Airway management in neonates and infants: European Society of Anaesthesiology and Intensive Care and British Journal of Anaesthesia joint guidelines.

Airway management is required during general anaesthesia and is essential for life-threatening conditions such as cardiopulmonary resuscitation. Evidence from recent trials indicates a high incidence of critical events during airway management, especially in neonates or infants. It is important to define the optimal techniques and strategies for airway management in these groups. In this joint European Society of Anaesthesiology and Intensive Care (ESAIC) and British Journal of Anaesthesia (BJA) guideline on airway management in neonates and infants, we present aggregated and evidence-based recommendations to assist clinicians in providing safe and effective medical care. We identified seven main areas of interest for airway management: i) preoperative assessment and preparation; ii) medications; iii) techniques and algorithms; iv) identification and treatment of difficult airways; v) confirmation of tracheal intubation; vi) tracheal extubation, and vii) human factors. Based on these areas, Population, Intervention, Comparison, Outcomes (PICO) questions were derived that guided a structured literature search. GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology was used to formulate the recommendations based on those studies included with consideration of their methodological quality (strong '1' or weak '2' recommendation with high 'A', medium 'B' or low 'C' quality of evidence). In summary, we recommend: 1. Use medical history and physical examination to predict difficult airway management (1C). 2. Ensure adequate level of sedation or general anaesthesia during airway management (1B). 3. Administer neuromuscular blocker before tracheal intubation when spontaneous breathing is not necessary (1C). 4. Use a videolaryngoscope with an age-adapted standard blade as first choice for tracheal intubation (1B). 5. Apply apnoeic oxygenation during tracheal intubation in neonates (1B). 6. Consider a supraglottic airway for rescue oxygenation and ventilation when tracheal intubation fails (1B). 7. Limit the number of tracheal intubation attempts (1C). 8. Use a stylet to reinforce and preshape tracheal tubes when hyperangulated videolaryngoscope blades are used and when the larynx is anatomically anterior (1C). 9. Verify intubation is successful with clinical assessment and end-tidal CO2 waveform (1C). 10. Apply high-flow nasal oxygenation, continuous positive airway pressure or nasal intermittent positive pressure ventilation for postextubation respiratory support, when appropriate (1B).

Airway management in neonates and infants: European Society of Anaesthesiology and Intensive Care and British Journal of Anaesthesia joint guidelines.

Airway management is required during general anaesthesia and is essential for life-threatening conditions such as cardiopulmonary resuscitation. Evidence from recent trials indicates a high incidence of critical events during airway management, especially in neonates or infants. It is important to define the optimal techniques and strategies for airway management in these groups. In this joint European Society of Anaesthesiology and Intensive Care (ESAIC) and British Journal of Anaesthesia (BJA) guideline on airway management in neonates and infants, we present aggregated and evidence-based recommendations to assist clinicians in providing safe and effective medical care. We identified seven main areas of interest for airway management: i) preoperative assessment and preparation; ii) medications; iii) techniques and algorithms; iv) identification and treatment of difficult airways; v) confirmation of tracheal intubation; vi) tracheal extubation, and vii) human factors. Based on these areas, Population, Intervention, Comparison, Outcomes (PICO) questions were derived that guided a structured literature search. GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology was used to formulate the recommendations based on those studies included with consideration of their methodological quality (strong '1' or weak '2' recommendation with high 'A', medium 'B' or low 'C' quality of evidence). In summary, we recommend: 1. Use medical history and physical examination to predict difficult airway management (1С). 2. Ensure adequate level of sedation or general anaesthesia during airway management (1B). 3. Administer neuromuscular blocker before tracheal intubation when spontaneous breathing is not necessary (1С). 4. Use a videolaryngoscope with an age-adapted standard blade as first choice for tracheal intubation (1B). 5. Apply apnoeic oxygenation during tracheal intubation in neonates (1B). 6. Consider a supraglottic airway for rescue oxygenation and ventilation when tracheal intubation fails (1B). 7. Limit the number of tracheal intubation attempts (1C). 8. Use a stylet to reinforce and preshape tracheal tubes when hyperangulated videolaryngoscope blades are used and when the larynx is anatomically anterior (1C). 9. Verify intubation is successful with clinical assessment and end-tidal CO 2 waveform (1C). 10. Apply high-flow nasal oxygenation, continuous positive airway pressure or nasal intermittent positive pressure ventilation for postextubation respiratory support, when appropriate (1B).

