Katrien Bonte

Maximum tolerated dose in a phase I trial on adaptive dose painting by numbers for head and neck cancer

PURPOSE To determine the maximum tolerated dose (MTD) in a phase I trial on adaptive dose-painting-by-numbers (DPBN) for non-metastatic head and neck cancer. MATERIALS AND METHODS Adaptive intensity-modulated radiotherapy was based on voxel intensity of pre-treatment and per-treatment [(18)F]fluoro-2-deoxy-d-glucose positron emission tomography ((18)F-FDG-PET) scans. Dose was escalated to a median total dose of 80.9 Gy in the high-dose clinical target volume (dose level I) and 85.9 Gy in the gross tumor volume (dose level II). The MTD would be reached, if ≥ 33% of patients developed any grade ≥ 4 toxicity (DLT) up to 3 months follow-up. RESULTS Between February 2007 and August 2009, seven patients at dose level I and 14 at dose level II were treated. All patients completed treatment without interruption. At a median follow-up for surviving patients of 38 (dose level I) and 22 months (dose level II) there was no grade ≥ 4 toxicity during treatment and follow-up but six cases of mucosal ulcers at latency of 4-10 months, of which five (36%) were observed at dose level II. Mucosal ulcers healed spontaneously in four patients. CONCLUSIONS Considering late mucosal ulcers as DLT, the MTD of a median dose of 80.9 Gy has been reached in our trial.

Intensity-Modulated Radiotherapy for Sinonasal Tumors: Ghent University Hospital Update

PURPOSE To report the long-term outcome of intensity-modulated radiotherapy (IMRT) for sinonasal tumors. METHODS AND MATERIALS Between July 1998 and November 2006, 84 patients with sinonasal tumors were treated with IMRT to a median dose of 70 Gy in 35 fractions. Of the 84 patients, 73 had a primary tumor and 11 had local recurrence. The tumor histologic type was adenocarcinoma in 54, squamous cell carcinoma in 17, esthesioneuroblastoma in 9, and adenoid cystic carcinoma in 4. The tumors were located in the ethmoid sinus in 47, maxillary sinus in 19, nasal cavity in 16, and multiple sites in 2. Postoperative IMRT was performed in 75 patients and 9 patients received primary IMRT. RESULTS The median follow-up of living patients was 40 months (range, 8-106). The 5-year local control, overall survival, disease-specific survival, disease-free survival, and freedom from distant metastasis rate was 70.7%, 58.5%, 67%, 59.3%, and 82.2%, respectively. No difference was found in local control and survival between patients with primary or recurrent tumors. On multivariate analysis, invasion of the cribriform plate was significantly associated with lower local control (p = 0.0001) and overall survival (p = 0.0001). Local and distant recurrence was detected in 19 and 10 patients, respectively. Radiation-induced blindness was not observed. One patient developed Grade 3 radiation-induced retinopathy and neovascular glaucoma. Nonocular late radiation-induced toxicity comprised complete lacrimal duct stenosis in 1 patient and brain necrosis in 3 patients. Osteoradionecrosis of the maxilla and brain necrosis were detected in 1 of the 5 reirradiated patients. CONCLUSION IMRT for sinonasal tumors provides low rates of radiation-induced toxicity without blindness with high local control and survival. IMRT could be considered as the treatment of choice.

Intensity-modulated radiotherapy for recurrent and second primary head and neck cancer in previously irradiated territory☆

PURPOSE To evaluate re-irradiation using IMRT for recurrent and second primary head and neck cancer in previously irradiated territory. MATERIALS AND METHODS Between 1997 and 2008, 84 patients with recurrent and second primary head and neck cancer were treated with IMRT to a median dose of 69 Gy. Median time interval between initial radiotherapy and re-irradiation was 49.5 (5.2-298.3) months. Salvage surgery preceded re-irradiation in 19 patients; 17 patients received concurrent chemotherapy. RESULTS Median follow-up of living patients was 19.8 (1.9-76.1) months. Five-year locoregional control and overall survival were 40% and 20%, respectively. Five-year disease-specific survival and disease-free survival were 29% and 15%, respectively. Stage T4 (p=0.015), time interval between initial treatment and re-irradiation (p=0.011) and hypopharyngeal cancer (p=0.013) were independent prognostic factors for worse overall survival in multivariate analysis. Twenty-six and 11 patients developed Grade 3 acute and late toxicity, respectively. No Grade 5 acute toxicity was encountered. There were 2 fatal vascular ruptures during follow-up. CONCLUSIONS High-dose IMRT for recurrent and second primary head and neck cancer in previously irradiated territory leads to approximately 20% long-term survival in a non-selected patient population. Identification of patients who would benefit most of curative IMRT is warranted.

