Radio-immunotherapy combination slows tumour growth
A study from the MD Anderson Cancer Center has shown that a combination of stereotactic body radiation therapy (SBRT) and immunotherapy can halt the growth of tumours in patients with end-stage cancer.

"This combination of immunotherapy and radiation therapy was safe and well-tolerated by patients with late-stage cancers. We were surprised that a large percentage of patients achieved stable disease several months after treatment—meaning that while their tumours didn't shrink, they did stop growing," said lead author James Welsh. "It appears that the radiation helped turn the tumour into a vaccine to stimulate an immune response. This heightened immune response was able to keep the tumours stable. Longer follow-up is needed to determine if this benefit of stable disease will endure over time."

The phase II trial included 100 patients with lung or liver metastases. All patients received four cycles of ipilimumab and SBRT to the site(s) of metastasis. Radiation was delivered either concurrently with (on day two of the first immunotherapy cycle, to a total dose of 50 Gy) or sequential to (one week after the second cycle, to 50 or 60 Gy for larger lesions) immunotherapy.

Patients were enrolled into one of five treatment cohorts: concurrent lung, sequential 50 Gy lung, concurrent liver, sequential 50 Gy liver, and sequential 60 Gy liver or lung. Stable disease was achieved for 50% of patients in the sequential 50 Gy lung cohort, 45% of the concurrent lung group, 35% of the concurrent liver group and 30% of the sequential 50-Gy liver group. In the 60 Gy group, 60% demonstrated a favourable response.

The median progression-free survival for all patients following the combined treatment was five months, and median overall survival was 12 months. There were no complete responses to treatment, but a partial response was found for three patients who received concurrent SBRT. No patients experienced Grade 4 or 5 treatment-related side effects, 27 experienced immunotherapy-related Grade 3 toxicities and two experienced Grade 3 toxicities related to combination therapy.

Accelerated radiotherapy possible following mastectomy
Radiation therapy after mastectomy for high-risk breast cancer can be shortened from five to three weeks while maintaining tumour control rates, according to the results of a Chinese clinical trial. The trial of more than 800 patients confirmed that tumour recurrence rates following 15 daily fractions of radiation delivered over three weeks were not inferior to those following 25 fractions over five weeks.

"This trial demonstrates that we can safely accelerate adjuvant radiation therapy and reduce treatment time by two weeks," said Shulian Wang, a radiation oncologist at the Chinese Academy of Medical Sciences. "This option makes treatment more convenient for patients, reduces medical expenses and allows providers to treat more patients with limited resources."

Most (93.9%) patients in the study had stage III breast cancer, while the rest had stage II disease. Following mastectomy, patients were randomly assigned to receive either hypofractionated (43.5 Gy in 15 fractions) or conventionally fractionated (50 Gy in 25 fractions) external-beam radiotherapy to the chest wall and supra-infraclavicular nodal region.

Five years after treatment, the rate of locoregional recurrence was 8.3% following accelerated treatment and 8.1% following standard treatment. Five-year overall and disease-free survival rates were 83.2% and 74.6%, respectively, for accelerated treatment, and 85.6% and 70.7% for standard treatment. Rates of distant metastases were 23.2% and 26.2% at five years for accelerated and standard treatment, respectively. Patients also experienced fewer side effects following the accelerated treatment.

HDR brachytherapy is effective for cervical cancer
A multicentre trial has confirmed the effectiveness of high-dose-rate (HDR) brachytherapy for treating patients with intermediate-stage cervical cancer. In the trial, which included 601 patients from seven countries, all patients received 46 Gy of pelvic external-beam radiotherapy in 23 fractions plus HDR brachytherapy, randomized to either four 7 Gy or two 9 Gy applications. Additionally, half of the patients in each group received chemotherapy.

"Cervical cancer is a leading cause of cancer death among women in the developing world, and 80% of these patients live in lower- or middle-income countries, such as the ones in our trial," said study co-author May Abdel-Wahab, from the International Atomic Energy Agency in Austria. "It is essential that we have data applicable to these real-world settings."

Overall survival at five years was 67.2% for all patients, with a higher survival rate for the 440 women with stage IIB disease (71%) than the 161 with stage IIIB disease (58%). Overall survival rates for patients in the 4x7 Gy HDR brachytherapy group were 73.1% and 62.2%, with and without chemotherapy, respectively; in the 2x9 Gy group, rates were 65.1% and 68.3%. For patients with stage IIB disease, neither brachytherapy dose nor the addition of chemotherapy significantly influenced the overall survival rate.

The study did, however, reveal a dose-dependence for tumour control. Five-year locoregional control rates for patients in the 4x7 Gy group were 88% and 89%, with and without chemotherapy, respectively, compared with 78% and 75% for the 2x9 Gy arm. Severe treatment-related side effects did not differ between treatment groups.

"Our trial demonstrates that combining pelvic radiation therapy with four fractions of 7 Gy HDR brachytherapy is effective for locally advanced cervical cancer," said Abdel-Wahab. "In addition, it gives physicians data-supported guidance from a large, randomized study on what to expect in terms of outcomes if a regimen of two, 9-Gy fractions is used in resource-constrained settings."

Immune response sheds light on radiotherapy outcome
A study headed up at the University of Michigan in Ann Arbor has shown that immune response in prostate cancer may predict how patients will respond to radiation therapy, as well as their likelihood of disease recurrence and survival outcomes. In an analysis of more than 9000 prostate tumours, the researcher team also found evidence that PD-L2, not PD-L1, may provide a key route for targeted therapies to slow disease progression.

"When the immune system responds to tumours, it sends specific types of immune cells directly to the tumour," explained lead author Shuang (George) Zhao. "Understanding this infiltration of immune cells allows researchers and oncologists to devise treatment strategies based on each patient's specific immune response and disease biology."

The researchers examined 7826 recently-collected and 1567 retrospective prostatectomy samples with long term clinical outcomes, using computational analysis with specific immune-related genes to identify immune content in the samples. Clustering analysis identified a subset of patients with higher expression of immune-related pathways.

They found that increased immune content was associated with worse progression-free survival, distant metastasis-free survival, prostate cancer-specific survival and overall survival. This immune content score also predicted response to radiation therapy following radical prostatectomy. Different immune cells were influential in different ways. Specifically, higher levels of active macrophages and T-cells were prognostic for worse distant metastasis-free survival, while active mast cells, NK cells and dendritic cells were associated with improved distant metastasis-free survival.

PD-L1, the target of several FDA-approved checkpoint inhibitors, was not associated with treatment outcome in this study, but PD-L2, which interacts with PD-1 similarly to PD-L1, was associated with worse outcomes. Higher levels of PD-L2 were associated with greater likelihood of disease recurrence, distant metastasis and prostate cancer death.

"As immune checkpoint blockers have come to market, PD-L1 has received a great deal of attention - but it does not appear to be widely expressed in prostate cancer," noted Zhao. "PD-L2, however, was much more highly expressed in these tumour samples, and it also was associated with worse outcomes. The understudied PD-L2 ligand may be the better therapeutic target for patients with localized prostate cancer."