Treatment/Prognosis

Question 1

What does total laryngectomy entail?

Answer 1

It entails the removal of the hyoid, thyroid and cricoid cartilage, epiglottis, and strap muscle with reconstruction of the pharynx as well as a permanent tracheostomy.

Question 2

What structures are removed with a supraglottic laryngectomy?

Answer 2

A supraglottic laryngectomy sacrifices the FVCs, epiglottis, and aryepiglottic folds.

Question 3

What is the preferred surgical option for dysplastic lesions on the glottic larynx?

Answer 3

Mucosal stripping is typically curative for dysplastic lesions. Close follow-up is needed.

Question 4

What are the Tx options for Tis lesions of the glottic larynx?

Answer 4

Cord stripping/laser excision (need close follow-up; cannot r/o microinvasive Dz) or definitive RT

Question 5

What are the ∼5-yr LC rates for glottic CIS with the use of stripping vs. laser vs. RT?

Answer 5

Stripping: 72%

Laser: 83%

RT: 88%–92% (all >95% after salvage)

Question 6

What are the Tx options for T1–T2 glottic cancer?

Answer 6

Cordectomy (CO2 laser)/partial laryngectomy, or definitive RT

Question 7

What are the 5-yr control and survival rates after hemilaryngectomy for T1–T2 glottic cancer?

Answer 7

After hemilaryngectomy, the ∼5-yr LC is 83% and the DFS is 88% for T1–T2 glottic cancer. (Scola B et al., Laryngology 1999)

Question 8

What is the salvage Tx of choice for glottic lesions after RT failure?

Answer 8

The salvage Tx of choice is total laryngectomy +/- neck dissection.

Question 9

What is the ∼5-yr CSS rate for T1 glottic cancers treated with definitive RT?

Answer 9

The 5-yr CSS rate with RT is >90% (95% with salvage; organ preservation rate is >90%).

Question 10

What are the advantages and disadvantages of using RT for early glottic cancer?

Answer 10

Advantages: better voice quality, noninvasive, organ preservation

Disadvantages: long Tx duration, RT changes could obscure post-Tx surveillance

Question 11

What is the voice quality preservation rate for early glottic tumors/pts treated with laser vs. RT?

Answer 11

The JHH data (Epstein BE et al., Radiology 1990) suggest better voice quality after RT (laser: 31%, RT: 74%, p = 0.012). More recent RCT from Finland (Aaltonen L et al., IJROBP 2014) also suggest better voice quality with RT.

Question 12

What are the initial and ultimate (after salvage) LC rates for T2 glottic lesions?

Answer 12

Initial LC is 70%–90% and 50%–70% after salvage for T2 glottic lesions.

Question 13

What are the currently accepted dose fractionation and total dose Rx for CIS and T1 glottic lesions?

Answer 13

The currently accepted RT doses are 60.75 Gy for CIS and 63 Gy for T1, at 2.25 Gy/fx.

Question 14

What is the typical RT dose used for T2 glottic lesions?

Answer 14

The typical RT dose for T2 lesions is 70 Gy at 2 Gy/fx or 65.25 Gy at 2.25 Gy/fx.

Question 15

What randomized data/trial highlighted the importance of hypofractionation for early glottic cancers?

Answer 15

Japanese data (Yamazaki H et al., IJROBP 2006): 180 pts, 2 fractionations: 2 Gy/fx (60–66 Gy) vs. 2.25 Gy/fx (56.25–63 Gy). 5-yr LC rate was better with 2.25 Gy/fx (92% vs. 72%). The greater toxicity for the hypofractionation regimen was acute skin erythema (83% vs. 63%).

Question 16

What RT field sizes/spans are employed for Tis/T1 glottic cancers?

Answer 16

5 × 5 cm opposed lat fields—from the upper thyroid notch to the lower border of the cricoid, post border at the ant edge of the vertebral body, and flash skin at the ant border.

Question 17

What RT planning technique can be used when treating T1 glottic lesions with ant commissure involvement?

Answer 17

Generally, for T1 glottic lesions, wedges are used (heel ant, usually 15 degrees) to reduce ant hotspots due to curvature of the neck. However, if there is ant commissure Dz, the wedges can be removed, or wedge angle reduced, to add hotspots to this region. Bolus/beam spoiler can be added for additional coverage anteriorly.

Question 18

What structures must be encompassed by the 95% IDL when irradiating T1 glottic cancer?