Difficult or impossible facemask ventilation in children with difficult tracheal intubation: a retrospective analysis of the PeDI registry.

BACKGROUND: Difficult facemask ventilation is perilous in children whose tracheas are difficult to intubate. We hypothesised that certain physical characteristics and anaesthetic factors are associated with difficult mask ventilation in paediatric patients who also had difficult tracheal intubation. METHODS: We queried a multicentre registry for children who experienced "difficult" or "impossible" facemask ventilation. Patient and case factors known before mask ventilation attempt were included for consideration in this regularised multivariable regression analysis. Incidence of complications, and frequency and efficacy of rescue placement of a supraglottic airway device were also tabulated. Changes in quality of mask ventilation after injection of a neuromuscular blocking agent were assessed. RESULTS: The incidence of difficult mask ventilation was 9% (483 of 5453 patients). Infants and patients having increased weight, being less than 5th percentile in weight for age, or having Treacher-Collins syndrome, glossoptosis, or limited mouth opening were more likely to have difficult mask ventilation. Anaesthetic induction using facemask and opioids was associated with decreased risk of difficult mask ventilation. The incidence of complications was significantly higher in patients with "difficult" mask ventilation than in patients without. Rescue placement of a supraglottic airway improved ventilation in 71% (96 of 135) of cases. Administration of neuromuscular blocking agents was more frequently associated with improvement or no change in quality of ventilation than with worsening. CONCLUSIONS: Certain abnormalities on physical examination should increase suspicion of possible difficult facemask ventilation. Rescue use of a supraglottic airway device in children with difficult or impossible mask ventilation should be strongly considered.

Anesthesia for pediatric rigid bronchoscopy and related airway surgery: Tips and tricks.

Bronchoscopy-guided diagnostic and interventional airway procedures are gaining in popularity and prominence in pediatric surgery. Many of these procedures have been used successfully in the adult population but have not been used in children due to a lack of appropriately sized instruments. Recent technological advances have led to the creation of instruments to enable many more diagnostic and therapeutic procedures to be done under bronchoscopic guidance. These procedures vary significantly in their length and invasiveness and require vastly different anesthetic plans that must be easily adapted to situational and procedural changes. In addition to close communication between the anesthesiology and procedural teams; an understanding of the type of procedure, anesthetic requirements, and potential patient risks is paramount to a successful anesthetic. This review will focus on new rigid bronchoscopic procedures, goals for their respective anesthetic management, and unique tips and trick for how to maintain adequate oxygenation and ventilation in each scenario.

Videolaryngoscopes versus direct laryngoscopes in children: Ranking systematic review with network meta-analyses of randomized clinical trials.

