Estimation of the relative biological effectiveness (RBE) of the Lu-DOTA-iPSMA177 radiopharmaceutical.

Relative biological effectiveness is a radiobiological parameter relevant in radiotherapy planning and useful in evaluating the physiological impact of radiation in different tissues. Targeted radionuclide therapy allows the selective and specific deposition of higher radiation doses in a noninvasive way and without collateral effects through the administration of radiopharmaceuticals. Lu-DOTA-177(hydrazinylnicotinoyl-Lys-(Nal)-NH-CO-NH-Glu) also called Lu-iPSMA177 is a third generation radiopharmaceutical composed by a peptide that recognizes the prostate-specific membrane antigen (PSMA), a membrane protein overexpressed in several types of cancer and that mediates the radiopharmaceutical's recognition of cancer cells. The present study reports radiobiological parameters of Lu-iPSMA177 and demonstrates the superiority of targeted radiopharmaceuticals over external radiotherapy treatment options in terms of their relative biological effectiveness. The relative biological effectiveness value of 1.020±0.003 for the LINAC, estimated by fitting the linear-quadratic model equation to the resulting survival curves, was like those of 1.25±0.04,1.060±0.005and1.00±0.04 obtained by an alternative method in relation to the mean lethal doses at 90, 80 or 60 survival percent respectively. While the relative biological effectiveness values of 5.65±0.13,4.72±0.27and2.87±0.19 estimated for Lu-iPSMA177 were significantly higher than those for the LINAC. The results confirm that the biological effect produced by the deposition of a radiation absorbed dose delivered by the LINAC can be induced with a quarter of that dose using Lu-iPSMA177 due to the energy distribution, dose-rate and energy fluence.

Towards reef restoration in Zihuatanejo, Guerrero, México: lessons learned

Introduction: Coral reef structures in Zihuatanejo, Guerrero are well-preserved. The coverage of living corals, near 60 % at several locations, makes them comparable to other coral reefs in the states of Oaxaca, Jalisco, and Nayarit and with high potential to promote their conservation. Objective: To present the outcome of 12 years of research in coral communities from Zihuatanejo, Guerrero, as a justifying argument for the current conservation efforts in the area. Methods: We developed a baseline on the conservation status of the reef structures, bioerosion processes and the source of major natural and anthropogenic impacts. We assessed the genetic diversity of the coral zooxanthellae symbionts, the outcome of a technique of coral transplantation to recover the coverage of living corals and the local ecological knowledge to involve local inhabitants to promote conservation. Results: At least five coral reefs remain exposed to a medium-low level of impact by bioerosion and anthropization. Coral transplantation experiments made in the area showed records of transplant survival nearing 90 %. Although the warming of the sea surface temperature that occurred during the El Niño of 2015-2016 caused coral bleaching and mortality in several coral populations in this area, there were no affectations attributed to this phenomenon in other locations. This response was not related to the level of exposure to anthropogenic impacts, and the presence of thermal resistant zooxanthellae was assessed using molecular tools, confirming the existence of zooxanthellae of the genus Durusdinium. The analysis of local ecological knowledge of the inhabitants of Zihuatanejo showed that they keep elaborate knowledge on the ecology of coral reefs. This is complemented with scientific knowledge that will encourage community participation in conservation strategies. Conclusions: A long-term multidisciplinary strategy is required for coral reef conservation that encompasses: 1) assessing the role of the overall holobiont in the thermal resistance of corals from this area and 2) establishing restoration strategies of coral reefs that include the local knowledge about marine ecology, for the establishment of coral reef protection and management schemes put in place by local inhabitants.

