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• Normal tissue radiation tolerance in children is different from adults. • In the abdomen, the pancreas and spleen are the most radiosensitive organs-at-risk. • The gonads should be considered the most radiosensitive pelvic organs in children. • Without quantifiable dose effect data, strive for 'as low as reasonably achievable'. As survival improves in childhood cancer, prevention of late treatment-related toxicity in survivors becomes increasingly relevant. Radiotherapy is an important contributor to late toxicity. Therefore, minimizing radiation exposure to normal tissues is an important step towards improving the long-term therapeutic window of childhood cancer treatment. Since children are growing and developing, they are particularly vulnerable to radiation exposure. This makes the 'as low as reasonably achievable (ALARA)' principle even more important. In order to guide and achieve clinically meaningful dose reductions through advanced and emerging radiation techniques, it is important to investigate age-dependent relationships between radiation exposure to healthy tissues and late radiation-induced toxicity. In this review, we provide an overview of literature on the association between radiotherapy dose and late toxicity after abdominal and pelvic irradiation in childhood cancer. With this information, we aim to aid in decision-making regarding radiotherapy for childhood cancer. [ABSTRACT FROM AUTHOR]

Background: Neurocognition and speech, relevant domains in head and neck cancer (HNC), may be affected pretreatment. However, the prevalence of pretreatment deficits and their possible concurrent predictors are poorly understood. Methods: Using an HNC prospective cohort (Netherlands Quality of Life and Biomedical Cohort Study, N ≥ 444) with a cross‐sectional design, we investigated the estimated prevalence of pretreatment deficits and their relationship with selected demographic, behavioral, and disease‐related factors. Results: Using objective assessments, rates of moderate‐to‐severe neurocognitive deficit ranged between 4% and 8%. From patient‐reported outcomes, 6.5% of patients reported high levels of cognitive failures and 46.1% reported speech deficits. Patient‐reported speech functioning was worse in larynx compared to other subsites. Other nonspeech outcomes were unrelated to any variable. Patient‐reported neurocognitive and speech functioning were modestly correlated, especially in the larynx group. Conclusions: These findings indicate that a subgroup of patients with HNC shows pretreatment deficits, possibly accentuated in the case of larynx tumors. [ABSTRACT FROM AUTHOR]

Purpose: Adaptive proton therapy (APT) of lung cancer patients requires frequent volumetric imaging of diagnostic quality. Cone‐beam CT (CBCT) can provide these daily images, but x‐ray scattering limits CBCT‐image quality and hampers dose calculation accuracy. The purpose of this study was to generate CBCT‐based synthetic CTs using a deep convolutional neural network (DCNN) and investigate image quality and clinical suitability for proton dose calculations in lung cancer patients. Methods: A dataset of 33 thoracic cancer patients, containing CBCTs, same‐day repeat CTs (rCT), planning‐CTs (pCTs), and clinical proton treatment plans, was used to train and evaluate a DCNN with and without a pCT‐based correction method. Mean absolute error (MAE), mean error (ME), peak signal‐to‐noise ratio, and structural similarity were used to quantify image quality. The evaluation of clinical suitability was based on recalculation of clinical proton treatment plans. Gamma pass ratios, mean dose to target volumes and organs at risk, and normal tissue complication probabilities (NTCP) were calculated. Furthermore, proton radiography simulations were performed to assess the HU‐accuracy of sCTs in terms of range errors. Results: On average, sCTs without correction resulted in a MAE of 34 ± 6 HU and ME of 4 ± 8 HU. The correction reduced the MAE to 31 ± 4HU (ME to 2 ± 4HU). Average 3%/3 mm gamma pass ratios increased from 93.7% to 96.8%, when the correction was applied. The patient specific correction reduced mean proton range errors from 1.5 to 1.1 mm. Relative mean target dose differences between sCTs and rCT were below ± 0.5% for all patients and both synthetic CTs (with/without correction). NTCP values showed high agreement between sCTs and rCT (<2%). Conclusion: CBCT‐based sCTs can enable accurate proton dose calculations for APT of lung cancer patients. The patient specific correction method increased the image quality and dosimetric accuracy but had only a limited influence on clinically relevant parameters. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to generate normal tissue complication probability (NTCP) models in patients treated with either proton beam therapy (PBT) or intensity-modulated radiation therapy (IMRT) for oropharynx cancer and to use a model-based approach to investigate the added value of PBT in preventing treatment complications.Methods and Materials: For patients with advanced-stage oropharynx cancer treated with curative intent (PBT, n = 30; IMRT, n = 175), NTCP models were developed using multivariable logistic regression analysis with backward selection. For PBT-treated patients, an equivalent IMRT plan was generated to serve as a reference to determine the benefit of PBT in terms of NTCP. The models were then applied to the PBT-treated patients to compare predicted and observed clinical outcomes (calibration-in-the-large). Five binary endpoints were analyzed at 6 months after treatment: dysphagia ≥ grade 2, dysphagia ≥ grade 3, xerostomia ≥ grade 2, salivary duct inflammation ≥ grade 2, and feeding tube dependence. Corresponding toxicity grading was based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4. Paired t tests and Wilcoxon rank tests were used to compare mean NTCP results for endpoints between PBT and IMRT.Results: NTCP models developed based on outcomes from all patients were applied to those receiving PBT. NTCP values were calculated for the equivalent IMRT plans for all PBT-treated patients, revealing significantly higher NTCP values with IMRT. PBT was associated with statistically significant reductions in the mean NTCP values for each endpoint at 6 months after treatment, with the largest absolute differences in rates of ≥grade 2 dysphagia and ≥grade 2 xerostomia.Conclusions: NTCP models predict significant improvements in the probability of short-term, treatment-related toxicity with PBT compared with IMRT for oropharyngeal cancer. This study demonstrates an NTCP model-based approach to compare predicted patient outcomes when randomized data are not available. [ABSTRACT FROM AUTHOR]

