David J Thomson

Dose intensified hypofractionated intensity-modulated radiotherapy with synchronous cetuximab for intermediate stage head and neck squamous cell carcinoma

Abstract Background. For stage II and III head and neck squamous cell carcinoma (HNSCC) treated with radiotherapy alone, loco-regional recurrence is the main cause of treatment failure. Strategies to improve loco-regional control should not be at the expense of increased late normal tissue toxicity. We investigated dose-intensified hypofractionated intensity-modulated radiotherapy (IMRT) with synchronous cetuximab. Material and methods. In a phase I/II trial, 27 patients with stage III or high risk stage II HNSCC were recruited. They received three dose level simultaneous integrated boost IMRT, 62.5 Gy in 25 daily fractions to planning target volume one over five weeks with synchronous cetuximab. The primary endpoint was acute toxicity. Secondary endpoints included: late toxicity and quality of life; loco-regional control, cause-specific and overall survival. Results. Radiotherapy was completed by 26/27 patients; for one (4%) the final fraction was omitted due to skin toxicity. All cycles of cetuximab were received by 23/27 patients. Grade 3 acute toxicities included: pain (81%), oral mucositis (78%) and dysphagia (41%). There were few grade 3 physician-recorded late toxicities, including: pain (11%), problems with teeth (8%) and weight loss (4%). At 12 months, only one (4%) patient required a feeding tube, inserted prior to treatment due to dysphagia. The maximal/peak rates of patient-reported late toxicities included: severe pain (11%), any dry mouth (89%) and swallowing dysfunction that required a soft/liquid diet (23%). At 12 months, all quality of life and most symptoms mean scores had resolved to baseline or were only a little worse; dry mouth, sticky saliva and dentition scores remained very much worse. At a median follow-up of 47 months, there were five (18.5%) loco-regional recurrences and the overall cause-specific survival was 79% (95% CI 53–92). Conclusions. This regimen is safe with acceptable acute toxicity, low rates of late toxicity and impact on quality of life at 12 months following treatment. Further evaluation is recommended.

Carotid dosimetry for T1 glottic cancer radiotherapy

OBJECTIVE Radiotherapy for T1 glottic cancer is commonly delivered using a lateral parallel opposed pair of megavoltage photon fields. There is increasing reported evidence of cerebrovascular events due to radiation-induced carotid stenosis. An alternative field arrangement is to use an anterior oblique technique. This study compares the carotid dosimetry between the two techniques and reviews the evidence for the risk of radiation-induced vascular events. METHODS The radiotherapy plans of 10 patients with T1 glottic cancer treated with an anterior oblique technique were examined for carotid dose. Alternative plans were then created using a parallel opposed pair of fields and the dose to the carotids compared. All patients received 50 Gy in 16 fractions treating once daily, for 5 days in a week. RESULTS The average of the mean dose to the carotids with the anterior oblique technique was 21 Gy compared with 37 Gy using the lateral parallel opposed pair arrangement (p < 0.0001). CONCLUSION An anterior oblique field arrangement for the treatment of T1 glottic cancer results in a significantly lower radiation dose to the carotid arteries, which may be clinically important in terms of reducing the risk of cerebrovascular events in long-term survivors. ADVANCES IN KNOWLEDGE Although the anterior oblique technique for treating early glottic cancers is well described, and it is predictable that the dose received by the carotid arteries should be lower with this technique, to our knowledge this is the first study to quantify that reduction in dose with a series of patients.

Prospective evaluation of relationships between radiotherapy dose to masticatory apparatus and trismus

Abstract Aims: This feasibility study aimed to identify relationships between radiation doses to the masticatory apparatus as a combined block or as individual subunits with changes in trismus following radiotherapy. Material and methods: Twenty patients from a single center were recruited prospectively as part of a randomized trial comparing proactive exercises in the management of trismus. Patients with stage III/IV oral cavity or oropharyngeal squamous cell cancers received intensity-modulated radiotherapy with concurrent systemic therapy. All patients had trismus prior to radiotherapy. Maximal inter-incisor distance (MID) was measured pre- and 6 months from the start of radiotherapy. Bilateral muscles of mastication: medial and lateral pterygoids (MP and LP), masseters (M), temporalis (T), temporomandibular joint (TMJ) were contoured on CT images. The block comprised all muscles excluding the TMJ below the orbital floor. Mean dose, equivalent uniform dose (EUD) and V35–V60 Gy were compared with change in MID. Results: In six patients, the MID deteriorated at 6 months from the start of radiotherapy compared with 14 whose MID improved. No significant association was observed between age, gender, smoking, alcohol status, exercise compliance, cisplatin, tumor site, stage, V35–V60 Gy or EUD with change in MID. A clinical outlier was excluded. Without the outlier (n = 19), a significant association was seen between mean dose and change in MID at 6 months for the ipsilateral block (p = .01), LP (p = .04) and M (p < .01). All patients where trismus deteriorated at 6 months received mean doses >40 Gy to the block. Conclusion: Higher mean radiation doses to the ipsilateral block, LP and M were significantly associated with deterioration in trismus. Limiting dose to these structures to ≤40 Gy for tumors not invading the masticatory muscles may improve treatment-related sequelae. The ipsilateral block, LP and M should be studied further as possible alternative avoidance structures in radiotherapy treatment planning.

PO-0733 PHASE II STUDY OF SORAFENIB IN ADVANCED SALIVARY ADENOID CYSTIC CARCINOMA: INITIAL OUTCOME AND TOXICITY

in 30 fractions over 6 weeks using the simultaneous integrated boost technique. Those with persistent or recurrent disease had imaging studies and clinical evaluation performed to determine the extent and sites of treatment failure. These were reconstructed on the planning CT images and analysed using the dose distribution of the IMRT plan. Results: 52 patients were included in the study. The median follow-up was 32.2 months. There were 7 isolated local failures, no regional recurrences and 1 with distant disease. None of the patients required post-treatment neck dissection. All local failures were in-field and occurred within the high-dose PTV. There were no marginal recurrences. There were no recurrences in the retropharyngeal or retrostyloid nodes, in the vicinity of the spared parotid gland or outside the treatment fields. Actuarial recurrence-free, diseasespecific and overall survival rates at 5 years were 83.9%, 85.9% and 75.7% respectively. Conclusions: The absence of marginal recurrences in our study validated our approach to IMRT target volume definition post-IC in locoregional advanced oropharyngeal SCC. We also observed no regional failure and a low incidence of distant relapse, suggesting that IC may provide additional benefit in improving nodal control and eradicating micrometastases.