Impact of geometric variations on delivered dose in highly focused single vocal cord IMRT.

PURPOSE: To investigate the robustness of single vocal cord intensity modulated radiation therapy (IMRT) treatment plans for set-up errors, respiration, and deformation. MATERIAL AND METHODS: Four-dimensional computed tomography (4D-CT) scans of 10 early glottic carcinoma patients, previously treated with conventional techniques, were used in this simulation study. For each patient a pre-treatment 4D-CT was used for IMRT planning, generating a reference dose distribution. Prescribed PTV dose was 66 Gy. The impact of systematic set-up errors was simulated by applying shifts of ± 2 mm to the planning CT scans, followed by dose re-calculation with original beam segments, MUs, etc. Effects of respiration and deformation were determined utilizing extreme inhale and exhale CT scans, and repeat scans acquired after 22 Gy, 44 Gy, and 66 Gy, respectively. All doses were calculated using Monte Carlo dose simulations. RESULTS: Considering all investigated geometrical perturbations, reductions in the clinical target volume (CTV) V95%, D98%, D2%, and generalized equivalent uniform dose (gEUD) were limited to 1.2 ± 2.2%, 2.4 ± 2.9%, 0.2 ± 1.8%, and 0.6 ± 1.1 Gy, respectively. The near minimum dose, D98%, was always higher than 89%, and gEUD always remained higher than 66 Gy. Planned contra-lateral (CL) vocal cord DMean, gEUD, and V40 Gy were 38.2 ± 6.0 Gy, 43.4 ± 5.6 Gy, and 42.7 ± 14.9%. With perturbations these values changed by -0.1 ± 4.3 Gy, 0.1 ± 4.0 Gy, and -1.0 ± 9.6%, respectively. CONCLUSIONS: On average, CTV dose reductions due to geometrical perturbations were very low, and sparing of the CL vocal cord was maintained. In a few observations (6 of 103 simulated situations), the near-minimum CTV-dose was around 90%, requiring attention in deciding on a future clinical protocol.

Clinical integration of software tool VEDO for adaptive and quantitative application of phased array hyperthermia in the head and neck.

BACKGROUND AND PURPOSE: In Rotterdam, patient-specific hyperthermia (HT) treatment planning (HTP) is applied for all deep head and neck (H&N) HT treatments. In this paper we introduce VEDO (the Visualisation Tool for Electromagnetic Dosimetry and Optimisation), the software tool required, and demonstrate its value for HTP-guided online complaint-adaptive (CA) steering based on specific absorption rate (SAR) optimisation during a H&N HT treatment. MATERIALS AND METHODS: VEDO integrates CA steering, visualisation of the SAR patterns and mean tumour SAR (SAR(target)) optimisation in a single screen. The pre-calculated electromagnetic fields are loaded into VEDO. During treatment, VEDO shows the SAR pattern, overlaid on the patients' CT-scan, corresponding to the actually applied power settings and it can (re-)optimise the SAR pattern to minimise SAR at regions where the patient senses discomfort while maintaining a high SAR(target). RESULTS: The potential of the quantitative SAR steering approach using VEDO is demonstrated by analysis of the first treatment in which VEDO was used for two patients using the HYPERcollar. These cases show that VEDO allows response to power-related complaints of the patient and to quantify the change in absolute SAR: increasing either SAR(target) from 96 to 178 W/kg (case 1); or show that the first SAR distribution was already optimum (case 2). CONCLUSION: This analysis shows that VEDO facilitates a quantitative treatment strategy allowing standardised application of HT by technicians of different HT centres, which will potentially lead to improved treatment quality and the possibility of tracking the effectiveness of different treatment strategies.

Risk model and nomogram for dysphagia and xerostomia prediction in head and neck cancer patients treated by radiotherapy and/or chemotherapy.

