Maternal pheochromocytoma and childbirth in Sweden 1973-2015: a population-based study on short and long-term outcome.

PURPOSE: Data guiding management of pheochromocytoma and paraganglioma (PPGL) in pregnant women is limited, and long-term effects on the child are unknown. The aim of this retrospective registry-based case-cohort study was to assess how maternal PPGL and treatment impacts maternal and fetal outcome, including long-term outcome for the child. The main outcomes were maternal and fetal mortality and morbidity at delivery and relative healthcare consumption in children born by mothers with PPGL during pregnancy. METHODS: The National Birth Register identified 4,390,869 pregnancies between 1973-2015. Data was crosslinked with three Swedish national registers to identify women diagnosed with pheochromocytoma or paraganglioma within one year before or after childbirth. Hospital records were reviewed and register data was collected for five age-matched controls for each child until age 18. RESULTS: 21 women and 23 children were identified (incidence 4.8/1.000.000 births/year), all women with adrenal pheochromocytomas (Pc). The majority (71%) were diagnosed post-partum. Nine women (43%) were hypertensive during pregnancy. Preterm delivery was more common in Pc patients compared to controls (30% vs 6%, p < 0.001). There was no maternal or fetal mortality. Timing of tumor removal did not affect gestational weight or APGAR scores. There was no observed difference in hospital admissions between children affected by maternal Pc and controls. CONCLUSION: Pc was commonly diagnosed after delivery and raised the risk of pre-term delivery, suggesting a need for an increased awareness of this diagnosis. However, reassuringly, there was no fetal or maternal mortality or any observed long-term impact on the children.

Management and outcome of metastatic pheochromocytomas/paragangliomas: a monocentric experience.

BACKGROUND: Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare neuroendocrine tumors releasing catecholamines. Metastatic pheochromocytomas/paragangliomas (PPGLs) occur in about 5-26% of cases. To date, the management of patients affected by metastatic disease is a challenge in the absence of guidelines. AIM: The aim of this study was to evaluate the overall survival (OS) and the progression-free survival (PFS) in metastatic PPGLs. METHODS: Clinical data of 20 patients referred to the Careggi University Hospital (Florence, Italy) were retrospectively collected. Follow-up ranged from 1989 to 2019. Site and size of primary tumor, biochemical activity, genetic analysis and employed therapies were considered. Data were analyzed with SPSS version 27. RESULTS: Nine PHEOs (45%) and 11 PGLs (55%) were enrolled. Median age at diagnosis was 43.5 years [30-55]. Mean follow-up was 104.6 ± 89.3 months. Catecholamines were released in 70% of cases. An inherited disease was reported in 50% of patients. OS from the initial diagnosis (OSpt) and from the metastatic appearance (OSmtx) were lower in older patients (OSpt p = 0.028; OSmtx p < 0.001), abdominal PGLs (OSpt p = 0.007; OSmtx p = 0.041), larger tumors (OSpt p = 0.008; OSmtx p = 0.025) and sporadic disease (OSpt p = 0.013; OSmtx p = 0.008). CONCLUSION: Our data showed that older age at the initial diagnosis, sympathetic extra-adrenal localization, larger tumors and wild-type neoplasms are related to worse prognosis. Notably, the employed therapies do not seem to influence the survival of our patients. At present, effective treatments for metastatic PPGLs are missing and a multidisciplinary approach is indispensably required.

Stereotactic body radiation therapy for adrenal gland metastases: outcome and predictive factors from a multicenter analysis.

