ASCO 2022–Advancing Equitable Cancer Care Through Innovation

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0603_1PM_EDUCATION SESSION_Biomarkers for Screening, Diagnosis, Monitoring, and Surveillance of Head and Neck Cancers

Time Sat, Jun 4, 2022 | 2:00 AM – 3:15 AM GMT+8
Chair(s) Nishant Agrawal, MD (這個人文章有夠多!!!)
Track(s) Prevention, Risk Reduction, and Hereditary Cancer | Head and Neck Cancer

Presentation 1: Screening for Oral Cavity Cancers and HPV-Associated Oropharvnaeal Cancers
person: Anil Chaturvedi, PhD, National Cancer Institute

  • Outline: Cancer Screening; Anatomy and etiologic heterogeneity; oral cavity vs oropharyngeal cancers; screening for oral cavity cancers; screening for HPV-associated OPC
  • Cancer screening: pre-cancer –> early cancer –> late cancer
  • secondary prevention: screen and treat to prevent precancer or early-stage cancer
  • Anatomy and etiologic heterogeneity
  • Screening for oral cavity cancers
    • Screening significantly reduces oral cancer mortality: The Kerala cluster-randomized trial (3 triennial screens with visual and tactile examination / control arm: no screening)
    • Original trial results: Sankaranarayanan et al Lancet 2005
    • Risk-based reanalysis using a risk predication model: Cheung et al., JCO 2021 (both overall and high-risk individuals show significant benefit in screening + no overdiagnosis)
  • Increased efficiency from risk-based screening: increased efficiency without loss in population-level mortality reductions
  • Best method for oral cancer screening? (Walsh et al., Cochrane Rev 2021)
  • Biomarkers for screening: clinical utility uncertain at this time.
  • Current standard: visual insepction, biopsy, histopathology
  • Screening for HPV-associated oropharyngeal cancers (OPC)
    • Strong serum and salivary biomarkers identified (serum: HPV16 E6 IgG antibodies | Saliva: oral HPV16 DNA, oral oncogenic HPV DNA)
    • Key knowledge gaps: screening not currently feasible (Tota et al., Cancer 2019)
    • Efficient design of clinical studies
    • High OPC burden in older individuals
  • Summary and take home points
    1. Screening for oral cavity cancers
      • Screening reduces oral cancer mortality (risk-based screening can enhance efficiency)
      • Clinical utility of biomarkers unclear
      • Current standard: visual and tactile examination, biopsy, histopathology
    2. Screening for oropharyngeal cancers
      • Strong serum and salivary biomarkers identified
      • Screening not currently feasible (No identifiable precancer / ear-stage cancer; Benefits and harms unknown)
      • Risk stratification can enable efficient design of clinical studies

Presentation 2: Dynamic Biomarkers for Treatment Adaptation and Surveillance in Head and Neck Squamous Cell Carcinoma
person Nishant Agrawal, MD, University of Chicago

  • Innovations in head and neck cancer (2000, HPV proven as causative agent of some HNSCCs; PFL1 found to be overexpressed in HNSCC tumors) Alsahafi et al., Cee Death and Diseases 2019)
  • Outline (Diagnosis Biomarkers (somatic mutations; p16/HPV); Therapeutics (PD-L1, Hypoxia, p16/HPV/HPV DNA); Surveillance (HPV DNA)
  • Mutational landscape of HNSCC (TCGA Nature 2015)
  • p16/HPV tissue biomarker (Larissa V Furtado, MD, 2014)
  • Seminal trials of immune checkpoint inhibitors in HNSCC (Cramer et al., Oral Oncology 2019)
  • Paradigm change in recurrent/metastatic HNSCC)
  • HPV+ oropharyngeal SCC de-escalations stratagies
  • Hypoxia
  • HPV DNA, induction chemotherapy, volumetric response, surgery, (chemo)radiation adjustment
  • EBV DNA and maintenance therapy (Brigette Ma @ Chinese University of Hong Kong)
  • HPV plasma DNA and surveillance (Chera et al., JCO 2020)
  • Detection of known or occult recurrence
  • Conclusion
    1. Monitoring during treatment (response-adaptive treatment, de-intensification, intensification, maintenance therapy, prognosis)
    2. Surveillance after completion of treatment

