Tag: radiotherapy

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A New Combined Therapy Extends Prostate Cancer Survival

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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

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Tissue-sparing Radiotherapy for Lung Cancer Brain Metastasis is Effective

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MRI or CT machine
Photo by Mart Production on Pexels

A new study appearing in The Lancet Oncology suggests that a targeted radiation therapy is as effective as standard care for patients with lung cancer brain metastasis.

The findings suggests that patients could benefit from this targeted approach as it is known to have have fewer negative cognitive consequences.

In non-small-cell (NSLC) lung cancer, about 57% of patients present with metastatic disease, and 20% present with brain metastases. Brain metastasis is currently treated with whole brain radiation therapy, which targets the entire brain. While this approach treats even microscopic tumours, it results in memory problems and decreases cognitive function. The alternative, stereotactic radiosurgery, spares healthy brain tissue by precisely targeting the tumour, has been shown to have less severe cognitive consequences but has not yet been studied in patients with small cell lung cancer that has metastasised to the brain.

“For many years, it made sense to treat these patients with whole brain radiation because their survival was quite poor,” said Karolina Gaebe, a research student in Dr Sunit Das’s lab, who led the study.

“For them, long-term consequences of the treatment were not as crucial as reducing the impact of disease in the short-term. But now, as treatments for their lung cancer have improved, these patients are surviving much longer.”

The researchers set out to learn more after noticing patients with longer survival times were also living with severe cognitive impairments due to the treatments for their brain metastases. They wanted to understand whether a more targeted brain radiation regimen might be as beneficial for these patients, as has been demonstrated for most other cancer types.

As a first step, they undertook this meta-analysis, reviewing current literature to examine survival and brain outcomes following stereotactic radiosurgery for patients with small cell lung cancer that had spread to the brain. The team analysed data from 31 studies and included 18 130 patients, the largest cohort of small cell lung cancer patients with brain metastases to be studied so far.

The next steps are to conduct a large clinical trial to investigate cognitive outcome differences between stereotactic radiosurgery and whole brain radiation therapy for such patients.

“Because this is a meta-analysis, we can’t use this as absolute evidence that all patients should be treated in this way,” Dr Das said. “But essentially, this means that we need to challenge our standing worldwide paradigms for treating patients with this disease and revisit the idea that these patients should receive whole brain radiation therapy.”

Source: EurekAlert!

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Radiation after Breast-conserving Surgery Reduces Cancer Recurrence

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Source: National Cancer Institute

A long-term follow up analysis of a trial has shown that breast radiation following lumpectomy significantly reduces incidence of ipsilateral breast recurrence (IBR) for “low risk” DCIS.

NRG-RTOG 9804 is a clinical study conducted by the National Cancer Institute National Clinical Trials Network group NRG Oncology. These results were recently published in JCO.

IBR occurs at a rate of 5-10% after breast-conserving surgery. The NRG-RTOG 9804 study enrolled 636 women with a median age of 58 between December 1999 and July 2006. Patients were randomised to breast radiation (RT) or observation (OBS) treatment groups. All patients who participated in the trial underwent annual mammography and specified clinical exam intervals. For this analysis, the median follow up time was 13.9 years.

Analysis focused on the long-term cumulative incidence of IBR, the primary endpoint in the study. The study hypothesised that radiation would significantly reduce IBR from 6% to 3.5% at 5 years, assuming that the reduction in IBR from RT would be less than previous trials that included higher grades and larger sizes of DCIS. With long-term follow-up, cumulative incidence of IBR remained statistically significantly lower with RT, as compared to OBS. At 10 and 15 years, the cumulative incidence of IBR with OBS was 9.2% and 15.1%, respectively, and was 1.5% and 7.1%, respectively, with RT. The 10 and 15 year invasive IBR incidence, respectively, was 0.4% and 5.4%  with RT; 4.3%  and 9.5% with OBS. A total of 52 IBRs were observed; 14 in the RT arm and 38 in the OBS arm.

No statistically significant differences in mastectomy, distant metastasis, overall or disease-free survival were seen between the two treatment arms.

“Since IBR risk continues to increase through at least 15 years, with radiation conferring both a delay and decrease in this risk, the data presented support the decision to treat patients who wish to minimise their IBR and particularly the invasive cancer risk long term. Factors such as age, life expectancy, and willingness (if oestrogen receptor–positive) to take antioestrogen therapy should be taken into consideration in this patient-doctor shared decision,” stated lead author Beryl McCormick, MD, of the Memorial Sloan Kettering Cancer Center.