Adrenal metastases occur in 15-35% of oncological patients. Surgery is the first treatment option. Stereotactic body radiotherapy (SBRT) has been largely explored in oligometastatic patients unfit for surgery, representing an effective and non-invasive local treatment. The results of a multi-institutional experience of SBRT on adrenal metastases in the oligorecurrent or oligoprogressive setting are herein reported. We collected data of adrenal gland metastases treated with SBRT in three Italian centers from 2010 to 2020. End-points of the present study were: Overall survival (OS), Local control of treated metastases (LC), Progression free survival (PFS), and toxicity. 149 adrenal gland metastases were treated with SBRT in 142 patients. The most common primary tumor was lung cancer (58.4%), followed by kidney cancer (9.4%). Median lesion's volume was 28.5 cm3 (2.5-323.4). The median SBRT dose was 40 Gy (10-60). Median follow-up was 14.4 months. One- and two-year OS were 72.3% and 53.5%. At univariate analysis performance status correlated with survival (HR 1.57, p = 0.006). One- and two-year LC were 85.4% and 79.2%, with lung primary tumor (HR 0.33, p = 0.021) and BED10 (HR 0.97, p = 0.036) significant independent factors. One- and two-year PFS were 37.7% and 24.8%. Median time to polymetastatic disease was 11.3 months. Grade 1 and 2 toxicity occurred in 21 (14.7%) and 3 (2.1%) patients. The results from this large multi-center study confirm the efficacy and safety of SBRT in the management of adrenal gland metastases, as a valid alternative to other more invasive local approaches.

Partial versus total adrenalectomy for pheochromocytoma: a population-based comparison of outcomes.

PURPOSE: The literature assessing outcomes of partial adrenalectomy (PA) among patients with pheochromocytoma patients is largely limited to isolated, single-institution series. We aimed to perform a population-level comparison of outcomes between patients undergoing PA versus those undergoing total adrenalectomy (TA). METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) was queried to identify adults with pheochromocytoma who underwent either PA or TA. Survival was assessed using multivariable Cox proportional hazards regression, Fine and Gray competing-risks regression, propensity score matching, Kaplan-Meier analysis, and cumulative incidence plots. RESULTS: 286 patients (PA: 101, TA: 185) were included in this study. As compared to those undergoing TA, patients undergoing PA had fewer tumors ≥ 8 cm in size (28.7% versus 42.7%, p = 0.048) and were more likely to have localized disease (61.4% versus 44.3%, p = 0.01). In multivariable analysis, patients undergoing PA demonstrated similar all-cause mortality (HR = 0.71, 95% CI 0.44-1.14, p = 0.16) and cancer-specific mortality (HR = 0.64, 95% CI 0.35-1.17, p = 0.15) compared to those who underwent TA. Following 1:1 propensity score matching, Kaplan-Meier analysis revealed no difference in overall survival between PA and TA groups (p = 0.26) nor was there a difference in the cumulative incidence of cancer-specific mortality (p = 0.29). CONCLUSIONS: In this first population-level comparison of outcomes among patients with pheochromocytoma undergoing PA and those undergoing TA, we found no long-term differences in any survival metric between groups. PA circumvents the need for lifelong corticoid replacement therapy and remains a promising option for patients with bilateral or recurrent pheochromocytoma.

Stereotactic body radiation therapy (SBRT) for patients with oligometastatic/oligoprogressive adrenal metastases: Outcomes and toxicities profile in a monoinstitutional study.

AIMS: To evaluate survival outcomes and toxicology profiles in oligometastatic/oligoprogressive patients treated with SBRT for adrenal metastases. METHODS: We retrospectively analyzed 25 metastatic adrenal lesions in 24 oligometastatic/oligoprogressive patients undergoing ablative Stereotactic Body Radiation Therapy (SBRT) between February 2010 and November 2019 in our department. The primary endpoint was overall survival (OS). Secondary endpoints were local overall response rate (ORR), acute and late toxicities. RESULTS: The most common primary tumor was non-small cell lung cancer (54%). Twenty-one patients received chemo or immuno-therapy. The median planning target volume (PTV) was 41.7 cm3. Median SBRT dose was 36 Gy. Median dose per fraction was 15 Gy. Median survival was 35-months with OS outcomes ranging from 6-months (100%), 1-year (87.5%) and 2-years (66.7%). ORR based on RECIST criteria was 66.5%. 12 patients experienced acute toxicities, mostly grade 1-2 (8 patients, 32%). CONCLUSIONS: SBRT for oligometastatic/oligoprogressive patients with adrenal metastases showed acceptable survival outcomes and a safe toxicity profile.

Single-nuclei transcriptomes from human adrenal gland reveal distinct cellular identities of low and high-risk neuroblastoma tumors.

