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Background and purpose: Dysphagia is a serious complaint but frequently underreported. This paper assesses for oropharyngeal cancer (OPC) the relationship between the dose received by the swallowing structures, and the findings of a fiberoptic endoscopic evaluation of the swallowing process (FEES). Materials and methods: Between 2000 and 2005, 60 of 67 OPC patients local-regionally NED for at least one year following treatment responded to three types of QoL questionnaires; i.e. Performance Status Scales, EORTC H&N35, and M.D. Anderson Dysphagia Inventory. Twenty-four patients agreed to the FEES procedure. The main swallowing muscles were delineated, with the mean dose per muscle calculated using the original 3D CT-based treatment plans. Regression analysis was performed between FEES variables and the doses in the different swallowing muscles and the dysphagia related questionnaires. Results: A significant relationship was found between the results of FEES and the mean dose in the superior constrictor muscle (SCM). Some of the subjective dysphagia complaints were significantly correlated with the FEES variables in this retrospectively study. Conclusion: A higher dose in the SCM generally results in worsening of the findings obtained by the FEES examination. (C) 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 89 (2008) 57-63.

HDR monotherapy for prostate cancer consists of four fractions. The first fraction is delivered with online TRUS-based treatment planning. For the last three fractions the treatment plan is based on a CT-scan acquired in between fractions 1 and 2. The patient position (high lithotomy, rectal US probe) during TRUS-guided catheter implantation and first fraction differs from the patient position in the CT-scan and the remaining three fractions (lowered legs, no TRUS probe). This study describes the effect of posture changes on dose distributions when a plan designed for the TRUS anatomy is applied to the CT-scan anatomy. The aim is to quantify dosimetrical errors that would result from skipping the use of a planning CT-scan, and rely for all fractions on the TRUS plan. Such a procedure would substantially reduce the involved workload, and would increase patient comfort. For three prostate cancer patients, images were acquired during TRUS-guided catheter implantation. Furthermore, a CT-scan (no US probe in rectum, different position of legs) was acquired and matched with the TRUS set. On both TRUS and CT, prostate, urethra and rectum were delineated and all catheters were traced. For each patient, an optimized treatment plan was designed using TRUS images and contours. Catheters with obtained dwell positions of the TRUS plan were transferred individually to the catheter positions in the CT. Changes in dose distribution due to relocation of catheters were evaluated using DVHs. For all patients the dose distributions changed significantly due to rearrangement of the catheters, having most impact on the urethra (maximum observed change: 32% volume receiving >= 120% of the prescribed dose) and a reduction of PTV coverage (6-28%). Implant deformation when changing from TRUS patient set-up to CT set-up affected negatively the quality of optimized treatment plans. Inclusion of more patients in this study was planned, but because of the observed strong negative effects it is already concluded that the TRUS plan cannot be used for the last three fractions with a deviating patient set-up. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

Purpose: To assess the relationship for oropharyngeal (OP) cancer and nasopharyngeal (NP) cancer between the dose received by the swallowing structures and the dysphagia related quality of life (QoL). Methods and Materials: Between 2000 and 2005, 85 OP and 47 NP cancer patients were treated by radiation therapy. After 46 Gy, OP cancer is boosted by intensity-modulated radiation therapy (IMRT), brachytherapy (BT), or frameless stereotactic radiation/cyberknife (CBK). After 46 Gy, the NP cancer was boosted with parallel-opposed fields or IMRT to a total dose of 70 Gy; subsequently, a second boost was given by either BT (11 Gy) or stereotactic radiation (SRT)/CBK (11.2 Gy). Sixty OP and 21 NP cancer patients responded to functional and QoL questionnaires (i.e., the Performance Status Scales, European Organization for Research and Treatment of Cancer H&N35, and M.D. Anderson Dysphagia Inventory). The swallowing muscles were delineated and the mean dose calculated using the original three-dimensional computed tomography-based treatment plans. Univariate analyses were performed using logistic regression analysis. Results: Most dysphagia problems were observed in the base of tongue tumors. For OP cancer, boosting with IMRT resulted in more dysphagia as opposed to BT or SRT/CBK. For NPC patients, in contrast to the first booster dose (46-70 Gy), no additional increase of dysphagia by the second boost was observed. Conclusions: The lowest mean doses of radiation to the swallowing muscles were achieved when using BT as opposed to SRT/CBK or IMRT. For the 81 patients alive with no evidence of disease for at least I year, a dose-effect relationship was observed between the dose in the superior constrictor muscle and the "normalcy of diet" (Performance Status Scales) or "swallowing scale" (H&N35) scores (p < 0.01). (C) 2008 Elsevier Inc.

