HPV-related oropharyngeal cancers in Flanders (Belgium): a multicenter study.

INTRODUCTION: Human papilloma virus (HPV) was recently reported to play a major role in oropharyngeal carcinoma. Large geographical differences in the disease prevalence have been described. Until now, no data have been reported for Flanders (Belgium). METHODS: A multicenter cooperative study was undertaken at the radiation-oncology departments of Flemish universities. Tumor blocks from patients diagnosed with oropharyngeal carcinoma between 2000 and 2010 were tested for HPV at a single center. Patients' characteristics, treatments, and follow-up data were recorded from medical files. Age standardized incidence rates of oropharyngeal carcinoma were collected from the Belgian Cancer Registry. RESULTS AND CONCLUSIONS: The incidence of oropharyngeal carcinoma has increased in males and females. Tissues were collected from 264 patients and the HPV status could be defined in 249 of them. The prevalence of HPV(+) oropharyngeal carcinoma was 24.78% (19.93-30.36%). In our cohort, HPV(+) tumors occurred in patients with more advanced tumor stages (p < 0.05), who smoked less (p < 0.05), consumed less alcohol (p < 0.05), had a tonsillar/base of tongue sublocalization (p < 0.05), and were older (p < 0.05). After radiotherapy, locoregional control and disease free survival were significantly better for patients with HPV(+) status (p < 0.05) in univariate analysis. HPV status remained a strong predictor of better locoregional control after multivariate analysis. We found that concurrent chemotherapy had an equal benefit for locoregional control in both HPV(+) and HPV(-) patients.

Reference dosimetry for helical tomotherapy: practical implementation and a multicenter validation.

PURPOSE: The aim of this study was to implement a protocol for reference dosimetry in tomotherapy and to validate the beam output measurements with an independent dosimetry system. METHODS: Beam output was measured at the reference depth of 10 cm in water for the following three cases: (1) a 5 × 10 cm(2) static machine specific reference field (MSR), (2) a rotational 5 × 10 cm(2) field without modulation and no tabletop in the beam, (3) a plan class specific reference (PCSR) field defined as a rotational homogeneous dose delivery to a cylindrical shaped target volume: plan with modulation and table-top movement. The formalism for reference dosimetry of small and nonstandard fields [Med.Phys.35: 5179-5186, 2008] and QA recommendations [Med.Phys.37: 4817-4853, 2010] were adopted in the dose measurement protocol. All ionization chamber measurements were verified independently using alanine∕EPR dosimetry. As a pilot study, the beam output was measured on tomotherapy Hi-art systems at three other centers and directly compared to the centers specifications and to alanine dosimetry. RESULTS: For the four centers, the mean static output at a depth of 10 cm in water and SAD = 85 cm, measured with an A1SL chamber following the TG-148 report was 6.238 Gy∕min ± 0.058 (1 SD); the rotational output was 6.255 Gy∕min ± 0.069 (1 SD). The dose stated by the center was found in good agreement with the measurements of the visiting team: D(center)∕D(visit) = 1.000 ± 0.003 (1 SD). The A1SL chamber measurements were all in good agreement with Alanine∕EPR dosimetry. Going from the static reference field to the rotational ∕ non modulated field the dose rate remains constant within 0.2% except for one center where a deviation of 1.3% was detected. CONCLUSIONS: Following the TG-148 report, beam output measurements in water at the reference depth using a local protocol, as developed at different centers, was verified. The measurements were found in good agreement with alanine∕EPR dosimetry. The presented methodology may provide a good concept for reference dosimetry.

Experimental determination of the energy response of alanine pellets in the high dose rate 192Ir spectrum.

