HN Cancer - Bogotá, 07.11.2019

1. Preservación de laringe – visión del oncólogo clínico
Mauricio Lema Medina MD
Clínica de Oncología Astorga / Clínica SOMA, Medellín

2. @onconerd

3. Conflicts of interest for this lecture
Mauricio Lema
None for this lecture

4. Induction chemotherapy Radiotherapy
Surgery Radiotherapy
LA-HNC: Hypopharynx/Larynx
VALCSG, NEJM, 1991
Merlano MC, ESMO Open, 2019

5. RTOG 91-11
Forastiere AA, JCO, 2013
Advanced
larynx
tumours
Concurrent chemoradiation
(CCRT)
Induction chemotherapy,
followed by radiation
Radiation
Primary endpoint: Laryngectomy-free survival
Stage III or IV squamous cell
cancer of the supraglottic or
glottic larynx curable with
laryngectomy and RT

6. Group 1 (induction, control arm)
Received up to three cycles of PF (cisplatin 100 mg/m2
on day 1 and fluorouracil 1,000 mg/m2 per day for 5
days) every 3 weeks. Responders (at least 50%
reduction of the primary tumor and at least stable
disease in the neck) received RT (2 Gy per fraction in
35 treatments to 70 Gy).
Group 2 (concomitant)
Received cisplatin 100 mg/m2 on days 1, 22, and 43 of
RT (70 Gy).
Group 3 (RT alone) Received RT (70 Gy).
Forastiere AA, JCO, 2013
Salvage surgery was performed for patients in group 1 who achieved less than a partial response at the
primary site or who experienced progressionin the neck after two cycles of PF or progression at any
time during induction
Salvage surgery was performed in all groups in patients with biopsy-proven persistent disease after
completing RT or for subsequent recurrence.
A planned neck dissection was recommendedfor patients with N2 or N3 disease at initial staging
RTOG 91-11

7. RTOG 91-11
Forastiere AA, JCO, 2013
LFS compared with RT alone
Induction chemotherapy v RT alone: HR, 0.75; 95% CI, 0.59 to 0.95;
Concomitant chemotherapy v RT alone: HR, 0.78; 95% CI, 0.78 to 0.98

8. RTOG 91-11
Forastiere AA, JCO, 2013
Deaths not attributed to larynx cancer or
treatment were higher with concomitant
chemotherapy (30.8% v 20.8% with induction
chemotherapy and 16.9% with RT alone).

9. Stage III - IV SCC of
the larynx (T3eT4,
N0eN2, M0) or
hypopharynx (T2-T4,
N0eN2, M0) who
would have required
a total laryngectomy
+/- a partial
pharyngectomy
Sequential Arm
Alternating Arm
Primary endpoint: Survival with functional larynx (SFL)
EORTC 24954
Henriques De Figueiredo B, Eur J Cancer, 2016
Two cycles of CT (cisplatin and 5fluorouracil) were delivered; for partial
responders (PR), two additional cycles were delivered followed by RT (70 Gy/7
weeks). Patients with less than a PR underwent total (pharyngo)-laryngectomy
and postoperative RT
Four cycles of cisplatin and 5fluorouracil were delivered at weeks 1, 4, 7 and 10, while
20 Gy of RT was delivered during weeks 2-3, 5-6, and 8-9 (total dose of 60 Gy)
N=450

10. EORTC 24954
Henriques De Figueiredo B, Eur J Cancer, 2016
Ten-year survival with functional larynx (primary end-
point) and overall survival were similar in both arms
(18.7% and 33.6% in SA versus 18.3% and 31.6% in AA)

11. Larynx and
hypopharynx
cancer that
required total
laryngectomy
TPF followed by RT
PF followed by RT
Primary endpoint: 3-yr larynx preservation rate
GORTEC 2000-01: RANDOMIZED TRIAL OF INDUCTION CHEMOTHERAPY WITH CISPLATIN
AND 5-FLUOROURACIL WITH OR WITHOUT DOCETAXEL FOR LARYNX PRESERVATION
Pointreau Y, JNCI, 2009
Docetaxel at 75 mg/m 2 on day 1, cisplatin at 75 mg/m 2 on day 1, and 5-
fluorouracil at a dose of 750 mg/m 2 by 24-hour continuous infusion for 5
days; three cycles with a 21-day interval were planned
Cisplatin 100 mg/m 2 on day 1 and 5-fluorouracil given at a dose of 1000 mg/m
2 by 24-hour continuous infusion for 5 days for three cycles with a 21-day
interval
N=213

12. GORTEC 2000-01: RANDOMIZED TRIAL OF INDUCTION CHEMOTHERAPY WITH CISPLATIN
AND 5-FLUOROURACIL WITH OR WITHOUT DOCETAXEL FOR LARYNX PRESERVATION
Pointreau Y, JNCI, 2009
Patients whose cancer responded well to chemotherapy
(complete response at the primary site or partial response and
recovered normal larynx mobility) were treated with
radiotherapy with or without additional chemotherapy.
Neck dissection was not planned but performed only in patients
with residual tumor in the lymph nodes.
Patients who did not respond to induction chemotherapy
underwent total laryngectomy with neck dissection, followed by
radiotherapy with or without additional chemotherapy.

13. GORTEC 2000-01: RANDOMIZED TRIAL OF INDUCTION CHEMOTHERAPY WITH CISPLATIN
AND 5-FLUOROURACIL WITH OR WITHOUT DOCETAXEL FOR LARYNX PRESERVATION
Pointreau Y, JNCI, 2009
3-year actuarial larynx preservation rate was 70.3%
with TPF vs 57.5% with PF (difference = 12.8%; P = .03)
ORR

14. A systematic review of current and emerging approaches in the field of
larynx preservation
Denaro N, Radiotherapy and Oncology, 2014

15. A systematic review of current and emerging approaches in the field of
larynx preservation
Denaro N, Radiotherapy and Oncology, 2014
Post-hoc analysis
Vs Surgery

16. A systematic review of current and emerging approaches in the field of
larynx preservation
Denaro N, Radiotherapy and Oncology, 2014
Induction Chemotherapy (IC) followed by RT has been shown to allow
laryngeal preservation in about two-thirds of pts with locally advanced
laryngeal or hypopharyngeal cancer without compromising survival.
IC is regarded as the landmark treatment of non-surgical larynx preservation
approaches.
Concomitant and alternating chemoradiotherapy treatments are also
acceptable in larynx preservation.

18. LA Larynx/Hypopharynx SCC
Cisplatin-elegible
Surgery
No

19. LA Larynx/Hypopharynx SCC
Cisplatin-elegible
TPF q21d x3
PR/CR
RT
Yes
yes

20. LA Larynx/Hypopharynx SCC
Cisplatin-elegible
TPF q21d x3
PR/CR
RTSurgery
No Yes
yesno

21. @onconerd