[ROQs] H&N

Question 1

What are the prominent skull foramina, and what are their contents?

Answer 1

Question 2

Which trials define the SOC and what are the expected outcomes, including OS, for NPX cancers?

Answer 2

• Induction CHT [Zhang et al. NEJM 2019]
• Intergroup 0099 [Maghami et al. JCO 2020]
• Chinese study [Chen et al. JNCI 2011]
• MAC-NPC [Blanchard et al Lacnert 202; Petit et al. Lancet 2023]

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Question 3

What are some unfav prognostic factors for NPX cancers?

Answer 3

• High stage
• Male gender
• Age > 40-50
• Histology (WHO I = poor prognosis)
• Plasma High EBV (> 1500/copies/mL) DNA

Question 4

Which WHO histologic grades for NPX cancers are more common in endemic vs. non-endemic areas?

Answer 4

• Non-endemic: WHO Grade I
  – Keratinizing → unrelated to EBV infections
• Endemic: WHO Grade III
  – Undiff non-keratinizing → most linked w/ EBV infections

Question 5

What are the general treatment paradigms for NPX cancers?

Question 6

Which trials define the SOC and what are the expected outcomes, including OS, for OPX cancers?

Answer 6

Oropharynx summary:
- HPV was discovered as a prognostic factor for response to treatment and OS, validated in RTOG 0129
- Studies seek to de-escalate therapy in HPV+ tumors by various means
- RTOG 1016 and De-Escalate found that chemo cannot be replaced by cetuximab
- A surgical technique, TORS, is developed that leads to less morbidity than standard surgery
- HN002 evaluated 60 Gy as definitive treatment as found that the results met criteria for further study.
- However in HN005, 60 Gy was found inferior and the arm was closed
- ECOG 3311 validates TORS and post-op approaches as options in low, int, and high risk HPV
- ORATOR2 compared chemoRT vs surgery in HPV+ and was closed due to deaths in the surgery arm, but some question the surgical quality in the trial
- EORTC ““Best of”” to evaluate TORS vs. chemoRT in HPV+

Question 7

Which trials define the SOC and what are the expected outcomes, including OS, for Larynx cancers?

Answer 7

Larynx summary
- VASLG establishes larynx preservation with chemotherapy and RT as an option, with no change in OS vs surgery
- RTOG 9111 evaluates the use of chemo in larynx preservation. Induction and concurrent both had favorable results, though results long-term were mixed and perhaps in favor of induction
- In the early stage of the glottic larynx, RT is an option.
- The Helskinki randomized trial found that RT seemed to have better voice outcomes than CO2 laser

Question 8

Which trials have explored different dosing regimen for H&N cancers?

Answer 8

H&N dose overview:
- MDACC Peters initially showed 57.6 Gy needed for post-op low risk neck and 63 Gy for ECE
- Concominant boost becomes standard from RTOG 9003 fx study
- 66 Gy used for ECE and +M with concurrent chemo in EORTC and RTOG. Benefit in OS with chemo for ECE and +M
- RTOG 0022 outlines use of IMRT SIB to spare salivary glands, combining MDACC Peters and CCB into an IMRT SIB regimen
- Doses as low as 45-50 Gy may be reasonable for untreated neck in Belgium study

Question 9

Which trials have explored different fx regimen for H&N cancers?

Answer 9

H&N fractionation overview:
- RTOG 9003 results initially show CCB and hyperfx improve LC; since more convenient, accel-CCB was favored. Split course no longer in use
- CCB goes on to become standard and have OS benefit with chemo
- Long term 9003 follow-up shows hyperfx has best OS, LC and the least late effects
- MARCH HN meta-analysis also confirms hyperfx gives best OS
- Overgaard DAHANCA and later IAEA show better LC with 6 fx per week, compared to conventional, if no chemo
- Transition from 2D to IMRT with RTOG 0222, using SIB technique, like a modified CCB, to spare salivary glands
- Whether IMRT SIB hyperfx with concurrent chemo is better than IMRT SIB qday with concurrent chemo is an open question

Question 10

What are the expected outcomes, including OS, for OPX cancers?

Question 11

What are the expected outcomes, including OS, for OC cancers?

Question 12

What are the expected outcomes, including OS, for early-stage laryngeal cancers?

Question 13

What are the expected outcomes, including OS, for cancers of unknown origin?

Question 14

What are the expected outcomes, including OS, for post-op H&N cancers?

Question 15

What are the S&S and management of an allergic reaction to contrast?

Answer 15

Question 16

What is the AJCC 8th ed. clinical and pathologic N staging for most H&N cancers w/ the exception of OPX 16+ and NPX cancers?

Answer 16

Question 17

What is the AJCC 8th ed. clinical and pathologic TNM staging for NPX cancers?

Answer 17

• Extension into the OOP, including soft palate, and NC still coutns as T1
• Contrast w/ NPX: Clivus involvement is T3 for NPX but T4b for NC

Question 18

What is the AJCC 8th ed. clinical and pathologic TNM staging for p16+ OPX cancers?