Purpose: The treatment of moving targets with scanned proton beams is challenging. For motion mitigation, an Active Breathing Coordinator (ABC) can be used to assist breath‐holding. The delivery of pencil beam scanning fields often exceeds feasible breath‐hold durations, requiring high breath‐hold reproducibility. We evaluated the robustness of scanned proton therapy against anatomical uncertainties when treating nonsmall‐cell lung cancer (NSCLC) patients during ABC controlled breath‐hold. Methods: Four subsequent MRIs of five healthy volunteers (3 male, 2 female, age: 25–58, BMI: 19–29) were acquired under ABC controlled breath‐hold during two simulated treatment fractions, providing both intrafractional and interfractional information about breath‐hold reproducibility. Deformation vector fields between these MRIs were used to deform CTs of five NSCLC patients. Per patient, four or five cases with different tumor locations were modeled, simulating a total of 23 NSCLC patients. Robustly optimized (3 and 5 mm setup uncertainty respectively and 3% density perturbation) intensity‐modulated proton plans (IMPT) were created and split into subplans of 20 s duration (assumed breath‐hold duration). A fully fractionated treatment was recalculated on the deformed CTs. For each treatment fraction the deformed CTs representing multiple breath‐hold geometries were alternated to simulate repeated ABC breath‐holding during irradiation. Also a worst‐case scenario was simulated by recalculating the complete treatment plan on the deformed CT scan showing the largest deviation with the first deformed CT scan, introducing a systematic error. Both the fractionated breath‐hold scenario and worst‐case scenario were dosimetrically evaluated. Results: Looking at the deformation vector fields between the MRIs of the volunteers, up to 8 mm median intra‐ and interfraction displacements (without outliers) were found for all lung segments. The dosimetric evaluation showed a median difference in D98% between the planned and breath‐hold scenarios of −0.1 Gy (range: −4.1 Gy to 2.0 Gy). D98% target coverage was more than 57.0 Gy for 22/23 cases. The D1 cc of the CTV increased for 21/23 simulations, with a median difference of 0.9 Gy (range: −0.3 to 4.6 Gy). For 14/23 simulations the increment was beyond the allowed maximum dose of 63.0 Gy, though remained under 66.0 Gy (110% of the prescribed dose of 60.0 Gy). Organs at risk doses differed little compared to the planned doses (difference in mean doses <0.9 Gy for the heart and lungs, <1.4% difference in V35 [%] and V20 [%] to the esophagus and lung). Conclusions: When treating under ABC controlled breath‐hold, robustly optimized IMPT plans show limited dosimetric consequences due to anatomical variations between repeated ABC breath‐holds for most cases. Thus, the combination of robustly optimized IMPT plans and the delivery under ABC controlled breath‐hold presents a safe approach for PBS lung treatments. [ABSTRACT FROM AUTHOR]

Background and purpose: Incontinence, hematuria, voiding frequency and pain during voiding are possible side effects of radiotherapy among patients treated for prostate cancer. The objective of this study was to develop multivariable NTCP models for these side effects. Material and methods: This prospective cohort study was composed of 243 patients with localized or locally advanced prostate cancer (stage T1-3). Genito-urinary (GU) toxicity was assessed using a standardized follow-up program. The GU toxicity endpoints were scored using the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE 3.0) scoring system. The full bladder and different anatomical subregions within the bladder were delineated. A least absolute shrinkage and selection operator (LASSO) logistic regression analysis was used to analyze dose volume effects on the four individual endpoints. Results: In the univariable analysis, urinary incontinence was significantly associated with dose distributions in the trigone (V55-V75, mean). Hematuria was significantly associated with the bladder wall dose (V40-V75, mean), bladder dose (V70-V75), cardiovascular disease and anticoagulants use. Pain during urinating was associated with the dose to the trigone (V50-V75, mean) and with trans transurethral resection of the prostate (TURP). In the final multivariable model urinary incontinence was associated with the mean dose of the trigone. Hematuria was associated with bladder wall dose (V75) and cardiovascular disease, while pain during urinating was associated with trigone dose (V75) and TURP. No significant associations were found for increase in voiding frequency. Conclusions: Radiation-induced urinary side effects are associated with dose distributions to different organs as risk. Given the dose effect relationships found, decreasing the dose to the trigone and bladder wall may reduce the incidence of incontinence, pain during voiding and hematuria, respectively. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to analyze the effect of fractionation schedule on local control in postoperative radiotherapy (RT) for sinonasal malignant melanoma. Methods Sixty-three patients who were treated with surgery and postoperative RT in 4 accredited head and neck cancer centers in the Netherlands between 1998 and 2013 were retrospectively studied. Outcomes with conventional fractionation (2-2.4 Gy per fraction; n = 27) were compared to hypofractionation (4-6 Gy per fraction; n = 36). The primary endpoint was local control and the secondary endpoint was toxicity. Results Comparable local control rates were found after 2 and 5 years (63% vs 64% and 47% vs 53%; P = .73 for, respectively, conventional fractionation vs hypofractionation). Local recurrences were predominantly present ipsilateral (92%) and within the irradiated volume (88%). Late toxicity grade ≥ 3 was observed in 2 of 63 patients, 1 patient in both groups. Conclusion Radiotherapy fractionation schedule did not influence the local control rate or the incidence of late toxicity in patients treated with surgery and RT for sinonasal malignant melanoma in this retrospective analysis. Due to this retrospective nature and the limited number of patients, strong recommendations cannot be made. Expected toxicity, patient convenience, and workload may be taken into account for the choice of fractionation schedule until conclusive evidence becomes available. [ABSTRACT FROM AUTHOR]

Background The optimal cumulative dose and timing of cisplatin administration in various concurrent chemoradiotherapy protocols for nonmetastatic head and neck squamous cell carcinoma (HNSCC) has not been determined. Methods The absolute survival benefit at 5 years of concurrent chemoradiotherapy protocols versus radiotherapy alone observed in prospective randomized trials reporting on the use of cisplatin monochemotherapy for nonnasopharyngeal HNSCC was extracted. In the case of nonrandomized studies, the outcome results at 2 years were compared between groups of patients receiving different cumulative cisplatin doses. Results Eleven randomized trials and 7 nonrandomized studies were identified. In 6 definitive radiotherapy phase III trials, a statistically significant association ( p = .027) between cumulative cisplatin dose, independent of the schedule, and overall survival benefit was observed for higher doses. Conclusion Results support the conclusion that the cumulative dose of cisplatin in concurrent chemoradiation protocols for HNSCC has a significant positive correlation with survival. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2151-E2158, 2016 [ABSTRACT FROM AUTHOR]

