Clinical and prognostic pan-cancer analysis of m6A RNA methylation regulators in four types of endocrine system tumors.

N6-methyladenosine (m6A), internal modification of mRNA, has recently been reported to be an important regulatory mechanism affecting tumor proliferation. However, its role in endocrine system tumors is poorly understood. We obtained datasets for four types tumors from the TCGA database, analyzed the GTEx database as a supplement to the control group, and used "Perl" and "R" software to analyze the datasets. Then we differentiated the expression level, used it to cluster consensus. Besides, we established lasso regression model to screen variables, used univariate and multivariate cox analyses to explore the independent risk factors associated with cancer prognosis. The results indicated that except for WTAP, the expression level of METTL3 was negatively correlated with other genes. The expression level of WTAP and METTL16 was positively correlated with overall survival (OS). Moreover, we found that different clinical subtypes of adrenal cortical carcinoma had significant differences in survival status, histologic grading, pathological T grade, and OS. Furthermore, different clinical subtypes of thyroid carcinoma had significant differences in histologic grading and pathological T grade. The differential expression of m6A regulatory genes is closely associated with the presence of endocrine-system-related tumors, and risk scores can be used to assess prognosis.

Epidemiological study of paediatric germ cell tumours revealed the incidence and distribution that was expected, but a low mortality rate.

AIM: Germ cell tumours (GCTs) are a rare heterogeneous tumour group derived from primordial germ cells, which can be benign or malignant and occur in the gonads or extragonadally. This study mapped the paediatric GCTs in Denmark from 1984 to 2013 to study the incidence and outcome. METHODS: We identified paediatric GCTs from the Danish Childhood Cancer and National Pathology Registries and reviewed the case records for patient characteristics, tumour characteristics and clinical outcome. RESULTS: We identified 403 (71% female) paediatric GCTs and the crude incidence was 1.43 per 100 000. Of these, 79 (20%) were malignant, 39 (10%) were potentially malignant and 285 (70%) were benign. Extragonadal GCTs (39%) were mainly observed in early childhood and were predominately sacrococcygeal teratomas. Gonadal GCTs (61%) in late childhood were most frequently mature teratomas in the ovaries. Nearly all patients underwent surgery. Of the malignant tumours, 62% were treated with chemotherapy. Radiotherapy was only administered to intracranial GCTs. In the cohort, 12 patients died (3%). CONCLUSION: Paediatric GCTs in Denmark were mainly benign and mortality was low, even for malignant tumours. We identified a peak of extragonadal GCTs in early childhood and a peak of gonadal GCTs in late childhood, which was comparable to previous reports.

Complete metastasectomy for renal cell carcinoma: Comparison of five solid organ sites.

BACKGROUND AND OBJECTIVES: Patients with metastatic RCC can undergo metastasectomy to improve survival time. Our goal was to provide and compare characteristics and oncological outcomes of RCC patients who underwent complete metastasectomy at a single organ site. METHODS: A total of 138 RCC patients were identified as undergoing complete metastasectomy at a single organ site including adrenal, lung, liver, pancreas, or thyroid. Competing risk regression analysis was used to assess RFS and CSS adjusting for several covariates. RESULTS: In this highly selected cohort, RFS and CSS was 27% and 84% at 5 years following metastasectomy, respectively. Univariate analysis revealed that removal of multiple tumors, younger age, and a shorter interval between nephrectomy and metastasis was associated with worse RFS. Larger tumors and sarcomatoid histology at nephrectomy was associated with worse CSS. We found no evidence that metastases at the time of RCC diagnosis influenced recurrence or survival. Tumor size, number of metastases resected, and time from nephrectomy to first recurrence was significantly different, but recurrence rates were not found to be significantly different, when compared across all organ sites. CONCLUSIONS: These findings inform clinical and surgical management of select RCC patients with isolated metastasis to one of several organ sites. J. Surg. Oncol. 2016;114:375-379. © 2016 Wiley Periodicals, Inc.

Outcomes in endocrine cancer surgery are affected by racial, economic, and healthcare system demographics.

