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ASTRO Updates Guidelines On Partial Breast Irradiation For Early Invasive Cancer

The American Society for Radiation Oncology (ASTRO) updated their guidelines on partial breast irradiation (PBI) for patients with early-stage invasive breast cancer or ductal carcinoma in situ (DCIS).

These new guidelines take into account results from multiple randomized controlled trials that have been published since ASTRO last issued recommendations for PBI in 2017. The trials included more than 10,000 women with about 10 years of follow-up, and, according to ASTRO guideline task force members, demonstrated "oncologic equivalence" between PBI and whole-breast irradiation (WBI) for the treatment of early-stage breast cancer and DCIS.

"For patients with early-stage breast cancer, many are eligible for consideration of partial breast irradiation," Task Force Chair Janice Lyons, MD, of the University Hospitals Seidman Cancer Center in Cleveland, told MedPage Today. "This is a conversation radiation oncologists should have with their patients and they can use the guidelines as a framework on how to have that discussion and how to deliver partial breast irradiation safely."

According to Lyons, one of the key differences in the updated guidelines is that they are "more liberal" regarding the age at which PBI may be appropriate.

The 2017 guidelines recommended that women ages 50 and older be considered "suitable" for PBI outside a clinical trial, while women ages 40 to 49 were included in the "cautionary" group, and those ages 40 and under be included in the "unsuitable" group.

The updated guidelines state that, for patients with early-stage, node-negative invasive breast cancer, PBI is strongly recommended as an alternative to WBI if the patient has favorable clinical features and tumor characteristics, including grade 1 to 2 disease, estrogen receptor (ER)-positive status, age 40 or older, and small tumor size.

PBI is conditionally recommended if the patient has an indication of higher recurrence risk, including grade 3 disease, ER-negative histology, or larger tumor size. It is not recommended for patients with positive lymph nodes, positive surgical margins, or germline BRCA1/2 mutations, or those who are younger than 40, and is conditionally not recommended for patients with less favorable risk features (e.G., lymphovascular invasion or lobular histology), due to the lack of robust data on these patient subsets.

For patients with DCIS, the recommendations align with those for early-stage breast cancer. PBI is strongly recommended as an alternative to WBI for patients with favorable clinical and tumor features outlined in the guideline, conditionally recommended for those with higher-grade disease or larger tumors, and not recommended for patients with positive surgical margins, BRCA mutations, or age less than 40.

"At this point so many randomized controlled trials have been conducted that we were able to really drill down into the subgroups of patients to better define those represented sufficiently enough to strongly recommend partial breast radiation rather than whole breast radiation," said Simona F. Shaitelman, MD, of the University of Texas MD Anderson Cancer Center in Houston, who served as the task force's vice chair.

Shaitelman pointed out that the updated guidelines also dealt with issues related to the delivery of PBI.

Recommended techniques for PBI include 3-D conformal radiation therapy, intensity-modulated radiation therapy, and multi-catheter interstitial brachytherapy, based on studies showing similar long-term rates of ipsilateral breast recurrence compared with WBI.

Single-entry catheter brachytherapy is conditionally recommended, while intraoperative radiation therapy (IORT) techniques, including electron IORT and photon (kV) IORT without WBI, are not recommended unless part of a clinical trial or multi-institutional registry.

The guideline also outlines the optimal dose-fractionation regimens, target volume delineation, and treatment planning parameters for different PBI techniques.

A daily or every-other-day course of PBI is recommended over twice-daily regimens, and the guidelines also pay particular attention to clinical and cosmetic side effects of PBI.

"I think the guidelines highlight how in certain scenarios, partial breast irradiation is actually more favorable than whole-breast irradiation," said Shaitelman. "And that's an important point to highlight to patients in order to improve their overall quality of life if they require radiation as part of their oncologic care."

Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

Lyons reported serving as a board examiner for the American Board of Radiology and consulting for Primum.

Shaitelman reported relationships with Alpha Tau Medical, Artios Pharma, Becton, Dickinson & Co., Elekta, the Emerson Collective Foundation, Exact Sciences, the NIH, and TAE Life Sciences, and serving on the editorial board of the journal Brachytherapy.

Primary Source

Practical Radiation Oncology

Source Reference: Shaitelman SF, et al "Partial breast irradiation for patients with early-stage invasive breast cancer or ductal carcinoma in situ: an ASTRO clinical practice guideline" Pract Radiat Oncol 2023; DOI: 10.1016/j.Prro.2023.11.001.

