The management of head and neck tumors with high technology radiation therapy

Squamous cell carcinoma is responsible for 90% of the head and neck cancers affecting over 600,000 people worldwide. Radiation therapy, surgery and chemotherapy are the most important treatment modalities in head and neck squamous cell carcinoma. The aim of this review is to summarize the recent innovations in head and neck radiation therapy, which intends to appreciate the cutting-edge intensity-modulated radiation therapy strategies to mitigate long-term toxicities and evaluate promising technologies in the field as adaptive treatment, dose painting and proton therapy.     

RCMI et voies aérodigestives supérieures : le fractionnement différentiel a-t-il un intérêt ?

For head and neck cancer, intensity-modulated radiation therapy (IMRT) provides benefits in terms of coverage of the target tumour volume and reduction of the dose to organs at risk. Altered fractionation called SMART (simultaneous modulated accelerated radiation therapy) or SIB (simultaneous integrated boost), equivalent to the “concomitant boost” of conventional techniques, provides additional theoretical gain in the therapeutic index and simplifies the practical implementation of the treatment. The impact on tumour control and acute and late toxicities is encouraging but needs to be confirmed by prospective clinical studies with sufficient follow-up. A lot of different protocols have been tested without really bringing out a “gold standard”. However, the current results tend to suggest a SIB/SMART-IMRT moderately accelerated without combined chemotherapy for limited stages (I and II), and SIB-IMRT slightly accelerated with induction and/or concomitant chemotherapy for more advanced stages (III and IV).     

Proton radiation therapy for head and neck cancer

Due to the close spatial relationship of head and neck and skull base tumors to numerous normal anatomical structures, conventional photon radiation therapy can be associated with significant acute and long-term treatment-related toxicities. Superior dose localization properties of proton radiation therapy allow smaller volumes of normal tissues to be irradiated than is feasible with any photon technique. Intensity-modulated proton therapy (IMPT) is a powerful delivery technique which results in improved dose distribution as compared to that of intensity-modulated radiation therapy (IMRT). Initial clinical experience with proton radiation therapy in treatment of head and neck and skull base tumors is promising. Prospective multi-institutional trials are underway to define the role of proton radiation therapy, particularly IMPT, in the treatment of head and neck and skull base tumors.     

Cancer de l’oropharynx

Oropharyngeal carcinomas, contrary to other head and neck carcinomas are of increasing frequency, mostly due to a frequent association with human papillomavirus infection. Pluridisciplinary management is necessary. New techniques as transoral surgery or intensity-modulated radiation therapy have the potential to reduce toxicities and morbidity while offering equivalent local control rates. Early stages may be treated with single modality treatment (surgery or radiotherapy) with five-year overall survival rate exceeding 80%. Advanced stages need therapeutic associations and five-years survival rates are inferior to 40%.     

Intensity-modulated radiation therapy: emerging cancer treatment technology

The use of intensity-modulated radiation therapy (IMRT) is rapidly advancing in the field of radiation oncology. Intensity-modulated radiation therapy allows for improved dose conformality, thereby affording the potential to decrease the spectrum of normal tissue toxicities associated with IMRT. Preliminary results with IMRT are quite promising; however, the clinical data is relatively immature and overall patient numbers remain small. High-quality IMRT requires intensive physics support and detailed knowledge of three-dimensional anatomy and patterns of tumour spread. This review focuses on basic principles, and highlights the clinical implementation of IMRT in head and neck and prostate cancer.     

Intensity-modulated radiation therapy in the management of head and neck cancer

PURPOSE OF REVIEW: Intensity-modulated radiation therapy (IMRT) represents a potentially significant new advance in the radiotherapeutic treatment of head and neck cancer patients. The capacity of IMRT to produce highly conformal dose distributions affords the opportunity to decrease the spectrum of toxicities associated with head and neck radiation. This review updates recent advances regarding the use of this emerging technology. RECENT FINDINGS: Mature clinical data demonstrating head and neck IMRT safety and efficacy remain relatively limited to date. Recent publications have sought to clarify target selection and delineation. Refinements in target design driven by clinical outcomes are beginning to emerge. Technical aspects of IMRT delivery such as the impact of daily set-up variation, planning methods, and optimal fractionation regimens are progressing. SUMMARY: Stepwise refinement in the practice of IMRT for head and neck cancer patients is advancing worldwide. However, mature clinical data remains relatively limited and specific aspects regarding the practice of head and neck IMRT remain heterogeneous.     