Introducción: Los arrecifes coralinos de Zihuatanejo Guerrero están bien conservados. La cobertura de corales vivos, cerca del 60 %, los hace comparables a otras comunidades coralinas presentes en Oaxaca, Jalisco y Nayarit y con un alto potencial para promover su conservación. Objetivo: Presentar los resultados de 12 años de investigación en las comunidades coralinas de Zihuatanejo, Guerrero, como un argumento que justifica los esfuerzos actuales de conservación en el área. Métodos: Desarrollamos una línea base del estado de conservación de la estructura arrecifal, los procesos de bioerosión y las fuentes principales de impactos naturales y antropogénicos. Evaluamos la diversidad genética de los simbiontes zooxantelados de los corales, el resultado de una técnica de trasplante de corales para recuperar la cobertura de corales vivos y el conocimiento ecológico local para desarrollar estrategias de conservación con participación local. Resultados: Cinco de esas comunidades coralinas permanecen expuestas a un nivel de impacto medio a bajo por bioerosión y antropización. Los experimentos de trasplante de corales en el área mostraron una supervivencia cercana al 90 %. Aunque el calentamiento de la temperatura superficial del mar ocurrido durante el evento El Niño 2015-16 causó blanqueamiento y mortalidad coralina en algunas poblaciones de corales del área, no hubo afectaciones atribuidas a este fenómeno en otras. Esta respuesta no se relacionó con el nivel de exposición a impactos antropogénicos y la presencia de poblaciones de zooxantelas fue examinada usando herramientas moleculares, confirmando la existencia de una población del género Durusdinium. El análisis del conocimiento ecológico local de los habitantes de Zihuatanejo mostró que estos resguardan conocimientos complejos sobre la ecología de las comunidades coralinas. Este conocimiento es complementario al conocimiento científico y servirá para promover estrategias de participación ciudadana en la conservación de las comunidades coralinas. Conclusiones: Se requiere una estrategia multidisciplinaria de largo plazo para la conservación de las comunidades coralinas que incluya: 1) examinar el papel del holobionte completo en la resistencia térmica de los corales de esta área y 2) establecer estrategias de restauración en arrecifes coralinos que incluyan el conocimiento ecológico local para el establecimiento de esquemas de protección y manejo de los arrecifes coralinos a cargo de los habitantes locales.

Early Bidirectional Glenn Procedure as Initial Surgical Palliation for Functionally Univentricular Heart with Common Arterial Trunk.

We report an unusual case of a 2-month-old baby with a diagnosis of common arterial trunk and double outlet right ventricle with a remote type ventricular septal defect. Taking into consideration the physiologic moment and anatomic findings of the patient, we planned and successfully performed a bidirectional Glenn procedure as its first palliative procedure.

The Lugones Procedure for Scimitar Syndrome Repair Through Right Axillary Thoracotomy: Not Only a Cosmetically Superior Approach.

Several surgical strategies to deal with scimitar syndrome have been described over the years. Among them, the technique described by Lugones and coworkers in 2014 has gained attention due to its simplicity, reproducibility and excellent results. Following the original report of the procedure, the defect is usually repaired through a midline sternotomy. Here, we describe an alternative approach using a right axillary thoracotomy, which not only exhibits superior cosmetic results but allows for an excellent view of all relevant anatomic structures.

Surgical Management for Late Presentation of Interrupted Aortic Arch with Aortopulmonary Window.

We report a case of advanced age at presentation of interrupted aortic arch with aortopulmonary window. Although the association between these two defects is well established, their overall prevalence is extremely low. This case presents us with an excellent opportunity to discuss decision making regarding aortic arch repair techniques according to age at which primary surgical correction is intended.

Early Extubation in a Pediatric Cardiac Surgery Program Located at High Altitude.

BACKGROUND: Early extubation is performed either in the operating room or in the cardiovascular intensive care unit during the first 24 postoperative hours; however, altitude might possibly affect the process. The aim of this study is the evaluation of early extubation feasibility of patients undergoing congenital heart surgery in a center located at 2,691 m (8,828 ft.) above sea level. MATERIAL AND METHODS: Patients undergoing congenital heart surgery, from August 2012 through December 2018, were considered for early extubation. The following variables were recorded: weight, serum lactate, presence or not of Down syndrome, optimal oxygenation and acid-base status according to individual physiological condition (biventricular or univentricular), age, bypass time, and ventricular function. Standardized anesthetic management with dexmedetomidine-fentanyl-rocuronium and sevoflurane was used. If extubation in the operating room was considered, 0.08 mL/kg of 0.5% ropivacaine was injected into the parasternal intercostal spaces bilaterally before closing the sternum. RESULTS: Four hundred seventy-eight patients were operated and 81% were early extubated. Mean pre- and postoperative SaO2 was 92% and 98%; postoperative SaO2 for Glenn and Fontan procedures patients was 82% and 91%, respectively. Seventy-three percent of patients who underwent Glenn procedure, 89% of those who underwent Fontan procedure (all nonfenestrated), and 85% with Down syndrome were extubated in the operating room. Reintubation rate in early extubated patients was 3.6%. CONCLUSION: Early extubation is feasible, with low reintubation rates, at 2,691 m (8,828 ft.) above sea level, even in patients with single ventricle physiology.