Source: NRG Oncology

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FLASH Radiation Treatment for Tumours a Step Closer

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Heavy ion bombardment in FLASH radiation treatment could be the future of radiotherapy, with encouraging findings from a German lab.

The GSI Helmholtzzentrum für Schwerionenforschung and the future accelerator centre FAIR succeeded in performing a carbon ion FLASH experiment for the first time in their Phase 0 experiment. 

The scientists involved were able to achieve the very high dose rates required to irradiate tumours. The success was a collective effort of the GSI Biophysics Department and the accelerator crew on the GSI/FAIR campus in close collaboration with the German Cancer Research Center DKFZ and the Heidelberg Ion Therapy (HIT) center.

FLASH irradiation involves utra-short and ultra-high radiation, delivering the treatment dose in fractions of a second. Traditional radiation therapy, as well as proton or ion therapy, deliver smaller doses of radiation to a patient over an extended time period, whereas FLASH radiotherapy is thought to require only a few short irradiations, all lasting less than 100 milliseconds.

In the field of electron radiation, recent in vivo investigations have shown that the FLASH method’s ultra-high dose rate is less harmful to healthy tissue, but just as efficient as conventional dose-rate radiation to inhibit tumour growth. Such an effect has not yet been demonstrated for proton and for ion beam irradiation, which is the basis of the tumour therapy with carbon ions developed at GSI. There is still a lot of research to be done here. The results of the current experiment at GSI are now being evaluated and will contribute to new knowledge.

There have also been technical barriers to FLASH radiation. Until now, FLASH technique has only been applicable using electron and proton accelerators. While the required dose rates for electrons and protons can be achieved with a cyclotron (circular accelerator), this is more difficult with the synchrotrons required in heavy ion therapy, such as the SIS18 at GSI.

That is why the current FAIR Phase 0 experiment is a very crucial step: Thanks to the improvements at the existing GSI accelerator facility as part of the preparations for FAIR, the necessary dose rate in millisecond range can now also be achieved for carbon ions. However,  much development work remains to be done before this procedure is mature enough to be routinely used on patients in the field of electron radiation.

Professor Marco Durante, Head of the GSI Biophysics Research Department, was very pleased with this important milestone in  the development of FLASH irradiation:

“It is a forward-looking method that could significantly increase the therapeutic window in radiotherapy. I am very happy that the researchers and the accelerator team were able to demonstrate the possibility to create conditions with carbon beams that are necessary for FLASH therapy of tumors. If we can combine the great effect and precision of heavy ion therapy with FLASH irradiation while maintaining efficacy and causing little damage to healthy tissue, this could pave the way of a future radiation therapy several years from now.”

Professor Paolo Giubellino, The Scientific Managing Director of GSI and FAIR, expressed his delight at the results: “The combination of expertise in biophysics and medicine as well as engineering excellence allows the first world-class experiments FLASH irradiation with ion beams to be performed. This could result in important complements to existing radiation therapies. Applications in tumour therapy are one of the research areas that can benefit from the recent increased intensities of GSI accelerators. However, modern radiobiology will substantially benefit from beams with even higher intensities, such as we will have at the FAIR facility currently under construction. FLASH is a first example of these future directions of work”.

Source: GSI Helmholtzzentrum für Schwerionenforschung GmbH

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New Radiotherapy Treatment for Metastatic Cancers is Safe

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MRI machine. Image by Michal Jarmoluk from Pixabay

A phase I trial showed that stereotactic body radiotherapy (SBRT) proved safe for treating cancer patients with multiple metastases. However, some late adverse effects underscored the need for long-term follow-up.

SBRT is a new radiotherapy treatment method that delivers high doses of ionising radiation to tumours with great precision, minimising damage to other parts of the body while killing tumour cells.

Increasingly used by clinicians, SBRT can improve survival in cancer patients with multiple metastases, explained first author Steve Chmura, MD, PhD, of University of Chicago Medicine, and colleagues, but there is little evidence as to its safety in this application.

“Existing data include mostly treatment of 1 or 2 metastases separated widely from each other and use of differing radiation doses, toxicity reporting, image guidance, and normal tissue constraints,” they wrote. “Given the critical need, NRG Oncology NRG-BR001 trial sought to determine the safety of delivering curative-intent SBRT to patients with 3 to 4 metastases or 2 metastases within close proximity to each other.”

