Hit me with your best shot.
Sip on some shooters of our favorite QuadShots over the past year as part of our annual rad onc in-service exam pre-game. And if that doesn’t quench your thirst, open wide for last year’s. | QuadShot 2018-2019
CNS | In NAO-09, adding lomustine to TMZ improved mOS 31 → 48 months for GBM. MGMT-methylation predicts for better survival with TMZ-RT for low-grade gliomas. Parotid-sparing WBRT prevents xerostomia. Radionecrosis rates drop from 23 → 7% with hypofractionated SRS for brain mets 2-3 cm while numerically improving local control. Asymptomatic brain mets from melanoma respond to ipi + nivo 46% to 56% of the time.
BREAST | In TAILORx there was no benefit with chemo for Oncotype DX scores 11-26, except in women <50 with scores 16-26. In RTOG 98-04 adjuvant RT for low-risk DCIS reduces 12y recurrence from 11.4 → 2.8%. In the Chinese hypofrac PMRT trial, en face electrons were used to deliver 43.5 Gy in 15 fractions to the chest & supraclav with no difference in locoregional recurrence (8%) or late toxicity. In NSABP B-39 APBI (external beam & brachy) resulted in not non-inferior local recurrences (4.1 → 4.8%) and flat-out inferior any recurrences (6.6 → 8.1%) and G≥3 toxicities (7.1 → 9.6%). In RAPID APBI (external beam only) did result in non-inferior local recurrences (2.8 → 3%) but doubled fair/poor cosmesis (19 → 38%). On the other hand, 28.5 Gy / 5 whole breast in UK FAST had similar cosmesis to 50 Gy / 25 while 30 / 5 was cosmetically worse. In AMAROS 10y ax recurrence was not non-inferior with omission of ax dissection if SLN(+) (<1 → <2%). In KATHERINE adjuvant TDM-1 over trastuzumab improved 3y DFS (77 → 88%) for residual HER2(+) residual disease. And don’t forget capecitabine for residual TNBC.
CUTANEOUS | Avelumab and pembro have shown promising phase 2 responses in Merkel cell carcinoma, as has the tongue-twister cemiplimab in SCC...but not weakly carbo when added to RT.
LUNG | For ALK-rearranged NSCLC, alectinib has more intracranial activity than crizotinib. And for EGFR-mutations, osimertinib has more than gefitinib or erolitinib. In IMpower133, adding atezo to carbo/etoposide for SCLC improved mPFS 4 → 5 mo and mOS 10 → 12 mo. In the Gomez study, adding SBRT for NSCLC with oligomets (≤3 sites) improved mOS 17 → 40 mo. By the way, in SABR-COMET adding SBRT for any cancer with oligomets (≤5 sites) improved mOS 28 → 41 mo. But don’t go SBRT’ing ultracentral lesions as this MSKCC data had a >10% G5 toxicity rate. Oy.
H&N | RTOG 1016 & De-ESCALaTE were De-FLATING. In 1016 (non-inferiority design), cetuximab instead of cisplatin reduced 5y OS from 85 → 78% and increased locoregional failure from 10 → 17%. Don’t forget that RT in 1016 was given accelerated at 6 fractions per week. In De-ESCALate, toxicity was the same but 2y OS (2° endpoint) was reduced with cetuximab 98 → 89%.
GU | In SPPORT treating pelvic nodes and adding short-term ADT to salvage prostate RT improved 5y PFS 71→ 83 → 89%. In STAMPEDE, prostate RT (55 Gy / 20 or 36 Gy / 6) improved 3y OS from 73→ 81% in low-volume mPC (<4 bone-only mets or any number of spine/pelvis-confined mets) but not in overall population. In the similar but smaller HORRAD trial, there was no benefit. Long-term results of RTOG 9413 showed nothing that makes any sense except that adding pelvic nodal RT doubles the rate of G3+ GI toxicity. A PSA of ≥0.5 at 3 mo after ADT-RT for int-high risk PC is associated with worse survival. In CARMENA nephrectomy for mRCC did not improve survival over sunitinib.
GI | In PREOPANC-1 neoadjuvant 36 Gy / 15 with weekly gemcitabine for borderline resectable pancreatic cancer improved mOS 13.5 → 17 mo and R0 rate 31→ 65%. In PRODIGE-24 adjuvant mFOLFIRINOX increased mOS from 34 → 54 mo over gemcitabine for resected pancreatic cancer. CRITICS showed pre-op ECF → post-op 45 Gy / 25 + CF doesn’t improve anything over the old standard peri-op ECF for gastric cancer. With the new standard being peri-op FLOT.
GYN | In a Tata trial, the addition of cisplatin to definitive RT for women with IIIB cervical cancer improved 5y DFS from 44 → 52% and OS 46 → 55%. In LACC, minimally invasive radical hysterectomy for cervical cancer resulted in worse PFS and OS. Oh, and modern imaging is now allowed in FIGO staging.
