Investigations into the abscopal effect

The abscopal effect occurs when targeted irradiation of one tumour site causes regression of metastatic tumours in distant un-irradiated sites; but the outcome is highly unpredictable. The finding that immunoadjuvants can enhance the abscopal effect has led to a resurgence of interest in this phenomenon. Sayeda Yasmin-Karim from Brigham and Women's Hospital is investigating this approach in an animal model, using the mouse anti-CD40 antibody (AbCD40). In particular, she has assessed the optimal time and dose of radiation and immunotherapy to achieve the highest enhancement of the abscopal effect.

In a first experiment, Yasmin-Karim, Wilfred Ngwa and colleagues examined mice bearing two pancreatic tumours. They treated one tumour with AbCD40, radiotherapy (six 5 Gy fractions or three 10 Gy fractions) or a combination of both, and then measured the tumour volumes up to four weeks post-treatment. The greatest reduction in the volume of the treated tumour was seen for 10 Gy irradiation plus AbCD40. For the untreated tumour, however, the largest regression (caused by the abscopal effect) occurred for 5 Gy fractions plus AbCD40. "The directly treated tumour was almost cured, while the other side was reduced in size," Yasmin-Karim explained.

Next, the researchers studied the best time for antibody delivery and irradiation, using a single 5 Gy dose, and found that early onset treatment produced longer survival. They also examined excised lungs at 9.5 weeks after tumour implant. In control animals, metastases were seen in 100% of lungs, whilst in the treated mice, disease was only seen in 10%. "This approach doesn't only kill tumour cells locally and at a distance, it also prevents metastases by killing circulating cancer cells," Yasmin-Karim told medicalphysicsweb.

X-ray diffraction spectra classify breast tissue

Lumpectomy surgery for breast cancer involves removing the tumour and a margin of surrounding tissue. The excised tissue is then sent for pathological analysis to ensure that all of the cancer cells have been removed. Unfortunately, around 25% of lumpectomy patients (in the USA) are recalled for additional surgery, with some being recalled up to three times.

Researchers at Duke University are developing an X-ray diffraction spectral imaging system to differentiate cancerous and healthy breast tissue. The initial application, explained James Spencer from Duke University Medical Center, is to reduce the burden on the pathologist, by limiting the number of slides that need to be sent off for analysis. "This is a direct application that we can implement in the very near future, because we don't have to worry about dose," he explained. "Looking further ahead, a longer-term goal is to implement this in the surgical suite." This could involve scanning excised tissue to assess the tumour margins in real-time – or ultimately even scanning the breast cavity.

The XRD system uses a collimated X-ray pencil beam (approximately 1.5 mm in diameter) to probe small regions of tissue. The researchers use the energy and scattering angle of the diffracted beam to classify the tissue in that region as healthy or cancerous. Green/red colour coding of the two tissue types then produces a tissue mapping. The Duke team, led by principal investigator Anuj Kapadia used the XRD system to scan 36 freshly excised tissue samples from lumpectomy surgeries. They validated the red/green classification mappings against H&E stained slides evaluated by a pathologist. The XRD system exhibited an overall accuracy of 82.4% versus pathology assessment, as well as a healthy sensitivity of 94% and healthy positive prediction value of 86%.

Dynamic trajectories enhance mixed beam radiotherapy

Silvan Mueller from Inselspital and the University of Bern described the development of a mixed beam radiotherapy (MBRT) technique that combines photon dynamic trajectories (DTs) with modulated electron beams shaped by the photon multileaf collimator. While the electrons are delivered using a step-and-shoot approach, photon beam delivery exploits all the degrees-of-freedom offered by advanced techniques such as volumetric-modulated arc therapy (VMAT) – including intensity modulation, and dynamic gantry, couch and collimator rotation.

DT-MBRT treatment plans are created via a four-step process, Mueller explained. First, the planning system determines the deliverable dynamic photon trajectories and defines the electron fields and beam directions. It then performs simultaneous optimization of the electron apertures and the photon apertures along the dynamic trajectory. The next step is dose calculation for the electron apertures; then the photon dynamic trajectories are re-optimized based on this final electron distribution (using a research version of the Varian photon optimizer).

To test their approach, the researchers compared DT-MBRT, photon DT and VMAT plans for a squamous cell carcinoma in the brain and left eye. While target dose homogeneity was similar in all plans, they found that the dose to organs-at-risk and the low-dose bath to normal tissue was considerably lower for the MBRT plan compared with the photon DT and VMAT plans. "For all dosimetric quantities examined, we saw that the mixed-beam plan performed best," said Mueller. He noted that the biggest benefit of DT-MBRT may be seen in treatments in the head-and-neck region, where there are many superficial lesions that would benefit from electrons, and where the target location provides more space to rotate the couch.

"Importantly, this approach uses the existing treatment unit – no extra hardware is required, you can just use what the treatment machine offers," Mueller told medicalphysicsweb.

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