Experimental drug could boost radiotherapy effects

A team from the Institute of Cancer Research (ICR) and The Royal Marsden Hospital has demonstrated that pre-treating cancerous cells with an experimental drug called CCT244747 improves the efficacy of radiotherapy. Discovered by scientists at the ICR, in collaboration with drug discovery company Sareum, CCT244747 is a type of molecule known as a Chk1 inhibitor. Chk1 inhibitors stop cells from entering a "rest and repair" state if they detect DNA mutations – a key survival mechanism for cancerous cells after radiotherapy. "Our study has shown that an experimental Chk1 inhibitor effectively sensitizes cancer cells grown in the lab and in mice to radiotherapy – and could in the future become a new and effective treatment option in bladder and head-and-neck cancer," said study co-leader Kevin Harrington, Joint Head of the Division of Radiotherapy and Imaging at the ICR.

In the study, the team irradiated cells from bladder and head-and-neck tumours after treatment with CCT244747. The cells continued to try to grow and divide despite the damage. As a result, they either died prematurely, or passed on irreparable mutations to their descendants. Importantly, the inhibitor only had this effect on cancerous cells – adding CCT244747 to radiation treatment of healthy cells did not increase cell damage. The drug also significantly slowed the growth of tumours grown in mice. After 70 days, tumours in mice treated with both CCT244747 and radiotherapy were around half the size of tumours in mice treated with radiotherapy alone (Radiother. Oncol. 122 470).

Combined radiation, immune therapy shows potential

An emerging cancer treatment that combines radiotherapy with immune checkpoint inhibitors (ICPIs) shows potential to more effectively control tumours in the chest with an acceptable risk of severe side effects, according to results presented at this week's Multidisciplinary Thoracic Cancers Symposium. Cancer cells produce proteins that stop the body's natural immune response. ICPIs block these proteins, allowing the immune system to remain active and attack malignant cells. For some patients, however, the immune system may also target healthy cells. "In previous analyses, our team found that a combination of radiation therapy and anti-PD-1 therapy was safe and effective in treating melanoma-related brain metastases," said lead author Kamran Ahmed from the Moffitt Cancer Center. "The current findings show potential for the tolerability and efficacy of this combined approach for treating thoracic tumours as well."

The study included 29 metastatic lung cancer patients treated with thoracic radiotherapy (10 to 70 Gy, in one to 35 fractions) in the six months before or after ICPI therapy. The median progression-free survival was 3.8 months, and median overall survival was 9.2 months – similar control rates to other prospective studies using ICPIs to treat lung cancer. Three patients who had radiotherapy after ICPI experienced severe toxicity, including one grade 5 toxicity and two cases of grade 3 pneumonitis. No patients who received radiation first experienced severe toxicity from irradiation. Two other cases of pneumonitis were noted following ICPI but before radiation; these patients subsequently received radiotherapy without additional pulmonary toxicity. "Our results suggest that a treatment regimen combining thoracic radiation therapy and immune checkpoint inhibitors may carry a modest risk of severe side effects," said Ahmed. "These findings should be evaluated further within the context of prospective clinical trials."

Radiosurgery is best choice for brain metastases

Stereotactic radiosurgery is a better choice than whole-brain radiation therapy for treatment of metastatic brain tumours, according to a study from the University of Missouri School of Medicine. The study examined the outcomes of patients treated at MU Health Care from 2010 to 2014. After brain surgery to remove a metastatic tumour, 46 patients received whole-brain radiotherapy, while 37 received radiosurgery, which is targeted to precise areas of the brain and causes less damage to healthy brain tissue. Radiosurgery controlled the spread of cancerous cells as effectively as whole-brain radiation, and patients who received radiosurgery experienced less cognitive decline than those who received whole-brain radiation. Additionally, the median survival rate for radiosurgery patients was 440 days, compared to 202 days for patients who had whole-brain radiation (Cureus 8 e885).

"For patients with metastatic cancer of the brain, the importance of surviving for a longer period of time cannot be overstated," said senior author N Scott Litofsky. "In our practice, we now treat patients almost exclusively with radiosurgery following their surgery. Although this therapy does cost more, results often can be achieved in one to three visits compared to 10 to 12 visits for whole-brain radiation. With these considerations, we strongly suggest physicians consider radiosurgery as an initial radiation treatment after surgery."

PET improves targeting for recurrent prostate cancer

A study from Emory University has shown that the PET radiotracer 18F-fluciclovine can help guide radiotherapy for recurrent prostate cancer, enabling individualized, targeted therapy. The researchers enrolled 96 patients in a randomized clinical trial of radiotherapy for recurrent prostate cancer after prostatectomy. All patients underwent initial treatment planning based on conventional abdominopelvic imaging (CT or MRI). Forty-five patients also underwent abdominopelvic 18F-fluciclovine PET/CT, and the resulting images were registered with the conventional images to determine whether they would modify the initial treatment plan (J. Nucl. Med. 58 412).

Inclusion of 18F-fluciclovine PET data in the treatment planning process led to significant changes in target volumes. It did result in higher radiation dose delivered to the penile bulb, but no significant differences in bladder or rectal radiation dose, or in acute genitourinary or gastrointestinal toxicity. The authors note that these are preliminary results in a three-year study hypothesizing that PET-based treatment plan modification will increase disease-free survival. "This is the first study of its kind demonstrating changes in post-surgery radiotherapy target design with advanced molecular imaging in recurrent prostate cancer, with no demonstrated increase in early radiotherapy side effects," explained first author Ashesh B Jani.

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