Childhood neuroblastoma has a remarkable variability in outcome. Age at diagnosis is one of the most important prognostic factors, with children less than 1 year old having favorable outcomes. Here we study single-cell and single-nuclei transcriptomes of neuroblastoma with different clinical risk groups and stages, including healthy adrenal gland. We compare tumor cell populations with embryonic mouse sympatho-adrenal derivatives, and post-natal human adrenal gland. We provide evidence that low and high-risk neuroblastoma have different cell identities, representing two disease entities. Low-risk neuroblastoma presents a transcriptome that resembles sympatho- and chromaffin cells, whereas malignant cells enriched in high-risk neuroblastoma resembles a subtype of TRKB+ cholinergic progenitor population identified in human post-natal gland. Analyses of these populations reveal different gene expression programs for worst and better survival in correlation with age at diagnosis. Our findings reveal two cellular identities and a composition of human neuroblastoma tumors reflecting clinical heterogeneity and outcome.

Prognostic Nomograms for Predicting Overall Survival and Cancer-Specific Survival of Patients With Malignant Pheochromocytoma and Paraganglioma.

Background: Malignant pheochromocytoma and paraganglioma (PPGL) are rare tumors with few prognostic tools. This study aimed to construct nomograms for predicting 3- and 5-year survival for patients with malignant PPGL. Methods: The patient data was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. A total of 764 patients diagnosed with malignant PPGL from 1975 to 2016 were included in this study. The patients were randomly divided into two cohorts; the training cohort (n = 536) and the validation cohort (n = 228). Univariate analysis, Lasso regression, and multivariate Cox analysis were used to identify independent prognostic factors, which were then utilized to construct survival nomograms. The nomograms were used to predict 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) for patients with malignant PPGL. The prediction accuracy of the nomogram was assessed using the concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves. Decision curve analysis (DCAs) was used to evaluate the performance of survival models. Results: Age, gender, tumor type, tumor stage, or surgery were independent prognostic factors for OS in patients with malignant PPGL, while age, tumor stage, or surgery were independent prognostic factors for CSS (P <.05). Based on these factors, we successfully constructed the OS and CSS nomograms. The C-indexes were 0.747 and 0.742 for the OS and CSS nomograms, respectively. In addition, both the calibration curves and ROC curves for the model exhibited reliable performance. Conclusion: We successfully constructed nomograms for predicting the OS and CSS of patients with malignant PPGL. The nomograms could inform personalized clinical management of the patients.

A population-based analysis of clinical features and lymph node dissection in head and neck malignant neurogenic tumors.

BACKGROUND: The influence of lymph node dissection (LND) on survival in patients with head and neck neurogenic tumors remains unclear. We aimed to determine the effect of LND on the outcomes of patients with head and neck neurogenic tumors. METHODS: Data of patients with surgically treated head and neck neurogenic tumors were identified from the Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) to investigate the relationship between LND and clinical outcomes by survival analysis. Subgroup analysis was performed in IVa and IVb group. RESULTS: In total, 662 head and neck neurogenic tumor patients (median age: 49.0 [0-91.0] years) met the inclusion criteria, of whom 13.1% were in the IVa group and 86.9% were in the IVb group. The median follow-up time was 76.0 months (range: 6.0-336.0 months), and the 5-year and 10-year overall survival was 82.4% (95% CI, 0.79-0.85) and 69.0% (95% CI, 0.64-0.73). Cox regression analysis revealed older age (P < .001), advanced stage (P = .037), African American race (P = .002), diagnosis before 2004 (P < .001), and chemotherapy administration (P < .001) to be independent negative predictors of overall survival. Kaplan-Meier analysis demonstrated that LND was not a predictor of clinical nodal negativity (cN0) in either IVa or IVb patients. CONCLUSIONS: In head and neck neurogenic patients, LND may not impact the outcome of cN0 in either IVa or IVb group. These data can be recommended in guiding surgical plan and future studies.

Association Between Mortality and Levels of Autonomous Cortisol Secretion by Adrenal Incidentalomas : A Cohort Study.