Purpose To report on the tumor control, adverse late normal tissue sequelae, and functional performance in patients with tonsillar fossa and/or soft palate (SP) tumors. The aim of the study is to validate the use of a more selective clinical target volume in conjunction with highly conformal radiotherapy (RT) techniques to better spare the surrounding normal tissues. Methods and materials Between 1986 and 2001, T1-T3 tonsillar fossa/SP tumors were treated in the Erasmus Medical Center using external beam radiotherapy (EBRT) to 46 Gy in 2-Gy fractions to the primary tumor and neck, followed by brachytherapy (BT) to the primary. Neck dissection was performed for node-positive disease (BT group; 104 patients). If BT was not feasible, patients underwent surgery and postoperative RT (PORT) to a dose of 50–70 Gy in 2-Gy fractions (surgery group; 86 patients). Local control, regional control, disease-free survival, and overall survival were determined. Late side effects were scored using the Radiation Therapy Oncology Group criteria. Univariate and multivariate Cox regression analyses were performed for regional failure (RF), with the parameters gender, age, site, TN stage, modality, dose, and overall treatment time. Recurrences in the contralateral neck were also related to significant ipsilateral involvement of the base of tongue and/or involvement of the SP crossing the midline. To determine the performance status scale scores and degree of xerostomia, a survey was conducted among patients living with no evidence of disease and a minimum of 2 years of follow-up. For that purpose, a research nurse interviewed patients regarding eating in public, normalcy of diet, normalcy of speech, and xerostomia. Results The tumor control rates after BT vs. surgery at 5 years were 88% vs. 88% for local control; 93% vs. 85% for regional control; 57% vs. 52% for disease-free survival; 67% vs. 57% for overall survival; and 5% vs. 6% for RF. No patient had RF in the contralateral untreated N0 neck (0 of 14 vs. 0 of 15). Multivariate Cox regression analysis for RF was statistically significant for Stage T2 vs. T3 (hazard ratio 0.09) and for the dose to the neck >46 Gy (hazard ratio, 8.7; 95% confidence interval, 1.3–57.1). The significant late side effects in the BT group vs. surgery group were ulcer in 39% vs. 7% (p = 0.001) and trismus in 1% vs. 21% (p = 0.005). The performance status scale scores and response to questions regarding xerostomia for BT vs. surgery revealed no statistically significant differences for eating in public, normalcy of diet, normalcy of speech, and xerostomia. The mean visual analog score for xerostomia was 5.5 in the BT group vs. 6 in the surgery group. conclusion Excellent locoregional control was obtained in T1-T3 tonsillar fossa and/or SP tumors. The rate at 10 years was 84% (BT group) vs. 78% (surgery group). However, adverse late side effects were not negligible. In addition to modality-specific side effects (ulcer/trismus), both treatment groups were significantly affected by xerostomia. Only 6 recurrences (4%) were observed in the 149 electively treated contralateral necks, and no relapses were seen in the 29 untreated contralateral necks. We, therefore, suggest that it is not necessary to treat the contralateral neck, unless the tumor extends beyond the midline of the soft palate (uvula) or beyond the lateral one-third of the ipsilateral base of the tongue. Moreover, with the currently available CT-based neck level definitions, more conformal contours (i.e., tighter boundaries) around the clinical target volume can be designed. In this way, critical structures such as the temporomandibular joint and part of the pterygoid muscles can be avoided more easily. Also, when using highly conformal treatment techniques (e.g., intensity-modulated RT), one can further reduce the dose to the major salivary glands and oral mucosa. We believe these measures will lead to less trismus and less xerostomia.