Answer 18

Note: no grading system for HPV+ cancers!

Question 19

What is the AJCC 8th ed. clinical and pathologic TNM staging for OC cancers?

Answer 19

Question 20

What is the AJCC 8th ed. clinical and pathologic T staging for p16-OPX cancers?

Answer 20

Question 21

What is the AJCC 8th ed. clinical and pathologic T staging for Larynx cancers?

Answer 21

MNEMONIC: A VISA

Question 22

What is the AJCC 8th ed. anatomic stage grouping for larynx cancers, as typified by the grouping for glottic cancers?

Answer 22

Question 23

What is the AJCC 8th ed. TNM staging and stage grouping for major salivary gland cancers?

Answer 23

Question 24

What is the AJCC 8th ed. TNM staging and stage grouping for nasal cavity and ethmoid sinus cancers?

Answer 24

Contrast w/ NPX: Clivus involvement is T3 for NPX but T4b for NC

Question 25

What is the AJCC 8th ed. TNM staging and stage grouping for maxillary sinus tumors?

Answer 25

Question 26

What is the visual representation of the T staging for maxillary sinus tumors?

Answer 26

Question 27

What are the similarities between AJCC 8th ed nodal staging for OPX and NPX cancers?

Answer 27

Question 28

What is a good ROT for the AJCC 8th ed stage grouping for NPX and OPX cancers?

Answer 28

Question 29

What is the AJCC 8th ed TNM staging and stage grouping for H&N tumors of the cervical LNs and unknown primaries?

Answer 29

- T0 (NOT Tx) - N staging similar to other cancers

Question 30

What is the T staging for cutaneous H&N SCC?

Answer 30

Question 31

What is the Kadish staging system for NC esthesioblastoma?

Answer 31

Question 32

What are the anatomic subsites of the supraglottis?

Answer 32

- FAVEA → False cords, AEs, Ventricles, Epiglottis, AE folds - Note that pyriform sinus, post-cricoid area, and posterior pharyngeal wall (3 P's) are part of the hypopharynx

Question 33

What were the findings for RTOG 1016 and De-ESCALaTE trials for OPX cancers?

Answer 33

- RTOF 1016 TL;DR version - 10**16** → p**16** OPX only - concurrent cetux vs. cis (both w/ RT, 70 Gy given 6 fx/week) -- 5yr OS: 78% vs. 85% -- 5-yr LRF: 17% vs. 10% -- 5-yr PFS: 67% vs. 79%

Question 34

Is there any data supporting hypofx RT w/o CHT in early-stage H&N cancers?

Answer 34

- Yes, but only for early-stage OPX - RTOG 00-22, phase I/II trial: Mem Hook, 00-22 → (2.2 Gy/fx) -- OPX only, T1-2, N0-1, M0 - → 66 Gy in 30 fx w/o CHT [subclin disease treated to 54-60 Gy in 1.8-2 Gy/fx] - 2-yr LRF: 9% - 2-yr DFS: 82% - 2-yr OS: 95.5% - Interpret w/ caution, since omitting CHT for these cancers (HN-002] led to inferior outcomes, though this trial did not include T1-2, N0 patients, so omitting CHT could still be considered for this subset

Question 35

What were the findings of the MAC-NPC meta-analysis [Blanchart et al. Lancet Oncol 2015] w/ regards to NPX cancers?

Answer 35

MAC-NPC meta-analysis [Blanchard et al. Lancet Oncol 2015]: - Adding CHT to RT improves overall survival (5-yrs: ↑5%. 10-yrs: ↑8%) - The timing of CHT administration affected outcomes. -- Superior OS w/ CCRT f/b aj. CHT and CCRT alone, compared to find. CHT vs. adj CHT alone

Question 36

Are there any positive trials investigating the role of induction CHT f/b CCRT vs. CCRT alone in locally advanced H&N cancers?

Answer 36

Yes, only one a few have been +ve so far, and the -ve trials should give us pause for the actual utility of induction CHT - ** TAX 324:** See attached image; Note that it compared two diff find. regimens, but not find vs. no mind. Also used carboplatin for concurrent CHGT. - **GSTTC Italian Study Group [Ghi et al, Ann Oncol, 2017]:** - locally advanced, Stage III-IV AJCC V, nonmetastatic SC -- unresectable or low suitability for surgery → 2x2 randomization - →🏆 induction TPF vs. no induction - →conc cis/5FU vs. conc cetuximab - Induction chemo improved OS, PFS, LRC, and CR -- Median OS induction 55 vs. 32 mos -- PFS 31 mos vs. 19 mos -- 3-yr OS 58% vs. 47% -- CR 43% vs. 28% -- DM ~15%, not different - On subanalysis, better effect with conc cetuximab and non-OPX site, but underpowered - More febrile neutropenia with induction - ChemoRT breaks not different - Induction chemo improves OS, PFS, LRC, and CR and maintains compliance with chemoRT. In the subanalysis, the best effect was found with concurrent cetuximab. - Given the history of other negative induction trials, results should be interpreted cautiously.