Place de la protonthérapie en cancérologie ORL

The absence of exit dose and the sharp lateral penumbra are key assets for proton therapy, which are responsible for its dosimetric superiority over advanced photon radiotherapy. Dosimetric comparisons have consistently shown a reduction of the integral dose and the dose to organs at risk favouring intensity-modulated proton therapy (IMPT) over intensity-modulated radiotherapy (IMRT). The structures that benefit the most of these dosimetric improvements in head and neck cancers are the anterior oral cavity, the posterior fossa, the visual apparatus and swallowing structures. A number of publications have concluded that these dosimetric differences actually translate into reduced toxicities with IMPT, for example with regards to reduced weight loss or need for feeding tube. Patient survival is usually similar to IMRT series, except in base of skull or sinonasal malignancies, where a survival advantage of IMPT could exist. The goals of the present review is to describe the major characteristics of proton therapy, to analyse the clinical data with regards to head and neck cancer patients, and to highlight the issue of patient selection and physical and biological uncertainties.     

Chimioradiothérapie concomitante des cancers des voies aérodigestives supérieures. Faut-il revoir les contraintes de dose dans les organes à risque ?

Concurrent chemoradiotherapy improves the outcome of locally advanced head and neck cancers and the current reference chemotherapy is cisplatin. These results are obtained at the cost of increased toxicities. To limit the risk of toxicity, organ at riskdose constraints have been established starting with 2D radiotherapy, then 3D radiotherapy and intensity-modulated radiotherapy. Regarding grade ≥ 3 acute toxicities, the scientific literature attests that concurrent chemoradiotherapy significantly increases risks of mucositis and dysphagia. Constraints applied to the oral mucosa volume excluding the planning target volume, the pharyngeal constrictor muscles and the larynx limit this adverse impact. Regarding late toxicity, concurrent chemoradiotherapy increases significantly the risk of postoperative neck fibrosis and hearing loss. However, for some organs at risk, concurrent chemotherapy appears to increase late radiation induced effect, even though the results are less marked (brachial plexus, mandible, pharyngeal constrictor muscles, parotid gland). This additional adverse impact of concomitant chemotherapy may be notable only when organs at risk receive less than their usual dose thresholds and this would be vanished when those thresholds are exceeded as seems to be the situation for the parotid glands. Until the availability of more robust data, it seems appropriate to apply the principle of delivering dose to organs at risk as low as reasonably achievable.     

Organes à risque en radiothérapie conformationnelle des tumeurs de la tête et du cou : aspect pratique de leur délinéation et des contraintes de dose

The aim of this article is to provide some practical guidelines for the delineation of organs at risk in intensity-modulated radiation therapy (IMRT) in head and neck cancer, drawn from anatomic, radiology, physiopathology date which will take into account the daily imperatives of radiation oncologists. Standardizing the delineation of organs at risk by consensus, might help for an objective comparison of toxicities induced by radiotherapy.     

