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Purpose: The aim of this study was to investigate the result of hyperbaric oxygen therapy (HBOT) in women with treated gynaecological malignancies who suffer from late radiation-induced tissue toxicity (LRITT). Moreover, which symptoms of LRITT benefit most from HBOT was evaluated as well., Material and Methods: An online literature search was conducted using PubMed; Embase and the Cochrane Library. Studies were included if the study examined gynaecological cancer patients who had been treated with radiotherapy, who suffered from LRITT and who subsequently received HBOT. In addition, the outcome measures were based on examining the effects of HBOT., Results: Twenty-one articles were included. The study investigating proctitis reported an improvement and three out of four studies investigating cystitis reported decreased complaints in women treated for gynaecological malignancies. In addition, all studies reported improvement in patients with wound complications and fifty percent of the studies reported better Patient Reported Outcome Measurements (PROMS) in women with gynaecological malignancies. Finally, all studies, except one related to pelvic malignancies reported reduced prevalence of symptoms for cystitis and proctitis and all studies reported better PROMS. However, only eleven studies reported p-values, nine of which were significant., Conclusion: This study demonstrated that HBOT has a positive effect in women with gynaecological LRITT. Within the included patient group, gynaecological cancer patients with wound complications seem to benefit most from this treatment compared to other late side effects of LRITT., (© 2022. The Author(s).)

Background: Hyperbaric oxygen treatment (HBOT) is often used in an attempt to reverse/treat late radiation-induced tissue fibrosis (LRITF). This study aimed to quantify the effects on skin elasticity., Methods: Skin retraction time was used as a marker of skin elasticity in 13 irradiated breast cancer patients. The measurements were carried out on the affected side as well as the unaffected/healthy side at a mirrored location. Readings were taken at the start and end of HBOT (mean 43 sessions, 80 min at 243 kPa)., Results: Patient age ranged from 39-70 years. All patients underwent surgical lumpectomy and radiotherapy prior to undergoing HBOT. The mean time between radiotherapy and HBOT was 70 months. Seven of the 13 patients underwent chemotherapy. Mean irradiated skin retraction time improved from 417 (SD 158) pre-HBOT to 171 (24) msec post-HBOT (P < 0.001). Mean pre-HBOT retraction time in the non-irradiated skin was 143 (20) msec and did not change., Conclusions: This promising pilot study that suggests that HBOT may improve skin elasticity in patients with LRITF., (Copyright: This article is the copyright of the authors who grant Diving and Hyperbaric Medicine a non-exclusive licence to publish the article in electronic and other forms.)

Background: Late side effects of radiotherapy in patients with head and neck cancer (HNCPs) result in decreased tissue vascularity, a compromised healing capacity and spontaneous breakdown of tissue. The aim of this study was to examine the in vivo effect of hyperbaric oxygen therapy (HBOT) on the microcirculation in irradiated oral tissue., Methods: Using a handheld microscope, the effect of HBOT on oral mucosal microcirculation parameters was measured in 34 previously irradiated HNCPs prior to HBOT and at 4 weeks and 6 months posttreatment., Results: A significant increase in mean buccal vessel density and decrease in buccal vessel diameter was found 6 months after HBOT compared to baseline, 22 ± 11 versus 25 ± 7 cpll/mm 2 (p < 0.05) and 20 ± 4 versus 16 ± 5 μm (p < 0.05), respectively., Conclusion: Our results indicate that oral microcirculation histopathology associated with irradiation is able to respond to HBOT by redirecting oral microcirculation parameters towards values consistent with healthy tissue., (© 2022 The Authors. Head & Neck published by Wiley Periodicals LLC.)

