Category: Cancer

‘Goldilocks’ Window for Immunotherapy Without Side Effects

Shown here is a pseudo-colored scanning electron micrograph of an oral squamous cancer cell (white) being attacked by two cytotoxic T cells (red), part of a natural immune response. Photo by National Cancer Institute on Unsplash

Researchers have developed a way to potentially reduce the toxic side-effects of CAR T cell immunotherapy, in findings that could overcome the pioneering treatment’s biggest limitation.

Their new study, reported in eLife, has come up with a way to identify a ‘goldilocks’ window that fine-tunes the cells used in the immunotherapy so that their activity is strong enough to eliminate the cancer but not so strong that they generate toxic side-effects.

Therapy provokes ‘perfect storm’

CAR T cell therapies involve collecting T cells from a cancer patient and supercharging the cells by individually re-engineering them in the laboratory. These enhanced cells are then put back into patients.

CAR T cell immunotherapy can be up to 90% effective in certain blood cancers, even curing some patients. But the treatment has harmful side-effects, with about 50% of patients experiencing dangerous complications.

The T cells are engineered to produce proteins on their surface called chimeric antigen receptors (CARs), which enable T cells to recognise and bind to specific proteins on the surface of cancer cells more efficiently.

Associate Professor Matthew Call said this synthetic sensor is what gives T cells the enhanced ability to attack and eliminate threats, like cancer cells.

“While putting these supercharged T cells into a patient with a high tumour burden can swiftly eradicate cancer cells, it also creates the perfect storm for an ongoing toxic response that can be harmful,” Associate Prof Call said.

There is currently no way of reliably predicting how strong CAR T cell therapy will be for a patient.

While previous studies have attempted to fine-tune T cells by targeting the end sections of the sensor, which either bind to the cancer cell or instruct the T cells to kill, the new research is the first to look at completely redesigning the middle part.

Researchers leveraged the computational expertise of the Weizmann Institute of Science to stitch together pieces of natural immune sensors with custom-designed synthetic elements, to generate new circuits that could be used to tune and assess variations of potency.

“Focusing on the connector fragment in the middle allows us to generate different versions of CARs that we know are stronger or weaker, enabling us to customise them to a patient’s potency requirements,” Associate Prof Call said.

“Being able to predictably tune this T cell activity significantly broadens our research, contrary to previous studies, because we are targeting something that exists in every immunotherapy scenario.

“For the first time, we can establish rules that will be applicable to any cancer where CAR T cell immunotherapy is being used.”

Enhanced treatment

Associate Prof Call said the ability to fine-tune T cells would dramatically reduce the number of patients experiencing severe side-effects from the treatment, which can include fever, high blood pressure and respiratory distress.

“CAR T cell therapy has proven effective in eradicating very advanced leukaemias and lymphomas, while also keeping the cancer at bay for many years – even after a patient has stopped taking cancer medication,” Associate Professor Call said.

“The therapy has incredible potential for cancer patients, but is currently used as a last resort due to these potentially severe side-effects.

“Our tools could lead to a fundamental rethink of the way CAR T cell therapy is offered by reducing a patient’s exposure risk to harmful side-effects. This would allow patients with a broad range of cancers to be given CAR T cell therapy far earlier in the treatment process.”

There are currently over 600 clinical trials of CAR T cell immunotherapy, with the treatment already being used for several blood cancers.

Researchers hope their new tool could be used to triage immunotherapy patients according to the potencies required in the early treatment phases, bringing the field closer to hitting that ‘goldilocks’ treatment window for many different cancers.

The next research phase will focus on progressing these findings into a clinical setting to see CAR T cell therapy used as a safer, first-line treatment.

Source: Walter and Eliza Hall Institute of Medical Research

Erectile Dysfunction Drugs Repurposed for Cancer Treatment

Killer T cells about to destroy cancer cell
Killer T cells about to destroy cancer cell (centre). Credit: NIH

Researchers report repurposing an unusual class of drugs to combat oesophageal cancer – PDE5 inhibitors, which are mainly used as erectile dysfunction treatments.