PHYSICS | FLASH-RT delivers >100 Gy per second and allows for significant dose escalation with dramatic sparing of normal tissue. But who are we kidding. Hope you know what a delta ray is.
CNS | In NAO-09, adding lomustine to TMZ improved mOS 31 → 48 months for GBM. MGMT-methylation predicts for better survival with TMZ-RT for low-grade gliomas. Parotid-sparing WBRT prevents xerostomia. Radionecrosis rates drop from 23 → 7% with hypofractionated SRS for brain mets 2-3 cm while numerically improving local control. Asymptomatic brain mets from melanoma respond to ipi + nivo 46% to 56% of the time.
BREAST | In TAILORx there was no benefit with chemo for Oncotype DX scores 11-26, except in women <50 with scores 16-26. In RTOG 98-04 adjuvant RT for low-risk DCIS reduces 12y recurrence from 11.4 → 2.8%. In the Chinese hypofrac PMRT trial, en face electrons were used to deliver 43.5 Gy in 15 fractions to the chest & supraclav with no difference in locoregional recurrence (8%) or late toxicity. In NSABP B-39 APBI (external beam & brachy) resulted in not non-inferior local recurrences (4.1 → 4.8%) and flat-out inferior any recurrences (6.6 → 8.1%) and G≥3 toxicities (7.1 → 9.6%). In RAPID APBI (external beam only) did result in non-inferior local recurrences (2.8 → 3%) but doubled fair/poor cosmesis (19 → 38%). On the other hand, 28.5 Gy / 5 whole breast in UK FAST had similar cosmesis to 50 Gy / 25 while 30 / 5 was cosmetically worse. In AMAROS 10y ax recurrence was not non-inferior with omission of ax dissection if SLN(+) (<1 → <2%). In KATHERINE adjuvant TDM-1 over trastuzumab improved 3y DFS (77 → 88%) for residual HER2(+) residual disease. And don’t forget capecitabine for residual TNBC.
CUTANEOUS | Avelumab and pembro have shown promising phase 2 responses in Merkel cell carcinoma, as has the tongue-twister cemiplimab in SCC...but not weakly carbo when added to RT.
LUNG | For ALK-rearranged NSCLC, alectinib has more intracranial activity than crizotinib. And for EGFR-mutations, osimertinib has more than gefitinib or erolitinib. In IMpower133, adding atezo to carbo/etoposide for SCLC improved mPFS 4 → 5 mo and mOS 10 → 12 mo. In the Gomez study, adding SBRT for NSCLC with oligomets (≤3 sites) improved mOS 17 → 40 mo. By the way, in SABR-COMET adding SBRT for any cancer with oligomets (≤5 sites) improved mOS 28 → 41 mo. But don’t go SBRT’ing ultracentral lesions as this MSKCC data had a >10% G5 toxicity rate. Oy.
H&N | RTOG 1016 & De-ESCALaTE were De-FLATING. In 1016 (non-inferiority design), cetuximab instead of cisplatin reduced 5y OS from 85 → 78% and increased locoregional failure from 10 → 17%. Don’t forget that RT in 1016 was given accelerated at 6 fractions per week. In De-ESCALate, toxicity was the same but 2y OS (2° endpoint) was reduced with cetuximab 98 → 89%.
GU | In SPPORT treating pelvic nodes and adding short-term ADT to salvage prostate RT improved 5y PFS 71→ 83 → 89%. In STAMPEDE, prostate RT (55 Gy / 20 or 36 Gy / 6) improved 3y OS from 73→ 81% in low-volume mPC (<4 bone-only mets or any number of spine/pelvis-confined mets) but not in overall population. In the similar but smaller HORRAD trial, there was no benefit. Long-term results of RTOG 9413 showed nothing that makes any sense except that adding pelvic nodal RT doubles the rate of G3+ GI toxicity. A PSA of ≥0.5 at 3 mo after ADT-RT for int-high risk PC is associated with worse survival. In CARMENA nephrectomy for mRCC did not improve survival over sunitinib.
GI | In PREOPANC-1 neoadjuvant 36 Gy / 15 with weekly gemcitabine for borderline resectable pancreatic cancer improved mOS 13.5 → 17 mo and R0 rate 31→ 65%. In PRODIGE-24 adjuvant mFOLFIRINOX increased mOS from 34 → 54 mo over gemcitabine for resected pancreatic cancer. CRITICS showed pre-op ECF → post-op 45 Gy / 25 + CF doesn’t improve anything over the old standard peri-op ECF for gastric cancer. With the new standard being peri-op FLOT.
GYN | In a Tata trial, the addition of cisplatin to definitive RT for women with IIIB cervical cancer improved 5y DFS from 44 → 52% and OS 46 → 55%. In LACC, minimally invasive radical hysterectomy for cervical cancer resulted in worse PFS and OS. Oh, and modern imaging is now allowed in FIGO staging.
PHYSICS | FLASH-RT delivers >100 Gy per second and allows for significant dose escalation with dramatic sparing of normal tissue. But who are we kidding. Hope you know what a delta ray is.
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