Impact on Health-Related Quality of Life of Induction Chemotherapy Compared With Concurrent Cisplatin and Radiation Therapy in Patients With Head and Neck Cancer

AimsOrgan preservation, an important goal in the treatment of head and neck squamous cell carcinoma (HNSCC), may include induction chemotherapy and cisplatin with radiation therapy (CRT). To our knowledge, no reports have directly compared the impact of induction chemotherapy with that of CRT on health-related quality of life (HRQOL).Materials and methodsIn a phase II trial, we assessed the HRQOL of patients treated with induction chemotherapy followed by CRT. Eligible patients had stage III–IV HNSCC. HRQOL questionnaires were administered at baseline, the end of induction (EOI), the end of CRT (EOCRT) and after CRT. Functional Assessment of Cancer Therapy (FACT version 4) assessed HRQOL. We carried out a comparison of changes in HRQOL from baseline to EOI and from EOI to EOCRT. This trial is registered with ClinicalTrials.gov (NCT01566435).ResultsThirty patients were enrolled in the study. Most HRQOL questionnaires were completed (88%). The mean total FACT scores did not differ from baseline to EOI (general: 83.8 versus 79.1, P = 0.08; head and neck: 109.7 versus 105.8, P = 0.33; Total Outcome Index: 69.7 versus 62.3, P = 0.03; respectively, using P ≤ 0.01 to adjust for multiple simultaneous tests of differences). However, total FACT scores significantly worsened from EOI to EOCRT (79.1 versus 62.3, P = 0.01; 105.8 versus 74.2, P < 0.01; 62.3 versus 34.2, P = 0.01; respectively). Within domains, the head and neck cancer subscale score did not differ from baseline to EOI (median 28.5 versus 27.0, P = 0.69), but significantly worsened from EOI to EOCRT (27.0 versus 9.5, P < 0.01). Swallowing, oral pain and voice quality improved from baseline to EOI, but worsened from EOI to EOCRT. Physical and functional scores worsened from baseline to EOI and from EOI to EOCRT. The emotional well-being score improved from baseline to EOI but worsened from EOI to EOCRT.ConclusionsOverall, HRQOL did not significantly change from baseline to EOI but dramatically worsened from EOI to EOCRT.     

Routine diagnostics for neural antibodies,clinical correlates,treatment and functional outcome

Objective

To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions.

Methods

Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters.

Results

Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6–46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-d-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention.

Conclusions

This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.

     

Midterm Outcomes of the Dissected Aorta Repair Through Stent Implantation Trial

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Modified Version of Baby-Led Weaning Does Not Result in Lower Zinc Intake or Status in Infants: A Randomized Controlled Trial

Background

Little is known about zinc intakes and status during complementary feeding. This is particularly true for baby-led approaches, which encourage infants to feed themselves from the start of complementary feeding, although self-feeding may restrict the intake of zinc-rich foods.

Translating Mechanism-Based Strategies to Break the Obesity−Cancer Link: A Narrative Review

Prevalence of obesity, an established risk factor for many cancers, has increased dramatically over the past 50 years in the United States and across the globe. Relative to normoweight cancer patients, obese cancer patients often have poorer prognoses, resistance to chemotherapies, and are more likely to develop distant metastases. Recent progress on elucidating the mechanisms underlying the obesity?cancer connection suggests that obesity exerts pleomorphic effects on pathways related to tumor development and progression and, thus, there are multiple opportunities for primary prevention and treatment of obesity-related cancers. Obesity-associated alterations, including systemic metabolism, adipose inflammation, growth factor signaling, and angiogenesis, are emerging as primary drivers of obesity-associated cancer development and progression. These obesity-associated host factors interact with the intrinsic molecular characteristics of cancer cells, facilitating several of the hallmarks of cancer. Each is considered in the context of potential preventive and therapeutic strategies to reduce the burden of obesity-related cancers. In addition, this review focuses on emerging mechanisms behind the obesity?cancer link, as well as relevant dietary interventions, including calorie restriction, intermittent fasting, low-fat diet, and ketogenic diet, that are being implemented in preclinical and clinical trials, with the ultimate goal of reducing incidence and progression of obesity-related cancers.     

Evaluation of Transdermal Drug Permeation as Modulated by Lipoderm and Pluronic Lecithin Organogel

The transdermal delivery of 2 fluorescent probes with similar molecular weight but different lipophilicity, into and through the skin from 2 commercially available transdermal bases, pluronic lecithin organogel, and Lipoderm^® has been evaluated. First, in vitro penetration of fluorescein sodium and fluorescein (free acid) through porcine skin was evaluated. Retention and depth distribution profiles in skin were obtained by tape stripping and then followed by optical sectioning using multiphoton microscopy. The results showed that Lipoderm^® led to an enhanced penetration of the hydrophilic compound, fluorescein sodium. For the lipophilic compound fluorescein (free acid), Lipoderm^® performed similar to pluronic lecithin organogel base, where minimal drug was detected in either receptor phase. The skin retention and depth distribution results also showed that the hydrophilic fluorescein sodium had high skin retention with Lipoderm^®, whereas fluorescein (free acid) had very low penetration and retention with increasing skin depth. Moreover, optical sectioning by multiphoton microscopy revealed an uneven distribution of probes across the skin in the x-y plane for both transdermal bases. This work showed that a hydrophilic compound has significantly increased skin penetration and retention when formulated with Lipoderm^®, and the skin retention of the probe was the main determinant of its skin flux.