Early Response Assessment on Mid-Treatment CT Predicts Loco-Regional Recurrence in Oropharyngeal Cancer Patients Treated with Definitive Radiation Therapy

Publication date: Available online 6 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Rafi Kabarriti, N. Patrik Brodin, George Lundgren, Nitin Ohri, Wolfgang A. Tomé, Shalom Kalnicki, Madhur K. Garg
Purpose/Objective(s)To evaluate if response assessment based on mid-treatment computed tomography (CT) scans during definitive radiation therapy (RT) for oropharyngeal head and neck cancer (HNC) can predict for loco-regional recurrence (LRR).Materials/MethodsHNC patients treated at our institution with RT undergo CT rescans at 15^th fraction and are replanned in case of inadequate dose to gross disease or increased dose to organs-at-risk. A retrospective cohort analysis was performed on 96 consecutive patients with oropharyngeal cancer treated in 2007-2015 with mid-treatment rescans. The volume of primary disease and involved lymph nodes were delineated on pre- and mid-treatment CT. Univariable and multivariable Cox proportional hazards regression analysis were used to evaluate the efficacy of mid-treatment reduction in tumor volume as a predictor of LRR. Risk-stratification was performed by dichotomizing patients into high- and low-risk groups based on mid-treatment response as well as p-16 status and smoking history.ResultsWith a median follow-up of 34 months, 14 patients experienced LRR. The median reduction in total tumor volume was 18.7% (IQR: 8.4%-30.9%). Reduction in total tumor volume > median is an independent predictor of LRR (HR: 0.22; 95%CI: 0.05–0.89; p=0.020), and the reduction in primary tumor volume is an even stronger predictor (HR: 0.11; 95%CI: 0.02–0.57; p=0.002). Stratifying patients into a high-risk group with reduction in total tumor volume at mid-treatment ≤ median, p-16 negative status, and smoking status >10 pack years, and a low-risk group without these factors, there was a clear separation in Kaplan-Meier curves with actuarial 3-year loco-regional control, progression-free survival and overall survival rates for the high-risk patients of 45.7%, 38.2%, 71.8% compared to 90.7%, 70.6%, 89.8% for low-risk patients, respectively (p≤0.021 for all).ConclusionOur study shows that early response assessment based on mid-treatment CT is an independent predictor of LRR and can be used to effectively distinguish high-risk and low-risk patients, allowing for risk-adaptive treatment stratification at the midway point.

Teaser

In a cohort study of 96 oropharyngeal cancer patients undergoing definitive radiation therapy, we identified early response assessment based on mid-treatment CT at the 15^th RT fraction as an independent predictor of locoregional recurrence. Combining this with p-16 and smoking status, we were able to effectively distinguish high-risk and low-risk patients, potentially allowing for more precise risk-adaptive treatment stratification.


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Neurocognitive testing in West African children 3 to 6 years of age: challenges and implications for data analyses

Publication date: Available online 6 April 2018
Source:Brain Research Bulletin
Author(s): Florence Bodeau-Livinec, Leslie L. Davidson, Roméo Zoumenou, Achille Masosugbodji, Michel Cot, Michael J. Boivin
ObjectiveWhen testing African children with developmental and cognitive standardized tests from high-income countries (HIC), investigators are uncertain as to whether to apply the HIC norms for these tests when standardizing a child's raw-score performance on the basis of age. The present study compared the construct validity of both raw and HIC-based standardized scores for the Mullen Scales of Early Learning (MSEL) and the Kaufman Assessment Battery in Children − 2nd edition (KABC-II) for Beninese children in a rural setting from three to six years of age.MethodsSeventy-four children 3 to 4 yrs of age were assessed with the MSEL, and 61 eligible older children (5 to 6 yrs of age) were assessed with the KABC-II. Assessors spoke the instructions to the children and caregivers for the assessment items in the local language. The developmental quality of the home environment was evaluated with the Caldwell HomeObservationfor Measurement of the Environment (HOME) inventory, and a material possessions and housing quality checklist was used as a measure of socio-economic status (SES). Children's mothers were given the Raven's Progressive Matrices test (nonverbal cognitive ability), and the Edinburgh Postpartum Depression Scale (EPDS) (emotional wellbeing).ResultsFor the MSEL, the 4-yr old group performed significantly better than the 3-yr old group on both the raw and standardized score comparisons for all scales. These differences were attenuated when using standardized scores, although the MSEL standardized cognitive composite score was still highly significant between years of age. When comparing 5- to 6-yr olds on KABC-II subtest and global scale performance, comparisons between the raw and standardized mean score performances were much less consistent. Generally, 6-yr olds performed significantly better than 5-yr olds on the raw score comparisons on the KABC-II subtests, but not so for standardized scores. Parent-child interactions assessed through the HOME measure was associated with both raw and standardized MSEL cognitive composite score outcomes on a multiple regression analysis. SES was the only significant predictor for KABC-II raw and standardized outcomes.ConclusionStandardization using HIC norms was not optimal, resulting in minimal impact to account for age when using the MSEL, and lower scores for oldest children compared with youngest children when using the KABC2. This is likely due to children in Benin drifting away from HIC-based norms with each passing year of age, systematically lowering standardized performance measures. These findings support the importance of having a local comparison group of reference or control children to allow for adjusted (for age, HOME, and SES) raw score comparisons when using western-based tests for developmental and neuropsychological evaluation.