Purpose: To compare the clinical benefit of robust optimized Intensity Modulated Proton Therapy (minimax IMPT) with current photon Intensity Modulated Radiation Therapy (IMRT) and PTV-based IMPT for head and neck cancer (HNC) patients. The clinical benefit is quantified in terms of both Normal Tissue Complication Probability (NTCP) and target coverage in the case of setup and range errors. Methods and Materials: For 10 HNC patients, PTV-based IMRT (7 fields), minimax and PTV-based IMPT (2, 3, 4, 5 and 7 fields) plans were tested on robustness. Robust optimized plans differed from PTV-based plans in that they target the CTV and penalize possible error scenarios, instead of using the static isotropic CTV-PTV margin. Perturbed dose distributions of all plans were acquired by simulating in total 8060 setup (±3.5 mm) and range error (±3%) combinations. NTCP models for xerostomia and dysphagia were used to predict the clinical benefit of IMPT versus IMRT. Results: The robustness criterion was met in the IMRT and minimax IMPT plans in all error scenarios, but this was only the case in 1 of 40 PTV-based IMPT plans. Seven (out of 10) patients had relatively large NTCP reductions in minimax IMPT plans compared to IMRT. For these patients, xerostomia and dysphagia NTCP values were reduced by 17.0% (95% CI; 13.0–21.1) and 8.1% (95% CI; 4.9–11.2) on average with minimax IMPT. Increasing the number of fields did not contribute to plan robustness, but improved organ sparing. Conclusions: The estimated clinical benefit in terms of NTCP of robust optimized (minimax) IMPT is greater than that of IMRT and PTV-based IMPT in HNC patients. Furthermore, the target coverage of minimax IMPT plans in the presence of errors was comparable to IMRT plans. [ABSTRACT FROM AUTHOR]

Background: Curative radiotherapy or chemoradiation for head and neck cancer (HNC) may result in severe acute and late side effects, including tube feeding dependence. The purpose of this prospective cohort study was to develop a prediction model for tube feeding dependence 6 months (TUBEM6) after curative (chemo-) radiotherapy in HNC patients. Patients and Methods: Tube feeding dependence was scored prospectively. To develop the multivariable model, a group LASSO analysis was carried out, with TUBEM6 as the primary endpoint (n = 427). The model was then validated in a test cohort (n = 183). The training cohort was divided into three groups based on the risk of TUBEM6 to test whether the model could be extrapolated to later time points (12, 18 and 24 months). Results: Most important predictors for TUBEM6 were weight loss prior to treatment, advanced T-stage, positive N-stage, bilateral neck irradiation, accelerated radiotherapy and chemoradiation. Model performance was good, with an Area under the Curve of 0.86 in the training cohort and 0.82 in the test cohort. The TUBEM6-based risk groups were significantly associated with tube feeding dependence at later time points (p<0.001). Conclusion: We established an externally validated predictive model for tube feeding dependence after curative radiotherapy or chemoradiation, which can be used to predict TUBEM6. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background The purpose of this study was to validate bioelectrical impedance analysis (BIA) using the Geneva equation for fat-free mass (FFM) in patients with head and neck cancer. Methods In 24 patients with head and neck cancer, agreement between BIA (FFMBIA) and dual energy x-ray absorptiometry (FFMDXA) 1 week before (T0), 1 month (T1), and 4 months (T2) after cancer treatment was analyzed. Results FFMBIA did not differ from FFMDXA (mean difference 0.71 ± 1.9, 0.30 ± 1.9, and 0.02 ± 2.1 kg) at any time point. Only at T0, mean FFM correlated to the difference between FFMDXA and FFMBIA ( r = 0.48; p = .017). Limits of agreement were 3.8, 3.7, and 4.1 kg, respectively. Concordance Correlation Coefficients were 0.98 at all time points. Conclusion BIA may be used to assess FFM with reasonable validity based on mean-level comparisons, but differences between BIA and DXA may vary by about 4 kg in an individual patient. These results require confirmation in a larger sample of patients with head and neck cancer. © 2013 Wiley Periodicals, Inc. Head Neck 36: 585-591, 2014 [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma of the hypopharynx represents a distinct clinical entity. Most patients present with significant comorbidities and advanced-stage disease. The overall survival is relatively poor because of high rates of regional and distant metastasis at presentation or early in the course of the disease. A multidisciplinary approach is crucial in the overall management of these patients to achieve the best results and maintain or improve functional results. Traditionally, operable hypopharyngeal cancer has been treated by total (occasionally partial) laryngectomy and partial or circumferential pharyngectomy, followed by reconstruction and postoperative radiotherapy in most cases. Efforts to preserve speech and swallowing function in the surgical treatment of hypopharyngeal (and laryngeal) cancer have resulted in a declining use of total laryngopharyngectomy and improved reconstructive efforts, including microvascular free tissue transfer. There are many surgical, as well as nonsurgical, options available for organ and function preservation, which report equally effective tumor control and survival. The selection of appropriate treatment is of crucial importance in the achievement of optimal results for these patients. In this article, several aspects of surgical and nonsurgical approaches in the treatment of hypopharyngeal cancer are discussed. Future studies must be carefully designed within clearly defined populations and use uniform terminology and standardized functional assessment and declare appropriate patient or disease endpoints. These studies should focus on improvement of resultsx, without increasing patient morbidity. In this respect, technical improvements in radiotherapy such as intensity-modulated radiotherapy, advances in supportive care, and incorporation of newer systemic agents such as targeted therapy, are relevant developments. © 2010 Wiley Periodicals, Inc. Head Neck, 2012 [ABSTRACT FROM AUTHOR]

Up-front surgery and postoperative radiotherapy constitute a well-recognized treatment concept for locally or regionally advanced squamous cell carcinoma of the head and neck. This 'treatment package' is further intensified with the concomitant application of chemotherapy during irradiation when high-risk features (ie, microscopically involved resection margins, extracapsular extension of the tumor from neck nodes, the presence of soft tissue deposits) are found on histopathologic examination of a resected specimen. With regard to neck disease, however, the demarcation line between low- and higher-risk clinical situations, which would differ with respect to the need for postoperative radiotherapy, is not clear. In an attempt to define the low-risk characteristics of disease in the neck that do not require adjuvant irradiation, we reviewed the available literature reports for any direct or indirect evidence on the value of postoperative radiotherapy in various clinical scenarios. The number of positive lymph nodes found in a dissected tissue specimen that should be used as a 'cut-off' point for introduction of postoperative radiotherapy was evaluated in the context of both primary tumor characteristics and type of neck dissection. © 2010 Wiley Periodicals, Inc. Head Neck, 2012 [ABSTRACT FROM AUTHOR]

