Emerging monoclonal antibody therapy for head and neck squamous cell carcinoma.

INTRODUCTION: The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing, particularly among younger populations. It is projected that the number of new cases will increase by almost 50% by 2040, with market revenues expected to triple in the same period. Despite the recent introduction of immune checkpoint inhibitors (ICIs) into the therapeutic armamentarium, the vast majority of patients with recurrent and/or metastatic (R/M) HNSCC fail to derive durable benefits from systemic therapy. AREAS COVERED: This article aims to review the multiple monoclonal antibodies (mAbs) regimens currently under development, targeting various growth factors, immune checkpoints, immune costimulatory receptors, and more. EXPERT OPINION: So far, the combination of anti-EGFR and ICI appears to be the most promising, especially in HPV-negative patients. It will be interesting to confirm whether the arrival of antibody-drug conjugates and bispecific mAb can surpass the efficacy of anti-EGFR, as they are also being tested in combination with ICI. Furthermore, we believe that immune costimulatory agonists and various ICIs combination are worth monitoring, despite some initial setbacks.

Association of Cabozantinib Dose Reductions for Toxicity With Clinical Effectiveness in Metastatic Renal Cell Carcinoma (mRCC): Results From the Canadian Kidney Cancer Information System (CKCis).

BACKGROUND: Cabozantinib, an oral multi-targeted tyrosine kinase inhibitor (TKI), has demonstrated efficacy in metastatic renal cell carcinoma (mRCC). The association between toxicity and therapeutic effectiveness has been established with other TKIs. We investigated whether cabozantinib dose reductions, a surrogate for toxicity and adequate drug exposure, were associated with improved clinical outcomes in mRCC. METHODS: Employing the CKCis database, we analyzed patients treated with cabozantinib in the second line or later between 2011 to 2021. The cohort was stratified into those needing dose reductions (DR) during treatment and those not (no-DR). Outcomes, including objective response rate (ORR), time to treatment failure (TTF), and overall survival (OS), were compared based on dose reduction status. The influence of the initial dose on outcomes was also explored. RESULTS: Among 319 cabozantinib-treated patients, 48.3% underwent dose reductions. Response rates exhibited no significant difference between the DR and no-DR groups (15.1% vs. 18.2%, P = .55). Patients with DR had superior median OS (26.15 vs. 15.47 months, P = .019) and TTF (12.74 vs. 6.44 months, P = .022) compared to no-DR patients. These differences retained significance following adjustment for IMDC risk group (OS HR = 0.67, P = .032; TTF HR = 0.65, P = .008). There was no association between the initial dose and ORR, OS, or TTF. CONCLUSION: This study highlights the link between cabozantinib dose reductions due to toxicity and improved survival and time to treatment failure in mRCC patients. These findings underscore the potential of using on-treatment toxicity as an indicator of adequate drug exposure to individualize dosing and optimize treatment effectiveness. Larger studies are warranted to validate these results and develop individualized strategies for cabozantinib when given alone or in combination with immunotherapy.

Gut microbiome predicts gastrointestinal toxicity outcomes from chemoradiation therapy in patients with head and neck squamous cell carcinoma.