Question 37

What are the findings of the TAX 324 trial for locally advanced H&N SCCs?

Answer 37

Question 38

Are there any negative trials investigating the role of induction CHT f/b CCRT vs. CCRT alone in locally advanced H&N cancers?

Answer 38

**All others, besides the Italian study, have been negative:** - **Madrid trial [Hitt et all Ann Oncol 2014]:** - unresectable, Stage III-IV AJCC V, nonmetastatic SCC - →Induction TPF, RT + conc cis vs. induction PF, RT + conc cis vs.🏆 RT + conc cis - For both: Median PFS ~14 mos, TTF 8 mos, OS 27 mos - More neutropenia, odynophagia, stomatitis with induction chemo - Conc: No benefit to induction chemotherapy. Toxicity is increased. - **DeCIDE trial [Cohen et al, JCO, 2014]:** - N2 or N3 SCC of H&N - →Induction TPF, RT + conc THF vs. 🏆 RT + conc THF -- H=hydroxyurea. RT to 74-75 Gy hyperfx - No benefit in 30-mos OS, RFS, or DMFS. Mortality ~30% in both arms - Serious adverse events more common in induction arm 47% vs. 28% - Conc: No benefit but increased tox - **PARADIGM trial [Haddad et al, Lancet, 2013]:** - unresectable, low surgical curability T3/T4, N2/3 (but not T1N2), or organ preservation - →Induction TPF, RT + conc carbo or docetaxel vs. 🏆 RT + conc cis - For both arms: 3-yr OS ~75% and 3-yr PFS ~68% - Serious AEs in 52 vs. 22 pts - Grade 3-4 mucositis 47% vs. 16% - More febrile neutropenia with induction - RT breaks similar, 6 vs. 5 pts - Terminated due to slow accrual - Conc: No benefit but increased tox Mnemonic: It's hard to **DeCIDE** on the **PARADIGM** of induction CHT when it keeps taking all these **Hitts.** But if you want to use it, you must pay the **ITALIAN* **TAX324**

Question 39

Are there any trials supporting the use of chemoradiotherapy vs. radiotherapy alone for NPX Cancers?

Answer 39

- Intergroup 0099 [al-sarraf et al]: RT alove vs. CCRT + adj. CHT -- Stage III-IV (would include some current T2)→ 70 Gy vs. 🏆 70 Gy + concurrent cisplatin x3 & adj cisplatin 5FU x3 -- 3-yr OS 78% vs. 47%. 3-yr PFS 69% vs. 24% -- 5-yr OS 67% vs. 37%. 5-yr PFS 58% vs 29% -- Conc: Concurrent and adjuvant chemo added to RT results in OS benefit in nasopharynx. -- Criticism: Trial term early 2/2 poor accrual. Poor compliance w/ CHT (conc 63%, and adj. 55%). It may not apply to endemic regions. - Chen et al. J Nat Cancer Inst 2011: AJCC stage II/III NPX → RT alone (68-70 Gy to the primary, 60-62 Gy LN+ neck, and 50 Gy to the elective neck) vs. CCRT w/ weekly cisplatin (30 mg/m2). -- 5-yr OS: 85.8% vs. 94.5% (SS) -- 5-yr PFS: 77.8% vs. 87.9% (SS) -- 5-yr DMFS: 83.9% vs. 94.8% (SS) -- 5-yr LRC: 91.1% vs. 93.0% (SS) -- On MVA, # of CHT cycles was the only independent predictor of OS

Question 40

What are some common criticisms of the INT0099 trial for NPX cancers, and have any subsequent trials addressed them?

Answer 40

Question 41

Which patients are considered good candidates for larynx preservation?

Answer 41

- < T4 - ≥ T4 → primarily surgical disease (60% required laryngectomy per the VA trial! -- Should be treated w/ laryngectomy f/b risk stratified adj treatment (CHT and/or RT) - RTOG 9111 excluded Large vol T4 (thyroid cartilage inv. or >1 cm into BOT)

Question 42

What trials support organ presevation for laryngeal cancers?

Answer 42

- VA Larynx trial [Wolf et al, NEJM 1991]: older model, ind CHT f/b RT, if CR or PR - Stage III-IV (not T1N1) -- → induction PF x**3**C → 70 Gy if CR or PR. If no response: surgery+post-op RT -- vs. total laryngectomy + post-op RT (50-70 Gy) (SOC at the time) -- PF: Cisplatin 100 mg/m² + 5-FU 1000 mg/m² - Results: No difference in 2-yr OS. CRT had worse LF but improved DM. - ~2-yr OS: ~68% - ~RF: 8% vs. 5% (NS) - ↑LF: 12% vs. 2% (SS) - ↓DM: 11% vs. 17% (SS) - 2-yr larynx preservation: ~64% -- Needing salvage laryngectomy, 1 cm BOT involvment. Limited T4 was allowed - → 🏆 RT with concurrent cis 100mg/m2 x3 qw3 vs. induction cis/5FU → RT (VA regimen) vs. RT alone 70 Gy - Results: -- 10-yr larynx sparing 82% vs. 68% vs. 64% -- 10-yr LC 69% vs. 54% vs. 50% -- 10-yr DM 16% vs. 16% vs. 24% -- Trend to better OS with induction vs. concurrent): 10-yr OS 28% vs. 39% vs. 32% (NS) -- Deaths not attributed to larynx cancer worse with concurrent: 31% vs. 21% vs. 17% -- ~3% with inability to swallow - Conc: CCRT improves LC and Larynx preservation, but there might be a trend towards ↑OS w/ induction

