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Background and purpose: Previously, PET image biomarkers (PET-IBMs) – the 90th percentile standardized uptake value (P90-SUV) and the Mean SUV (Mean-SUV) of the contralateral parotid gland (cPG) – were identified as predictors for late-xerostomia following head and neck cancer (HNC) radiotherapy. The aim of the current study was to assess in an independent validation cohort whether these pre-treatment PET-IBM can improve late-xerostomia prediction compared to the prediction with baseline xerostomia and mean cPG dose alone. Materials and methods: The prediction endpoint was patient-rated moderate-to-severe xerostomia at 12 months after radiotherapy. The PET-IBMs were extracted from pre-treatment 18 F-FDG PET images. The performance of the model (base model) with baseline xerostomia and mean cPG dose alone and models with additionally P90-SUV or Mean-SUV were tested in the current independent validation cohort. Specifically, model discrimination (area under the curve: AUC) and calibration (calibration plot) were evaluated. Results: The current validation cohort consisted of 137 patients of which 40% developed moderate-to-severe xerostomia at 12 months. Both the PET-P90 model (AUC:PET-P90 = 0.71) and the PET-Mean model (AUC: PET-Mean = 0.70) performed well in the current validation cohort. Moreover, their performance were improved compared to the base model (AUC:base model= 0.68). The calibration plots showed a good fit of the prediction to the actual rates for all tested models. Conclusion: PET-IBMs showed an improved prediction of late-xerostomia when added to the base model in this validation cohort. This contributed to the published hypothesis that PET-IBMs include individualized information and can serve as a pre-treatment risk factor for late-xerostomia.

Mature lymphoproliferative diseases are a heterogeneous group of neoplasms arising from different stages of B-cell and T-cell development. With improved understanding of the molecular processes in lymphoma and novel treatment options, arises a growing need for the molecular characterisation of tumours. Molecular imaging with single-photon-emission CT and PET using specific radionuclide tracers can provide whole-body information to investigate cancer biology, to evaluate phenotypic heterogeneity, to identify resistance to targeted therapy, and to assess the biodistribution of drugs in patients. In this Review, we evaluate the existing literature on molecular imaging in lymphoma, other than 18F-fluordeoxyglucose molecular imaging. The aim is to examine the contribution of molecular imaging to the understanding of the biology of lymphoma and to discuss potential implications for the diagnostics and therapy of this disease. Finally, we discuss possible applications for molecular imaging of patients with lymphoma in the clinical context.

Purpose: This study investigated whether Magnetic Resonance image biomarkers (MR-IBMs) were associated with xerostomia 12 months after radiotherapy (Xer(12m)) and to test the hypothesis that the ratio of fat-to-functional parotid tissue is related to Xer(12m). Additionally, improvement of the reference Xer(12m) model based on parotid gland dose and baseline xerostomia, with MR-IBMs was explored.Methods: Parotid gland MR-IBMs of 68 head and neck cancer patients were extracted from pre-treatment T1-weighted MR images, which were normalized to fat tissue, quantifying 21 intensity and 43 texture image characteristics. The performance of the resulting multivariable logistic regression models after bootstrapped forward selection was compared with that of the logistic regression reference model. Validity was tested in a small external cohort of 25 head and neck cancer patients.Results: High intensity MR-IBM P90 (the 90th intensity percentile) values were significantly associated with a higher risk of Xer(12m). High P90 values were related to high fat concentration in the parotid glands. The MR-IBM P90 significantly improved model performance in predicting Xer(12m) (likelihood-ratio-test; p = 0.002), with an increase in internally validated AUC from 0.78 (reference model) to 0.83 (P90). The MR-IBM P90 model also outperformed the reference model (AUC = 0.65) on the external validation cohort (AUC = 0.83).Conclusion: Pre-treatment MR-IBMs were associated to radiation-induced xerostomia, which supported the hypothesis that the amount of predisposed fat within the parotid glands is associated with Xer(12m). In addition, xerostomia prediction was improved with MR-IBMs compared to the reference model. (C) 2018 The Authors. Published by Elsevier B.V.