BACKGROUND: Autonomous cortisol secretion in patients with adrenal incidentalomas is associated with increased mortality, but detailed information about the risk associated with specific levels of autonomous cortisol secretion is not available. OBJECTIVE: To measure the association between mortality and levels of autonomous cortisol secretion in patients with adrenal incidentalomas. DESIGN: Retrospective cohort study. (ClinicalTrials.gov: NCT03919734). SETTING: Two hospitals in southern Sweden. PATIENTS: Consecutive patients who had adrenal incidentalomas identified between 2005 and 2015 and were followed for up to 14 years. Outcome data were collected from national registers. MEASUREMENTS: Patients were grouped according to plasma cortisol level after a 1-mg dexamethasone suppression test (cortisolDST; <50, 50 to 82, 83 to 137, or ≥138 nmol/L). RESULTS: During a median follow-up of 6.4 years, 170 of 1048 patients died. Compared with a cortisolDST less than 50 nmol/L, a cortisolDST of 50 to 82 nmol/L was not associated with increased mortality (hazard ratio [HR], 1.15 [95% CI, 0.78 to 1.70]). However, a cortisolDST of 83 to 137 nmol/L (n = 119) had an HR of 2.30 (CI, 1.52 to 3.49), and a cortisolDST of 138 nmol/L or higher (n = 82) had an HR of 3.04 (CI, 1.86 to 4.98). Analyses using restricted cubic splines indicated that the association between cortisolDST and mortality was linear up to a cortisolDST of 200 nmol/L. LIMITATION: The results are not based on verified autonomous cortisol secretion; thus, the association may be underestimated. CONCLUSION: The association between mortality and cortisolDST increased linearly until cortisolDST reached 200 nmol/L. A cortisolDST of 83 to 137 nmol/L was associated with a 2-fold increase in mortality, and a cortisolDST of 138 nmol/L or higher was associated with a 3-fold increase in mortality. Additional studies should be done, and until those studies are completed some clinicians may consider these findings when deciding which patients to recommend for surgery. PRIMARY FUNDING SOURCE: Lisa and Johan Grönberg Foundation and Gyllenstiernska Krapperup Foundation.

Modeling of Tumor Control Probability in Stereotactic Body Radiation Therapy for Adrenal Tumors.

PURPOSE: Stereotactic body radiation therapy (SBRT) in the management of adrenal metastases is emerging as a well-tolerated, effective method of treatment for patients with limited metastatic disease. SBRT planning and treatment utilization are widely variable, and publications report heterogeneous radiation dose fractionation schemes and treatment outcomes. The objective of this analysis was to review the current literature on SBRT for adrenal metastases and to develop treatment guidelines and a model for tumor control probability of SBRT for adrenal metastases based on these publications. METHODS AND MATERIALS: A literature search of all studies on SBRT for adrenal metastases published from 2008 to 2017 was performed, and outcomes in these studies were reviewed. Local control (LC) rates were fit to a statistically significant Poisson model using maximum likelihood estimation techniques. RESULTS: One-year LC greater than 95% was achieved at an approximated biological equivalent dose with α/ß = 10 Gy of 116.4 Gy. CONCLUSIONS: While respecting normal tissue tolerances, tumor doses greater than or equal to a biological equivalent dose with α/ß = 10 Gy of 116.4 Gy are recommended to achieve high LC. Further studies following unified reporting standards are needed for more robust prediction.

Recurrence-Free Survival Analysis in Locally Advanced Pheochromocytoma: First Appraisal.

CONTEXT: The behavior of locally advanced pheochromocytoma (LAP) remains unknown. OBJECTIVE: We characterized the population with LAP and recurrence-free survival (RFS). METHODS: This retrospective multicentric study was run within the ENDOCAN-COMETE network and French Group of Endocrine Tumors (GTE) from 2003 to 2018, including patients from 11 French referral centers with LAP as defined by capsular invasion, vascular invasion, adipose tissue invasion, and/or positive locoregional lymph nodes at diagnosis without evidence of distant metastasis. The main outcome measure was recurrence, defined as tumor reappearance, including local site and/or distant metastasis. The primary endpoint was RFS analysis; secondary endpoints were characterization, overall survival (OS), and prognostic factors of recurrence. RESULTS: Among 950 patients, 90 (9%) exhibited LAP criteria and 55 met inclusion criteria (median age, 53 years; 61% males; 14% with germline mutation; 84% with catecholamine excess). LAP was defined by 31 (56%) capsular invasions, 27 (49%) fat invasions, 6 (11%) positive lymph nodes, and 22 (40%) vascular invasions. After median follow-up of 54 months (range, 6-180), 12 patients (22%) had recurrences and 3 (5%) died of metastatic disease. Median RFS was 115 months (range, 6-168). Recurrences were local in 2 patients, distant in 2, and both local and distant in 8 patients. Median OS of patients was not reached. Size above 6.5 cm (P = 0.019) and Ki-67 > 2% (P = 0.028) were identified as independent significant prognostic factors in multivariate analysis. CONCLUSION: LAP represents 9% of pheochromocytoma's population and has a metastatic behavior. This study paves the way for future pathological TNM classification.