Norwood Procedure in a Patient With Hypoplastic Left Heart Syndrome, Right Aortic Arch, and Right Descending Aorta.

We describe the surgical treatment of a patient with hypoplastic left heart syndrome and right aortic arch.

Outcomes of the Non-fenestrated Fontan Procedure at High Altitude.

BACKGROUND: Although high altitude has been considered a risk factor for the Fontan operation, and an indication for fenestration, there is a paucity of data to support its routine use. Fenestration, with its necessary right to left induced shunt, together with the lower partial pressure of oxygen found with progressive altitude, can significantly decrease hemoglobin oxygen saturation, and therefore, it would be desirable to avoid it. OBJECTIVE: To analyze immediate and medium-term results of the non-fenestrated, extracardiac, Fontan procedure at high altitude. METHODS: Retrospective analysis of data from consecutive patients who underwent non-fenestrated, extracardiac, Fontan procedure at two institutions located in Mexico City at 2,312 m (7,585 ft) and 2,691 m (8,828 ft) above sea level. High altitude was not considered a risk factor. RESULTS: Thirty-nine patients were included, with a mean age of 6.7 years. Mean preoperative indexed pulmonary vascular resistance was 1.7 Wood units. Seventy-nine percent of the patients extubated in the operating room. There was one in-hospital death (2.56%) and one at follow-up. Median chest tube drainage time was 6.5 and 6 days for the right and left pleural spaces. Median oxygen saturation at discharge was 90%. At a median follow-up of six months, all survivors, except one, had good tolerance to daily life activities. CONCLUSIONS: The present study shows good short- and medium-term results for the non-fenestrated, extracardiac, Fontan operation at altitudes between 2,300 and 2,700 m and might favor this strategy over fenestration to improve postoperative oxygen saturation. Further studies to examine the long-term outcomes of this approach need to be considered.

Theoretical and experimental characterization of emission and transmission spectra of Cerenkov radiation generated by 177Lu in tissue.

Cerenkov radiation (CR) is the emission of UV-vis light generated by the de-excitation of the molecules in the medium, after being polarized by an excited particle traveling faster than the speed of light. When ß particles travel through tissue with energies greater than 219 keV, CR occurs. Tissues possess a spectral optical window of 600 to 1100 nm. The CR within this range can be useful for quantitative preclinical studies using optical imaging and for the in-vivo evaluation of Lu177-radiopharmaceuticals (ß-particle emitters). The objective of our research was to determine the experimental emission light spectrum of Lu177-CR and evaluate its transmission properties in tissue as well as the feasibility to applying CR imaging in the preclinical studies of Lu177-radiopharmaceuticals. The theoretical and experimental characterizations of the emission and transmission spectra of Lu177-CR in tissue, in the vis-NIR region (350 to 900 nm), were performed using Monte Carlo simulation and UV-vis spectroscopy. Mice Lu177-CR images were acquired using a charge-coupled detector camera and were quantitatively analyzed. The results demonstrated good agreement between the theoretical and the experimental Lu177-CR emission spectra. Preclinical CR imaging demonstrated that the biokinetics of Lu177-radiopharmaceuticals in the main organs of mice can be acquired.

Sponge diversity in Eastern Tropical Pacific coral reefs: an interoceanic comparison.

Sponges are an important component of coral reef communities. The present study is the first devoted exclusively to coral reef sponges from Eastern Tropical Pacific (ETP). Eighty-seven species were found, with assemblages dominated by very small cryptic patches and boring sponges such as Cliona vermifera; the most common species in ETP reefs. We compared the sponge patterns from ETP reefs, Caribbean reefs (CR) and West Pacific reefs (WPR), and all have in common that very few species dominate the sponge assemblages. However, they are massive or large sun exposed sponges in CR and WPR, and small encrusting and boring cryptic species in ETP. At a similar depth, CR and WPR had seven times more individuals per m2, and between four (CR) and five times (WPR) more species per m2 than ETP. Perturbation, at local and large scale, rather than biological factors, seems to explain the low prevalence and characteristics of sponge assemblages in ETP reefs, which are very frequently located in shallow water where excessive turbulence, abrasion and high levels of damaging light occur. Other factors such as the recurrence of large-scale phenomena (mainly El Niño events), age of the reef (younger in ETP), isolation (higher in ETP), difficulty to gain recruits from distant areas (higher in ETP), are responsible for shaping ETP sponge communities. Such great differences in sponge fauna between the three basins might have consequences for coral reef structure and dynamics.