OBJECTIVES: Chemoradiation (CRT) in patients with locally advanced head and neck squamous cell cancer (HNSCC) is associated with significant toxicities, including mucositis. The gut microbiome represents an emerging hallmark of cancer and a potentially important biomarker for CRT-related adverse events. This prospective study investigated the association between the gut microbiome composition and CRT-related toxicities in patients with HNSCC, including mucositis. MATERIALS AND METHODS: Stool samples from patients diagnosed with locally advanced HNSCC were prospectively collected prior to CRT initiation and analyzed using shotgun metagenomic sequencing to evaluate gut microbiome composition at baseline. Concurrently, clinicopathologic data, survival outcomes and the incidence and grading of CRT-emergent adverse events were documented in all patients. RESULTS: A total of 52 patients were included, of whom 47 had baseline stool samples available for metagenomic analysis. Median age was 62, 83 % patients were men and 54 % had stage III-IV disease. All patients developed CRT-induced mucositis, including 42 % with severe events (i.e. CTCAE v5.0 grade ≥ 3) and 25 % who required enteral feeding. With a median follow-up of 26.5 months, patients with severe mucositis had shorter overall survival (HR = 3.3, 95 %CI 1.0-10.6; p = 0.02) and numerically shorter progression-free survival (HR = 2.8, 95 %CI, 0.8-9.6; p = 0.09). The gut microbiome beta-diversity of patients with severe mucositis differed from patients with grades 1-2 mucositis (p = 0.04), with enrichment in Mediterraneibacter (Ruminococcus gnavus) and Clostridiaceae family members, including Hungatella hathewayi. Grade 1-2 mucositis was associated with enrichment in Eubacterium rectale, Alistipes putredinis and Ruminococcaceae family members. Similar bacterial profiles were observed in patients who required enteral feeding. CONCLUSION: Patients who developed severe mucositis had decreased survival and enrichment in specific bacteria associated with mucosal inflammation. Interestingly, these same bacteria have been linked to immune checkpoint inhibitor resistance.

Real-world Assessment of Clinical Outcomes in Patients with Metastatic Renal Cell Carcinoma with or Without Sarcomatoid Features Treated with First-line Systemic Therapies.

BACKGROUND AND OBJECTIVE: Metastatic renal cell carcinoma (mRCC) patients have been reported to have better outcomes when treated with immunotherapies (IO) compared to targeted therapies (TT). This study aims to evaluate the impact of first-line systemic therapies on survival of mRCC patients with or without sarcomatoid features using real-world data. METHODS: Metastatic RCC patients of International mRCC Database Consortium (IMDC) intermediate or high risk, diagnosed from January 2011 to December 2022, treated with first-line systemic therapies, and with histological documentation of the presence or absence of sarcomatoid features in nephrectomy specimens were identified using the Canadian Kidney Cancer information system. Patients were classified by initial treatment: (1) targeted therapy (TT) used alone or (2) immunotherapy (IO)-based systemic therapies used in combination of either IO-IO or IO-TT. The inverse probability of treatment weighting using propensity scores was used to balance for covariates. Cox proportional hazard models were used to assess the impact of initial treatment received on overall survival (OS). KEY FINDINGS AND LIMITATIONS: Of the 1202 eligible patients, 791 were treated with TT and 411 with IO combinations. Of the patients, 76% were male, and the majority (91%) had a nephrectomy before systemic therapy. In nonsarcomatoid patients (639 TT and 320 IO patients), treatment with IO was associated with improved OS compared with patients treated with TT (median of 72 vs 48 mo, hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.50-0.80, objective response rate [ORR] of 38.5% for IO and 23.5% for TT). In sarcomatoid patients (152 TT and 91 IO patients), treatment with IO was associated with improved OS (median of 48 vs 18 mo, HR 0.41, 95% CI 0.26-0.64, ORR of 49.5% for IO and 13.8% for TT). Similar results were observed in patients with synchronous metastatic disease only. CONCLUSIONS AND CLINICAL IMPLICATIONS: IO treatment was associated with improved survival in mRCC patients. The magnitude of benefit is increased in patients with sarcomatoid mRCC, consequently, identifying the sarcomatoid status early on could help healthcare providers make a better treatment decision. PATIENT SUMMARY: Metastatic renal cell carcinoma (mRCC) patients of International mRCC Database Consortium intermediate and high risk, diagnosed from January 2011 to December 2022, treated with first-line systemic therapies, and with histological documentation of the presence or absence of sarcomatoid features in nephrectomy specimens were identified using the Canadian Kidney Cancer information system (CKCis). In this study, treatment with immunotherapy was associated to an improved survival and response rates for mRCC patients with and without sarcomatoid features. The magnitude of benefit is increased in patients with sarcomatoid mRCC.

Predictors of prolonged treatment time intervals in oral cavity cancer.

