H&N Unknown primary Flashcards
H&N cancers of an unknown primary represent what % of H&N cancers?
∼3%–5% of all H&N cancers are of an unknown primary.
What is the most commonly presumed general site of origin for H&N cancers of an unknown primary?
The OPX is the presumed site of origin for most cases (less common are the NPX, hypopharynx [HPX], and larynx).
What are the 2 most common originating sites/primary locations if the cancer is presumed to be of oropharyngeal origin?
Tonsils and base of tongue (BOT). Up to 80% of presumed oropharyngeal tumors are thought to originate from these 2 sites.
Appx what % of pts with tonsillar primaries harbor Dz in both tonsils?
∼5%–10% of pts with tonsillar primaries harbor Dz in both tonsils.
A primary can be identified in what % of H&N cancers of unknown primary?
A primary site of origin can be identified in ∼20%–40% of pts.
What is the most common presentation for H&N cancers of an unknown primary?
Painless upper neck LAD (IB–III) is the most common presentation.
What is the T staging if no primary H&N site is found after workup?
T0 (not TX) is the assigned T stage if no primary is found.
On what are the overall stage groupings based if the primary is not known?
LN involvement and p16 status determine stage groupings, with p16(+) denoting more favorable prognostic stage groups than p16(-). (Please see
AJCC staging, 8th edition).
What % of pts with an unknown primary present with bilat LAD (N2c)?
∼10% of pts present with bilat neck Dz.
What does the workup include for pts with an unknown H&N primary (NCCN 2018)?
Unknown H&N primary workup: H&P including skin exam, EUA/panendoscopy + directed Bx with HPV testing, FNA of involved node, CT/MRI, PET/CT (before EUA), thyroglobulin, calcitonin, PAX8, and TTF
staining if adenoCa and/or anaplastic/undifferentiated, consider bilat tonsillectomy (bronchoscopy, esophagoscopy)
If FNA is negative in H&N pts with an unknown primary, what other kind of nodal Bx can be attempted?
If FNA is negative, a core Bx can be attempted next. Avoid incisional/excisional Bx, b/c this would result in “neck violation.”
What does cystic appearance of the involved LNs suggest in pts with H&N cancers?
Cystic appearance on imaging suggests HPV positivity/etiology.
What is the significance of nodal location in terms of likely primary sites?
If upper neck nodes are involved, they are more likely to be d/t a H&N primary (e.g., if level I LNs, OC; if upper level V, NPX primary). If lower neck or SCV nodes are involved, they are more likely to be d/t a chest or abdominal primary (below the clavicle). Bilat nodes suggest midline structures. Intraparotid LN involvement suggests a cutaneous primary.
What is the significance of histology in terms of likely primary sites?
Squamous cell: more likely to be a H&N primary (upper aerodigestive mucosal axis)
Adenocarcinoma: more likely to be a chest or abdominal primary
What sites are traditionally biopsied for level II nodal involvement?
The BOT, NPX, pyriform sinus, and tonsils are typically biopsied with level II LN involvement
Why is it problematic to obtain the PET scan after endoscopy and Bx in pts with an unknown H&N primary?
Post-Bx inflammation may lead to false+ results. This is why some advocate that if used, PET scans should be done initially
When is triple endoscopy indicated in pts with neck Dz and an unknown primary?
Triple endoscopy is generally done in pts with levels IV–V LAD (more likely to be lung/abdominal primary). Also, PET/CT C/A/P should be considered in such cases.
Site-directed Bx will reveal the primary in roughly what % of unknown primary cases?
Site-directed Bx will reveal the H&N primary in ∼50% of cases.
Unilat tonsillectomy will reveal the primary in appx what % of cases?
Unilat tonsillectomy will reveal the primary in ∼20%–25% of cases.
PET/CT will reveal the primary in appx what % of unknown H&N primary cases?
PET/CT will reveal the primary in ∼15%–20% of cases.
What do the data show in regard to bilat tonsillectomy for pts with an unknown H&N primary?
Data from the JHH (McQuone S et al., Laryngoscope 1998) showed improved diagnostic yields with bilat tonsillectomy. Additionally, it may render f/u with PET/CT easier.
When should tonsillectomy be performed in pts being worked up for an unknown primary?
Tonsillectomy is generally performed at the time of direct laryngoscopy.
What are the approximate predictive values of PET for pts with an unknown primary?
The PPV is ∼90% and the NPV is ∼75% for pts with an unknown primary.
What % of pts with an unknown H&N primary have metastatic Dz on PET/CT?
∼10% have metastatic Dz on PET/CT—yet another reason to consider upfront PET.
What is the general Tx paradigm for H&N cancers if a primary is found vs. if there is an unknown primary?
H&N cancer Tx paradigm:
If primary found: treat according to the primary location
If no primary found: Sg +/– RT, RT alone, or chemo/RT +/– neck dissection
Which unknown primary pts can be treated with neck dissection alone?
