Controlled trials of synchronous chemotherapy with radiotherapy in head and neck cancer: Overview of radiation morbidity

doi:10.1016/S0936-6555(05)80064-0

Clinical Oncology

Volume 9, Issue 5, 1997, Pages 308-312

https://doi.org/10.1016/S0936-6555(05)80064-0 Get rights and content

Abstract

Recently published overviews of randomized controlled trials of simultaneous chemotherapy with radiotherapy in squamous cell carcinoma of the head and neck have demonstrated a significant survival advantage from the combined treatment compared with radiotherapy alone. However, they also showed that chemotherapy increased acute radiation morbidity, but there was no information on late effects. The 19 publications of trials of simultaneous chemotherapy contained in the overview by Munro were reviewed for morbidity data. It was found that chemotherapy significantly enhanced both acute and late effects, suggesting that the drugs may be merely dose-modifying. Future trials should be designed to determine whether or not chemotherapy improves the therapeutic ratio.

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Cited by (64)

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In patients with head and neck squamous cell carcinoma (HNSCC), curative-intent radiotherapy (RT) and chemoradiotherapy (CRT) are associated with substantial acute morbidity and 5–10% of patients die within 180 days of treatment initiation. Most of these early deaths occur without HNSCC recurrence or progression and may therefore be preventable to some extent. We developed a prediction tool to estimate the risk of non-HNSCC mortality occurring within the first 180 days following RT/CRT initiation.
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In our study, radiation alone and chemotherapy alone were not significant risk factors for PCF formation, but concurrent chemoradiation therapy was significantly associated with development of PCF. Concurrent chemoradiation therapy might result in more severe mucositis, infection, fistula formation, and skin necrosis [33,34]. Intraoperative factors included transfusion, type of flap (patch vs. tube, skin vs. GI flap), occurrence of hematoma after TL, and operation time.
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Diverse clinical factors were identified as PCF risk factors using AI models and the neural network demonstrated highest predictive power. This first study about prediction of PCF using AI could be used to select high risk patients for PCF when performing TL.
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Citation Excerpt :
The subgroup analysis comparing radiotherapy and chemoradiotherapy failed to find any difference, probably because of the small size of the population in each subgroup. Studies comparing the two treatment modalities point to the greater immediate and long-term local toxicity of chemoradiotherapy.28 These results are influenced by the type of molecule used: anti-metabolic agents (5-FU and methotrexate) would appear to be the most troublesome.29
The aim of this study was to analyze the causal mechanisms of severe swallowing disorders after the treatment of oropharyngeal cancer. Twenty-six patients with severe swallowing disorders at ≥12 months after treatment for oropharyngeal cancer were analyzed retrospectively using videofluoroscopy. Fourteen patients (54%) had been treated with surgery (±postoperative radiotherapy), while 12 patients (46%) had been treated with (chemo)radiotherapy. Videofluoroscopy analysis showed a localized alteration in the surgical excision area resulting in impaired tongue root retraction in the surgical group (P = 0.012), while general impairment of the pharyngeal, laryngeal, and upper oesophagus sphincter was found in the non-surgical group. Aspirations in the surgical group most often occurred after swallowing, while in the non-surgical group, they occurred during and after swallowing (P = 0.039). This analysis by videofluoroscopy provides important insights into the mechanisms giving rise to swallowing disorders after the treatment of oropharyngeal cancer.
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The incidence of human papillomavirus (HPV)-associated oropharyngeal cancer continues to increase in contrast to other head and neck cancer sites. There is a growing role for upfront surgery to treat these cancers in the era of organ preservation treatment strategies. This is becoming especially important in younger, healthier patients with HPV-associated squamous cell carcinoma. Surgery for oropharyngeal cancer has evolved from large, open transcervical and transmandibular approaches to minimally-invasive transoral endoscopic techniques. Advances in transoral endoscopic surgery (TES) have led to renewed interest in upfront surgical treatment for oropharyngeal carcinoma. Transoral laser microsurgery (TLM) and transoral robotic surgery (TORS) are two techniques that allow for complete oncologic resection through the mouth in select patients, with minimal cosmetic deformity and optimal speech and swallow function after completion of therapy. In this article we will review transoral approaches to oropharyngeal carcinoma: its oncologic and functional outcomes, and its role in the multi-disciplinary treatment of oropharyngeal cancer.
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Citation Excerpt :
The anti-metabolites such as methotrexate and 5-fluorouracil seem to be the drugs most associated with the oral, pharyngeal, and oesophageal symptoms of dysphagia.143 Even though combined modality treatment significantly increased late toxicity,58,144 when both chemoradiation and DARS-dose were studied together as predictive variables of SWALL6 months, the effect of CT was hidden by DARS-dose.54 Eisbruch et al.24 observed aspiration in 65% of patients soon after treatment and in 62% several months later.
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The review of literature was focused on studies reporting dysphagia as a pre-treatment evaluation and as cancer and cancer therapy related side-effects, respectively. Relevant literature through the primary literature search and by articles identified in references was considered. The members of the group discussed the results and elaborated recommendations according to the Oxford CRBM levels of evidence and recommendations. The recommendations were revised by external Radiation Oncology, Ear Nose and Throat (ENT), Medical Oncology and Speech Language Pathology (SLP) experts.
Recommendations on pre-treatment assessment and on patients submitted to radiotherapy were given. The effects of concurrent therapies (i.e. surgery or chemotherapy) were taken into account.
In HNCPs treatment, disease control has to be considered in tandem with functional impact on swallowing function. SLPs should be included in a multidisciplinary approach to head and neck cancer.

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Original articleControlled trials of synchronous chemotherapy with radiotherapy in head and neck cancer: Overview of radiation morbidity

Abstract

Int J Radiat Oncol Biol Phys

Clin Radiol

Clin Radiol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Chemotherapy in conjunction with radiotherapy and/or surgery in head and neck cancer

Adjuvant and adjunctive chemotherapy in the management of squamous cell carcinoma of the head and neck region: a meta- analysis of prospective and randomized trials

J Clin Oncol

An overview of randomised controlled trials of adjuvant chemotherapy in head and neck cancer

Br J Cancer

Original article
Controlled trials of synchronous chemotherapy with radiotherapy in head and neck cancer: Overview of radiation morbidity