Top 10 ASTRO Abstracts 2018

Cleveland Clinic’s radiation oncologists select highlights

The results of hundreds of important studies were presented at the recent 2018 American Society for Radiation Oncology (ASTRO) annual meeting.

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Many Cleveland Clinic Cancer Center clinicians and researchers attended and presented. Since then, we’ve discussed and debated which presentations we found most intriguing or that we feel have the greatest potential to change the practice of radiation oncology.

Here are our top 10:

1. NRG-RTOG 1016: Phase 3 trial comparing radiation/cetuximab to radiation/cisplatin in HPV-related cancer of the oropharynx

RTOG 1016 was a prospective noninferiority trial of radiation with cetuximab compared with radiation with cisplatin in patients with locoregionally advanced HPV-related oropharyngeal cancer. Radiation was accelerated, 70 Gy delivered in six weeks, 6 fractions per week. A total of 805 patients were analyzed. Estimated five-year survival rates were 84.6 percent with cisplatin compared with 77.9 percent with cetuximab. Progression-free survival (PFS) was significantly worse with cetuximab [hazard ratio 1.72 (1.29-2.29); one-sided log-rank P < 0.0001] with five-year estimates of 78.4 percent with cisplatin and 67.3 percent with cetuximab. This study failed to establish the noninferiority of radiation with cetuximab for patients with locoregionally advanced HPV-related oropharyngeal cancer. Cisplatin and radiation remains the standard approach for HPV-related cancer of the oropharynx.

2. Local consolidative therapy (LCT) improves overall survival (OS) compared to maintenance therapy/observation in oligometastatic non-small cell lung cancer (NSCLC): final results of a multicenter, randomized controlled phase 2 trial

This study examined maintenance therapy/observation (MTO) compared with LCT in patients with oligometastatic lung cancer. A total of 49 patients with stage IV NSCLC met the eligibility criteria of three or fewer metastases with at least stable response to initial systemic therapy. The primary endpoint was PFS. The trial was stopped early due to an observed PFS benefit. PFS improved from 4.4 months to 14.2 months (P = 0.014) with the addition of LCT. OS also improved from 17.0 months to 41.2 months (P = 0.017). No additional grade 3 or higher toxicities were observed in either arm.

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3. Stereotactic ablative radiation therapy for the comprehensive treatment of oligometastatic tumors (SABR-COMET): results of a randomized trial

This phase 2 randomized study compared stereotactic ablative radiation therapy (SBRT) to all sites of metastatic disease with standard therapy with the primary endpoint of OS. To be eligible, patients needed a controlled primary site of disease, defined as a treated primary site without progression for at least three months. In addition, patients could not have more than five sites of metastatic disease. Cancer histologies permitted on this trial included prostate, breast, lung and colorectal cancer. There was an OS benefit to SBRT (not driven by prostate patients) from 28 months to 41 months median survival (P = 0.09). Grade 2 or higher toxicities increased from 9 to 30 percent with SBRT.

4. Preoperative chemoradiotherapy potentially improves outcomes for (borderline) resectable pancreatic cancer: preliminary results of the Dutch randomized phase 3 Preopanc trial

The Preopanc Trial randomized 246 patients with borderline resectable pancreatic cancer > 2 cm to immediate surgery versus preoperative chemoradiotherapy, both followed by adjuvant chemotherapy. Preoperative chemoradiotherapy was 36 Gy in 15 fx with concurrent gemcitabine. Primary endpoint was OS. Median OS was 13.5 months for immediate surgery versus 17.1 months for preoperative chemoradiotherapy followed by surgery (P = 0.074). Subgroup analysis of patients who were ultimately eligible for resection and started adjuvant gemcitabine had median OS of 19.1 months in immediate surgery arm and 42.1 months in preoperative chemoradiotherapy arm (P < 0.001). Preoperative chemoradiotherapy followed by surgical resection was associated with improved locoregional recurrence-free interval, distant metastasis-free interval and rate of R0 resection.

5. Short-term androgen deprivation therapy without or with pelvic lymph node treatment added to prostate bed-only salvage radiotherapy: the NRG/RTOG 0534 SPPORT trial

This was a randomized three-arm trial to determine whether there is improvement in freedom from progression (FFP, defined as increase in PSA of 2.0 ng/ml, clinical progression or death due to any cause) from the addition of four to six months of short term ADT (STADT), without or with pelvic lymph node radiotherapy (PLNRT), to prostate bed salvage radiotherapy (PBRT). A total of 1,792 patients were randomized to (1) PBRT alone, (2) PBRT with STADT or (3) PBRT with PLNRT and STADT. The five-year FFP rates for arms one, two and three were 71.2, 82.7 and 89.1 percent respectively (P < 0.0001). Among all patients, with eight years of follow-up, the rate of distant metastases trended towards benefit in the triple therapy compared with PBRT alone (HR 0.52, 95% CI 0.32-0.85, P = 0.014) and PBRT plus ADT (HR 0.64, 95% CI 0.39-1.06, P = 0.28). No increase in late GI/GU toxicity with nodal radiotherapy (RT) was reported.

