Total Lesion Glycolysis Assessment Identifies a Patient Fraction With a High Cure Rate Among Esophageal Adenocarcinoma Patients Treated With Definitive Chemoradiation.

OBJECTIVE: We aimed to determine whether tumor metabolism could be prognostic of cure in L-EAC patients who receive definitive chemoradiation. SUMMARY BACKGROUND DATA: Patients with inoperable localized esophageal adenocarcinoma (L-EAC) often receive definitive chemoradiation; however, biomarkers and/or imaging variables to prognosticate cure are missing. METHODS: Two hundred sixty-six patients with L-EAC who had chemoradiation but not surgery were analyzed from the prospectively maintained EAC databases in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center (Texas, USA) between March 2002 and April 2015. Maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG) from the positron emission tomography data were evaluated. RESULTS: Of 266 patients, 253 (95%) were men; the median age was 67 years (range 20-91 yrs) and 153 had poorly differentiated L-EAC. The median SUVmax was 10.3 (range 0-87) and the median TLG was 85.7 (range 0-3227). Both SUVmax and TLG were higher among those with: tumors >5 cm in length, high clinical stage, and high tumor and node categories by TNM staging (all P < 0.0001). Of 234 patients evaluable for cure, 60 (25.6%) achieved cure. In the multivariable logistic regression model, low TLG (but not low SUVmax) was associated with cure (continuous TLG value: odds ratio 0.70, 95% confidence interval (CI) 0.54-0.92). TLG was quantified into 4 quartile categorical variables; first quartile (Q1; <32), second quartile (Q2; 32.0-85.6), third quartile (Q3; 85.6-228.4), and fourth quartile (Q4; >228.4); the cure rate was only 10.3% in Q4 and 5.1% in Q3 but increased to 28.8% in Q2, and 58.6% in Q1. The cross-validation resulted in an average accuracy of prediction score of 0.81 (95% CI, 0.75-0.86). CONCLUSIONS: In this cross-validated model, 59% of patients in the 1st quartile were cured following definitive chemoradiation. Baseline TLG could be pursued as one of the tools for esophageal preservation.

Ramucirumab and Paclitaxel Administered Every 2 Weeks (mRAINBOW Regimen) in Advanced Gastroesophageal Adenocarcinoma.

BACKGROUND: The RAINBOW trial established ramucirumab combined with paclitaxel as a second-line option in metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma. Ramucirumab was given on days 1 and 15 with paclitaxel on days 1, 8, and 15 of a 28-day cycle. The median overall survival (OS) was significantly longer with ramuciru-mab plus paclitaxel (p = 0.017), and it led to 41% grade 3 or higher neutropenia. We review our experience with both ramucirumab plus paclitaxel given biweekly (mRAINBOW) to assess efficacy and safety. OBJECTIVES: The primary objective was to assess OS. Secondary end points were progression-free survival (PFS), overall response, and safety. METHODS: We identified 129 patients retrospectively from our database between November 2014 and May 2017. Patients were included if they were followed up at our institution. RESULTS: Median doses given were ramucirumab 8 mg/kg i.v. plus paclitaxel 110 mg/m2 i.v. given once every 2 weeks. The median performance status was 1, and ∼60% had poorly differentiated histology; 55.8% had progression in < 6 months on first-line therapy, and the majority had measurable cancer. Median overall OS and PFS for the entire cohort was 9.4 months (95% CI: 8.05-10.74) and 3.68 months (95% CI: 2.73-4.5), respectively. Median OS was 9.46 months (95% CI: 8.05-14.95) and median PFS was 4.14 months (95% CI: 2.96-5.29) in those patients that received ramucirumab plus paclitaxel in the second-line setting. CONCLUSION: Biweekly administration of ramucirumab plus paclitaxel did not compromise efficacy. Delays, adjustments, or doses held were similar to the RAINBOW trial, with 31% requiring a dose or schedule modification.

Influence of induction chemotherapy in trimodality therapy-eligible oesophageal cancer patients: secondary analysis of a randomised trial.