Summary: Treatment choice in elderly pharyngeal cancer patient is disputed. This study was aimed to asses association of co-morbidity, complications and survival in different treatment modalities of pharyngeal cancer patients. Retrospective analysis of pharyngeal cancer patients, diagnosed between 1997 and 2007 in a tertiary referral hospital was performed. Patients 75years and older (n =42), were matched with two control patients 64years and younger (n =84). Co-morbidity (ACE-27), treatment related complications and survival data were assessed and analyzed. Frequency of co-morbidity was similar in both age groups, although discarding alcohol abuse resulted in higher incidence of co-morbidity in the elderly group. Complication rate was not significantly different. In a multivariate analysis only stage found to be a significant predictor of complications. Survival estimates adjusted to sex, age and birth cohort revealed co-morbidity to be a significant predictor for survival in elderly and young patients. No evidence has been found to treat elderly pharyngeal cancer patients differently than younger ones. Treatment related complications are not predicted by co-morbidities in young and elderly patients; however survival is predicted by comorbidity. Therefore thorough pre-treatment evaluation and care necessary in the elderly population. [Copyright &y& Elsevier]

Loco-regional control rate of nasopharyngeal carcinoma (NPC) has improved significantly in the past decade. However, local recurrence still represents a major cause of mortality and morbidity in advanced stages, and management of local failure remains a challenging issue in NPC. The best salvage treatment for local recurrent NPC remains to be determined. The options include brachytherapy, external radiotherapy, stereotactic radiosurgery, and nasopharyngectomy, either alone or in different combinations. In this article we will discuss the different options for salvage of locally recurrent NPC. Retreatment of locally recurrent NPC using radiotherapy, alone or in combination with other treatment modalities, as well as surgery, can result in long-term local control and survival in a substantial proportion of patients. For small-volume recurrent tumors (T1-T2) treated with external radiotherapy, brachytherapy or stereotactic radiosurgery, comparable results to those obtained with surgery have been reported. In contrast, treatment results of advanced-stage locally recurrent NPC are generally more satisfactory with surgery (with or without postoperative radiotherapy) than with reirradiation. [ABSTRACT FROM AUTHOR]

Summary: This review discusses the role of adjuvant treatment after curative surgery for patients with head and neck squamous cell carcinoma (HNSCC). In general, patients with unfavourable prognostic factors have a high-risk of loco-regional recurrence and subsequent worse survival after surgery alone and are therefore considered proper candidates for adjuvant treatment by either postoperative radiotherapy alone or postoperative chemoradiation. Selection of the most optimal adjuvant treatment strategy should be based on the most important prognostic factors. In this review, the different treatment strategies will be discussed in general. More specifically, we will discuss the role of the interval between surgery and radiotherapy, the overall treatment time of radiation, the selection of target volumes for radiation and the value of adding concomitant chemotherapy to postoperative radiation. [Copyright &y& Elsevier]

Background: The shift from conventional two-dimensional (2D) to three-dimensional (3D)-conformal target definition and dose-planning seems to have introduced volumetric as well as geometric changes. The purpose of this study was to compare coverage of computed tomography (CT)-based breast and boost planning target volumes (PTV), absolute volumes irradiated, and dose delivered to the organs at risk with conventional 2D and 3D-conformal breast conserving radiotherapy. Methods: Twenty-five patients with left-sided breast cancer were subject of CT-guided target definition and 3D-conformal dose-planning, and conventionally defined target volumes and treatment plans were reconstructed on the planning CT. Accumulated dose-distributions were calculated for the conventional and 3D-conformal dose-plans, taking into account a prescribed dose of 50 Gy for the breast plans and 16 Gy for the boost plans. Results: With conventional treatment plans, CT-based breast and boost PTVs received the intended dose in 78% and 32% of the patients, respectively, and smaller volumes received the prescribed breast and boost doses compared with 3D-conformal dose-planning. The mean lung dose, the volume of the lungs receiving > 20 Gy, the mean heart dose, and volume of the heart receiving > 30 Gy were significantly less with conventional treatment plans. Specific areas within the breast and boost PTVs systematically received a lower than intended dose with conventional treatment plans. Conclusion: The shift towards CT-guided target definition and planning as the golden standard for breast conserving radiotherapy has resulted in improved target coverage at the cost of larger irradiated volumes and an increased dose delivered to organs at risk. Tissue is now included into the breast and boost target volumes that was never explicitly defined or included with conventional treatment. Therefore, a coherent definition of the breast and boost target volumes is needed, based on clinical data confirming tumour control probability and normal tissue complication probability with the use of 3D-conformal radiotherapy. [ABSTRACT FROM AUTHOR]

Patients with squamous cell carcinoma of the oropharynx are generally treated with (chemo) radiation. Patients with oropharyngeal cancer have better survival than patients with squamous cell carcinoma of other head and neck subsites, especially when related to human papillomavirus. However, radiotherapy results in a substantial percentage of survivors suffering from significant treatment-related side-effects. Late radiation-induced side-effects are mostly irreversible and may even be progressive, and particularly xerostomia and dysphagia affect health-related quality of life. As the risk of radiation-induced side-effects highly depends on dose to healthy normal tissues, prevention of radiation-induced xerostomia and dysphagia and subsequent improvement of health-relatedquality of life can be obtained by applying proton therapy, which offers the opportunity to reduce the dose to both the salivary glands and anatomic structures involved in swallowing. This review describes the results of the first cohort studies demonstrating that proton therapy results in lower dose levels in multiple organs at risk, which translates into reduced acute toxicity (i.e. up to 3 months after radiotherapy), while preserving tumour control. Next to reducing mucositis, tube feeding, xerostomia and distortion of the sense of taste, protons can improve general well-being by decreasing fatigue and nausea. Proton therapy results in decreased rates of tube feeding dependency and severe weight loss up to 1 year after radiotherapy, and may decrease the risk of radionecrosis of the mandible. Also, the model-based approach for selecting patients for proton therapy in the Netherlands is described in this review and future perspectives are discussed. [ABSTRACT FROM AUTHOR]

