Outcomes in older adults with metastatic esophageal and gastric carcinoma treated with palliative chemotherapy.

BACKGROUND: The incidence of esophageal and gastric carcinoma (GEC) in elderly patients is increasing, yet patients ≥75 years have historically been underrepresented in clinical trials. We sought to investigate palliative chemotherapy administration patterns and survival outcomes in older adults. MATERIALS AND METHODS: A retrospective analysis identified patients aged 65-74 (young-old) and ≥75 years (older-old) diagnosed with advanced GEC. Patient and tumor characteristics were recorded, with descriptive analysis, time-to-event data analysis using Kaplan-Meier curves and multivariate Cox proportional hazards regression analysis performed. RESULTS: One hundred and ninety-eight "young-old" and 109 'older-old' patients were identified. Patient characteristics were similar between groups except for Charlson Co-morbidity Index (CCI), with lower co-morbidities in the "young-old" compared to "older-old" cohort (P < .001; CCI = 0 in 103 (52%) "young-old" vs 31 (28%) "older-old"). The primary diagnosis in both groups was adenocarcinoma. 119 (60%) "young-old" and 25 (23%) "older-old" patients received chemotherapy (P < .001). Performance status was the primary explanation for chemotherapy non-receipt in both cohorts; age was the explanation in 21 (25%) "older-old" patients and none in the "young-old" patients. PFS for first-line systemic therapy in "young-old" patients was 6.4 (95% CI 5.9-7.6) versus 7.5 months (95% CI 5.1-11.3) in "older-old" patients (P = .69) whilst respective OS was 12.3 (95% CI 10.1-15.5) and 10.4 months (95% CI 9.0-14.6) (P = .0816). Toxicity prompted chemotherapy cessation in 17 (15%) "young-old" and 3 (13%) "older-old" patients (P = .97). Multivariate analysis identified CCI and ECOG performance status as predictive for PFS and OS, respectively. No causative relationship was identified with other variables. CONCLUSION: Our study of real-world older-adults show that significant number of "older-old" patients with GEC do not receive chemotherapy. Among "older-old" adults who do receive systemic therapy, outcomes are comparable; this underscores the importance of geriatric assessment-guided care and suggests that age alone should not be a barrier to receipt of chemotherapy in patients with advanced GEC.

Integrating Patient-Reported Outcomes Into Prognostication in Gastroesophageal Cancer: Results of a Population-Based Retrospective Cohort Analysis.

BACKGROUND: Patient-reported outcomes measures (PROM) are self-reflections of an individual's physical functioning and emotional well-being. The Edmonton Symptom Assessment Scale (ESAS) is a simple and validated PRO tool of 10 common symptoms and a patient-reported functional status (PRFS) measure. The prognostic value of this tool is unknown in patients with gastroesophageal cancer (GEC). In this study, we examined the association between the ESAS score and overall survival (OS) in patients with GEC, the prognostication difference between ESAS and Eastern Cooperative Oncology Group (ECOG), and assessed the correlation between PRFS and the physician-reported ECOG performance status (PS). METHODS: The study was a retrospective cohort study of 211 patients with GEC with localized (stages I-III) and metastatic disease who completed at least one baseline ESAS prior to treatment. Patients were grouped into 3 cohorts based on ESAS score. OS was assessed using the Kaplan-Meier method, and the concordance index (c-index) was calculated for ESAS and physician-reported ECOG. The agreement between PRFS and physician-ECOG was also assessed. RESULTS: In total, 211 patients were included. The median age was 60.8 years; 90% of patients were ECOG PS 0-1; 38% of patients were stages I-III, while 62% were de novo metastatic patients. Median OS in low, moderate, high symptom burden (SB) patients' cohorts was 19.17 m, 16.39 mm, and 12.68 m, respectively (P < .04). The ability to predict death was similar between physician-ECOG and ESAS (c-index 0.56 and 0.5753, respectively) and PRFS and physician-ECOG (c-index of 0.5615 and 0.5545, respectively). The PS agreement between patients and physicians was 50% with a weighted Kappa of 0.27 (95% CI: 0.17-0.38). CONCLUSION: Patient's SB seems to carry a prognostic significance. ESAS and physician-reported ECOG exhibit comparable prognostic values. Physicians and patients can frequently have divergent opinions on PS. ESAS takes a patient-centered approach and should be encouraged in practice among patients with GEC as an additional tool for prognostication.

