Prediction of patient-rated radiation-induced xerostomia

Een onderdeel van de behandeling van patiënten met tumoren in het hoofdhalsgebied omvat meestal radiotherapie. Bij bestraling in het hoofdhalsgebied worden delen van de speekselklieren meebestraald. Een van de meest voorkomende bijwerkingen na curatieve bestraling voor hoofdhalstumoren is daarom ook de verminderde productie van speeksel door de speekselklieren. Verminderde productie van speeksel kan leiden tot klachten van droge mond, veranderde smaak, slik- en spraakproblemen en is van invloed op de kwaliteit van leven. Het hoofddoel van dit promotieonderzoek was het ontwikkelen en valideren van multivariate predictie modellen voor verschillende aspecten van patiëntgescoorde drogemond klachten na behandeling met radiotherapie. In de analyses werden zowel de dosisverdelingen in verschillende speekselklieren als andere klinische factoren meegnomen. Uit dit proefschrift kunnen we concluderen dat verminderde speekselproductie, resulterende in matig tot ernstige patiëntgescoorde xerostomie en plakkerig speeksel, nog een frequent voorkomende bijwerking is bij patiënten die curatief behandeld zijn met (chemo)radiatie voor hoofd-halskanker. Het risico op klachten van patiëntgescoorde xerostomie en plakkerig speeksel hangt van verschillende factoren af. De bevindingen in dit proefschrift bieden mogelijke aanknopingspunten om groepen patiënten te selecteren die voordeel zouden kunnen hebben van behandelingen met nieuwe bestralingstechnieken, zoals een behandeling met protonen

The impact of late treatment-toxicity on generic health-related quality of life in head and neck cancer patients after radiotherapy

SummaryTo examine the impact of late treatment-related xerostomia and dysphagia on health-related quality of life (HRQOL) in head and neck cancer (HNC) patients after radiotherapy. A multi-center cross-sectional survey was performed. Patients with a follow-up of at least 6months after curative radiotherapy, without evidence of recurrent disease were eligible for inclusion. The Euroqol-5D questionnaire (EQ-5D) was filled out and toxicity was scored and converted to the RTOG scale. The EQ-5D measures generic HRQOL in terms of utility and visual analogue scale (VAS) scores. Missing data on the EQ-5D were imputed using multiple imputation. HRQOL was compared between subgroups of patients with and without toxicity. Subsequently, the impact of xerostomia and dysphagia on HRQOL was analyzed using multivariate regression analyses. Both analyses were performed separately for utility scores and VAS scores. The study population was composed of 396 HNC patients. The average utility and VAS scores were 0.85 (scale 0–1) and 75 (scale 0–100). Subgroups of patients with xerostomia and/or dysphagia showed statistically significantly lower utility and VAS scores (P=0.000–0.022). The multivariate regression model showed that xerostomia and dysphagia were negative predictors of both utility and VAS scores. Other factors which influenced HRQOL in at least one of the two regression models were: sex, tumor location and the addition of surgery to radiotherapy. Xerostomia and dysphagia diminish generic HRQOL. Moreover dysphagia affects patients’ HRQOL stronger than xerostomia

High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients

Background. Hyperphosphataemia is associated with increased mortality in patients with chronic kidney disease (CKD) stage IV or on dialysis. Furthermore, in animal studies, elevated plasma phosphate has been shown to be associated with an accelerated decline in renal function. The aim of this study was to determine the association of plasma phosphate with renal function loss and mortality in CKD stage IV - V pre-dialysis patients with GFR <20 ml/min/1.73 m(2). Methods. Incident pre-dialysis patients were included between 1999 and 2001 in the multi-centre PREPARE study, and followed until 2003 or death. Rate of decline in renal function for each patient was calculated by linear regression using the Modification of Diet in Renal Disease (MDRD) formula to estimate GFR (eGFR). Results. A total of 448 patients were included [mean (SD) age 60 (15) years, eGFR 13 (5.4) ml/min/1.73 m(2), decline in renal function 0.38 (0.95) ml/min/ month]. Phosphate concentration at baseline was 4.71 (1.16) mg/dl, calcium 9.25 (0.77) mg/dl and calcium - phosphate product 43.5 (10.9) mg(2)/dl(2). For each mg/dl higher phosphate concentration, the mean (95% CI) decline in renal function increased with 0.154 (0.071 - 0.237) ml/min/ month. After adjustment, this association remained [beta 0.178 ( 0.082 - 0.275)]. Seven percent of the patients died. Crude mortality risk was 1.25 (0.85 - 1.84) per mg/dl increase in phosphate, which increased to 1.62 (1.02 - 2.59) after adjustment. Conclusions. High plasma phosphate is an independent risk factor for a more rapid decline in renal function and a higher mortality during the pre-dialysis phase. Plasma phosphate within the normal range is likely of vital importance in pre-dialysis patients

Role of minor salivary glands in developing patient-rated xerostomia and sticky saliva during day and night