The present article evaluates the results of the treatment with adjuvant hyperbaric oxygen therapy (HBOT) of patients with nonhealing, chronic wounds. In the period 2013 to 2016, 248 patients were referred from various hospitals because of chronic wounds that were recalcitrant in healing despite standard wound care as described in national and international guidelines. After inclusion, all patients were treated with HBOT and subjected to a weekly standard wound care treatment. During each HBOT session, 100% O 2 was administered for 75 minutes under increased pressure of 2.4 ATA. Wounds and quality of life were assessed before and after the total treatment period. A total of 248 patients have been evaluated. Diabetic foot ulcers were present in 134 patients, the remainder (114 patients) showed a variety of wound locations and etiologies. The number of HBOT treatments amounted to an average of 48 (range 20-68) sessions. Before referral to our clinic, 31% of all wounds had existed for at least 18 months (72 patients). After HBOT, 81% of all wounds were near complete healing or completely healed, in 13% of the cases the wound was stable, and in 2% minor or major amputation had to be carried out. The mean treatment time for wounds pre-existing fewer than 6 weeks ("early referrals") was 67 days, and 119 days for wounds pre-existing more than 18 months ("late referrals"). A majority of the patients in our study referred with nonhealing wounds clinically improved when adjuvant HBOT was added to standard wound care protocols. No differences in success rate were seen between diabetic and nondiabetic wounds. It showed that HBOT is a well-tolerated treatment., (© 2020 The Authors. Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

Background: Calcific uremic arteriolopathy (calciphylaxis) is a rare and highly lethal vascular disease. Vascular calcification with calcium depositions lead to ischemic ulcers associated with gangrene, severe pain and poor healing. Although hyperbaric oxygen (HBO2) therapy has been used in the treatment of calciphylaxis, evidence of its effectiveness is limited., Objective: To determine whether HBO2 therapy has a beneficial effect in the healing of calciphylaxis ulcers., Methods: A search was made in PubMed using a comprehensive strategy to identify the effect of HBO2 on calciphylaxis wounds. Included in the analysis were studies published up to October 2018 involving a minimum of four patients receiving HBO2 therapy., Results: Ten retrospective (case) series were included. This review included a total of 131 patients with calciphylaxis who were treated with HBO2 therapy; of these, 58 patients (45%) had full response on HBO2 with complete wound closure. Regarding partial response, 17 of the patients (13%) experienced substantial wound improvement on different wound scale scores., Conclusion: Patients with calcific uremic arteriolopathy can benefit from HBO2. More research is needed using standardized wound scores. Outcomes related to quality of life and pain relief should also be assessed., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

Purpose: To determine the clinical feasibility of examining and measuring late irradiation changes in the oral microcirculation of head and neck (HN) cancer patients using the novel CytoCam video microscope system., Methods and Materials: In 30 HN cancer patients and 30 age-matched controls, bilateral video images were recorded noninvasively of the oral microcirculation of the buccal mucosa and mandibular gingiva. Tissue perfusion parameters, such as functional capillary density (FCD), buccal blood vessel diameter, and microcirculatory flow index, were analyzed., Results: No difference was observed for mean buccal mucosa FCD in irradiated versus healthy tissue, whereas a lower mean gingival FCD in irradiated versus healthy tissue was observed (34 ± 17 capillaries per millimeter squared [cpll/mm 2 ] vs 68 ± 19 cpll/mm 2 ; P < .001). A significant difference in mean buccal blood vessel diameter of 16 ± 3 μm was measured, compared with 14 ± 1 μm in control buccal mucosa (P < .001). No significant difference in microcirculatory flow index was observed between the 2 groups., Conclusions: Quantifying oral microcirculatory injury associated with late irradiation effects using the CytoCam was feasible in HN cancer patients. Results indicate that marked differences in tissue-specific microcirculatory measurements of angioarchitecture, diminished capillary density, and extensively dilated blood vessel diameters are associated with late irradiation effects in HN cancer patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: This study examines patient reported outcome measures of women undergoing hyperbaric oxygen treatment (HBOT) after breast-conserving therapy., Method: Included were 57 women treated with HBOT for late radiation-induced tissue toxicity (LRITT) referred in the period January 2014-December 2015. HBOT consisted of (on average) 47 sessions. In total, 80 min of 100 % O 2 was administered under increased pressure of 2.4 ATA. Quality of life was assessed before and after treatment using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23, and a NRS pain score., Results: Fifty-seven women were available for evaluation before and after treatment. Before HBOT, patients had severe complaints of pain in the arm/shoulder (46 %), swollen arm/hand (14 %), difficulty to raise arm or move it sideways (45 %), pain in the area of the affected breast (67 %), swollen area of the affected breast (45 %), oversensitivity of the affected breast (54 %), and skin problems on/in the area of the affected breast (32 %); post HBOT, severe complaints were still experienced in 17, 7, 22, 15, 13, 15, and 11 % of the women, respectively. Differences were all significant. The NRS pain score improved at least 1 point (range 0-10) in 81 % of the patients (p < 0.05)., Conclusion: In these breast cancer patients treated with HBOT for LRITT, the patient-reported outcomes were positive and improvements were observed. HBOT was a well-tolerated treatment for LRITT and its side-effects were both minimal and reversible.