Tumours are surrounded by a microenvironment made up of blood vessels, immune cells, enzymes and a variety of other cells the tumour needs to survive, including cells called fibroblasts that are essential in building connective tissue.

Research suggests that this microenvironment is key to a cancer’s development, and now researchers have found that an erectile dysfunction drug that targets the tumour microenvironment that could improve treatment for certain cancers.

Finding a new target

In some cancers, the tumour microenvironment allows tumours to resist treatment, preventing chemotherapy from having a beneficial effect.

This is the case in oesophageal cancers, which, though rare, currently has poor survival outcomes.

To try to overcome this resistance, a team of researchers led by Professor Tim Underwood at the University of Southampton, wanted to identify the cells in the tumour microenvironment that protect the tumour from treatment so they could target them.

“Where targeting cancer cells with one specific treatment can be difficult because they differ between patients, targeting the microenvironment cells may be more likely to have traction because they are similar across patients,” said Prof Underwood.

“Rather than going after the cancer cells, actually, if we take away their ‘soil’ and go after the environment they live in, we might have more success.

“The plants might be different, but if you poison the soil, they’ll all die.”

New uses for old drugs

By examining cells from oesophageal cancers called adenocarcinomas, the team found that levels of an enzyme called PDE5 are higher in these cancer cells than in health oesophageal tissues.

Specifically, the high levels of PDE5 were found in cells called cancer associated fibroblasts (CAFs), which are important for tumour growth. They also found that the more PDE5 a tumour contained, the worse the prognosis was, suggesting that PDE5 would be an effective target for treatment.

Luckily, PDE5 inhibitors already exist, commonly used to treat erectile dysfunction.

The researchers discovered that in addition to its usual function of relaxing muscles to allow increased blood flow, PDE5 inhibitors were able to suppress CAF activity, and make them behave like normal fibroblasts again.

Improving treatment safely

Once Prof Underwood’s team had found that PDE5 inhibitors worked, a collaborating team took samples of tumour cells from 15 tissue biopsies from 8 patients and used them to create artificial lab-grown tumours. With these tumours, the researchers could test a combination of PDE5 inhibitions and standard chemotherapy in the lab.

Twelve of these samples were taken from people whose tumours had shown a poor response to chemotherapy in the clinic. Of these, 9 were made sensitive to chemotherapy following the addition of the PDE5 inhibitor targeting CAFs.

They also tested the treatment on mice implanted with chemotherapy resistant oesophageal tumours and found that there were no adverse side effects to the treatment, and that chemotherapy combined with PDE5 inhibitors shrunk the tumours more than chemotherapy alone.

Repurposing existing drugs like PDE5 inhibitors takes advantage of well-established safety profiles.

However giving PDE5 inhibitors to people with oesophageal cancer would be extremely unlikely to cause erections without the appropriate stimulation.

“The chemotherapy resistant properties of oesophageal tumours mean that many patients undergo intensive chemotherapy that won’t work for them,” said Prof Underwood.

“Finding a drug, which is already safely prescribed to people every day, could be a great step forward in tackling this hard-to-treat disease.”

Source: Cancer Research UK

Study Reveals That Breast Cancer Spreads at Night

Sleeping woman
Photo by Cottonbro on Pexels

Researchers previously assumed that metastasising tumours release cells continuously. However, a new study has reached a surprising conclusion: circulating cancer cells that later form metastases mainly arise during the sleep phase of the affected individuals. This may have implications for oncologists, as timing of samples may affect their results. The study findings have just been published in Nature.