Leptomeningeal carcinomatosis and brain metastases in gastroesophageal carcinoma: a real-world analysis of clinical and pathologic characteristics and outcomes.

BACKGROUND: Brain metastasis (BrM) and Leptomeningeal Carcinomatosis (LMC) are uncommon complications in gastroesophageal carcinoma (GEC) patients. These patients have a poor prognosis and are challenging to treat. We described the clinicopathologic features and outcomes in the largest cohort of Central Nervous System (CNS) metastasis in GEC patients. METHODS: single-center retrospective study of GEC treated from 2007 to 2021. Clinicopathologic characteristics and treatment modalities were reviewed. Survival was calculated from the date of CNS diagnosis until date of death/last follow-up using the Kaplan-Meier method. A multivariable Cox proportional hazards regression model was used. RESULTS: Of 3283 GEC patients, 100 (3.04%) were diagnosed with BrM and 20 with LMC (0.61%). Patients with known human epidermal growth factor receptor 2 (HER2) status (N = 48), 60% were HER2 positive (defined as IHC 3 + or IHC 2+/FISH+). Among LMC patients most were signet-ring subtype (85%), and only 15% (2/13) were HER2 positive. Median survival was 0.7; 3.8; and 7.7 months in BrM patients treated with best supportive care, radiation, and surgery, respectively (p < 0.001). In LMC, median survival was 0.7 month in patients who had best supportive care (7/19) and 2.8 months for those who had whole brain radiation therapy (p = 0.015). Multivariate analysis showed worse outcomes in ECOG ≥ 2 (p = 0.002), number of BrM ≥ 4 (p < 0.001) and number of metastatic sites (p = 0.009). CONCLUSION: HER2 expression were enriched in patients with BrM, while it is uncommon in LMC. Patients treated with surgery followed by radiation had an improved OS in BrM and WBRT benefited patients with LMC.

First impressions: A prospective evaluation of patient-physician concordance and satisfaction following the initial medical oncology consultation.

BACKGROUND: An especially significant event in the patient-oncologist relationship is the initial consultation, where many complex topics-diagnosis, treatment intent, and often, prognosis-are discussed in a relatively short period of time. This study aimed to measure patients' understanding of the information discussed during their first medical oncology visit and their satisfaction with the communication from medical oncologists. METHODS: Between January and August 2021, patients without prior systemic treatment of their gastrointestinal malignancy (GI) attending the Princess Margaret Cancer Centre (PMCC) were approached within 24 h of their initial consultation to complete a paper-based questionnaire assessing understanding of their disease (diagnosis, treatment plan/intent, and prognosis) and satisfaction with the consultation. Medical oncology physicians simultaneously completed a similar questionnaire about the information discussed at the initial visit. Matched patient-physician responses were compared to assess the degree of concordance. RESULTS: A total of 184 matched patient-physician surveys were completed. The concordance rates for understanding of diagnosis, treatment plan, treatment intent, and prognosis were 92.9%, 59.2%, 66.8%, and 59.8%, respectively. After adjusting for patient and physician variables, patients who reported treatment intent to be unclear at the time of the consultation were independently associated with lower satisfaction scores (global p = 0.014). There was no statistically significant association between patient satisfaction and whether prognosis was disclosed (p = 0.08). CONCLUSION: An in-depth conversation as to what treatment intent and prognosis means is reasonable during the initial medical oncology consultation to ensure patients and caregivers have a better understanding about their cancer.

Combination of clinical, radiomic, and "delta" radiomic features in survival prediction of metastatic gastroesophageal adenocarcinoma.