Intensity-modulated radiotherapy for cervical lymph node metastases from unknown primary cancer

PURPOSE To compare the effectiveness of intensity-modulated radiotherapy (IMRT) and conventional (two-dimensional) radiotherapy in the treatment of cervical lymph node metastases from unknown primary cancer (UPC). METHODS AND MATERIALS Between February 2003 and September 2006, 23 patients with UPC of squamous cell carcinoma were treated with IMRT. Extended putative mucosal and bilateral nodal sites were irradiated to a median dose of 66 Gy. In 19 patients, IMRT was performed after lymph node dissection, and in 4 patients primary radiotherapy was given. The conventional radiotherapy group (historical control group) comprised 18 patients treated to a median dose of 66 Gy between August 1994 and October 2003. RESULTS Twenty patients completed treatment. As compared with conventional radiotherapy, the incidence of Grade 3 acute dysphagia was significantly lower in the IMRT group (4.5% vs. 50%, p = 0.003). By 6 months, Grade 3 xerostomia was detected in 11.8% patients in the IMRT group vs. 53.4% in the historical control group (p = 0.03). No Grade 3 dysphagia or skin fibrosis was observed after IMRT but these were noted after conventional radiotherapy (26.7%, p = 0.01) and 26.7%, p = 0.03) respectively). With median follow-up of living patients of 17 months, there was no emergence of primary cancer. One patient had persistent nodal disease and another had nodal relapse at 5 months. Distant metastases were detected in 4 patients. The 2-year overall survival and distant disease-free probability after IMRT did not differ significantly from those for conventional radiotherapy (74.8% vs. 61.1% and 76.3% vs. 68.4%, respectively). CONCLUSIONS Use of IMRT for UPC resulted in lower toxicity than conventional radiotherapy, and was similar in efficacy.

Postoperative radiotherapy for adenocarcinoma of the ethmoid sinuses: treatment results for 47 patients

PURPOSE Ethmoid sinus cancer is a rare malignancy. Treatment results are mostly reported together with other sinonasal tumors, grouping a wide range of different histologies and treatment approaches. This study reports on the treatment outcome of 47 patients diagnosed with adenocarcinoma of the ethmoid sinuses and treated with surgery and high-dose postoperative radiation therapy. METHODS AND MATERIALS Between September 1985 and October 2001, 51 patients with adenocarcinoma of the ethmoid sinuses were referred to the Ghent University Hospital. Four patients were treated with low-dose palliative radiation because of very extended inoperable disease or distant metastasis at the time of diagnosis. They were not included in this analysis. The other 47 patients, all staged as N0M0, were treated with surgery and postoperative high-dose radiation therapy. The median follow-up was 32 months. The T-stages were T1 for 2, T2 for 17, T3 for 11, and T4 for 17 patients. All 47 patients were staged as N0M0. RESULTS The 3-year, 5-year, and 7-year overall survival are respectively 71%, 60%, and 38%. The 3-year and 5-year disease-free survival are respectively 62% and 36%. The 3-year and 5-year disease-free survival for T1-T2 stages are respectively 87% and 55%, for T3 stages 57% and 28%, and for T4 stages 41% and 25%. The locoregional tumor control was 70% and 59% at respectively 3 and 5 years. Patients presenting with intracranial tumor invasion at the time of diagnosis relapsed within 7 months after the end of radiotherapy. Radiation-induced severe dry eye syndrome and optic neuropathy was observed in respectively 7 and 2 of the 47 cases. CONCLUSION Postoperative radiotherapy for adenocarcinoma of the ethmoid sinuses is associated with good local control rates. Crucial for a favorable prognosis is the absence of intracranial invasion. The rarity of these tumors makes it difficult to evaluate new therapeutic advances.

The nasality severity index: an objective measure of hypernasality based on a multiparameter approach - a pilot study

There is a need for an objective measure that describes normal resonance and resonance disorders. The current standard of practice has not led to mismanagement but a refined objective assessment protocol will benefit a more precise objective assessment of velopharyngeal disorders. The purpose of the present study is to construct a nasality severity index (NSI) that reflects the multidimensional nature of resonance. Objective and subjective assessment techniques were used to determine the nasalance, the nasality and aerodynamic capacities in 21 children with cleft palate and a control group of 25 children without cleft palate. Stepwise logistic regression was used to determine the optimal index. The NSI consists of a linear combination of 4 variables, where each variable has a different weight. The equation is: NSI = –60.69 – (3.24 × percent oral text) – (13.39 × Glätzel value /a/) + [0.244 × maximum duration time (seconds)] – (0.558 × % /a/) + (3.38 × percent oronasal text). NSI sensitivity is 88% and specificity is 95%. Daily clinical use of the NSI has shown it to be an efficient and practical tool to describe the presence of hypernasality. Three distinct follow-up cases are presented to illustrate the impact of a surgical technique, the use of a speech bulb and velopharyngeal biofeedback training on NSI. The implementation of the NSI may help clinicians to quantitatively assess the severity of nasality disorders beside the perceptual judgments.

