancer-free for six years. She says she's grateful she got screened and caught her lung cancer early enough that treatment has been effective.

The key breakthrough, says Robert Winn, a lung cancer specialist at Virginia Commonwealth University, is the ability to better pinpoint the mutations of a patient's particular form of cancer. In the past, treatments were blunt tools that caused lots of collateral damage to healthy parts of the body while treating cancer.

"We've gone from that to molecular characterization of your lung cancer, and it has been a game changer," Winn says. "This is where science and innovation has an impact."

One of those game-changing treatments is called targeted therapy . Scientists identify genetic biomarkers in the mutated cancer cells to target and then deliver drugs that attack those targets, shrinking tumors.

CRISPR gene-editing may boost cancer immunotherapy, new study finds

Another is immunotherapy, usually taken as a pill, which stimulates the body's own defense system to identify foreign cells, then uses the immune system's own power to fight the cancer as if it were a virus.

As scientists identify new cancer genes, they're creating an ever-broader array of these drugs.

Combined, these treatments have helped increase national survival rates by 22% in the past five years – a rapid improvement over a relatively short time, despite the fact that screening rates are very slow to increase. Winn says as these treatments get cheaper and readily available, the benefits are even reaching rural and Black populations with historic challenges accessing health care.

The most remarkable thing about the drugs is their ability to, in some cases, reverse late-stage cancers. Chi-Fu Jeffrey Yang, a thoracic surgeon at Massachusetts General Hospital and faculty at Harvard Medical School, recalls seeing scans where large dark shadows of tumor would disappear: "It was remarkable to see the lung cancer completely melting away."

To Yang, such progress feels personal. He lost his beloved grandfather to the disease when Yang was in college. If he were diagnosed today, he might still be alive.

"Helping to take care of him was a big reason why I wanted to be a doctor," Yang says.

But the work of combating lung cancer is far from over; further progress in lung cancer survival hinges largely on getting more people screened.

Low-dose CT scans are recommended annually for those over 50 who smoked the equivalent of a pack a day for 20 years. But nationally, only 4.5% of those eligible get those scans , compared to rates of more than 75% for mammograms.

Andrea McKee, a radiation oncologist and spokesperson for the American Lung Association, says part of the problem is that lung cancer is associated with the stigma of smoking. Patients often blame themselves for the disease, saying: "'I know I did this to myself. And so I don't I don't think I deserve to get screened.'"

McKee says that's a challenge unique to lung cancer. "And it just boggles my mind when I hear that, because, of course, nobody deserves to die of lung cancer."

Denise Lee acknowledges that fear. "I was afraid of what they would find," she admits. But she urges friends and family to get yearly scans, anyway.

"I'm just so grateful that my diagnosis was early because then I had options," she says. "I could have surgery, I could have chemotherapy, I could be a part of a clinical trial."

And all of that saved her life.

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June 5, 2024

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Lung cancer treatment produces progression-free survival results in Phase III trial

by Andrea Clement, Emory University

In a recent study led by Suresh Ramalingam, MD, executive director of Winship Cancer Institute of Emory University, a new drug has shown remarkable promise in treating patients with a specific type of advanced lung cancer.

Osimertinib, produced by AstraZeneca under the brand name Tagrisso, significantly extends the time patients live without their cancer worsening, offering the first effective therapy and new hope for those with stage III non-small cell lung cancer (NSCLC) who have mutations in the epidermal growth factor receptor (EGFR), a protein that controls cell division and survival.

Key findings

Findings of the study, known as the LAURA Phase III trial, were presented by Ramalingam on June 1 during the Plenary Session at the world's largest clinical cancer research meeting—the American Society of Clinical Oncology Annual Meeting ( ASCO 2024 ) in Chicago, IL, and were simultaneously published in the New England Journal of Medicine .

Patients participating in the trial had already undergone standard treatments, including chemotherapy and radiation, without their cancer progressing further. Participants were randomly assigned to receive either osimertinib or a placebo.

The results were compelling: Patients taking osimertinib experienced a median progression-free survival of 39.1 months, compared to just 5.6 months for those on the placebo. This means that osimertinib reduced the risk of disease progression or death by an impressive 84%.

Broader impacts

Osimertinib is the first and only EGFR inhibitor to show such a benefit in the stage III setting, extending progression-free survival by more than three years. The study demonstrated a clinically meaningful benefit across various patient subgroups, including differences in sex, race, type of EGFR mutation, age, smoking history and prior treatments.

While overall survival data are still maturing, early results indicate a favorable trend for osimertinib. The trial will continue to monitor overall survival as a secondary endpoint.

