Fire up that loud, another round of shots.

Let’s keep the tradition alive with another year-in-review of bottom lines for the annual radiation oncology in-service exam. | QuadShot 2019-2020

GU | The death rate from localized prostate cancer (PC) was 31% with watchful waiting versus 20% with treatment in the >20-year follow-up of SPCG-4. 18 versus 6 months of ADT improved 10-year prostate cancer specific mortality from 10% → 13% for men with mostly HRPC in TROG RADAR. In ARAMIS, darolutamab joins apalutamide and enzalutamide in improving metastasis-free survival for men with CRPC but without an increase in toxicity. In RTOG 0521, adjuvant docetaxel after RT+ADT improved 6-year overall survival (81→ 86%) for men with HRPC. A huge meta-analysis of prostate SBRT for mostly low and intermediate risk prostate cancer showed >90% 7-year rate of biochemical control and only 2% GU and 1% GU G3+ toxicity. In ENZAMET, enzalutamide improved 3-year OS 72→ 79% when added to ADT in men with metastatic CSPC. Long-term results of GETUG AFU 16 suggest that only 6 months of ADT with salvage prostate radiation in men with PSA < 2 improves distant mets-free survival 69 → 75%. A secondary analysis of RTOG 9601 suggests the benefit of ADT is limited to men with PSA >1.5 and a detriment with ADT with <0.6. HYPO-RT-PC showed that 42.7 Gy in 7 fractions was non-inferior to conventional fractionation with a 5-year rate of failure-free survival of 84%. PACE-B toxicity showed no difference in G2+ toxicity at 12 weeks (~25%) for 5 fraction SBRT versus standard or moderately hypofractionated radiation. In ProtecT, about 5% of men per year on active surveillance moved to treatment. Prostate fossa SBRT seems to have issues with late G3 GU toxicity. Abiraterone → enzalutamide sequence has the longest time to second progression. After progression on an AR blocker and taxane, switching to cabazitaxel improved survival from 11 → 14 months. RADICALS-RT showed that adjuvant versus salvage radiation doesn’t improve bPFS—and only one-third of men in the salvage arm received radiation. FinnProstataX showed an improvement in bRFS with “adjuvant” radiation—although half the patients had PSA between 0.2 and 0.5.  PSMA has a better detection rate than fluciclovine (56 vs 26%) with post-prostatectomy PSA <2. The IROCK consortium says 25 Gy x 1 to RCC in a solitary kidney is safe with a median change in GFR of -3 mL/min.

BREAST | A hypofractionated PMRT regimen (43.5 Gy in 15 fractions using an electron field) was non-inferior to conventional fractionation for locoregional control—but no patients had reconstruction and the IMN weren’t treated. In TAM-01, 5 mg tamoxifen, aka baby Tam (as opposed to 20 mg), still reduced breast events while having much less toxicity. A nomogram from MA.20 data showed that the extent of axillary dissection was the main driver of lymphedema risk. 40% of patients with ER+, HER2- metastatic breast cancer have PIK3CA mutations, and in SOLAR-1, adding alpelisib (a PI3K inhibitor) to endocrine therapy improved PFS. APBI both is and isn’t non-inferior to whole breast radiation when it comes to breast recurrence and cosmesis. In both the RAPID and B-39 trials, the absolute difference in breast tumor recurrence was <1%, but RAPID found the difference non-inferior while B-39 found it not non-inferior. Also, a difference in technique was the 1 cm CTV margin in RAPID versus a 1.5 cm margin in B-39. The Canadian ACCEL trial found favorable outcomes (>90% good/excellent cosmesis) with 27 Gy in 5 daily fractions APBI to the lumpectomy + 1 cm CTV. ARTIC is a genomic classifier that is prognostic of the risk of locoregional recurrence (11% if “high”) and predictive of the benefit of breast-only radiation. Ribociclib finally improved OS in MONALEESA-3. Tucatinib significantly improves overall survival from 27 → 45% for advanced HER2+ breast cancer in HER2CLIMB. Staged implant reconstruction (as opposed to direct) has a higher complication rate, and PMRT scar boost further boosts complication risk. Women with atypical hyperplasia, LCIS, or an estimated 3% risk of breast cancer in 5 years should consider primary chemoprevention (baby Tam?). Neoadjuvant taselisib and letrozole had a 2% rate of pCR (50% objective response rate) for HR+ breast cancer while pembro + chemo had a 65% rate for TNBC.