BACKGROUND: A randomised phase 2 trial of trimodality with or without induction chemotherapy (IC) in oesophageal cancer (EC) patients showed no advantage in overall survival (OS) or pathologic complete response rate. To identify subsets that might benefit from IC, a secondary analysis was done. METHODS: The trial had accrued 126 patients (NCT 00525915). Recursive partitioning and proportional hazards regression with interactions were performed. RESULTS: The median follow-up of surviving patients was 6.7 years and the median OS duration was 3.8 years (95% confidence interval (CI), 2.6-5.8 years). OS was associated with tumour length (P=0.03), cT (P=0.02), cN (P=0.04), clinical stage (P=0.01), and tumour grade (P<0.001). The effect of IC differed according to tumour grade. Among patients with well or moderately differentiated (WMD) ECs (n=59), the 5-year survival rate was 74% with IC and 50% without IC, P=0.001. IC had no effect on OS of patients with poorly differentiated (PD) ECs (31% and 28%, respectively; interaction, P=0.04; IC, P=0.03). In the multivariate reduced model, WMD with IC was an independent prognosticator for better OS (HR=0.41, 95% CI, 0.25-0.67; P=<0.001). The following four EC phenotypes emerged for OS: (1) very high risk (PD, cN2/N3), (2) high risk (PD, cN0/N1, stage cIII), (3) moderate risk (PD, cN0/N1, stage cI/II or WMD without IC), and (4) low risk (WMD with IC). The 5-year survival rates were 11%, 27%, 48%, and 74%, respectively (P<0.001). CONCLUSIONS: Our data show that IC significantly prolonged OS of WMD EC patients who undergo trimodality; prospective evaluation is needed.

Barrett's Esophagus after Bimodality Therapy in Patients with Esophageal Adenocarcinoma.

INTRODUCTION: Barrett's esophagus (BE) may be present in patients with esophageal adenocarcinoma (EAC) after bimodality therapy (BMT). There is no specific guidance for follow-up of these patients with regard to the presence of BE or dysplasia. In this study, we assessed the outcomes of patients who, after BMT, had BE and those who did not. METHOD: Patients with EAC who had BMT were identified and analyzed retrospectively in two groups, with and without BE. We compared patient characteristics and outcome variables (local, distant, and no recurrence). RESULTS: Of 228 patients with EAC, 68 (29.8%) had BE before BMT. Ninety-eight (42.9%) had BE after BMT, and endoscopic intervention was done in 11 (11.2%). With a median follow-up of 37 months, the presence of post-BMT BE was not significantly associated with overall survival (OS) and local recurrence-free survival (LRFS). Similarly, endoscopic intervention was not significantly associated with OS and LRFS. Fifty (73.5%) patients with BE before BMT had BE after BMT (p < 0.0001). CONCLUSION: The presence of BE after BMT was not associated with increased risk of local recurrence. The local recurrence rate was not influenced by endoscopic intervention. Prospective studies are warranted to generate guidance for intervention, if necessary, for this group of EAC patients.

Risk of peritoneal metastases in patients who had negative peritoneal staging and received therapy for localized gastric adenocarcinoma.

BACKGROUND: Positive peritoneal cytology (+PCyt) or gross carcinomatosis (GPC) carries a poor prognosis. Laparoscopic staging to detect +PCyt/GPC is recommended for all ≥T1b gastric adenocarcinoma (GAC). The natural history of patients with GAC who have baseline -PCyt and then undergo multimodality therapy is not well documented, particularly for the risk of subsequent GPC. METHODS: We identified 238 GAC patients with baseline -PCyt who were followed for the development of peritoneal carcinomatosis (PC). Standard statistical methods were employed. RESULTS: Of 238 patients, 192 had attempted surgery after preoperative therapy. Of these, 13 patients (6.8%) had GPC and one had liver metastases, thus surgery was aborted. We followed 164 patients who had an R0 resection. The median follow-up duration was 3.4 (range, 0.6-18) years. The rate of PC was 13.4%, (22/164 patients) and the median time to PC was 15.6 months. Female gender was associated with PC on multivariate analysis. The 5-year OS rate for patients without subsequent PC was 75%. Conclusion Even with baseline -Cyt, ∼25% of patients develop PC following multimodality therapy. Patients who do not develop PC have an excellent OS rate. Further research is warranted to detect PC at baseline by the use of biomarkers.