Question 43

What is the evidence for altered fractionation as the SOC for T1 and T2 laryngeal cancers?

Answer 43

- T1N0 Glottic [Yamazaki et al. IJROBP 2006] - → 2 Gy (60 - 66 Gy) vs. 2.25 Gy fx (56.25 - 63 Gy) -- Minimal tumors (≤2/3 vocal cord) 60Gy vs. 56.25Gy -- Larger tumors 66Gy vs. 63Gy - 5-yr LC 77% vs. 92% for 2.25 Gy/fx - No difference in 5-yr CSS (~100%) or toxicity

Question 44

Are there any trials supporting the use of neoadj. CHT f/b CCRT vs. CCRT alone for NPX Cancers?

Answer 44

- Sun et al. Lancet Oncol 2016, phase III trial of locally advanced stage III-IVB MPX - → Induction CHT f/b CCRT (70 Gy, bolus 100 mg/m2 cisplatin q3 weeks) vs. CCRT alone - Induction regimen: IV docetaxel (60 mg/m2 on day 1), IV cisplatin (60 mg/m on day 1), and CVI 5-FU (600 mg/m2 per day, days 1-5) q3weeks. - The primary EP: FFS - Results: Neoadj. arm vs. CCRT alone - 3-yr FFS: 80% vs. 72% (SS) - 3-yr OS: 92% vs. 86% (SS) - 3-yr DFFS: 90% vs. 83% (SS) - 3-yr locoregional FFS: 92% vs. 89% (NS) - Conc: Ind. CHT improves FFS, OS, and Distant FFS, but NOT LR FFS - Induction CHT [Zhang et al. NEJM 2019, JCO 2022] - Stage III-IVB (not T3 or T4N0), nonkeratinizing! - → 🏆 gem/cis induction f/b CCRT vs. CCRT alone -- RT to 66-70 Gy/ 30-33 fx with concurrent cisplatin - 5-yr OS 88% vs. 79% - 5-yr FFS 81% vs. 67% - 5-yr DMFS 90% vs. 78% - 5-yr LRFS 88% vs 83% (NS) - Pretreatment cf EBV >4k/mL: 5-yr OS 86% vs. 71% [No OS benefit if ≤4000: ~91%] - Response to neoajd CHT prognostic of OS: -- 5-yr OS for CR vs. PR vs. stable/progression: 100% vs. 89% vs. 62% - Acute grade 3-4 toxicity 76% vs. 56% - Late grade 3-4 toxicity 11% both arm - Conc: Ind. CHT improves FFS, DMFS, and OS, but NOT LRFS, w/ similar late G3 tox - Response after CHT prognostic of OS; Pre-treatment EBV DNA may be a biomarker of who benefits most from neoadj. CHT

Question 45

Are there any trials comparing neoadj. vs. adj. vs. CCRT alone for NPX cancers?

Answer 45

Question 46

How is brachial plexus contoured for H&N cancers?

Answer 46

- Includes 5 nerve roots! - Lies b/w anterior and middle scalenes - Lateral most of the contour ends at the lateral edge of the scalene muscles superiorly, but extends more laterally as the NV bundle goes into the armpit

Question 47

Are H&N cancers more common in men vs. women?

Answer 47

- Total # of cases: 55,000 - Men: 75% - Women: 25%

Question 48

For NPX cancers, which substructures are always covered for NPX SCCs?

Answer 48

Include the following for NPX cancers, per HN001 - Entire nasopharynx - Anterior 1/3 of clivus (entire clivus if clivus is involved) - Bilateral ovale and rotundum - Bilateral pteryoid fossa and parapharyngeal space - Posterior 1/4 (or 0.5 cm) of the nasal cavity and maxillary sinus (to cover pterygopalatine fossa (to ensure V2 coverage) - Inferior 1/2 of the sphenoid sinus in T1-T2 patients but entire sphenoid sinus in T3-T4 disease - Ipsilateral or bilateral cavernous sinus for T3/T4

Question 49

What is the evidence for treatment de-escalation for int-risk HPV+ OPX cancers s/p TORS and b/l neck dissection?