Purpose: Setup, range, and anatomical uncertainties influence the dose delivered with intensity modulated proton therapy (IMPT), but clinical quantification of these errors for oropharyngeal cancer is lacking. We quantified these factors and investigated treatment fidelity, that is, robustness, as influenced by adaptive planning and by applying more beam directions., Methods and Materials: We used an in-house treatment planning system with multicriteria optimization of pencil beam energies, directions, and weights to create treatment plans for 3-, 5-, and 7-beam directions for 10 oropharyngeal cancer patients. The dose prescription was a simultaneously integrated boost scheme, prescribing 66 Gy to primary tumor and positive neck levels (clinical target volume-66 Gy; CTV-66 Gy) and 54 Gy to elective neck levels (CTV-54 Gy). Doses were recalculated in 3700 simulations of setup, range, and anatomical uncertainties. Repeat computed tomography (CT) scans were used to evaluate an adaptive planning strategy using nonrigid registration for dose accumulation., Results: For the recalculated 3-beam plans including all treatment uncertainty sources, only 69% (CTV-66 Gy) and 88% (CTV-54 Gy) of the simulations had a dose received by 98% of the target volume (D98%) >95% of the prescription dose. Doses to organs at risk (OARs) showed considerable spread around planned values. Causes for major deviations were mixed. Adaptive planning based on repeat imaging positively affected dose delivery accuracy: in the presence of the other errors, percentages of treatments with D98% >95% increased to 96% (CTV-66 Gy) and 100% (CTV-54 Gy). Plans with more beam directions were not more robust., Conclusions: For oropharyngeal cancer patients, treatment uncertainties can result in significant differences between planned and delivered IMPT doses. Given the mixed causes for major deviations, we advise repeat diagnostic CT scans during treatment, recalculation of the dose, and if required, adaptive planning to improve adequate IMPT dose delivery., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to reduce the incidence of radiation-induced toxicity in patients with early-stage oropharyngeal cancer, using highly conformal radiation techniques., Methods: Between 2000 and 2011, 167 patients with T1-3N0-3 oropharyngeal cancer were treated with 46-Gy intensity-modulated radiation therapy (IMRT) followed by 22-Gy brachytherapy boost. In patients with node-positive disease, neck dissection was performed., Results: The 5-year Kaplan-Meier estimates of local control, regional control, disease-free survival (DFS), and overall survival (OS) were 94%, 97%, 84%, and 72%, respectively. Feeding tubes were required in 26% of the patients. Grade ≥2 late xerostomia and dysphagia were 11% and 8%, respectively. Chemotherapy, tumor subsite, and bilateral neck irradiation correlate significantly with toxicity. Quality of life (QOL) scores deteriorate during and shortly after treatment but returned in all scales to baseline scores within 6 to 12 months, with the exception of xerostomia., Conclusion: Brachytherapy boost and neck dissection (in node-positive oropharyngeal cancer) after 46-Gy of IMRT resulted in excellent outcomes with low incidence of late toxicity and good QOL scores., (Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company.)