Purpose: Acute coronary events (ACEs) are considered the most important side effect of radiation therapy (RT) for breast cancer, but underlying mechanisms still have to be identified. Process-oriented models mathematically describe the development of disease and provide a link between mechanisms and subsequent risk. Here, this link is exploited to learn about the underlying mechanisms from the observed age-time patterns of ACE risk.Methods and Materials: A process-oriented model of atherosclerosis and subsequent ACEs was applied to a contemporary breast cancer cohort of 810 patients with measurements of coronary artery calcification. Patients with prior ischemic heart disease were excluded. The process-oriented model describes disease development as a series of different stages. Different variants of the model were fitted to the data. In each variant, one stage was assumed to be accelerated in relation to mean heart dose.Results: During a mean follow-up of 9.1 years, 25 ACEs occurred. The model reproduced the prevalence and associated risk of coronary calcifications. Mean heart dose significantly improved the fit only when implemented as affecting a late stage of atherosclerosis on already-existing complicated lesions (achieving P = .007). This can be understood by atherosclerosis being a slowly progressing disease. Therefore, an increase in ACEs a few years after RT requires advanced atherosclerosis at the time of RT.Conclusions: Risk of ACE increases within a few years in patients with advanced atherosclerosis at RT. Therefore, patients should be assessed for cardiovascular risk, and older patients need to be considered for heart-sparing techniques. [ABSTRACT FROM AUTHOR]

Re-irradiation can be considered for local recurrence or new tumours adjacent to a previously irradiated site to achieve durable local control for patients with cancer who have otherwise few therapeutic options. With the use of new radiotherapy techniques, which allow for conformal treatment plans, image guidance, and short fractionation schemes, the use of re-irradiation for different sites is increasing in clinical settings. Yet, prospective evidence on re-irradiation is scarce and our understanding of the underlying radiobiology is poor. Our consensus on re-irradiation aims to assist in re-irradiation decision making, and to standardise the classification of different forms of re-irradiation and reporting. The consensus has been endorsed by the European Society for Radiotherapy and Oncology and the European Organisation for Research and Treatment of Cancer. The use of this classification in daily clinical practice and research will facilitate accurate understanding of the clinical implications of re-irradiation and allow for cross-study comparisons. Data gathered in a uniform manner could be used in the future to make recommendations for re-irradiation on the basis of clinical evidence. The consensus document is based on an adapted Delphi process and a systematic review of the literature was done according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). [ABSTRACT FROM AUTHOR]

• Brachytherapy (BT) provided superior 3-year local control over EBRT (95% vs 71%). • Survival with preserved nose was significantly higher after BT compared to EBRT. • Late toxicity mainly comprised grade 1–2 ulcers and was transient in 50% of cases. • Tumor diameter >1.5 cm and T2-stage predicted worse regional control. Primary radiotherapy is often preferred for early-stage cancer of the nasal vestibule (CNV), combining high disease control with preservation of nasal anatomy. However, due to practice variation and an absence of comparative trials, no consensus exists on preference for brachytherapy (BT) or external beam radiotherapy (EBRT). We compared these modalities in terms of disease control, nose preservation rates and toxicity. Medical records of 225 patients with T1-T2 squamous cell carcinoma of the nasal vestibule treated with 3D image-guided primary radiotherapy between Jan 2010 and Dec 2016 in 6 Dutch institutions were reviewed retrospectively. 153 of 225 patients were treated with BT, 65 with EBRT and 7 with other modalities. Median follow-up was 46 months. Overall 3-year local control (LC) and regional control (RC) were 87% and 89%. Five-year disease-specific survival (DSS) and overall survival (OS) were 94% and 82%. Three-year survival with preserved nose (SPN) was 76%. BT provided higher 3-year LC (95% vs 71%, p < 0.01) and SPN compared with EBRT (82% vs 61%, p < 0.01). Multivariable and propensity-score-matched cohort analyses confirmed better outcomes after BT. No difference was seen in DSS or OS. Five-year incidence of CTCAE 5.0 grade ≥2 toxicity was higher after BT (20% vs 3%, p = 0.03) and consisted mostly of radiation ulcers. 50% of all late toxicity recovered. In this largest-to-date multicenter analysis of T1-T2 CNV, BT achieved superior LC and SPN compared with EBRT. Grade 1–2 radiation ulcers occurred more frequently after brachytherapy, but were transient in half the cases. Considering these results, BT can be recommended as first-line treatment for T1-T2 CNV. [ABSTRACT FROM AUTHOR]

• Significant dosimetric sparing of organs is seen with protons for esophageal cancer. • Retrospective studies showed improved clinical benefit and lymphopenia with protons. • One randomized trial demonstrated toxicity burden reduction of protons vs. IMRT. • Future larger randomized trials are needed to confirm these findings. Esophageal cancer remains one of the leading causes of death from cancer across the world despite advances in multimodality therapy. Although early-stage disease can often be treated surgically, the current state of the art for locally advanced disease is concurrent chemoradiation, followed by surgery whenever possible. The uniform midline tumor location puts a strong importance on the need for precise delivery of radiation that would minimize dose to the heart and lungs, and the biophysical properties of proton beam makes this modality potential ideal for esophageal cancer treatment. This review covers the current state of knowledge of proton therapy for esophageal cancer, focusing on published retrospective single- and multi-institutional clinical studies, and emerging data from prospective clinical trials, that support the benefit of protons vs photon-based radiation in reducing postoperative complications, cardiac toxicity, and severe radiation induced immune suppression, which may improve survival outcomes for patients. In addition, we discuss the incorporation of immunotherapy to the curative management of esophageal cancers in the not-too-distant future. However, there is still a lack of high-level evidence to support proton therapy in the treatment of esophageal cancer, and proton therapy has its limitations in clinical application. It is expected to see the results of future large-scale randomized clinical trials and the continuous improvement of proton radiotherapy technology. [ABSTRACT FROM AUTHOR]

[Display omitted] • Proton therapy can be as robust as photon therapy to inter-fraction motion. • Proton therapy significantly reduces organ at risk doses compared to photon therapy. • Two ITV-based treatment planning techniques for PBS-PT presented. Large-field photon radiotherapy is current standard in the treatment of cervical cancer patients. However, with the increasing availability of Pencil Beam Scanning Proton Therapy (PBS-PT) and robust treatment planning techniques, protons may have significant advantages for cervical cancer patients in the reduction of toxicity. In this study, PBS-PT and photon Volumetric Modulated Arc Therapy (VMAT) were compared, examining target coverage and organ at risk (OAR) dose, taking inter- and intra-fraction motion into account. Twelve cervical cancer patients were included in this in-silico planning study. In all cases, a planning CT scan, five weekly repeat CT scans (reCTs) and an additional reCT 10 min after the first reCT were available. Two-arc VMAT and robustly optimised two- and four-field (2F and 4F) PBS-PT plans were robustly evaluated on planCTs and reCTs using set-up and range uncertainty. Nominal OAR doses and voxel-wise minimum target coverage robustness were compared. Average voxel-wise minimum accumulated doses for pelvic target structures over all patients were adequate for both photon and proton treatment techniques (D98 > 95%, [91.7–99.3%]). Average accumulated dose of the para-aortic region was lower than the required 95%, D98 > 94.4% [91.1–98.2%]. With PBS-PT 4F, dose to all OARs was significantly lower than with VMAT. Major differences were observed for mean bowel bag V 15Gy : 60% [39–70%] for VMAT vs 30% [10–52%] and 32% [9–54%] for PBS-PT 2F and 4F and for mean bone marrow V 10Gy : 88% [82–97%] for VMAT vs 66% [60–73%] and 67% [60–75%] for PBS-PT 2F and 4F. Robustly optimised PBS-PT for cervical cancer patients shows equivalent target robustness against inter- and intra-fraction variability compared to VMAT, and offers significantly better OAR sparing. [ABSTRACT FROM AUTHOR]

