December 2016

Reporter's Notebook: News From ASTRO 2016
Radiology Today
Vol. 17 No. 12 P. 30

Editor's note: This article is based on materials distributed at the American Society for Radiation Oncology (ASTRO) 2016 conference in Boston.

Researchers Favor Radiation Boost for DCIS Patients
A supplemental "boost" of radiation improves local control and provides an incremental benefit in decreasing breast cancer recurrence for patients with ductal carcinoma in situ (DCIS) who receive whole breast radiation therapy (WBRT) following lumpectomy, according to research presented at the 58th annual meeting of ASTRO. Researchers concluded that use of a radiation boost should be considered in DCIS patients who have life expectancies of 10 or more years following breast-conserving surgery and WBRT.

DCIS patients undergoing breast conservation therapy typically receive a lumpectomy to remove the tumor, followed by WBRT to eliminate any residual cancerous cells within the breast. Following WBRT, many patients receive an additional boost of radiation of four-to-eight fractions to the surgical bed, which is the region at the highest risk for recurrence. While multiple clinical trials have demonstrated a modest but statistically significant reduction in ipsilateral breast tumor recurrence (IBTR) from a radiation boost after WBRT for invasive breast cancer, there are, to date, no published phase III studies examining radiation boost for DCIS.

Ten academic institutions from the United States, Canada, and France provided deidentified patient level data for 4,131 cases of DCIS, collaborating to analyze the benefit of the DCIS boost by assembling the largest cohort of patients with DCIS treated with or without boost to date. Eligible patients included those with pure DCIS (ie, no microinvasion) who received WBRT with or without radiation boost and reached a minimum of five years' follow-up. Eligible patients received either electron or photo radiation boost, and the median boost dose was 14 Gy. Records documenting patients receiving a brachytherapy boost, those having an unknown boost status, or those receiving partial breast radiation were not included in the analyses. Among the 4,131 cases included in this analysis, 2,661 patients received a radiation boost, and 1,470 did not. Use of radiation boost was more common for patients with positive margins following breast-conserving surgery, those with unknown estrogen receptor (ER) status, and individuals with the presence of necrosis documented on their pathology report. Median follow-up for all study participants was nine years.

DCIS patients who received a radiation boost following WBRT experienced a reduction in local recurrence. The IBTR-free survival for boost vs no boost, respectively, was 97.1% vs 96.3% at five years, 94.1% vs 92.5% at 10 years, and 91.6% vs 88% at 15 years following treatment, with these differences achieving statistical significance (p = 0.013).

"Many radiation oncologists routinely deliver a boost after WBRT for DCIS, anticipating a similar benefit to our experience with invasive cancers. But we haven't had consistent data to demonstrate this benefit in DCIS. Our study has demonstrated that the use of a radiation boost provides an albeit small but significant long-term benefit in reducing breast tumor recurrence for DCIS patients and supports the consideration of a DCIS boost in patients undergoing WBRT who have life expectancies of 10 or more years," said Meena Savur Moran, MD, lead study author, a professor of therapeutic radiology at Yale School of Medicine, and director of the Radiation Oncology Breast Program at Smilow Cancer Hospital at Yale New Haven.

The benefit in reducing in-breast recurrence was demonstrated across all DCIS age subgroups. Furthermore, treatment with the DCIS boost was an independent predictor for decreasing IBTR on multivariate analyses controlling for other patient and disease characteristics (ie, grade, necrosis, margin status, patient age, tumor size, and use of tamoxifen). On subset analysis, though the boost did not convey a statistically significant benefit in the subset of patients with positive margins (p = 0.99), it did independently predict for reducing IBTR in all DCIS age groups with negative margins (all p <0.02). Moran explained, however, that only 4% of study participants comprised the subset of patients with positive margins, so it is highly likely the positive margin subset was underpowered to show a statistically significant benefit.

"Our findings suggest that adding several additional fractions of radiation directed to the lumpectomy cavity after whole breast radiation for DCIS provides an incremental benefit in decreasing local relapse, similar in magnitude to the 4% at 20 years benefit of the boost for invasive cancers," Moran said. "While these small numbers may not seem substantial, the invasive boost data have highlighted to us the clinical importance that small decreases in local relapse provide for patients. Ultimately, these small decreases in IBTR resulted in a reduced number of mastectomies for recurrence by approximately 40% in patients who had received a boost, compared with no boost." ■

Study Finds SBRT Effective for Prostate Cancer Treatment
High-dose stereotactic body radiation therapy (SBRT) for men newly diagnosed with low- or intermediate-risk prostate cancer results in shorter treatment times, low severe toxicity, and excellent cancer control rates, according to research presented at the 58th annual meeting of ASTRO. The study is the first large, multi-institutional study of SBRT in prostate cancer with long-term follow-up.

Although prostate tumors generally respond well to radiation therapy (RT), the possibility of radiation exposure to healthy tissue in the genitourinary (GU) and gastrointestinal (GI) systems can be of concern. SBRT is an advanced technique that precisely targets high doses of RT to the tumor in a small number of fractions, simultaneously avoiding surrounding tissue and reducing toxicity to noncancerous cells. The technique has become the standard of care for many nonsurgical lung cancer patients, as it limits exposure to the heart and surrounding lungs. When treating tumors in the prostate, SBRT avoids the adjacent bladder, sex organs, and rectum.

A total of 309 men with newly diagnosed prostate cancer were enrolled in the trial at 21 community, regional, and academic hospitals across the United States. Eligible patients had either low-risk disease (clinical stage [CS] T1-T2a with Gleason 6 and prostate-specific antigen [PSA] <10) (n = 172) or intermediate-risk disease (CS T1c-T2b with either Gleason 7 and PSA <10 or Gleason 6 and PSA 10-20). All of the men received SBRT via a nonisocentric robotic platform, with an RT dose to the prostate of 40 Gy administered in five treatment sessions of 8 Gy each. Intermediate risk patients received a dose of 36.25 Gy to the seminal vesicles. Concurrent and adjuvant androgen ablation therapy were prohibited among study participants.
Primary outcomes included GU and GI toxicities and relapse-free survival (RFS). Researchers measured toxicity using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3.0. Biochemical failure was assessed using the ASTRO-consensus and the nadir+2 definitions. Overall survival (OS) was measured as a secondary outcome for the study. Actuarial OS and RFS were calculated with the Kaplan-Meier statistical method. Median follow-up was 61 months.

At five years following SBRT, 97% of patients were free from prostate cancer progression. In low-risk patients, the cancer control rates were superior to historical controls. Specifically in the low-risk group, the five-year RFS rate was 97.3%, which is superior to the 93% historical comparison disease-free survival control rate (p = 0.014). Actuarial five-year OS was 95.6% for the entire cohort. Actuarial five-year nadir+2 RFS was 97.1% for all patients, representing 97.3% of low-risk and 97.1% of intermediate-risk patients. Actuarial five-year ASTRO RFS was 92.3% and 91.3% for low- and intermediate-risk groups, respectively.

Fewer than 2% of all patients experienced serious side effects in the five years following SBRT. Five grade three GU side effects were reported in four of the 309 study participants. There were no reported grade four or five toxicities nor any grade three GI toxicities. Between one-half and two-thirds of patients experienced less serious side effects, with rates of 53% and 59% for grade one GU and GI toxicities and rates of 35% and 10% for grade two GU and GI toxicities, respectively. These side effects were usually temporary. ■