6. Preservation of neurocognitive function (NCF) with conformal avoidance of the hippocampus during whole-brain radiotherapy (HA-WBRT) for brain metastases: preliminary results of phase 3 trial NRG Oncology CC001

This trial compared whole-brain radiation therapy (WBRT) (30 Gy in 10 fx) and memantine with hippocampal avoidance (HA) WBRT and memantine. A total of 518 patients were enrolled, and the primary endpoint was time to NCF using HVLT-R, COWA and Trail Making A and B tests. Patients were stratified by recursive partitioning analysis (RPA) class. The median follow-up time was 6.1 months. The time to NCF was significantly longer in the HA-WBRT arm, 69.1 percent, versus 58 percent in the WBRT arm at six months (P = 0.012). Differences in NCF appeared after four months of follow-up. Adjusting for stratification, HA-WBRT (P = 0.016) and age < 61 (P = 0.006) were associated with longer time to NCF, and the benefit was not limited by age. PFS and OS were the same in both groups. The authors concluded that in patients with a life expectancy greater than four months, HA-WBRT should strongly be considered for patients who are candidates for WBRT.

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7. Eliminating postoperative radiation to the pathologically node-negative neck: long-term results of a prospective phase 2 study

This was a single-arm study of omitting postoperative radiation therapy (PORT) to pathologically negative contralateral and/or ipsilateral neck in patients with tumors of the oral cavity, oropharynx, larynx, hypopharynx and unknown primary. The primary objective was to determine the rate of local control, regional control, PFS and OS. The authors hypothesized omission of RT as described would result in > 90 percent control in the unirradiated neck. The trial met the primary endpoint with 97 percent control in the unirradiated neck. This preliminary study suggests that omitting radiation to the pathologically node-negative neck is feasible and safe.

8. Randomized trial evaluating radiation following surgical excision for “good risk” DCIS: 12-year report from NRG/RTOG 9804

RTOG 9804 assessed the impact of whole breast irradiation (WBI) versus observation in women with “good risk” ductal carcinoma in situ (DCIS), following breast conservation. A total of 636 patients were randomized. Eligible patients had clinically occult DCIS, < 2.5 cm in size, final margin > 3 mm with low to intermediate nuclear grade. The 12-year rates of local recurrence were 2.8 versus 11.4 percent (P = 0.0001) in patients who received WBI versus observation, respectively. Twelve-year rates of invasive recurrence were 1.5 percent with WBI versus 5.8 percent with observation (P = 0.016). In conclusion, WBI significantly reduced local recurrences as well as invasive local recurrences in good risk DCIS patients despite not meeting target accrual.

9. Plasma circulating tumor HPV DNA for the surveillance of cancer recurrence in HPV-associated oropharyngeal cancer

This study was a prospective biomarker trial in 89 patients with p16 positive oropharyngeal SCC (OPSCC). It assessed the performance of plasma circulating tumor HPV DNA (ctHPVDNA) as a surveillance blood test. All patients received definitive chemoradiotherapy. Of the patients included in the trial, 78 received de-intensified chemoradiotherapy to 60 Gy. Every patient received a PET/CT three months post-treatment followed by chest X-ray or CT scan every six months. Blood specimens were collected at baseline, weekly during treatment and with each follow-up. Baseline ctHPVDNA was detectable in 88 percent of patients. Performance of ctHPVDNA was exceptional with a negative predictive value of 100 percent. ctHPVDNA appears to be a promising biomarker for this disease.

10. FAST phase 3 RCT of radiotherapy hypofractionation for treatment of early breast cancer: 10-year results

FAST was a trial of standard WBI versus hypofractionated WBI delivered once weekly over a course of five weeks for early stage breast cancer (pT1-2N0). The hypofractionated arm had two doses, 30 Gy/5 fx and 28.5 Gy/5 fx. The primary endpoint of this study was the two-year change in photographic breast appearance, which was previously published with the 10-year update presented. The incidence of late marked/moderate changes in breast appearance at 10 years was low. However, 30 Gy/5 fx resulted in the highest rates of breast changes. Low rates of recurrences were seen. The findings support the use of a once-weekly, 5-fraction whole breast regimen for those patients unable to undergo daily WBI.