In our randomized trial on hyperbaric oxygen (HBO), it was shown that HBO could reduce dysphagia and xerostomia, which are frequently encountered after (chemo-) radiotherapy (RT) and/or surgery for head and neck cancer (HNC). A risk model and nomogram are developed to select those patients who most likely will respond to HBO treatment. A total of 434 HNC patients treated from 2000 to 2008 were analyzed and filled out the EORTC QLQC-30 and H&N35 questionnaires. Age, gender, chemotherapy, T and N stages, site, radiotherapy technique, RT boost, surgery of the primary tumor and neck, bilateral RT, and dose were analyzed in a statistical model. The discriminative value of the model was evaluated based on receiver operating characteristics (ROC), the area under the curve (AUC), sensitivity, specificity, and proportion of correctly classified measures. Significant factors in predicting swallowing problems are age, follow-up duration, tumor site, chemotherapy, surgery of the primary tumor and neck, and dose. For dry mouth, the significant factors are age, gender, tumor site, N stage, chemotherapy, and bilateral irradiation. For dysphagia and xerostomia, the area under the ROC curve is 0.7034 and 0.7224, respectively, with a specificity of 89/77%, sensitivity of 27/58%, and a positive predictive value of 83/67% for dysphagia and xerostomia, respectively. The developed predictive risk model could be used to select patients for costly hyperbaric oxygen treatment to prevent or reduce severe late side effects of HNC treatment. Our model serves as a guideline for the Department of Radiation Oncology to reduce costs by excluding patients not amenable to hyperbaric oxygen protocols. The nomogram presented is a useful tool for clinicians in assessing patient risks when deciding on follow-up strategies (e.g., hyperbaric oxygen treatment) after RT or surgery for HNC.

Combined-modality treatment improved outcome in sinonasal undifferentiated carcinoma: single-institutional experience of 21 patients and review of the literature.

The optimal treatment of sinonasal undifferentiated carcinoma (SNUC) remains unclear. We report our results on the outcome and toxicity of patients with SNUC treated by a combined modality and attempt to define the optimal treatment strategies by reviewing the literature. Between 1996 and 2010, 21 consecutive patients with SNUC were treated by any combination of surgery, chemotherapy and radiotherapy. End points were local control (LC), regional control (RC), disease-free (DFS), cause-specific (CSS) overall survival (OS), and late toxicity. Organ preservation was defined as visual preservation without orbital exenteration. After median follow-up of 54 months, the 5-year actuarial rates of LC, RC, DFS, CSS, and OS were 80, 90, 64, 74, and 74 % respectively. On multivariate analysis, T-stage and multimodality treatment approach correlated significantly with LC. Elective nodal irradiation was given to 42 % of high-risk node-negative patients. None of them developed regional failure. The overall 5-year incidence of grade ≥ 2 late toxicity was 30 %. Treatment-related blindness was significantly decreased in patients treated with intensity-modulated radiotherapy (IMRT), compared to 2D and 3D-conformal radiotherapy (3DCRT), with organ preservation rates of 86 and 14 % respectively (p = 0.006). We concluded that combined-modality treatment with three, or at least two, modalities resulted in good LC, but with high overall rate of late toxicity. However, the incidence of late toxicity and permanent visual impairment were decreased over time by the introduction of IMRT. Because of the improvement in therapeutic ratio achieved by using IMRT, this highly conformal radiation technique should be the standard of care in patients with SNUC.

Integrated multicriterial optimization of beam angles and intensity profiles for coplanar and noncoplanar head and neck IMRT and implications for VMAT.