Can Dose Reduction to One Parotid Gland Prevent Xerostomia? — A Feasibility Study for Locally Advanced Head and Neck Cancer Patients Treated with Intensity-modulated Radiotherapy

AimsDryness of the mouth is one of the most distressing chronic toxicities of radiation therapy in head and neck cancers. In this study, parotid function was assessed in patients with locally advanced head and neck cancers undergoing intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Parotid function was assessed with the help of a questionnaire and parotid scintigraphy, especially with regards to unilateral sparing of the parotid gland.Materials and methodsIn total, 19 patients were treated with compensator-based IMRT between February 2003 and March 2004. The dose to the clinical target volume ranged between 66 and 70 Gy in 30–35 fractions to 95% of the isodose volume. Ipsilateral high-risk neck nodes received an average dose of 60 Gy and the contralateral low-risk neck received a dose of 54–56 Gy. Eight of 19 patients also received concomitant chemotherapy.ResultsSubjective toxicity to the parotid glands was assessed with the help of a questionnaire at 0, 3 and 6 months and objective toxicity was assessed with parotid scintigraphy at 0 and 3 months. The mean dose to the ipsilateral parotid gland ranged from 19.5 to 52.8 Gy (mean 33.14 Gy) and the mean dose to the contralateral gland was 11.1–46.6 Gy (mean 26.85 Gy). At a median follow-up of 13 months, 9/19 patients had no symptoms of dryness of the mouth (grade I), 8/19 had mild dryness of the mouth (grade II) and only 2/19 had grade III xerostomia, although the parotid gland could only be spared on one side in most of the patients.ConclusionsMinimising the radiation dose to one of the parotid glands with the help of IMRT in patients with advanced head and neck cancers can prevent xerostomia in most patients and parotid scintigraphy is a useful method of documenting xerostomia.     

Intensity-modulated radiation therapy in head and neck cancers: dosimetric advantages and update of clinical results

Intensity-modulated radiation therapy (IMRT) is an exciting new modality in radiation therapy. The head and neck region is an ideal target for this new technology for several reasons. First, IMRT offers the potential for improved tumor control through delivery of high doses to the target volume. Second, because of sharp dose gradients, IMRT results in the relative sparing of normal structures in the head and neck region. Third, organ motion is virtually absent in the head and neck region, so, with proper immobilization, treatment can be delivered accurately. Although this is a relatively new technology, preliminary studies show excellent dosimetric profiles and clinical results. Salivary gland sparing has also resulted in reduced incidence and severity of xerostomia. Early reports of improvement in tumor control with better side effect profiles versus conventional techniques are promising, but will need to be confirmed with longer follow-up.     

Current management options for liposarcoma and challenges for the future

Disease outcome in locally advanced head and neck cancer patients is far from satisfactory. The main causes of failure remain linked to locoregional recurrences, which are due to incomplete eradication of clonogenic cells. Conventional radiation therapy or 3-dimensional conformal radiation therapy are currently carried out at their extreme possibilities due to their intrinsic limitation – namely the impossibility to generate concave dose distributions without compromising tumor irradiation. Approximately a third of patients treated with radiotherapy and most head and neck cancer cases present concave shapes of the target volumes. With the advent of intensity modulated radiation therapy – clinically available for only few years – head and neck patients can now benefit from strategies based on highly conformal techniques. It is possible to exploit efficiently dose-escalation protocols to increase probabilities to eradicate clonogens, to reduce overall treatment time, to control repopulation problems and to keep as low as reasonably necessary the irradiation of healthy tissues minimizing acute and late complications. Today, both planning and clinical studies demonstrate these advantages but larger controlled trials are necessary to assess the true potentialities of techniques based on intensity modulation for head and neck cancers. In a speculative view, proton therapy, possibly with intensity modulation, or light ion therapy should be considered for selected cases or for reirradiation due to their higher biological efficacy and their degree of dose-conformation to target volumes.     

Organ-sparing radiation therapy for head and neck cancer

To improve locoregional tumor control and survival in patients with locally advanced head and neck cancer (HNC), therapy is intensified using altered fractionation radiation therapy or concomitant chemotherapy. However, intensification of therapy has been associated with increased acute and late toxic effects. The application of advanced radiation techniques, such as 3D conformal radiation therapy and intensity-modulated radiation therapy, is expected to improve the therapeutic index of radiation therapy for HNC by limiting the dose to critical organs and possibly increasing locoregional tumor control. To date, Review articles have covered the prevention and treatment of radiation-induced xerostomia and dysphagia, but few articles have discussed the prevention of hearing loss, brain necrosis, cranial nerve palsy and osteoradionecrosis of the mandible, which are all potential complications of radiation therapy for HNC. This Review describes the efforts to prevent therapy-related complications by presenting the state of the art evidence regarding advanced radiation therapy technology as an organ-sparing approach.     