CNS | In ACNS0121, a reduced target volume (tumor bed + 1 cm to 59.4 Gy if > 18 months or 54 Gy between 12 and 18 months) was effective for pediatric ependymoma. Overall and event-free survival were very good for the patients <3 years old who previously had delayed radiation. The rate of salvage WBRT (12-16%) is similar for patients who get SRS to 1 met or 5-15 mets. Tucatinib improved 1-year PFS from 0→ 24% in women with HER2+ brain mets. The rate of 3-year PFS for high-risk meningioma (WHO III, recurrent or STR WHO II) was 59% in RTOG 0539. V33.5 > 0.05cc is a good predictor of necrosis following fSRS to brain met resection cavity. 37.5/15 WBRT doesn’t improve cognitive outcomes over 30/10. The addition of lomustine to temozolomide improves median OS 31→ 48 months for MGMT-methylated GBM. In NRG CC001 risk of cognitive failure was significantly lower after HA-WBRT versus WBRT (both with memantine).

GI | Despite what the statisticians said, adjuvant capecitabine appeared beneficial for patients with resected cholangiocarcinoma and gallbladder cancer in the BILCAP trial. Around the same time, PRODIGE-12 showed no improvements with GEMOX for those same tumors. In POLO-1, olaparib significantly improved PFS for patients with metastatic, BRCA-mutated pancreatic cancer. In ADORE, patients with residual T3+ or N+ rectal cancer after nCRT had improved DFS with adjuvant FOLFOX. Even though FOLFOX increased the pCR rate (7% FU/RT v 14% FOLFOX v 28% FOLFOX/RT), it didn’t improve DFSfor T3/N+ rectal cancer in FORWARC. The most common pattern of pancreatic cancer progression on ESPAC-4 was local only progression (50%).

LUNG | In CHISEL, SBRT had superior 2-year local control (89% versus. 65%) and median OS compared to both hypofractionated and conventional radiation alone for early stage NSCLC. PCI for patients with stage III NSCLC reduces the rate of brain mets by 57% and improves DFS, although it doesn’t improve OS. RTOG 0813 demonstrated the safety of 5-fraction SBRT for “central” lung tumors with only 7% dose-limiting toxicities in the 12 Gy x 5 arm. Adding durvalumab to chemo improves OS (10-13 months) for SCLC in CASPIAN—which didn’t give PCI.

H&N | Sixty percent of HPV(+) oropharyngeal cancers appear to express the estrogen receptor, which was associated with improved OSl. The rate of occult path positive nodes is 13% when the PET scan shows the hemi-neck to be negative. An ascending pattern of tumor spread (i.e. higher T stage) is associated with better outcomes than descending (i.e. nodal) spread for NPC, and induction gem/cis improves OS 90 → 95%. 85% of patients with recurrent HNSCC have a combined positive score (CPS) for immunotherapy of 1 or more. The ORATOR trial showed that TORS actually had more toxicity (dysphagia) than radiation for early stage HNSCC.

SARCOMA | Despite doubling survival in phase II and gaining accelerated FDA approval, olaratumab didn’t improve survival (it was actually worse at median 5 vs. 7 months) in the phase III ANNOUNCE trial.

GYN | In GOG-249, there was no difference in the 76% DFS rate for whole pelvis alone versus carbo/taxol and VBT. In GOG-0213, cytoreductive surgery for advanced ovarian cancer didn’t improve (and possibly worsened) survival outcomes. The rate of G3+ toxicity with a 28 Gy in 4 fraction SBRT boost in lieu of brachytherapy for cervical cancer was 27%. Over half of women with advanced ovarian cancer have homologous recombination repair deficiency, and three different PARP inhibitors improved PFS for these patients. For locally advanced cervical cancer receiving chemoradiation, neoadjuvant chemo decreased response rate and overall survival.

PEDS | Tandem ASCT for high-risk neuroblastoma improves 3-year EFS 48→ 63%—in addition, 36 Gy was not better than 21.6 Gy at reducing local progression.

PHYSICS | Cherenkov light is the cause of flashes of blue light seen by some patients during RT near the eyes. 

PALLIATIVE | 8 Gy x 1 improves pain score by 3 points in 58% of patients compared to just 40% for SBRT in RTOG 0631. Similarly, SBRT for other bone mets didn't improve pain response versus conventional treatment.

LYMPHOMA | In HD16, omitting radiation for patients with GHSG-favorable HL with negative PET after 2 cycles of ABVD reduced PFS from 93 → 86%.

OLIGO | This has become a category of its own. The Gomez trial and SABR-COMET made headlines with each showing improved median OS with aggressive local therapy for patients with oligomets and no progression after initial systemic therapy. The Gomez trial was specifically for NSCLC with up to 3 sites of disease and “SBRT” wasn’t required. SABR-COMET was for any malignancy with mostly 1-3 sites and did require SBRT treatment.

CARDIAC | Yep, that’s right. ENCORE-VT demonstrated the safety and efficacy of 25 Gy x 1 at reducing the burden of refractory ventricular tachycardia.