head and neck cancer Flashcards
most common locations of HPV-related squamous cell H and N cancer
palatine tonsils, lingual, base of tongue
role of EGFR in pathogenesis of SCCHN
leads to activation of growth pathways and resistance to apoptosis
virus associated with nasopharyngeal cancer
EBV
“field cancerization” concept?
diffuse epithelial injury in aerodigestive tract due to chronic exposure to carcinogens
Management of early stage head and neck cancer in general + exception to rule
primary surgery or definitive radiation therapy (oral cavity cancers are usually surgery because cure rates are better and less toxic)
current classifications of surgical neck dissection
comprehensive and selective
comprehensive surgical neck dissection – structures removed and intent
remove all five lymph node levels with curative intent
selective surgical neck dissection – structures removed and intent
remove fewer than all five lymph nodes based on common pathways, performed electively to improve staging. Usually reserved for NO (no palpable lymph nodes) or occasionally N1-N2.
new mode of radiation therapy used for head and neck cancer and point
intensity-modulated RT (IMRT), decreases toxicity (especially xerostomia)
xerostomia
dry mouth due to reduced or absent salivary flow
common SE’s of radiation in head and neck
dermatitis, xerostomia, mucositis, loss of taste, dysphagia, loss of hair
role of concomitant chemoradiation as first-line therapy?
- To spare patients with locally advanced from surgery.
- very advanced SCCHN
concomitant vs sequential chemo and radiation for H and N cancer
concomitant preferred for organ preservation (except for laryngeal)
Radiation sensitizer + RT dose + schedule for head and neck
70 Gy at daily Gy fractions for 7 weeks with cisplatin q 3 weeks
IO drugs approved for head and neck cancer
cetuximab, nivolumab, pembrolizumab
role for cetuximab in metastatic head and neck cancer
…
Major RF’s for local recurrence
- positive margins
- extracapsular nodal spread of tumor
combination therapy vs monotherapy in head and neck cacner
combination therapy is superior
Second line for recurrent/metastatic head and neck cancer
- Immunotherapy –> nivolumab or pembrolizumab
- If not immunotherapy candidate –> single agent cetuximab, weekly docetaxel, weekly methotrexate
poor prognostic factors for lip cancer
Lower lip –> low incidence of mets
Upper lip –> higher incidence of mets
most common presentation of nasopharyngeal carcinoma
Neck mass (regional lymph node mets)
Standard therapy for nasopharyngeal carcinoma Stages I and IIA
+ IIB, III, IV
Stages I and IIA – Radiation alone
IIB, III, IV – chemoradiation with cisplatin
IVC – cisplatin with gemcitabine or cisplatin with 5-FU or single agent taxane
hypopharyngeal cancer managment
Induction therapy w/ cisplatin + 5-FU followed by followed by XRT or cisplatin with XRT
T4A –> total laryngectomy followed by radiation +/- chemotherapy
division of laryngeal cancers + prognosis
Supraglottic, glottic, and subglottic
Management of laryngeal cancer, locally advanced
resection followed by radiation vs. organ preservation (induction chemo (cisplatin + 5 FU) followed by XRT
management of cancer of nasal cavity and paranasal sinuses
Surgical resection generally preferred (but difficult to perform due to advanced presentations), thus most patients treated with chemoradiation
Primary treatment modality for salivary gland tumors
complete surgical resection
primary therapy for cancers of oral cavity
surgical resection
management of persistent oropharyngeal cancer
modified radical neck dissection
CPS (clinical performance score)
Score of PD-L1 expression. Number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
tumors with high somatic mutation burden + relevance to immunotherapy
Preliminary data suggest that tumors with high rates of somatic mutations (ie, sun-exposed cutaneous melanoma, NSCLC, bladder cancer, and microsatellite-unstable colorectal carcinomas) have a higher chance of benefiting from immune checkpoint blockade than tumors with lower rates of somatic mutations
staging
Contrast CT +/- MRI (depends on what head and neck surgery want)
IF palpable LAD → PET/CT
clinical significance of PNI
Mechanism of tumor dissemination that can provide a challenge to tumor eradication and that is correlated with poor survival. Squamous cell carcinoma, the most common type of head and neck cancer, has a high prevalence of PNI.