Circadian rhythm-regulated hormones control metastasis

“When the affected person is asleep, the tumour awakens,” said study leader Professor Nicola Aceto at ETH Zurich. During their study, which included 30 female cancer patients and mouse models, the researchers found that the tumour generates more circulating cells when the organism is asleep. Cells that leave the tumour at night also divide more quickly and therefore have a higher potential to form metastases, compared to circulating cells that leave the tumour during the day.

“Our research shows that the escape of circulating cancer cells from the original tumour is controlled by hormones such as melatonin, which determine our rhythms of day and night,” said Zoi Diamantopoulou, the study’s lead author and a postdoctoral researcher at ETH Zurich.

An accidental discovery led to the study

In addition, the study indicates that the time in which tumour or blood samples are taken for diagnosis may influence the findings of oncologists. It was an accidental finding along these lines that first put the researchers on the right track, “Some of my colleagues work early in the morning or late in the evening; sometimes they’ll also analyse blood at unusual hours,” Prof Aceto said with a smile. The scientists were surprised to find that samples taken at different times of the day had very different levels of circulating cancer cells.

Another clue was the surprisingly high number of cancer cells found per unit of blood in mice compared to humans. The reason was that as nocturnal animals, mice sleep during the day, which is when scientists collect most of their samples.

“In our view, these findings may indicate the need for healthcare professionals to systematically record the time at which they perform biopsies,” Prof Aceto said. “It may help to make the data truly comparable.”

The researchers’ next step will be to figure out how these findings can be incorporated into existing cancer treatments to optimise therapies. As part of further studies with patients, Prof Aceto wants to investigate whether different types of cancer behave similarly to breast cancer and whether existing therapies can be made more successful if patients are treated at different times.

Source: ETH Zurich

Parabens in Hair Products May Increase Breast Cancer Risk for Black Women

Parabens, chemicals which are found in widely used hair and personal care products, cause harmful effects in breast cancer cells from Black women, according to a new study presented at ENDO 2022, the Endocrine Society’s annual meeting.

In the US, the lifetime risk of breast cancer is one in eight, and Black women are at a higher risk of getting breast cancer under the age of 40 than any other racial or ethnic group in that country. Breast cancer rates among Black South African women are also on the increase, but the cause remains unexplained and research in this area has been lacking.

“One reason for the higher risk of breast cancer may be exposure to harmful chemicals called endocrine-disrupting chemicals in hair and personal care products,” said lead researcher Lindsey S. Treviño, PhD. “These chemicals mimic the effects of hormones on the body.”

Parabens are endocrine-disrupting chemicals that are commonly used as preservatives in hair and other personal care products. Parabens cause breast cancer cells to grow, invade, spread, and express genes linked to cancer and to hormone action. Research showed that fewer paraben-free options are marketed to Black women.

“Black women are more likely to buy and use hair products with these types of chemicals, but we do not have a lot of data about how parabens may increase breast cancer risk in Black women,” Dr Treviño said. “This is because Black women have not been picked to take part in most research studies looking at this link. Also, studies to test this link have only used breast cancer cell lines from White women.”

The new study tested the effects of parabens on breast cancer cells from Black women. Parabens were found to increase the growth of a Black breast cancer cell line but not in the White breast cancer cell line. Parabens increased expression of genes linked to hormone action in breast cancer cell lines from both Black and White women. Parabens also promoted the spread of breast cancer cells, with a bigger effect seen in the Black breast cancer cell line.

“These results provide new data that parabens also cause harmful effects in breast cancer cells from Black women,” Dr Treviño said. 

The study is a part of a community-led project called the Bench to Community Initiative (BCI), which brings together scientists and community members (including breast cancer survivors) to create ways to reduce exposures to harmful chemicals in hair and personal care products in Black women with breast cancer. 

“While this project focuses on Black women, the knowledge we gain about the link between exposure to harmful chemicals in personal care products and breast cancer risk can be used to help all women at high risk of getting breast cancer,” Dr Treviño said.

