The American Society for Radiation Oncology’s (ASTRO) 2019 annual meeting presented the results of hundreds of important studies from the nation’s top cancer programs. The staff of Cleveland Clinic Cancer Center’s Department of Radiation Oncology has compiled the following list of ASTRO 2019 abstracts that our physicians consider to be the most intriguing, the most clinically relevant, or that have the greatest potential to change the practice of radiation oncology in the near future.
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1. Radiosurgery Compared To External Beam Radiotherapy for Localized Spine Metastasis: Phase III Results of NRG Oncology/RTOG 0631
Comment: In this phase III NRG Oncology/RTOG trial, 339 patients with 1-3 sites of spine metastases were randomized 2:1 to stereotactic body radiation therapy (SBRT, 16 or 18 Gy in 1 fraction) versus conventional radiotherapy (RT, 8 Gy in 1 fraction). The primary endpoint was pain control, defined as a 3-point improvement on the numeric pain scale (0-10). The 3-month change in pain score was not different between arms (-3.00 with SBRT vs. -3.83 with conventional RT). In addition, no difference in the rate of pain response at 3 months was observed (40.3% with SBRT vs. 57.9% with conventional RT, p = 0.99).
Conclusion: Spine SBRT failed to improve pain response from the patient’s perspective at 1, 3, and 6 months in patients with localized spine metastases.
2. PET-Guided Treatment of Early-Stage Favorable Hodgkin Lymphoma: Final Results of the International, Randomized Phase III Trial HD16 by the GHSG
Comment: This phase III trial randomized 1,150 patients undergoing positron emission tomography (PET)-guided treatment of early-stage favorable Hodgkin’s lymphoma to standard Adriamycin/bleomycin/vinblastine/dacarbazine (ABVD) for 2 cycles + 20 Gy involved-field radiation therapy (IFRT) versus PET-guided treatment where IFRT was only given to patients with PET-positive disease after 2 cycles of ABVD. Median follow-up was 47 months. Among patients with PET-negative disease after two cycles of ABVD (PET-2), 5-year progression-free survival (PFS) was 93.4% (90.4-96.5%) with combined modality therapy and 86.1% (81.4-90.9%) with chemotherapy only (hazard ratio 1.78; 95% confidence interval 1.02-3.12). The PFS difference primarily resulted from a significant increase in the in-field recurrence rates (2.1 vs 8.7%, p = 0.0003), with no difference in out-of-field recurrences. Five-year overall survival was 98.1% with combined modality vs 98.4% with chemotherapy only. In the combined modality group, 5-year PFS in the PET-negative group was 93.2% vs 88.1% in PET-positive group. Using Deauville score 4 for PET-positive, this difference was more pronounced with 5-year PFS, 93.1% vs 80.1%.
Conclusion: In early-stage favorable Hodgkin’s lymphoma, even when PET is negative, RT improves PFS after 2 cycles of ABVD. Positive PET after 2 cycles ABVD is a risk factor for worse PFS, even with 20 Gy of consolidation RT, particularly with Deauville score of 4.
3. Two Years of Anti-Androgen Treatment Increases Other-Cause Mortality in Men Receiving Early Salvage Radiotherapy: A Secondary Analysis of the NRG/RTOG 9601 Randomized Phase III Trial
Comment: This phase III NRG Oncology trial randomized 760 post-radical prostatectomy prostate cancer patients with biochemical failure (post-op prostate-specific antigen [PSA] 0.2-4.0 ng/mL) and either pathologic T2 disease with positive surgical margins or pathologic T3, who then received salvage RT (64.8 Gy/36 fractions) plus 150 mg daily bicalutamide versus placebo for 24 months. This secondary analysis demonstrated a significant overall survival (OS) benefit for bicalutamide in men with PSA >1.5 ng/mL (hazard ratio [HR] 0.45; 0.25-0.81), but not for PSA 0.2-1.5 ng/mL (HR 0.87; 0.66-1.16). Men with PSA ≤0.6 ng/mL had increased other-cause mortality from bicalutamide (HR 1.94; 1.17-3.20). There was increased grade 3-5 cardiac events in the bicalutamide arm (p = 0.04).