BACKGROUND: Videolaryngoscopes improve tracheal intubation in adult patients, but we currently do not know whether they are similarly beneficial for children. We designed this ranking systematic review to compare individual video and direct laryngoscopes for efficacy and safety of orotracheal intubation in children. METHODS: We searched PubMed and five other databases on January 27, 2021. We included randomized clinical trials with patients aged ≤18 years, comparing different laryngoscopes for the outcomes: failed first intubation attempt; failed intubation within two attempts; failed intubation; glottic view; time for intubation; complications. In addition, we assessed the quality of evidence according to GRADE recommendations. RESULTS: We included 46 studies in the meta-analyses. Videolaryngoscopy reduced the risk of failed first intubation attempt (RR = 0.43; 95% CI: 0.31-0.61; p = .001) and failed intubation within two attempts (RR = 0.33; 95% CI: 0.33-0.33; p < .001) in children aged <1 year. Videolaryngoscopy also reduced the risk of major complications in both children aged <1 year (RR = 0.33; 95% CI: 0.12-0.96; p = .046) and children aged 0-18 years (RR = 0.40; 95% CI: 0.25-0.65; p = .002). We did not find significant difference between videolaryngoscopy and direct laryngoscopy for time to intubation in children aged <1 year (MD = -0.95 s; 95% CI: -5.45 to 3.57 s; p = .681), and children aged 0-18 years (MD = 1.65 s; 95% CI: -1.00 to 4.30 s; p = .222). Different videolaryngoscopes were associated with different performance metrics within this meta-analysis. The overall quality of the evidence ranged from low to very low. CONCLUSION: Videolaryngoscopes reduce the risk of failed first intubation attempts and major complications in children compared to direct laryngoscopes. However, not all videolaryngoscopes have the same performance metrics, and more data is needed to clarify which device may be better in different clinical scenarios. Additionally, care must be taken while interpreting our results and rankings due to the available evidence's low or very low quality.

First-attempt success rate of video laryngoscopy in small infants (VISI): a multicentre, randomised controlled trial.

BACKGROUND: Orotracheal intubation of infants using direct laryngoscopy can be challenging. We aimed to investigate whether video laryngoscopy with a standard blade done by anaesthesia clinicians improves the first-attempt success rate of orotracheal intubation and reduces the risk of complications when compared with direct laryngoscopy. We hypothesised that the first-attempt success rate would be higher with video laryngoscopy than with direct laryngoscopy. METHODS: In this multicentre, parallel group, randomised controlled trial, we recruited infants without difficult airways abnormalities requiring orotracheal intubation in operating theatres at four quaternary children's hospitals in the USA and one in Australia. We randomly assigned patients (1:1) to video laryngoscopy or direct laryngoscopy using random permuted blocks of size 2, 4, and 6, and stratified by site and clinician role. Guardians were masked to group assignment. The primary outcome was the proportion of infants with a successful first attempt at orotracheal intubation. Analysis (modified intention-to-treat [mITT] and per-protocol) used a generalised estimating equation model to account for clustering of patients treated by the same clinician and institution, and adjusted for gestational age, American Society of Anesthesiologists physical status, weight, clinician role, and institution. The trial is registered at ClinicalTrials.gov, NCT03396432. FINDINGS: Between June 4, 2018, and Aug 19, 2019, 564 infants were randomly assigned: 282 (50%) to video laryngoscopy and 282 (50%) to direct laryngoscopy. The mean age of infants was 5·5 months (SD 3·3). 274 infants in the video laryngoscopy group and 278 infants in the direct laryngoscopy group were included in the mITT analysis. In the video laryngoscopy group, 254 (93%) infants were successfully intubated on the first attempt compared with 244 (88%) in the direct laryngoscopy group (adjusted absolute risk difference 5·5% [95% CI 0·7 to 10·3]; p=0·024). Severe complications occurred in four (2%) infants in the video laryngoscopy group compared with 15 (5%) in the direct laryngoscopy group (-3·7% [-6·5 to -0·9]; p=0·0087). Fewer oesophageal intubations occurred in the video laryngoscopy group (n=1 [<1%]) compared with in the direct laryngoscopy group (n=7 [3%]; -2·3 [-4·3 to -0·3]; p=0·028). INTERPRETATION: Among anaesthetised infants, using video laryngoscopy with a standard blade improves the first-attempt success rate and reduces complications. FUNDING: Anaesthesia Patient Safety Foundation, Society for Airway Management, and Karl Storz Endoscopy.

A comparison of videolaryngoscopy using standard blades or non-standard blades in children in the Paediatric Difficult Intubation Registry.