Source: Endocrine Society

Encouraging Findings from Immunotherapy Trial for Rectal Cancer

Colon cancer cells
Colon cancer cells. Source: National Cancer Institute on Unsplash

A recent study reported encouraging findings that the immunotherapy drug dostarlimab was especially effective in a phase II clinical trial of 12 patients with a subtype of rectal cancer. Writing in the New England Journal of Medicine, author Hanna K. Sanoff, MD, MPH, from the UNC Lineberger Comprehensive Cancer Center, outlined prospects for future treatment of the disease.

About 5–10% of rectal cancers are molecularly characterised as being deficient in mismatch repair enzymes (dMMR). These cancers tend to be less responsive to chemotherapy and radiation, increasing the need for surgical treatments. Unfortunately, surgery can result in notable health consequences, including nerve damage, infertility, and bowel and sexual dysfunction.

“Historical treatment of the disease has included radiation, surgery and chemotherapy, which can be debilitating despite its curative potential, pointing to the need for better and more effective treatments that can prolong longevity while maintaining quality of life,” said Prof Sanoff. “These initial findings of the remarkable benefit with the use of dostarlimab are very encouraging but also need to be viewed with caution until the results can be replicated in a larger and more diverse population.”

Still awaiting long-term findings
Prof Sanoff also cautioned that little is known about how long the benefit of the drug will last or whether it will be curative in the long-term. So far, the trial participants have only been observed for six months to two years.

“The responses in these first 12 of a planned-for 30 patients in the trial were remarkable and exceed what we would expect with the standard chemotherapy plus radiation,” Prof Sanoff said. “Although quality of life measures have not been reported yet, it’s encouraging that some of the most difficult symptoms, such as pain and bleeding, all resolved with the use of dostarlimab.”

Prof Sanoff noted there are other immunotherapy drugs that potentially could be tested against this form of rectal cancer. “As a gastrointestinal medical oncologist, I can think of nothing better for my patients than being able to offer them a drug that is more effective, less toxic and avoids surgery, chemotherapy, and radiation; that day can’t come soon enough,” she said.

Source: UNC Lineberger Comprehensive Cancer Center

New KRAS-mutated Lung Cancer Treatment Effective in 43% of Cases

MRI or CT machine
Photo by Mart Production on Pexels

Nearly 43% of patients with non-small cell lung cancer (NSCLC) that had a specific KRAS mutation responded to the experimental drug adagrasib, which also showed activity against metastases, according to results of a study published in the New England Journal of Medicine.

Mutations in the potent oncogene known as KRAS occur in about one in four patients with NSCLC, and approximately 13% of NSCLC patients’ tumours are driven by a specific KRAS mutation called G12C. KRAS mutations have long been considered nearly impossible to attack with targeted drugs after many years of research attempts. However, in 2021 a targeted drug, sotorasib, became the first drug approved by the Food and Drug Administration for NSCLC patients with the G12C mutation, based on a clinical trial showing a 36% response rate in those patients after having initially received treatment with chemotherapy and a PD-1 immune checkpoint inhibitor.

Reporting the results of a new phase 2 trial, investigators led by Pasi Jänne, MD, PhD, director of the Lowe Center for Thoracic Oncology at Dana-Farber, showed that treatment with a different KRASG12C mutant inhibitor, adagrasib, yielded a 42.9% objective response rate and a median overall survival rate of 12.6 months in a cohort of 112 patients who had previously received both chemotherapy and immunotherapy with a PD-1 immune checkpoint blocker. Notably, adagrasib treatment also achieved a 33.3% response rate in 33 patients who had stable metastatic lesions in the brain and central nervous system that had spread from the lung tumours.

“These data highlight that inhibiting KRASG12C can lead to clinically meaningful benefits to NSCLC patients with this form of lung cancer,” said Dr Jänne. “Brain metastases are challenging to treat and having a pharmacologic agent that shows activity in this setting is an advancement and movement in the right direction.”