An experimental determination of the energy correction factor for alanine/paraffin pellets in the 192Ir spectrum at varying distances from the source is presented. Alanine dosimeters were irradiated in water under full scatter conditions with a high dose rate (HDR) 192Ir source (Flexisource), using a dedicated holder. Up to six line sources (catheters) fit in a regular pattern at fixed radial distances from the holder axis, the alanine detector being placed at the centre of the holder. The HDR source was stepping every 0.5 cm within a trocar needle within ± 3.0 cm around the medial plane through the detector in order to achieve dose homogeneity within the detector volume. The energy correction factor of alanine/paraffin pellets in 192Ir relative to 60Co was experimentally determined as the inverse ratio of the dose to water measured in water around the 192Ir source to the dose to water calculated in water using the TG-43 formalism. The pellets were read out with a Bruker EMX(micro) spectrometer (X-band). The amplitude of the central line in the alanine absorption spectrum from pellets irradiated within the 192Ir spectrum was directly compared with the amplitude from 60Co-irradiated pellets. The energy correction factors of Harwell pellets irradiated in the 192Ir spectrum are 1.029 ± 0.02, 1.027 ± 0.02 and 1.045 ± 0.02 at a mean weighted source­detector distance of 2.0, 2.9 and 5.3 cm, respectively. The experimentally obtained values for the energy response are 1.3% lower compared to the theoretical values for radial distances smaller than 3 cm.

Intensity-modulated radiotherapy in patients with head and neck cancer: a European single-centre experience.

OBJECTIVE: The purpose of this study was to analyse retrospectively the intensity-modulated radiotherapy (IMRT) results in patients with head and neck cancer (HNC) treated between November 2003 and June 2007. METHODS: Patients with early and locoregionally advanced HNC were treated with inverse-planned step-and-shoot IMRT. The prescribed dose varied from 66 Gy to 70 Gy in those receiving IMRT as definitive treatment and from 60 Gy to 70 Gy in the post-operative setting. IMRT was given alone, after induction chemotherapy (ICT), with concomitant chemotherapy (CRT) or with both. Acute and late toxicities are reported; locoregional control (LRC), locoregional relapse-free survival (LRRFS) and overall survival (OS) were calculated from the start of radiation. RESULTS: IMRT was used in 78 patients (48 as definitive treatment, 30 post-operatively), of whom 20 also received ICT and 35 CRT. Three patients stopped IMRT early, one for toxicity (mucosa). Acute toxicity scoring revealed 5 cases (6%) of severe skin toxicity and 65 cases (83%) of severe mucosal toxicity. After a median follow-up of 18.7 months, late toxicities included xerostomia (44%), loss of taste (14%) and fibrosis of the neck (9%). 16 patients had died, of whom 10 due to tumour recurrence/progression and 2 due to treatment (but not IMRT related). The LRC, LRRFS and OS at 3 years are 66.1%, 48.5% and 60.3% in the definitive IMRT group and 85.4%, 82.5% and 85.9% in the post-operative setting, respectively. CONCLUSION: We consider IMRT for locoregional HNC feasible not only as a single modality but also after surgery, after induction chemotherapy and concurrently with chemotherapy.

Difluorodeoxyuridine plasma concentrations after low-dose gemcitabine during chemoradiation in head and neck cancer patients.

PURPOSE: The aim of this study was to investigate whether relevant plasma levels of dFdU could be detected during concurrent chemoradiation (CRT) with low doses of dFdC administered in patients with head and neck cancer and to assess the toxicity related to dose. METHODS: dFdC was administered at doses of 5 mg/m² twice weekly or 10, 50, or 100 mg/m² weekly. Plasma concentrations of dFdU were determined daily for 7 days after the first administration and before each administration, thereafter. A high-performance liquid chromatographic method was used. During CRT, skin and mucosal toxicity were scored weekly according to the RTOG toxicity scoring system. RESULTS: Eight patients were sampled at the 10-50 mg/m² dose and nine at the 5-100 mg/m² dose. dFdU levels were in the micromolar range, inducing RS in vitro. There was a strong correlation between the area under the curve of dFdU and the dose of dFdC (r = 0.803, P < 0.001) and a weak correlation between trough concentrations and total dose of dFdC (r = 0.408, P = 0.017). Duration of severe mucositis correlated with dFdC dose. CONCLUSIONS: During CRT with 10-100 mg/m(2) of dFdC weekly or 5 mg/m(2) twice weekly, dFdU remains detectable at potentially radiosensitizing concentrations.

Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323).