Co-morbidities Rather than Age Impact Outcomes in Patients Receiving Preoperative Therapy for Gastroesophageal Adenocarcinoma.

BACKGROUND: Older patients with localized gastric adenocarcinoma (LGAC) have substantial postoperative morbidity and mortality; however, postoperative outcomes of the patients who receive preoperative chemotherapy and/or chemoradiation have not been reported. We examined the impact of age at baseline on potential predictors of postoperative outcomes. METHODS: Patients with LGAC who were treated with chemotherapy and/or chemoradiation followed by surgery (n = 203) formed two groups: (1) ≥65 years old (n = 70) and (2) <65 years old (n = 133). We assessed postoperative morbidity and mortality as well as overall survival (OS) and progression-free survival (PFS). Potential predictors of 90-day postoperative outcomes were identified i) by age groups and ii) other clinical covariates. Descriptive statistics and survival analyses were utilized. RESULTS: 90-day postoperative morbidity was similar in older and younger patients (61 % vs 58 %; P = 0.655). 90-day mortality was similar (3 % vs 0 %; P = 0.118). Major Clavien grade III/IV complications were similar (17 % vs 12 %; P = 0.392). OS and PFS were also similar for both groups (P = 0.863 and P = 0.558, respectively). Other factors, such as Charlson comorbidity index (P < 0.001) and median operative time (P = 0.002) were strongly associated with postoperative complications. CONCLUSION: Our data show that older patients with LGAC generally have similar outcomes as do younger patients after preoperative therapy but comorbidity indices have significant impact on complications and the long-term outcomes rather than age.

101 Long-Term Survivors Who Had Metastatic Gastroesophageal Cancer and Received Local Consolidative Therapy.

BACKGROUND: Through a multidisciplinary decision-making process, we developed a strategy of systemic therapy followed by local consolidative therapy (chemoradiation with/without surgery) in selected patients with metastatic gastroesophageal carcinoma (mGEAC). Only after a consensus during multidisciplinary discussions, local therapy was initiated. METHODS: We identified 101 patients with mGEAC who had local consolidation. We evaluated the association between various clinical variables (location of the primary, location of metastases, duration of initial chemotherapy, histologic grade, and radiation dose) and overall survival (OS). RESULTS: Of 101 patients, 71 had a proximal primary (esophageal, Siewert type I or II), and 30 patients had a distal primary (Siewert type III or distal). The median OS was 25.7 months (95% confidence interval [CI] 22.3-32.8). The OS rates at 2 and 5 years were 53.8% (95% CI 44.7-64.8) and 20.7% (95% CI 13.4-31.9), respectively. OS was highly associated with the location of the primary (median of 22.8 months for Siewert I/II vs. 41.5 months for Siewert III or distal, p = 0.03). The duration of initial chemotherapy was highly associated with OS (median of 21.8 months for <3 months vs. 32.5 months for ≥3 months, p = 0.004). CONCLUSION: Some mGEAC patients with a favorable clinical course can achieve a ∼20% 5-year survival rate with an approach that uses initial chemotherapy followed by multidisciplinary discussion to proceed with consolidation with local therapy. Patients with distal GEAC and those who receive initial chemotherapy for ≥3 months are the maximum beneficiaries.

Taxane-based or platinum-based combination chemotherapy given concurrently with radiation followed by surgery resulting in high cure rates in esophageal cancer patients.