Patients with KRASG12C have had few options after initial chemotherapy and immunotherapy stopped working. In the new clinical trial of adagrasib, taking the oral drug twice daily resulted in a median progression-free survival (the time patients lived before the cancer began to worsen again) was 6.5 months and the median response duration was 8.5 months.

Because the KRASG12C tumor cells typically continue to proliferate, researchers believe sustained inhibition with drugs may be necessary. Thus, adagrasib was optimised for favourable properties including a long half-life of 23 hours and the ability to penetrate the central nervous system. Clinical activity with adagrasib has been shown in patients with other KRASG12C tumors, including colorectal, pancreatic, biliary tract, and other cancers.

Source: Dana-Farber Cancer Institute

Bariatric Surgery Reduces Cancer Risks with Obesity

Image source: Pixabay CC0

A study published in JAMA shows that weight loss through bariatric surgery for adults with obesity was associated with a 32% lower risk of developing cancer and a 48% lower risk of cancer-related death compared with those who did not have the surgery.

Rising obesity numbers are being seen all over the world. The International Agency for Research on Cancer describes 13 types of cancer as obesity-associated cancers such as endometrial cancer, postmenopausal breast cancer, and cancers of the colon, liver, pancreas, ovary and thyroid.

Lead author of the study, Ali Aminian, MD, at Cleveland Clinic, said that bariatric surgery is currently the most effective treatment for obesity. “Patients can lose 20 to 40% of their body weight after surgery, and weight loss can be sustained over decades. The striking findings of this study indicate that the greater the weight loss, the lower the risk of cancer,” said Dr Aminian.

From 2004 and 2017, the SPLENDID (Surgical Procedures and Long-term Effectiveness in Neoplastic Disease Incidence and Death) study matched a group of 5053 adult patients with obesity who had bariatric surgery 1:5 to a control group of 25 265 patients with obesity who did not undergo the surgery.

After 10 years, 2.9% of patients in the bariatric surgery group and 4.9% of patients in the non-surgical group developed an obesity-associated cancer.

After 10 years, 0.8% of patients in the surgery group and 1.4% of patients in the non-surgical group died from cancer, indicating that bariatric surgery is associated with a 48% lower cancer mortality risk.

Researchers noted that the benefits of bariatric surgery were seen in a wide range of study participants in terms of age, sex and race. In addition, benefits were similarly observed after both gastric bypass and gastric sleeve operations.

“According to the American Cancer Society, obesity is second only to tobacco as a preventable cause of cancer in the United States,” said the study’s senior author, Steven Nissen, MD, Chief Academic Officer of the Heart, Vascular and Thoracic Institute. “This study provides the best possible evidence on the value of intentional weight loss to reduce cancer risk and mortality.”

Numerous studies have shown the health benefits of bariatric or weight-loss surgery in patients with obesity. The Cleveland Clinic-led STAMPEDE study showed that following bariatric surgery, significant weight loss and control of type 2 diabetes last over time. The SPLENDOR study showed that in patients with fatty liver, bariatric surgery decreases the risk of the progression of liver disease and serious heart complications.

The SPLENDID study adds important findings to the literature focused on the link between obesity and cancer. Given the growing epidemic of obesity worldwide, these findings have considerable public health implications.

“Based on the magnitude of benefit shown in our study, weight loss surgery can be considered in addition to other interventions that can help prevent cancer and reduce mortality,” said Jame Abraham, M.D., chairman of the Hematology and Medical Oncology Department at Cleveland Clinic. “Further research needs to be done to understand the underlying mechanisms responsible for reduced cancer risk following bariatric surgery.”

Source: Cleveland Clinic

Supplementation Effective in Slowing Age-related Macular Degeneration

Credit: National Eye Institute

A pair of major studies established that dietary supplements can slow progression of age-related macular degeneration (AMD). In a new report published in JAMA Ophthalmology, scientists went through 10 years of Age-Related Eye Disease Studies (AREDS2) data and showed that the AREDS2 formula, which substituted antioxidants lutein and zeaxanthin for beta-carotene, not only reduces risk of lung cancer due to beta-carotene, but is also more effective at reducing risk of AMD progression, compared to the original formula.