"The impressive progression-free survival results from the LAURA Phase III trial represent a major breakthrough for patients with stage III EGFR-mutated lung cancer for whom no targeted treatments are available," says Ramalingam. "Osimertinib delayed the risk of disease progression or death by an unprecedented 84% and should become the new standard of care for patients in this setting based on these data."

Safety and approval

Regarding safety, 35% of patients on osimertinib experienced serious side effects, compared to 12% in the placebo group. The most common issue was radiation pneumonitis, an inflammation of the lungs caused by radiation therapy , affecting nearly half of the patients in both groups. Importantly, no new safety concerns were identified.

Osimertinib is already approved as a monotherapy in over 100 countries, including the US, EU, China, and Japan, for various stages and types of EGFR-mutated NSCLC. These latest findings further solidify its role as a crucial treatment option.

The positive results from the LAURA Phase III trial underscore the importance of early testing and diagnosis in lung cancer, which remains the leading cause of cancer death worldwide, accounting for about one-fifth of all cancer deaths. Each year, an estimated 2.4 million people are diagnosed with lung cancer globally, with non-small cell lung cancer (NSCLC) being the most common form.

EGFR mutations are found in a significant subset of NSCLC patients, particularly in Asia, making targeted therapies like osimertinib vital in treatment.

"Tagrisso extended progression-free survival by more than three years in this potentially curative setting, reinforcing the need to test and diagnose patients early. These practice-changing data cement the powerful impact Tagrisso can make as backbone therapy in EGFR-mutated lung cancer," says Susan Galbraith, executive vice president of oncology R&D at AstraZeneca.

For more information about the clinical trial, details can be found under the identifier NCT03521154 .

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Lung Cancer Research Results and Study Updates

See Advances in Lung Cancer Research for an overview of recent findings and progress, plus ongoing projects supported by NCI.

Lorlatinib (Lorbrena) is superior to crizotinib (Xalkori) as an initial treatment for people with ALK-positive advanced non-small cell lung cancer, according to new clinical trial results. Treatment with lorlatinib also helped prevent new brain metastases.

The immunotherapy drug durvalumab (Imfinzi) can help people with early-stage small cell lung cancer live longer, results from a large clinical trial show. Three years after starting treatment, nearly 60% of people who received the drug were still alive.

FDA has approved alectinib (Alecensa) as adjuvant therapy for people with lung cancer who have ALK-positive tumors. In a clinical trial, alectinib helped people live longer after surgery without their cancer returning than chemotherapy.

The results of the clinical trial that led to FDA’s 2023 approval of repotrectinib (Augtyro) for lung cancers with ROS1 fusions have been published. The drug shrank tumors in 80% of people receiving the drug as an initial treatment.

A collection of material about the ALCHEMIST lung cancer trials that will examine tumor tissue from patients with certain types of early-stage, completely resected non-small cell lung cancer for gene mutations in the EGFR and ALK genes, and assign patients with these gene mutations to treatment trials testing post-surgical use of drugs targeted against these mutations.

Tarlatamab, a new type of targeted immunotherapy, shrank small cell lung cancer (SCLC) tumors in more than 30% of participants in an early-stage clinical trial. Participants had SCLC that had progressed after previous treatments with other drugs.

For people with lung cancer and medullary thyroid cancer whose tumors have changes in the RET gene, selpercatinib improved progression-free survival compared with other common treatments, according to new clinical trial results.

In the ADAURA clinical trial, people with early-stage lung cancer treated with osimertinib (Tagrisso) after surgery lived longer than people treated with a placebo after surgery. Despite some criticisms about its design, the trial is expected to change patient care.

For certain people with early-stage non-small cell lung cancer, sublobar surgery to remove only a piece of the affected lung lobe is as effective as surgery to remove the whole lobe, new research shows.

Pragmatica-Lung is a clinical trial for people with non-small cell lung cancer that has spread beyond the lungs (stage 4 cancer). The trial will help confirm if the combination of pembrolizumab and ramucirumab helps people with advanced lung cancer live longer.

On August 11, the Food and Drug Administration (FDA) gave accelerated approval to trastuzumab deruxtecan (Enhertu) for adults with non-small cell lung cancer (NSCLC) that has a specific mutation in the HER2 gene. Around 3% of people with NSCLC have this kind of HER2 mutation.

Giving people with early-stage lung cancer the immunotherapy drug nivolumab (Opdivo) and chemotherapy before surgery can substantially delay the progression or return of their cancer, a large clinical trial found.

Atezolizumab (Tecentriq) is now the first immunotherapy approved by FDA for use as an additional, or adjuvant, treatment for some patients with non-small cell lung cancer. The approval was based on results of a clinical trial called IMpower010.

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NCI scientists and their international collaborators have found that the majority of lung cancers in never smokers arise when mutations caused by natural processes in the body accumulate. They also identified three subtypes of lung cancer these individuals.