Answer 18

The 95% IDL must encompass the TVCs, FVCs, and the sup subglottis.

Question 19

What RT fields are used for T2 glottic lesions?

Answer 19

This is controversial and may depend on the degree of supraglottic/subglottic extension. Most advocate using 6 × 6 cm opposed lat fields; others advocate covering levels II–III nodes (2 cm above the angle of the mandible, splitting vertebral body, down to the bottom of the cricoid) to 50–54 Gy, with CD to the 5 × 5 cm box covering the larynx to 70 Gy.

Question 20

What are the Tx options for early-stage supraglottic LCX?

Answer 20

Supraglottic laryngectomy, transoral laser resection, or definitive RT

Question 21

What are the 5-yr LC and OS rates for early supraglottic cancers treated with Sg and LND?

Answer 21

The 5-yr LC rate is -85%, whereas the 5-yr OS is -100% for T1 and -80% for T2 supraglottic lesions.

Question 22

What are the LC rates for early-stage supraglottic cancers after definitive RT alone?

Answer 22

Retrospective series demonstrate LC rates of 73%–100% for T1 and 60%–89% for T2 lesions (e.g., University of Florida and Italian data).

Question 23

Describe the standard RT fields used in treating supraglottic cancers.

Answer 23

B/c 20%–50% of T1–T2 supraglottic cancers have +LNs (occult), necks need to be covered for all pts (levels II–IV). This required an off-cord CD after 45 Gy and a boost to the post neck to 50 Gy with electron fields. Most of these are currently treated with IMRT.

Question 24

What definitive RT doses are typically recommended for early-stage supraglottic cancers?

Answer 24

T1 dose: 70 Gy in 2 Gy/fx

T2–3 dose: hyperfractionated dosing to 79.2–81.6 Gy in 1.2 Gy/fx bid or with concomitant boost techniques to 72 Gy (1.8 Gy in AM × 30 fx to 54 Gy to areas of subclinical Dz, and 1.5 Gy in PM for the last 12 days of Tx to boost GTV + 1.5–2 cm to 72 Gy)

Question 25

What early data showed feasibility/effectiveness of reirradiation for previously treated early-stage LCX pts?

Answer 25

Massachusetts General Hospital data (Wang CC et al., IJROBP 1993): 20 pts treated with 1.6 Gy bid to 65 Gy. 5-yr OS was 93%, and LC was 61% after reirradiation.

Question 26

What are the Tx options for pts with advanced LCX?

Answer 26

Total laryngectomy (with adj RT or CRT for +margin, +ECE) or organ preservation with definitive CRT (RTOG 91–11) or RT alone (altered fractionation)

Question 27

What are the Tx options for pts with advanced HPxC?

Answer 27

Induction chemo → RT or Sg depending on response for T1–3N+ Dz; total laryngectomy/laryngoesophagectomy (with CRT for +margin, +ECE) for T4 Dz

Question 28

What are the typical RT doses used to treat advanced LCX/HPxC?

Answer 28

Subclinical Dz (2nd-echelon nodal regions) to 50–54 Gy; high-risk regions (1st-echelon or involved nodal regions) to 60–63 Gy, primary tumor to 70 Gy (in 2 Gy/fx)

Question 29

What are the 3 indications for boosting the stoma with PORT?

Answer 29

Indications for boosting the stoma with PORT: Emergency tracheostomy Subglottic extension Ant ST extension

Question 30

What are some indications for performing an elective neck dissection after definitive RT?

Answer 30

This is controversial, but elective neck dissection should be done for persistent Dz and can be considered with >N2 Dz, although it is now common to observe if clinical and radiographic CR is obtained after RT.

Question 31

What randomized data/study compared preop RT to PORT for (predominantly) HPxC?

Answer 31

RTOG 73–03 (Tupchong L et al., IJROBP 1991): 354 pts, 50 Gy preop vs. 60 Gy postop; 69% of pts had advanced supraglottic or HPxC. LC was better with PORT but not OS.

Question 32

What are the 2 randomized phase III trials that demonstrated a benefit with postop CRT vs. PORT alone for high-risk H&N pts?