Image-Guided Percutaneous Ablation of Adrenal Metastases: A Meta-Analysis of Efficacy and Safety.

PURPOSE: To evaluate the efficacy and safety of percutaneous ablation of adrenal metastases through a meta-analysis of various image-guided percutaneous ablation techniques. MATERIALS AND METHODS: A comprehensive literature search of PubMed and Embase databases was performed for studies evaluating the efficacy and/or safety of image-guided percutaneous ablation of adrenal metastases. A total of 37 studies published between 2009 and 2020 were analyzed, comprising a sample size of 959 patients. Proportion estimates of overall survival, local control, and toxicity were analyzed in a pooled meta-analysis. The pooled prevalence of adverse events after ablation was calculated based on common terminology criteria for adverse events (CTCAE) grading. RESULTS: Of the 959 included patients, 320 (33.3%) underwent radiofrequency ablation, 72 (7.5%) microwave ablation, 95 (9.9%) cryoablation, and 46 (4.8%) ethanol injections for treatment of adrenal metastases. The remaining 426 (44.4%) patients were from studies involving a mixture of the 4 listed percutaneous ablation techniques. The pooled 1-year local control rate was 80% (95% confidence interval [CI], 76%-83%). The pooled 1-year overall survival rate was 77% (95% CI, 70%-83%). The overall rate of severe adverse events after ablation (CTCAE grade 3 or higher) was 16.1%. The overall rate of low-grade adverse events after ablation (CTCAE grade 2 or lower) was 32.6%. Approximately 21.9% (n = 203) of patients experienced intraprocedural hypertensive crises, the majority of which were reversed with antihypertensive medications. CONCLUSIONS: This study demonstrates that image-guided percutaneous ablation can be effective in achieving acceptable short- to mid-term local tumor control and overall survival with a moderate safety profile.

Review of Palliative Radiation Therapy Patterns of Practice for Adrenal Metastases in British Columbia.

PURPOSE: The adrenal gland is a common site of metastasis in patients with advanced cancer, but it is rarely symptomatic. A subset of patients develop a complex pain syndrome with anorexia, nausea, and poorly localized visceral pain in the back, flank, or epigastric region. These symptoms can affect quality of life and are occasionally challenging to palliate. The role of palliative radiation therapy (PRT) in these patients is unclear. This population-based retrospective study evaluates PRT practices for patients with adrenal metastases and aims to describe treatment response and acute toxicity. METHODS AND MATERIALS: Patients who received PRT to an adrenal metastasis between the years of 1985 and 2015 were identified in a provincial database. Patient demographics, tumor factors, symptom burden, radiation therapy prescriptions, and response to treatment were collected. Variables were summarized using descriptive statistics. The Kaplan-Meier test was used to assess survival. Factors associated with clinical response were evaluated using univariate and logistic regression analysis. Factors associated with survival were evaluated using univariate and Cox proportional hazards model. RESULTS: One hundred patients who received 103 separate courses of PRT were identified. The majority had a lung primary (82%). The most common baseline symptoms were pain (90%) and gastrointestinal upset (13%). Prescriptions ranged from 600 cGy in a single fraction to 4500 cGy in 25 fractions. Seventy percent of patients experienced an improvement in pain (either a complete or partial response). Forty-three percent of patients developed acute toxicity from treatment. Median survival was 3 months. CONCLUSIONS: Compared with other anatomic sites, conventional PRT is uncommonly delivered to adrenal metastases. Despite heterogeneity in tumor histology and radiation therapy prescriptions, treatment was associated with an overall pain response of 70%. Prophylactic antiemetics to decrease radiation-induced nausea are required before treatment. Given the poor prognosis of this population, short fractionations are indicated.

Uncommon tumors in multiple endocrine neoplasia (MEN) type 1: Do they have a relationship with the prognosis of these patients?