PURPOSE: To quantify improved salivary gland sparing for head and neck cancer patients using intensity-modulated radiotherapy (IMRT) plans based on integrated computerized optimization of beam orientations and intensity profiles. To assess if optimized nonzero couch angles also improve VMAT plans. METHODS: Our in-house developed algorithm iCycle was used for automated generation of multicriterial optimized plans with optimized beam orientations and intensity profiles, and plans with optimized profiles for preselected beam arrangements. For 20 patients, five IMRT plans, based on one "wish-list," were compared: (i) and (ii) seven- and nine-beam equiangular coplanar plans (iCycle(7equi), iCycle(9equi)), (iii) and (iv) nine-beam plans with optimized coplanar and noncoplanar beam orientations (iCycle(copl), iCycle(noncopl)), and (v) a nine-beam coplanar plan with optimized gantry angles and one optimized couch rotation (iCycle(couch)). VMAT plans without and with this optimized couch rotation were evaluated. RESULTS: iCycle(noncopl) resulted in the best salivary gland sparing, while iCycle(couch) yielded similar results for 18 patients. For iCycle(7equi), submandibular gland NTCP values were on average 5% higher. iCycle(9equi) performed better than iCycle(7equi). iCycle(copl) showed further improvement. Application of the optimized couch angle from iCycle(couch) also improved NTCP values in VMAT plans. CONCLUSIONS: iCycle allows objective comparison of competing planning strategies. Integrated optimization of beam profiles and angles can significantly improve normal tissue sparing, yielding optimal results for iCycle(noncopl).

Controversies in the treatment of high-risk prostate cancer--what is the optimal combination of hormonal therapy and radiotherapy: a review of literature.

BACKGROUND: In high-risk prostate carcinoma, there is controversy whether these patients should be treated with escalated-dose (> or =74 Gy) or conventional-dose radiotherapy (<74 Gy) combined with hormonal therapy. Furthermore, the issue of the optimal duration and timing of hormonal therapy are not well crystallized. PATIENTS AND METHODS: A search for evidence from randomized- and large non-randomized studies in order to address these issues, was therefore initiated. For this purpose, MedLine, EMbase, and PubMed and the data base of the Dutch randomized dose-escalation trial, were consulted. RESULTS AND CONCLUSIONS: From this search it was concluded that the benefit of hormonal therapy in combination with conventional-dose radiotherapy (<74 Gy) in high-risk prostate cancer is evident (Level 2 evidence); Levels 2 and 3 evidence were provided by several studies supporting the use of escalated-dose radiotherapy in high-risk prostate cancer. For the combination of hormonal therapy with escalated-dose radiotherapy in these patients, there is Level 2 evidence for moderately escalated dose (74 Gy) and high escalated dose (> or =78 Gy). The optimal duration and timing of hormonal therapy are not well defined. More randomized-controlled trials and meta-analyses are therefore needed to clearly determine the independent role of dose-escalation in high-risk patients treated with hormonal therapy and the optimal duration and timing of hormonal therapy.

A novel flexible framework with automatic feature correspondence optimization for nonrigid registration in radiotherapy.

Technical improvements in planning and dose delivery and in verification of patient positioning have substantially widened the therapeutic window for radiation treatment of cancer. However, changes in patient anatomy during the treatment limit the exploitation of these new techniques. To further improve radiation treatments, anatomical changes need to be modeled and accounted for Nonrigid registration can be used for this purpose. This article describes the design, the implementation, and the validation of a new framework for nonrigid registration for radiotherapy applications. The core of this framework is an improved version of the thin plate spline robust point matching (TPS-RPM) algorithm. The TPS-RPM algorithm estimates a global correspondence and a transformation between the points that represent organs of interest belonging to two image sets. However, the algorithm does not allow for the inclusion of prior knowledge on the correspondence of subset of points, and therefore, it can lead to inconsistent anatomical solutions. In this article TPS-RPM was improved by employing a novel correspondence filter that supports simultaneous registration of multiple structures. The improved method allows for coherent organ registration and for the inclusion of user-defined landmarks, lines, and surfaces inside and outside of structures of interest. A procedure to generate control points from segmented organs is described. The framework parameters r and lambda, which control the number of points and the nonrigidness of the transformation, respectively, were optimized for three sites with different degrees of deformation (head and neck, prostate, and cervix) using two cases per site. For the head and neck cases, the salivary glands were manually contoured on CT scans, for the prostate cases the prostate and the vesicles, and for the cervix cases the cervix uterus, the bladder, and the rectum. The transformation error obtained using the best set of parameters was below 1 mm for all the studied cases. The lengths of the deformation vectors were on average (+/- 1 standard deviation) 5.8 +/- 2.5 and 2.6 +/- 1.1 mm for the head and neck cases, 7.2 +/- 4.5 and 8.6 +/- 1.9 mm for the prostate cases, and 19.0 +/- 11.6 and 14.5 +/- 9.3 mm for the cervix cases. Distinguishable anatomical features were identified for each case and were used to validate the registration by calculating residual distances after transformation: 1.5 +/- 0.8, 2.3 +/- 1.0, and 6.3 +/- 2.9 mm for the head and neck, prostate, and cervix sites, respectively. Finally, the authors demonstrated how the inclusion of these anatomical features in the registration process reduced the residual distances to 0.8 +/- 0.5, 0.6 +/- 0.5, and 1.3 +/- 0.7 mm for the head and neck, prostate, and cervix sites, respectively. The inclusion of additional anatomical features produced more anatomically coherent transformations without compromising the transformation error. The authors concluded that the presented nonrigid registration framework is a powerful tool to simultaneously register multiple segmented organs with very different complexities.

