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either. In conclusion, no advantage in combining MF-EBRT of PORT in patients pN1 with oral cavity and oropharynx
and CMT have been proved so far. primaries. Any firm conclusions could be drawn due to
the heterogeneity of the studies, although it was evident
Target therapy more mortality (not significant) in the group treated with
[4]
EGFR over expression leads to decreased survival and increased PORT (44% vs. 34%). Shrime analyzed the benefit of PORT
risk of local and regional recurrence in head and neck cancer. in patients with OCSCC pT1-2 pN1. PORT improved OS at 5
[54]
The inhibition of EGFR by monoclonal antibodies (cetuximab) years [41.4% vs. 54.2% (P < 0.001)] of note PORT improved OS
associated with EBRT in patients with non-operated AHNC in T2 tongue and floor of mouth subgroup [52.3% vs. 37.9%
showed an increase 5-year OS (46% vs. 36%) and LRC (47% vs. 34%) (P = 0.002) and 39.9% vs. 17.7% (P =0.003), respectively] but
compared with EBRT alone. Notably in this trial did not include not significantly in T1 subgroup.
[55]
patients with OCSCC therefore clinical benefit in this group of
patients is presently unknown. The hypothesis that early nodal metastases may express a more
aggressive biology supports adjuvant therapy in stage III. [64]
Nowadays, the standard of treatment for non-operable
AHNC, including OCSCC, is EBRT plus CMT despite the Risk factors for locoregional recurrence
fact that its benefit in OS and LRC probability equals of Extracapsular extension (ECE) in cervical lymph node
the hyperfractionated-EBRT. The reasons that have led to metastases and the involvement of surgical resection
this situation are basically two: (1) logistics, due to the margins (ISRM) are the most important prognostic factors
consumption of resources and the drawbacks associated for risk of LRC and death.
with treating patients twice a day, for 7-8 weeks; and (2) the
development of high conformation techniques as IMRT, which RTOG stratified patients treated with PORT into 3 risk groups
[65]
allow to exploit the different sensitivity to radiation of the tumor according to the presence of ECE, 2 or more lymph nodes with
and healthy tissues using a single fraction per day with a shorter metastasis or ISRM. Group I were those with no more than 2
overall time of treatment, usually 5-6 weeks. nodes affected without ECE; group II included patients with more
than 2 positive lymph nodes or ECE, negative margins; group III
Postoperative radiation therapy comprised patients with ISRM. Significant difference was found
Adjuvant EBRT in the rate of loco-regional recurrence at 5 years between groups
The value of postoperative radiotherapy (PORT) for AHNC, was I, II and III of 17%, 27% and 67% respectively and median OS at 5.6
established by Fletcher and Evers and Marcus et al. in 1970’s. years, 2 years and 1.5 years, respectively.
[56]
[57]
The evidence that proves the usefulness of PORT has been based
[66]
on retrospective studies of large groups of patients. Due to the Langendijk et al. conducted a multivariate analysis to define
inherent bias in such kind of studies the survival benefit of PORT different prognostic groups based on pathologic features a series
is not fully confirmed, although there are no doubts about the of 801 patients with AHNC treated with PORT. The final model
gain in LRC. identified 6 prognostic factors and grouped the patients into
3 risk groups [Table 2]. This model was validated by the Dutch
Lundahl et al. performed a retrospective, matched-pair analysis Head and Neck Oncology Cooperative Group (DHNOCG) in a
[58]
to compare surgery alone vs. surgery plus PORT. They found multicenter study. [67]
significant improvement in LRC and OS in the PORT group.
Nowadays, there is consensus to identify patients at high
[68]
Lavaf et al. and Kao et al. analyzed patients with AHNC risk of recurrence after surgery who benefit from PORT: (1)
[60]
[59]
stage III-IV treated with surgery alone or surgery plus major criteria: ECC or ISRM; and (2) minor criteria: inadequate
PORT from Surveillance Epidemiology End Results (SEER) surgical margins (< 5 mm), ≥ 2 lymph nodes metastases
data base. In multivariate analysis the survival benefit of (N2b-N3), stage pT3-T4 even with negative margins, in primary
PORT vs. surgery alone at 5-year was significant in both oral cavity, metastases in levels IV and V, presence of PNI or LVI.
non-locally advanced tumors with lymph node metastasis
(51.6% vs. 40.6%) as in the case of locally advanced tumors Perineural infiltration
with lymph node metastasis (35.3 % vs. 25.2%). Overall One of most controversial point is the value of PORT when
PORT significantly improved OS by 11% and cancer-specific there is PNI but the absence of other factors associated with
survival by 8.6%. They showed a greater reduction in the risk risk of recurrence. Neither in the analysis of Jonkman et al.
[66]
of death in stage N2b-N3 compared to N1-N2a (HR = 0.62, or its further validation, PNI was found to be an independent
[67]
0.78 and 0.82 respectively). The magnitude of the reduction prognostic factor. Bur et al. after a systematic review on the
[69]
was larger for tumors of the oropharynx, hypopharynx and potential benefit of PORT in patients with PNI concluded that
larynx compared to oral cavity (HR = 0.72, 0.66 and 0.62 there is insufficient evidence to recommend PORT routinely in
respectively) Patients with lymph node metastasis and any these cases. The author suggests that in case of infiltration of
tumor sites, all benefited from the administration of PORT cranial nerves or multiple PNI, PORT might be justified. PNI is
although the gain is greater in high-risk disease. associated with increased risk of nodal recurrence, therefore it is
recommended to treat the neck in this scenario.
Whereas PORT is not routinely indicated in patients with
HNSCC stage pT1-2 pN1 because there is not definitive Time factor in PORT
[61]
data supporting that approach. Moergel et al. published Evidence exists suggesting that the risk of LRC is higher in
[62]
a meta-analysis of studies in order to elucidate the role patients with AHNC when receiving PORT more than 6 weeks
162 Plast Aesthet Res || Volume 3 || May 25, 2016