Background: The toxicity of endobronchial brachytherapy (EB), in particular fatal haemoptysis and bronchial wall necrosis, has been correlated with the total dose, fraction size, volume encompassed by the 100% isodose, and a proximal tumor location. We describe a CT-based planning method which, by improving target volume definition and volumetric dose information, can improve the therapeutic ratio of EB. Materials and methods: Sixteen CT-assisted EB procedures were performed in patients who were treated with palliative high-dose rate EB. The CT data were used to analyze applicator position in relation to anatomy. An example of a three-dimensional optimized treatment plan was generated and analyzed using different types of dose-volume histograms. Results: The procedure was well tolerated by patients and no post-procedure complications were observed. The bronchial applicator was eccentrically positioned at the level of the carina/mainstem bronchus in 12 (of 14) CT scans. A planning CT prior to EB was not found to be useful as the final target volume and/or the final applicator position were not reliably predicted before the therapeutic bronchoscopy. CT-scans performed with the applicator in situ allowed the bronchial segments in the target volume to be identified and enabled dose prescription to the bronchial mucosa. Conclusions: CT-assisted EB is feasible and underlines the need for using centered applicators for proximally located tumors. By enabling accurate mucosal dose prescription, CT-assisted EB may reduce the toxicity of fractionated EB in the curative setting. However, faster on-line EB treatment planning is needed for the routine clinical application of this technique. Copyright (C) 2000 Elsevier Science Ireland Ltd.

PURPOSE A growing body of data suggests that local control in nasopharyngeal cancer (NPC) is related to the radiation dose administered. We conducted a single-institution study of high-dose radiotherapy (RT), which incorporated high-dose-rate (HDR) brachytherapy (BT). These results were analyzed together with data obtained from controls who did not receive BT. PATIENTS AND METHODS The BT group comprised 42 consecutive patients of whom 29 patients were staged according to the tumor, node, metastasis system as T1 through 3, 13 patients were T4, and 34 patients were N+ disease. BT was administered on an outpatient basis by means of a specially designed flexible nasopharyngeal applicator, and the dose distributions were optimized. Treatment for T1 through 3 tumors comprised 60 Gy of external-beam radiotherapy (ERT) followed by six fractions of 3 Gy BT (two fractions per day). Patients with parapharyngeal tumor extension and/or T4 tumors received 70 Gy ERT and four fractions of 3 Gy BT. The no-BT group consisted of all patients treated from 1965 to 1991 (n = 109), of whom 82 patients had stages T1 through 3, 27 patients had T4, and 80 patients had N+ disease. Multivariate Cox proportional hazards analyses were performed by using the end points time to local failure (TTLF), time to distant failure (TTDF), disease-free survival (DFS), cause-specific survival (CSS), and the prognostic factors age, tumor stage, node stage, and grade. Because the overall treatment time varied substantially in the no-BT group, the dependence of local failure (LF) on the physical dose as well as the biologic effective dose (BED) corrected for the overall treatment time (OTT) (BEDcor10) was studied. RESULTS The BT group had a superior 3-year local relapse-free rate (86% v 60%; univariate analysis, P = .004). Multivariate analysis showed hazards ratios for BT versus no-BT of 0.24 for TTLF (P = .003), 0.35 for TTDF (P = .038), 0.31 for DFS (P < .001), and 0.44 for CSS (P = .01). The best prognostic group consisted of patients with T1 through 3, N0 through 2b tumors treated with BT who attained a 5-year TTLF of 94% and CSS of 91%. In contrast, the worst prognostic group, i.e., 5-year TTLF of 47% and CSS of 24%, was composed of patients with T4 and/or N2c through 3 tumors who did not receive BT. CONCLUSION High doses of radiation (73 to 95 Gy) can be administered to patients with NPC with minimal morbidity by means of optimized HDR-BT. The use of a BT boost proved to be of significant benefit, particularly in patients with T1 through 3, N0 through 2b disease. The steep dose-effect relationship seen for the physical dose and the BEDcor10 indicates that the results are dose related. The analysis has identified a poor prognostic group in whom treatment intensification with chemotherapy (CHT) is indicated.

