Discussion
IC is an organ-preserving therapeutic approach for treating locally
advanced hypopharyngeal cancers. Our study represents a retrospective
single-center analysis of assessment of CCRT or RT after IC and
demonstrated that IC+CCRT could improve LRPFS and OS in the group of IC
responders. To the best of our knowledge, this study is the first to
compare the efficacy and toxicity of CCRT and RT following IC in
patients with HPSCC.
In our study, the CR rate for primary sites and survival were lower than
their counterparts reported in the European Organization for Research
and Treatment of Cancer (EORTC) 24891.9 Several
factors could cause this difference. Firstly, it may be due to the
majority of patients in our study belonging to T3-4 (79.5%) and stage
IV (97.6%), according to the EORTC 24891, patients with T2 stage HPSCC
(18/22, 82%) were found to be more accessible to CR (P =0.002)
than patients with T3 (34/71, 48%) and T4 stages (0/4). Secondly, this
is likely due to the different measurements involved in the efficiency
assessment in our study. Both laryngoscopy and neck CT scan were
involved in our study; however, a neck CT scan was not mandatory in
EORTC 24891. Lastly, our study included patients with PR and
non-responders besides CR patients.
Except for EORTC 24891, the OS in our study resembled that of a previous
study.14 Some other RCTs showed higher CR rate and OS
in patients with a higher proportion of T2-3 and N0-1 compared to our
study.10, 15 Moreover, laryngeal cancer was included
in the research cohorts in some of those RCTs.
In our study, higher LRPFS and OS occurred in the IC responders who
received CCRT than in those who received RT alone. Based on our
findings, an effort to improve responsiveness to IC becomes the key
point. Admittedly, compared to CCRT alone, IC+CCRT has not yet been
validated to be advantageous for the survival of patients with locally
advanced head and neck cancers in phase III clinical
trials.16, 17 But it has been demonstrated that IC
could reduce the risk of distant metastasis 18.
Besides, IC was considered advantageous for survival when performing in
the patients with heavily affected primary sites or advanced nodal
involvement (cN2c-N3) 19. Based on the high proportion
of N2c (n=27, 32.5%) and N3b (n=37,44.6%) in our study, which had the
high risk of distant metastasis, IC was chosen as the prior treatment.
A recent phase II/III trial indicated that patients who underwent IC
followed by CCRT had better survival outcomes than those who underwent
CCRT alone for head and neck cancer (median survival: 54.7 vs. 31.7%,P =0.03).20 Furthermore, a retrospective study
aiming at laryngeal and hypopharyngeal cancers demonstrated a similar
conclusion that IC+CCRT resulted in a longer median OS (64.7 vs. 21%,P =0.003) than CCRT alone for hypopharyngeal cancers, but no
survival benefit was found in laryngeal cancers.21 IC
plays a crucial role in laryngeal preservation(LP)-oriented combination
therapy for HPSCCs. This is also supported by the NCCN guideline in
which IC was recommended as a strategy for LP.13
As concluded in our study, the effect of CCRT after IC correlated with
IC responses. The French Groupe d’Oncologie Radiothérapie Tête et Cou
(GORTEC) 2000-01 trial, which included 213 patients with laryngeal or
hypopharyngeal cancer, demonstrated the superiority of the TPF regimen
over PF in terms of ORR (80.0% vs. 59.2%, P =0.002) and LP rate
(70.3% vs. 57.5%, P =0.03).15 With the
exception of ORR and LP rates, another two RCT trials showed that TPF
markedly improved PFS and OS in locally advanced head and neck
cancers.22, 23 Conceivably, aiming at the
effectiveness of CCRT combined with IC, TPF should be prioritized for IC
treatment rather than PF.
Regarding IC non-responders, more careful therapeutic considerations are
required. Nowadays, with the advancement of individualized cancer care
with increasing precision and more implications, and with the
incorporation of multicenter novel therapies, such as immunotherapy, the
access to an ideal trade-off status between the expected clinical
outcomes and a less-affected quality of life potentially comes into real
practice.24
Regarding the exclusiveness of this series, owing to the prevailing
characteristics of many studies involving multiple sites of head and
neck cancer, HPSCC comprises only a minority of the ensemble population
due to its low prevalence. In some researchers about head and neck
subsites, hypopharyngeal cancer generally merged with laryngeal cancer.
Therefore, critical featured information for HPSCC treatment would be
incomprehensive, leading to a shortage of definite conclusions.
Exploration of optimal treatment for HPSCCs to some degree counts on the
personal experiences of clinicians and the results, including the
confounding factors that may render them less convincing. Herein, our
study focused only on patients with HPSCC and offered exclusive
information regarding their treatment, which will be helpful in clinical
practice. The overall efficacy assessment for IC was used to group the
patients in our study rather than only aiming for the primary sites,
which brought about more reasonable evaluations for the comparison of
CCRT and RT alone.
Regarding limitations of our study, due to the small sample size and
retrospective nature of our study, the comparison of CCRT and RT alone
according to IC responses requires further investigation with larger
cohorts or prospective trials. Moreover, as no patients achieved CR
after IC treatment, more studies are required to investigate the
necessity of CCRT.