INTRODUCTION: The prognosis of MEN 1 patients is not only determined by pancreatic disease; it is also related to other uncommon tumors. The objective of this study is to analyze the tumors associated with MEN 1 outside the classic triad and to investigate their relationship with mortality. MATERIALS AND METHODS: One hundred and five MEN 1 patients were studied in a tertiary referral hospital (1980-2019). RESULTS: With a follow-up of 11 ± 4 years, seven patients died (8%), four as a consequence MEN syndrome. Thirty-three percent had adrenal gland tumors. One patient died of adrenal cancer. Eight percent presented with a neuroendocrine thoracic neoplasm, and one patient died. Another patient died due to cutaneous T-cell lymphoma. A further patient died because of a gastrinoma with liver metastasis. CONCLUSIONS: To conclude, 75% of MEN-related deaths were the result of an uncommon pathology, and we, therefore, recommend that these tumors should be taken into account in the screening and follow-up of these patients.

Aggressive surgical approach in patients with adrenal-only metastases from hepatocellular carcinoma enables higher survival rates than standard systemic therapy.

BACKGROUND: Although guidelines recommend systemic therapy even in patients with limited extrahepatic metastases from hepatocellular carcinoma (HCC), a few recent studies suggested a potential benefit for resection of extrahepatic metastases. However, the benefit of adrenal resection (AR) for adrenal-only metastases (AOM) from HCC was not proved yet. This is the first study to compare long-term outcomes of AR to those of sorafenib in patients with AOM from HCC. METHODS: The patients with adrenal metastases (AM) from HCC were identified from the electronic records of the institution between January 2002 and December 2018. Those who presented AM and other sites of extrahepatic disease were excluded. Furthermore, the patients with AOM who received other therapies than AR or sorafenib were excluded. RESULTS: A total of 34 patients with AM from HCC were treated. Out of these, 22 patients had AOM, 6 receiving other treatment than AR or sorafenib. Eventually, 8 patients with AOM underwent AR (AR group), while 8 patients were treated with sorafenib (SOR group). The baseline characteristics of the two groups were not significantly different in terms of age, sex, number and size of the primary tumor, timing of AM diagnosis, Child-Pugh and ECOG status. After a median follow-up of 15.5 months, in the AR group, the 1-, 3-, and 5-year overall survival rates (85.7%, 42.9%, and 0%, respectively) were significantly higher than those achieved in the SOR group (62.5%, 0% and 0% at 1-, 3- and 5-year, respectively) (P = 0.009). The median progression-free survival after AR (14 months) was significantly longer than that after sorafenib therapy (6 months, P = 0.002). CONCLUSIONS: In patients with AOM from HCC, AR was associated with significantly higher overall and progression-free survival rates than systemic therapy with sorafenib. These results could represent a starting-point for future phase II/III clinical trials.

Adrenalectomy for Secondary Malignancy: Patients, Outcomes, and Indications.

OBJECTIVE: The goal of this study was to examine a multi-institutional experience with adrenal metastases to describe survival outcomes and identify subpopulations who benefit from adrenal metastasectomy. BACKGROUND: Adrenalectomy for metastatic disease is well-described, although indications and outcomes are incompletely defined. METHODS: A retrospective cohort study was performed of patients undergoing adrenalectomy for secondary malignancy (2002-2015) at 6 institutions. The primary outcomes were disease free survival (DFS) and overall survival (OS). Analysis methods included Kaplan-Meier and Cox proportional hazards. RESULTS: Of 269 patients, mean age was 60.1 years; 50% were male. The most common primary malignancies were lung (n = 125, 47%), renal cell (n = 38, 14%), melanoma (n = 33, 12%), sarcoma (n = 18, 7%), and colorectal (n = 12, 5%). The median time to detection of adrenal metastasis after initial diagnosis of the primary tumor was 17 months (interquartile range: 6-41). Post-adrenalectomy, the median DFS was 18 months (1-year DFS: 54%, 5-year DFS: 31%). On multivariable analysis, lung primary was associated with longer DFS [hazard ratio (HR): 0.49, P = 0.008). Extra-adrenal oligometastatic disease at initial presentation (HR: 1.84, P = 0.016), larger tumor size (HR: 1.07, P = 0.013), chemotherapy as treatment of the primary tumor (HR: 2.07 P = 0.027) and adjuvant chemotherapy (HR: 1.95, P = 0.009) were associated with shorter DFS. Median OS was 53 months (1-year OS: 83%, 5-year OS: 43%). On multivariable analysis, extra-adrenal oligometastatic disease at adrenalectomy (HR: 1.74, P = 0.031), and incomplete resection of adrenal metastasis (R1 margins; HR: 1.62, P = 0.034; R2 margins; HR: 5.45, P = 0.002) were associated with shorter OS. CONCLUSIONS: Durable survival is observed in patients undergoing adrenal metastasectomy and should be considered for subjects with isolated adrenal metastases.