BACKGROUND: Preoperative chemoradiotherapy (CRT) is one standard option for localized esophageal or gastroesophageal junction (GEJ) cancer patients but an optimal concurrent chemotherapy combination is not established. METHODS: 412 patients with resectable (cT1N1M0 or cT2-4N0-3M0) esophageal or GEJ cancer treated at the MDACC between October 2002 and June 2016 were analyzed. Exposures: CRT with DF or FOX followed by surgery (trimodality; TMT). Main outcomes and measures: Primary endpoints were overall survival (OS) and disease-free survival (DFS). Univariate and multivariate Cox analyses were performed. RESULTS: Of the 412 patients analyzed, 264 (64%) received DF and 148 (36%) FOX. The median age was 60 years, and 95% had adenocarcinoma. The clinical complete response, positron-emission tomography response, and pathologic complete response rates were 73%, 73%, and 30%, respectively. Median follow-up was 60.4 months. Median OS for the entire cohort was 81.6 months (95% confidence interval [CI], 56.3-122.0); 81.6 months (95% CI, 55.9-not estimable) for the DF group and 67.7 months (95% CI, 41.6-not estimable) for the FOX group (P = .24). The median DFS was 45.6 months (95% CI, 33.1-61.7) for the entire cohort; 49.5 months (95% CI, 38.6-70.3) for DF and 33.0 months (95% CI, 18.1-70.4; P = .38) for FOX. Higher tumor location (unfavorable) and clinical complete response (favorable) were prognostic for both OS and DFS in the multivariate analysis. CONCLUSION: At our high-volume center, the outcome of 412 TMT esophageal cancer patients was excellent. Taxane-based chemotherapy produces nonsignificant favorable trend.

Customization of therapy for gastroesophageal adenocarcinoma patients.

Gastroesophageal adenocarcinomas (GEACs) remain a global health problem. These are most often diagnosed at advanced stage and the estimated 5-year relative survival rate is about 5%. Although cure is not possible for patients with advanced GEAC, systemic therapy (chemotherapy or biochemotherapy) can palliate symptoms, improve survival and provide a better quality of life. One of the most promising options for some patients with advanced stage GEAC is immunotherapy, which can result in durable responses. Numerous phase III trials evaluating targeted therapies in different lines are ongoing and it is hoped that better biomarkers will emerge to identify patients who can benefit from targeted agents and immunotherapy in the future. Surgery remains as the corner stone for localized GEAC and adjunctive therapies can increase the survival rates by about 10%. The high toxicity and low completion rates of adjuvant therapy led to the strategies of preoperative treatment. With the results of ongoing pre-operative therapy trials we will be able to determine the optimal adjunctive approach for resectable GEAC.

Potentially curable gastric adenocarcinoma treated without surgery.

BACKGROUND: Surgery is the best option for cure of localised gastric adenocarcinoma (GAC). When surgery is not possible due to comorbidities or patient choice, definitive chemoradiation is an option. We report on one of the largest cohorts of localised GAC patients who did not have surgery. METHODS: We identified 71 patients with localised GAC who received chemo/chemoradiation therapy but did not have surgery. We assessed various end-points: overall survival (OS), relapse-free survival (RFS), and clinical complete response (cCR; negative post therapy biopsy and no evidence of cancer by imaging). RESULTS: The median follow-up time was 1.8 years (range; 0.4-10.6). Most of the patients were men (64.8%), and the median age was 73 years (range; 30-96). Reason for not having surgery included comorbidities in 34 (47.9%), poor performance status 14 (19.7%), and patient refusal 23 (32.4%). Of all 71 patients, a complete restaging evaluation with endoscopy and imaging could be performed for 50, and 32 (45.1%) achieved a cCR. For the entire cohort, the median OS was 2.1 years (95% confidence interval [CI] 1.78-2.55). The estimated OS rates at 2 and 5 years were 54% and 18%, respectively. Female gender (HR 0.39, 95% CI 0.16-0.98, p = 0.045) and chemoradiation (HR 0.25, 95% CI 0.06-1.01; p = 0.05) were independently associated with longer OS in the multivariate analysis. CONCLUSION: Our data show that patients with localised GAC treated with chemotherapy and/or chemoradiation, who do not undergo surgery, have a 5-year OS rate of 18%.