Answer 49

- ECOG-ACRIN 3311, phase II trial [Ferris et al, JCO 2022]: Investigates optimat adj therapy for OPX p16+ - Resectable oropharynx cancer stage III-IVA AJCC 7, p16+, who undergo TORS and b/l neck dissection -- Low risk (-margins, 0-1 +LN, -ECE): → observation -- Intermediate risk (margin <3 mm, 2-4 +LNs, ENE ≤1 mm) → 50 Gy vs. 60 Gy -- High risk (+margins, ≥5 +LNs, or >1 mm ENE) → 66 Gy RT weekly cisplatin (SOC) - Resutls: -- Low risk (obs): 2-yr PFS 97% -- Int risk (50 Gy vs. 60 Gy): 2-yr PFS 95% vs 96%. 4.5-yr PFS 95% vs. 90% -- High risk (chemoRT): 2-yr PFS 91%. 4.5-yr PFS 86% -- no signficant differences between groups in exploratory comparisons -- Grade 5 toxicity in n=1 - Decline in QOL and FACT-HN for all arms with recovery to baseline in low-int risk groups, however not for high-risk (P=0.005) - Conc: TORS and adjuvant 50 Gy RT for int risk warrants comparison to definitive chemoRT in a phase III trial

Question 50

How can HPV+ OPX cancers be risk stratified into low, int, and high risks?

Answer 50

- Per RTOG 0129, RPA risk groups [py → pack years of smoking] - Low:p16+ with <10 py any, or p16+ with >10 py and N0-2a - Int: p16+ and >10py and N2b-3 -- or p16- and <10py and T2-3 - High: p16- with >10py, or p16- with <10 py and T4

Question 51

What were the results of RTOG 0129 exploring altered fractionation for H&N cancers?

Answer 51

- Stage III-IV SCC or oral cavity, oropharynx, hypopharyx, or larynx - Standard RT 70 Gy with cisplatin (SFX) vs. accelerated fractionation with concominant boost (AFX-CB) 72 Gy in 6 weeks concurrent cis (AFX) - Overall results SFX vs. AFX: 8-yr OS 48%, PFS 42%, DM 15%, LRF, or toxicity (NS; no difference b/w AFX vs. SFX) - Results stratified by HPV+ vs. HPV-: -- 3-yr OS by risk grouping → Low risk: 93%. Int risk: 71%. High risk: 46% -- 3-yr OS HPV+/HPV-: 82% vs. 57% → 8-yr OS HPV+/HPV-: 71% vs. 31% -- 3-yr DM HPV+/HPV-: 9% vs. 15% → 8-yr DM HPV+/HPV-: 10% vs. 16% -- 3-yr LRC HPV+/HPV-: 86% vs. 65% → 8-yr LRC HPV+/HPV-: 80% vs. 48% -- "Good risk" HPV+ (T1-2N1-2b or T3N0-N2b, and ≤10 py): 8-yr LRF 86%, OS 81%, DM 8.3% - Conc: -- Overall: There is no difference in LRF, PFS, OS, DM, and toxicity in AFX-CB vs. standard RT -- HPV+: HPV+ tumors have a very different prognosis and can do well w/o surgery -- Significant trial for its prognostic algorithms!

Question 52

What are the steps in managing laryngeal edema in patients undergoing RT for H&N cancers?

Answer 52

- Mild to moderate → Pred and obs - Severe or if the first one fails → emergent trach

Question 53

How do you manage patients w/ bulky lymphadenopathy who have sig. shrinkage of disease during RT/CCRT?

Answer 53

Re-simulate!

Question 54

What are the outcomes for OPX pts who undergo TORS but decline adjuvant RT? Can they be successfully salvages?

Answer 54

Despite skipping adjuvant RT, 75% of patients were successfully salvaged!

Question 55

What are the findings of the HYPNO trial for locally advanced H&N SCCs?

Answer 55

Cisplatin was optional on both arms This may apply to low income countries, but not the USA population!

Question 56

Is there any benefit to the use of induction CHT for the treatment of locally advanced H&N SCC?

Answer 56

Most studies have not found any benefit!

Question 57

What are the findings of the MACH-NC meta-analysis [Lacas et al. Radiother Oncol 2017] regarding the use of concurrent CHT for locally advanced H&N cancers?

Answer 57

≥ 70 YO and PS ≥ 1 may not derive much benefit from the use of concurrent CHT Benefit vs. risk assessment in this patient population

Question 58

What were the findings of the second publication of the MACH-NC meta-analysis [Lacas et al. Radiother Oncol 2021]?

Answer 58

THe update shows that benefits of CCRT persist over time.

Question 59

Are there any studies showing the benefit of the addition of CHT to RT in >70 YO, in contrast to RT alone for LA H&N cancers?

Answer 59

- Ward et al, Cancer 2016, an NCDB study; interpret w/ caution - Showed deleterious impact of omission of CHT on OS

Question 60

Is there any data on what kind of radiation dose should be used for non-metastatic H&N SCC patients deemed unfit for curative treatment?