OBJECTIVES/HYPOTHESIS: Surgeon experience has been recognized in several clinical fields as a significant element of superior management outcomes. In this study, we seek to assess the association between surgeon volume and patients' community health status with the outcomes of thyroid and parathyroid surgery indicated for primary malignancies. STUDY DESIGN: A cross-sectional study utilizing the State Inpatient Databases, 2010-2011, for Florida, New York, and Washington was merged with the County Health Rankings database. METHODS: International Classification of Diseases, Ninth Revision codes were used to identify adult (≥18 years) patients who underwent thyroidectomy or parathyroidectomy indicated for primary malignancies. RESULTS: A total of 6,347 records were included. Compared to high-volume surgeons, patients treated by low-volume surgeons were more likely to develop postoperative complications in the 1-month period after the operation (odds ratio: 4.34, 95% confidence interval: 3.31-5.70, P < .001). Furthermore, both low- and intermediate-volume surgeons were associated with a longer hospital stay (>2 days) and a higher risk of admission to the intensive care unit (P < .01 each). Cost of health services was significantly in the highest quartile (>$10,254.66) for patients treated by low-volume surgeons (P < .001). Patients who lived in communities of poor health measures had a higher risk of postoperative complications (16.3% vs. 11.8%, P = .030) independent of the clinical presentation and management type. Patients living in high health-risk communities and those of black and Hispanic backgrounds were more likely to be treated by low-volume surgeons (P < .001 each). CONCLUSIONS: The surgeon's volume and the patient's living conditions are crucial and independent factors in multiple aspects of endocrine cancer management. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:775-781, 2016.

Long-term outcome of primary endocrine non-Hodgkin lymphomas: does the site make the difference?

AIM: Primary lymphomas of endocrine glands are extremely rare. Our study adds more data to the few published series regarding the incidence, clinical characteristics, management and overall survival (OS) by comparing the various diffuse large B-cell endocrine lymphomas. Moreover, it contributes to a better understanding of these neoplasms and provides concepts for future research. METHODS: We retrospectively evaluated the clinical profile and the patterns of outcome among patients who were treated in our center with the diagnosis of aggressive, B-cell, primary endocrine lymphoma. RESULTS: Between May 1980 and December 2011, 450 patients were diagnosed as primary extranodal non-Hodgkin lymphomas. Among them, 18 cases (4%) were primary testicular lymphoma (PTL), 8 cases (2%) were primary thyroid lymphoma (PTHL) and 4 cases (1%) were primary adrenal lymphoma (PAL). The therapeutic approaches employed were variable, including mainly chemotherapy in combination with radiotherapy and surgery. The median OS for the patients with PTL and PAL was 27 and 6 months, respectively. Better outcome was observed in patients with PTHL for whom the median OS has not been reached yet, whereas the PAL group had the worst prognosis. CONCLUSIONS: The discrepancies in the outcome among endocrine lymphomas could be partly attributed to their biologic variability, which might be determined by the initial site involved. We conclude that treatment decisions should be made according to a multi-disciplinary approach to avoid unnecessary surgery. Existing treatment strategies for PTL and PAL fail to provide long-term survival, rendering the application of novel therapeutic approaches essential.

Carcinoma of endocrine organs: results of the RARECARE project.

The rarity or the asymptomatic character of endocrine tumours results in a lack of epidemiological studies on their incidence and survival patterns. The aim of this study was to describe the incidence, prevalence and survival of endocrine tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002, registered in 89 population-based cancer registries (CRs) with follow-up until 31st December 2003. These data give an unique overview of the burden of endocrine carcinomas in Europe. A list of tumour entities based on the third International Classification of Diseases for Oncology was provided by the project Surveillance of rare cancer in Europe (RARECARE) project. Over 33,594 cases of endocrine carcinomas were analysed in this study. Incidence rates increased with age and were highest in patients 65 years of age or older. In 2003, more than 315,000 persons in the EU (27 countries) were alive with a past diagnosis of a carcinoma of endocrine organs. The incidence of pituitary carcinoma equalled four per 1,000,000 person years and showed the strongest decline in survival with increasing age. Thyroid cancer showed the highest crude incidence rates (four per 100,000 person years) and was the only entity with a gender difference: (female-to-male ratio: 2:9). Parathyroid carcinoma was the rarest endocrine entity with two new cases per 10,000,000 person years. For adrenal carcinoma, the most remarkable observations were a higher survival for women compared to men (40% compared to 32%, respectively) and a particularly low relative survival of 24% in patients 65 years of age or older. More high quality studies on rare cancers, with additional information, e.g. on stage and therapeutic approach, are needed and may be of help in partly explaining the observed variation in survival.