BACKGROUND: The design of a videolaryngoscope blade may affect its efficacy. We classified videolaryngoscope blades as standard and non-standard shapes to compare their efficacy performing tracheal intubation in children enrolled in the Paediatric Difficult Intubation Registry. METHODS: Cases entered in the Registry from March 2017 to January 2020 were analysed. We compared the success rates of initial and eventual tracheal intubation, complications, and technical difficulties between the two groups and by weight stratification. RESULTS: Videolaryngoscopy was used in 1313 patients. Standard and non-standard blades were used in 529 and 740 patients, respectively. Both types were used in 44 patients. In children weighing <5 kg, standard blades had significantly greater success than non-standard blades at initial (51% vs 26%, P=0.002) and eventual (81% vs 58%, P=0.002) attempts at tracheal intubation. In multivariable logistic regression analysis, standard blades had 3-fold greater odds of success at initial tracheal intubations compared with non-standard blades (adjusted odds ratio 3.0, 95% confidence interval): 1.32-6.86, P=0.0009). Standard blades had 2.6-fold greater odds of success at eventual tracheal intubation compared with non-standard blades in children weighing <5 kg (adjusted odds ratio 2.6, 95% confidence interval: 1.08-6.25, P=0.033). There was no significant difference found in children weighing ≥5 kg. CONCLUSIONS: In infants weighing <5 kg, videolaryngoscopy with standard blades was associated with a significantly greater success rate than videolaryngoscopy with non-standard blades. Videolaryngoscopy with a standard blade is a sensible choice for tracheal intubation in children who weigh <5 kg.

Risk of Hypoxemia by Induction Technique Among Infants and Neonates Undergoing Pyloromyotomy.

BACKGROUND: In patients presenting for pyloromyotomy, most practitioners prioritize rapid securement of the airway due to concern for aspiration. However, there is a lack of consensus and limited evidence on the choice between rapid sequence induction (RSI) and modified RSI (mRSI). METHODS: The medical records of all patients presenting for pyloromyotomy from May 2012 to December 2018 were reviewed. The risk of hypoxemia (peripheral oxygen saturation [Spo2], <90%) during induction was compared between RSI and mRSI cohorts for all patients identified as well as in the neonate subgroup by univariate and multivariable logistic regression analysis. Complications (aspiration, intensive care unit admission, bradycardia, postoperative stridor, and hypotension) and initial intubation success for both cohorts were also compared. RESULTS: A total of 296 patients were identified: 181 in the RSI and 115 in the mRSI cohorts. RSI was associated with significantly higher rates of hypoxemia than mRSI (RSI, 30% [23%-37%]; mRSI, 17% [10%-24%]; P = .016). In multivariable logistic regression analysis of all patients, the adjusted odds ratio (OR) of hypoxemia for RSI versus mRSI was 2.8 (95% confidence interval [CI], 1.5-5.3; P = .003) and the OR of hypoxemia for multiple versus a single intubation attempt was 11.4 (95% CI, 5.8-22.5; P < .001). In multivariable logistic regression analysis of neonatal subgroup, the OR of hypoxemia for RSI versus mRSI was 6.5 (95% CI, 2.0-22.2; P < .001) and the OR of hypoxemia for multiple intubation versus single intubation attempts was 18.1 (95% CI, 4.7-40; P < .001). There were no induction-related complications in either the RSI and mRSI cohorts, and the initial intubation success rate was identical for both cohorts (78%). CONCLUSIONS: In infants presenting for pyloromyotomy, anesthetic induction with mRSI compared with RSI was associated with significantly less hypoxemia without an observed increase in aspiration events. In addition, the need for multiple intubation attempts was a strong predictor of hypoxemia. The increased risk of hypoxemia associated with RSI and multiple intubation attempts was even more pronounced in neonatal patients.

Airway Abnormalities in Patients With Congenital Heart Disease: Incidence and Associated Factors.