Early Metabolic Change after Induction Chemotherapy Predicts Histologic Response and Prognosis in Patients with Esophageal Cancer: Secondary Analysis of a Randomized Trial.

BACKGROUND: Early metabolic response after preoperative induction chemotherapy (IC) appears to predict histologic response and prognosis in esophageal cancer (EC), but the usefulness of this approach needs further development. OBJECTIVE: We evaluated metabolic response after one cycle of IC using positron emission tomography (PET) to correlate PET response and outcomes. PATIENTS AND METHODS: We retrospectively analyzed PET data from a randomized phase 2 trial (NCT00525915) of chemoradiation and surgery with or without IC for the treatment of EC. PET was performed at baseline, after one cycle of IC, and 5-7 weeks after chemoradiation. The relationship between PET response (≥35% reduction in standardized uptake value [SUV]) after IC and treatment response was analyzed. RESULTS: In 63 patients who received IC, the mean initial SUVmax prior to treatment was 11.9 ± 8.04 and mean SUVmax after one cycle of IC was 6.47 ± 4.45. The mean SUV reduction after IC was 39.3%. Eleven of 37 PET responders achieved a pathologic complete response (pCR), but only two of 22 PET non-responders did (univariate logistic regression; odds ratio: 4.25, 95% confidence interval: 0.83-21.77; p = 0.08). PET responders to IC had significantly longer overall survival (OS) than PET nonresponders (log-rank p = 0.009). PET response after chemoradiation was not correlated with OS (log-rank p = 0.15). CONCLUSION: Early PET response after IC is prognostic, but subsequent PET changes (for example, after chemoradiation) are not prognostic. Early PET response might have the potential of predicting pCR.

The role of chemotherapy in unresectable or metastatic adenocarcinoma of the stomach and gastroesophageal junction.

Gastric cancer including gastroesophageal junction adenocarcinomas are most challenging and deadly cancers of the gastrointestinal tract. Gastric cancer has a fatality-to-case ratio of 0.66, translating that nearly two thirds of newly diagnosed patients will have disseminated disease and in need of systemic therapy. Advanced gastric adenocarcinoma (AGC) is a heterogenous disease with differences in geographical distribution, histopathology, and molecular subtypes. Fluoropyrimidines (5-FU, S-1, and capecitabine), platinum compounds (cisplatin, oxaliplatin), taxanes (paclitaxel, docetaxel), and the topoisomerase inhibitory irinotecan are active drugs against AGC. The combination of fluoropyrimidines with a platinum compound is the optimal first-line treatment. Trastuzumab (given in combination with chemotherapy for HER2 positive tumors) and ramucirumab are the only targeted agents approved by the food and drug administration for the treatment in AGC for first and second line respectively. Efforts are being directed to harness the immune system with checkpoint inhibitors and to combining these drugs with chemotherapy in clinical trials. Genomic technology advancements might provide us with the tools to create personalized treatment for AGC in the near future with the goal to improve outcomes. In this article we aimed to review current therapeutic regimens for AGC with an update of ongoing clinical trials.

Advanced gastric adenocarcinoma: optimizing therapy options.

INTRODUCTION: Gastric adenocarcinoma (GAC) is the fifth most common cancer and third leading cause of cancer related mortality worldwide. When localized, cure is achievable with surgery and adjunctive therapies in some patients, however, once advanced, GAC is not a curable condition. Only two targeted agents (trastuzumab and ramucirumab) have been approved and apatinib was approved only in China. Because of the heterogeneous nature of GAC, it is not possible to assess a standard therapeutic approach. Areas covered: In this review, we aimed to describe the optimal systemic therapy regimens for advanced GAC. A literature search was performed to identify all phase II-III studies about advanced GAC from PubMed, clinicaltrials.gov, American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) websites. Expert commentary: A combination of a platinum compound and a fluoropyrimidine is ideal as first line therapy. Trastuzumab should be added if the tumor is HER2 positive. In the second line setting, paclitaxel/ramucirumab is preferred over ramucirumab alone. Recently, two similar molecular classifications for GAC have been proposed. A better understanding of molecular and immune biology of GAC could identify new therapeutic targets.