Hyperthermic pelvic perfusion with tumor necrosis factor-α for locally advanced cancers: encouraging results of a phase II study.

PURPOSE: To assess the efficacy of isolated pelvic perfusion (IPP) with tumor necrosis factor (TNF)-α and melphalan in patients with locally advanced cancers in the pelvic and groin area requiring mutilating surgery. METHODS: A total of 27 patients were enrolled (carcinoma, n = 17; sarcoma/melanoma, n = 4; and endocrine tumor, n = 6). They were candidates for exarticulation (n = 3) or exenteration (n = 11) or were judged unresectable (n = 13). In installing IPP, tourniquets were positioned around both thighs, and an inflated pressure suit was placed at a subthoracic position. Tumor necrosis factor-α (300 µg) was injected in the perfusate, followed 5 minutes later by melphalan at 1.5 mg/kg. After 30 minutes, the remaining drugs were washed out. Leakage was assessed with technetium Tc 99m radiolabeled human serum albumin, and a pharmacokinetic study was performed. Efficacy was based on the complete response rate observed on magnetic resonance imaging. RESULTS: Pelvic/systemic ratios of melphalan/TNF/technetium Tc 99m were 14.2/7/3.6. Responses on magnetic resonance imaging were as follows: 30% complete, 30% partial, 19% no change, and 15% progression. Two patients were not evaluable because they did not receive the treatment. Pre-IPP/post-IPP median percentage of necrosis on magnetic resonance imaging was 10%/70%. Median follow-up was 43 months. Median overall survival was 17 months. Twelve-month survival rate, disease-free survival, and local and metastatic recurrence rates were 67%, 30%, 57%, and 26%, respectively. CONCLUSIONS: Isolated pelvic perfusion with TNF-α compares favorably with historical data, as it was observed in limb perfusion and could provide a chance to translate its successful combination with chemotherapy into treatment of locally advanced pelvic cancers.

Pancreatic neoplasms in childhood and adolescence.

Pancreatic neoplasms are rare in children and adolescents; thus, our understanding of these tumors is still quite limited. We retrospectively reviewed clinical features and outcomes of all patients below 18 years of age with pancreatic neoplasms who were treated at Asan Medical Center between December 1994 and March 2010. Thirty-two patients were identified. Abdominal pain was the most common symptom. The median duration of diagnostic delay was 21 days. Nineteen patients were diagnosed with solid pseudopapillary tumors, 3 with lymphomas, 2 with pancreatoblastomas, 2 with poorly differentiated carcinomas, 2 with acinar cell cancers, 2 with endocrine tumors, 1 with peripheral (primitive) neuroectodermal tumor, and 1 with hemangioendothelioma. Gross complete resection of the primary tumor was achieved in 24 patients (75%), and 8 patients (25%) received chemotherapy. At a median follow-up of 34 months, the 5-year overall survival rate was 92.0 ± 5.5%. On multivariate analysis, histologic type was the only factor significantly predictive of survival (P=0.009). Patients with poorly differentiated carcinoma showed the worst survival probability. In cases of solid pseudopapillary tumors, surgical resection was generally curative and the prognosis was excellent. Patients with other malignant tumors, however, may require therapeutic strategies other than surgery.

The role of surgery for pancreatic cancer: a 12-year review of patient outcome.

INTRODUCTION: Pancreatic cancer has a poor prognosis with <5% alive at 5 years, despite active surgical treatment. The study aim was to review patients undergoing pancreatic resection and assess the effect of clinical and pathological parameters on survival. PATIENTS AND METHODS: All patients who had undergone radical pancreatic surgery, January 1996 to December 2008, were identified from the unit database. Additional information was retrieved from the patient records. The demographic, clinical, and pathological records were recorded using Microsoft Excel. Survival was assessed using Kaplan-Meier and predictors of survival determined by multinominal logistic regression and log rank test. RESULTS: 126 patients were identified from the database. The majority (106) had a Whipple's procedure, 14 had a distal pancreatectomy and 6 had local periampullary excision. The average age of the Whipple's group of patients was 61.7 years (± 11.7) with most procedures performed for malignancy (n=100). Survival was worse with adenocarcinoma compared to all other pathologies (p=0.013), while periampullary tumours had a better prognosis compared to other locations (p=0.019). Survival decreased with poorer differentiation (p=0.001), increasing pT (p<0.001) and pN stage (p<0.001). Survival was worse with perineural (p=0.04) or lymphovascular invasion (p=0.05). A microscopic postive resection margin (R1) was associated with a worse survival (p=0.007). Tumour differentiation (p=0.001) and positive nodal status (p<0.001) were found to be independent predictors of mortality. CONCLUSION: Tumour differentiation and nodal status are important predictors of outcome. A positive resection margin is associated with a poorer survival.

