title: Strategy of Using Intratreatment Hypoxia Imaging to Selectively and Safely Guide Radiation Dose De-escalation Concurrent With Chemotherapy for Locoregionally Advanced Human Papillomavirus-Related Oropharyngeal Carcinoma.
abstract: To report a small substudy of an ongoing large, multi-arm study using functional imaging to assess pre-/intratreatment hypoxia for all head and neck cancer, in which we hypothesized that pre- and early-treatment hypoxia assessment using functional positron emission tomography (PET) imaging may help select which human papillomavirus (HPV)-positive (HPV(+)) oropharyngeal cancer (OPC) patients can safely receive radiation de-escalation without jeopardizing treatment outcomes.
  
  
  
  Patients with HPV(+) oropharyngeal carcinoma were enrolled on an institutional review board-approved prospective study of which de-escalation based on imaging response was done for node(s) only. Pretreatment (18)F-fluorodeoxyglucose and dynamic (18)F-FMISO (fluoromisonidazole) positron emission tomography (PET) scans were performed. For patients with pretreatment hypoxia on(18)F-FMISO PET (defined as a >1.2 tumor to muscle standard uptake value ratio), a repeat scan was done 1 week after chemoradiation. Patients without pretreatment hypoxia or with resolution of hypoxia on repeat scan received a 10-Gy dose reduction to metastatic lymph node(s). The 2-year local, regional, distant metastasis-free, and overall survival rates were estimated using the Kaplan-Meier product-limit method. A subset of patients had biopsy of a hypoxic node done under image guidance.
  
  
  
  Thirty-three HPV(+) OPC patients were enrolled in this pilot study. One hundred percent showed pretreatment hypoxia (at primary site and/or node[s]), and among these, 48% resolved (at primary site and/or node[s]); 30% met criteria and received 10-Gy reduction to the lymph node(s). At the median follow-up of 32 months (range, 21-61 months), the 2-year locoregional control rate was 100%. One patient failed distantly with persistence of hypoxia on (18)F-FMISO PET. The 2-year distant metastasis-free rate was 97%. The 2-year OS rate was 100%. Hypoxia on imaging was confirmed pathologically.
  
  
  
  Hypoxia is present in HPV(+) tumors but resolves within 1 week of treatment in 48% of cases either at the primary site and/or lymph node(s). Our 100% locoregional control rate suggests that intratreatment functional imaging used to selectively de-escalate node(s) to 60 Gy was confirmed safe using our stringent imaging criteria. Intratreatment functional imaging warrants further study to determine its ultimate role in de-escalation treatment strategies.
authors: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York. Electronic address: leen2@mskcc.org.
authors: Nancy
authors: N
authors: Lee
authors: Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Heiko
authors: H
authors: Schoder
authors: Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Brad
authors: B
authors: Beattie
authors: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Ryan
authors: R
authors: Lanning
authors: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Nadeem
authors: N
authors: Riaz
authors: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Sean
authors: S
authors: McBride
authors: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Nora
authors: N
authors: Katabi
authors: Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Duan
authors: D
authors: Li
authors: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Brett
authors: B
authors: Yarusi
authors: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Susie
authors: S
authors: Chan
authors: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Lindsey
authors: L
authors: Mitrani
authors: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Zhigang
authors: Z
authors: Zhang
authors: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: David G
authors: DG
authors: Pfister
authors: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Eric
authors: E
authors: Sherman
authors: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Shrujal
authors: S
authors: Baxi
authors: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Jay
authors: J
authors: Boyle
authors: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Luc G T
authors: LG
authors: Morris
authors: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Ian
authors: I
authors: Ganly
authors: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Richard
authors: R
authors: Wong
authors: Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: John
authors: J
authors: Humm
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000000981:diagnostic imaging / Q000556:secondary* / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives*; D009959:Oropharyngeal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000628:therapy*; D010100:Oxygen / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D011835:Radiation Protection / Q000379:methods; D019275:Radiopharmaceuticals; D011879:Radiotherapy Dosage; D061089:Radiotherapy, Image-Guided / Q000379:methods*; D016896:Treatment Outcome; D000072258:Tumor Hypoxia / Q000187:drug effects
chemical_list: D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D008920:Misonidazole; D010100:Oxygen