Bone microarchitecture and estimated bone strength in men with active acromegaly.

CONTEXT: Both acromegaly and adult growth hormone deficiency (GHD) are associated with increased fracture risk. Sufficient data are lacking regarding cortical bone microarchitecture and bone strength, as assessed by microfinite element analysis (µFEA). OBJECTIVE: To elucidate both cortical and trabecular bone microarchitecture and estimated bone strength in men with active acromegaly or GHD compared to healthy controls. DESIGN AND SUBJECTS: Cross-sectional study at a clinical research center, including 48 men (16 with acromegaly, 16 with GHD and 16 healthy controls). OUTCOME MEASURES: Areal bone mineral density (aBMD), cortical and trabecular bone microarchitecture and estimated bone strength (µFEA) at the radius and tibia. RESULTS: aBMD was not different between the 3 groups at any skeletal site. At the radius, patients with acromegaly had greater cortical area (P < 0.0001), cortical thickness (P = 0.0038), cortical pore volume (P < 0.0001) and cortical porosity (P = 0.0008), but lower trabecular bone density (P = 0.0010) compared to controls. At the tibia, patients with acromegaly had lower trabecular bone density (P = 0.0082), but no differences in cortical bone microstructure. Compressive strength and failure load did not significantly differ between groups. These findings persisted after excluding patients with hypogonadism. Bone microarchitecture was not deficient in patients with GHD. CONCLUSIONS: Both cortical and trabecular microarchitecture are altered in men with acromegaly. Our data indicate that GH excess is associated with distinct effects in cortical vs trabecular bone compartments. Our observations also affirm the limitations of aBMD testing in the evaluation of patients with acromegaly.

Post-trimodality expression levels of metadherin (MTDH) as a prognostic biomarker for esophageal adenocarcinoma patients.

Resectable esophageal adenocarcinoma (EAC) patients often receive chemoradiation followed by surgery. However, most patients experience recurrences. Overexpression of MTDH, an oncoprotein with multiple functions, has been found to be associated with poor prognosis in breast cancer, glioblastoma, melanoma and various gastrointestinal malignancies, but not in EAC. We sought to establish its role in resistant EAC (post-treatment residual EAC). MTDH was assessed by immunohistochemistry in resected EAC, and results were correlated with clinical outcomes. MTDH expression was detectable in 72.5% (50/69) of patients, while expression levels were high (positive) in 50.7% (35/69). Of 69 patients analyzed, 25 had no relapse and 44 patients had a relapse (8 with local-regional and 36 with distant). The median follow-up duration was 3 years (0.4-11.6). The median overall survival was not associated with MTDH status (2.79 years for MTDH-negative and 3.60 years for MTDH-positive patients, p = 0.121). In addition, MTDH was not associated with either the type of relapse (local or distant), baseline clinical stage, tumor grade, presence of signet ring cells, surgical (yp) stage, percentage of residual EAC or presence of lymphovascular invasion. Our data reveal that MTDH is not a prognostic biomarker in resistant EAC after trimodality therapy.

Utility of endoscopic ultrasound-guided fine-needle aspiration of regional lymph nodes that are proximal to and far from the primary distal esophageal carcinoma.