• IMPT accomplishes a significant and consistent dose reduction to OARs. • IMPT has comparable robustness compared to VMAT for oesophageal cancer. • Re-planning was required more often for IMPT compared to VMAT. Intensity-modulated proton therapy (IMPT) is expected to result in clinical benefits by lowering radiation dose to organs-at-risk (OARs). However, there are concerns about plan robustness due to motion. To address this uncertainty we evaluated the robustness of IMPT compared to the widely clinically used volumetric modulated arc therapy (VMAT) on weekly repeated computed tomographies (CT). 19 patients with oesophageal cancer were evaluated. IMPT and VMAT plans were created on a planning 4-Dimensional CT (p4DCT) and evaluated on weekly repeated 4DCTs (r4DCT). In case of inadequate target coverage or unacceptable high dose to normal tissue, re-planning was performed. Dose distributions of the r4DCTs were warped to p4DCT, resulting in an estimated actual given dose (EAGD). Compared to VMAT, IMPT resulted in significantly lowered dose to heart, lungs, spleen, liver and kidneys. For IMPT, target coverage was adequate (after max 1 replanning) in 17/19 cases. In two cases target coverage remained insufficient. However, in one of these patients the summed dose was insufficient (due to tumor shrinkage) while weekly coverage was adequate. For the other patient the target coverage was also insufficient by VMAT, due to large anatomical changes during treatment. For VMAT, adequate target coverage was achieved in 18/19 cases without re-planning. However, for reasons of high OAR dose re-planning was required in two cases. IMPT reduces the dose to OARs significantly, while achieving adequate target coverage in the majority of patients. Re-planning was necessary for both IMPT and VMAT due to anatomical changes. [ABSTRACT FROM AUTHOR]

• Dose degradations caused by anatomy are larger than DIR uncertainties. • Averaged results from several DIRs provide a good representation of dose degradation. • We caution the use of only one DIR algorithm for dose accumulation. Non-small cell lung cancer (NSCLC) patients show typically large anatomical changes during treatment, making recalculation or adaption necessary. For report and review, the applied treatment dose can be accumulated on the reference planning CT using deformable image registration (DIR). We investigated the dosimetric impact of using six different clinically available DIR algorithms for dose accumulation in presence of inter-fractional anatomy variations. For seven NSCLC patients, proton treatment plans with 66 Gy-RBE to the planning target volume (PTV) were optimised. Nine repeated CTs were registered to the planning CT using six DIR algorithms each. All CTs were acquired in visually guided deep-inspiration breath-hold. The plans were recalculated on the repeated CTs and warped back to the planning CT using the corresponding DIRs. Fraction doses warped with the same DIR were summed up to six different accumulated dose distributions per patient, and compared to the initial dose. The PTV-V95 of accumulated doses decreased by 16% on average over all patients, with variations due to DIR selection of 8.7%. A separation of the dose effects caused by anatomical changes and DIR uncertainty showed a good agreement between the dose degradation caused by anatomical changes and the dose predicted from the average of all DIRs (differences of only 1.6%). The dose degradation caused by anatomical changes was more pronounced than the uncertainty of employing different DIRs for dose accumulation, with averaged results from several DIRs providing a good representation of dose degradation caused by anatomy. However, accumulated dose variations between DIRs can be substantial, leading to an additional dose uncertainty. [ABSTRACT FROM AUTHOR]

• For 42 oropharyngeal patients robust optimized proton arc therapy plans were generated and we compared the plans to clinical IMPT and VMAT plans. • Compared to VMAT and IMPT, Proton Arc Therapy significantly reduces integral dose and dose to numerous organs-at-risk and thus normal tissue complication probabilities for oropharyngeal cancer patients. • For our 230 oropharyngeal cancer patient cohort, an additional 14% of patients would qualify for proton therapy if PAT instead of IMPT treatment planning is used in model-based patient selection. In the model-based approach, patients qualify for proton therapy when the reduction in risk of toxicity (ΔNTCP) obtained with IMPT relative to VMAT is larger than predefined thresholds as defined by the Dutch National Indication Protocol (NIPP). Proton arc therapy (PAT) is an emerging technology which has the potential to further decrease NTCPs compared to IMPT. The aim of this study was to investigate the potential impact of PAT on the number of oropharyngeal cancer (OPC) patients that qualify for proton therapy. A prospective cohort of 223 OPC patients subjected to the model-based selection procedure was investigated. 33 (15%) patients were considered unsuitable for proton treatment before plan comparison. When IMPT was compared to VMAT for the remaining 190 patients, 148 (66%) patients qualified for protons and 42 (19%) patients did not. For these 42 patients treated with VMAT, robust PAT plans were generated. PAT plans provided better or similar target coverage compared to IMPT plans. In the PAT plans, integral dose was significantly reduced by 18% relative to IMPT plans and by 54% relative to VMAT plans. PAT decreased the mean dose to numerous organs-at-risk (OARs), further reducing NTCPs. The ΔNTCP for PAT relative to VMAT passed the NIPP thresholds for 32 out of the 42 patients treated with VMAT, resulting in 180 patients (81%) of the complete cohort qualifying for protons. PAT outperforms IMPT and VMAT, leading to a further reduction of NTCP-values and higher ΔNTCP-values, significantly increasing the percentage of OPC patients selected for proton therapy. [ABSTRACT FROM AUTHOR]