Purpose: The purpose of this prospective study was to investigate the relationship between xerostomia during the day (XERday) and night (XERnight) and sticky saliva during the day (STICday) and night (STICnight) and dose distributions in different major and minor salivary glands among head and neck cancer (HNC) patients treated with primary radiotherapy (RT) or chemoradiation (CHRT). Methods and materials: The study population was composed of 201 consecutive HNC patients treated with intensity modulated radiotherapy (IMRT) or 3-dimensional conformal radiotherapy (3D-CRT). All patients were included in a standard follow up programme in which acute and late side effects and quality of life (QoL) were prospectively assessed, prior to, during and after treatment. The primary endpoints were XERday, XERnight, STICday, STICnight as assessed by the Groningen Radiotherapy Induced Xerostomia questionnaire. (GRIX) six months after completion of treatment. Organs at risk (OARs) potentially involved in salivary function were delineated on planning-CT, including the parotid, submandibular and sublingual glands and the minor glands in the soft palate, buccal mucosa and lips. Patients with moderate-to-severe xerostomia or moderate-to-severe sticky saliva, respectively, at baseline were excluded. In order to determine which salivary glands were most important, a multivariate logistic regression analysis with an extended bootstrapping technique was used. Results: In total, 29% and 19% of the cases suffered from XERday and XERnight, respectively. The multivariate analysis showed that baseline xerostomia and the mean parotid gland dose were the most important predictors for XERday and XERnight. At 6 months after (CH)RT, 10% and 12% of the cases reported STICday and STICnight respectively. We were not able to identify prognostic factors related to dose distributions with regard to STICday. The mean submandibular gland dose was associated with STICnight. Baseline xerostomia and sticky saliva scores on the GRIX were associated with XERday, XERnight, STICday. Increasing age was correlated with both XERnight and STICnight. Conclusion: Organs at risk for XERday and STICday are similar to organs at risk for XERnight and STICnight. (C) 2013 Published by Elsevier Ireland Ltd

The QUANTEC criteria for parotid gland dose and their efficacy to prevent moderate to severe patient-rated xerostomia

Background. Recently, the Quantitative Analysis of Normal Tissue Effect in the Clinic (QUANTEC) Group defined dose-volume constraints for the parotid glands to avoid severe xerostomia. The aim of this study was to determine if application of these QUANTEC criteria also protected against moderate-to-severe patient-rated xerostomia. Material and methods. The study population consisted of 307 head and neck cancer patients treated with primary (chemo) radiotherapy, either with 3D-CRT (56%) or with IMRT (44%). All patients participated in a standard follow-up program in which radiation-induced toxicity and quality of life were prospectively assessed. Patients who met the QUANTEC criteria were classified as low risk and otherwise as high risk. Results. In total, 41% of the patients (treated with 3D-CRT and IMRT) were classified as low risk patients. In the group treated with 3D-CRT and IMRT, it was possible to meet the QUANTEC criteria in 47% and 32% of the patients, respectively. Sparing the parotid glands with IMRT was considerably more difficult in patients with lymph node metastases and in patients with nasopharyngeal and oropharyngeal tumours. Low risk patients reported significantly less moderate-to-severe xerostomia than high risk patients. However, the predicted risk of elderly patients and patients with pre-existing minor patient-rated xerostomia at baseline was > 20%, even when the QUANTEC criteria were met. Conclusions. Significantly lower rates of radiation-induced patient-rated xerostomia were found among low risk patients treated according to the QUANTEC criteria, but these criteria do not completely protect against xerostomia. Particularly in elderly patients and patients already suffering from minor xerostomia at baseline, the QUANTEC criteria do not sufficiently protect against persistent, moderate-to-severe patient-rated xerostomia

A Prospective Cohort Study on Radiation-induced Hypothyroidism: Development of an NTCP Model

Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism. Methods and Materials: The thyroid-stimulating hormone (TSH) level of 105 patients treated with (chemo-) radiation therapy for head-and-neck cancer was prospectively measured during a median follow-up of 2.5 years. Hypothyroidism was defined as elevated serum TSH with decreased or normal free thyroxin (T4). A multivariate logistic regression model with bootstrapping was used to determine the most important prognostic variables for radiation-induced hypothyroidism. Results: Thirty-five patients (33%) developed primary hypothyroidism within 2 years after radiation therapy. An NTCP model based on 2 variables, including the mean thyroid gland dose and the thyroid gland volume, was most predictive for radiation-induced hypothyroidism. NTCP values increased with higher mean thyroid gland dose (odds ratio [OR]: 1.064/Gy) and decreased with higher thyroid gland volume (OR: 0.826/cm(3)). Model performance was good with an area under the curve (AUC) of 0.85. Conclusions: This is the first prospective study resulting in an NTCP model for radiation-induced hypothyroidism. The probability of hypothyroidism rises with increasing dose to the thyroid gland, whereas it reduces with increasing thyroid gland volume. (C) 2012 Elsevier Inc