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Scar Tissue Holds Hints About Pancreatic Cancer Outcome, Research Finds

Scar tissue that forms around a growing pancreatic tumor called a pancreatic ductal adenocarcinoma harbors valuable clues as to how long people with these cancers are likely to live, according to a new study led by researchers at Stanford Medicine.

The architecture and organization of cells in the scar tissue can be used to categorize patients into two groups. Members of one group lived a median of nearly two years longer than members of the other group—a substantial difference for a cancer with a five-year survival rate after surgery of only 20% to 25%.

In fact, the researchers found that the patterns of a patient's scar tissue are among the most predictive prognostic elements for this type of cancer—second only to the stage of the tumor at diagnosis.

The finding suggests that cells in the scar tissue, as well as its overall structure, interact with the cancer cells to either egg on or tamp down their growth. Drugs that intercept pro-growth messages, or mimic cellular conversations that discourage growth, may lead to new avenues of therapy.

"Our study puts new therapeutic approaches on the table," said professor of surgery Michael Longaker, MD. "Should we be treating not just the tumor but also the scar tissue? I would say yes. Both obviously play a role in patient outcome."

Longaker, the Deane P. And Louise Mitchell Professor in the School of Medicine, is the senior author of the study, which was published in the Nov. 21 issue of Cell Reports Medicine. Post-doctoral scholar Jason Guo, Ph.D., and former graduate student Shamik Mascharak, MD, Ph.D., are the lead authors of the research.

Deaths increasing

Deaths from pancreatic ductal adenocarcinoma, the most common type of pancreatic cancer, are rising, and it is projected to be the second leading cause of cancer deaths in the next 10 years. Because the disease metastasizes, or invades other parts of the body, early and quickly, it often recurs within two years of initial treatment.

Pancreatic ductal adenocarcinoma sparks a particularly strong response by cells called fibroblasts found in the connective tissue surrounding the pancreas. The fibroblasts secrete collagen and other components of what's known as the extracellular matrix to bind the tumor in a web of cancer-associated scar tissue called desmoplasia. Earlier research has hinted that this scar tissue affects patient prognosis, but the analyses were confined primarily to simple quantitative measurements.

"Previous studies have focused on the cancer cells themselves, or how much fibrosis, or scarring, surrounds the tumor," Guo said. "But our findings reveal that maybe the critical information comes not from the quantity or mass of the scar tissue, but from its internal components and organization."

Guo and his colleagues studied hundreds of samples of pancreatic ductal adenocarcinoma tissue collected during surgery to remove the cancerous portion of the pancreas—a standard treatment for the condition. They used a computer algorithm to identify and analyze nearly 300 distinct attributes of the desmoplasia, including the length, width, alignment and density of their fibers, and another technique called CODEX to assess the prevalence and location of immune and other types of cells in the desmoplasia.

The results effectively allowed the researchers to zoom in to get a cell's-eye view of who's rubbing shoulders with whom (and how tightly they are pressed together) versus others exchanging friendly waves across a crowded room. They were particularly interested in investigating the interactions between immune cells called B and T cells and specialized cancer-associated fibroblasts that promote inflammation.

Survival patterns

The researchers then used a machine-learning approach to combine the data about multiple cellular interactions and fiber architecture with clinical information about each patient to uncover specific patterns associated with overall survival in the months and years after the initial diagnosis. They found that the presence of a specific type of T cell called a cytotoxic T cell was strongly associated with longer overall survival, while an abundance of tumor cells that modulate the immune system, as well as activated B cells, were associated with poorer survival.

"Pro-inflammatory fibroblasts also popped up in our analyses, which we were happy to see," Guo said. "Knocking out these fibroblasts or inhibiting their activity is a potential target for new therapies. We also saw close relationships between B cells and these fibroblasts, which is interesting. What are they talking about? We'd love to follow up and see what cellular signals are being exchanged."

They also found that thinner fibers predicted better survival than the beefy, densely packed fibers found in samples from patients who died soon after diagnosis.

When all the data were incorporated, the computers were able to categorize patients with pancreatic ductal carcinoma into two main groups. Patients in one group lived a median of 655 days longer than the other.