Hypofractionated radiotherapy denoted as the "Christie scheme": an effective means of palliating patients with head and neck cancers not suitable for curative treatment.

OBJECTIVES: A prospective study of the efficacy and toxicity profile of patients with squamous cell carcinoma of the head and neck (HNSCC) without curative treatment options treated consistently with hypofractionated radiotherapy schedule. PATIENTS AND METHODS: Between 1995 and 2006, 158 patients with HNSCC, unsuitable for curative treatment, were treated with a hypofractionated scheme of radiotherapy consisting of 16 fractions of 3.125 Gy. Endpoints of the study were response rates, loco-regional control, disease-free survival, overall survival, acute and late toxicity, and quality of life (QoL). RESULTS: Seventy four percent of patients were male, 31% had oropharyngeal cancer and 81% stage IV disease. With 45% complete response and 28% partial response an overall response rate of 73% was achieved, 6% had stable disease, and 21% progressed during or directly after completion of treatment. Median survival time was 17 months and 62 patients (40%) survived > or =1 year after RT. The actuarial rates of loco-regional control, disease-free survival and overall survival were 62%, 32% and 40% at 1-year, respectively and 32%, 14% and 17% at 3-years, respectively. Acute grade > or =3 skin and mucosal toxicities were observed in 45% and 65% of patients, respectively. Severe late toxicity was reported in 4.5% of patients. Of patients surviving > or =1 year after RT, retrospective chart review showed that 50% gained weight, pain improved in 77%, performance status in 47% and only 29% of them was still feeding-tube dependent. CONCLUSIONS: Our hypofractionated radiotherapy scheme is an effective, well-tolerated and safe palliative schedule in HNSCC who are unsuitable for curative treatment options. Using 3.125 Gy per fraction (Christie scheme), excellent palliation was achieved resulting in acceptable response rates, excellent symptom control, acceptable toxicity profile, and good QoL of patients surviving > or =1 year after completion of treatment.

Quality of life of oropharyngeal cancer patients treated with brachytherapy.

Brachytherapy (BT) is a highly conformal (accurate clinical target volume delineation, no planning target volume margin) radiotherapy technique; the radioactive source, guided by afterloading catheters, is implanted into the heart of the tumor. The localized high dose of radiation enables high tumor control rates and, because of rapid dose fall-off, sparing of the adjacent normal tissues. At the Erasmus Medical Center, excellent results were observed: 5-year local regional control of 84%, 5-year disease-free survival of 59%, and 5-year overall survival of 64%. Therefore, in the case of moderately sized tumors, for well-trained, skillful physicians, BT is the therapy of choice (if technically feasible). However, side effects are not totally negligible, partly because of the cumulative dose of BT and the first series of 46/2 Gy. However, patients treated with BT still have a better swallowing-related quality of life, which might improve further if summation of BT and the first series of 46/2 Gy, as well as autocontouring of the neck levels, are realized. So far, there is no significant relationship between the -quality index of the BT implants and local control/overall survival and/or quality of life.