A Novel Private-Public Hybrid Model for Treatment of Congenital Heart Disease in Mexico.

Mortality after surgery for congenital heart disease (CHD) in Mexico is significantly higher than in high-income countries due to structural, medical, and financial factors. In Mexico, public hospitals have a large volume of patients but inadequate quality control systems, whereas private hospitals, although having higher quality control systems, have an insufficient number of patients to build programs of excellence. We describe the creation of a novel hybrid private-public program in Mexico that leverages the advantages of both sectors while establishing an integrated multidisciplinary unit that has allowed us to improve the quality of care for patients with CHD.

Complete pathologic response is independent of the timing of esophagectomy following neoadjuvant chemoradiation for esophageal cancer.

BACKGROUND: The relationship of complete pathologic response (cPR) with the timing of esophagectomy after neoadjuvant chemoradiation (nCRT) is not well defined. We sought to determine if a delay in esophagectomy after nCRT would result in increased likelihood of cPR and improved survival. METHODS: This is a retrospective analysis of a prospectively maintained database of all patients treated with nCRT and esophagectomy between 2004 and 2014. Patients were divided into two groups based on timing of esophagectomy (≤50 vs. >50 days) after completion of nCRT. Survival outcomes were compared using standard Kaplan-Meier curves, and multivariable analyses were performed using Cox regression models. RESULTS: This study included 226 patients (males, 211 and median age, 61 years) for analysis. Fifty-two patients (23%) in the early group (≤50 days) were compared to 174 patients (77%) in the delayed group (>50 days). The two groups were similar with respect to age, gender, comorbid conditions, ECOG status, location, grade, and tumor histology. There was no statistically significant difference in cPR rate between the early and late groups (26.9% vs. 19.0%, respectively, P=0.24). On multivariable analysis, lower age, absence of signet cell histology, better ECOG status, shorter length of stay and cPR were independent predictors of improved survival. The median follow-up was 52 months (range, 2-110 months), and there was no difference in the median overall survival (OS) between the early and late groups (48.9 vs. 42.6 months, respectively, P=0.73). CONCLUSIONS: This analysis of a large cohort of patients with esophageal cancer undergoing multi-modality therapy shows that cPR is independent of the timing of esophagectomy. Other considerations for the timing of surgery, including recovery from nCRT and patient performance, may have more relevant roles than cPR when deciding when to perform esophagectomy.

Estimation of the effectiveness ratio (α/ß) for resistant cancer cells in U87MG human glioblastoma.

Glioblastoma contains self-renewing, tumorigenic cancer stem-like cells that contribute to tumor initiation and therapeutic resistance. The aim of this research was to estimate and compare the effectiveness ratio (α/ß) of stem-like cells and differentiated glioma cells derived from the U87MG glioblastoma cell line. Cell survival experiments were obtained in a dose range of 0-20 Gy (13.52 ± 0.09 Gy/h) as a hyperfractionationated accelerated radiotherapy scheme. Biochemical characterization of the post-irradiated cells was performed by flow cytometry analysis and the percentage of stem-like cells that resisted irradiation was determined by the CD133 expression. Results showed that U87MG stem-like cells are highly proliferative and more radioresistant than the U87MG adherent group (with a lesser stem-like character), this in association with the calculated α/ß ratio of 17 and 14.1, respectively.