Patients in the study had metastatic breast, prostate, or non-small-cell lung carcinoma (NSCLC). Each metastasis was assigned to a metastatic location based on the potential for toxicity.

Dose-limiting toxicity (DLT; side effects severe enough to discontinue treatment) was the primary study outcome, defined as specific AEs of grades 3 to 5 related to SBRT within 180 days of treatment. Dose levels were considered to be safe if DLTs were seen in no more than one of six patients per location with metastases.

Of the evaluable 35 patients, 12 (34.3%) had breast cancer, 10 NSCLC (28.6%), and 13 (37.1%) prostate cancer, with a median of three metastases per patient.

DLT analysis WAS based on six evaluable patients in all of the metastatic locations save the liver (five evaluable patients). The authors reported there were no protocol-specified DLTs in any of the seven metastatic locations within 180 days of the initiation of treatment.

There were 50 grade 3 or 4 AEs reported in 18 patients, and eight were deemed to be linked to the treatment. Of those eight, six (including bone pain, pulmonary fibrosis, bronchial fistula, bronchial stenosis, spinal fracture, and humeral fracture) were reported in six patients over 180 days from the start of the treatment. No treatment-related deaths occurred, according to the authors.

The authors suggested that, with the number of late AEs reported in this trial, patients should be monitored closely for late toxic effects.

“Given the potential for ablative radiotherapy to improve outcomes of patients with oligometastatic cancer, the finding that SBRT is safe when delivered to 3 to 4 metastases or 2 metastases in close proximity to one another is important, and serves as the foundation for ongoing randomized trials,” wrote the authors. They noted that these include studies such as the phase II/III NCI-sponsored NRG-BR002 trial.

Source: MedPage Today

Journal information: Chmura S, et al “Evaluation of safety of stereotactic body radiotherapy for the treatment of patients with multiple metastases” JAMA Oncol 2021; DOI: 10.1001/jamaoncol.2021.0687.

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Tumour Weakened against Radiation by Tweaking a Certain Protein

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The vulnerability of specific tissues to ionising radiation has been linked to the time-varying levels of a tumour-suppressing protein, opening new avenues for cancer combination therapy.

The ability for cells to survive radiation damage has been known to be connected to p53, but tissues with vastly different levels of p53 have been shown to have great differences in sensitivity. In the face of this apparent paradox, researchers from Blavatnik Institute at Harvard Medical School, Massachusetts General Hospital, and the Novartis Institutes for BioMedical Research investigated the behaviour of p53 in irradiated tissues.

“Dynamics matter. How things change over time matters,” said co-corresponding author Galit Lahav, the Novartis Professor of Systems Biology at HMS. “Our ability to understand biology is limited when we only look at snapshots. By seeing how things evolve temporally, we gain much richer information that can be critical for dissecting diseases and creating new therapies.”

Ionising radiation randomly damages a cell’s molecular machinery, causing it to initiate cell death if it is too serious. The arbitrator of cellular suicide is p53, which is also involved in tumour suppression. 

The findings opened new avenues for combination cancer therapies, as they discovered that administering a drug that blocks p53 levels from oscillating resulted in tumours in mice being more susceptible to radiation. 
Administering to the mice an experimental anti-cancer drug that inhibits MDM2, a protein which degrades p53, they forced p53 to stay elevated. The large intestine, which is normally radiation resistant, showed increased vulnerability.

Testing out this enhanced vulnerability on human tumours transplanted into mice, a significant tumour shrinkage was seen following radiation and then MDM2 inhibitor administration.

Co-corresponding author Galit Lahav, Novartis Professor of Systems Biology, Harvard Medical School explained: “By irradiating first, we force the cancer cells to activate p53, and by adding MDM2 inhibitor on top of that, we can keep p53 active longer. This combination has a much stronger effect than either alone.”

The findings showed the importance of understanding the role of p53 in cancer, the dynamic nature of which is not being looked at in studies testing MDM2. More research into the biological pathways of p53 is called for. 
“For a lab studying p53, cancer is always a major motivation. Our goal is to acquire knowledge to help develop better and more efficient therapies,” Lahav said. “Understanding how p53 behaves over time in different conditions is a critical piece of the puzzle.”

Source: News-Medical.Net

Journal information: Stewart-Ornstein, J., et al. (2021) p53 dynamics vary between tissues and are linked with radiation sensitivity. Nature Communications.doi.org/10.1038/s41467-021-21145-z