H&N Flashcards
For PORT when is chemo added?
Chemo and dose
ENE and 0r +ve Margin
Highdose cisplatin 100mg/m2 q3weeks is superior to low 30mg/m2 q1week in terms of LRC. BUT much worse tox and ultimately if chem abandoned pt may receive much less dose.
Basic doses for PORT
in 30# (to reduce OTT)
63 to +ve margin/ECE
60 to surgical bed/high risk including pre-operative GTV + 0.5cm margin.
54 to dissected neck
52 to elective nodes
DOI is important (e.g. oral cavity).
Give some examples of how it influences decision making
> 2mm, even T1-T2 get a neck dissection
> 4mm (Ganly) cutoff point where risk +ve nodes goes from 5-25%. An indication for RT.
> 10mm is T3 in oral cavity
Indications for PORT in H&N?
1) ENE or +ve margin (same as chemo)
2) T3-T4a
3) T1-T2 and any of LVI/PNI, <5mm maring
4) DOI>4mm
5) A 3-6cm ipsilateral node or muliple ips nodes
6) Recurrence
In the oral cavity a margin is considered +ve if?
<2mm
Similarly <2mm following TORS for oropharynx cancer is and indication for adjuvant
Pre CT sim for H&N:
Dental review
Consider PEG/dietician/Speech path
Med onc may consider auidometry
General imaging and its purpose on H&N workup:
CT neck with contrast + bone erosion
MRI for extent of local disease, involvement of glossal muscle, perineural spread. In oropharynx, MRI may not be essential unless concern for nerve invasion (but I would do one, helps at contouring ).
FDG PET for nodal and distant staging, can be difficult to interpret in oral cavity
Anatomical boundaries of oral cavity:
Ant: vermillion border
PostInf: Circumvallate Papillaae
Postsup: Junction of hard and soft palate.
The boundaries of the nasopharynx:
Superior: floor of sphenoid sinus and clivus;
Anteriorly: nasal choanae; posterior margin of nasal septum
Inferior: Soft Palate Posterior: the prevertebral musculature covering C1 and C2;
Laterally: Opening of Eustacian tube/torus tubarius, fossa of Rosenmuller and parapharyngeal space
When can chemo be omitted from the primary treatment of nasopharynx cancer?
Disease limited to the nasopharynx (and not bone invasive, but can have parapharyngeal extension): T1-T2.
At most N1: Unilateral Cx node <3cm, or uni/bilater retropharynx node. Nodes must be above cricoid.
Ie stage II
Primary Tx for a T2NOMO nasopharyngeal carcinoma:
What 2 factors may change volumes?
EBRT (VMAT partial arc 6MV photons) alone:
CTV_70Gy/35# = GTV+5mm
CTV_63/35 (EQD2 60Gy) = Entire nasopharynx +
Sup: Skull base w/ovale and rotundum, inf sphenoid sinus
if >=T3 - whole sphenoid and cavernous sinus
Inf: Soft palate
Ant: posterior 1/3 of max and nasal sinus
Post: Bilateral retropharynx nodes, ant 1/3 of clivus (whole clivus if involved - i.e. T3)
Lateral: Pterygoids and parapharyngeal space.
CTV 56 (EQD2 50): CTV 63+ Levels II-V.
If node +ve include 1B.
The OARS of head and neck and Dmax
Brain stem/ optic chiasm = Dmax <54Gy
Optic nerve Spinal cord = Dmax <45Gy
Temporal lobe/Brain = Dmax< 60Gy, V40Gy<5cc
Brachial plexus= Dmax< 66Gy
Retina/ eye = Dmax< 50Gy
Lens = Dmax < 8Gy
Lacrima = Dmax < 30Gy
Manidble = Dmax < 70Gy
Parotids Dmean <26Gy
Carotid = Dmax < 100Gy
In the case of a patient unfit for chemo, having primary radiation to their H&N cancer (except nasopharyngeal carcinoma), name 2 approaches to radiation that could be considered?
Logic and Pros/Cons?
Altered fractionation:
1) Accelerated like DHANCA regimen 70Gy/35#, 6#s/week
Reduces OTT (2 wks). REDUCES period of time in which accelerated repopulation may occur (e.g. onset ~ 4 weeks).
DAHANCA and others: Improved LC of primary, DFS (but definitely not OS). Much more acute grd III
2) Hyperfractionation to higher dose - e.g 80Gy/70#, BD over 6 weeks. Rationale decrease late effects, while isoeffective or better tumour control. Older data but, less late tox, same early, and better LC w/trend to OS.
Briefly describe the key molecular steps by which HPV 16 leads to tumour oncogenesis?
Where does p16 fit?
HPV DNA is integrated into host genome -> over-expression of E6 and E7 proteins:
E6 allows G1/S evasion by degrading p53 whose
normal function: DNA damage → p53 upregulate CDK1-p21 → inactive cyclin-CDK complex → cell cycles halted at G1/S check point
- Absent/ degraded p53 → cells progress through G1/S check point w/ f’d up DNA.
E7 phosphorylates Rb
Normal: Rb binds transcription factor E2F → inhibit E2F in G1 checkpoint of all cell cycles
- Phosphorylated Rb: Rb releases E2F → active E2F → transition of cell from G1 to S phase w/ f’d up DNA.
p16 provides -ve feedback to increase Rb binding E2F - therefore surrogate marker of HPV/E7.
What is p16
p16 is a CDK inhibitor. CDK 4/6 binds cyclin D forming a complex that phosphorylates Rb causing it to release E2F. By inhibiting this p16 inhibits progression through G1/S. Oncoprotein E7 conversely phosphorylates Rb, causing an increase in p16 (as negative feedback) - therefore p16 is surrogate marker of HPV/E7.
