Genetic predisposition to depression and inflammation impacts symptom burden and survival in patients with head and neck cancer: A longitudinal study.

OBJECTIVE: The primary purpose of this study was to investigate the contribution of genetic predispositions to depression and inflammation, as measured through polygenic risk scores, on symptom burden (physical and psychological) in patients with head and neck cancer in the immediate post-treatment period (i.e., at three months post-diagnosis), as well as on 3-, 6-, 12-, 24- and 36-month survival. METHODS: Prospective longitudinal study of 223 adults (72 % participation) newly diagnosed with a first occurrence of primary head and neck cancer, paired with genetic data (Illumina PsychArray), validated psychometric measures, Structured Clinical Interviews for DSM Disorders (SCID-I), and medical chart reviews. RESULTS: Symptom burden at 3 months was predicted by (R2 adj. = 0.38, p < 0.001): a baseline SCID-I Anxiety Disorder (b = 1.69, B = 0.23, 95%CI = 0.43-2.94; p = 0.009), baseline levels of HADS anxiety (b = 0.20, B = 0.29, 95%CI = 0.07-0.34; p = 0.003), the polygenic risk score (PRS) for depression (b = 0.66, B = 0.18, 95%CI = 0.003-1.32; p = 0.049), and cumulated dose of radiotherapy (b = 0.002, B = 0.46, 95%CI = 0.001-0.003; p < 0.001). When controlling for factors known to be associated with cancer survival, patients with a higher PRS associated with depression and inflammation, respectively, presented higher risk of death within 36 months (b = 1.75, Exp(B) = 5.75, 95%CI = 1.55-21.27, p = 0.009 and b = 0.14, Exp(B) = 1.15, 95%CI = 1.01-1.30, p = 0.03). CONCLUSIONS: Our results outline three potential pathways of symptom burden in patients with head and neck cancer: a genetic predisposition towards depression; an initial anxiety disorder upon being diagnosed with cancer or high levels of anxiety upon diagnosis; and a dose-related response to radiotherapy. One may want to investigate early interventions in these areas to alleviate symptom burden in patients faced with a life-threatening disease, as well as consider targeting genetic predisposition towards depression and inflammation implicated in survival. The high prevalence of distress in patients with head and neck cancer is an opportunity to study genetic predispositions, which could potentially be broadly generalized to other cancers and diseases.

The risks associated with the widespread use of telemedicine in oncology: Four cases and review of the literature.

BACKGROUND: COVID-19 changed the way we practice oncology in multiple ways. Because most cancer patients are comorbid or immunocompromised, we are trying as much as possible to reduce their risk of infection. Marginal just 2 years ago, telemedicine quickly became preeminent with the pandemic to reduce hospital exposure. However, using only virtual visits in oncology patients risk delaying cancer diagnosis or the identification of a complication. CASE SERIES: We present here four cases where a serious medical problem evident on physical exam was overlooked during a virtual visit. Two of our patients experienced a delay in cancer diagnosis thus putting them at risk of local or distant spread. The two others were established oncology patients where a serious medical complication was missed on a virtual visit. CONCLUSIONS: Now more than a year into the pandemic, telemedicine has clearly been a useful tool by limiting unnecessary hospital visits. Yet, as our cases illustrate, its use in oncology without clear boundary can undermine the quality of care. Now that effective vaccines are reducing the transmission and the severity of infection, most oncology patients can be evaluated by a real-time visit.

Clinical Practice Patterns in Chemotherapeutic Treatment Regimens for Metastatic Colorectal Cancer.

BACKGROUND: The treatment of patients with metastatic colorectal cancer (mCRC) has evolved during the past 2 decades, and patient survival has increased. Consequently, patients are exposed to more chemotherapeutic agents and regimens. Little is known about therapeutic drug sequencing and the factors influencing these choices. MATERIALS AND METHODS: An observational, retrospective medical record review was conducted of patients with newly diagnosed adult mCRC from January 2002 to September 2013 identified in the McGill University-Jewish General Hospital's local tumor registry. All patients presented with mCRC (stage IV) and received ≥ 2 cycles and/or ≥ 28 days of first-line chemotherapy. The patient demographics, CRC characteristics, treatment patterns, and outcomes were recorded. The reason for changing or halting therapy was also reported. RESULTS: Of the 215 patients who underwent treatment, 74.4% received second-line, 36% third-line, and 16.3% fourth-line treatment. In total, 88% received ≥ 3 classes of cytotoxic chemotherapy and 80% received ≥ 1 biologic agent. The most common first-line treatment was FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) (47.4%) or CAPOX (capecitabine, oxaliplatin) (28.8%), and more than one half received bevacizumab (56%). Among the second- and third-line treatments, FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) was the most common (40.3% and 30.3%, respectively), and bevacizumab was the most frequently used biologic agent (48.1% and 39.2%, respectively). For fourth-line treatment and beyond, most patients participated in clinical trials (45.7%) or received panitumumab monotherapy (31.4%). Across the first 4 therapy lines, disease progression was the primary motive for discontinuation (39.5%, 53.8%, 58.2%, and 37.1%). CONCLUSION: FOLFOX was the most common first-line and FOLFIRI the most common second- and third-line mCRC therapy. Bevacizumab was the most frequently used targeted therapy across all 3 treatment lines. Therapy discontinuation was primarily due to disease progression.

High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

BACKGROUND: Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail. METHODS AND FINDINGS: We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement. CONCLUSIONS: Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy regimen and IVC in which exceptional responses occur frequently enough to justify appropriately focused clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT01050621.

Oxalic acid excretion after intravenous ascorbic acid administration.

Ascorbic acid is frequently administered intravenously by alternative health practitioners and, occasionally, by mainstream physicians. Intravenous administration can greatly increase the amount of ascorbic acid that reaches the circulation, potentially increasing the risk of oxalate crystallization in the urinary space. To investigate this possibility, we developed gas chromatography mass spectrometry methodology and sampling and storage procedures for oxalic acid analysis without interference from ascorbic acid and measured urinary oxalic acid excretion in people administered intravenous ascorbic acid in doses ranging from 0.2 to 1.5 g/kg body weight. In vitro oxidation of ascorbic acid to oxalic acid did not occur when urine samples were brought immediately to pH less than 2 and stored at -30 degrees C within 6 hours. Even very high ascorbic acid concentrations did not interfere with the analysis when oxalic acid extraction was carried out at pH 1. As measured during and over the 6 hours after ascorbic acid infusions, urinary oxalic acid excretion increased with increasing doses, reaching approximately 80 mg at a dose of approximately 100 g. We conclude that, when studied using correct procedures for sample handling, storage, and analysis, less than 0.5% of a very large intravenous dose of ascorbic acid is recovered as urinary oxalic acid in people with normal renal function.