Abstract
Background and purpose
Historically, radiation therapy (RT) has been an available treatment option for patients
with early resectable head and neck squamous cell carcinoma (HNSCC) and the sole therapy
for those with unresectable or inoperable disease. Recently, four noteworthy strategies
have emerged for the improvement of therapeutic outcome in the curative treatment
of HNSCC: they include the development of altered fractionation radiotherapy, integration
of chemotherapy with radiotherapy, incorporation of intensity-modulated radiotherapy
and the introduction of targeted biological therapy. These strategies are briefly
reviewed in an effort to help interpret evidence-based data and to facilitate clinical-decision
making in a clinical context.
Materials and methods
For patients with early stage HNSCC no level 1 study exists in which radiation therapy
is compared with conservative surgery for the evaluation of local control or survival.
Only evidence from prospective and retrospective cohort studies is available to evaluate
the role external radiotherapy and/or brachytherapy currently play in limited disease.
For patients with locally advanced HNSCC the recommendations to address the questions
about better treatment in resectable and unresectable tumors are based on more than
100 randomized Phase III trials included in six meta-analyses on chemo-radiotherapy
and/or altered fractionation. Data from phase II trials and cohort studies help interpret
the advances in intensity-modulated radiotherapy.
Results
External radiotherapy and/or brachytherapy are crucial treatment options in patients
with early stage HNSCC. For patients with locally advanced HNSCC, where outcome with
conventional radiotherapy is poor, meta-analyses and collective data showed that loco-regional
control may be improved at high level of evidence by altered fractionation radiotherapy,
chemo-radiotherapy with concomitant approach or association of selected hypoxic cell
radiosensitizer with radiotherapy. For these patients, overall survival may be improved
at high level of evidence by concomitant chemo-radiotherapy or hyperfractionated RT
delivered with increased total dose. Also EGFR-inhibitors (cetuximab)-radiotherapy
strategy offers at a lower level of evidence better loco-regional control and overall
survival than radiotherapy alone. Chemo-radiotherapy programs can achieve an improved
larynx-function preservation program without the risk of overall survival reduction,
for patients with larynx or hypopharynx tumors who are candidates to radical surgery
followed by radiotherapy. Recently, strong evidence for an improved outcome for high-risk resected patients has been shown by the use of adjuvant concomitant chemo-radiotherapy. Despite improved
results, a higher severe toxicity has been largely evidenced with concomitant chemo-radiotherapy
by reducing the gain in the therapeutic index with new treatment strategies. Three-dimensional
conformal radiotherapy is the minimal standard of technique in HNSCC: however, as
advances are promising, intensity-modulated radiotherapy should be largely implemented.
Conclusions
Stepwise improvements in HNSCC non-surgical therapy have shown favorable impact on
loco-regional control and overall survival. However, despite hundreds of clinical
trials in patients with advanced disease, there is no absolute consensus about patient
selection for altered fractionation regimens, type of chemo-radiotherapy association,
radiation or chemotherapy dose schedule. Nevertheless, many well-conducted clinical
studies have expanded therapy options besides standard radiotherapy and have contributed
to defining the evolving standard of care for patients with HNSCC.
Keywords
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Recommended Readings
- Targeting the epidermal growth factor receptor in radiotherapy: radiobiological mechanisms, preclinical and clinical results.Radioth Oncol. 2004; 72: 257-266
- Alteration of radiotherapy fractionation and concurrent chemotherapy: a new frontier in head and neck oncology?.Nature Clinical Practice Oncol. 2005; 2: 305-314
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Article info
Publication history
Published online: May 10, 2007
Accepted:
April 4,
2007
Received in revised form:
March 26,
2007
Received:
October 31,
2006
Identification
Copyright
© 2007 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