FDA has approved the first KRAS-blocking drug, sotorasib (Lumakras). The approval, which covers the use of sotorasib to treat some patients with advanced lung cancer, sets the stage for other KRAS inhibitors already in development, researchers said.

Combining the chemotherapy drug topotecan and the investigational drug berzosertib shrank tumors in some patients with small cell lung cancer, results from an NCI-supported phase 1 clinical trial show. Two phase 2 trials of the combination are planned.

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A large clinical trial showed that adding the immunotherapy drug durvalumab (Imfinzi) to standard chemotherapy can prolong survival in some people with previously untreated advanced small cell lung cancer.

The investigational drug selpercatinib may benefit patients with lung cancer whose tumors have alterations in the RET gene, including fusions with other genes, according to results from a small clinical trial.

FDA has approved entrectinib (Rozlytrek) for the treatment of children and adults with tumors bearing an NTRK gene fusion. The approval also covers adults with non-small cell lung cancer harboring a ROS1 gene fusion.

Clinical recommendations on who should be screened for lung cancer may need to be reviewed when it comes to African Americans who smoke, findings from a new study suggest.

Use of a multipronged approach within hospitals, including community centers, not only eliminated treatment disparities among black and white patients with early-stage lung cancer, it also improved treatment rates for all patients, results from a new study show.

In everyday medical care, there may be more complications from invasive diagnostic procedures performed after lung cancer screening than has been reported in large studies.

The Lung Cancer Master Protocol, or Lung-MAP, is a precision medicine research study for people with advanced non-small cell lung cancer that has continued to grow after treatment. Patients are assigned to different study drug combinations based on the results of genomic profiling of their tumors.

On December 6, 2018, the Food and Drug Administration (FDA) approved atezolizumab (Tecentriq) in combination with a standard three-drug regimen as an initial treatment for advanced lung cancer that does not have EGFR or ALK mutations.

A new study has identified a potential biomarker of early-stage non–small cell lung cancer (NSCLC). The biomarker, the study’s leaders said, could help diagnose precancerous lung growths and early-stage lung cancers noninvasively and distinguish them from noncancerous growths.

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Recent advances in lung cancer research: unravelling the future of treatment

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• Published: 06 April 2024

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• Luca Bertolaccini   ORCID: orcid.org/0000-0002-1153-3334 1 ,
• Monica Casiraghi 1 , 2 ,
• Clarissa Uslenghi 1 ,
• Sebastiano Maiorca 1 &
• Lorenzo Spaggiari 1 , 2  

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Lung cancer, a multifaceted disease, demands tailored therapeutic approaches due to its diverse subtypes and stages. This comprehensive review explores the intricate landscape of lung cancer research, delving into recent breakthroughs and their implications for diagnosis, therapy, and prevention. Genomic profiling and biomarker identification have ushered in the era of personalised medicine, enabling targeted therapies that minimise harm to healthy tissues while effectively combating cancer cells. The relationship between pulmonary tuberculosis and lung cancer is examined, shedding light on potential mechanisms linking these two conditions. Early detection methods, notably low-dose computed tomography scans, have significantly improved patient outcomes, emphasising the importance of timely interventions. There has been a growing interest in segmentectomy as a surgical intervention for early-stage lung cancer in recent years. Immunotherapy has emerged as a transformative approach, harnessing the body's immune system to recognise and eliminate cancer cells. Combining immunotherapy with traditional treatments, such as chemotherapy and targeted therapies, has shown enhanced efficacy, addressing the disease's heterogeneity and overcoming drug resistance. Precision medicine, guided by genomic profiling, has enabled the development of targeted therapies like tyrosine kinase inhibitors, offering personalised treatments tailored to individual patients. Challenges such as drug resistance and limited accessibility to advanced therapies persist, emphasising the need for collaborative efforts and innovative technologies like artificial intelligence. Despite challenges, ongoing interdisciplinary collaborations and technological advancements offer hope for a future where lung cancer is treatable and preventable, reducing the burden on patients and healthcare systems worldwide.

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Acknowledgements

This work was partially supported by the Italian Ministry of Health with Ricerca Corrente and 5x1000 funds.

Ministero della Salute, 5 × 1000, Ricerca Corrente.

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Bertolaccini, L., Casiraghi, M., Uslenghi, C. et al. Recent advances in lung cancer research: unravelling the future of treatment. Updates Surg (2024). https://doi.org/10.1007/s13304-024-01841-3

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Researchers also continue to look into some of the other causes of lung cancer, such as exposure to asbestos , radon , and diesel exhaust . Finding new ways to limit these exposures could possibly save many more lives.

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Researchers are looking for ways to use vitamins or medicines to prevent lung cancer in people at high risk, but so far none have been shown to clearly reduce risk.