Answer 60

- OpRAH Trial, phase III (Optimum RAdiation dose for H&n SCC) [Mallick et al., Radiothera Onc. 2024] - LA H&N SCC not fit for curative intent treatments → 20/5 vs. 30/5 - PFS: 7.4 mos and OS 10.03 mos; Similar tox b/w both - No benefit to dose-escalation in palliation of incurable H&N SCC - "No significant benefit in OS or PFS was observed in patients who received neoadjuvant chemotherapy (NACT), underwent definitive conversion, or received palliative chemotherapy at progression."

Question 61

Is there any evidence for the role of elective vs. therapeutic neck dissection (ND) for oral cavity cancers?

Answer 61

- Cruz et. al NEJM 2015: Elective ND (upfront) vs. Therapeutic ND (at relapse) for oral cavity cancers only! - TL; Dr -- 3-yr OS: 80% vs. 67% -- Rate of nodal positivity in the elective group: 30% --- Most closely re: to DOI: 3 mm vs. 4 mm → 6% vs. 17% -- In the therapeutic group, 114 pts relapsed and 53% died, highlighting that salvage is digg

Question 62

Is there any data to guide the Quad shot palliative RT in the management of non-metastatic but unfit or metastatic H&N cancers?

Answer 62

- QUAD shot: -- Grewal et al, IJROBP 2019 -- Louisville Carrascosa et al, J Palliat Med -- Fan et al, Oral Oncol 2020 - Various regimens: 3.5-3.7 Gy/fx x 4 fx given BID -- Can be repeated q 3-4 weeks for upto 3-4 times for more durable LC -- Subj Palliation rates: 56-95% -- May also improve PFS, OS. -- KPS > 70, and proton therapy a/w survival improvements - Advantages: Low tox, BED low enough to avoid mucositis, rapid tx course

Question 63

What cells of the thyroid give rise to different types of thyroid cancers?

Answer 63

- Parafollicular neuroendocrine cells → Medullary Thyroid Carcinoma (4% of all thyroid cancers -- Primary tx → surgery. lack TSH receptors, and nor responsive to RAI or CHT. TKIs may be used in the metastatic setting. - Hurthle cells → Hurthle cell carcinomas - Follicular epithelial cells → all other carcinomas

Question 64

What is the most common histology of oral cavity cancers?

Answer 64

- SCC (90%)

Question 65

What were the findings of EORTC 24891 [Lefebvre et al, Ann Onc 2010]?

Answer 65

- Phase III trial, Noninferiority - SCC of pyriform sinus or AE fold → surgery + post-op RT vs. 🏆 induction cis/5FU → RT if CR, surgery if PR -- Similar to VA trial Larynx trial - Results: LF trend to higher with RT. Trend to less DM with chemo - 3/5-yr larynx preservation 42% / 35% (10-yr chemoRT survival with functional larynx 8.7%) - 5/10-yr OS: ~33% / 13.5% (NS) - 10-yr PFS 8.5% vs. 11% (trend) - 10-yr DM 36% vs. 28% (trend) - More than 1/2 survivors at 10 yrs retain their larynx - Long term outcomes are poor regardless

Question 66

What is Lhermitte sign, when does it occur, and what this the management?

Answer 66

Dex does not help!

Question 67

Is there any evidence for using more aggressive, curative-like treatment for oligometastatic H&N cancers?

Answer 67

- Yes!: [Leeman et al. JAMA Oncol 2017 - # of mets sig correlated w/ OS -- 1 → 25.7 mos -- ↑2 yr OS for those who received def. tx vs. not: 55.7% vs. 20% (SS) -- Caveat: those who received def. tx had better KPS to begin w/, so did def. therapy do anything? Debatable. -- 2 → 11.3 mos -- ≥ 5 → 7.5 mos

Question 68

What is the sensory innervation of the auricle, and which nerve is innerveated by a branch of the vagus nerve, and thus causes the gag reflex when you are cleaning your ears?

Answer 68

Question 69

What were the findings of the HN002 trial for H&N cancers [Yom et al 2021]?

Answer 69

- Phase II trial designed to select the appropriate de-escalation arm for the HN002 - p16+ OPX cancers → cCRT (60 Gy + Cisplatin q weekly) vs. RT (60 Gy alone) - To be considered for HN005, each arm had to have a 2-yr PFS > 85% (historical control) - 2-yr PFS: 90% (SS compared to hist control) vs. 88% (NS w/ respect to historical control) - LRF: 3.3% vs. 9.5% (SS) - 2-yr OS: ~97% - Gr 3-4 Tox: 80% vs. 53%

Question 70

What are traditional boundaries of a T2 glottic cancer radiation treatment field?

Answer 70

Question 71

What are the boundaries of NPX?

Answer 71

* Anterior: Posterior nasal choanae * Posterior: Pharyngeal mucosa, clivus, C1 * Superior: Sphenoid sinus and pharyngeal mucosa * Inferior: Superior surface soft palate * Lateral: torus tubarius, pharyngeal walls

Question 72

What is the rate of involvement of different cervical LN levels for an OPX cancer?

Answer 72

Question 73

What are the management options for oral candidiasis?

Answer 73

Question 74

What dosing is recommended when treating a H&N cancer of the cervical LN w an unknown primary?