European disparities in malignant digestive endocrine tumours survival.

The aim of this study was to report on malignant digestive endocrine tumours (MDET) prognosis in several European countries. We analysed survival data from 19 cancer registries in 12 European countries on 3,715 MDET diagnosed between 1985 and 1994. The overall 5-year survival rate was 47.5%. It was 58.1% for differentiated MDET and 8.1% for small-cell MDET (p < 0.001), 55.9% for patients under 65 and 37.0% for older patients. Survival rates for small intestinal and colorectal were higher than for the other sites. The 5-year relative survival rates were 60.3% in Northern Europe, 53.6% in Western Continental Europe, 42.5% in the UK, 37.6% in Eastern Europe (p < 0.001). Among well-differentiated pancreatic tumours, 5-year relative survival was 55.6% for insulinoma, 48.4% for gastrinoma, 33.4% for glucagonoma, 28.8% for carcinoid tumours and 49.9% for non-functioning tumours. The relative excess risk of death was significantly lower in Western Continental Europe and Northern Europe and significantly higher in Easter European compared to the UK. MDET differentiation, site, geographic area, age and sex, were independent prognostic factors. Overall, in Europe approximately half of the patients with MDET survive 5 years after the initial diagnosis. Prognosis varies with tumour differentiation, anatomic site and histological type. There are significant differences in survival from MDET among European countries, independently of other prognostic factors.

Long-term outcome of chemotherapy for advanced testicular and extragonadal germ cell tumors: a single-center 27-year experience.

OBJECTIVE: We retrospectively assessed long-term outcomes of chemotherapy for advanced germ cell tumors (GCTs) at our institution. METHODS: Ninety-five consecutive males with advanced GCTs of the testis or extragonadal origin who received chemotherapy between 1980 and 2006 were enrolled. All patients underwent induction chemotherapy including cisplatin. RESULTS: The median follow-up period was 36.1 months (0 - 288.5) for all patients and 52.6 months (2.2 - 288.5) for the 73 current survivors. Totally, 75 patients (78.9%) achieved complete remission (CR). CR was achieved in 61.1%, 37.9% and 75.0% of the patients after induction therapy, second-line therapy and third-line or more, respectively. As salvage therapy, high-dose chemotherapy was performed in 11 patients (11.7%) and regimens with novel anticancer agents such as paclitaxel and irinotecan were employed for 8 patients (8.5%) from 2003 and later. The era of the treatment, extrapulmonary metastasis and serum alpha-fetoprotein were independent prognostic factors for patients. The 5-year overall survival of patients after 1992 was 83.0%, which was significantly higher than that of those before 1992 (56.3%). CR was never achieved in 20 patients and most of them met the criteria of the poor-prognosis group. Disease recurrence after CR was found in nine patients who were initially classified into the good- or intermediate-prognosis group. CONCLUSIONS: Improvement of medical management during chemotherapy and the development of several regimens for salvage chemotherapy seemed to contribute to improving outcomes of patients with advanced testicular cancer. Newly established chemotherapy regimens are needed for improvement of survival of patients in the poor-prognosis group.

Prognostic factor of recurrence for resected digestive endocrine tumors.