Pregnancy and phaeochromocytoma/paraganglioma: clinical clues affecting diagnosis and outcome - a systematic review.

BACKGROUND: Phaeochromocytoma and paraganglioma (PPGL) in pregnancy, if not diagnosed antepartum, pose a high risk for mother and child. OBJECTIVE: To examine the clinical clues of antepartum and postpartum/postmortem diagnosis of PPGL. SEARCH STRATEGY: Case reports on PPGL in pregnancy published between 1 January 1988 and 30 June 2019 in English, German, Dutch or French. SELECTION CRITERIA: Case reports containing a predefined minimum of clinical data on PPGL and pregnancy. DATA COLLECTION AND ANALYSIS: Two authors independently performed data extraction and assessed data quality. We calculated odds ratios (OR) (with 95% confidence intervals) and used uni- and multivariable logistic regression analysis. MAIN RESULTS: Maternal and fetal/neonatal mortalities were 9.0% (18/200) and 14.2% (29/204), respectively. Maternal mortality was 42-fold higher with PPGL diagnosed postpartum/postmortem (17/58; 29.3%) than antepartum (1/142; 0.7%) (adjusted OR 45.9, 95% CI 5.67-370, P = 0.0003). Offspring mortality was 2.6-fold higher with PPGL diagnosed postpartum/postmortem than antepartum (OR 3.1, 95% CI 1.38-6.91, P = 0.0044). Hypertension at admission (OR 2.29, 95% CI 1.12-4.68, P = 0.022), sweating (OR 3.14, 95% CI 1.29-7.63, P = 0.014) and a history of PPGL, a known PPGL-associated gene mutation or adrenal mass (OR 8.87, 95% CI 1.89-41.64, P = 0.0056) were independent factors of antepartum diagnosis. Acute onset of symptoms (OR 8.49, 95% CI 3.52-20.5, P < 0.0001), initial diagnosis of pre-eclampsia (OR 6.34, 95% CI 2.60-15.5, P < 0.0001), admission for obstetric care (OR 10.71, 95% CI 2.70-42.45, P = 0.0007) and maternal tachycardia (OR 2.72, 95% CI 1.26-5.85, P = 0.011) were independent factors of postpartum diagnosis. CONCLUSION: Several clinical clues can assist clinicians in considering an antenatal diagnosis of PPGL in pregnancy, thus potentially improving outcome. TWEETABLE ABSTRACT: Systematic review of 204 pregnant patients with phaeochromocytoma identified clinical clues for a timely antepartum diagnosis.

Evaluating the efficacy and safety of ultrasound-guided percutaneous microwave ablation for the treatment of adrenal metastasis.

CONTEXT: Microwave ablation (MWA) has been proven as a promising method to treat solid tumors. AIMS: This study aims to evaluate the efficacy and safety of ultrasound (US)-guided MWA for treating adrenal metastasis and to explore the factors affecting survival. SETTINGS AND DESIGN: This was a retrospective study performed on patients treated at our department. SUBJECTS AND METHODS: A total of 43 patients with adrenal metastasis (22 hepatocellular carcinoma, eight renal cell carcinoma, five non-small cell lung cancer, four colorectal cancer, three liposarcoma, and one malignant fibrous histiocytoma) were enrolled. All patients were treated at our department at least once. The treatment protocol for each patient, the technique used, and the survival details were recorded. STATISTICAL ANALYSIS USED: Statistical analyses were performed using SPSS 26.0 software. RESULTS: Technical success was achieved in all cases. MWA was a safe technique for treating all types of metastasis. No major complications were observed. The pathology of adrenal lesions was the significant risk factor contributing to overall survival (OS) (P = 0.040). The 1-year and 3-year OS rates for all patients were 0.828 and 0.389, respectively. CONCLUSIONS: Percutaneous US-guided MWA is safe and effective in terms of local control and survival of adrenal metastasis.