• ΔNTCP based on (reconstructed) delivered dose is compared to ΔNTCP based on planned dose. • ΔNTCP based on the planned dose is an unbiased predictor of ΔNTCP based on the delivered dose. • For a single patient, variations of ±2% compared to planned ΔNTCP can be expected. • The deformable image registration algorithm affects ΔNTCP up to 1.6%. • The choice of α / β ratio has only a minor effect on the ΔNTCP. Model-based selection of proton therapy patients relies on a predefined reduction in normal tissue complication probability (NTCP) with respect to photon therapy. The decision is necessarily made based on the treatment plan, but NTCP can be affected when the delivered treatment deviates from the plan due to delivery inaccuracies. Especially for proton therapy of lung cancer, this can be important because of tissue density changes and, with pencil beam scanning, the interplay effect between the proton beam and breathing motion. In this work, we verified whether the expected benefit of proton therapy is retained despite delivery inaccuracies by reconstructing the delivered treatment using log-file based dose reconstruction and inter- and intrafractional accumulation. Additionally, the importance of two uncertain parameters for treatment reconstruction, namely deformable image registration (DIR) algorithm and α / β ratio, was assessed. The expected benefit or proton therapy was confirmed in 97% of all studied cases, despite regular differences up to 2 percent point (p.p.) NTCP between the delivered and planned treatments. The choice of DIR algorithm affected NTCP up to 1.6 p.p., an order of magnitude higher than the effect of α / β ratio. For the patient population and treatment technique employed, the predicted clinical benefit for patients selected for proton therapy was confirmed for 97.0% percent of all cases, although the NTCP based proton selection was subject to 2 p.p. variations due to delivery inaccuracies. [ABSTRACT FROM AUTHOR]

Background: The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials.Methods: For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival.Findings: Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0·94, 95% CI 0·90-0·98; p=0·0033), with an absolute difference at 5 years of 3·1% (95% CI 1·3-4·9) and at 10 years of 1·2% (-0·8 to 3·2). We found a significant interaction (p=0·051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0·83, 0·74-0·92), with absolute differences at 5 years of 8·1% (3·4 to 12·8) and at 10 years of 3·9% (-0·6 to 8·4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1·22, 1·05-1·42; p=0·0098), with absolute differences at 5 years of -5·8% (-11·9 to 0·3) and at 10 years of -5·1% (-13·0 to 2·8).Interpretation: This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested.Funding: Institut National du Cancer; and Ligue Nationale Contre le Cancer. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC).Methods and Materials: Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2. The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D2 - D98, where D2 and D98 are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans.Results: The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively.Conclusions: In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters. [ABSTRACT FROM AUTHOR]

Objectives: To compare cumulative cisplatin dose and toxicity between patients who received 3-weekly versus weekly cisplatin during adjuvant radiotherapy for high-risk head and neck squamous cell carcinoma (HNSCC).Materials and Methods: Consecutive HNSCC patients with involved resection margins and/or extra-capsular extension in two tertiary cancer centers with different institutional practices were identified. Cumulative cisplatin dose was calculated and information on toxicity reviewed and compared between patients who received 3-weekly versus weekly cisplatin.Results: Of 270 high risk patients, 60 received 3-weekly 100mg/m(2) and 48 received weekly 50mg/m(2) cisplatin during adjuvant radiotherapy (60-66Gy in 30-33 fractions). Fourteen patients received other chemotherapy schedules and 148 received no chemotherapy. Mean cumulative cisplatin dose was 199.4mg/m(2) (standard error (SE) 5.4) in 3-weekly versus 239.8mg/m(2) (SE 11.0, P=0.001) in weekly treated patients. Cumulative cisplatin ⩾200mg/m(2) was given to 67.7% of patients in the 3-weekly cohort and 85.2% (P=0.039) in the weekly cohort. The rate of feeding tube dependency 6months after treatment, osteoradionecrosis, neutropenic fever, and persistent renal function decline were not statistically different.Conclusions: About one half of high-risk HNSCC patients are not eligible for cisplatin during postoperative radiotherapy. Patients treated with weekly 50mg/m(2) cisplatin received a higher cumulative dose with comparable toxicity as patients who received 3-weekly 100mg/m(2) cisplatin. Efficacy and applicability to the frequently used weekly 40mg/m(2) schedule remains to be evaluated. [ABSTRACT FROM AUTHOR]

Objectives: The introduction of intensity modulated radiation therapy (IMRT) has led to new possibilities in the treatment of head and neck cancer (HNC). Limited information is available on how this more advanced radiation technique affects the oral microflora. In a prospective study we assessed the effects of various advanced treatments for HNC on the oral microflora, as well as the effects of elimination of oral foci of infection.Materials and Methods: All consecutive dentate patients >18years, diagnosed with a primary oral or oropharynx carcinoma and seen for a pre-treatment dental screening (May 2011-May 2013) were included. Patients were grouped by oncologic treatment: surgery (SURG), IMRT (IMRT) or IMRT+chemotherapy (CHIMRT). Dental screening data, demographic data, subgingival biofilm samples, oral lavages and whole saliva samples were obtained to microbiologically analyze the effects of cancer treatments (1-year follow-up).Results: This study included 82 patients (29 SURG, 26 IMRT and 27 CHIMRT). The trends in changes in prevalence and proportions of microorganisms were comparable in the IMRT and CHIMRT group. However, relative to the SURG group, increased prevalence of enteric rods, staphylococci and Candida species was observed in the IMRT and CHIMRT groups. In these groups, elimination of oral foci decreased the frequency of detection of pathogens such as Porphyromonas gingivalis, Tannerella forsythia and Streptococcus mutans.Conclusion: Different treatments in HNC patients result in different changes in the oral microflora. Opportunistic pathogens such as staphylococci, enteric rods and Candida sp. tend to increase in prevalence after IMRT with or without chemotherapy, but not after surgical intervention. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Stereotactic ablative radiotherapy (SABR; or stereotactic body radiotherapy, SBRT) emerges as treatment option for pulmonary oligometastatic disease (OMD), but there are no studies comparing SABR with pulmonary metastasectomy (PME). We analysed consecutive patients referred via a university-hospital based multidisciplinary team. Material and methods: Patients were offered PME as first choice and SABR in case they were considered to be less suitable surgical candidates. Overall survival was the primary endpoint. Secondary endpoints were progression-free-survival, local control of treated metastases, and freedom-from-failure of a local-only treatment strategy without systemic therapy. Results: From 2007 until 2010, 110 patients were treated and analysed (PME, n =68; SABR, n =42). Median follow-up time was 43months (minimally, 25). Estimated overall survival rates at one, three, and five years were 87%, 62%, and 41% for PME, and 98%, 60%, and 49% for SABR, respectively (logrank-test, p =0.43). Local control at two years was 94% for SABR and 90% for PME. Progression-free survival was 17% at three years, but 43% of the patients still had not failed a local-only treatment strategy. Conclusions: Although SABR was second choice after PME, survival after PME was not better than after SABR. Prospective comparative studies are clearly required to define the role of both, SABR and PME in OMD. [Copyright &y& Elsevier]