BACKGROUND/AIMS: The aim of the present study was to identify the factors of recurrence for digestive endocrine tumours resected with curative intent. METHODOLOGY: 170 endocrine digestive tumours were reviewed from January 1997 to January 1997, Twenty eight patients were selected in this study. Localization of tumours were as follows: 14 duodenopancreatic (DP) and 14 Digestive (DT: 9 small bowel and 4 appendix). The following factors were investigated: primary site, hormonal clinical symptom, and differentiation. RESULTS: Twenty eight patients (12 men) were selected. Median age was 48 (range, 23-79) yrs. All resection of metastasis were performed during the same procedure of primary tumour resection. There were 14 DT and 14 non functional DP tumours. For 28 patients, the only factor of recurrence was endocrine pancreatic tumour (p = 0.02). For non functional DP, the rate of recurrence was significantly dependent on histology and the expression of ki67 antigen and presence of metastasis. Survival free of disease for DT were: 100%,80% at 1, 5 yrs, and for DP they were 93%, 50%, 33% at 1, 3, 5 yrs, respectively. CONCLUSION: The expression of the Ki67 antigen and differentiation seem to be good indicators for DP recurrence and may need an adjuvant treatment despite the R0 resection.

Temozolomide: a safe and effective treatment for malignant digestive endocrine tumors.

BACKGROUND: Systemic chemotherapies are associated with limited response rates and significant toxicity in patients with malignant digestive endocrine tumors (DET). Preliminary studies have reported interesting results with temozolomide in patients with DET. AIM: It was the aim of this study to assess the efficacy and safety of temozolomide in patients with malignant DET. PATIENTS AND METHODS: Twenty-one patients, median age 61 years (range 56-77), with metastatic well-differentiated DET were retrospectively studied. All patients except 1 had received prior treatment (hepatic resection, chemotherapy). All patients had progressive disease in the 3 months prior to entry into the study. Temozolomide was administered at doses of 200 mg/m(2) daily for 5 days, every 28 days. Treatment was assessed for safety, progression-free and overall survival. RESULTS: The median number of temozolomide cycles was 5 (range 2-15). Grade 3 hematological toxicity occurred in 5 patients. There were no toxic deaths. According to the Response Evaluation Criteria in Solid Tumors criteria, partial response and stabilization were obtained in 1 (5%) and 17 patients (81%), respectively. The median time to progression was 9 months (range 3-26). The 1-year progression-free survival and overall survival were 42 and 77%, respectively. CONCLUSION: Temozolomide is a well-tolerated oral chemotherapy in patients with malignant DET, including those who have already received treatment. In patients with progressive disease, temozolomide controls tumor progression in 86% of cases.

Predictive value of 18F-FDG PET and somatostatin receptor scintigraphy in patients with metastatic endocrine tumors.

UNLABELLED: The treatment of metastatic neuroendocrine tumors depends on the aggressiveness of the disease. We wanted to know whether (18)F-FDG PET and somatostatin receptor scintigraphy (SRS) can predict early disease progression and patient survival. METHODS: We undertook a prospective study of patients with metastatic neuroendocrine tumor diagnosed between September 2003 and January 2006. After obtaining signed informed consent from the patients, we performed CT, SRS, and (18)F-FDG PET and reviewed histologic data. CT was repeated every 3 mo to assess the risk of early progressive disease (first 6 mo), progression-free survival, and overall survival. RESULTS: Thirty-eight patients (mean age, 60 +/- 15 y) were included. Histologically, 4 patients had a high-grade and 34 a low-grade tumor. The results of (18)F-FDG PET and SRS were positive in 15 and 27 patients. The 2-y overall survival and progression-free survival were 73% and 45%; 16 patients had early progressive disease. Most (18)F-FDG PET-positive patients had early progressive disease (14/15, vs. 2/23 (18)F-FDG PET-negative patients), and most SRS-negative patients had early progressive disease (9/11, vs. 7/27 SRS-positive patients); (18)F-FDG PET gave excellent negative and positive predictive values of 91% and 93%; (18)F-FDG PET results correlated with progression-free survival (P < 0.001) and overall survival (P < 0.001) even when only low-grade tumors were considered. SRS was associated with progression-free survival (P < 0.001) and overall survival (P < 0.03). At multivariate analysis, only (18)F-FDG PET was predictive of progression-free survival. CONCLUSION: (18)F-FDG PET exhibits excellent predictive values for early tumor progression. (18)F-FDG PET and SRS results correlate with progression-free survival and overall survival even for histologically low-grade tumors. These explorations could be included in the initial work-up for metastatic neuroendocrine tumor.