OBJECTIVES: Delays in treatment time intervals have been associated with overall survival in oral cavity squamous cell carcinoma (OCSCC). The aim of this study was to identify bottlenecks leading to prolonged treatment intervals. MATERIAL AND METHODS: A retrospective analysis was conducted using a cohort of OCSCC patients who underwent surgery and adjuvant radiation therapy. The endpoints of interest were prolonged treatment intervals. Multivariable logistic regression was used to adjust for patient and tumour characteristics. RESULTS: Median diagnosis-to-treatment interval (DTI) and surgery to initiation of postoperative radiation therapy interval (S-PORT) were 39 days (IQR 30-54) and 64 days (IQR 54-66), respectively. Prolonged DTI was associated with older age, worse Charlson Comorbidity index scores and worse T stages. Patients with prolonged DTI had longer times to preoperative imaging reports (25 vs 9 days; P < 0.01). Time to preoperative pathology did not differ. Prolonged S-PORT was associated with longer times to pathology report (28 vs 18 days; P < 0.01), to maxillofacial consult (38 vs 15 days; P < 0.01) and to maxillofacial approval of radiation (50 vs 28 days; P < 0.01). In patients requiring medical oncology consults, those with prolonged S-PORT had longer waiting times until consultation (58 vs 38 days; P = 0.02). Multivariate analysis showed independent predictors of prolonged DTI: time to preoperative imaging; and prolonged S-PORT: time to pathology report, time to maxillofacial consult, and time to medical oncology consult. CONCLUSIONS: Strategies targeting these organizational bottlenecks may be effective for shortening treatment time intervals, hence representing potential opportunities for improving oncological outcomes in OCSCC patients.

Trends of Utilization of Systemic Therapies for Metastatic Renal Cell Carcinoma in the Canadian Health Care System.

PURPOSE: Standard-of-care therapies for metastatic renal cell carcinoma (mRCC) have greatly evolved. However, the availability of emerging options in global health care systems can vary. We sought to describe the integration and usage of systemic therapies for mRCC in Canada since 2011. METHODS: We included patients with mRCC enrolled in the Canadian Kidney Cancer Information System, a prospective cohort of patients from 14 Canadian academic centers, who received systemic therapy from January 1, 2011, to December 31, 2021. Patients were stratified by treatment era (cohort 1: 2011-2015, cohort 2: 2016-2021). Stacked bar charts were used to present treatment proportions; Sankey diagrams were used to show the evolution of treatment sequencing between the two cohorts. RESULTS: Four thousand one hundred seven patients were diagnosed with mRCC, of whom 2,752 (67%) received systemic therapy. Among these patients, mean age was 64 years, 74% were male, 75% had clear cell histology, and International Metastatic RCC Database Consortium risk classification was favorable, intermediate, and poor in 16%, 56%, and 28%, respectively. Utilization of immune checkpoint inhibition (ICI)-based treatments has increased in Canada and reflects global and local patterns of approval and adoption. The use of therapies after doublet ICI has mostly shifted toward vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs) that were previously used in first line with subsequent treatments reflecting approved and available agents after previous VEGF-TKI. Clinical trial participation among patients who received systemic therapy was 18% in first, 21% in second, and 24% in third line. CONCLUSION: In Canada's publicly funded health care system, availability of standard mRCC therapies broadly reflects access from government-funded clinical trials and compassionate access program sources. In an evolving therapeutic landscape, ongoing advocacy is required to continue to facilitate patient access to efficacious therapies.

The Use of Salvage Chemotherapy for Patients with Relapsed Testicular Germ Cell Tumor (GCT) in Canada: A National Survey.