“Because beta-carotene increased the risk of lung cancer for current smokers in two NIH-supported studies, our goal with AREDS2 was to create an equally effective supplement formula that could be used by anyone, whether or not they smoke,” said Emily Chew, MD, lead author of the study report. “This 10-year data confirms that not only is the new formula safer, it’s actually better at slowing AMD progression.”

AMD is a degenerative disease of the retina, the light-sensitive tissue at the back of the eye. Progressive death of retinal cells in the macula, the part of the retina that provides clear central vision, eventually leads to blindness. Treatment can slow or reverse vision loss; however, no cure for AMD exists.

The original AREDS study, launched in 1996, showed that a dietary supplement formulation (50 mg vitamin C, 400 international units vitamin E, 2mg copper, 80mg zinc, and 15mg beta-carotene) could significantly slow the progression of AMD from moderate to late disease. However, two concurrent studies also revealed that people who smoked and took beta-carotene had a significantly higher risk of lung cancer than expected.

In AREDS2, begun in 2006, Dr Chew and colleagues compared the beta-carotene formulation to one with 10 mg lutein and 2 mg zeaxanthin instead. Like beta-carotene, lutein and zeaxanthin are antioxidants with activity in the retina. The beta-carotene-containing formation was only given to participants who had never smoked or who had quit smoking.

At the end of the five-year AREDS2 study period, the researchers concluded that lutein and zeaxanthin did not increase risk for lung cancer, and that the new formation could reduce the risk of AMD progression by about 26%. After the completion of the five-year study period, the study participants were all offered the final AREDS2 formation that included lutein and zeaxanthin instead of beta-carotene.

In this new report, the researchers followed up with 3883 of the original 4203 AREDS2 participants an extra five years from when the AREDS2 study ended in 2011, collecting information AMD progression, and lung cancer diagnosis. Even though all the participants had switched to the formula containing lutein and zeaxanthin after the end of the study period, the follow up study continued to show that beta-carotene increased risk of lung cancer for people who had ever smoked by nearly double. No increased risk for lung cancer was seen in those receiving lutein/zeaxanthin. In addition, after 10 years, the group originally assigned to receive lutein/zeaxanthin had an additional 20% reduced risk of progression to late AMD compared to those originally assigned to receive beta-carotene.

“These results confirmed that switching our formula from beta-carotene to lutein and zeaxanthin was the right choice,” said Dr Chew.

Source: NIH/National Eye Institute

A New Combined Therapy Extends Prostate Cancer Survival

Credit: Darryl Leja / National Human Genome Research Institute / National Institutes of Health

Practice-changing research published in The Lancet shows that a new combined therapy involving androgen deprivation therapy plus pelvic lymph node radiation kept nearly 90% of clinical trial patients’ prostate cancer at bay for five years.

The study also shows that patients with prostate cancer who didn’t receive androgen deprivation therapy — and who did not receive pelvic lymph node radiation — had a five-year survival of 70%.

“We can now confirm that pelvic lymph node treatment used together with androgen deprivation therapy, or even used as a stand-alone treatment option, greatly improves outcomes in patients with postoperative prostate cancer,” said Howard Sandler, MD, of Cedar Sinai Medical Center, senior author of the study. “These findings are an encouraging step forward, both for the medical community and for the patients and their loved ones seeking curative treatment options.”

The trial enrolled 1716 patients between March 31, 2008, and March 30, 2015. Enrollees were separated into three groups.

Group one received salvage prostate bed radiotherapy — a standard radiation targeted to the area in which the prostate used to exist before its surgical removal. Median five-year survival was 71% in these patients.

The second group received the standard radiation treatment, in combination with androgen deprivation therapy. Median five-year survival was 81%.

