Benefit of particle therapy in re-irradiation of head and neck patients. Results of a multicentric in silico ROCOCO trial.

BACKGROUND AND PURPOSE: In this multicentric in silico trial we compared photon, proton, and carbon-ion radiotherapy plans for re-irradiation of patients with squamous cell carcinoma of the head and neck (HNSCC) regarding dose to tumour and doses to surrounding organs at risk (OARs). MATERIAL AND METHODS: Twenty-five HNSCC patients with a second new or recurrent cancer after previous irradiation (70Gy) were included. Intensity-modulated proton therapy (IMPT) and ion therapy (IMIT) re-irradiation plans to a second subsequent dose of 70Gy were compared to photon therapy delivered with volumetric modulated arc therapy (VMAT). RESULTS: When comparing IMIT and IMPT to VMAT, the mean dose to all investigated 22 OARs was significantly reduced for IMIT and to 15 out of 22 OARs (68%) using IMPT. The maximum dose to 2% volume (D2) of the brainstem and spinal cord were significantly reduced using IMPT and IMIT compared to VMAT. The data are available on www.cancerdata.org. CONCLUSIONS: In this ROCOCO in silico trial, a reduction in mean dose to OARs was achieved using particle therapy compared to photons in the re-irradiation of HNSCC. There was a dosimetric benefit favouring carbon-ions above proton therapy. These dose reductions may potentially translate into lower severe complication rates related to the re-irradiation.

Quantification of renal and diaphragmatic interfractional motion in pediatric image-guided radiation therapy: A multicenter study.

BACKGROUND AND PURPOSE: To quantify renal and diaphragmatic interfractional motion in order to estimate systematic and random errors, and to investigate the correlation between interfractional motion and patient-specific factors. MATERIAL AND METHODS: We used 527 retrospective abdominal-thoracic cone beam CT scans of 39 childhood cancer patients (<18 years) to quantify renal motion relative to bony anatomy in the left-right (LR), cranio-caudal (CC) and anterior-posterior (AP) directions, and diaphragmatic motion in the CC direction only. Interfractional motion was quantified by distributions of systematic and random errors in each direction (standard deviations Σ and σ, respectively). Also, correlation between organ motion and height was analyzed. RESULTS: Inter-patient organ motion varied widely, with the largest movements in the CC direction. Values of Σ in LR, CC, and AP directions were 1.1, 3.8, 2.1 mm for the right, and 1.3, 3.0, 1.5 mm for the left kidney, respectively. The σ in these three directions was 1.1, 3.1, 1.7 mm for the right, and 1.2, 2.9, 2.1 mm for the left kidney, respectively. For the diaphragm we estimated Σ=5.2 mm and σ=4.0 mm. No correlations were found between organ motion and height. CONCLUSIONS: The large inter-patient organ motion variations and the lack of correlation between motion and patient-related factors, suggest that individualized margin approaches might be required.

Aggressive fibromatosis in the head and neck region: Benign tumor with often mutilating effects.

BACKGROUND: Aggressive fibromatosis (AF) or desmoid tumor of the head and neck region is a rare, usually unresectable, benign soft tissue tumor with locally aggressive behavior. METHODS AND RESULTS: A 31-year-old woman presented with a progressive trismus, a swelling in the retromandibular area, as well as loss of sensibility of the maxillary and mandibular branch of the trigeminal nerve. MRI of the head and neck revealed an infiltrative mass involving the masticator, parapharyngeal, and prevertebral and paravertebral space on the left with intracranial extension through the orbital fissure. After the fifth biopsy, 15 months after presentation, the diagnosis of AF was made. The tumor was unresectable, so intensity-modulated radiotherapy was given with curative intent using a total dose of 60 Gy in 30 fractions of 2 Gy. After 16 months, she showed progressive disease, for which tamoxifen 40 mg twice daily was started with a good response for 2 years. After that, she started with sorafinib, on which she has stable disease now. CONCLUSION: The often long delay in proper diagnosis and the treatment challenges of a desmoid tumor are illustrated in this case. Furthermore, this article reviews the literature concerning AF, especially of the head and neck region.

Trends in sinonasal cancer in The Netherlands: more squamous cell cancer, less adenocarcinoma. A population-based study 1973-2009.