Presentation 3: Next Generation Biomarkers and Targeting of Thyroid and Salivary Gland Cancers
Person : Avatar Image Marcia S. Brose, MD, PhD, FASCO, FASCO; Sidney Kimmel Cancer Center, Jefferson Health

  • Trk-fusion thyroid cancer targeted with larotrectinib: best overall response and maximum change in target lesions
0603_3PM_Head_and_Neck_Cancer

01-PRESENTATION207083 Jun Ma 馬俊 NPC
Radiotherapy alone versus concurrent chemoradiotherapy in intermediate risk nasopharyngeal carcinoma: A multicentre, open-label, noninferiority, randomised phase III trial. Take home messages are list below

  • In IMRT era, stage II and T3N0 NPC with small LNs (< 3 cm), no rEBE and low EBV DNA viral load (<4000 copies/ml) are at low risk for recurrence.
  • This low risk NPC subgroup can be safely treated with IMRT alone instead of CCRT which
    • Provides non-inferior survival and disease control
    • Reduces toxicities and improved quality of life
  • These trials supports “IMRT alone as a valid option for low risk T1-2N1 and T3No NPC
0604_8AM_Introducing Checkpoint Inhibitors into the Curative Setting of Head and Neck Cancers- Lessons Learned, and Future Considerations

01-Lara Dunn MD-Depertmant of Medicine, Memorial Sloan Kettering Cancer Center
Combination Chemotherapy Immuno-oncology Approaches in Locally Advanced Head and Neck Cancer: Timing and Patient Selection

  1. Standard management of locally advanced head and neck cancer
  2. Potential benefits of introducing checkpoint inhibition into curative setting
    • Neoadjuvant Setting
      • reduces extensiveness of surgical resection/morbidity of surgery
      • modify adjuvant radiation-based therapy (pathological downstaging / resolution of high-risk features)
      • decrease risk of recurrence / improve event-free survival (induce anti-tumor immunity and memory against tumor-associated Ags before en bloc removal (in situ vaccine)
    • Adjuvant Setting
      • decrease risk of recurrence / improve event-free survival
  3. Mouse model oral cavity cancer suggests neoadjuvant anti-PD1 therapy maximizes anti-tumor immunity/T-cell responses compared to adjuvant therapy
Neoadjuvant checkpoint blockade–Prior to surgery
  • Unique advantages compared to chemotherapy: (1) increase levels of peripheral antigenic-specific CD8 T-cells, such that after removing the tumor, CD8 T-cells are releases from chronic antigen exposure and form anti-tumor memory T-cells to strengthen immunologic memory (2) more favorable toxicity profile
  • Disadvantage: (1) modest radiologic/clinical/pathologic response (2) longer neoadjuvant phase required to maximize overall response and depth of response balanced with delay in surgery
Induction chemotherapy (4 slides)
Potential advantages of combination neoadjuvant immunotherapy and chemotherapy
  • Improved response rate compared to immunotherapy alone
  • Induces anti-tumor immunologic memory
Combination neoadjuvant immunotherapy and chemotherapy in Breast Cancer and NSCLC
Combination in R/M HNSCC
Cetuximab combination
Neoadjuvant combination strategies in HNSCC
  • Patient selection (Clinical Features include stage and pathological risk features + molecular features such as PD-L1 %, CPS, TMB)
  • Current studies evaluating a combination approach
    • Thomas Jefferson University (NCT03342911)
    • MSKCC (NCT04722523)
Summary/Future Directions
  • Potential advantages of a combination strategy
    • Improved response rate compared to immunotherapy alone (allows for enhanced downstaging, less extensive surgeries and modifications of post-operative RT-based treatments)
    • Potentially improves depth of response compared to chemotherapy alone
    • Enhanced immunologic memory (generate anti-tumor memory T-cells with potential reduction in locoregional and distant recurrences
  • Important Outstanding Questions
    • Does pathologic response to neoadjuvant therapy correlate with clinical efficacy?
    • Is there a quantifiable QoL benefit?
      • Reducing extensiveness of surgery
      • Modifying adjuvant RT-based treatment

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