Objectives: To identify combined clinical, radiomic, and delta-radiomic features in metastatic gastroesophageal adenocarcinomas (GEAs) that may predict survival outcomes. Methods: A total of 166 patients with metastatic GEAs on palliative chemotherapy with baseline and treatment/follow-up (8-12 weeks) contrast-enhanced CT were retrospectively identified. Demographic and clinical data were collected. Three-dimensional whole-lesional radiomic analysis was performed on the treatment/follow-up scans. "Delta" radiomic features were calculated based on the change in radiomic parameters compared to the baseline. The univariable analysis (UVA) Cox proportional hazards model was used to select clinical variables predictive of overall survival (OS) and progression-free survival (PFS) (p-value <0.05). The radiomic and "delta" features were then assessed in a multivariable analysis (MVA) Cox model in combination with clinical features identified on UVA. Features with a p-value <0.01 in the MVA models were selected to assess their pairwise correlation. Only non-highly correlated features (Pearson's correlation coefficient <0.7) were included in the final model. Leave-one-out cross-validation method was used, and the 1-year area under the receiver operating characteristic curve (AUC) was calculated for PFS and OS. Results: Of the 166 patients (median age of 59.8 years), 114 (69%) were male, 139 (84%) were non-Asian, and 147 (89%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. The median PFS and OS on treatment were 3.6 months (95% CI 2.86, 4.63) and 9 months (95% CI 7.49, 11.04), respectively. On UVA, the number of chemotherapy cycles and number of lesions at the end of treatment were associated with both PFS and OS (p < 0.001). ECOG status was associated with OS (p = 0.0063), but not PFS (p = 0.054). Of the delta-radiomic features, delta conventional HUmin, delta gray-level zone length matrix (GLZLM) GLNU, and delta GLZLM LGZE were incorporated into the model for PFS, and delta shape compacity was incorporated in the model for OS. Of the treatment/follow-up radiomic features, shape compacity and neighborhood gray-level dependence matrix (NGLDM) contrast were used in both models. The combined 1-year AUC (Kaplan-Meier estimator) was 0.82 and 0.81 for PFS and OS, respectively. Conclusions: A combination of clinical, radiomics, and delta-radiomic features may predict PFS and OS in GEAs with reasonable accuracy.

Long-Term Outcomes of Unrepaired Isolated Partial Anomalous Pulmonary Venous Connection With an Intact Atrial Septum.

The natural history of an unrepaired isolated partial anomalous pulmonary venous connection(s) (PAPVC) and the absence of other congenital anomalies remains unclear. This study aimed to expand the understanding of the clinical outcomes in this population. Isolated PAPVC with an intact atrial septum is a relatively uncommon condition. There is the perception that patients with isolated PAPVC are usually asymptomatic, that the lesion generally has a limited hemodynamic impact, and that surgical repair is rarely justified. For this retrospective study, we reviewed our institutional database to identify patients with either 1 or 2 anomalous pulmonary veins that drain a portion of but not the complete ipsilateral lung. Patients with previous surgical cardiac repair, coexistence of other congenital cardiac anomalies that would result in either pretricuspid or post-tricuspid loading of the right ventricle (RV), or scimitar syndrome were excluded. We reviewed their clinical course over the follow-up period. We identified 53 patients; 41 with a single and 12 with 2 anomalous PAPVC. A total of 30 patients (57%) were men, with a mean age at the latest clinic visit of 47 ± 19 years (18 to 84 years). Turner syndrome (6 of 53, 11.3%), bicuspid aortic valve (6 of 53, 11.3%), and coarctation of the aorta (5 of 53, 9.4%) were commonly associated anomalies. A single anomalous left upper lobe vein was the most commonly identified variation. More than half of the patients were asymptomatic. Cardiopulmonary exercise test demonstrated a maximal oxygen consumption of 73 ± 20% expected (36 to 120). Transthoracic echocardiography demonstrated a mean RV basal diameter of 4.4 ± 0.8 cm, RV systolic pressure of 38 ± 13 (16 to 84) mm Hg. A total of 8 patients (14.8%) had ≥moderate tricuspid regurgitation. Cardiac magnetic resonance in 42 patients demonstrated a mean RV end-diastolic volume index of 122 ±3 0 ml/m2 (66 to 188 ml/m2), of which in 8 (14.8%), it was >150 ml/m2. Magnetic resonance imaging-based Qp:Qs was 1.6 ± 0.3. A total of 5 patients (9.3%) had established pulmonary hypertension (mean pulmonary artery pressure ≥25 mm Hg). In conclusion, isolated single or dual anomalous pulmonary venous connection is not necessarily a benign congenital anomaly because a proportion of patients develop pulmonary hypertension and/or RV dilation. Regular follow-up and on-going patient surveillance with cardiac imaging is advised.

Comparison of Four Clinical Prognostic Scores in Patients with Advanced Gastric and Esophageal Cancer.