Diagnosis, Management and Surgical Treatment of Non-Tuberculous Mycobacterial Head and Neck Infection in Children

The aim of this study was to present our experience with the clinical characteristics of non-tuberculous mycobacterial (NTM) head and neck lymph node infections, the use of modern diagnostic tools and the appropriate therapeutic measures. We have reviewed the cases of 14 Caucasian children with NTM head and neck lymphadenitis who were treated in our clinic in the last 5 years. Three of the patients were male and 11 were female. Their age ranged from 15 to 98 months (mean age 45.7 ± 21.76 months). Cervical lymph nodes were involved in all of our cases, while the submandibular region was found to be the area mostly affected. Overlying skin was involved in 7 cases. Diagnosis was based on intradermal skin testing with specific antigens for atypical mycobacteria, histological examination and specimen culture. Skin tests were positive for NTM in all of the patients with a predilection for Mycobacteriumavium complex. The diagnosis was confirmed by histological examination in 13 cases. Specimen culture was positive in 9 cases, most of them growing M. avium-intracellulare complex. Treatment included complete surgical excision of the affected lymph nodes and the overlying skin, as well as functional neck dissection when required. A second procedure was performed in 2 patients. Successful evaluation of NTM infections of the head and neck lymph nodes should include a detailed history, thorough physical examination and specific laboratory investigations. The treatment of choice is complete surgical excision of all affected tissue.

Superficial parotidectomy via facelift incision.

The stigma of a visually prominent facial scar following parotid surgery can be distressing to a young patient. The surgical technique of parotidectomy via a facelift incision is described and evaluated. Thirty patients with a benign lesion of the parotid gland underwent a partial superficial parotidectomy via a modified facelift incision. After operation, all patients had excellent cosmesis and complete function of the facial nerve. The facelift incision provides adequate exposure of the parotid gland for (partial) superficial parotidectomy. It can be offered as an alternative to a select group of patients who present with a small, mobile tumor in the tail of the parotid gland and an explicit request for an invisible postoperative scar.

High-dose reirradiation with intensity-modulated radiotherapy for recurrent head-and-neck cancer: Disease control, survival and toxicity

PURPOSE To evaluate disease control, survival and severe late toxicity after high-dose fractionated reirradiation using intensity-modulated radiotherapy (IMRT) for recurrent head-and-neck cancer. MATERIALS AND METHODS Sixty consecutive patients were reirradiated with IMRT between 1997 and 2011. The median prescribed dose was 70 Gy in 35 daily fractions until 2004 and 69.12 Gy in 32 daily fractions thereafter. The median cumulative dose was 132 Gy. Sixty-seven percent of patients had non-metastatic stage IV disease. Surgery prior to reirradiation and concomitant systemic therapy was performed in 13 (22%) and 20 (33%) patients, respectively. RESULTS Median follow-up in living patients was 18.5 months. Actuarial 1-, 2- and 5-year locoregional control was 64%, 48% and 32%, respectively. Median overall (OS) and disease-free survival was 9.6 and 6.7 months, respectively. Actuarial 1-, 2- and 5-year OS was 44%, 32% and 22%, respectively. Seventeen (27%) and 2 (3%) patients had grade 3 and 4 acute toxicity, respectively. Cumulative incidence of late grade≥3 toxicity was 23%, 27% and 66% at 1, 2 and 5 years, respectively. In 4 patients, death was attributed to toxicity: fatal bleeding (n=2), aspiration pneumonia (n=1) and skin necrosis (n=1). CONCLUSIONS High-dose fractionated reirradiation with IMRT offers 5-year disease control and OS in recurrent head-and-neck cancer for 1/3 and 1/4 patients, respectively. Severe late toxicity after 1-2 and 5 years occurs in 1/4 and 2/3 patients, respectively.

Regional relapse after intensity-modulated radiotherapy for head-and-neck cancer.

PURPOSE To evaluate the regional relapse rate in the elective neck using intensity-modulated radiotherapy (IMRT) for head-and-neck cancer. METHODS AND MATERIALS We retrospectively analyzed the data from 285 patients treated with IMRT between 2000 and 2008. The median dose prescription to the primary tumor and involved lymph nodes was 69 Gy in 32 fractions. The elective neck was treated simultaneously according to Protocol 1 (multiple dose prescription levels of 56-69 Gy; 2-Gy normalized isoeffective dose, 51-70 Gy; 222 patients) or Protocol 2 (one dose prescription level of 56 Gy; 2-Gy normalized isoeffective dose, 51 Gy; 63 patients). Primary surgery or lymph node dissection was performed before IMRT in 72 (25%) and 157 (55%) patients, respectively. Also, 92 patients (32%) received concomitant chemotherapy. The median follow-up of living patients was 27.4 months (range, 0.3-99). RESULTS Regional, local, and distant relapse were observed in 16 (5.6%), 35 (12.3%), and 47 (16.5%) patients, respectively. The 2- and 5-year rate of regional relapse was 7% and 10%, respectively, with a trend favoring Protocol 2 (p = 0.06). Seven isolated regional relapses were detected at a median follow-up of 7.3 months in patients treated with Protocol 1 and none in those treated with Protocol 2. Percutaneous gastrostomy was required more frequently in patients who received Protocol 1 (p = 0.079). CONCLUSION Isolated regional relapse is rare after IMRT for head-and-neck cancer. Elective neck node doses >51 Gy for a 2-Gy normalized isoeffective dose do not seem to improve regional control.