OBJECTIVES: Airway abnormalities complicate the perioperative course of patients with congenital heart disease (CHD), leading to significant morbidity and mortality. The literature describing airway abnormalities in those patients is scarce. This study aimed to determine the incidence of airway abnormalities in CHD patients and identify associated factors, genetic syndromes, and cardiac diagnoses. DESIGN: Retrospective study conducted after institutional review board approval. SETTING: Tertiary children's hospital. PARTICIPANTS: Patients presenting for cardiac diagnostic, interventional, or surgical procedures from 2012 to 2018. A total of 9,495 encounters were reviewed. EXCLUSION CRITERIA: age >18 years. Methods/Interventions: Age, weight, sex, intubation technique, number of intubation attempts, and difficult intubation (DI) were recorded. Using the International Classification of Diseases, Ninth and Tenth Revisions codes, genetic syndromes, acquired and congenital airway abnormalities, and cardiac diagnoses were identified. Multivariate generalized estimating equations modeling was used to identify independent predictors of airway abnormalities. RESULTS: A total of 4,797 patients, with 8,657 encounters were included. The median age was 1.3 years (interquartile range [IQR]: 0.2-6.0) and weight was 9.2 kg (IQR: 4.3-19.2), and 55% were male. A total of 16.7% had at least 1 genetic syndrome; 8.5% had congenital airway abnormalities and 9.7% acquired. Incidence of DI was 1.1%. The most common syndromes were Down, 22q11.2 microdeletion, and CHARGE. The most frequent congenital airway abnormalities were laryngomalacia and bronchomalacia, and the most frequent acquired were partial and total vocal cord paralysis. CONCLUSION: The likelihood of a coexistent airway abnormality should be considered in premature CHD patients, weight <10 kg, and in those with specific cardiac lesions and a concomitant genetic syndrome. Preoperative identification of patients at high risk of airway abnormalities is useful in planning their perioperative airway management.

Trends in Pediatric MRI sedation/anesthesia at a tertiary medical center over time.

BACKGROUND: Each year, hundreds of thousands of children require sedation/anesthesia to facilitate MRI scans. Anesthetic techniques for accomplishing sedation/anesthesia vary widely between institutions and providers, with unclear implications for patient safety. AIMS: We sought to establish trends in anesthetic practice for pediatric MRI sedation/anesthesia across a 7-year period and determine rates of adverse events, considering technique used, age, and ASA physical classification status (ASA-PS). METHODS: Using established data resources, we analyzed 24 052 anesthetics performed by anesthesiologists for MRI scans between 5/1/2013 and 12/31/2019 on patients less than 18 years old, focusing on medications used, trends of use, and associated adverse events. Adverse events (hypoxia, hypotension, bradycardia) were defined by deviation from age norms and accessed via the electronic anesthetic record database. The Cochran-Armitage test was used to assess trends over time in categorical data, and one-way ANOVA was used to analyze continuous data. Multivariable logistic regression analysis was implemented to determine the independent associations between anesthetic technique and adverse events while adjusting for age, ASA-PS, and weight. RESULTS: The most significant trends noted were a decrease in "propofol-only" anesthetic techniques and an increase in propofol and dexmedetomidine combination techniques. Mild desaturation (80-89% SpO2 ) occurred in 4.22% of cases with more significant hypoxia much rarer (0.44% of cases having desaturation <70% SpO2 ). Bradycardia occurred in 2.39% of cases and hypotension in 1.75% of cases. Major adverse events were rare. CONCLUSIONS: We provide the largest report of the nature of MRI sedation/anesthesia as practiced by anesthesiologists in a large children's hospital. We demonstrate that, even in a large system, anesthetic techniques are pliable and shift significantly over time. Our data also support a high level of safety within our system, despite a case mix likely higher in risk than those in most of the previously published studies.

Error traps in pediatric difficult airway management.

Difficult airway management in children is associated with significant morbidity. This narrative review on error traps in airway management aims to highlight the common pitfalls and proposes solutions to optimize best practices for pediatric difficult airway management. We have categorized common errors of pediatric difficult airway management into three main error traps: preparation, performance, and proficiency, and present potential strategies to improve patient safety and successful tracheal intubation in infants and children with difficult airways.