BACKGROUND: Although metastatic germ cell tumor (GCT) is highly curable with initial cisplatin-based chemotherapy (CT), 20-30% of patients relapse. Salvage CT options include conventional (CDCT) and high dose chemotherapy (HDCT), however definitive comparative data remain lacking. We aimed to characterize the contemporary practice patterns of salvage CT across Canada. METHODS: We conducted a 30-question online survey for Canadian medical and hematological oncologists with experience in treating GCT, assessing treatment availability, patient selection, and management strategies used for relapsed GCT patients. RESULTS: There were 30 respondents from 18 cancer centers across eight provinces. The most common CDCT regimens used were TIP (64%) and VIP (25%). HDCT was available in 13 centers (70%). The HDCT regimen used included carboplatin and etoposide for two cycles (76% in 7 centers), three cycles (6% in 2 centers), and the TICE protocol (11%, in 2 centers). "Bridging" CDCT was used by 65% of respondents. Post-HDCT treatments considered include surgical resection for residual disease (87.5%), maintenance etoposide (6.3%), and surveillance only (6.3%). CONCLUSIONS: HDCT is the most commonly used GCT salvage strategy in Canada. Significant differences exist in the treatment availability, selection, and delivery of HDCT, highlighting the need for standardization of care for patients with relapsed testicular GCT.

Pembrolizumab Plus Axitinib Versus Sunitinib as First-line Treatment of Advanced Renal Cell Carcinoma: 43-month Follow-up of the Phase 3 KEYNOTE-426 Study.

Previous analyses of KEYNOTE-426, an open-label, phase 3 randomized study, showed superior efficacy of first-line pembrolizumab plus axitinib to sunitinib in advanced clear cell renal cell carcinoma (ccRCC). We report results of the final protocol-prespecified analysis of KEYNOTE-426. Patients received pembrolizumab 200 mg intravenously every 3 wk plus axitinib 5 mg orally twice daily or sunitinib 50 mg orally once daily (4 wk per 6-wk cycle). The dual primary endpoints were overall survival (OS) and progression-free survival (PFS) as per RECIST v1.1 by a blinded independent central review. The secondary endpoints included objective response rate (ORR) and duration of response (DOR). The median study follow-up was 43 (range, 36-51) mo. Benefit with pembrolizumab plus axitinib versus sunitinib was maintained for OS (hazard ratio [HR], 0.73 [95% confidence interval {CI}, 0.60-0.88]), PFS (HR, 0.68 [95% CI, 0.58-0.80]), and ORR (60% vs 40%). The median DOR was 24 (range, 1.4+ to 43+) versus 15 (range, 2.3-43+) mo in the pembrolizumab plus axitinib versus the sunitinib arm. No new safety signals emerged. These results support pembrolizumab plus axitinib as a standard of care for patients with previously untreated advanced ccRCC. PATIENT SUMMARY: Extended results of KEYNOTE-426 support pembrolizumab plus axitinib as the standard of care for advanced clear cell renal cell carcinoma.

Prospective Evaluation of Fetal Hemoglobin Expression in Maternal Erythrocytes: An Analysis of a Cohort of 345 Parturients.

It is believed that fetal hemoglobin (HbF) expression in adults is largely genetically regulated. The increased expression of HbF in pregnancy has been reported in a small number of articles. Different mechanisms have been proposed, but the description of HbF expression during pregnancy remains unclear. The objectives of this study were to document HbF expression during peri and postpartum periods, confirm its maternal origin, and assess clinical and biochemical parameters potentially associated with HbF modulation. In this observational prospective study, 345 pregnant women were followed. At baseline, 169 had HbF expression (≥1% of total hemoglobin) and 176 did not have HbF expression. Women were followed at the obstetric clinic during their pregnancy. Clinical and biochemical parameters were measured at each visit. Analyses were made to determine which parameters had a significant correlation to HbF expression. Results show that HbF expression of ≥1% during peri and postpartum periods in pregnant women without influencing comorbidities is at its highest peak during the first trimester. In all women, it was proven that HbF was of maternal origin. A significant positive correlation between HbF expression, ßeta-human chorionic gonadotropin (ß-HCG), and glycosylated hemoglobin (HbA1c) was present. A significant negative association between HbF expression and total hemoglobin was found. HbF expression induction during pregnancy is probably associated with an increase in ß-HCG and HbA1C, and a decrease in total hemoglobin, which could temporarily reactivate the fetal erythropoietic system.

Efficacy and Safety of Nivolumab Plus Ipilimumab vs Nivolumab Alone for Treatment of Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: The Phase 2 CheckMate 714 Randomized Clinical Trial.