This study investigates whether 'pencil beam resampling', i.e. iterative selection and weight optimization of randomly placed pencil beams (PBs), reduces optimization time and improves plan quality for multi-criteria optimization in intensity-modulated proton therapy, compared with traditional modes in which PBs are distributed over a regular grid. Resampling consisted of repeatedly performing: (1) random selection of candidate PBs from a very fine grid, (2) inverse multi-criteria optimization, and (3) exclusion of low-weight PBs. The newly selected candidate PBs were added to the PBs in the existing solution, causing the solution to improve with each iteration. Resampling and traditional regular grid planning were implemented into our in-house developed multi-criteria treatment planning system 'Erasmus iCycle'. The system optimizes objectives successively according to their priorities as defined in the so-called 'wish-list'. For five head-and-neck cancer patients and two PB widths (3 and 6 mm sigma at 230 MeV), treatment plans were generated using: (1) resampling, (2) anisotropic regular grids and (3) isotropic regular grids, while using varying sample sizes (resampling) or grid spacings (regular grid). We assessed differences in optimization time (for comparable plan quality) and in plan quality parameters (for comparable optimization time). Resampling reduced optimization time by a factor of 2.8 and 5.6 on average (7.8 and 17.0 at maximum) compared with the use of anisotropic and isotropic grids, respectively. Doses to organs-at-risk were generally reduced when using resampling, with median dose reductions ranging from 0.0 to 3.0 Gy (maximum: 14.3 Gy, relative: 0%-42%) compared with anisotropic grids and from -0.3 to 2.6 Gy (maximum: 11.4 Gy, relative: -4%-19%) compared with isotropic grids. Resampling was especially effective when using thin PBs (3 mm sigma). Resampling plans contained on average fewer PBs, energy layers and protons than anisotropic grid plans and more energy layers and protons than isotropic grid plans. In conclusion, resampling resulted in improved plan quality and in considerable optimization time reduction compared with traditional regular grid planning.

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.

Because of the scarcity of randomized trials comparing toxicity and outcomes of intensity-modulated radiotherapy (IMRT) for oropharyngeal cancer (OPC) with 3D-conformal radiotherapy (3DCRT), we performed a matched-pair analysis from prospectively collected data from the Head and Neck Tumor Registry of our institution. In the absence of phase III trials, we believe this approach provides the highest quality data possible. Ninety-two patients treated with 3DCRT were matched (1:1) to 92 patients treated with IMRT for 9 potential predictive factors for toxicity and outcome: gender, age, T-stage, N-stage, tumor subsite, unilateral neck irradiation, chemotherapy, neck dissection and boost technique. Groups were compared for acute and late toxicity, locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). Oncologic outcomes were estimated using Kaplan-Meier analyses and toxicity was analyzed according to Common Terminology Criteria for Adverse Events v3.0. The overall incidence of grade 3 acute toxicity was significantly reduced by IMRT, compared to 3DCRT (45% vs. 70%, p = 0.001). The need for tube feeding was reduced from 50% to 37% (p = 0.04). The 3-year actuarial incidence of grade ≥2 late toxicity was also significantly reduced by IMRT, compared to 3DCRT (20% vs. 45%, respectively; p ≤ 0.0001). The incidence of grade ≥ 2 late dysphagia and xerostomia for IMRT vs. 3DCRT were 10% vs. 31% for dysphagia, p = 0.004 and 13% vs. 37%, for xerostomia, respectively (p = 0.001). The 3-year Kaplan-Meier estimates of LRC, DFS, and OS for IMRT vs. 3DCRT were 90% vs. 82% (p = 0.1), 82% vs. 76% (p = 0.3), and 72% vs. 64% (p = 0.2), respectively. In conclusion, the presented non-randomized comparative study of well-matched groups demonstrates the superiority of IMRT vs. 3DCRT for OPC by significantly reducing radiation-induced toxicity without jeopardizing outcomes. The improved therapeutic ratio achieved by the use of IMRT would allow dose escalation of radiotherapy to further improve outcomes of patients with OPC.