Background: Since its introduction, the outcome of the SLNB is one of the most important prognostic factors in melanoma patients. A negative sentinel node however, does not guarantee a recurrence-free follow-up. This study was performed to determine risk factors of regional or systemic disease recurrence in node negative melanoma patients. Material and methods: Data concerning patients treated between 1996 and 2014 in the University Medical Center Groningen were prospectively collected. The database contained patient and tumor characteristics, follow-up, recurrence and survival data. Cox regression analyses were used to determine variables associated with systemic first site of recurrence in sentinel node negative patients. Results: A total of 668 SLNB's were performed between 1996 and 2014. The SLNB was positive in 27.8% of the patients and negative in 68.6% of the patients. Recurrence rates were 53.2% in the SLNB positive group and 17.9% in the SLNB negative group. Thirty and a half percent of all patients recurred (204/668), 77% of these patients progressed to stage IV during the course of their disease. Multivariate cox regression analysis of factors associated with immediate stage IV recurrence in sentinel node negative patients revealed melanoma located on the head/neck (HR 3.09, p: 0.035) and the presence of ulceration (HR 2.31, p: 0.035) as significant factors. In sentinel node negative patients with a nodular melanoma the ever recurrence rate was 38/128 (29.7%), if ulceration was present the recurrence rate was 43.1%, the first site of recurrence was systemic in 64% of these patients. Analysis of ever stage IV recurrence in all patients revealed SLNB positive results of strong predictive value (HR 3.00, P

Background: The treatment landscape of metastatic castration resistant prostate cancer (mCRPC) has changed with the introduction of abiraterone acetate (AA), enzalutamide (EN) and radium-223 (Ra-223). Little is known about the cost-effectiveness of these novel agents. This study investigates the cost-effectiveness of Ra-223 in the Netherlands. First, the costeffectiveness of Ra-223 will be evaluated against best supportive care (BSoC) in the mCRPC population. Second, the cost-effectiveness of Ra-223 in the post-chemo setting will be evaluated against the active comparators AA and EN. Material and Methods: A Markov model with five health states is used to describe disease progression and evaluate the cost-effectiveness. The health states are: progression-free survival (PFS) without a symptomatic skeletal event (SSE), progressed disease without SSE, PFS after experiencing a SSE, progressed disease after experiencing a SSE, and death. Disease progression is measured by alkaline phosphatase (comparator=BSoC) or prostate specific antigen. Efficacy, safety and quality adjusted life year (QALY) data were extracted from Phase III RCT's. Efficacy and safety of Ra-223 versus AA and EN was obtained by indirect treatment comparisons. The model has been validated by specialists treating mCRPC. Analyses were performed from a societal perspective, including costs outside the health care budget. Results: Compared to BSoC, Ra-223 has higher quality adjusted survival (0.29 QALYs) and lifetime costs (€22.485) in mCRPC patients, resulting in an incremental cost-effectiveness ratio of €78.642 per QALY. This is below the proposed Dutch threshold of €80.000. Probabilistic sensitivity analyses reveal a 33% chance for Ra-223 to be cost-effective compared to BSoC at this threshold. Cost-effectiveness of Ra-223 in the postchemo setting compared to active comparators is as follows. While quality adjusted survival of Ra-223 is similar to AA, Ra-223 has lower lifetime costs (€5.905), which are mainly driven by lower drug and SSE treatment costs. Probabilistic sensitivity analyses show a 78% chance for Ra-223 to be cost-effective compared to AA at a threshold of €80.000. Compared to EN, Ra-223 has a slightly lower QALY gain (-0.06) and lower lifetime costs (-€7.255), resulting in only a 19% chance of EN to be cost-effective compared to Ra-223 at a €80.000 threshold. Conclusions: Our model suggests that Ra-223 may be cost-effective compared to BSoC and AA in the Netherlands, with Ra-223 even dominating AA (evaluated in post-chemo patients only). Although EN may lead to slightly more health in post-chemo patients, this health gain is accompanied by extra costs resulting in EN not being considered costeffective compared to Ra-223 according to the Dutch threshold. Ra-223's cost-effectiveness compared to AA and EN should be interpreted with caution due to indirect treatment comparisons.