Importance: There remains an unmet need to improve clinical outcomes in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Objective: To evaluate clinical benefit of first-line nivolumab plus ipilimumab vs nivolumab alone in patients with R/M SCCHN. Design, Setting, and Participants: The CheckMate 714, double-blind, phase 2 randomized clinical trial was conducted at 83 sites in 21 countries between October 20, 2016, and January 23, 2019. Eligible participants were aged 18 years or older and had platinum-refractory or platinum-eligible R/M SCCHN and no prior systemic therapy for R/M disease. Data were analyzed from October 20, 2016 (first patient, first visit), to March 8, 2019 (primary database lock), and April 6, 2020 (overall survival database lock). Interventions: Patients were randomized 2:1 to receive nivolumab (3 mg/kg intravenously [IV] every 2 weeks) plus ipilimumab (1 mg/kg IV every 6 weeks) or nivolumab (3 mg/kg IV every 2 weeks) plus placebo for up to 2 years or until disease progression, unacceptable toxic effects, or consent withdrawal. Main Outcomes and Measures: The primary end points were objective response rate (ORR) and duration of response between treatment arms by blinded independent central review in the population with platinum-refractory R/M SCCHN. Exploratory end points included safety. Results: Of 425 included patients, 241 (56.7%; median age, 59 [range, 24-82] years; 194 males [80.5%]) had platinum-refractory disease (nivolumab plus ipilimumab, n = 159; nivolumab, n = 82) and 184 (43.3%; median age, 62 [range, 33-88] years; 152 males [82.6%]) had platinum-eligible disease (nivolumab plus ipilimumab, n = 123; nivolumab, n = 61). At primary database lock, the ORR in the population with platinum-refractory disease was 13.2% (95% CI, 8.4%-19.5%) with nivolumab plus ipilimumab vs 18.3% (95% CI, 10.6%-28.4%) with nivolumab (odds ratio [OR], 0.68; 95.5% CI, 0.33-1.43; P = .29). Median duration of response for nivolumab plus ipilimumab was not reached (NR) (95% CI, 11.0 months to NR) vs 11.1 months (95% CI, 4.1 months to NR) for nivolumab. In the population with platinum-eligible disease, the ORR was 20.3% (95% CI, 13.6%-28.5%) with nivolumab plus ipilimumab vs 29.5% (95% CI, 18.5%-42.6%) with nivolumab. The rates of grade 3 or 4 treatment-related adverse events with nivolumab plus ipilimumab vs nivolumab were 15.8% (25 of 158) vs 14.6% (12 of 82) in the population with platinum-refractory disease and 24.6% (30 of 122) vs 13.1% (8 of 61) in the population with platinum-eligible disease. Conclusions and Relevance: The CheckMate 714 randomized clinical trial did not meet its primary end point of ORR benefit with first-line nivolumab plus ipilimumab vs nivolumab alone in platinum-refractory R/M SCCHN. Nivolumab plus ipilimumab was associated with an acceptable safety profile. Research to identify patient subpopulations in R/M SCCHN that would benefit from nivolumab plus ipilimumab over nivolumab monotherapy is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02823574.

Evaluating the impact of early identification of asymptomatic brain metastases in metastatic renal cell carcinoma.