BACKGROUND: Prognostic scores that can identify patients at risk for early death are needed to aid treatment decision-making and patient selection for clinical trials. We compared the accuracy of four scores to predict early death (within 90 days) and overall survival (OS) in patients with metastatic gastric and esophageal (GE) cancer. METHODS: Advanced GE cancer patients receiving first-line systemic therapy were included. Prognostic risks were calculated using: Royal Marsden Hospital (RMH), MD Anderson Cancer Centre (MDACC), Gustave Roussy Immune (GRIm-Score), and MD Anderson Immune Checkpoint Inhibitor (MDA-ICI) scores. Overall survival (OS) was estimated using the Kaplan-Meier method. Cox proportional hazards models were used to analyze associations between prognostic scores and OS. The predictive discrimination was estimated using Harrell's c-index. Predictive ability for early death was measured using time-dependent AUCs. RESULTS: In total, 451 patients with metastatic GE cancer were included. High risk patients had shorter OS for all scores (RMH high- vs. low-risk median OS 7.9 vs. 12.2 months, P < .001; MDACC 6.8 vs. 11.9 months P < .001; GRIm-Score 5.3 vs. 13 months, P < .001; MDA-ICI 8.2 vs. 12.2 months, P < .001). On multivariable analysis, each prognostic score was significantly associated with OS. The GRIm-Score had the highest predictive discrimination and predictive ability for early death. CONCLUSIONS: The GRIm-Score had the highest accuracy in predicting early death and OS. Clinicians may use this score to identify patients at higher risk of early death to guide treatment decisions including clinical trial enrolment. This score could also be used as a stratification factor in future clinical trial designs.

Impact of Sites of Metastatic Dissemination on Survival in Advanced Gastroesophageal Adenocarcinoma.

INTRODUCTION: Metastatic gastroesophageal adenocarcinoma (GEA) is a heterogeneous disease with an overall poor prognosis. The impact of sites of metastatic dissemination on survival is not well characterized. This study aimed to evaluate whether certain sites of metastatic disease impacts survival. METHODS: A retrospective analysis of 375 patients with metastatic GEA treated at the Princess Margaret Cancer Centre from 2006 to 2016 was performed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to assess the association between sites of metastases and OS adjusting for baseline patient characteristics. RESULTS: Median duration of follow-up was 47.8 months. Median OS in this cohort was 11.8 months (95% CI: 10.2-12.9 months). Patients with lymph node only disease, compared to those with other sites of metastases, had the longest median OS (20.4 vs. 10.6 months; p < 0.001) and PFS (11.4 vs. 6.3 months; p < 0.001). On multivariable analysis adjusting for relevant clinical factors including age, sex, and Eastern Cooperative Oncology Group performance status, the presence of lung (HR 1.67, 95% CI: 1.23-2.26; p < 0.001) or bone metastases (HR 1.84, 95% CI: 1.31-2.59; p < 0.001) were independently associated with shorter OS. The majority of patients (68%) were treated with palliative intent first-line platinum-based chemotherapy. DISCUSSION/CONCLUSION: Patients with metastatic GEA have an overall poor prognosis. The presence of lung or bone metastases is an independent risk factor for decreased survival. Prognostic models incorporating sites of metastasis should be considered in the clinical evaluation of metastatic GEA.

Prognostic significance of nutritional markers in metastatic gastric and esophageal adenocarcinoma.

BACKGROUND: Malnutrition and sarcopenia are poor prognostic factors in many cancers. Studies in gastric and esophageal (GE) cancer have focused on curative intent patients. This study aims to evaluate the prognostic utility of malnutrition and sarcopenia in de novo metastatic GE adenocarcinoma. METHODS: Patients with de novo metastatic GE adenocarcinoma seen at the Princess Margaret Cancer Centre from 2010 to 2016 with an available pre-treatment abdominal computed tomography (CT) were included. Malnutrition was defined as nutritional risk index (NRI) <97.5. Skeletal muscle index (SMI) was measured at the L3 level (sarcopenia defined as SMI <34.4 cm2 /m2 in women and <45.4 cm2 /m2 in men). Patients receiving chemotherapy had NRI and SMI recalculated at the time of first restaging CT. RESULTS: Of 175 consecutive patients, 33% were malnourished and 39% were sarcopenic at baseline. Patients with pretreatment malnourishment had significantly shorter overall survival (OS; 5.8 vs. 10.9 months, p = 0.000475). Patients who became malnourished during chemotherapy had worse OS compared to those who maintained their nutrition (12.2 vs. 17.5 months p = 0.0484). On univariable analysis, ECOG (p < 0.001), number of metastatic sites (p = 0.029) and NRI (p < 0.001) were significant prognostic factors while BMI (p = 0.57) and sarcopenia (p = 0.19) were not. On multivariable analysis, ECOG (p < 0.001), baseline NRI (p = 0.025), and change in NRI during treatment (p < 0.001) were significant poor prognostic factors for OS. CONCLUSIONS: In de novo metastatic GE adenocarcinoma patients, ECOG, pretreatment NRI and change in NRI were significant prognostic factors for OS while sarcopenia was not. Use of NRI at baseline and during treatment can provide useful prognostic information.