Time dependence of intrafraction patient motion assessed by repeat stereoscopic imaging.

PURPOSE: To quantify intrafraction patient motion and its time dependence in immobilized intracranial and extracranial patients. The data can be used to optimize the intrafraction imaging frequency and consequent patient setup correction with an image guidance and tracking system, and to establish the required safety margins in the absence of such a system. METHOD AND MATERIALS: The intrafraction motion of 32 intracranial patients, immobilized with a thermoplastic mask, and 11 supine- and 14 prone-treated extracranial spine patients, immobilized with a vacuum bag, were analyzed. The motion was recorded by an X-ray, stereoscopic, image-guidance system. For each group, we calculated separately the systematic (overall mean and SD) and the random displacement as a function of elapsed intrafraction time. RESULTS: The SD of the systematic intrafraction displacements increased linearly over time for all three patient groups. For intracranial-, supine-, and prone-treated patients, the SD increased to 0.8, 1.2, and 2.2 mm, respectively, in a period of 15 min. The random displacements for the prone-treated patients were significantly higher than for the other groups, namely 1.6 mm (1 SD), probably caused by respiratory motion. CONCLUSIONS: Despite the applied immobilization devices, patients drift away from their initial position during a treatment fraction. These drifts are in general small if compared with conventional treatment margins, but will significantly contribute to the margin for high-precision radiation treatments with treatment times of 15 min or longer.

Local anatomic changes in parotid and submandibular glands during radiotherapy for oropharynx cancer and correlation with dose, studied in detail with nonrigid registration.

PURPOSE: To quantify the anatomic changes caused by external beam radiotherapy in head-and-neck cancer patients in full three dimensions and to relate the local anatomic changes to the planned mean dose. METHODS AND MATERIALS: A nonrigid registration method was adapted for RT image registration. The method was applied in 10 head-and-neck cancer patients, who each underwent a planning and a repeat computed tomography scan. Contoured structures (parotid, submandibular glands, and tumor) were registered in a nonrigid manner. The accuracy of the transformation was determined. The transformation results were used to summarize the anatomic changes on a local scale for the irradiated and spared glands. The volume reduction of the glands was related to the planned mean dose. RESULTS: Transformation was accurate with a mean error of 0.6 +/- 0.5 mm. The volume of all glands and the primary tumor decreased. The lateral regions of the irradiated parotid glands moved inward (average, 3 mm), and the medial regions tended to remain in the same position. The irradiated submandibular glands shrank and moved upward. The spared glands showed only a small deformation ( approximately 1 mm in most regions). Overall, the primary tumors shrank. The volume loss of the parotid glands correlated significantly with the planned mean dose (p <0.001). CONCLUSION: General shrinkage and deformation of irradiated glands was seen. The spared glands showed few changes. These changes were assessed by a nonrigid registration method, which effectively described the local changes occurring in the head-and-neck region after external beam radiotherapy.

Quality of life after stereotactic body radiation therapy for primary and metastatic liver tumors.