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Excessive endoplasmic reticulum stress and decreased neuroplasticity-associated proteins in prefrontal cortex of obese rats and the regulatory effects of aerobic exercise

Publication date: Available online 6 April 2018
Source:Brain Research Bulletin
Author(s): Feng Li, Bei bei Liu, Ming Cai, Jing jing Li, Shu-jie Lou
Studies have shown high fat diet induced obesity may cause cognition impairment and down-regulation of neuroplasticity-associated proteins, while aerobic exercise could improve that damage. Endoplasmic reticulum stress (ERS) has been reported to play a key role in regulating neuroplasticity-associated proteins expression, folding and post-translational modification in hippocampus of obese rodent models, however, the effects of ERS on neuroplasticity-associated proteins and possible underlying mechanisms in prefrontal cortex are not fully clear. In order to clarify changes of neuroplasticity-associated proteins and ERS in the prefrontal cortex of obese rats, male SD rats were fed on high fat diet for 8 weeks to establish the obese model. Then, 8 weeks of aerobic exercise treadmill intervention was arranged for the obese rats. Results showed that high fat diet induced obesity caused hyperlipidemia, and significantly promoted FATP1 expression in the prefrontal cortex, meanwhile, we found up-regulation of GRP78, p-PERK, p-eIF2α, caspase-12, CHOP, and Bax/Bcl-2, reflecting the activation of ERS and ERS-mediated apoptosis. Moreover, reduced BDNF and SYN was found in obese rats. However, FATP1, GRP78, p-PERK, p-eIF2α, caspase-12, CHOP, and Bax/Bcl-2 expressions were obviously reversed by aerobic exercise intervention. These results suggested that dietary obesity could induce Prefrontal ERS in SD rats and excessive ERS may play a critical role in decreasing the levels of neuroplasticity-associated proteins. Moreover, aerobic exercise could relieve ERS, thus promoted the expression of neuroplasticity-associated proteins.



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Bilateral pneumothorax, surgical emphysema and pneumomediastinum in a young male patient following MDMA intake

MDMA (3,4-methylenedioxymethamphetamine) or 'Ecstasy' is an illicit drug frequently used by young people at parties and 'raves'. It is readily available in spite of the fact that it is illegal.¹ It is perceived by a lot of young people as being 'harmless', but there have been a few high-profile deaths associated with its use.² Known side effects of MDMA include hyperthermia, rhabdomyolysis, coagulopathy and cardiac arrhythmias.³ Rarer side effects include surgical emphysema and pneumomediastinum, which have been better described with cocaine abuse.^4–6 We present a case of bilateral pneumothorax, surgical emphysema and pneumomediastinum in a young man after taking ecstasy.

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Low-dose warfarin maternal anticoagulation and fetal warfarin syndrome

Fetuses exposed to warfarin during pregnancy are at an increased risk of developing an embryopathy known as fetal warfarin syndrome or warfarin embryopathy. The most consistent anomalies are nasal hypoplasia and stippling of vertebrae or bony epiphyses. Management of pregnant patients on anticoagulation is challenging. Current guidelines suggest the use of warfarin if the therapeutic dose is ≤5 mg/day. We report the case of a newborn with signs of warfarin embryopathy born from a mother anticoagulated with warfarin due to mechanical mitral and aortic heart valves. Warfarin was required at the dose of 5 mg/day and was withheld without medical advice between weeks 8 and 10 with no other anticoagulation. The newborn presented with skeletal abnormalities and a ventricular septal defect that have not required specific treatment during the first year of life. Low-dose warfarin is associated with a lower risk of warfarin-related fetopathy but the risk of embryopathy seems unchanged.

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Pemphigoid gestationis successfully treated with intravenous immunoglobulin

Pemphigoid gestationis (PG), also known as herpes gestationis, is a rare autoimmune blistering disease specific to pregnancy, which usually presents in the second or third trimesters and, in 15%–25% of cases, during the immediate postpartum period.¹Although the ethiopathogeny of PG is not fully clarified, most patients develop antibodies against a 180 kDa transmembrane hemidesmosomal protein (BP180; BPAG2; collagen XVII).² PG has a strong association with human leucocyte antigens DR3 and DR4.³

We report a case of a 29-year-old female patient with PG successfully treated with intravenous immunoglobulin.

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Novel MRI of mediastinal masses: internal differentiation of a thymoma and lymphoma with T1 and T2 mapping

Routine imaging for mediastinal malignancies includes chest X-ray, CT or MRI. T1 and T2 mapping are novel MRI techniques which may have a role in expanding the assessment of internal tumour characteristics. This case report details two middle-aged women who had similar clinical presentations of mediastinal masses of comparable size and appearance when assessed with routine imaging. T1 and T2 maps were acquired on MRI to investigate whether these tumours could be further differentiated prior to surgery. T1 and T2 mapping supported suspicion for which tumour components were solid and cystic, as subsequently confirmed histologically. Furthermore, comparison between the two tumours showed native T1 values differed within the solid components by 37%, correlating to differences in proteinaceous material within the tumour types. This radiological–pathological correlation provides evidence that T1 and T2 mapping has clinical utility in the assessment and differentiation of mediastinal masses.

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