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Caliman E, Fancelli S, Petroni G, Gatta Michelet MR, Cosso F, Ottanelli C, Mazzoni F, Voltolini L, Pillozzi S, Antonuzzo L. Challenges in the treatment of small cell lung cancer in the era of immunotherapy and molecular classification. Lung Cancer. 2023 Jan;175:88-100. doi: 10.1016/j.lungcan.2022.11.014. Epub 2022 Nov 23. PMID: 36493578.

Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ Jr, Wu YL, Paz-Ares L. Lung cancer: current therapies and new targeted treatments. Lancet. 2017 Jan 21;389(10066):299-311. doi: 10.1016/S0140-6736(16)30958-8. Epub 2016 Aug 27. PMID: 27574741.

Meijer JJ, Leonetti A, Airò G, Tiseo M, Rolfo C, Giovannetti E, Vahabi M. Small cell lung cancer: Novel treatments beyond immunotherapy. Semin Cancer Biol. 2022 Nov;86(Pt 2):376-385. doi: 10.1016/j.semcancer.2022.05.004. Epub 2022 May 11. PMID: 35568295.

Petrella F, Rizzo S, Attili I, Passaro A, Zilli T, Martucci F, Bonomo L, Del Grande F, Casiraghi M, De Marinis F, Spaggiari L. Stage III Non-Small-Cell Lung Cancer: An Overview of Treatment Options. Curr Oncol. 2023 Mar 7;30(3):3160-3175. doi: 10.3390/curroncol30030239. PMID: 36975452; PMCID: PMC10047909.

Wang M, Herbst RS, Boshoff C. Toward personalized treatment approaches for non-small-cell lung cancer. Nat Med. 2021 Aug;27(8):1345-1356. doi: 10.1038/s41591-021-01450-2. Epub 2021 Aug 12. PMID: 34385702.

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August 8, 2024

Merck stops phase 3 TIGIT trial in lung cancer for futility—and sees immune side effects again

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June 26, 2024

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Wednesday, August 12, 2020

New treatments spur sharp reduction in lung cancer mortality rate

According to a new study, mortality rates from the most common lung cancer, non-small cell lung cancer (NSCLC), have fallen sharply in the United States in recent years, due primarily to recent advances in treatment.

The study was led by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health. The findings were published August 12, 2020, in the New England Journal of Medicine.

“Reduced tobacco consumption in the U.S. has been associated with a progressive decrease in lung cancer deaths that started around 1990 in men and around 2000 in women. Until now, however, we have not known whether newer treatments might contribute to some of the recent improvement,” said Douglas R. Lowy, M.D., NCI deputy director and co-author of this study. “This analysis shows for the first time that nationwide mortality rates for the most common category of lung cancer, non-small cell lung cancer, are declining faster than its incidence, an advance that correlates with the U.S. Food and Drug Administration approval of several targeted therapies for this cancer in recent years.”

In this study, researchers looked at data for both NSCLC, which accounts for 76% of lung cancer in the U.S., and small-cell lung cancer (SCLC), which accounts for 13% (other subtypes of lung cancer that constitute the remaining share of cases were not covered in this study). In the last decade, new treatments for NSCLC have become available, including those that target genetic changes seen in some NSCLC tumors as well as immune checkpoint inhibitors that help the immune system better attack NSCLC. In contrast, there have been limited treatment advancements for SCLC.

Although death records do not distinguish between lung cancer deaths attributable to NSCLC versus SCLC, the cancer diagnosis records compiled by NCI’s Surveillance, Epidemiology, and End Results (SEER) cancer registry program do distinguish between these two subtypes of lung cancer. Therefore, the researchers were able to estimate lung cancer mortality trends for these specific lung cancer subtypes by linking the lung cancer death records for each patient back to the incidence data for these patients in the SEER cancer database.

The researchers found that, in recent years, deaths from NSCLC decreased even faster than the decrease in NSCLC incidence and the decrease in deaths was associated with a substantial improvement in survival. Among men, for example, deaths from NSCLC decreased 3.2% annually from 2006 to 2013 and 6.3% annually from 2013 to 2016, whereas incidence decreased 1.9% annually during 2001 to 2008 and 3.1% annually from 2008 to 2016.

Two-year survival for men with NSCLC improved over this time, from 26% for patients diagnosed in 2001 to 35% for those diagnosed in 2014. Similar improvement was observed for women. In addition, improvements in two-year survival were seen for all races/ethnicities, despite concerns that the newer cancer treatments, many of which are expensive, might increase disparities.

The researchers had originally considered the possibility that lung cancer screening might help explain the decreases in NSCLC mortality, but their findings suggest that lung cancer screening rates, which remained low and stable, do not explain the mortality declines. Instead, the rapid decline in deaths reflects both declines in incidence (due in large part to reductions in smoking) and improvement in treatment.

