Head and Neck Flashcards
Describe the 5 phases of the cell cycle
- G0 = resting phase
- G1 = Growth phase 1 in preparation for DNA synthesis
- S = DNA synthesis
- G2 = Growth phase 2 in preparation for division
- M = Mitosis
During which stages of the cell cycle are cells most and least susceptible to damage from Chemo/XRT?
- S = DNA synthesis (most resistant phase)
- G2 = Growth phase 2 in preparation for division (2nd most sensitive phase)
- M = Mitosis (most susceptible phase)
Describe 5 methods for targeting a Vector to a specific cell type
- Tumor-specific promoter
- Activate promoter gene expression specifically in tumor cells (ex CEA, AFP)
- Non-specific promoter
- Drive replication in all susceptible cell types, higher risk for toxicity (ex CMV)
- Direct, receptor-targeting
- Create ligand for specific receptor characteristic of tumor cells
- Indirect, inverse-targeting
- DEtarget healthy, non-tumor cells to improve vector selectivity for cancer cells
- Indirect, protease-targeting
- Selective infection of cells w/ specific surface protease (which activate the viral receptor and allow viral entry)
List different viral vectors currently in use in H&N cancer
- Adenovirus
- Reovirus
- Rhabdovirus
- Measles
- Mumps
- HSV
- Vaccinia
What are two gene types involved in cell growth in cancer?
- Tumor Suppressor Genes (limit cell growth through negative feedback)
- ProtoOncogenes > Mutated Oncogenes (induce cell growth)
Which Tumor Suppressor Genes are involved in H&N Cancer?
p53 - Regulates cell cycle & apoptosis
- Involved in > 50% of HNSCC
- Bad prognosis
p16 (protein from CDKN2A gene) - Suppresses cyclin-dependent pathways
- Involved in > 70% of HNSCC
- Surrogate marker for HPV
- Good prognosis
RB - Inhibits transcription factor E2F
- Involved in > 60% HNSCC
Which Oncogenes are involved in H&N Cancer?
EGFR - Mutation promotes epidermal overgrowth
- Involved in > 90% HNSCC
- Poor prognosis
Cyclin D1 - Phosphorylates Rb, accelerates cell cycle
- Associated with increased recurrence, nodal mets, death
RET Translocation - Receptor TK involved in cell growth
- Associated with MEN2
RAS - Signal transducer for surface growth factor receptors
BRAF - Protein kinase activated by oncogenic RAS to increase growth factor signaling
- Associated with PTC
C-MYC - Transcription regulator
- Common in HNSCC
- Associated with Burkitt’s Lymphoma
- Poor prognosis
BCL-2 - Counteracts p53 & inhibits apoptosis
- Good prognosis
In what situation does HPV+ status NOT improve prognosis
History of smoking > 10 years
Discuss possible mechanisms of immunocompromise in HNSCC
HOST-related:
- Comorbid condition (ex. HPV, SLE, DM2, etc)
- Circulating immune complexes
- Suppressor T-cells
- Ig-blocking Antibodies
- TGF-B
TUMOUR-related:
- Tumor production of immunosuppressant agents (ex. VEGF, IL-1, IL-10)
- Tumor suppression of innate immunity
- Tumor antigenic modulation
EXOGENOUS:
- Chemo/XRT
- Immunosuppressant medications (ex. steroids, IFN, methotrexate, cyclophosphamide, etc)
Methods to assess adequate cerebral perfusion prior to carotid ligation
- Balloon occlusion test
- 4-vessel angiography (carotids & vertebrals)
- SPECT
- Xenon-133 flow scan
- CTA/MRA
What is the incidence of CVA/stroke following carotid occlusion at different speeds?
Acute occlusion (ex. ligation in OR w/o pre-op measures) = 50%
Gradual occlusion over <7d (ex. intraluminal tumor invasion) = 30%
Gradual occlusion over >7d (ex. vessel compression by tumor, or pre-op tx) = 5%
What intervention can be done pre-op to reduce the likelihood of CVA post surgical ICA ligation
Pre-op embolization (aka permanent balloon occlusion):
- Embolization of ICA just proximal to ophthalmic artery takeoff
- Reduces stump emboli
- 2 weeks pre-op
- Monitor for 72h post-procedure
List the segments of the ICA
C1 = Cervical
C2 = Petrous TB
C3 = Foramen Lacerum
C4 = Cavernous Sinus
C5 = Clinoid
C6 = Ophthalmic
C7 = Communicating
Define Simultaneous Tumors
Separate primary tumors diagnosed at same time
Define Synchronous Tumors
Separate primary tumors diagnosed within 6 months of each other
Define Metachronous Tumors
Separate primary tumors diagnosed > 6 months of each other
Define 2nd Primary
Separate primary tumor, based on:
- Different cell type
- Different location
- Different metastatic nodal group
**10% risk 2nd primary in non-smokers
**Risk increases to 50% in smokers
**50% develop within 2 years of 1st primary
How does continued smoking & ETOH use affect risk of recurrence and 2nd primary?
Up to 50% risk recurrence and/or 2nd primary
Describe the phases of clinical trials
PHASE 1 = Safety trial (dose determination, side effects)
PHASE 2 = Efficacy trial (does it work?)
PHASE 3 = Comparative trial (how does it compare to standard therapies?)
PHASE 4 = Post-marketing assessment of long-term complications
What is RECIST?
Response Evaluation Criteria in Solid Tumours
According to RECIST, what qualifies as a measurable lesion?
10mm in long axis on clinical or CT exam
According to RECIST, what qualifies as a pathological LN?
15mm in short axis on CT
According to RECIST, what is a target (or index) lesion?
Largest, most representative lesion (max 5 total, or 2/organ
- Used to track and assess treatment response
- More does not yield more accurate assessment and just wastes time & resources)
Define Objective Response (OR) according to WHO and RECIST
RECIST = Change in sum of longest dimensions of target lesions (max 2 lesion/organ, max 5 lesions overall)
WHO = change in sum of [longest dimension x cross dimension]s of all lesions