Purpose: To analyze whether local tumor control in advanced nasopharyngeal cancer (NPC) can be optimized by boosting the primary dose by endocavitary brachytherapy (EBT)., Methods and Materials: To study the role of EBT, three data sets on NPC, that is, the "Vienna", "Rotterdam," and "Amsterdam" series, with a total number of 411 advanced NPC patients, were available. The Rotterdam series consisted of 72 patients (34 T1,2N+ and 38 T3,4N0,+) and were treated with neoadjuvant chemotherapy followed by external beam radiotherapy (dose 70/2Gy). After 70/2Gy, a boost was applied by EBT (in case of T1,2N+) or stereotactic radiation (in case of T3,4 tumors). The Amsterdam (Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute) series consisted of 76 patients (40 T1,2N+ and 36 T3,4N0,+) and were irradiated to a dose of 70/2Gy with concomitant chemotherapy. No second boost by EBT was applied., Results: In the case of T1,2N+ tumors, the local relapse rate (LRR) was significantly smaller if a boost was applied, that is, 0% (0/34, EBT boost) vs. 14% (14/102, no EBT boost) (p=0.023). For the T3,4 tumors, an LRR of 10% (4/38, EBT or stereotactic radiation boost) vs. 15% (17/111, no boost) was found (p=0.463)., Conclusions: In the case of advanced NPC (T1,2N+ vs. T3,4N+,0), for early T-stages (T1,2N+), an EBT boost seems an excellent way to deliver highly conformal high doses of radiation to the nasopharynx, with high local control rates. For advanced T-stages (T3,4N+,0), the reduction in LRR (10% vs. 15%) was not significant (p=0.463)., (Copyright © 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To prospectively assess the outcome and toxicity of frameless stereotactic body radiotherapy (SBRT) as a treatment option for boosting primary oropharyngeal cancers (OPC) in patients who not suitable for the standard brachytherapy boost (BTB)., Methods and Materials: Between 2005 and 2010, 51 patients with Stage I to IV biopsy-proven OPC who were not suitable for BTB received boosts by means of SBRT (3 times 5.5 Gy, prescribed to the 80% isodose line), after 46 Gy of IMRT to the primary tumor and neck (when indicated). Endpoints of the study were local control (LC), disease-free survival (DFS), overall survival (OS), and acute and late toxicity., Results: After a median follow-up of 18 months (range, 6-65 months), the 2-year actuarial rates of LC, DFS, and OS were 86%, 80%, and 82%, respectively, and the 3-year rates were 70%, 66%, and 54%, respectively. The treatment was well tolerated, as there were no treatment breaks and no Grade 4 or 5 toxicity reported, either acute or chronic. The overall 2-year cumulative incidence of Grade ≥2 late toxicity was 28%. Of the patients with 2 years with no evidence of disease (n = 20), only 1 patient was still feeding tube dependent and 2 patients had Grade 3 xerostomia., Conclusions: According to our knowledge, this study is the first report of patients with primary OPC who received boosts by means of SBRT. Patients with OPC who are not suitable for the standard BTB can safely and effectively receive boosts by SBRT. With this radiation technique, an excellent outcome was achieved. Furthermore, the SBRT boost did not have a negative impact regarding acute and late side effects., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: The treatment of choice for early glottic cancer is still being debated; ultimately it relies on the functional outcome. This paper reports on a novel sparing 4D conformal technique for single vocal cord irradiation (SVCI)., Material and Methods: The records of 164 T1a patients with SCC of the vocal cord, irradiated in the Erasmus MC between 2000 and 2008, were analyzed for local control and overall survival. The quality of life was determined by EORTC H&N35 questionnaires. Also the VHI (voice handicap index), and the TSH (thyroid stimulating hormone) blood levels, were established. On-line image guided SVCI, using cone beam CT or stereotactic radiation therapy (SRT) techniques, were developed., Results: A LC rate at five-years of 93% and a VHI of 12.7 (0-63) was determined. It appeared feasible to irradiate one vocal cord within 1-2mm accuracy. This way sparing of the contralateral (CL) vocal cord and CL normal tissues, could be achieved., Conclusions: Given the accuracy (1-2mm) and small volume disease (CTV limited to one vocal cord), for the use of stereotactic RT techniques SVCI with large fraction sizes is currently being investigated in clinic. It is argued that hypofractionated SVCI can be a competitive alternative to laser surgery., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To validate and clinically evaluate autocontouring using atlas-based autosegmentation (ABAS) of computed tomography images., Methods and Materials: The data from 10 head-and-neck patients were selected as input for ABAS, and neck levels I-V and 20 organs at risk were manually contoured according to published guidelines. The total contouring times were recorded. Two different ABAS strategies, multiple and single subject, were evaluated, and the similarity of the autocontours with the atlas contours was assessed using Dice coefficients and the mean distances, using the leave-one-out method. For 12 clinically treated patients, 5 experienced observers edited the autosegmented contours. The editing times were recorded. The Dice coefficients and mean distances were calculated among the clinically used contours, autocontours, and edited autocontours. Finally, an expert panel scored all autocontours and the edited autocontours regarding their adequacy relative to the published atlas., Results: The time to autosegment all the structures using ABAS was 7 min/patient. No significant differences were observed in the autosegmentation accuracy for stage N0 and N+ patients. The multisubject atlas performed best, with a Dice coefficient and mean distance of 0.74 and 2 mm, 0.67 and 3 mm, 0.71 and 2 mm, 0.50 and 2 mm, and 0.78 and 2 mm for the salivary glands, neck levels, chewing muscles, swallowing muscles, and spinal cord-brainstem, respectively. The mean Dice coefficient and mean distance of the autocontours vs. the clinical contours was 0.8 and 2.4 mm for the neck levels