TORS meaning
transoral robotic surgery. innovative, minimally invasive treatment option to remove head and neck cancers through the mouth, especially those related to the human papilloma virus (HPV)
MRND meaning
Modified radical neck dissection
ENE clinical significance
- Presence of ENE in squamous cell carcinoma of the head and neck, found postoperatively, is associated with higher rates of locoregional recurrence, distant metastasis, and poorer survival.
- Critical importance because determines need for chemo.
adverse features defined as:
Presence of ENE in squamous cell carcinoma of the head and neck, found postoperatively, is associated with higher rates of locoregional recurrence, distant metastasis, and poorer survival.
management of locally advanced head and neck cancer
IF PS good → Primary surgery +/- Radiation
IF declined surgery → concurrent chemo + RT
IF positive surgical margins OR nodal mets with extracapsular extension → chemo (usually cetuximab or cisplatin)
oral cavity vs oropharynx
The oral cavity lies anterior to the oropharynx and is separated from it by the circumvallate papillae; soft palate; and anterior tonsillar pillars, which make up its posterior boundary. The oral cavity is bounded superiorly by the hard palate, laterally by the cheek, and inferiorly by the mylohyoid muscle.
clinical relevance of HPV vs non HPV head and neck cancers
no data at present to indicate that human papilloma virus (HPV) associated cancers should be treated differently than other squamous cell carcinomas arising in the oropharynx, although several reports suggest that patients with HPV associated cancer have improved survival rates relative to patients with HPV negative cancers
what is CPS?
Combined Positive Score (CPS), which is the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
cellular origin of squamous cells
epithelial lineage or characteristics.[citation needed] SCCs arise from squamous cells, which are flat cells that line many areas of the body
where does nasopharyngeal cancer typically present?
Fossa of Rosenmuller
Effect of HPV vaccination on incidence of HPV-related SCCHN
Hasn’t been demonstrated yet…
Basic staging system based on…
Tumor size, nodal involvement, mets
Presentation of nasopharyngeal cancer
Persistent nasal congestion and fullness
Presentation of laryngeal cancer
hoarseness
Why field cancerization topic is important
- Diffuse epithelial injury within aerodigestive tract may lead to second metachronous and synchronous cancers of aerodigsestive tract.
- Mandates chest imaging because of risk of concurrent lung malignancy
How does presence of palpable lymph nodes in neck effect survival rate compared to patients with the same T stage
Decreases survival rate by 50%
Importance of timing in SCCHN cancer
IMPORTANT. Shouldn’t be any delays in staging and therapy, which can decrease survival.
Sequence of interventions in SCCHN
Depends on cancer center location and expertise – surgery followed by radiation/chemo OR chemoradiotherapy followed by surgery
Involvement of which structures makes SCCHN tumor unresectable
- tumor extension to skull base
- direct tumor extension to superior nasopharynx or Eustachian tube
- encasement of common or internal carotid artery
- direct extension to mediastinum, prevertebral fascia, or cervical vertebra
- direct extension of neck disease to external skin
- involvement of pterygoid muscles
major advantage of radiation therapy in SCCHN
organ preservation
What is organ preservation approach
Induction chemo (cisplatin + 5 FU) followed by XRT
Which laryngeal cancers have the best and worst prognosis?
Supraglottic have worst prognosis
Glottic have best prognosis
Clinical presentation of oral cavity tumors
Mouth pain, nonhealing mouth ulcers, dysphagia, odynophagia, weight loss, bleeding, otalgia
Clinical presentation of tongue cancer
Pain, with or without dysarthria
Clinical presentation of oropharyngeal tumors
Dysphagia, pain, OSA or snoring, bleeding, or a neck mass
Clinical presentation of hypopharyngeal tumors
Usually remain asymptomatic for a long period and present late
Clinical presentation of laryngeal cancer
- persistent hoarseness, later on – dysphagia, otalgia, chronic cough, hemoptysis, stridor
Histology of head and neck cancer
pretty much all squamous cell (90-95%)
Preferred method for determining HPV tumor status
p16 IHC
Term for exam ENT usually does to examine laryngeal and hypopharyngeal malignancies
EUA (examination under anesthesia)
Biopsy type for neck mass
FNA
Management if FNA from suspicious neck node is initially negative
Repeat FNA before excisional bx
How is pathologic LAD defined radiographically with head and neck cancer?