PURPOSE: Stereotactic body radiation therapy (SBRT) provides a high local control rate for primary and metastatic liver tumors. The aim of this study is to assess the impact of this treatment on the patient's quality of life. This is the first report of quality of life associated with liver SBRT. METHODS AND MATERIALS: From October 2002 to March 2007, a total of 28 patients not suitable for other local treatments and with Karnofsky performance status of at least 80% were entered in a Phase I-II study of SBRT for liver tumors. Quality of life was a secondary end point. Two generic quality of life instruments were investigated, EuroQol-5D (EQ-5D) and EuroQoL-Visual Analogue Scale (EQ-5D VAS), in addition to a disease-specific questionnaire, the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ C-30). Points of measurement were directly before and 1, 3, and 6 months after treatment. Mean scores and SDs were calculated. Statistical analysis was performed using paired-samples t-test and Student t-test. RESULTS: The calculated EQ-5D index, EQ-5D VAS and QLQ C-30 global health status showed that mean quality of life of the patient group was not significantly influenced by treatment with SBRT; if anything, a tendency toward improvement was found. CONCLUSIONS: Stereotactic body radiation therapy combines a high local control rate, by delivering a high dose per fraction, with no significant change in quality of life. Multicenter studies including larger numbers of patients are recommended and under development.

Four-dimensional CT analysis of vocal cords mobility for highly focused single vocal cord irradiation.

BACKGROUND AND PURPOSE: To quantify respiratory motion of the vocal cords during normal respiration using 4D-CT. The final goal is to develop a technique for single vocal cord irradiation (SVCI) in early glottic carcinoma. Sparing the non-involved cord and surrounding structures has the potential to preserve voice quality and allow re-irradiation of recurrent and second primary tumors. MATERIAL AND METHODS: Four-dimensional CTs of 1mm slice thickness from 10 early glottic carcinoma patients were acquired. The lateral dimensions of the air gap separating the vocal cords were measured anteriorly, at mid-level and posteriorly at each phase of the 4D-CTs. The corresponding anterior-posterior gaps were similarly measured. Cranio-caudal vocal cords movements during breathing were derived from the shifts of the arythenoids. RESULTS: The population-averaged mean gap size+/-the corresponding standard deviation due to breathing (SD(B)) for the lateral gaps was 5.8+/-0.7mm anteriorly, 8.7+/-0.9mm at mid-level, and 11.0+/-1.3mm posteriorly. Anterior-posterior gap values were 21.7+/-0.7mm, while cranio-caudal shift SD(B) was 0.8mm. CONCLUSION: Vocal cords breathing motions were found to be small relative to their separation. Hence, breathing motion does not seem to be a limiting factor for SVCI.

Results of fiberoptic endoscopic evaluation of swallowing vs. radiation dose in the swallowing muscles after radiotherapy of cancer in the oropharynx.

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.

Reducing monitor units for robotic radiosurgery by optimized use of multiple collimators.

Advances in image guidance and dose delivery techniques, and increased use of hypofractionation, have led to prolonged radiotherapy fraction duration. This is also the case with robotic radiosurgery, as extensive on-line image guidance procedures, many beams, and usually high fraction doses are used for tumor irradiation. At this institution, early stage non-small-cell lung cancer patients are treated with image guided tumor tracking for respiratory motion compensation. Approximately 130 circular beams and up to approximately 39 000 monitor units (MUs) are used for delivery of a total treatment dose of 60 Gy. The large number of MUs leads to long treatment times and the radiation leakage increases with the number of MUs. Generally, per patient, a single (small) cone is used. To substantially reduce the number of MUs, the authors have developed a new planning strategy for combined use of a small and a large cone. The large cone aims at dose delivery around the PTV center, while the small cone shapes the dose around the (irregular) PTV edges. The authors systematically investigated relationships between the number of MUs, the plan quality, the selected cone diameters, and the beam-direction setup. Plan quality was assessed with the conformity index, mean lung dose (MLD), V20 of the lungs, and by visual inspection. The reduction in MUs was determined by comparing two-cone plans with corresponding one-cone plans that yielded equal MLD, i.e., equal predicted lung toxicity. With the proposed two-cone approach, the required number of MUs reduced by on average 31% (range 4%-56%). The beam-on time per treatment fraction reduced by on average 8 min (range 1-15.2 min). All plans obeyed the clinically applied constraints and were considered clinically acceptable by an involved physician.

Longitudinal changes in quality of life and costs in long-term survivors of tumors of the oropharynx treated with brachytherapy or surgery.