Lessons from COVID-19: A reflection on the strengths and weakness of early consensus recommendations for pediatric difficult airway management during a respiratory viral pandemic using a modified Delphi method.

BACKGROUND: The authors recognized a gap in existing guidelines and convened a modified Delphi process to address novel issues in pediatric difficult airway management raised by the COVID-19 pandemic. METHODS: The Pediatric Difficult Intubation Collaborative, a working group of the Society for Pediatric Anesthesia, assembled an international panel to reach consensus recommendations on pediatric difficult airway management during the COVID-19 pandemic using a modified Delphi method. We reflect on the strengths and weaknesses of this process and ways care has changed as knowledge and experience have grown over the course of the pandemic. RECOMMENDATIONS: In the setting of the COVID-19 pandemic, the Delphi panel recommends against moving away from the operating room solely for the purpose of having a negative pressure environment. The Delphi panel recommends supplying supplemental oxygen and using videolaryngoscopy during anticipated difficult airway management. Direct laryngoscopy is not recommended. If the patient meets extubation criteria, extubate in the OR, awake, at the end of the procedure. REFLECTION: These recommendations remain valuable guidance in caring for children with anticipated difficult airways and infectious respiratory pathology when reviewed in light of our growing knowledge and experience with COVID-19. The panel initially recommended minimizing involvement of additional people and trainees and minimizing techniques associated with aerosolization of viral particles. The demonstrated effectiveness of PPE and vaccination at reducing the risk of exposure and infection to clinicians managing the airway makes these recommendations less relevant for COVID-19. They would likely be important initial steps in the face of novel respiratory viral pathogens. CONCLUSIONS: The consensus process cannot and should not replace evidence-based guidelines; however, it is encouraging to see that the panel's recommendations have held up well as scientific knowledge and clinical experience have grown.

Aerosol barriers in pediatric anesthesiology: Clinical data supports FDA caution.

BACKGROUND: The onset of the COVID19 pandemic drove the rapid development and adoption of physical barriers intended to protect providers from aerosols generated during airway management. We report our initial experience with aerosol barrier devices in pediatric patients and raise concerns that they may increase risk to patients. METHODS: In March 2020, we developed and implemented simulation training and use of plastic aerosol barrier devices as a component of our perioperative COVID-19 workflow. As part of our quality improvement process, we obtained detailed feedback via a web-based survey after cases were performed while using these aerosol barriers. RESULTS: Between March and June 2020, 36 pediatric patients age 1mo-18years with anatomically normal airways and either PCR confirmed or suspected COVID-19 were intubated under an aerosol barrier as part of urgent or emergent anesthetic care at our institution. Experienced providers had more difficulty than expected in six (16.7%) of the cases with four cases requiring multiple attempts to secure the airway and two cases involving pronounced difficulty in a single attempt. The aerosol barrier was perceived as a contributing factor to difficulty in all cases. CONCLUSION: The use of barriers may result in unanticipated difficulties with airway management, particularly in pediatric patients, which could lead to hypoxemia or other patient harm. Our initial experience in pediatric patients is the first such report in patients and provides clinical data which corroborates the simulation data prompting the FDA to withdraw support of barriers.

Pediatric Airway Management in COVID-19 Patients: Consensus Guidelines From the Society for Pediatric Anesthesia's Pediatric Difficult Intubation Collaborative and the Canadian Pediatric Anesthesia Society.

The severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) pandemic has challenged medical systems and clinicians globally to unforeseen levels. Rapid spread of COVID-19 has forced clinicians to care for patients with a highly contagious disease without evidence-based guidelines. Using a virtual modified nominal group technique, the Pediatric Difficult Intubation Collaborative (PeDI-C), which currently includes 35 hospitals from 6 countries, generated consensus guidelines on airway management in pediatric anesthesia based on expert opinion and early data about the disease. PeDI-C identified overarching goals during care, including minimizing aerosolized respiratory secretions, minimizing the number of clinicians in contact with a patient, and recognizing that undiagnosed asymptomatic patients may shed the virus and infect health care workers. Recommendations include administering anxiolytic medications, intravenous anesthetic inductions, tracheal intubation using video laryngoscopes and cuffed tracheal tubes, use of in-line suction catheters, and modifying workflow to recover patients from anesthesia in the operating room. Importantly, PeDI-C recommends that anesthesiologists consider using appropriate personal protective equipment when performing aerosol-generating medical procedures in asymptomatic children, in addition to known or suspected children with COVID-19. Airway procedures should be done in negative pressure rooms when available. Adequate time should be allowed for operating room cleaning and air filtration between surgical cases. Research using rigorous study designs is urgently needed to inform safe practices during the COVID-19 pandemic. Until further information is available, PeDI-C advises that clinicians consider these guidelines to enhance the safety of health care workers during airway management when performing aerosol-generating medical procedures. These guidelines have been endorsed by the Society for Pediatric Anesthesia and the Canadian Pediatric Anesthesia Society.

Anesthesia for shared airway surgery in children.

Shared airway surgery in children is a complex, high-risk undertaking that requires continuous communication and cooperation between the anesthetic and surgical teams. Airway abnormalities commonly seen in children, the surgical options, and the anesthetic techniques that can be used to care for this vulnerable population are discussed. Many of these procedures were traditionally carried out using jet ventilation, or intermittent tracheal intubation, but increasingly spontaneously breathing "tubeless" techniques are being used. This review has been written from both the surgical and anesthetic perspective, highlighting the concerns that both specialties have in relation to the maintenance of surgical access and operating conditions, and the need for the provision of anesthesia, oxygenation, and ventilation where the airway is the primary site of operation.

A Phase II Study with Lead-In Safety Cohort of 5-Fluorouracil, Oxaliplatin, and Lapatinib in Combination with Radiation Therapy as Neoadjuvant Treatment for Patients with Localized HER2-Positive Esophagogastric Adenocarcinomas.

LESSONS LEARNED: Neoadjuvant 5-fluorouracil, oxaliplatin, and lapatinib in combination with radiation therapy is safe for neoadjuvant treatment for patients with localized human epidermal growth receptor 2-positive esophagogastric adenocarcinoma.Evaluation of this drug combination in a larger patient pool would allow for more accurate analysis of its efficacy. BACKGROUND: The optimal design of neoadjuvant chemoradiation for the treatment of localized esophagogastric cancers is the subject of much debate. In this nonrandomized trial, we evaluated neoadjuvant 5-fluorouracil (5-FU), oxaliplatin, and lapatinib in combination with radiation therapy as neoadjuvant treatment for patients with localized human epidermal growth receptor 2 (HER2)-positive esophagogastric adenocarcinomas. METHODS: Patients received neoadjuvant 5-FU (225 mg/m2 continuous intravenous infusion, days 1-42), oxaliplatin (85 mg/m2 intravenously [IV], days 1, 15, and 29), and lapatinib (six patients, 1,000 mg p.o., days 1-42; six patients, 750 mg p.o., days 1-42) plus radiation (1.8 Gy/day Monday through Friday for 50.4 Gy total). Following restaging, eligible patients underwent definitive resection, and pathologic response to neoadjuvant therapy was assessed. Planned enrollment was 42 patients. The primary endpoint was the pathologic complete response (pCR) rate. RESULTS: Twelve patients (median age 64 years; 67% male) received a median of 5.6 weeks of treatment (range: 1.1-8.4). The pCR rate was 8%; four of the 12 patients underwent tumor resection and one patient had a pCR, with pathologic partial response in the remaining three. The most common lapatinib-related adverse events included (all grades) nausea (67%) and diarrhea (58%), although these were all grade 1 or 2. Enrollment was halted due to low accrual. CONCLUSION: The treatment regimen was determined to be safe. The study was terminated early due to low accrual.