Generally, N1 (<3 cm) without ECE. B/c of this, some advocate upfront neck dissection at the time of direct laryngoscopy. (Coster JR et al., IJROBP
1992)
For which H&N pts is upfront neck dissection a reasonable approach?
Upfront neck dissection is reasonable if better staging is desired (e.g., if the path is unclear), if the neck has been “violated” (i.e., after incisional Bx), and with a small, unilat, single +node (N1).
What % of pts with N1 Dz fail at the primary site after neck dissection alone?
∼25% of N1 pts ultimately fail at the primary site after neck dissection alone. However, this can vary from 10%–50%.
What is the approximate overall neck failure rate after neck dissection alone?
The overall neck failure rate is ∼15% after neck dissection alone. (Coster JR et al., IJROBP 1992)
What pathologic factor is associated with the highest risk of Tx failure for pts with an unknown primary?
ECE is associated with the highest risk of Tx failure in these pts.
What is the approximate neck failure rate after neck dissection if there is evidence of ECE?
The approximate neck failure rate after neck dissection alone is ∼60% with ECE. (Coster JR et al., IJROBP 1992)
What are the indications for PORT in pts with an unknown H&N primary?
≥N2 Dz, ECE/+margin, or neck violation (e.g., after open/excisional Bx)
What do the standard RT fields include in pts with an unknown H&N primary?
The fields generally include both neck and the mucosal sites at risk (NPX, OPX, HPX, larynx). Some advocate omission of the HPX/larynx from the RT fields, especially if HPV+.
What are the historical 5-yr LC and OS rates after definitive RT for pts with an unknown H&N primary?
University of Florida data (Erkal HS et al., IJROBP 2001): LC 78% and OS 47% Danish data (Grau C et al., Radiother Oncol 2000): OS 37%
What factors have been traditionally associated with inf OS after definitive RT for H&N tumors of an unknown primary?
More advanced N stage, ECE, and lower RT doses have been associated with inf outcomes. (Erkal HS et al., IJROBP 2001)
What standard RT fields have been traditionally used for H&N tumors of an unknown primary?
Opposed lats matched with an ant low neck/SCV field (with post neck electron fields after 40–44 Gy). However, conformal techniques such as IMRT should be now used as standard of care.
What were the anatomical borders of the traditional setup for the 2D lat fields used for H&N tumors of an unknown primary?
Anterior: behind OC/hard palate
Superior: to base of skull to include NPX
Posterior: below tragus to post edge of spinous processes
Inferior: sup edge of thyroid cartilage; if level III or IV, inf edge of cricoid to cover larynx
What definitive RT doses are generally employed?
- CTV1: 66 (2.2. Gy/fx) or 70 Gy (2 Gy/fx) to gross Dz with margin (5–8
mm) - CTV2: 50–66 Gy (2 Gy/fx) to intermediate-risk areas 1 nodal station above
and below in ipsi side and putative primary mucosal sites (NPX, OPX,
HPX) - CTV3: 50–54 Gy to low-risk areas and uninvolved neck
What evidence supports the omission of the larynx/HPX from the standard RT fields?
University of Florida data (Baker CA et al., Am J Clin Oncol 2005): larynx sparing RT is just as effective with less toxicity.
What is the evidence in favor of bilat neck irradiation for H&N tumors of an unknown primary?
Loyola data (Reddy SP et al., IJROBP 1997): contralat nodal failure is higher (44%) in pts receiving unilat nodal RT (vs. 14% for bilat nodal RT). Also, there is a higher primary emergence rate with unilat RT (44% vs. 8%). No difference in 5-yr OS.
What are a few of the advantages of IMRT for H&N tumors of an unknown primary?
Greater parotid sparing, can consider concurrent chemo (Klem ML et al., IJROBP 2008), dose painting to avoid sequential CDs, can use SIB dosing (e.g., 212 × 33 = 69.96 Gy, 180 × 33 = 59.4 Gy, and 170 × 33 = 56.1 Gy).
When is neck dissection entertained after definitive RT for H&N tumors of an unknown primary?
Post-RT neck dissection is considered with persistence of Dz (e.g., on PET or clinically; LN >1 cm and/or PET+). Some still consider it standard for all pts with ≥N2 Dz, although more commonly, elective neck dissection after RT is not performed if there is no clinical evidence of Dz on clinical exam and radiographic restaging.
Within what timeframe after RT should neck dissection be performed if decided upon upfront (i.e., regardless of response to RT)?
Neck dissection should occur ∼3–4 mos (and no later than 6 mos) after RT.
What are common acute side effects from RT to the H&N region?
Pain, mucositis, hoarseness, and malnutrition (weight loss).
What are common long-term complications from RT to the H&N region?
Xerostomia, dysphagia, neck scarring and edema (especially if combined with neck dissection), hypothyroidism, and laryngeal dysfunction (aspiration,
hoarseness, etc.).
After RT, when should PET be performed to assess for nodal response?
PET should be performed no sooner than 3 mos after RT. (NCCN 2018)