Impact of dose and volume on radiation-induced mucositis

There is a relationship between a given radiation dose and the resulting biological effect in the management of head and neck cancer. Radiation mucositis represents a frequent complication in cancer chemoradiation. Its prevention and treatment are major goals in radiation therapy schedules. Critical tissues can be spared using high conformal radiation therapy (3DCRT) based on consensus guidelines for target volume. Current approaches to radiation mucositis with respect to the dose and volume impact are illustrated. The monitoring system of late toxicity used by the authors is presented.     

IMRT in the treatment of head and neck cancer: is the present already the future?

Disease outcome in locally advanced head and neck cancer patients is far from satisfactory. The main causes of failure remain linked to locoregional recurrences, which are due to incomplete eradication of clonogenic cells. Conventional radiation therapy or 3-dimensional conformal radiation therapy are currently carried out at their extreme possibilities due to their intrinsic limitation--namely the impossibility to generate concave dose distributions without compromising tumor irradiation. Approximately a third of patients treated with radiotherapy and most head and neck cancer cases present concave shapes of the target volumes. With the advent of intensity modulated radiation therapy--clinically available for only few years--head and neck patients can now benefit from strategies based on highly conformal techniques. It is possible to exploit efficiently dose-escalation protocols to increase probabilities to eradicate clonogens, to reduce overall treatment time, to control repopulation problems and to keep as low as reasonably necessary the irradiation of healthy tissues minimizing acute and late complications. Today, both planning and clinical studies demonstrate these advantages but larger controlled trials are necessary to assess the true potentialities of techniques based on intensity modulation for head and neck cancers. In a speculative view, proton therapy, possibly with intensity modulation, or light ion therapy should be considered for selected cases or for reirradiation due to their higher biological efficacy and their degree of dose-conformation to target volumes.     

头颈部肿瘤IMRT中适应性再计划预测因素和时间节点的研究进展

在头颈部肿瘤IMRT疗程中,适应性再计划有助于改善由于解剖结构变化导致的剂量学不确定性,并能提高患者的局部控制率和生活质量。研究表明患者治疗前有较大淋巴结、治疗中体重明显下降等是疗程中再计划的重要预测因素;在放疗开始第4周后靶区及危及器官的缩小趋于稳定,建议第3或第4周行 1~2次适应性再计划。     

Intensity modulated radiotherapy treatment planning for dynamic multileaf collimator delivery: influence of different parameters on dose distributions.

BACKGROUND AND PURPOSE: This is an investigation of a dose-based conjugated gradient optimization method (implemented in the CadPlan/Helios system) applied for head and neck tumours. Optimized field fluence distributions are created and transformed into dynamic multileaf collimator (MLC) movements. The aim was to gain knowledge about the influence of different parameters on the dose distribution and how to use the optimization algorithm in an optimum way. MATERIAL AND METHODS: Parameters such as the number of beams, collimator angle and constraints and weight factors have been investigated. Dose escalation to the target volume, the target volume in the build-up region and the way of prescribing the target dose were also investigated. The dose distributions were mainly analysed with physical parameters. RESULTS AND CONCLUSIONS: The optimization algorithm is well suited to create clinical Intensity modulated radiation therapy (IMRT) treatment plans for head and neck tumours even when the target volume is situated in the build-up region. The number of beams is a critical parameter and has a great influence on the dose distribution. The choice of collimator angles is not a critical parameter. The constraints and weight factors have a great influence on the dose distribution and varying these could easily control priorities regarding dose to the target volume or to the surrounding critical organs. Because of dose variations inside the target volume, prescribing to, normalizing to and reporting the mean dose in the target volume for IMRT treatment plans is preferable to the absorbed dose at a point, for example the isocentre point.