In contrast, the decrease in deaths from SCLC corresponded with the decrease in incidence, and two-year survival was largely unchanged. Among men, for example, deaths declined 4.3% annually and incidence 3.6% annually. Findings were similar among women. The reduced mortality from SCLC over time, therefore, primarily reflects declines in incidence — again, due largely to reduced smoking.

The researchers note that the accelerating decline in NSCLC mortality that began in 2013 corresponds with the time when clinicians began routinely testing patients for genetic alterations targeted by newly approved drugs. In 2012, the National Comprehensive Cancer Network recommended that all patients with nonsquamous NSCLC undergo genetic testing. Subsequently, genetic testing for EGFR (epidermal growth factor receptor) mutations and ALK (anaplastic lymphoma kinase) gene rearrangements — which are targeted by the newer treatments — increased substantially. Because immune checkpoint inhibitors were not in widespread use over the period of the analysis, the authors suspect that most of the survival benefit was attributable to effective EGFR or ALK inhibitors or other advances in therapy. The effect of immune checkpoint inhibitors on NSCLC survival is significant, which suggests that this improving trend in survival should continue beyond 2016.

“The survival benefit for patients with non-small cell lung cancer treated with targeted therapies has been demonstrated in clinical trials, but this study highlights the impact of these treatments at the population level,” said Nadia Howlader, Ph.D., of NCI’s Division of Cancer Control and Population Sciences, who led the study. “We can now see the impact of advances in lung cancer treatment on survival.”

About the National Cancer Institute (NCI): NCI leads the National Cancer Program and NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website at cancer.gov or call NCI’s contact center, the Cancer Information Service, at 1-800-4-CANCER (1-800-422-6237).

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MSK Research Highlights, August 13, 2024

Tuesday, August 13, 2024

New research from Memorial Sloan Kettering Cancer Center (MSK) found patients with non-small cell lung cancer brain metastases may benefit from up-front stereotactic radiosurgery; identified a connection between antibiotic use and autoimmune diseases; and uncovered a previously unknown structural role for messenger RNAs in the cytoplasm of cells.

Patients with non-small cell lung cancer brain metastases may benefit from upfront stereotactic radiosurgery

For patients with  non-small cell lung cancer that has  spread to the brain , targeted therapies called tyrosine kinase inhibitors (TKIs) can be effective at shrinking these tumors. Another treatment for these brain metastases is a type of radiation therapy called  stereotactic radiosurgery (SRS) , in which powerful and highly targeted radiation is delivered in a focused way to brain metastases, with the help of sophisticated imaging technologies. Traditionally, SRS was the first treatment for brain metastases, but recently there has been a growing trend toward deferring up-front SRS in favor of TKIs. However, these approaches have never been directly compared in a clinical trial.

In a multicenter, retrospective study, a team led by  Luke Pike, MD, DPhil , director of brain  radiation oncology at MSK, looked at whether giving SRS at the same time as targeted therapy may make treatment more effective. The team reviewed data from 200 patients who received TKIs alone and 117 patients who received TKIs and SRS. They found that although adding SRS to drug treatment did not help patients live longer, it extended the time it took for their disease to progress. This is particularly significant because the patients who got SRS tended to have larger tumors. Based on the findings, the researchers conclude that patients with brain metastases may benefit from having SRS in addition to drug therapy up-front, especially those with larger tumors.

Dr. Pike is now working to initiate a randomized phase 2 clinical trial that will selectively use SRS for patients receiving TKIs that target the EGFR gene — the most commonly altered subtype of non-small cell lung cancer, and one with a high likelihood of spreading to the brain. “Instead of treating all patients up-front, this trial seeks to selectively add SRS to the care of those patients who are likely to be at the highest risk of their brain metastases growing and causing harm, while de-intensifying treatment for most patients,” he says. “We hope that this will result in meaningful improvements in quality of life for our patients living with brain metastases.”

Read more in the  Journal of Clinical Oncology .

