Table 9.
Personalized Radiation Deintensification Trials
| Study | Treatment Arms | Outcomes | Toxicities |
|---|---|---|---|
| MSKCC 30 ROC136–137 / NCT03323463 | Baseline FMISO-PET scan prior to CRT start. | Pilot Study (n=15 de-escalated patients): | 0 grade 3 RT-related toxicities on the pilot trial. |
| (Phase II). | If first FMISO-PET +hypoxia, second FMISO-PET performed 2 wks after CRT start. | −2 yr LRC 100% | |
| p16+ OPC. | −2 yr PFS 92.9% | Acute grade 3 toxicity on the Phase II trial: | |
| AJCC7 T1–2 N1–2C. Any PYSH. | Hypoxia-neg: 30Gy CRT (with HD cis) | −2 yr OS 92.9% | - 2 diarrhea, 2 syncope, 1 vasovagal, 1 dysphagia |
| Pilot Study: | - n=19 Pilot trial (15 de-escalated) | −11 of 15 pathological CR. | - No grade 3 mucositis, 0 pegs. |
| - primary site resection before CRT | - n=158 Phase II trial (128 de-escalated) | Phase II (whole cohort): | |
| - planned ND at 4 months post-CRT. | −1 yr LRC 94% | ||
| Phase II FU: | Hypoxia+: 70Gy CRT (with HD cis) | −1 yr DMFS 100% | |
| - primary site resection before CRT | Median FU = 34 months (pilot study) | −1 yr PFS 94% | |
| - no planned ND at 4 months post-CRT. | Median FU = 12 months (Phase II). | −1 yr OS 100% | |
| - No 30Gy patients failed in the primary site | |||
| - 8 patients with LN recurrences, all | |||
| successfully salvaged with surgery. | |||
| UNC+UF / NCT03077243 | >10 PYSH AND p53 wild-type, Or ≤10 PYSH: | Ongoing, not reported | Ongoing, not reported |
| (Phase II) | Deintensified def CRT (60Gy + LD cis 30–40 mg/m2 wkly) | ||
| p16+ and/or HPV+ OPC. | p53 mutant: SOC CRT 70Gy + LD cis 30–40 mg/m2 wkly | ||
| AJCC7 T0-3 N0-2C. | - ctHPVDNA will be prospectively assessed and correlated with outcomes. | ||
| The ReACT Study/ NCT04900623 | NavDX ctHPVDNA test (detects HPV16) at baseline, 4 wks and end of treatment. | Ongoing, not reported | Ongoing, not reported |
| (Phase II) | LR: 5–6 wks reduced dose def RT ± chemo | ||
| p16+ and HPV+ OPC. | HR: 7–8 wks SOC def RT ± chemo | ||
| AJCC8 Stage I, II, or III. | Chemo: HD cis, LD cis, or carbo/pacl. | ||
| MSKCC / NCT05307939 | Must have preoperative NavDX ctHPVDNA >50 copies/mL. | Ongoing, not reported | Ongoing, not reported |
| (Phase II) | Check NavDX ctHPVDNA levels (Frag/mL) postoperatively and every 3–6 months | ||
| HPV-16 OPC or unknown primary | to select patients for active surveillance (OBS) or SOC adjuvant therapy | ||
| cancer with no residual disease on | LR: <5 (OBS), 5–7 (repeat NavDX), >7 (SOC adjuvant therapy) | ||
| postoperative imaging. | IR: <5 (OBS), ≥5 (SOC adjuvant therapy) | ||
| T1N1-T4N3. No positive margin or ECE. | |||
| Univ of Michigan / NCT03416153 | Pre- and mid-treatment PET scans to select patients for de-escalation. | Ongoing, not reported | Ongoing, not reported |
| (Phase II) | Deintensified def CRT (54Gy + carbo/pacl) | ||
| p16+ or HPV+ OPC. | |||
| AJCC8 Stage I or II. | |||
| NYU / NCT03215719 | Interval CT scan at 4 wks to select responders. | Ongoing, not reported | Ongoing, not reported |
| (Phase II) | >40% LN shrinkage → reduced dose def RT (60Gy + cis) | ||
| p16+ OPC. | |||
| AJCC7 T1–3 N1–2B. |
AJCC7=American Joint Committee on Cancer 7th Edition, AJCC8=American Joint Committee on Cancer 8th Edition, carbo=carboplatin, chemo=chemotherapy, cis=cisplatin, CRT=chemoradiation therapy, ctHPVDNA=circulating tumor HPV DNA, def=definitive, DM=distant metastasis, FU=follow-up, Gy=gray, HD=high-dose, HPV=human papillomavirus, HR=high-risk, IR= intermediate-risk, LD=low-dose, LN=lymph node, LR=low-risk, LRC= locoregional control, OBS=observation, OPC= oropharyngeal cancer, OS=overall survival, +=positive, pacl=paclitaxel, PET=positron emission tomography, PFS=progression-free survival, PYSH=pack-year smoking history, RT=radiation therapy, SOC=standard of care, wkly=weekly, wks=weeks, yr=year.