Conclusion: PSA is both prognostic and predictive for benefit of hormone therapy with salvage RT. Long-term androgen deprivation therapy did not improve OS in patients receiving early salvage RT, and may increase other-cause mortality.
4. A Phase III Multi-Centre Randomized Trial Comparing Adjuvant versus Early-Salvage Radiotherapy Following a Radical Prostatectomy: Results of the TROG 08.03 and ANZUP “RAVES” Trial
Comment: This phase III trial randomized 333 patients with extraprostatic extension (EPE), seminal vesicle invasion (SVI), or positive margins and prostate specific antigen (PSA) < 0.10 ng/mL to adjuvant radiotherapy (RT) within 6 months of radical prostatectomy versus salvage RT triggered by rise in PSA ≥0.20 ng/mL. Treatment consisted of 64 Gy/32 fractions to the prostate bed alone, with or without androgen deprivation therapy. Primary aim was to exclude 10% inferiority in freedom from biochemical failure (FFBF) in the salvage RT arm. Enrollment closed early due to low number of events. No difference in 8-yr FFBF for adjuvant RT vs salvage RT (79% vs. 76%; NS) was noted. ~50% of men received salvage RT due to rising PSA. Grade ≥2 genito-urinary (GU) toxicity rate was lower in the salvage RT arm (odds ratio 0.34; p = 0.002). There was no difference in grade ≥2 gastrointestinal toxicity.
Conclusion: Salvage RT spares half of men from pelvic RT and is associated with lower GU toxicity.
5. Primary Outcomes of a Phase II Randomized Trial of Observation versus Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer (ORIOLE)
Comment: This phase II trial randomized 54 patients with recurrent, hormone-sensitive oligometastatic (1-3 sites) prostate cancer to stereotactic body radiation therapy (SBRT) versus observation. Primary endpoint was progression at 6 months. Significantly less progression at 6 months was noted with SBRT, 19% vs 61% for the observation group. Interestingly, all 35 patients in the SBRT group had blinded prostate-specific membrane antigen (PMSA) positron emission tomography (PET)/computed tomography at baseline and 6 months, which was not used for SBRT planning. Patients who had total consolidation of PET-positive lesions were less likely to develop new metastatic lesions at 6 months (16% vs 63% p = 0.006) and had significantly longer progression-free survival (PFS, not reached vs 11.8 months, p = 0.003) as well as improved distant metastasis-free survival (29 vs 6 months, p = 0.0008). SBRT induces a systemic adaptive immune response, and greater baseline clonality was correlated with progression at 180 days in the SBRT arm only, indicating baseline clonality is predictive of response to SBRT.
Conclusion: SBRT to metastatic sites for patients with oligometastatic, hormone-sensitive prostate cancer is associated with improved PFS.
6. Significant Preservation of Neurocognitive Function and Patient-Reported Symptoms with Hippocampal Avoidance during Whole-Brain Radiotherapy for Brain Metastases: Final Results of NRG Oncology CC001
Comment: This phase III NRG Oncology trial randomized 518 patients with brain metastases to whole-brain radiotherapy (WBRT) and memantine (M) versus hippocampal avoidance (HA)-WBRT and M. Median follow-up was 7.9 months for surviving patients. HA-WBRT+M was associated with lower risk of neurocognitive failure at 4 months (62.7% vs 54.5% WBRT+M, p = 0.02). There was no difference in toxicity, overall survival or intracranial progression between the two arms.
Conclusion: HA-WBRT+M better preserves neurocognitive function and results in fewer patient-reported symptoms compared to WBRT+M.
7. Cosmetic Outcome from Post Lumpectomy Whole-Breast Irradiation (WBI) Versus Partial Breast Irradiation (PBI) on the NRG Oncology/NSABP B39-RTOG 0413 Phase III Clinical Trial
Comment: This phase III NRG Oncology/NSABP-RTOG trial randomized women with early-stage breast cancer following lumpectomy to partial-breast irradiation versus whole-breast irradiation. Ten-year local outcomes were previously reported, demonstrating a difference of less than 1% for in breast recurrence rates. In this quality-of-life sub-study (900 analyzable patients), cosmetic results were compared between arms by patients, physicians and central review. Patient-rated cosmetic outcomes were equivalent. On physician rating, while initial outcomes were equivalent, partial-breast irradiation resulted in worse cosmetic outcomes at 3 years. On blinded central review, no difference in cosmetic outcomes were noted at 3 years; however, partial-breast was associated with worse cosmesis for patients who received chemotherapy, while whole-breast was associated with worse cosmesis for patients who did not receive chemotherapy.