and salivary glands, respectively. For the autocontours vs. the edited autocontours, the mean Dice coefficient and mean distance was 0.9 and 1.6 mm, respectively. The expert panel scored 100% of the autocontours as a "minor deviation, editable" or better. The expert panel scored 88% of the edited contours as good compared with 83% of the clinical contours. The total editing time was 66 min., Conclusion: Multiple-subject ABAS of computed tomography images proved to be a useful novel tool in the rapid delineation of target and normal tissues. Although editing of the autocontours is inevitable, a substantial time reduction was achieved using editing, instead of manual contouring (180 vs. 66 min)., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To develop and evaluate a method for adding dose distributions of combined external beam radiotherapy (EBRT) and brachytherapy (BT) for oropharyngeal patients., Methods and Materials: Two computed tomography (CT) scans were used for 5 patients: the EBRT CT, used for EBRT planning, and the BT CT, acquired after catheter implantation. For each scan, the salivary glands and the chewing and swallowing muscles were contoured, and a dose distribution was calculated. A nonrigid transformation was obtained by registering the organs' surfaces. Then the BT dose distribution was mapped onto the EBRT dose distribution by applying the transformation obtained. To account for differences in fractionation, the physical doses were converted to equivalent dose in 2 Gy (EQD(2)), and the total dose was found by adding dose voxel by voxel. The robustness of the dose addition was investigated by varying delineations and input parameters of the registration method and by varying the α/β parameter for EQD(2). The effect of the perturbations was quantified using dose-volume histograms (DVH) and gamma analyses (distance-to-agreement/dose-difference = 1 mm/1 Gy)., Results: The variations in input parameters and delineations caused only small perturbations in the DVH of the added dose distributions. For most organs the gamma index was low, and it was moderately elevated for organs lying in areas with a steep gradient (median gamma index ≤ 2.3 for constrictor muscles, ≤ 0.7 for all other organs)., Conclusions: The presented method allows adding dose distributions of combined EBRT and BT for oropharyngeal patients. In general, the method is reliable and robust with respect to uncertainties in organ delineation, perturbations in input parameters of the method, and α/β values., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background and Purpose: To investigate the dosimetric impact of not editing auto-contours of the elective neck and organs at risk (OAR), generated with atlas-based autosegmentation (ABAS) (Elekta software) for head and neck cancer patients., Materials and Methods: For nine patients ABAS auto-contours and auto-contours edited by two observers were available. Based on the non-edited auto-contours clinically acceptable IMRT plans were constructed (designated 'ABAS plans'). These plans were then evaluated for the two edited structure sets, by quantifying the percentage of the neck-PTV receiving more than 95% of the prescribed dose (V(95)) and the near-minimum dose (D(99)) in the neck PTV. Dice coefficients and mean contour distances were calculated to quantify the similarity of ABAS auto-contours with the structure sets edited by observer 1 and observer 2. To study the dosimetric importance of editing OAR auto-contours a new IMRT plan was generated for each patient-observer combination, based on the observer's edited CTV and the non-edited salivary gland auto-contours. For each plan mean doses for the non-edited glands were compared with doses for the same glands edited by the observer., Results: For both observers, edited neck CTVs were larger than ABAS auto-contours (p≤ 0.04), by a mean of 8.7%. When evaluating ABAS plans on the PTVs of the edited structure sets, V(95) reduced by 7.2%±5.4% (1 SD) (p<0.03). The mean reduction in D(99) was 14.2 Gy (range 1-54 Gy). Even for Dice coefficients >0.8 and mean contour distances <1mm, reductions in D(99) up to 11Gy were observed. For treatment plans based on observer PTVs and non-edited auto-contoured salivary glands, the mean doses in the edited glands differed by only -0.6 Gy±1.0 Gy (p=0.06)., Conclusions: Editing of auto-contoured neck CTVs generated by ABAS is required to avoid large underdosages in target volumes. Often used similarity measures for evaluation of auto-contouring algorithms, such as dice coefficients, do not predict well for expected PTV underdose. Editing of salivary glands is less important as mean doses achieved for non-edited glands predict well for edited structures., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Comparison of quality of life (QoL) and side effects in a randomized trial for early hyperbaric oxygen therapy (HBOT) after radiotherapy (RT)., Methods and Materials: From 2006, 19 patients with tumor originating from the tonsillar fossa and/or soft palate (15), base of tongue (1), and nasopharynx (3) were randomized to receive HBOT or not. HBOT consisted of 30 sessions at 2.5 ATA (15 msw) with oxygen breathing for 90 min daily, 5 days per week, applied shortly after the RT treatment was completed. As of 2005, all patients received validated questionnaires (i.e., the European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30, EORTC QLQ Head and Neck Cancer Module (H&N35), Performance Status Scale): before treatment; at the start of RT treatment; after 46 Gy; at the end of RT treatment; and 2, 4, and 6 weeks and 3, 6, 12, and 18 months after follow-up., Results: On all QoL items, better scores were obtained in patients treated with hyperbaric oxygen. The difference between HBOT vs. non-HBOT was significant for all parameters: EORTC H&N35 Swallowing (p = 0.011), EORTC H&N35 Dry Mouth (p = 0.009), EORTC H&N35, Sticky Saliva (p = 0.01), PSS Eating in Public (p = 0.027), and Pain in Mouth (visual analogue scale; p < 0.0001)., Conclusions: Patients randomized for receiving hyperbaric oxygen after the RT had better QoL scores for swallowing, sticky saliva, xerostomia, and pain in mouth.