Summary: Distant metastases from head and neck squamous cell carcinoma (HNSCC), though rare at initial presentation, remain an important manifestation of cancer recurrence and mortality. Although generally considered incurable with a dismal prognosis despite palliative therapy, highly selected patients with distant metastases may have a long term survival benefit from aggressive surgery or radiotherapy. Advances in systemic treatments also may improve patient survival. This article reviews the current state of management of HNSCC patients with distant metastases. [ABSTRACT FROM AUTHOR]

Abstract: Speech impairment often occurs in patients after treatment for head and neck cancer. A specific speech characteristic that influences intelligibility and speech quality is voice-onset-time (VOT) in stop consonants. VOT is one of the functionally most relevant parameters that distinguishes voiced and voiceless stops. The goal of the present study is to investigate the role and validity of acoustic-phonetic and artificial neural network analysis (ANN) of stop consonants in a multidimensional speech assessment protocol. Speech recordings of 51 patients 6months after treatment for oral or oropharyngeal cancer and of 18 control speakers were evaluated by trained speech pathologists regarding intelligibility and articulation. Acoustic-phonetic analyses and artificial neural network analysis of the phonological feature voicing were performed in voiced /b/, /d/ and voiceless /p/ and /t/. Results revealed that objective acoustic-phonetic analysis and feature analysis for /b, d, p/ distinguish between patients and controls. Within patients, /t, d/ distinguish for tumour location and tumour stage. Measurements of the phonological feature voicing in almost all consonants were significantly correlated with articulation and intelligibility, but not with self-evaluations. Overall, objective acoustic-phonetic and feature analyses of stop consonants are feasible and contribute to further development of a multidimensional speech quality assessment protocol. [Copyright &y& Elsevier]

Purpose: To test the hypothesis that scanned intensity-modulated proton therapy (IMPT) results in a significant dose reduction to the parotid and submandibular glands as compared with intensity-modulated radiotherapy with photons (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for oropharyngeal cancer. In addition, we investigated whether the achieved dose reductions would theoretically translate into a reduction of salivary dysfunction and xerostomia. Methods and Materials: Ten patients with N0 oropharyngeal carcinoma were used. The intensity-modulated plans delivered simultaneously 70 Gy to the boost planning target volume (PTV2) and 54 Gy to the elective nodal areas (PTV1). The 3D-CRT technique delivered sequentially 70 Gy and 46 Gy to PTV2 and PTV1, respectively. Normal tissue complication probabilities were calculated for salivary dysfunction and xerostomia. Results: Planning target volume coverage results were similar for IMPT and IMRT. Intensity-modulated proton therapy clearly improved the conformity. The 3D-CRT results were inferior to these results. The mean dose to the parotid glands by 3D-CRT (50.8 Gy), IMRT (25.5 Gy), and IMPT (16.8 Gy) differed significantly. For the submandibular glands no significant differences between IMRT and IMPT were found. The dose reductions obtained with IMPT theoretically translated into a significant reduction in normal tissue complication probability. Conclusion: Compared with IMRT and 3D-CRT, IMPT improved sparing of the organs at risk, while keeping similar target coverage results. The dose reductions obtained with IMPT vs. IMRT and 3D-CRT varied widely per individual patient. Intensity-modulated proton therapy theoretically translated into a clinical benefit for most cases, but this requires clinical validation. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: FDG-PET/CT has proven to be useful in the staging process of esophageal tumours. This review analysed the role of FDG-PET/CT in tumour delineation and radiotherapy planning in comparison with CT alone among patients with esophageal cancer. Thereby we focused on the detection of the primary tumour and lymph nodes by FDG-PET/CT, changes in target volume (TV) delineation based on FDG-PET/CT and its validity, changes in inter- and intra-observer variability in TV delineation, consequences for radiotherapy treatment planning with regard to either target volumes or organs at risk and finally on the validation of FDG-PET/CT-based TVs in terms of treatment outcome. Methods: A literature search was performed in MEDLINE and Cochrane library databases for studies concerning the current value of FDG-PET/CT in tumour detection and delineation and radiotherapy-planning procedures among patients with esophageal cancer. Both prospective and retrospective studies were included. Results: Fifty publications met the eligibility criteria, of which 19 were review papers and one was a case report. The remaining 30 publications reported on the results of original studies. FDG-PET was able to identify most primary tumours, with a sensitivity and specificity for the detection of metastatic lymph nodes of 30–93% and 79–100%. The use of FDG-PET/CT resulted in changes of target volumes, and consequently in changes in treatment planning. However, evidence supporting the validity of the use of FDG-PET/CT in the tumour delineation process is very limited. Only three studies reported a significant positive correlation between FDG-PET-based tumour lengths and pathological findings. There were two studies that tested the influence of FDG-PET/CT to the inter- and intra-observer variability. One of them found a significant decrease in inter- and intra-observer variability, while the others did not. Furthermore, there are no studies demonstrating the use of PET/CT in terms of improved locoregional control or survival. Conclusion: Since the literature is very limited standard implementation of FDG-PET/CT into the tumour delineation process for radiation treatment seems unjustified and needs further clinical validation first. [Copyright &y& Elsevier]

Purpose: After treatment for early glottic cancer, a considerable number of patients end up with voice problems interfering with daily life activities. A 5-item screening questionnaire was designed for detection of voice impairment. The purpose of this study is to assess psychometric properties of this questionnaire in clinical practice. Methods and Materials: The questionnaire was completed by 110 controls without voice complaints and 177 patients after radiotherapy or laser surgery for early glottic cancer. Results: Based on normative data of the controls, a score of 5 or less on at least 1 of the 5 questions was considered to state overall voice impairment. Reliability of the questionnaire proved to be good. Voice impairment was reported in 44% of the patients treated with radiotherapy vs. 29% of the patients treated with endoscopic laser surgery. Conclusions: The questionnaire proved to be a reliable, valid, and feasible method to detect voice impairment in daily life. The questionnaire is easy to fill in, and interpretation is straightforward. It is useful for both radiation oncologists and otorhinolaryngologists in their follow-up of patients treated for early glottic cancer. [Copyright &y& Elsevier]