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Printable Handouts
Navigable Slide Index
- Introduction
- Disclosures
- Head and neck cancer
- Squamous cell carcinomas
- Long term outcomes are poor for non-HPV-mediated cancers
- Outcomes are poor despite most patients being diagnosed with localized disease
- Radiation frequently used in the definitive or post operative setting
- Chemoradiation therapy
- PD-1 blockade in recurrent/metastatic disease (1)
- PD-1 blockade in recurrent/metastatic disease (2)
- PD-L1 and HPV as predictive biomarkers
- Higher CPS cutoff (CPS>50) is associated with higher response rates (1)
- Higher CPS cutoff (CPS>50) is associated with higher response rates (2)
- HPV-status and response to PD-1 inhibition (1)
- HPV-status and response to PD-1 inhibition (2)
- PD-L1 expression and HPV-status are related
- First-line metastatic disease
- Keynote 48: pembrolizumab monotherapy
- Keynote 48: pembrolizumab/chemotherapy
- Questionable benefit in CPS<1 patients
- Less benefit for ICI in patients with more advanced disease
- Avelumab plus CRT followed by avelumab maintenance vs. CRT in patients with LA SCCHN
- Why did studies adding immune checkpoint blockade to standard HN radiation fail to achieve their primary endpoints? (1)
- Why did studies adding immune checkpoint blockade to standard HN radiation fail to achieve their primary endpoints? (2)
- Why might preoperative IO yield better long-term results?
- Neoadjuvant nivolumab +/- ipilimumab in patients with oral cavity cancer
- Neoadjuvant immunotherapy results in volumetric, RECIST and pathologic response
- Pathologic complete response after 2.5 weeks of nivolumab/ipilimumab
- Disease-specific outcomes
- Neoadjuvant immune checkpoint HNSCC trials
- More promising results for preoperative radiation immunotherapy trials
- KEYNOTE-689: Phase 3 study of neoadjuvant and adjuvant pembrolizumab
- Neoadjuvant trials allow for in depth analysis of immune response
- Elective lymph node radiation: Evidence of immune response in neoadjuvant trials (1)
- Elective lymph node radiation: Evidence of immune response in neoadjuvant trials (2)
- Other agents may work with radiation to stimulate immune cells: IAP inhibitors
- Randomized phase 2 study of IAP inhibitor Xevinapant
- The addition of xevinapant to CRT nearly doubled cure rates
- Ongoing Trial: Trilynx
- Abscopal (out-of-field) effects
- Abscopal effects: Phase 2 data have been mixed (but generally negative)
- Radiation for immunotherapy resistance
- Isolated resistance and translational studies
- Keynote 48 (1)
- Keynote 48 (2)
- Schoenfeld et al., IJROBP, 2018
- Treating resistant metastases/oligoprogression
- Treatment for oligoprogression
- Summary
Topics Covered
- Head and neck cancer
- PD-1 blockade
- Predictive markers
- PDL1 expression and HPV status
- Keynote 48
- Neoadjuvant immunotherapy
- Immunotherapy trials
- Keynote 689
- IAP inhibitors
Links
Series:
Categories:
Therapeutic Areas:
External Links
Talk Citation
Schoenfeld, J. (2023, June 29). Immunotherapy and radiation for head and neck cancers [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 14, 2024, from https://doi.org/10.69645/JSLW2434.Export Citation (RIS)
Publication History
Financial Disclosures
- Research support paid to the institution: Merck, BMS, Regeneron, Debiopharm, EMD Serono Consulting / Scientific Advisory Board / Travel fees: Castle Biosciences, Genentech, Immunitas, Debiopharm, BMS, Tilos, AstraZeneca, ACI Clinical, Astellas, Stimit, Merck KGA, SIRPant, EMD Serono. Stock options: Immunitas.
Other Talks in the Series: Immunotherapy of Cancer
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Jonathan Schoenfeld.
I'm an Associate Professor of
Radiation Oncology at
Harvard Medical School and
a senior physician in
Radiation Oncology at
the Dana-Farber Brigham
and Women's Cancer Center.
It's a privilege to speak about
immunotherapy and radiation
for head-neck cancers.
0:17
Here are my relevant
disclosures.
0:21
For those who are not familiar
head-neck cancers occur at
different sub-sites with some of
the major sub-sites
including the nasopharynx,
oropharynx, oral cavity,
hypopharynx, and larynx.
These regions are very
important functionally,
for speaking, swallowing
and breathing.
Functional importance
makes treatment of
head-neck cancers complex
and patients with
head-neck cancers typically have
a multi-modality evaluation to
consider treatment options
including surgery,
radiation, and systemic
treatments to best
treat the cancer while
minimizing effects
on quality of life.
In addition to the
different sub-sites
and types of treatments,
there are also different
types of tumors.
This talk focuses on
the most common type of
tumor in the head and neck
squamous cell carcinomas.
Although the concepts that
I'll discuss apply to
some of the other common types
of head and neck tumors as well.
1:22
Among squamous cell carcinomas,
there are generally
considered to be
two biologically
different types.
The first is the more
traditional type
of head and neck
cancer caused by
tobacco and alcohol use that
leads to progressive
genomic changes over time.
That causes head and
neck malignancies.
The second type of squamous
cell carcinomas are
head and neck tumors
that are related to
the human papilloma
virus or HPV.
HPV is a common infection that
impacts epithelial cells and
particularly the cells among
the lymphoid tissue and
the base of tongue and tonsils
within the oropharynx.
As shown, chronic HPV
infection can lead to
HPV integration into
the host DNA or into
the nucleus and give rise
to the expression of
the E6 and E7
oncoprotein that in
turn inhibit tumor
suppressors p53 and RB.
Over a period of
likely many years or
even decades expression of
the E6 and E7 proteins and
subsequent inhibition
of p53 and RB leads to
progressive genomic changes and
the formation of HPV
associated cancers.
The number of HPV associated
oropharyngeal cancers
is significant,
peaking among men aged
50 and older and
increasing in many
countries around the world.