BACKGROUND: Brain metastases (BM) in metastatic renal cell carcinoma (mRCC) have been reported to be present in up to 25% of patients diagnosed with mRCC. There is limited published literature evaluating the role of routine intra-cranial imaging for the screening of asymptomatic BM in mRCC. AIMS: To evaluate the potential utility of routine intra-cranial imaging, a retrospective cohort study was conducted to characterize the outcomes of mRCC patients who presented with asymptomatic BM, as compared to symptomatic BM. METHODS AND RESULTS: The Canadian Kidney Cancer Information System (CKCis) database was used to identify mRCC patients diagnosed with BM. This cohort was divided into two groups based on the presence or absence of BM symptoms. Details regarding patient demographics, disease characteristics, systemic treatments, BM characteristics and survival outcomes were extracted. Statistical analysis was through chi-square tests, analysis of variance, and Kaplan-Meier method to characterize survival outcomes. A p-value of <0.05 was considered statistically significant for all analyses. A total of 267 mRCC patients with BM were identified of which 106 (40%) presented with asymptomatic disease. The majority of patients presented with multiple (i.e., >1) BM (75%) with no significant differences noted in number of BM or BM-directed therapy received in symptomatic, as compared to asymptomatic BM patients. Median [95% confidence interval (CI)] overall survival (OS) from mRCC diagnosis was 42 months (95% CI: 32-62) for patients with asymptomatic BM, and 39 months (95% CI: 29-48) with symptomatic BM (p = 0.10). OS from time of BM diagnosis was 28 months (95% CI: 18-42) for the asymptomatic BM group, as compared to 13 months (95% CI: 10-21) in the symptomatic BM group (p = 0.04). CONCLUSIONS: Given a substantial proportion of patients may present with asymptomatic BM, limiting intra-cranial imaging to patients with symptomatic BM, may be associated with a missed opportunity for timely diagnosis and treatment. The utility of routine intra-cranial imaging in patients with renal cell carcinoma, warrants further prospective evaluation.

Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study.

PURPOSE: Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048. Post hoc analysis of long-term efficacy and progression-free survival on next-line therapy (PFS2) is presented. METHODS: Patients were randomly assigned (1:1:1) to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy. Efficacy was evaluated in programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, CPS ≥ 1, and total populations, with no multiplicity or alpha adjustment. RESULTS: The median study follow-up was 45.0 months (interquartile range, 41.0-49.2; n = 882). At data cutoff (February 18, 2020), overall survival improved with pembrolizumab in the PD-L1 CPS ≥ 20 (hazard ratio [HR], 0.61; 95% CI, 0.46 to 0.81) and CPS ≥ 1 populations (HR, 0.74; 95% CI, 0.61 to 0.89) and was noninferior in the total population (HR, 0.81; 95% CI, 0.68 to 0.97). Overall survival improved with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.62; 95% CI, 0.46 to 0.84), CPS ≥ 1 (HR, 0.64; 95% CI, 0.53 to 0.78), and total (HR, 0.71; 95% CI, 0.59 to 0.85) populations. The objective response rate on second-course pembrolizumab was 27.3% (3 of 11). PFS2 improved with pembrolizumab in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.84) and CPS ≥ 1 (HR, 0.79; 95% CI, 0.66 to 0.95) populations and with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.86), CPS ≥ 1 (HR, 0.66; 95% CI, 0.55 to 0.81), and total (HR, 0.73; 95% CI, 0.61 to 0.88) populations. PFS2 was similar after pembrolizumab and longer after pembrolizumab-chemotherapy on next-line taxanes and shorter after pembrolizumab and similar after pembrolizumab-chemotherapy on next-line nontaxanes. CONCLUSION: With a 4-year follow-up, first-line pembrolizumab and pembrolizumab-chemotherapy continued to demonstrate survival benefit versus cetuximab-chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma. Patients responded well to subsequent treatment after pembrolizumab-based therapy.

COVID-19 and Sickle Cell Disease in the Province of Quebec, Canada: Outcomes after Two Years of the Pandemic.