BACKGROUND: The EORTC 24971/TAX 323, a phase III study of 358 patients with unresectable locoregionally advanced squamous cell carcinoma of the head and neck, showed an improved progression-free and overall survival (OS) with less toxicity when docetaxel (T) was added to cisplatin and 5-fluorouracil (PF) for induction and given before radiotherapy (RT). The impact of the addition of docetaxel on patients' health-related quality of life (HRQOL) and symptoms was investigated. METHODS: HRQOL was assessed at baseline, at end of cycle 2, and 4, 6, and 9 months after completion of RT using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC QLQ Head and Neck Cancer-Specific Module (EORTC QLQ-H&N35). The primary HRQOL scale was global HRQOL per protocol. RESULTS: Compliance to HRQOL assessments was 97% at baseline, but dropped to 54% by 6 months. Data were analysed up to 6 months. There was a trend towards improved global HRQOL during the treatment period. At 6 months after the end of RT, global HRQOL was higher in the TPF arm than in the PF arm, but the low compliance does not allow to draw definitive conclusions. Swallowing and coughing problems decreased more in the TPF arm than in the PF arm at the end of cycle 2, but to a limited extent. CONCLUSION: Induction chemotherapy with TPF before RT not only improves survival and reduces toxicity compared with PF but also seems to improve global HRQOL in a more sustainable manner.

Alanine/EPR dosimetry applied to the verification of a total body irradiation protocol and treatment planning dose calculation using a humanoid phantom.

PURPOSE: To avoid complications in total body irradiation (TBI), it is important to achieve a homogeneous dose distribution throughout the body and to deliver a correct dose to the lung which is an organ at risk. The purpose of this work was to validate the TBI dose protocol and to check the accuracy of the 3D dose calculations of the treatment planning system. METHODS: Dosimetry based on alanine/electron paramagnetic resonance (EPR) was used to measure dose at numerous locations within an anthropomorphic phantom (Alderson) that was irradiated in a clinical TBI beam setup. The alanine EPR dosimetry system was calibrated against water calorimetry in a Co-60 beam and the absorbed dose was determined by the use of "dose-normalized amplitudes" A(D). The dose rate of the TBI beam was checked against a Farmer ionization chamber. The phantom measurements were compared to 3D dose calculations from a treatment planning system (Pinnacle) modeled for standard dose calculations. RESULTS: Alanine dosimetry allowed accurate measurements which were in accordance with ionization chamber measurements. The combined relative standard measurement uncertainty in the Alderson phantom was U(r)(A(D))=0.6%. The humanoid phantom was irradiated to a reference dose of 10 Gy, limiting the lung dose to 7.5 Gy. The ratio of the average measured dose midplane in the craniocaudal direction to the reference dose was 1.001 with a spread of +/- 4.7% (1 sd). Dose to the lung was measured in 26 locations and found, in average, 1.8% lower than expected. Lung dose was homogeneous in the ventral-dorsal direction but a dose gradient of 0.10 Gy cm(-1) was observed in the craniocaudal direction midline within the lung lobe. 3D dose calculations (Pinnacle) were found, in average, 2% lower compared to dose measurements on the body axis and 3% lower for the lungs. CONCLUSIONS: The alanine/EPR dosimetry system allowed accurate dose measurements which enabled the authors to validate their TBI dose protocol. Dose calculations based on a collapsed cone convolution dose algorithm modeled for regular treatments are accurate within 3% and can further be improved when the algorithm is modeled for TBI.

Phase II feasibility study of concurrent radiotherapy and gemcitabine in chemonaive patients with squamous cell carcinoma of the head and neck: long-term follow up data.