Seguridad de la re-esternotomía media en el tratamiento paliativo de pacientes con corazón univentricular / Safety of repeat median sternotomy in the palliative treatment of patients with a univentricular heart

Resumen: Objetivo: Describir la morbimortalidad operatoria relacionada a re-esternotomía media en pacientes con corazón univentricular en el Instituto Nacional de Pediatría. Método: Estudio de serie de casos retrospectiva, descriptiva y analítica del año 2001 al 2016. Resultados: Se encontraron 65 pacientes que requirieron 76 procedimientos. Hubo 59 primeras re-esternotomías, con promedio de edad de 36 meses (4-176 meses) y peso 12.2 kg (3.2-21.5 kg); se realizaron 40 procedimientos de Glenn y 19 procedimientos de Fontan. Se practicaron 17 segundas re-esternotomías, con promedio de edad de 89 meses (48-156 meses) y 22.7 kg de peso (14.4-41 kg), en quienes se realizaron 17 procedimientos de Fontan. Hubo dos lesiones en primeras re-esternotomías, una lesión a la coronaria derecha con cambios electrocardiográficos, y una apertura incidental de la aurícula derecha que causó hipotensión. Reportamos una muerte secundaria a lesión de la aorta con sangrado masivo durante una segunda re-esternotomía, lo que representa una morbimortalidad del 3.9%. Conclusiones: Concluimos que la re-esternotomía es un procedimiento seguro en nuestro centro.

Abstract: Objective: To establish the morbidity and mortality of patients with univentricular hearts who underwent a repeat median sternotomy at the Instituto Nacional de Pediatría. Method: A retrospective review was performed on the clinical charts of all patients who under-went a repeat median sternotomy from 2001 to 2016. Results: Sixty-five patients underwent 76 surgeries by repeat median sternotomy. Fifty-nine patients had a first repeat median sternotomy, with a mean age of 36 months (range: 4-176 months) and a mean weight of 12.2 kg (range: 3.2-21.5 kg). Forty patients had a Glenn procedure, and 19 patients had a Fontan procedure. There were 17 patients with a second repeat median sternotomy, with a mean age of 89 months (range 48-156 months), and a mean weight of 22.7 kg (14.4-41 kg). A Fontan procedure was performed on all these 17 patients. A section of the right coronary artery with electrocardiographic changes and a right atrium tear that caused hypotension occurred during first repeat sternotomy. An aortic tear occurred during a second repeat sternotomy with massive bleeding and subsequent death. This represents 3.9% of re-entry injuries. Conclusion: It is concluded that repeat median sternotomy is a safe procedure.

Fluorescent, Plasmonic, and Radiotherapeutic Properties of the 177Lu-Dendrimer-AuNP-Folate-Bombesin Nanoprobe Located Inside Cancer Cells.

The integration of fluorescence and plasmonic properties into one molecule is of importance in developing multifunctional imaging and therapy nanoprobes. The aim of this research was to evaluate the fluorescent properties and the plasmonic-photothermal, therapeutic, and radiotherapeutic potential of 177Lu-dendrimer conjugated to folate and bombesin with gold nanoparticles in the dendritic cavity (177Lu-DenAuNP-folate-bombesin) when it is internalized in T47D breast cancer cells. The intense near-Infrared (NIR) fluorescence emitted at 825 nm from the conjugate inside cells corroborated the usefulness of DenAuNP-folate-bombesin for optical imaging. After laser irradiation, the presence of the nanosystem in cells caused a significant increase in the temperature of the medium (46.8°C, compared to 39.1°C without DenAuNP-folate-bombesin, P < 0.05), resulting in a significant decrease in cell viability (down to 16.51% ± 1.52%) due to the 177Lu-DenAuNP-folate-bombesin plasmonic properties. After treatment with 177Lu-DenAuNP-folate-bombesin, the T47D cell viability decreased 90% because of the radiation-absorbed dose (63.16 ± 4.20 Gy) delivered inside the cells. The 177Lu-DenAuNP-folate-bombesin nanoprobe internalized in cancer cells exhibited properties suitable for optical imaging, plasmonic-photothermal therapy, and targeted radiotherapy.