BACKGROUND: Patients with sickle cell disease (SCD) are considered at higher risk of severe COVID-19 infection. However, morbidity and mortality rates are variable among countries. To date, there are no published reports that document outcomes of SCD patients with COVID-19 in Canada. METHODS: A web-based registry was implemented in June 2020 capturing outcomes of SCD patients with COVID-19 from March 2020 to April 2022 and comparing them to the general population of Quebec, Canada. RESULTS: After 24 months of the pandemic, 185 SCD patients with confirmed SARS-CoV-2 infection were included in the registry. Overall, the population was young (median age 12 years old) and had few comorbidities. No deaths were reported. Risk of hospitalization and admission to intensive care unit (ICU) because of COVID-19 was higher in patients with SCD than in the general population (relative risks (RR) 5.15 (95% confidence interval (95% CI) 3.84-6.91), p ˂ 0.001 and 4.56 (95% CI 2.09-9.93) p ˂ 0.001). A history of arterial hypertension or acute chest syndrome in the past 12 months was associated with a higher risk of severe disease (RR = 3.06 (95% CI 1.85-5.06) p = 0.008 and 2.27 (95% CI 1.35-3.83) p = 0.01). Hospitalized patients had lower hemoglobin F than non-hospitalized patients (12% vs. 17%, p = 0.02). For those who had access to vaccination at the time of infection, 25 out of 26 patients were adequately vaccinated and had mild disease. CONCLUSIONS: The SCD population is at higher risk of severe disease than the general population. However, we report favorable outcomes as no deaths occurred. Registries will continue to be critical to document the impact of novel COVID-19 specific therapy and vaccines for the SCD population.

Should Magnetic Resonance Angiography Be Used for Screening of Intracranial Aneurysm in Adults with Sickle Cell Disease?

Magnetic resonance imaging (MRI) is used in patients with sickle cell disease (SCD) to detect silent cerebral infarcts. MR angiography (MRA) can identify arterial stenoses and intracranial aneurysms (ICANs) associated with SCD. In this study, we aimed to estimate the prevalence of ICANs in asymptomatic adult patients with SCD referred from the SCD clinic for routine screening by MRI/MRA using a 3T-MRI scanner. Findings were independently reviewed by two neuroradiologists. Between 2016 and 2020, 245 asymptomatic adults with SCD were stratified according to genotype (SS/S-ß0thalassemia and SC/Sß+). ICANs were found in 27 patients (11%; 0.95 CI: 8-16%). ICANs were more frequent in SS/S-ß0thalassemia patients (20/118 or 17%; 0.95 CI: 11-25%) than in SC/ßb+ patients (7/127 or 6%; 0.95 CI: 2-11%; p = 0.007). Individuals with SCD (particularly SS/S-ß0thalassemia) have a higher prevalence of ICANs than the general population. We believe that MRA should be considered in the current American Society of Hematology guidelines, which already contain a recommendation for MRI at least once in adult SCD patients. However, the clinical significance of preventive treatment of unruptured aneurysms remains controversial.

Numb Chin Syndrome in Sickle Cell Disease: A Systematic Review and Recommendations for Investigation and Management.

Numb chin syndrome (NCS) is a rare sensory neuropathy resulting from inferior alveolar or mental nerve injury. It manifests as hypoesthesia, paraesthesia, or, rarely, as pain in the chin and lower lip. Several case reports suggest that sickle cell disease (SCD) could be a cause of NCS. However, information about NCS is scarce in this population. Our objectives were to synthesize all the available literature relevant to NCS in SCD and to propose recommendations for diagnosis and management based on the best available evidence. A systematic review was performed on several databases to identify all relevant publications on NCS in adults and children with SCD. We identified 73 publications; fourteen reports met the inclusion/exclusion criteria. These described 33 unique patients. Most episodes of NCS occurred in the context of typical veno-occlusive crises that involved the mandibular area. Radiological signs of bone infarction were found on some imaging, but not all. Neuropathy management was mostly directed toward the underlying cause. Overall, these observations suggest that vaso-occlusion and bone infarction could be important pathophysiological mechanisms of NCS. However, depending on the individual context, we recommend a careful evaluation to rule out differential causes, including infections, local tumors, metastatic disease, and stroke.

PI3K Inhibition for Squamous Cell Head and Neck Carcinoma.

ABSTRACT: The phosphoinositide 3-kinase (PI3K) pathway is aberrantly activated in most head and neck squamous cell carcinomas, making it a prized target for targeted therapy development. Multiple PI3K inhibitors have been studied in early phase trials, with unfavorable risk-benefit ratios in molecularly unselected patient populations. Buparlisib, a potent pan-class I PI3K inhibitor, shows promising efficacy in combination with paclitaxel for advanced head and neck squamous cell carcinoma. Results of the phase III BURAN trial are awaited.