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.

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 1 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).

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.

Background: Our aim was to assess the correlation between the radiation therapy (RT) dose to the mastication apparatus and trismus of oropharyngeal cancer patients., Methods: Eighty-one patients treated with RT were analyzed. The masseter, pterygoid, and temporalis muscles and the coronoid and condyl were delineated on axial CT slices. The mean dose in these structures was correlated with outcome of quality of life questionnaires., Results: Fifty-six (88%) patients responded; 16% of the patients scored grade 3/4 on the Head & Neck 35 "opening mouth" question. A significant correlation was observed between dose in masseter and pterygoid muscles and trismus (p= .02)., Conclusion: Patients treated with brachytherapy received a lower dose in masticatory muscles. A steep dose-effect relationship between mean dose in masseter muscle and pterygoid muscles and the probability of having trismus complaints was observed; with every additional 10 Gy to the pterygoid muscle, an increase of the probability of trismus of 24% was observed.

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.

Treatment planning for high precision radiotherapy of head and neck (H&N) cancer patients requires accurate delineation of many structures and lymph node regions. Manual contouring is tedious and suffers from large inter- and intra-rater variability. To reduce manual labor, we have developed a fully automated, atlas-based method for H&N CT image segmentation that employs a novel hierarchical atlas registration approach. This registration strategy makes use of object shape information in the atlas to help improve the registration efficiency and robustness while still being able to account for large inter-subject shape differences. Validation results showed that our method provides accurate segmentation for many structures despite difficulties presented by real clinical data. Comparison of two different atlas selection strategies is also reported.

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.