BACKGROUND: Radiotherapy (RT) with concurrent chemotherapy is the current standard of care for patients with unresectable locally advanced squamous cell carcinoma of the head and neck (SCCHN). Gemcitabine (GEM) is a potent radiosensitizer and in addition has activity as an anticancer agent in SCCHN. PATIENTS AND METHODS: Twenty-six patients with locally far advanced SCCHN were enrolled in a chemoradiation feasibility study between November 1998 and September 2003. Use was made of conventionally fractionated RT and GEM 100 mg/m(2), which was given within 2 h prior to radiotherapy on a weekly basis starting on day 1 of RT. Response was assessed according to WHO criteria, toxicity according to NCI-CTC version 2. RESULTS: The patients received a median of 7 (2-8) weekly cycles of gemcitabine and a median cumulative RT dose of 70 Gy (66-84.75). Hematologic toxicity was mild, but non-hematologic toxicity was severe: grade 3-4 stomatitis occurred in 85% of patients, dermatitis in 69%, pharyngitis/esophagitis in 81% and 80% of the patients needed a feeding tube during treatment. All 22 evaluable patients responded (50% complete, 50% partial). Median follow up of the surviving patients is 46 months. Median disease-free and overall survival is 13 months and 19 months, respectively; 27% of the patients are alive without evidence of recurrence beyond 3 years. CONCLUSIONS: Conventionally fractionated RT in combination with GEM 100 mg/m(2) weekly is feasible and highly active in the treatment of locally advanced SCCHN. In particular, long-term local control rate is promising. Acute mucosal toxicities are significant but manageable. Long-term toxicity interferes with normal food intake.

Docetaxel, cisplatin and 5-fluorouracil in patients with locally advanced unresectable head and neck cancer: a phase I-II feasibility study.

PURPOSE: To determine the safety profile and activity of the combination of docetaxel, cisplatin and 5-fluorouracil (5-FU) in chemotherapy-naive patients with squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with locally advanced unresectable SCCHN were treated with docetaxel and cisplatin both as a 1-h infusion on day 1 followed by a continuous infusion of 5-FU for 5 days. Cycles were planned every 3 weeks up to four cycles, whereafter the patients were treated with locoregional radiotherapy. Two dose levels were studied. Doses in level I were 75 mg/m(2) of docetaxel, 75 mg/m(2) of cisplatin and 750 mg/m(2)/day of 5-FU; in level II the cisplatin dose was escalated to 100 mg/m(2). Following chemotherapy, all patients were to receive curative radiotherapy according to the standards in the different institutions. RESULTS: Twenty-five patients were treated at dose level I with 86 cycles (median four; range one to four), and 23 at dose level II with 84 cycles (median four; range two to four). The median relative dose intensity was 0.99 (range 0.86-1.04) at level I and 0.94 (range 0.79-1.02) at level II. The response rate in the intention-to-treat population was 64% [95% confidence interval (CI) 42.5% to 82%] in level I and 78.3% (95% CI 56.3% to 92.5%) in level II; all were partial responses. The maximum tolerated dose was reached at level II with renal toxicity, nausea, stomatitis and thrombocytopenia as principal dose-limiting toxicities. The median survival of the 48 patients was 18.5 months. The survival at 12, 18, 24 and 30 months was 69, 54, 41 and 31%, respectively. CONCLUSIONS: The combination of docetaxel, cisplatin and 5-FU associated with prophylactic ciprofloxacin is feasible and active in patients with SCCHN. Dose level I is recommended for phase III testing.

Surgical management of stage I and II vulvar cancer: the role of the sentinel node biopsy. Review of literature.

Recognition of the psychosexual consequences of radical vulvectomy and better understanding of the lymphatic drainage and histopathologic features of vulvar cancer have led to a more conservative surgical approach, especially in patients with early-stage disease. Every patient with early vulvar cancer should be managed individually and the risk of conservative therapy balanced against the dangers and advantages of more radical therapy. The results of the sentinel node (SN) procedure in early cancer of the vulva are encouraging, and it might be possible in the near future to avoid the morbidity of inguino-femoral lymphadenectomy. This article reviews surgical management of early vulvar cancer and the place of SN biopsy.

Does sucralfate reduce the acute side-effects in head and neck cancer treated with radiotherapy? A double-blind randomized trial.

