1. Samson, Kurt

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Cancer patients with more than one brain metastases respond better to stereotactic radiosurgery (SRS) than to whole brain radiation therapy (WBRT), according to final analysis of Phase III study data presented at the ASTRO 2020 Annual Meeting (Abstract 4).

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For the most part, SRS has replaced WBRT as the standard of care for patients with 1-3 brain metastases; however, evidence in patients with more than that number is limited, said lead investigator Jing Li, MD, PhD, Associate Professor of Radiation Oncology and Director of Gamma Knife Radiosurgery at MD Anderson Cancer Center.


She presented findings from a Phase III randomized controlled trial in adults with 4-15 untreated non-melanoma brain metastases stratified by histology, number of lesions, baseline Hopkins Verbal Learning Test-Revised Total Recall (HVLT-R TR) score, extracranial disease, KPS, and age who were randomly assigned to SRS or WBRT. Use of the dementia drug memantine was encouraged in the WBRT arm.


Neurocognitive function (NCF) tests were administered at baseline and longitudinally, and included tests of learning, memory, verbal fluency, processing speed, and executive function. HVLT-R TR and local control (LC) were assessed at 4 months. Secondary endpoints included additional NCF tests, overall survival (OS), distant brain failure, toxicity, and time to systemic therapy.


The researchers randomized 72 patients to receive SRS or WBRT, with 36 individuals in each arm. The median number of brain metastases at enrollment was eight, and the estimated median follow-up time was 6.6 months. Thirty-one patients were available to be evaluated for verbal learning/revised total recall testing at 4 months.


In the WBRT arm, 62 percent of patients received memantine. In the primary endpoint analysis, relative to baseline, the 4-month HVLT-R TR standardized z-score increased by +0.21 for SRS-treated patients and declined by -0.74 among WBRT-treated patients (p=0.041).


Based on the Clinical Trial Battery Composite (the mean z-score for the HVLT-R, COWA, TMT), at 4 months the NCF of patients in the SRS arm improved on average +0.23 (SE 0.14) and the NCF of patients in the WBRT arm declined on average -0.73.


Survival Rate

The researchers reported that median overall survival was 10.4 months for SRS and 8.4 months for WBRT. Preliminary analyses of LC at 4 months demonstrated 100 percent LC rate for SRS and 95.5 percent for WBRT, and median time to distant brain failure (DBF) was 4.3 months for SRS versus 18.1 months for WBRT. LC and DBF results are currently being independently confirmed by the trial radiologist.


In non-melanoma patients with 4-15 brain metastases, SRS was associated with reduced risk of neurocognitive deterioration relative to WBRT without compromising OS. These results provide level 1 evidence to support the use of SRS in patients with 4-15 brain metastases amenable to SRS.


Kurt Samson is a contributing writer.


Pelvic Radiation in Women With Cervical Cancer

In another final analysis of a randomized Phase III trial data, Supriya Chopra, MD, Assistant Professor of Radiation Oncology at Tata Memorial Centre in Mumbai, India, presented data from the PARCER study of pelvic radiation in women with cervical cancer (Abstract 2).


She said image-guided intensity-modulated radiation therapy (IMRT) was as effective as 3-dimensional conformal radiation (3D-CRT) at controlling tumors with fewer gastrointestinal side effects in women who receive radiation after undergoing hysterectomy for cervical cancer.


"For the first time, we have confirmed that image-guided IMRT for pelvic radiation can improve cervical cancer patients' quality of life without compromising disease-free survival rates," she said.


Chopra and her colleagues randomized 283 patients who had undergone hysterectomy into two arms-half received image-guided IMRT and the other half received 3D-CRT. A majority received concurrent chemotherapy as well as a brachytherapy boost after external radiation treatments. Four years later, 19 percent of patients in the image-guided IMRT group experienced moderate-to-severe gastrointestinal side effects, compared to 38 percent in the 3D-CRT group.


In 2015, Chopra reported preliminary results at ASTRO showing that the group treated with image-guided IMRT had fewer bowel-related side effects after a median follow-up of 20 months, but the difference was not statistically significant in the earlier analysis.


PARCER investigators measured 11 different gastrointestinal side effects over the follow-up duration. There were no significant differences between groups for nausea and vomiting, but large differences emerged over time between the two groups for other symptoms. Specifically, in the group receiving image-guided IMRT, significantly fewer patients reported moderate-to-severe acute diarrhea (17% vs. 27%), as well as late abdominal bloating (14% vs. 28%), bowel obstruction (1% vs. 7%), or anorexia/appetite loss (1% vs. 7%).


"This is the first study in gynecological cancer to show a clear impact of advanced technology in reducing long-term morbidity and potentially improving the survivorship experience of women with gynecological cancers. Given these results, women undergoing postoperative radiation for these cancers should receive image-guided IMRT."


Grade 2 toxicity-free survival rates were significantly higher for patients treated with image-guided IMRT (78% vs. 57%), as were grade 3 toxicity-free survival rates (97.6% vs. 81.6%). The groups did not differ in disease-free survival (73% vs. 68%).


"Our results show that, with image-guided IMRT, there is a clear reduction in toxicity, with no difference in pelvic relapse," Chopra noted. A planned subset analysis also found that the benefit of image-guided IMRT was more pronounced in the setting of concurrent chemotherapy.