The third group received salvage prostate bed radiotherapy, androgen deprivation therapy and pelvic lymph node radiation. These patients had a five-year freedom from progression of just over 87%.

“The combined treatment approach proved to be the most beneficial approach,” said Dr Sandler.

Prostate cancer is the most common non-skin cancer in the US, affecting 1 in every 6 to 7 men. Though early warning signs are rare for prostate cancer, screening tests can catch it early. Diagnosis usually accompanies an elevated level of PSA, an acronym for prostate-specific antigen.

After prostatectomy, a man’s PSA level should be near zero. However, some men start to see their PSA levels rise several years after surgery. This is typically an indication that radiation therapy is needed.

Dr Sandler says men with postoperative prostate cancer can have excellent outcomes, especially if radiation is given early — when PSA levels are at their lowest — and in combination with proven therapies, as suggested in this new research.

Source: Cedars-Sinai Medical Center

For Large Breast Sizes, Prone Positioning is Less Toxic for Radiotherapy

Woman receiving mammogram
A woman receiving a mammogram, Source: National Cancer Institute

For women with large breast sizes, receiving radiotherapy with prone positioning is less toxic than while supine, according to a study published in JAMA Oncology.

Patients treated in the supine position had significantly higher rates of moist desquamation anywhere in the breast compared with those treated in the prone position (39.6% vs 26.9%).

“Treatment in the prone position has several dosimetric advantages for these patients,” the researchers explained. “It allows for more homogeneous dose distribution owing to the smaller separation when compared with the supine position, which decreases deposition of higher doses in the inframammary fold and axilla.”

Fewer toxic effects of the skin were seen when patients were treated with hypofractionated radiotherapy compared with extended fractionation, they added.

“Prone radiotherapy appears to be an excellent option for patients with large breast size and right-sided breast cancer, and may benefit many women with left-sided breast cancer with large breast size if acceptable cardiac avoidance is feasible,” observed Mayo Clinic’s Dean Shumway, MD, and Cedars-Sinai Medical Center’s Katelyn Atkins, MD, PhD, in an accompanying editorial. “In summary, prone positioning for whole-breast radiotherapy represents a valuable addition to the armamentarium of treatment techniques to reduce the adverse effects associated with whole-breast radiotherapy.”

Of the 357 women (mean age 61 years) included, 182 were treated in the supine position and 175 were treated in the prone position.

From April 2013 until June 2016, 167 patients received 50 Gy in 25 fractions (extended fractionation) with or without boost (range 10-16 Gy). After the trial was amended in June 2016, the majority of patients (93.2%) received the hypofractionation regimen of 42.5 Gy in 16 fractions.

The researchers also found that the supine position was associated with more grade 3 desquamation compared with the prone position (15.4% vs 8.0%; OR 2.09, 95% CI 1.62-2.69, P<0.001).

In addition, when broken down by treatment with either extended fractionation or hypofractionation, extended fractionation was associated with more:

  • Toxic effects (43.3% vs 23.2%)
  • Grade 3 desquamation (17.2% vs 6.3%)
  • Pain (9.4% vs 3.4%)

“These differences were primarily driven by the rates of toxic effects in patients treated in the supine position,” the authors noted.

Specifically, in patients treated in the supine position, extended fractionation was associated with increased desquamation compared with hypofractionation (51.1% vs 27.8%), and grade 3 desquamation (23.9% vs 6.7%).

Extended fractionation was also associated with increased toxicity in patients treated in the prone position, although the link was less pronounced. Desquamation occurred in 35.2% of patients treated with extended fractionation versus 18.4% of patients treated with hypofractionation (OR 2.41), while grade 3 desquamation occurred in 10.2% versus 5.7% of patients (OR 1.87).

No differences in quality of life as measured by global health status, breast symptoms, or pain scales between the supine and prone groups were seen, the researchers noted.