New evidence for a connection between antibiotic use and autoimmune diseases

Scientists at MSK have uncovered a new connection between depletion of gut bacteria caused by antibiotics and the development of autoimmune diseases. The study, conducted in mouse models, shows that clearance of dead cells — which is necessary for health and the prevention of autoimmune responses — involves not only local signals from within a tissue but also distant signals from other parts of the body, such as the gut. The study looked at mice whose gut bacteria had been depleted by antibiotics and found that immune cells in the abdomen (large peritoneal macrophages) were not clearing out dead cells as well as they should be. When butyrate — a short-chain fatty acid produced by gut bacteria when they breakdown dietary fiber — was given to the mice, it improved the ability of the macrophages to clear out the dead cells. Using a variety of techniques, the team further uncovered key genes and transcription programs involved in the process. They also found that cell clearance remained impaired for a time after the antibiotics were stopped. The study, overseen by  immunologist Justin Perry, PhD , a member of the  Sloan Kettering Institute and led by postdoctoral fellow  Pedro Saavedra, PhD (who now heads a lab at Northeastern University), also looked at the phenomenon in a mouse model of lupus. They found mice treated with antibiotics had significantly worse disease symptoms. Overall, the findings suggest that gut bacteria-produced butyrate and its impact on the body’s ability to clear out dead cells may be a key factor linking antibiotic use to autoimmune disease. Read more in Nature Metabolism .

New research uncovers structural role for messenger RNAs in the cytoplasm

A new study from the lab of  Christine Mayr, MD, PhD , at MSK’s  Sloan Kettering Institute has unveiled a novel structural role for mRNAs in the cytoplasm. The research introduces the FXR1 network, a messenger RNA-protein network that plays a pivotal role in cellular signaling and organization.

The FXR1 network is formed by FXR1-mediated packaging of exceptionally long messenger RNAs expressed in cells — which are 3-6 times longer than most mRNAs and make up about 10% of the total.

“Think of the FXR1 network as a bustling hub where FXR1 and messenger RNAs interact and help each other to assemble,” says study first author  Xiuzhen Chen, PhD , a postdoctoral researcher in the Mayr Lab who received a  2022 Kravis Women in Science Endeavor (WISE) fellowship . “More importantly, signaling proteins that cannot bind RNAs directly get attracted into the network by FXR1. This way, the FXR1 network acts as a hub where signaling proteins can easily find each other.”

The findings show that messenger RNAs do more than just encode proteins, they also serve as structural components that organize signaling reactions in the cell, Dr. Mayr adds. “This discovery opens up new avenues for understanding cellular processes and the molecular basis of diseases like Fragile X Syndrome,” she says.

Mutations in FXR1 are similar to those found in the closely related gene FMR1 that are associated with Fragile X syndrome, a genetic disorder that affects cognitive development, Dr. Mayr notes. These mutations disrupt the FXR1 network and prevent signaling reactions. This disruption highlights the network’s importance in maintaining cellular functions. The principles revealed in the study provide a new path for understanding human diseases stemming from dysfunctional RNA binding proteins by showing that in addition to their well-studied functions, messenger RNAs can also be organizers of signaling reactions. Read more in  Cell .

Immunotherapy significantly improves survival rates for advanced lung cancer patients, study finds

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Since the first immunotherapy drug to boost the body's immune response against advanced lung cancer was introduced in the United States in 2015, survival rates of patients with the disease have improved significantly. That's the conclusion of a recent real-world study published by Wiley online in CANCER , a peer-reviewed journal of the American Cancer Society.

For the research, a team led by Dipesh Uprety, MD, FACP, of the Barbara Ann Karmanos Cancer Institute and the Wayne State University School of Medicine, analyzed data from the National Cancer Institute Surveillance, Epidemiology, and End Results database, which compiles cancer-related data covering approximately 48% of the US population. The investigators' analysis focused on non–small cell lung cancer (NSCLC), which accounts for up to 90% of all cases of lung cancer and is the leading cause of cancer-related death among both men and women in the United States.

In a comparison of 100,995 patients with metastatic NSCLC treated in 2015–2020 (after immunotherapy was deemed the standard of care) and 90,807 patients with metastatic NSCLC in the pre-immunotherapy era of 2010–2014, patients in the immunotherapy era were less likely to die from any cause. The overall survival rates at one, three, and five years were 40.1% versus 33.5%, 17.8% versus 11.7%, and 10.7% versus 6.8%. The median overall survival was eight months in patients in the immunotherapy era and seven months in those in the pre-immunotherapy era.

Similarly, patients treated after immunotherapy was available were less likely to die specifically from cancer than those treated before immunotherapy. The one-, three-, and five-year cancer-specific survival rates were 44.0% versus 36.8%, 21.7% versus 14.4%, and 14.3% versus 9.0%, with a median survival of 10 months versus eight months.

Survival rates remained significantly better in the immunotherapy era even after accounting for factors including age, sex, race, income, and geographical area.

By utilizing a large national database, our study provided real-world evidence of the positive impact of immunotherapy in patients with lung cancer." Dr. Dipesh Uprety, MD, FACP, of the Barbara Ann Karmanos Cancer Institute and the Wayne State University School of Medicine

The investigators stressed that additional studies are needed, however. "Immunotherapy provides long-term benefits. Since the durable benefits of immunotherapy are limited to a small subset of patients, future research should aim to optimize immunotherapy with new agents that can benefit a broader population," said lead author Yating Wang, MD, of Ascension Providence Hospital.