BACKGROUND AND PURPOSE: We evaluated sucralfate, well-known in the treatment of gastric ulcers, in relation to its possible reduction of radiation-induced acute complications in the treatment of head and neck cancers. MATERIALS AND METHODS: One hundred two patients were randomized in a double-blind placebo-controlled prospective setting. All patients were treated to a minimum dose of 55 Gy in 5 weeks. Oral intake of sucralfate was started at the beginning of radiotherapy and continued during the whole treatment at a dose of 1 g six times a day. All patients were scored according to a scoring system developed in our department. Weight was checked once a week. RESULTS: Comparing the time course of the mean scores for subjective intolerance, mucositis, dysphagia, dermatitis and nausea, no statistically significant differences between the two treatment arms (sucralfate, n = 38; placebo, n = 45) were observed. The mean weight loss in the sucralfate arm was 1.6 +/- 3.4 kg while it was 1.3 +/- 2.0 kg in the placebo arm. Apart from gastrointestinal upset, the administration of sucralfate did not cause any side-effects. CONCLUSION: This trial produced no clinical evidence indicating that the oral intake of sucralfate reduces the acute radiation-induced side-effects. Therefore, we do not recommend the prophylactic use of sucralfate in patients with head and neck cancer treated by radiotherapy.

Obstructive hydrocephalus as complication of a giant nonfunctioning pituitary adenoma: therapeutical approach.

We report the case of a 61-year-old male presenting with a giant nonfunctioning pituitary tumour extending into the third ventricle and thereby causing obstructive hydrocephalus. The main complaints consisted of disturbed vision and somnolence. The patient was initially treated by ventriculoperitoneal shunting, with immediate improvement of his mental status. Transcranial resection of the tumour was performed shortly thereafter, but only a limited part of the tumour could safely be removed. By immunohistochemistry the diagnosis of gonadotroph adenoma was made. After the operation, the patient's vision deteriorated temporarily. Because of the risk of further damage to the optic nerve, radiation therapy was postponed. Instead, treatment with the long-acting dopamine agonist cabergoline was instituted, which resulted in a gradual improvement of vision. Two years later a transsphenoidal operation was performed because of acute worsening of the visual fields due to central tumour necrosis with slight volume expansion. Vision improved considerably after surgery. Radiotherapy is scheduled in the near future. This case is an illustration of the complications of giant nonfunctioning pituitary adenomas. The therapeutical approach to obstructive hydrocephalus in these instances is reviewed.

Surgery or radiation: is there really a choice for early prostate cancer.

One of the most difficult tasks for the practicing urologist is to counsel the patient in a decision for the optimal treatment for his localized prostate cancer. After providing the patient with contemporary and unbiased information and data, it is important to find the preferred treatment based on his age, the medical realities and, last but not least, the patient's personal preference. Radical prostatectomy, radiotherapy and observation are standard treatment options. TRUS-guided brachytherapy and cryosurgery are considered investigational treatment options since follow-up is inadequate to provide sufficiently precise outcome estimates. The literature does not provide clear-cut evidence for the superiority of any one treatment. The patient most likely to benefit from radical prostatectomy would have a relatively long life expectancy, no significant surgical risk factors and a preference to undergo surgery. The major advantage of radical prostatectomy is its potential for total removal of the cancer and cure in properly selected patients. Potential harm includes urinary incontinence and impotence. The patient most likely to benefit from radiation therapy would have a relatively long life expectancy, no significant risk factors for radiation toxicity and a preference for radiotherapy. The advantages of radiotherapy are that it has a potential for cure and it is well tolerated in the majority of men when the modern techniques are used. Potential harm includes radiation cystitis, proctitis and impotence, persisting severe complications are only seen in 1% of patients. The patient most likely to benefit from surveillance are those with a shorter life expectancy and/or a low grade tumour. Benefits are lack of treatment related morbidity with only marginal compromise of disease-specific survival at 5-10 years follow-up.

Merkel cell carcinoma: the use of surgery and radiotherapy for locoregional control.

Merkel cell tumours are rare skin cancers with an unpredictable clinical course. Correct diagnosis requiring immunohistochemical staining is essential since the treatment differs entirely from that of basalioma. Locally limited disease as well as rapidly fatal course have been observed. In a small series of 5 patients and from literature data, surgery continued with radiotherapy for locoregional control is advocated as optimal approach since this type of tumour can behave differently compared to basal cell carcinomas.