Conclusion: While shown to have worse outcomes as assessed by physicians, partial-breast irradiation was found to provide cosmetic outcomes equal to whole-breast irradiation as assessed by patients and blinded review.
8. NRG-HN002: A Randomized Phase II Trial for Patients with p16-Positive, Non-Smoking-Associated, Locoregionally-Advanced Oropharyngeal Cancer
Comment: This Phase II NRG Oncology trial randomized 306 patients with locally advanced p16-positive oropharyngeal cancer with ≤10 pack year smoking history to 60 Gy of intensity-modulated radiation therapy (IMRT) with weekly cisplatin (40 mg/m2) versus modestly accelerated 60 Gy IMRT over 5 weeks (6 fractions/week) without chemotherapy. The study’s endpoint was maintaining acceptable progression-free survival (PFS, ≥85% at 2 yrs) without unacceptable dysphagia as measured by the MD Anderson Dysphagia Inventory (MDADI). Of the eligible patients, 62% had T2-3 disease, 76% had N2 disease, and 80% received bilateral neck irradiation. Of the patients receiving cisplatin, 73% received ≥200 mg/m2. At 2.6 years median follow-up, the 2-year PFS estimate for chemoradiation was 90.5% (p = 0.035), and the 2-year PFS estimate for radiation alone was 87.6% (p = 0.2284).
Conclusion: De-escalation of therapy with 60 Gy with cisplatin met the study endpoint. The IMRT-alone arm also had a high PFS but failed to reject the null hypothesis and did not meet the PFS acceptability criteria. Both arms demonstrated satisfactory swallowing function as measured by the MDADI at 1 year. Estimated 2-year overall survival rates were similar (96.7% vs. 97.3%).
9. Patient-Reported Acute Toxicity in PACE-B, an International Phase III Randomized Controlled Trial Comparing Stereotactic Body Radiotherapy to Conventionally Fractionated or Moderately Hypofractionated Radiotherapy for Localized Prostate Cancer
Comment: This phase III non-inferiority trial randomized 874 patients with low- and intermediate-risk prostate cancer (Gleason score 4+3 excluded) to conventional (78 Gy in 39 fractions) or moderately hypofractionated (62 Gy in 20 fractions) radiotherapy versus stereotactic body radiation therapy (SBRT, 36.25 Gy in 5 fractions over 1-2 weeks). Primary endpoint: freedom from biochemical or clinical failure. Co-primary endpoint: worst acute grade 2 or more severe Radiation Therapy Oncology Group genito-urinary/gastrointestinal (GU/GI) toxicity (patient-reported outcomes). There was no difference in worst acute grade 2 or more GI or GU toxicity between the arms. Recently reported evidence from the HYPO-RT-PC trial suggested higher patient-reported toxicity with ultrahypofractionation (SBRT).
Conclusion: Results from PACE-B showed no significant differences in key patient-reported outcome measures, suggesting SBRT does not increase either GI or GU acute toxicity.
10. Radiotherapy versus Trans-Oral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Results of a Randomized Trial
Comment: This phase II study randomized 68 patients with T1-T2, N0-N2 (≤4 cm, no extracapsular spread on imaging) oropharyngeal squamous cell carcinoma (OPSCC) to trans-oral robotic surgery (TORS) versus definitive radiation (70 Gy/35 fractions) alone for T1-2N0 or chemoradiation for T1-2N1-2. Patients were stratified by p16 status. The primary endpoint of the study was swallowing quality of life at 1 year using the MD Anderson Dysphagia Inventory (MDADI). Median follow-up was 27 months. The radiation arm demonstrated a statistically significant improvement in MDADI scores at 1 year (p = 0.04) but did not meet the pre-specified definition of a clinically meaningful change (i.e., 10-point improvement in MDADI). In subset analyses, no subgroup was identified favoring TORS. There was one TORS-related bleeding death.
Conclusion: Toxicity patterns differed between the groups. Patients with OPSCC should be informed about both treatment options.