Implications of assessing the proximal and far para-tracheal or sub-carinal nodes (para-tracheal [PTN] or sub-carinal [SCN]) associated with lower primary esophageal carcinomas (ECs) are unclear. To evaluate the value of endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) for PTN and SCN, we analyzed results by positron emission tomography (PET) avidity, 4 EUS node malignancy features, and EUS-FNA results in all patients with Siewert's I or II EC. Of 133 patients (PTN, n=102; SCN, n=31) with EUS-FNA, 47 (35%) patients had malignant node, leading to treatment modifications. EUS-FNA diagnosed significantly more patients with malignant nodes (p=0.02) even when PET and EUS features were combined. Among 94 PET-negative and EUS-negative patients, 9 (10%) had malignant EUS-FNA. At a minimum follow-up of 1 year, only 3 (5%) of 62 patients with benign EUS-FNA had evidence of malignancy in the nodal area of prior EUS-FNA. Patients with malignant EUS-FNA independently had a much shorter overall survival (OS) than those with benign EUS-FNA (p<0.001). Our data suggest that a benign EUS-FNA is highly accurate and need not be pursued further. However, malignant EUS-FNA of PTN/SCN was independently prognostic, conferred a shorter OS, and altered the management of 35% of patients.

Thyrotropin-secreting pituitary adenomas: epidemiology, diagnosis, and management.

Inappropriate secretion of TSH was first described in 1960 in a patient with evidence of hyperthyroidism and expanded sella on imaging. It was later found that a type of pituitary adenoma that secretes TSH (thyrotropinoma) was the underlying cause. The objective of the present review article is to summarize data on the epidemiology, pathogenesis, diagnosis, and management of thyrotropinomas. The prevalence of thyrotropinomas is lower than that of other pituitary adenomas. Early diagnosis is now possible thanks to the availability of magnetic resonance imaging and sensitive laboratory assays. As a corollary, many patients now present earlier in the course of their disease and have smaller tumors at the time of diagnosis. Treatment also has evolved over time. Transsphenoidal surgery is still considered definitive therapy. Meanwhile, radiation therapy, including radiosurgery, is effective in achieving tumor control in the majority of patients. In the past, radiation therapy was used as second line treatment in patients with residual or recurrent tumor after surgery. However, the availability of somatostatin analogs, which can lead to normalization of thyroid function as well as shrink these tumors, has led to an increase in the role of medical therapy in patients who are not in remission after pituitary surgery. In addition, dopamine agonists have shown some efficacy in the management of these tumors. Better understanding of the molecular pathogenesis of thyrotropinomas may lead to rationally designed therapies for patients with thyrotropinomas.

Accuracy of Late-Night Salivary Cortisol in Evaluating Postoperative Remission and Recurrence in Cushing's Disease.

CONTEXT: Late-night salivary cortisol (LNSC) is well-validated in the diagnosis of Cushing's disease (CD). The accuracy of LNSC during follow-up of patients undergoing transsphenoidal surgery (TSS) has not been fully characterized. OBJECTIVES: We examined the accuracy of LNSC in establishing remission and identifying recurrence in postoperative patients with CD. DESIGN: This is a retrospective study. PATIENTS: Records of patients with CD who underwent TSS by a single neurosurgeon in our tertiary center (2005-2014) were analyzed (N = 224). Patients were selected for further investigation (n = 165) if there was at least one available LNSC test obtained after TSS (either within 3 months or during long-term follow-up). Extracted data included demographic and clinical characteristics, magnetic resonance imaging and laboratory data (morning serum cortisol, 24-hour urine free cortisol [UFC], LNSC) . MAIN OUTCOMES AND MEASURES: Remission was defined as nadir morning serum cortisol less than 5 mcg/dl and nadir 24-hour UFC less than 23 mcg. Recurrence was considered definite if confirmed surgically or prompted radiotherapy. RESULTS: Surgical remission occurred in 89% of 89 patients with available LNSC data. LNSC, obtained within 3 months of TSS, established remission with 94% sensitivity and 80% specificity at a cutpoint of 1.9 nmol/l (area under the curve [AUC] = 0.90). At a median follow-up of 53.5 months, LNSC established recurrence (75% sensitivity and 95% specificity) at a cutpoint of 7.4 nmol/l (AUC = 0.87), and 24-hour UFC established recurrence (68% sensitivity and 100% specificity) at a cutpoint of 1.6-fold above normal (AUC = 0.82). CONCLUSIONS: LNSC may accurately establish remission after TSS and identify recurrence more accurately than 24-hour UFC during long-term follow-up.