The effect of carbon fibre inserts on the build-up and attenuation of high energy photon beams.

BACKGROUND AND PURPOSE: The use of new materials in radiotherapy requires an investigation of the effects of these materials on the relevant beam parameters. The high strength and low density of carbon fibre suggest an excellent material for table inserts with minimal attenuation, without changing the skin sparing effect in the build-up zone. MATERIALS AND METHODS: In this paper three different carbon fibre plates and two conventionally table top materials are studied in Co-60, 6 MV and 23 MV photon beams. RESULTS AND CONCLUSIONS: From depth dose measurements it is clear that the dose in the build-up zone is influenced in the qualities of the beams. The mutual differences for the three carbon plates are minimal. For Co-60 the depth of the maximum dose is decreased by carbon from 5 to 2 mm and the surface dose is increased from 18 to 76%. For 6 and 23 MV the surface dose is increased from 21 to 52% and 20 to 32%, respectively, as well as the dose in the build-up region. A transmission of 99% was measured for two carbon plates out of three in Co-60 and for one out of three in 6 MV.

Deep cerebral invasion by basal cell carcinoma of the scalp.

We report recurrent basal cell carcinoma of the scalp with deep cerebral invasion in an 82-year-old man. Plain films and CT showed extensive, full thickness, skull destruction at the vertex. Gadolinium-enhanced MRI revealed neoplastic invasion of the meninges and left cerebral hemisphere, down to the lateral ventricle. We postulate that tumour extended into the brain along perivascular spaces of transcerebral vessels. This hypothesis is supported by the cleft-like contrast enhancement on MRI.

Palliative effectiveness of radiation therapy in the treatment of superior vena cava syndrome.

A study was made of 34 patients concerning the palliation effect of radiation therapy in the treatment of superior vena cava syndrome (SVCS). They were seen between 1986-1993, at the Department of Radiotherapy in Middelheim General Hospital, Belgium, Antwerp. All patients had a syndrome of superior vena cava obstruction secondary to malignancy. The histologic diagnosis delivered an equal distribution of small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). All patients with a SCLC received chemotherapy as initial treatment, but showed no response, relapse or evolution during treatment. Each treatment began with rapid-high dose irradiation, to continue after re-evaluation with rapid high-dose in cases of poor response or with the conventional fractionation of 2 Gy daily in patients showing good relief of symptoms. The initial rapid-high dose schedules depended on the performance status of the patients. Seventy-six percent of the patients with NSCLC showed good relief of their symptoms. It was very unexpected but the majority of NSCLC patients responded more quickly than SCLC patients, within three days after initiating treatment. In SCLC, 94% of the patients responded up until death. The palliation index defined as the ratio of the symptom-free period on the total survival which is 1 in ideal circumstances, was 0.55 in NSCLC and 0.90 in SCLC. In this last group, death was mainly due to disease progression in distant sites.

Metastases seen on SPECT imaging despite a normal planar bone scan.

Although bone scintigraphy is an extremely sensitive method for the detection of focal bone disease, small lesions below the resolution of planar imaging may be missed. This is a report of a patient with carcinoma of the breast who showed tumor progression 1 year after initial treatment. Complete evaluation was performed in order to detect the origin of increased level of a tumor marker. Although planar bone scintigraphy could not demonstrate any lesion in the spine, multiple metastases were detected in the lumbar and the thoracic spines on SPECT imaging. Only some of these lesions were seen with MRI. Repeat planar bone imaging 6 weeks later showed multiple bone lesions in the lumbar and thoracic areas.

[Preoperative radiotherapy and medial maxillectomy. Treatment concept for carcinomas of the nasal cavity and paranasal sinuses]. / Preoperatieve radiotherapie en mediale maxillectomie. Behandelingsconcept voor carcinoma's van neusholte en paranasale sinussen.

Multimodal treatment modality for paranasal sinus malignancies is discussed. Therapy consists in pre-operative 50 Gy radiotherapy delivered over 5 weeks, followed three weeks later by a medial maxillectomy. Although local control rate is improved through this treatment, an increase in late metastases is observed.