Predicting Metastatic Potential in Pheochromocytoma and Paraganglioma: A Comparison of PASS and GAPP Scoring Systems.

PURPOSE: The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) are scoring systems to predict metastatic potential in pheochromocytomas (PCC) and paragangliomas (PGLs). The goal of this study is to assess PASS and GAPP as metastatic predictors and to correlate with survival outcomes. METHODS: The cohort included PCC/PGL with ≥5 years of follow-up or known metastases. Surgical pathology slides were rereviewed. PASS and GAPP scores were assigned. Univariable and multivariable logistic regression, Kaplan-Meier survival analysis, and Cox proportional hazards were performed to assess recurrence-free survival (RFS) and disease-specific survival (DSS). RESULTS: From 143 subjects, 106 tumors were PCC and 37 were PGL. Metastases developed in 24%. The median PASS score was 6.5 (interquartile range [IQR]: 4.0-8.0) and median GAPP score was 3.0 (IQR: 2.0-4.0). Interrater reliability was low-moderate for PASS (intraclass correlation coefficient [ICC]: 0.6082) and good for GAPP (ICC 0.7921). Older age (OR: 0.969, P = .0170) was associated with longer RFS. SDHB germline pathogenic variant (OR: 8.205, P = .0049), extra-adrenal tumor (OR: 6.357, P < .0001), Ki-67 index 1% to 3% (OR: 4.810, P = .0477), and higher GAPP score (OR: 1.537, P = .0047) were associated with shorter RFS. PASS score was not associated with RFS (P = .1779). On Cox regression, a GAPP score in the moderately differentiated range was significantly associated with disease recurrence (HR: 3.367, P = .0184) compared with well-differentiated score. CONCLUSION: Higher GAPP scores were associated with aggressive PCC/PGL. PASS score was not associated with metastases and demonstrated significant interobserver variability. Scoring systems for predicting metastatic PCC/PGL may be improved by incorporation of histopathology, clinical data, and germline and somatic tumor markers.

Stereotactic body radiotherapy for adrenal oligometastasis in lung cancer patients.

OBJECTIVE: To report our experience on stereotactic body radiotherapy (SBRT) in adrenal metastases from lung cancer. METHODS: 37 oligometastatic lung cancer patients with 38 adrenal metastases submitted to SBRT were retrospectively analyzed. SBRT was delivered by volumetric modulated arc therapy (VMAT) or helical tomotherapy (HT). Primary study end point was local recurrence-free survival (LR-FS) and secondary end points were distant-progression free survival (d-PFS) and overall survival (OS). RESULTS: Median age was 67 years and primary tumor was non-small-cell lung cancer in 27 (73%) and small-cell lung cancer in 10 (27%) patients. Adrenal metastases were in the left side in 66% cases. Median prescribed dose was 30 Gy in 5 fractions for a median biologically equivalent dose (α/ß ratio 10 Gy, BED10) of 48 Gy. Most patients (62%) were submitted to SBRT alone, while the others (38%) received chemo-, immune- or target- therapies. Median follow-up was 10.5 months, median OS 16 months and median d-PFS 3 months. 27 (70%) patients obtained a local control with a median LR-FS of 32 months. LR-FS was significantly related to BED10 with a better LC with BED10 ≥72 Gy, 1- and 2 year LR-FS rates were 54.1±11.6% and 45±12.7% vs 100 and 100% for BED ≤59.5 Gy and BED ≥72 Gy, respectively (p = 0.05). There was no severe toxicity. CONCLUSION: SBRT was effective and safe in lung cancer adrenal metastases. A dose-response relationship was found between BED10 >72 Gy and better local control. No significant toxicity was registered thanks to the respect of dose constraints and suspension of chemo- and target-therapies. ADVANCES IN KNOWLEDGE: SBRT with a BED10 >72 Gy is an effective treatment for adrenal oligometastatic lung cancer patients.