PURPOSE: Based on earlier studies we were interested in finding out if longitudinal assessment of quality of life (QoL) and costs in long-term survivors of oropharyngeal cancers treated with external beam radiation therapy and brachytherapy (BT) or surgery and postoperative radiotherapy showed a change in QoL over the years. Besides, we were curious to know how much the costs per life year and the QALY would be for this patient group. METHODS AND MATERIALS: Performance status scales: eating in public, understandability of speech, normalcy of diet, xerostomia and ability to swallow were determined in 2003 and 2005. In 2005, the responses to EORTC QLQ-C30, EORTC H&N35, and the Euroqol questionnaire were also measured. Costs and quality-adjusted life years (QALYs) were calculated. RESULTS: Eating in public, understandability of speech, and normalcy of diet significantly differed in favor of BT. Surgical patients experienced more speech, teeth, and mouth-opening problems. Mean costs and QALYs for BT were 16,112 euros and 56,060 euros and for surgery 26,590 euros and 93,275 euros, respectively. CONCLUSIONS: QoL scores don't change over time. Due to the number of admission days, surgery is more costly. Difference in costs for QALYs in favor of BT was observed.

Quantification of trade-off between parotid gland sparing and planning target volume underdosages in clinically node-negative head-and-neck intensity-modulated radiotherapy.

PURPOSE: To quantify the trade-off between parotid gland sparing and planning target volume (PTV) underdosages for head-and-neck intensity-modulated radiotherapy. METHODS AND MATERIALS: A planning study was performed for 4 patients with either soft palate or tonsil tumors treated with external radiotherapy up to 46 Gy. The trade-off between underdosages in the PTV and sparing of the parotid glands was investigated by systematically varying the optimization objectives for the inverse planning. A new way of presenting dose-volume information allows easy detection of small PTV subvolumes with underdosages that cannot be assessed in conventional cumulative dose-volume histograms. A simple radiobiological model to estimate the control probability for an electively irradiated neck level was developed. RESULTS: The average dose to the parotid glands can decrease by >10 Gy by allowing the PTV to be underdosed in such a way that the radiobiological model predicts a decrease in subclinical disease control probability of (typically) 1% to a few percent. CONCLUSION: The trade-off between parotid gland sparing and underdosages in the PTV has been quantified by the use of an alternative method to present dose-volume information and by the use of a radiobiological model to predict subclinical disease control probability.

Can IMRT or brachytherapy reduce dysphagia associated with chemoradiotherapy of head and neck cancer? The Michigan and Rotterdam experiences.

PURPOSE: Dysphagia is a major late complication of intensive chemoradiotherapy of head and neck cancer. The initial clinical results of intensity-modulated radiotherapy (IMRT), or brachytherapy, planned specifically to reduce dysphagia are presented. PATIENTS AND METHODS: Previous research at Michigan University has suggested that the pharyngeal constrictors and glottic and supraglottic larynx are likely structures whose damage by chemo-RT causes dysphagia and aspiration. In a prospective Michigan trial, 36 patients with oropharyngeal (n = 31) or nasopharyngeal (n = 5) cancer underwent chemo-IMRT. IMRT cost functions included sparing noninvolved pharyngeal constrictors and the glottic and supraglottic larynx. After a review of published studies, the retropharyngeal nodes at risk were defined as the lateral, but not the medial, retropharyngeal nodes, which facilitated sparing of the swallowing structures. In Rotterdam, 77 patients with oropharyngeal cancer were treated with IMRT, three dimensional RT, or conventional RT; also one-half received brachytherapy. The dysphagia endpoints included videofluoroscopy and observer-assessed scores at Michigan and patient-reported quality-of-life instruments in both studies. RESULTS: In both studies, the doses to the upper and middle constrictors correlated highly with the dysphagia endpoints. In addition, doses to the glottic and supraglottic larynx were significant in the Michigan series. In the Rotterdam series, brachytherapy (which reduced the doses to the swallowing structures) was the only significant factor on multivariate analysis. CONCLUSION: The dose-response relationships for the swallowing structures found in these studies suggest that reducing their doses, using either IMRT aimed at their sparing, or brachytherapy, might achieve clinical gains in dysphagia.