Longaker, Guo and their colleagues hope that new information about the contributions of the desmoplasia to pancreatic cancer growth will not just open doors for new therapies but that it will also be used to guide clinical decisions.

"In the future, I envision that a patient gets a biopsy before treatment has started, and doctors will look not just at the cancer but also at the patterns and types of cells in the desmoplasia," Longaker said.

"This could also help doctors decide which patients are likely to need more aggressive therapy early in the course of their disease, and who could be spared invasive or harsh chemotherapy or radiation. I hope we can develop a chemotherapeutic approach that doesn't just focus on the cancer but that also impacts fibroblasts and their role in promoting tumor growth."

More information: Shamik Mascharak et al, Desmoplastic stromal signatures predict patient outcomes in pancreatic ductal adenocarcinoma, Cell Reports Medicine (2023). DOI: 10.1016/j.Xcrm.2023.101248

Citation: Scar tissue holds hints about pancreatic cancer outcome, research finds (2023, November 24) retrieved 27 November 2023 from https://medicalxpress.Com/news/2023-11-scar-tissue-hints-pancreatic-cancer.Html

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Researchers Develop Gene Classifier To Predict DCIS Risk Of Cancer Progression

A team of researchers mapping a molecular atlas for ductal carcinoma in situ (DCIS) has made a major advance toward distinguishing whether the early pre-cancers in the breast will develop into invasive cancers or remain stable.

Analyzing samples from patients who had undergone surgery to remove areas of DCIS, the team identified 812 genes associated with cancer progression. Using this gene classifier, they were then able to predict the risk of cancer cells recurring or progressing.

The study, which published this week in the journal Cancer Cell, was led by E. Shelley Hwang, M.D., of the Duke Cancer Institute, and Rob West, M.D., Ph.D., of the Stanford University Medical Center. Their work is part of the Human Tumor Atlas Network under the Moonshot Initiative funded by the National Cancer Institute.

"There has been a long-standing debate over whether DCIS is cancer or a high-risk condition," Hwang said. "In the absence of a way to make that determination, we currently treat everyone with surgery, radiation, or both.

"DCIS is diagnosed in more than 50,000 women a year, and about a third of those women have a mastectomy, so we are increasingly concerned that we might be overtreating many women," Hwang said. "We need to understand the biology of DCIS better, and that's what our research has been designed to do."

Hwang, West and colleagues analyzed 774 DCIS samples from 542 patients who were a median of 7.4 years post-treatment. They identified 812 genes associated with recurrence within five years from treatment.

The gene classifier was able to predict both recurrence and invasive progression of cancer, with progression appearing to be dependent on a process that requires interactions between invasive DCIS cells and the unique features of the tumor environment.

Hwang said most of the DCIS cancers analyzed in the study were identified to be at low risk for cancer progression or recurrence - a factor that underscores the need to have an accurate predictive model that can be used during clinical visits to guide care.

We've made great progress in our understanding of DCIS, and this work gives us a real path forward to being able to personalize care by scaling treatments to the risk of cancer progression. The real goal is diminishing treatment-related harms without compromising outcomes, and we are excited to be getting closer to achieving this for our patients with DCIS."

E. Shelley Hwang, M.D., Duke Cancer Institute

In addition to Hwang and West, study authors include co-principal investigator Carlo Maley, Ph.D., of Arizona State School of Life Sciences, and Graham Colditz, Ph.D., of Washington University at St. Louis, for the Breast Pre-Cancer Atlas Center, as well as collaborators from 12 other institutions as part of the Translational Breast Cancer Consortium.

The study is part of the Human Tumor Atlas Network Consortium of the National Cancer Institute, which is part of the National Institutes of Health (R01 CA185138-01, U2C CA-17-035, UO1 CA214183, R01CA193694). Other funding support was from the Department of Defense (BC132057); The Breast Cancer Research Foundation (19-074, 19-028, 18-006); PRECISION CRUK Grand Challenge (AEI RYC2019- 026576-I); "la Caixa" Foundation (LCF/PR/PR17/51120011); the Lundbeck Foundation (R288-2018-35); the Danish Cancer Society (R229-A13616); and Susan G. Komen.

Source:

Journal reference:

Strand, S. H., et al. (2022). Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts. Cancer Cell. Doi.Org/10.1016/j.Ccell.2022.10.021.

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