Identificación de un patrón tromboelastográfico en niños sometidos a cirugía cardiaca con exposición prolongada a circulación extracorpórea / Identification of a thromboelastographic pattern in children undergoing cardiac surgery with prolonged exposure to cardiopulmonary bypass

Background: Point-of-care thromboelastography is used for guiding peri-operative haemostatic therapy. Objective: To identify a thromboelastographic pattern in children with prolonged cardiopulmonary bypass exposure. Material and methods: A cohort study of 62 patients undergoing prolonged cardiopulmonary bypass was performed. Patients with preexisting coagulopathy, use of drugs known to interfere with clotting, hematocrit > 60%, weight < 3 kg, or hepatic disease were excluded. The thromboelastography study was conducted at the point of care. Results: Baseline and rewarming reaction time values were 8.24 ± 6.35 and 7.66 ± 2.15min, respectively (p = 0.102). Baseline and rewarming angle values were 64.88 ± 13.08 and 54.67 ± 8.98 degrees, respectively (p < 0.001). Baseline and rewarming maximum amplitude values were 64.54 ± 12.31 and 43.14 ± 12.47 mm, respectively (p = 0.001). The same trend was observed when the cohort was divided into patients under and over 3 years of age, and patients under and over 10 kg of body weight. Discussion: This study suggests the existence of a thromboelastographic pattern independent of age or weight in patients undergoing paediatric cardiac surgery with prolonged cardiopulmonary bypass exposure, characterised by a reduction of angle and maximum amplitude values, with no change in reaction time.

Introducción: La tromboelastografía se emplea para la orientación en el manejo de la coagulación perioperatoria en el sitio de atención. Objetívo: Identificar un patrón de coagulación en niños sometidos a tiempos prolongados en circulación extracorpórea así como su asociación con edad y peso. Material y Métodos: Realizamos un estudio de cohorte en 62 pacientes sometidos a circulación extracorpórea prolongada. Excluimos pacientes con coagulopatía pre - existente, empleo de medicamentos interfiriendo con la coagulación, hematocrito > 60%, peso < 3 Kg o con enfermedad hepática. El estudio de tromboelastografía fue realizado en el sitio de atención. Resultados: Los valores para el tiempo de Reacción basales y durante recalentamiento fueron: 8,24 +/- 6,35 y 7,66 +/- 2,15 minutos respectivamente (p= 0,102). Los valores para el Ángulo basales y durante recalentamiento fueron: 64,89 +/- 13,08 y 54,67 +/- 8,98 grados (p< 0,001). Los valores para Amplitud Máxima basales y durante recalentamiento fueron: 64,54 +/-12,31 y 43,14 +/- 12,47 mm respectivamente (p = 0,001). Dividiendo la cohorte en pacientes menores o mayores a 3 años o bien en menores o mayores a 10 Kg se observó el mismo comportamiento. Discusión: Este estudio sugiere la existencia de un patrón tromboelastográfico independiente de la edad o peso en pacientes sometidos cirugía cardiaca pediátrica con permanencia prolongada en circulación extracorpórea caracterizado por reducción en los valores de ángulo y amplitud máxima, sin modificación en el tiempo de reacción.

[Safety of repeat median sternotomy in the palliative treatment of patients with a univentricular heart]. / Seguridad de la re-esternotomía media en el tratamiento paliativo de pacientes con corazón univentricular.

OBJECTIVE: To establish the morbidity and mortality of patients with univentricular hearts who underwent a repeat median sternotomy at the Instituto Nacional de Pediatría. METHOD: A retrospective review was performed on the clinical charts of all patients who underwent a repeat median sternotomy from 2001 to 2016. RESULTS: Sixty-five patients underwent 76 surgeries by repeat median sternotomy. Fifty-nine patients had a first repeat median sternotomy, with a mean age of 36 months (range: 4-176 months) and a mean weight of 12.2 kg (range: 3.2-21.5 kg). Forty patients had a Glenn procedure, and 19 patients had a Fontan procedure. There were 17 patients with a second repeat median sternotomy, with a mean age of 89 months (range 48-156 months), and a mean weight of 22.7 kg (14.4-41 kg). A Fontan procedure was performed on all these 17 patients. A section of the right coronary artery with electrocardiographic changes and a right atrium tear that caused hypotension occurred during first repeat sternotomy. An aortic tear occurred during a second repeat sternotomy with massive bleeding and subsequent death. This represents 3.9% of re-entry injuries. CONCLUSION: It is concluded that repeat median sternotomy is a safe procedure.

Pathologic Complete Response Is an Independent Predictor of Improved Survival Following Neoadjuvant Chemoradiation for Esophageal Adenocarcinoma.