BACKGROUND: Cancer of the nasal cavity or the paranasal sinuses (sinonasal cancer) is rare. Sinonasal cancer has been associated with various occupational risk factors such as exposure to dust of hard wood and leather. Also, a relationship with smoking habits has been suggested. We studied the long term trends in incidence to evaluate a putative effect of past preventive measures or changes in risk factors. DESIGN: A retrospective population-based descriptive study. OBJECTIVE: To interpret the long term trends in incidence of sinonasal cancer in The Netherlands. METHODS: Data of all 3329 patients >15 years registered during 1989-2009 by the Netherlands Cancer Registry (NCR) were analysed, by data of 447 patients registered by the Eindhoven Cancer Registry (ECR) during 1973-2009 were analysed separately. Information on patients and tumour characteristics was obtained from both registries. The incidence was calculated per 1,000,000 person years and standardised using the European Standard Population. RESULTS: Squamous cell carcinoma (SCC) was the most prominent histological type (48%), followed by adenocarcinoma (15%) and melanoma (8%). SCC was more frequently located in the nasal cavity or sinus maxillaris, but adenocarcinoma was more located in the ethmoid sinus. The male incidence increased during 1973-1995 with a peak of 15/1,000,000/year, decreasing since then to 11/1,000,000/year due to a declining incidence of both SCC and adenocarcinoma. In females the incidence remained stable around 5/1,000,000/year up to 2006 and increased to 7.5/1,000,000 in 2009 as a result of more SCC. The male/female ratio for SCC decreased from 2.7 to 2.0, and for adenocarcinoma from 3.4 to 2.8 since 1989. CONCLUSIONS: The higher incidence in males and the different trends in incidence in males and females may reflect differences in previous exposure to risk factors. Adenocarcinoma, related to occupational exposures, tend to decline. The trends in both male and female sinonasal SCC are comparable with the trends in lung cancer.

Optimal normal tissue sparing in craniospinal axis irradiation using IMRT with daily intrafractionally modulated junction(s).

PURPOSE: To develop a treatment technique for craniospinal irradiation using intensity-modulated radiotherapy (IMRT) with improved dose homogeneity at the field junction(s), increased target volume conformity, and minimized dose to the organs at risk (OARs). METHODS AND MATERIALS: Five patients with high-risk medulloblastoma underwent CT simulation in supine position. For each patient, an IMRT plan with daily intrafractionally modulated junction(s) was generated, as well as a treatment plan based on conventional three-dimensional planning (3DCRT). A dose of 39.6 Gy in 22 daily fractions of 1.8 Gy was prescribed. Dose-volume parameters for target volumes and OARs were compared for the two techniques. RESULTS: The maximum dose with IMRT was <107% in all patients. V<95 and V>107 were <1 cm3 for IMRT compared with 3-9 cm3 for the craniospinal and 26-43 cm3 for the spinal-spinal junction with 3DCRT. These observations corresponded with a lower homogeneity index and a higher conformity index for the spinal planning target volume with IMRT. IMRT provided considerable sparing of acute and late reacting tissues. V75 for the esophagus, gastroesophageal junction, and intestine was 81%, 81%, and 22% with 3DCRT versus 5%, 0%, and 1% with IMRT, respectively. V75 for the heart and thyroid was 42% and 32% vs. 0% with IMRT. CONCLUSION: IMRT with daily intrafractionally modulated junction results in a superior target coverage and junction homogeneity compared with 3DCRT. A significant dose reduction can be obtained for acute as well as late-reacting tissues.

Long-term outcome and morbidity after treatment with accelerated radiotherapy and weekly cisplatin for locally advanced head-and-neck cancer: results of a multidisciplinary late morbidity clinic.

PURPOSE: To evaluate the long-term outcome and morbidity after intensified treatment for locally advanced head-and-neck cancer. METHODS AND MATERIALS: Between May 2003 and December 2007, 77 patients with Stage III to IV head-and-neck cancer were treated with curative intent. Treatment consisted of accelerated radiotherapy to a dose of 68 Gy and concurrent cisplatin. Long-term survivors were invited to a multidisciplinary outpatient clinic for a comprehensive assessment of late morbidity with special emphasis on dysphagia, including radiological evaluation of swallowing function in all patients. RESULTS: Compliance with the treatment protocol was high, with 87% of the patients receiving at least five cycles of cisplatin and all but 1 patient completing the radiotherapy as planned. The 5-year actuarial disease-free survival and overall survival rates were 40% and 47%, respectively. Locoregional recurrence-free survival at 5 years was 61%. The 5-year actuarial rates of overall late Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) Grade 3 and Grade 4 toxicity were 52% and 25% respectively. Radiologic evaluation after a median follow-up of 44 months demonstrated impaired swallowing in 57% of the patients, including 23% with silent aspiration. Subjective assessment using a systematic scoring system indicated normalcy of diet in only 15.6% of the patients. CONCLUSION: This regimen of accelerated radiotherapy with weekly cisplatin produced favorable tumor control rates and survival rates while compliance was high. However, comprehensive assessment by a multidisciplinary team of medical and paramedical specialists revealed significant long-term morbidity in the majority of the patients, with dysphagia being a major concern.

(18)F-fluoro-L-thymidine-PET for the evaluation of primary brain tumours in children: a report of three cases.