Size (node greater than 10 mm in maximal diameter)
Central necrosis
Other features that suggest pathological lymph nodes
- Rounded shape
- loss of normal fatty hilum
- increased or heterogeneous contrast enhancement
- lymph node clustering
To be aware of with lymphadenopathy and head and neck cancer
Microscopic or occult nodale adenopathy is not uncommon
most commonly used agent for PET/CT in
fluorodeoxyglucose (FDG)
Test characteristics + main utility of PET/CT for head and neck cancer + comparison to surgical dissection
- Reliable for detecting occult cervical mets but not as sensitive as neck dissection
- Main utility is in finding occult distant mets + unknown primary lesions + synchronous second primary tumors
Most common sites of mets in head and neck cancer
Lungs followed by the liver and bone
Incidence of second and multiple primaries
Relatively more common in head and neck cancer, particularly in those with strong tobacco and alcohol use or FH
Early stage means
Stage I or II
Efficacy of RT vs. surgery for early stage
- similar rates of local control and survival
Behavior or oral cavity tumors
Aggressive – high rates of locoregional recurrence
Organ-sparing approach is typically used for which type of head and neck cancer
Oropharnyx, hypopharynx, and larynx
Management of persistent nodal involvement
salvage surgery
term for toxicity arising a ways out from treatment for cancer
delayed toxicity
Problem with obtaining PET/CT to early after head and neck treatment
Increases rate of false-positive results
Initial evaluation of locoregionally recurrent head and neck cancer
Restage to look for distant mets
Other clinically defining feature of HPV associated head and neck cancer aside from improved prognosis
Frequent nodal involvement
Difference in management between HPV associated and HPV not associated head and neck cancer
None for now. There are trials underway looking at deintensification of treatment.
Management of locoregional nasopharyngeal cancer in general
- RT is the mainstay
- chemo integral for stage III and IV
- No surgery typically (due to deep location of nasopharynx and close proximity to critical neurovascular structures and base of skull)
Management of oropharyngeal cancers with bony involvement
- surgery (mandibulectomy) over RT (mandibular invasion is difficult to cure with nonsurgical approaches)
Preffered chemo for chemoradiotherapy
Cisplatin
Localized Oropharyngeal cancer management in elderly patient who is not ideal candidate for chemoRT
Definitive RT
Oropharyngeal cancer chemo for patient who isn’t cisplatin eligible
Carboplatin
Typical management of locally advanced oropharyngeal cancer
- organ-preservation approaches using chemoradiation are more commonly used than primary surgery
How synchronous vs. metachronous is typically defined
- Synchronous cancers = occurring within 6 months of the first primary cancer
- metachronous cancers = occurring more than 6 months later (12).
Why carboplatin is not first line
Considered less effective than cisplatin (but little direct evidence)
Higher toxicity of carboplatin vs cisplatin
carboplatin causes more myelosuppression
Immunotherapy for head and neck cancer?
Pembro and nivo both approved for patients who have been treated previously with platinum-based chemo for metastatic or recurrent SCC
Other active chemo agents aside from platinum-based
taxanes
Targeted therapies for head and neck cancer?
Cetuximab
Second line
Immunotherapy with pembro or nivo (if eligible for immunotherapy)
Repeating cytotoxic chemotherapy after initial trial?
Never done because objective response is uncommon
Mechanism of palbociclib
CDK inhibitor
Management of locally recurrent disease
- salvage surgery and/or reirradiation
workup of head and neck cancer/staging
- CT head and neck
- Chest CT
- FDG PET/CT
locoregional head and neck cancer with nodal involvement surgery
Ipsilateral or bilateral neck dissection
Preferred interval between resection and postoperative RT
6 weeks or less
Role for IO in metastatic head and neck cancer?
CPI’s approved for patients who’ve progressed on platinum-based chemo
backbone of most chemo regimens in metastatic head and neck cancer
cisplatin and carboplatin
chemo with activity in metastatic head and neck cancer
- platinums
- taxanes
- 5-Fu
Management of metastatic head and neck with poor PS
Palliative RT or palliative debulking
Preferred radiation sensitizer for concurrent chemoRT of locally advanced disease
1) high dose cisplatin
2) carboplatin/5-Fu
Preferred induction systemic therapy for metastatic with good PS
Docetaxel + cisplatin + 5-Fu