INTRODUCTION: Reports of improved survival in patients with pathologic complete response (pCR) to neoadjuvant therapy for esophageal and gastroesophageal junction (GEJ) adenocarcinoma is extrapolated from heterogeneous studies that include squamous cell histology. We sought to determine if pCR is associated with a survival advantage in a homogenous group of patients with esophageal adenocarcinoma. METHODS: This is a single institution analysis of all patients with T2-T4 or node positive esophageal adenocarcinoma treated with neoadjuvant chemoradiotherapy and esophagectomy between 2004 and 2014. Patients were divided into two groups based on pathological response, pCR vs. incomplete pathological response (iPR). Survival outcomes were evaluated using standard Kaplan-Meier methods and multivariable Cox regression models. RESULTS: A total of 205 patients were included in the study: 38 (19 %) patients with pCR and 167 patients (81 %) with iPR. The two groups were similar with respect to clinical stage, age, gender, comorbid conditions, ECOG status, smoking, and alcohol use. Patients in the pCR group had a higher percentage of tumors located in middle third of esophagus (11 vs. 2 %, p = 0.04) while tumor grade was similar in both groups. Median follow-up was 50 months, range 2-109 months. The 3-year overall (OS) and recurrence-free survival (RFS) for iPR was 48 and 39 %, respectively, vs. 86 and 80 % for pCR group, respectively. CONCLUSION: This analysis of a cohort of homogeneous patients with esophageal adenocarcinoma undergoing multimodality therapy showed that pCR is an independent predictor of improved RFS and OS. This data contributes to a growing body of evidence highlighting the benefits of neoadjuvant therapy specific to esophageal adenocarcinoma particularly when pCR is achieved.

Role of Repeat 18F-Fluorodeoxyglucose Positron Emission Tomography Examination in Predicting Pathologic Response Following Neoadjuvant Chemoradiotherapy for Esophageal Adenocarcinoma.

IMPORTANCE: Predicting complete pathologic response (CPR) preoperatively can significantly affect surgical decision making. There are conflicting data regarding positron emission tomography computed tomography (PET CT) characteristics and the ability of PET CT to predict pathologic response following neoadjuvant chemoradiotherapy in esophageal adenocarcinoma because most existing studies that include squamous histology have limited numbers and use nonstandardized PET CT imaging. OBJECTIVE: To determine if PET CT characteristics are associated with CPR in patients undergoing trimodality treatment for esophageal adenocarcinoma. DESIGN, SETTING, AND PARTICIPANTS: A retrospective medical record review was conducted at a large tertiary cancer center from a prospectively maintained database from January 1, 2005, to December 31, 2012. Inclusion criteria were patients undergoing esophagectomy for locally advanced esophageal adenocarcinoma post-neoadjuvant chemoradiotherapy with 2 standardized PET CT studies done at our institution (pre-neoadjuvant chemoradiotherapy and post-neoadjuvant chemoradiotherapy) for review. Data collected included clinical, pathologic, imaging, and treatment characteristics. MAIN OUTCOME AND MEASURE: The primary study outcome was the association of PET CT characteristics with histologic confirmed pathologic response. RESULTS: Of the total participants, 77 patients met the inclusion criteria. Twenty-two patients (28.6%) had CPR vs 55 patients (71.4%) who had incomplete pathologic response. The 2 groups were similar in age, sex, race/ethnicity, comorbid conditions, Eastern Cooperative Oncology Group status, tumor grade, chemotherapy, and radiation regimen and days between the 2 PET CTs. The mean prestandardized uptake variable (SUV; 14.5 vs 11.2; P = .05), δ SUV (10.3 vs 5.4; P = .02), and relative δ SUV (0.6 vs 0.4; P = .02) were significantly higher in those with CPR vs incomplete pathologic response. Using the Youden Index, a δ SUV value less than 45% was predictive of residual disease with a positive predictive value of 91.7% (95% CI, 73-99; P < .05). CONCLUSIONS AND RELEVANCE: To our knowledge, this is the largest study examining the role of PET CT characteristics in esophageal adenocarcinoma for patients undergoing neoadjuvant chemoradiotherapy that demonstrates that δ SUV of less than 45% is associated with patients with residual disease but not CPR. Based on the findings from our study, the current recommendation is still surgical resection regardless of the posttherapy PET SUV in the primary tumor. However, our study highlights the ability to detect patients with residual disease and the need to critically evaluate these patients for consideration of additional therapies.