Answer 32

EORTC 22931 (Bernier J et al., NEJM 2004): 334 pts randomized to PORT 66 Gy vs. PORT + cisplatin 100 mg/m2 on days 1, 22, and 43. Eligibility: ECE, +margin, PNI, LVI, and levels 4–5 +N from oral cavity cancer/oropharyngeal cancer. There was better OS, DFS, and 5-yr LC with CRT but ↑ grades 3–4 toxicity. RTOG 95–01 (Cooper JS et al., NEJM 2004): 459 pts randomized to 60–66 PORT vs. PORT + cisplatin 100 mg/m2 on days 1, 22, and 43. Eligibility: >2 LNs, ECE, +margin. There was better DFS (43% vs. 54%) and 2-yr LRC (72% vs. 82%) with CRT but only a trend to improvement in OS (57% vs. 63%).

Question 33

What are the presumed reasons why EORTC 22931 showed an OS benefit while RTOG 9501 did not?

Answer 33

The EORTC trial included more margin+ pts (28% vs. 18%), pts with worse tumor differentiation (19% vs. 7%), more HPX cases (20% vs. 10%), and more pts who started RT 6 wks or later after Sg (32%).

Question 34

Which randomized trials demonstrated a benefit with altered fractionation RT in advanced H&N cancer?

Answer 34

EORTC 22851 (Horiot JC et al., Radiother Oncol 1997): 512 pts (all H&N except the HPX) randomized to conventional RT to 70 Gy (7 wks) or 1.6 Gy tid to 72 Gy (5 wks). There was better 5-yr LRC with tid RT (59% vs. 46%) but not OS. RTOG 9003 (Fu KK et al., IJROBP 2000): 1,073 pts (all H&N sites) randomized to (1) standard fx 70 Gy/2 qd; (2) 81.6 Gy/1.2 bid; (3) accelerated with split 67.2 Gy/1.6 bid; and (4) accelerated with concomitant boost 72 Gy/1.8 qd × 17 → 1.8 Gy AM + 1.5 Gy PM × 33 fx. All altered fx schemes were better than conventional RT in terms of LRC (54% vs. 46%) but not OS.

Question 35

Which studies investigated induction CRT for organ preservation in pts with advanced LCX?

Answer 35

Department of Veterans Affairs (VA) larynx study (Wolf GT et al., NEJM 1991): stages III–IV resectable LCX; 332 pts randomized to 3 cycles induction PF f/b definitive RT (if Dz response, else TL) vs. upfront Sg + PORT. 2-yr larynx preservation rate was 64%. There was no OS difference (68%). There were more LRs with CRT and less mets. GETTEC (Richard JM et al., Oral Oncol 1998): early closure due to poor accrual; only 68 pts, mostly T3N0, design similar to the VA study. There was poorer 2-yr survival for the chemo group (69% vs. 84%). 3-yr laryngectomy-free survival was 20%.

Question 36

What is the only randomized study that investigated organ preservation for advanced HPxC with induction CRT?

Answer 36

EORTC 24891 (Lefebvre JL et al., JNCI 1996 and Ann Oncol 2012): 194 pts randomized to Sg + PORT vs. induction chemo (5-FU/cisplatin) + RT; if NR to chemo → Sg + PORT. 5-yr larynx preservation rate was 35%. At 3 yrs, OS was better with induction therapy, but there was no difference at 5 and 10 yrs (DMs were less in the chemo arm; no difference in LRF).

Question 37

Which study established concurrent CRT over both RT alone and induction approaches for larynx preservation?

Answer 37

RTOG 91–11 (Forastiere AA et al., NEJM 2003): 547 pts, T2–T4 (T4 with thyroid cartilage invasion or >1-cm base of tongue invasion excluded) randomized to (1) CRT (platinum 100 mg/m2 q3wks), (2) induction PF chemo → RT (like the VA study), and (3) RT alone (all to 70 Gy). There was a better rate of laryngeal preservation at 3.8 yrs with concurrent CRT (84% vs. 72% vs. 67%); better 2-yr LRC (78% vs. 61% vs. 56%); and better DM rate with any chemo arm than with RT alone. There was no OS benefit. There was ↑ acute grades 3–4 toxicity but no ↑ late toxicity with concurrent CRT.

Question 38

What are the survival/LC numbers based on the latest update of RTOG 91–11?

Answer 38

Long-term Results RTOG 91–11 (Forastiere AA et al., JCO 2013) median follow-up 10.8 yrs. CRT improved larynx preservation over chemo → RT (HR, 0.58; p = 0.005) and over RT alone (p < 0.001), while chemo → RT and RT were equivalent (HR = 1.26; p = 0.35). Late effects were not different. The 10-yr OS was the same (27.5% CRT, 38.8% chemo → RT, and 31.5% RT). Deaths not attributed to larynx cancer or Tx were higher with CRT.