Wang, Y., et al . (2024). Survival trends among patients with metastatic non–small cell lung cancer before and after the approval of immunotherapy in the United States: A Surveillance, Epidemiology, and End Results database–based study.  Cancer . doi.org/10.1002/cncr.35476 .

Posted in: Medical Research News | Medical Condition News

Tags: Cancer , Cell , Epidemiology , Hospital , Immune Response , Immunotherapy , Lung Cancer , Medicine , Non-Small Cell Lung Cancer , Research , Small Cell Lung Cancer

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Small-cell lung cancer articles from across Nature Portfolio

Small-cell lung cancer is a highly malignant form of lung cancer, also known as oat-cell carcinoma, that accounts for approximately 15% of lung cancer cases. Composed of small, ovoid cells with very little cytoplasm, small-cell lung cancer usually originates in the bronchi and is caused by smoking.

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Emerging advances in defining the molecular and therapeutic landscape of small-cell lung cancer

Traditionally, patients with small-cell lung cancer (SCLC), a malignancy with a dismal prognosis, have had limited treatment options. Over the past few years, advances in the molecular characterization of SCLC have revealed novel therapeutic targets. The authors of this Review summarize these findings and discuss emerging opportunities and challenges for their translation into new treatment approaches.

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CDK9 inhibition as an effective therapy for small cell lung cancer

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FAK-LINC01089 negative regulatory loop controls chemoresistance and progression of small cell lung cancer

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Evolutionary trajectories of small cell lung cancer under therapy

We uncover key processes of the genomic evolution of small cell lung cancer under therapy, identify the common ancestor as the source of clonal diversity at relapse and show central genomic patterns associated with drug response.

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The pancancer overexpressed NFYC Antisense 1 controls cell cycle mitotic progression through in cis and in trans modes of action

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A SWI/SNF-dependent transcriptional regulation mediated by POU2AF2/C11orf53 at enhancer

POU2AF2 is a co-activator of POU2F3 in normal and neoplastic tuft cells, such as small cell lung cancer. Here, the authors report that POU2AF2 dictates opposing transcriptional regulation at distal enhance elements.

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Anlotinib plus benmelstobart and chemotherapy are effective in es-sclc.

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Pegargiminase improves outcomes in nonepithelioid MPM

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Deciphering the role of immunoglobulin secreting malignant lineages in the invasive frontiers of small cell lung cancer by scRNA-seq and spatial transcriptomics analysis

Selective regulation of tuft cell-like small cell lung cancer by novel transcriptional co-activators C11orf53 and COLCA2

New capstone of sclc therapy.

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Dual PD-L1 and CTLA4 inhibition in ES-SCLC

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Pignon JP, Arriagada R, Ihde DC, et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med ; 327: 1618–24.

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Research trends in lung cancer and the tumor microenvironment: a bibliometric analysis of studies published from 2014 to 2023

Affiliations.

• 1 The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China.
• 2 Department of Respiratory Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.
• PMID: 39144829
• PMCID: PMC11322073
• DOI: 10.3389/fonc.2024.1428018

Background: Lung cancer (LC) is one of the most common malignant tumors in the world and the leading cause of cancer-related deaths, which seriously threatens human life and health as well as brings a heavy burden to the society. In recent years, the tumor microenvironment (TME) has become an emerging research field and hotspot affecting tumor pathogenesis and therapeutic approaches. However, to date, there has been no bibliometric analysis of lung cancer and the tumor microenvironment from 2014 to 2023.This study aims to comprehensively summarize the current situation and development trends in the field from a bibliometric perspective.

Methods: The publications about lung cancer and the tumor microenvironment from 2014 to 2023 were extracted from the Web of Science Core Collection (WoSCC). The Microsoft Excel, Origin, R-bibliometrix, CiteSpace, and VOSviewer software are comprehensively used to scientifically analyze the data.

Results: Totally, 763 publications were identified in this study. A rapid increase in the number of publications was observed after 2018. More than 400 organizations published these publications in 36 countries or regions. China and the United States have significant influence in this field. Zhou, CC and Frontiers in Immunology are the most productive authors and journals respectively. Besides, the most frequently cited references were those on lung cancer pathogenesis, clinical trials, and treatment modalities. It suggests that novel lung cancer treatment models mainly based on the TME components, such as cancer-associated fibroblasts (CAFs) may lead to future research trends.

Conclusions: The field of lung cancer and the tumor microenvironment research is still in the beginning stages. Gene expression, molecular pathways, therapeutic modalities, and novel detection technologies in this field have been widely studied by researchers. This is the first bibliometric study to comprehensively summarize the research trend and development regarding lung cancer and tumor microenvironment over the last decade. The result of our research provides the updated perspective for scholars to understand the key information and cutting-edge hotspots in this field, as well as to identify future research directions.