BACKGROUND: F-fluoro-L-thymidine (FLT) has been shown to be a useful PET tracer in the evaluation of brain tumours in adults. No studies of this modality in children with brain tumours, however, have been published. OBJECTIVE: In this report three children with brain tumours are presented in which FLT-PET was used for different diagnostic purposes, in addition to imaging with MRI and F-fluorodeoxyglucose-PET. The first patient showed that FLT-PET could be helpful in differentiating between infection and malignancy. In the second patient FLT-PET was used for differentiating recurrent disease from radiotherapy effects. In the third patient, in which biopsy was not possible, FLT-PET was used for the characterization of the tumour. CONCLUSION: These patients show that FLT-PET might be a useful modality in different stages of the evaluation of primary brain tumours in children. However, further research to determine the clinical value, relative to MRI and fluorodeoxyglucose-PET, is required before routine implementation of FLT-PET.

[Diagnostic image; a man with severe radiation dermatitis]. / Een man met ernstige radiodermatitis.

A 51-year-old man with concurrent radiotherapy and cetuximab for tongue cancer developed a moist desquamation, spontaneous bleeding and necrosis of the skin after 42 Gy. The skin healed after cetuximab was discontinued.

The role of hypofractionation radiotherapy for diffuse intrinsic brainstem glioma in children: a pilot study.

PURPOSE: Most children with a diffuse intrinsic brainstem glioma will die within 1 year after diagnosis. To reduce patient burden, we investigated the feasibility of a radical hypofractionation radiotherapy schedule, given over 3 weeks, as an alternative to the standard regimen (30 fractions over 6 weeks). METHODS AND MATERIALS: Nine children, ages 3-13, were treated by 13 fractions of 3 Gy (n = 8) or 6 fractions of 5.5 Gy (n = 1) given over 3 weeks. All patients had symptoms for or=2 signs of the neurologic triad (long tract signs, ataxia, cranial nerve deficit). Bilateral involvement of the pons (n = 8), encasement of the basilar artery (n = 7) and extension into the cerebellar peduncle (n = 6) was visible on magnetic resonance imaging. RESULTS: Symptom improvement occurred in all patients within 2 weeks after start of radiotherapy. At a mean follow-up time of 15 months, 7 patients have died. Median time to progression and overall survival was 4.9 and 8.6 months, respectively. Median time to death after progression was 3.6 months. No Grade 3 or 4 toxicity was observed. In a recently published review of clinical trials, median time to progression, overall survival, and time between progression and death ranged from 5.0-8.8, 7.0-16, and 1.0-4.5 months, respectively, with more aggressive regimens. CONCLUSION: This radical hypofractionation radiotherapy regimen for children with diffuse intrinsic brainstem glioma is feasible and associated with no Grade 3 or 4 toxicities. With a minimal overall treatment time, it offers quick symptom relief and outcome results within the range of published data.

Malignant tumors of the nasal cavity and paranasal sinuses: long-term outcome and morbidity with emphasis on hypothalamic-pituitary deficiency.

PURPOSE: To evaluate the long-term outcome after surgery and radiotherapy for patients with sinonasal cancer and assess late toxicity, with special emphasis on hypothalamic-pituitary dysfunction. METHODS AND MATERIALS: A retrospective analysis of 168 patients treated for sinonasal cancer in a single institute between 1986 and 2006. A more detailed analysis was performed on a subgroup of 76 patients with adenocarcinoma or squamous cell carcinoma treated with curative intent. Long-term survivors were evaluated for late toxicity by a multidisciplinary team using the late effects of normal tissues (LENT SOMA) scoring system. Additional endocrinologic tests were performed for assessment of hypothalamic-pituitary function. RESULTS: Five-year actuarial local control and overall survival rates were 62% and 35% for all patients and 64% and 42% for the subgroup with squamous cell carcinoma and adenocarcinoma. In multivariate analysis, T stage was the only significant factor predicting local relapse (79% at 5 years for T1-T3 vs. 53% for T4; p = 0.006). Sinonasal mucosal melanomas had the highest rate of regional failure (33% at 5 years). Thirteen of 21 patients (62%) evaluated at the late morbidity clinic had hormonal disturbances, of whom 5 (24%) had definitive evidence of hypopituitarism with multiple hormonal deficiencies. CONCLUSION: Local failure is the dominant cause of treatment failure for patients with sinonasal cancer, with T4 stage the only independent predictor. Because of a high rate of radiation-induced hypopituitarism, we recommend endocrinologic surveillance for these patients.

Multiple complications due to osteoradionecrosis in a patient with thromboangiitis obliterans.

A case is presented of a patient with thromboangiitis obliterans (TAO) who developed severe necrosis of the intraoral soft tissues and maxillary and mandibular bone after radiotherapy for a cT2N0M0 squamous cell carcinoma of the soft palate. Multiple surgical procedures including partial resection of the mandible and maxilla and reconstruction of intraoral and extraoral defects with a pectoralis major myocutaneous flap and anterolateral thigh flap were performed with partial success. Although a causal relationship between TAO and the described complications cannot be verified, close monitoring of patients with TAO who are being treated with radiotherapy is advised.