Periprocedural Outcomes of Fluoroscopy-Guided Patent Foramen Ovale Closure With Selective Use of Intracardiac Echocardiography.

BACKGROUND: Recent randomized trials have confirmed the role of patent foramen ovale (PFO) closure in the secondary prevention of cryptogenic stroke. Guidelines have suggested a central role for intraprocedural imaging using intracardiac echocardiography (ICE). However, this modality may not be required to achieve safe and effective closure. We aimed to examine the periprocedural outcomes of PFO closure retrospectively, using fluoroscopic guidance in patients with cryptogenic stroke, with provisional ICE guidance driven by anatomic and procedural factors. METHODS: A retrospective chart review of consecutive patients who underwent PFO closure in a single centre using the Amplatzer PFO occluder (AGA Medical Corporation, Plymouth, Minnesota) for cryptogenic stroke was conducted. Outcomes analyzed included procedural data, periprocedural complications, length of stay, and factors contributing to the use of intraprocedural imaging. RESULTS: Between 2006 and 2017, 467 patients underwent PFO closure for cryptogenic stroke with the Amplatzer PFO occluder; 381 patients underwent closure with fluoroscopy alone, and 86 with ICE and fluoroscopic guidance. Periprocedural arrhythmic complications occurred in 1.3% in the fluoroscopy group and 1.2% in the ICE group (P = 1.000). Vascular complications occurred in 0.5% in the fluoroscopy group and 2.3% (P = 0.323) in the ICE group. One device embolized requiring surgical intervention. There was no in-hospital mortality or stroke. Same-day discharge occurred in 97.6% of patients. CONCLUSION: Our single-centre experience suggests that PFO closure can be safely conducted under fluoroscopic guidance alone with provisional adjunctive ICE use limited to specific anatomic situations.

Long-term outcomes of percutaneous closure of coronary artery fistulae in the adult: A single-center experience.

Coronary artery fistulae (CAF) are rare congenital cardiac abnormalities. With increasing age, patients with moderate to large fistulae are likely to become symptomatic and encounter complications. Percutaneous closure has been accepted as a safe and effective alternative to surgery; however, information regarding long-term outcomes in adult patients after transcatheter closure is limited. METHODS: We describe our 20-year experience with percutaneous closure of CAF in adult patients, focusing on long-term outcomes. RESULTS: From 1995 to 2015, 25 adult patients underwent 33 transcatheter interventions to close 26 CAF at our institution. Mean age was 51.4 ± 16.8 years, and 14 (56%) were female. All the patients were symptomatic with dyspnea (21/25, 84%) being the most common complaint followed by chest pain (17/25, 68%), palpitations (9/25, 36%), and heart failure (2/25, 8%). Two patients presented with acute coronary syndrome, whereas 10/25 (40%) also had inducible ischemia on stress test. These CAFs were classified as medium (12, 46.2%), large (5, 19.2%), and giant (9, 34.6%). Immediately postprocedure complete occlusion was achieved in 21 (21/26, 81%), and residual trace leak was observed in three fistulae, whereas we could not deliver coils/device in two cases. Periprocedural complications occurred in the form of coronary dissection (n = 1), myocardial infarction (n = 2), coil embolization (n = 1), transient ST elevation (n = 1); the majority of complications were observed in the early years of our experience. Patients reported marked improvement in symptoms after the intervention. During a mean follow-up of 76 ± 69 (5-214 months) (n = 22), 15 patients were investigated by either conventional (n = 6) or CT angiography (n = 8) or both (n = 1) that demonstrated thrombotic occlusion of a proximal coronary artery where a distal fistula was treated. Another patient was noted to have thrombus proximal to a vascular plug in a distal giant fistula. Three patients were lost to follow-up. None of the investigated patients had recanalization of their fistula. We did not observe remodeling of the native coronary artery that was feeding the fistula, even after successful complete closure. CONCLUSION: Percutaneous device closure of CAF is a feasible and effective therapeutic intervention in adult patients; however, patients with distal fistulas represent a significant challenge and the outcomes of these procedures are in question. All patients should have long-term angiographic follow-up.