Keywords: Lung cancer; bibliometric; the tumor microenvironment (TME); trend; visualized analysis.

Copyright © 2024 Huang, Xie, Xie, Chen, Wen and Yang.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Process of publications selection in…

Process of publications selection in lung cancer and the tumor microenvironment.

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• Schabath MB, Cote ML. Cancer progress and priorities: lung cancer. Cancer Epidemiol Biomarkers Prev. (2019) 28:1563–79. doi: 10.1158/1055-9965.EPI-19-0221 - DOI - PMC - PubMed
• Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. (2023) 73:17–48. doi: 10.3322/caac.21763 - DOI - PubMed
• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. (2021) 71:209–49. doi: 10.3322/caac.21660 - DOI - PubMed
• Muthusamy B, Berktas M, Li J, Thomas DS, Sun P, Taylor A, et al. . EGFR mutation testing, treatment and survival in stage I-III non-small-cell lung cancer: CancerLinQ Discovery database retrospective analysis. Future Oncol. (2024), 1–14. doi: 10.1080/14796694.2024.2347826 - DOI - PubMed
• Dai J, Su Y, Zhong S, Cong L, Liu B, Yang J, et al. . Exosomes: key players in cancer and potential therapeutic strategy. Signal Transduct Target Ther. (2020) 5:145. doi: 10.1038/s41392-020-00261-0 - DOI - PMC - PubMed

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Body Mass Index May Play a Role in Lung Cancer Treatment Decisions

Patients with NSCLC who are overweight or obese should discuss chemotherapy versus immunotherapy for frontline treatment, research showed.

The body mass index of patients with non-small cell lung cancer may affect whether they should receive chemotherapy or immunotherapy.

Patients with advanced non-small cell lung cancer (NSCLC) who are overweight or obese may have better outcomes if they are initially treated with chemotherapy rather than immunotherapy, according to recent research.

The study, which was published in JAMA Network Open , collected data from 31,257 patients with advanced NSCLC — 12,816 of whom were treated with immunotherapy, while 18,441 were treated with conventional chemotherapy.

Findings showed that for patients who had a body mass index (BMI) less than 28, immunotherapy was associated with a lower risk of death compared to those who had conventional chemotherapy. Conversely, the researchers did not observe a survival benefit with immunotherapy in patients with a BMI of 28 or higher.

“The findings of this study suggest that immune checkpoint inhibitor therapy may not be the optimal first-line therapy in patients with overweight or obesity [advanced] NSCLC,” the authors wrote. “Hence, the use of conventional chemotherapy should also be considered in such patients.

Of note, according to the World Health Organization, BMIs between 25 and 29.9 are classified as being in the overweight range; 30 to 39.9 are considered in the obese range; and BMIs of 40 or above are considered severely obese.

These findings might help determine treatment strategies for patients who are overweight or obese.

“The optimal choice between conventional chemotherapy and immunotherapy for first-line therapy remains uncertain in patients with obesity. This is why this study was conducted,” study author Yasutaka Ihara, professor in the Department of Medical Statistics at Osaka Metropolitan University Graduate School of Medicine in Japan, said in an interview with CURE®. “If there is one finding that patients should know, they should know that personalized medicine is developing, tailored to each patient's constitution and other factors.”

With regard to specific immunotherapy drugs used, among the 12,816 patients who received immunotherapy, the majority (77.3%; 9,905) received Keytruda (pembrolizumab), while 12.7% (1,630) received Opdivo (nivolumab), either with or without Yervoy (ipilimumab) and 10% (1,281) received Tecentriq (atezolizumab).

A total of 28% of patients in the immunotherapy group and 35.9% of patients in the conventional chemotherapy group died within three years of receiving treatment. In both groups, the researchers observed an association between a higher BMI and lower death risk compared to those with a lower BMI.

READ MORE: Findings Link Higher BMI to Better Immunotherapy Outcomes in NSCLC

The authors wrote, “The results of this study support the preclinical findings suggesting that patients with obesity may exhibit inadequate therapeutic response to anti-PD-1 therapy…”

Looking forward, the researchers noted that more research is needed regarding the association between BMI and response or outcomes to oncologic therapies. In the meantime, Ihara mentioned that cancer treatment continues to become more personalized. As such, patients should have open discussions with their health care teams to determine the best therapies.

“Patients should discuss with health care providers how personalized treatments suit their unique diagnosis, potential benefits and risks, the need for genetic testing, costs, lifestyle preferences, and follow-up plans to ensure the best care,” he said.

For more news on cancer updates, research and education, don’t forget to  subscribe to CURE®’s newsletters here.

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