Answer 74

Question 75

What is involved in the initial WU for H&N cancers w/ an unknown primary

Answer 75

Question 76

What is involved in the workup for a carcinoma of an unknown primary?

Answer 76

WU is directed at identifying the primary!

Question 77

Is there any benefit to using cetuximab instead of cisplatin for locally advanced H&N cancers?

Answer 77

- Not really; cetuximab is likely inferior, but it is an essential point from ROQ discussions: - Alternative fractionation appears to provide no benefit in the setting of concurrent cisplatin, while it does appear to provide a benefit in concurrent cetuximab.

Question 78

When using concurrent cetuximab for locally advanced H&N SCCs, how is it given?›

Answer 78

Cetuximab dosing for H&N cancers; [monoclonal antibody against EGFR] - Loading dose 400mg/m2 1 week befor the start of RT - 250mg/m2 weekly throughout RT.

Question 79

For patients receiving cetuximab for H&N cancers, what odd clinical finding may suggest better treatment outcomes?

Answer 79

- Acneiform rash! (median OS 25 → 69 mos [Bonner et al, NEJM 2006]

Question 80

What are the findings of the Bonner trial for H&N cancers?

Answer 80

- Most relevent to HPV+ OPX only - Biggest OS benefit in cetux + concomitant boost RT regimen

Question 81

How are teeth numbered?

Question 82

Which medication may be used for the management of xerostomia in pt's receiving tx for H&N cancers?

Answer 82

- Pilocarpine, 5 - Can cause excessive sweating, leading to patient discontinuation! - Rate of excessive sweating related to dose -- Placebo → 8% -- 5 mg → 37% -- 10 mg → 80%!

Question 83

What are the treatment options for recurrent NPX cancers?

Answer 83

If tumor recurs within the high dose 65-70 Gy IDL, it's likely radioresistant and unlikely to benefit from re-RT.

Question 84

Are there any trials investigating the role of altered fractionation in locally advanced head and neck cancers?

Answer 84

- Yes, a few actually - RTOG 9003: Stage III-IV (or II for BOT/hypopharynx), previously untreated, to have primary RT - → Conventional 70/35 fx in 2Gy vs. -- 🏆 Hyperfx 81.6/68 fx in 7 wks in 1.2Gy BID vs. -- Accel Split: 67.2/42 fx in 6 wks at 1.6Gy BID with 2-wk break at 38.4Gy vs. -- Accel-con boost: 72Gy/42 fx in 6 wks at 1.8Gy and 1.5Gy - IMRT not allowed! - Results: -- Initial: Hyperfrac and delayed concominant boost had better LRC (54%), with trend for better DFS. OS not different. -- Update: Hyperfx increased OS, LC when 5 year patients are censored, and decreased late effects. 97% of LR occurred within 5 years. After five years, more second cancers arose though small amounts. Severe late grade 3+ toxicity trended worse for Accel. - Caveats: Before IMRT era, no conc CHT

Question 85

What were the results of the DAHANCA 6&7 trials ["Overgaard et al, Lancet, 2003. Lyhne et al, Radiother Oncol, 2015]?

Answer 85

- glottic, supraglottic pharynx, oral cavity not receiving chemo, treated with primary RT - →5 fx per week vs. 🏆 6 fx per week -- 66-68 Gy/ 33-34 fx, no chemo -- Nimorazole for all except for glottic - Results: 6fx vs. 5 fx -- 5-yr LRC 70% vs. 60% --14.5-yr LRF 22% vs. 29% -- Larynx preservation 80% vs. 68% -- 5-yr DSS 73% vs. 66% -- No change in OS -- Acute morbidity more frequent with 6 fx but was transient - Conc: For those not receiving chemo, six fractions per week of RT with nimorazole results in better LC and DFS than 5 fractions per week

Question 86

What is the role of nimorazole in the treatment of H&N cancers?

Answer 86

It is a hypoxic radiosensistizer

Question 87

What is the ideal time from surgery to start of CHT/RT in oral cavity SCC?

Answer 87

- Per the retrospective Standord Study [Daly et al. IJROBP 2011], < 6 weeks - ↑LC <6 weeks vs. > 6 weeks: -- 60 mo LC: 80% vs. 40% (SS) - SImilar effect w/ total treatment package time < 12 weeks vs. > 12 weeks (SS) - Altered fractionation can be considered if a pt is delayed beyond 6 weeks

Question 88

What are the findings of RTOG 0522 trial [Ang et al. JCO 2014]?

Answer 88

Question 89

What is the utility of EBV antibodies in the paradigm of NPX Ca management?

Answer 89

Question 90

Is there any trial supporting or disputing the use of adj. CCRT in the management of previously irradiated H&N cancers?

Answer 90

Janot et al. JCO 2008: While DFS is worse in the observation arm, ↑Tox w/ CCRT counters this benefit, and there is no ↑ in OS anyway.

Question 91

Are there any studies guiding the use of adj. RT ± CHT for resected high-risk cutaneous SCC?