Target coverage in image-guided stereotactic body radiotherapy of liver tumors.

PURPOSE: To determine the effect of image-guided procedures (with computed tomography [CT] and electronic portal images before each treatment fraction) on target coverage in stereotactic body radiotherapy for liver patients using a stereotactic body frame (SBF) and abdominal compression. CT guidance was used to correct for day-to-day variations in the tumor's mean position in the SBF. METHODS AND MATERIALS: By retrospectively evaluating 57 treatment sessions, tumor coverage, as obtained with the clinically applied CT-guided protocol, was compared with that of alternative procedures. The internal target volume-plus (ITV(+)) was introduced to explicitly include uncertainties in tumor delineations resulting from CT-imaging artifacts caused by residual respiratory motion. Tumor coverage was defined as the volume overlap of the ITV(+), derived from a tumor delineated in a treatment CT scan, and the planning target volume. Patient stability in the SBF, after acquisition of the treatment CT scan, was evaluated by measuring the displacement of the bony anatomy in the electronic portal images relative to CT. RESULTS: Application of our clinical protocol (with setup corrections following from manual measurements of the distances between the contours of the planning target volume and the daily clinical target volume in three orthogonal planes, multiple two-dimensional) increased the frequency of nearly full (> or = 99%) ITV(+) coverage to 77% compared with 63% without setup correction. An automated three-dimensional method further improved the frequency to 96%. Patient displacements in the SBF were generally small (< or = 2 mm, 1 standard deviation), but large craniocaudal displacements (maximal 7.2 mm) were occasionally observed. CONCLUSION: Daily, CT-assisted patient setup may substantially improve tumor coverage, especially with the automated three-dimensional procedure. In the present treatment design, patient stability in the SBF should be verified with portal imaging.

Dysphagia disorders in patients with cancer of the oropharynx are significantly affected by the radiation therapy dose to the superior and middle constrictor muscle: a dose-effect relationship.

PURPOSE/OBJECTIVE: To assess the relationship between the radiation therapy (RT) dose received by the muscular components of the swallowing (sw) apparatus and - dysphagia related - quality of life (QoL) in oropharyngeal cancer. MATERIALS/METHODS: Between 2000 and 2005, 81 patients with SCC of the oropharynx were treated by 3DCRT or IMRT, with or without concomitant chemotherapy (CHT); 43 out of these 81 patients were boosted by brachytherapy (BT). Charts of 81 patients were reviewed with regard to late dysphagia complaints; 23% experienced severe dysphagia. Seventeen patients expired. Fifty-six out of 64 (88%) responded to quality of life (QoL) questionnaires; that is, the Performance Status Scales of List, EORTC H&N35, and the M.D. Anderson Dysphagia Inventory. The superior (scm), middle (mcm), and inferior constrictor muscle (icm), the cricopharyngeus muscle and the inlet of the esophagus, are considered of paramount importance for swallowing. The mean dose was calculated in the muscular structures. Univariate analysis and multivariate analysis were performed using the proportional odds model. RESULTS: Mean follow-up was 18 months (range 2-34) for IMRT, and 46 months for 3DCRT (range 2-72). At 3-years, a LRC of 84%, DFS of 78% and OS of 77% were observed. A significant correlation was observed between the mean dose in the scm and mcm, and severe dysphagia complaints (univariate analysis). A steep dose-effect relationship, with an increase of the probability of dysphagia of 19% with every additional 10 Gy, was established. In the multivariate analysis, BT (dose) was the only significant factor. CONCLUSION: A dose-effect relationship between dose and swallowing complaints was observed. One way to improve the QoL is to constrain the dose to be received by the swallowing muscles.