Question 39

What is the only randomized study that compared Sg + RT to concurrent CRT in advanced H&N SCC (Non-NPX)?

Answer 39

Singapore study (Soo KC et al., Br J Cancer 2005): 119 pts, most bulky T4 (56%) or stage IVA (78%) Dz; closed early d/t poor accrual; nonstandard PF chemo, nonstandard RT (66 Gy). 44% pts larynx/HPX (majority supraglottis). No difference in 3-yr DFS, primary larynx/HPX organ preservation 62% vs. nonlaryngeal sites 30%.

Question 40

What study demonstrated an OS and DFS benefit with CRT over RT alone for unresectable H&N cancers?

Answer 40

Cleveland Clinic (Adelstein DJ et al., JCO 2003): 295 pts with unresectable stages III–IV H&N cancers (15% OC, 55% OPX, 20% HPX), RT alone vs. CRT with cisplatin 100 mg q3wks × 3. 3-yr OS (37% vs. 23%) and DFS (51% vs. 33%) were better with CRT.

Question 41

What study demonstrated improvement in OS with the addition of cetuximab (C225) to RT in H&N cancers?

Answer 41

Bonner et al. (NEJM 2006): 424 pts with stages III–IV SCC of the OPX, larynx, or HPX randomized to RT vs. RT + C225; RT options were conventional to 70 Gy, 1.2 bid to 72–76.8 Gy, or concomitant boost to 72 Gy. There was better 3-yr LRC (47% vs. 34%) and OS (55% vs. 45%) with RT + C225. Subset analysis showed improvement mostly in OPC and in the altered fractionation RT arms (∼50% with altered fractionation).

Question 42

What 2 randomized studies demonstrated a benefit with induction taxane/platinum/5-FU (TPF) chemo over PF → in pts with unresectable H&N cancers?

Answer 42

TAX 324 study (induction chemo → CRT) (Posner MR et al., NEJM 2007): 501 pts, unresectable stages III–IV H&N cancers (52% OPX; 13%–18% OC, larynx, HPX) randomized to induction platinum + 5-FU or TPF → CRT with carboplatin. There was better 3-yr OS (62% vs. 48%), MS (71 mos vs. 30 mos), and LRC (70% vs. 62%) in the TPF arm. Pts in the TPF arm had fewer Tx delays than those who rcvd platinum/5-FU despite higher myelotoxicity in the TPF arm (98% rcvd planned Tx in TPF vs. 90% in the platinum/5-FU arm). TAX 323 study (induction chemo → RT) (Vermorken JB et al., NEJM 2007): 358 pts, unresectable stages III–IV H&N cancers (46% OPX, 18% OC, 29% HPX, 7% larynx) randomized to induction platinum + 5-FU or TPF → RT alone. TPF resulted in better median PFS (11 mos vs. 8.2 mos), MS (18.8 mos vs. 14.5 mos), with an HR of 0.73. The rate of toxic deaths was greater in the platinum/5-FU group (5.5% vs. 2.3%). There was also more grades 3–4 thrombocytopenia, anemia, stomatitis, n/v, diarrhea, and hearing loss in the platinum/5-FU arm. Neutropenia, leukopenia, and alopecia were more common in the TPF arm.

Question 43

Which studies compared induction chemo vs. upfront CRT?

Answer 43

1. PARADIGM study (induction TPF → CRT vs. CRT)(Haddad H et al., Lancet Oncology 2013): 145 pts, stages III–IV (25% larynx and HPX), randomized to induction TPF → CRT vs. CRT. At a median f/u of 49 mos, there was no difference in 3-yr OS (73% for induction vs. 78% for CRT), with a higher rate of febrile neutropenia observed in the induction arm. 2. DeCIDE study (induction TPF(×2) → CRT vs. CRT) (Cohen E et al., JCO 2014): 285 pts, N2–N3 Dz, docetaxel-based concurrent CRT regimen (Docetaxel, 5-FU, hydroxyurea “DFHX”). Randomized to induction TPF → CRT vs. CRT. At a min f/u of 30 mos, there was no difference in OS (median not reached), DFS, LRC or DMFS. HPV status did not impact findings, nor did OPX vs. Non-OPX primary. Toxicity higher with induction (heme).