Introduction : In attempting to improve local tumor control by higher doses of radiation, there has been a resurgence of interest in the implementation of brachytherapy in the management of primary and recurrent cancers of the nasopharynx. Brachytherapy with its steep dose fall-off is of particular interest because of the proximity of critical dose limiting structures. Recent developments in brachytherapy, such as the introduction of pulsed-dose-rate and high-dose-rate computerized afterloaders, have encouraged further evolution of brachytherapy techniques. Materials and methods : We have designed an inexpensive, re-usable and flexible silicone applicator, tailored to the shape of the soft tissues of the nasopharynx, which can be used with either low-dose-rate brachytherapy or high (pulsed)-dose-rate remote controlled afterloaders. Results and conclusions : This Rotterdam nasopharynx applicator proved to be easy to introduce, patient friendly and can remain in situ for the duration of the treatment (2–6 days). The design, technique of application and the first consecutive 5 years of clinical experience in using this applicator are presented.

Purpose: Fractionated high-dose-rate (fr.HDR) and pulsed-dose, rate (PDR) brachytherapy (BT) regimens, which simulate classical continuous low- dose-rate (LDR) interstitial radiation therapy (IRT) schedules, have been developed for clinical use. This article reports the initial results using these novel schedules in squamous cell carcinoma (SCC) of the tonsillar fossa (TF) and/or soft palate (SP). Methods and Materials: Between 1990 and 1994, 38 patients with TF and SP tumors (5 T1, 22 T2, 10 T3, and 1 T4) were treated by fr. HDR or PDR brachytherapy, either alone or in combination with external irradiation (ERT). Half of the patients were treated with fr. HDR, which entailed twice-daily fractions of ≤3 Gy. The other 19 patients were administered PDR, which consisted of pulses of ≤2 Gy delivered 4-8 times/day. The median cumulative dose of IRT ± ERT series was 66 Gy (range 55-73). The results in these patients treated by brachtherapy were compared to 72 patients with similar tumors treated in our institute with curative intent, using ERT alone. The median cumulative dose of ERT-only series was 70 Gy (range 40-77). Results: Excellent locoregional control was achieved with the use of IRT ± ERT, with only 13% (5 of 38) developing local failure, and salvage surgery being possible in three of the latter (60%). Neither BT scheme (fr. HDR vs. PDR) nor tumor site (TF vs. SP) significantly influenced local control rates. The type and severity of the side effects observed are comparable to those reported in the literature for LDR-IRT. These results contrast sharply with our ERT-only series, in which 39% of patients (28 of 72) developed local failure, with surgical salvage being possible only in three patients (11%). Taking the data set of 110 patients, in a univariate analysis IRT, T stage, N stage, overall treatment time (OTT), and BEDcor10 (biological effective dose with a correction for the OTT) were significant prognostic factors for local relapse-free survival (LRFS) and overall survival (OS) at 3 years. Using Cox proportional hazard analysis, only T stage and BEDcor10, remained significant for LRFS (p < 0.001 and 0.008, respectively), as well as for OS (p < 0.001 and 0.003, respectively). With regard to the current (IRT) and historical (ERT) series, for the LRFS at 3 years, dose- response relationships were established, significant, however, only for the BEDcor10 (p = 0.03). Conclusion: The 3- year LRFS of approximately 90% for TF and SP tumors reported here is comparable with the best results in the literature, particularly given the fact that 30% of the patients (11 of 38) presented with T3/4 tumors. When compared with our historical (ERT-only) controls, the patients treated with IRT had superior local control. A dose-response relationship was established for the BEDcor10.

Purpose : No adequate high dose rate brachytherapy technique exists to cover all known tumor volume by using one type of applicator in patients presenting with a cervix carcinoma extending to the vaginal wall and the parametria. Methods and Materials : We adapted the existing high dose rate applicator, existing of two ovoids and one intrauterine tube, to achieve adequate irradiation of the uterus, the parametria, and the vaginal wall in these patients. Using the optimization program of the Nucletron Planning System, isodose curves were obtained to apply a specified dose of 8.5 Gy at point A and at 5 mm depth of the vaginal wall by using a single applicator for both fractions. Results : Fractionated high dose rate brachytherapy can be given with both higher dosimetric accuracy and more adequate irradiation of the vaginal and the parametrial tumor component after adapting the existing high dose rate applicator for brachytherapy in cervical cancer.