Answer 91

- TROG 05:01; TL:DR - SCC -- High risk primary: T3-T4 (excluding nose, EAC, lip); intransit mets -- High risk nodal: ECE, intraparotid node, >2 cervical nodes or size >3 cm - Conc: No benefit with adjuvant carboplatin in high-risk post-op cutaneous SCC. There is excellent FFLRR in both arms. - Comm: -- Carboplatin used, not cisplatin. ~ 50% had ECE, and 5-10% had a positive margin. PNI was not an inclusion criterion. 77% were high-risk nodal, 19% were high-risk primary, and 4% were both.

Question 92

What is the risk of LN involvement in tumors of the paranasal sinuses?

Answer 92

- Low (5-10%) but risk ↑ w/ invasion into adjacent structures

Question 93

Is there any data supporting the use of CCRT vs. RT alone for unresectable H&N SCCs?

Answer 93

- [Adelstein et al. JCO 2003] TL:DR - Result: CCRT is superior to SC-CRT and RT alone for unresectable H&N SCCs -- 3-yr DSS: 51% vs. 41% vs. 33% (SS b/w 1 and 3) -- 3-yr OS: 37% vs. 27% vs. 23% (SS b/w 1 and 3) -- CR: 40% vs. 49% vs. 27% (SS b/w 2 and 3 only)

Question 94

How do patterns of failures, OS, distant recurrence rates, and recurrence sites differ b/w HPV+ vs. HPV- OPX cancers?

Answer 94

- RTOG 0129: HPV+ vs. HPV- -- LRR: 14% vs. 35% (SS) -- DR: 9% vs. 15% (SS) - Trasmane et al. 2015 JAMA OHNS: HPV+ vs. HPV- -- 3-yr distant control: 88% vs. 78% -- Time to dev. of distant recurrent: 16 most vs. 7.2 mos -- HPV+ have a higher # of distant metastatic sites -- OS following DR: 25 ms vs. 11 mos - Relatively speaking, as a % of total failures for each, HPV+ are more likely to fail distantly (38%) compared to HPV- (30%), but the absolute risk of LR of distant failures for HPV+ is lower than HPV-!

Question 95

What factors influence the rate of false positives when evaluating post-def CCRT response for OPX SCC?

Answer 95

- Sivarajah et al, H&N Surg 2018: ↑ false +ve rates: -- primary CRT vs. RT alone -- HPV+ tumors -- non-smokers - SUV max > 5 → prompt close clinical eval - MEM HOOK: Those who tend to do better have increased false +ve rates

Question 96

Is there data supporting the use of ENI is cancers of the maxillary sinus?

Answer 96

- ENI a/w ↓LN recurrence, distant mets, and recurrence-free survival - Usuallty cover ipsilateral IB-V

Question 97

Is there any data for treating Stage I and IIE nasal type NK/T-cell Lymphoma (lethal midline granuloma)?

Answer 97

- NB: another study shows seq RT f/b SMILE CHT may be beneficial -- SMILE: methotrexate, dexamethasone, ifosfamide, etoposide, and Pegasparaginase

Question 98

What were the results of the Phase II avoid trial for treatment de-intensification for HPV+ OPX cancers?

Answer 98

NB: the "unirradiated" primary site still received 30 Gy or so, this can make salvage treatment difficult!

Question 99

Is there any connection between the trigeminal nerve and the facial nerve?

Answer 99

- Yes! -- PPF and the vidian nerve (V2 → VII) - Lingual nerve via chroda tympani (V3 → VII) - Auriculotemporal nerve w/i parotid (V3 → VII)

Question 100

What LN levels drain the paranasal sinuses?

Answer 100

Question 101

Is there any data for using adjuvant CHT for NPX cancers w/ high post-tx EBV titers?

Answer 101

- No, it has not shown to be of any benefit - Gemcis was tested in the ATC Chan et al. study, JCO 2018

Question 102

What are the outcomes a/w cancers of the nasal vestibule?

Answer 102

Question 103

What are the expected outcomes for anaplastic thyroid cancers treated w/ trimodality therapy?

Answer 103

LRC outcomes can be acceptable but DM are a sig source of failure and compromise OS

Question 104

Is there any data to support ENI dose reduction for H&N cancers, such as using doses lower than 50-54 Gy?

Answer 104

Question 105

What are the guidelines for constructing radiation treatment volumes post-induction CHT for LA H&N SCC besides NPX?

Answer 105

NB: There is data for using post-induction RT volumes for NPX cancers [Tang et al., CA Cancer J Clin, 2025]

Question 106

Is there any data guiding treatment for Sinonasal Undifferentiated Carcinomas (SNUC)?

Answer 106

TL:DR: Induction CHT f/b CCRT for CR or PR has great outcomes

Question 107

What were GORTEC 94-01 findings investigating CCRT for OPX cancers?

Answer 107

Question 108

Are there any studies showing the effect of treatment time on outcomes for H&N cancers?

Answer 108

Yes, the DAHANCA studies