The outcomes after surgical resection in pancreatic endocrine tumors: an institutional experience.

AIM: Sporadic pancreatic endocrine tumors (PET) can be managed surgically with excellent outcomes. The aim of this study was to analyze surgical outcomes and factors influencing survival. METHODS: Between 1995 and 2007, 96 patients with sporadic PET who underwent surgery at our institution were retrospectively reviewed for clinicopathologic variables and outcomes according to the World Health Organization (WHO) classifications. RESULTS: Thirty-nine patients had well-differentiated tumors (WDT) with benign behavior, 23 had uncertain behavior, 27 had low-grade carcinoma, and 7 were diagnosed with high-grade carcinoma. R0 resection was performed in 84 patients. No recurrence was observed in WDT regardless of its behavior or curability but 16 of 34 patients with carcinoma had recurrence. Five-year overall survival (OS) for R0-resected patients with carcinoma was 57%, and OS at 3 years for R1/R2-resected patients was 23% (P = 0.012). The WHO classification and R0 resection were independent prognostic factors in multivariate analysis. CONCLUSIONS: This single institutional experience demonstrated that surgical resection is curative for WDT and recurrences are frequent in spite of curative resection for malignant PET. The WHO classification and R0 resection remained independent prognostic factor.

Somatostatin receptor subtypes 2 and 5 are associated with better survival in well-differentiated endocrine carcinomas.

The majority of gastroenteropancreatic well-differentiated endocrine carcinomas (WDEC) express somatostatin receptors (SSTR). To correlate the expression of SSTR subtypes by reverse transcriptase-polymerase chain reaction (RT-PCR) with clinicopathological features and survival in a group of WDEC patients, 42 WDEC tissue specimens from 33 patients were analysed. All patients were treated with somatostatin analogues and had a median follow-up period of 45 months (range 6-196). Neither SSTR2 and SSTR5 expression nor Ki-67 level alone correlated with survival. A significantly better survival rate was observed in patients with tumours expressing SSTR2, SSTR5 and Ki-67 <2%, compared to those with SSTR2- and SSTR5-negative tumours and Ki-67 >or=2% (p < 0.038), with 5-year survival rates of 91 vs. 43%, respectively. Expression of SSTR2 and SSTR5 appears to play a positive prognostic role, possibly correlated with the high affinity that the available somatostatin analogues display for these 2 specific SSTR subtypes.

Survival and prognostic factor analysis in patients with metastatic pancreatic endocrine carcinomas.

OBJECTIVES: Pancreatic endocrine carcinomas (PECAs) are uncommon, with an incidence of 1 per 100,000. Past studies of chemotherapy and hepatic arterial embolization have described median survival durations of approximately 2 to 3 years. Overall survival from time of diagnosis of metastases has never been reported in a large cohort of patients. Our objective was to evaluate the stage-specific prognosis of patients with metastatic PECAs and to assess the impact of clinical and pathologic prognostic factors. METHODS: We evaluated all cases of differentiated, metastatic PECAs seen at the H. Lee Moffitt Cancer Center between the years 1999 and 2003, measuring survival from time of diagnosis of metastases. RESULTS: Ninety cases of metastatic PECAs were identified. Median overall survival was 70 months, and the 5-year survival rate was 56%. Age, sex, and tumor type (functional vs nonfunctional) did not impact prognosis. Tumor grade, however, was highly prognostic for survival. CONCLUSIONS: Median overall survival is 70 months (5.8 years) among patients with metastatic PECAs. This prolonged survival duration may reflect the impact of multimodality treatments. Tumor grade (low vs intermediate grade) represents a highly significant prognostic factor.

Is adjuvant therapy with streptozotocin and 5-fluorouracil useful after resection of liver metastases from digestive endocrine tumors?

BACKGROUND: In patients with digestive endocrine tumors (DET) and liver metastases (LM) surgical resection is the only curative treatment. However, 5-year recurrence occurs in 50-80% of patients in the literature. The effect of adjuvant chemotherapy (CT) on relapse-free survival (RFS) and overall survival (OS) is unknown. AIM: To assess the safety and the efficacy of systemic adjuvant CT with streptozotocin and 5-fluorouracil (5-FU) following LM resection in patients with DET. PATIENTS AND METHODS: Between 1996 and 2006, 52 consecutive patients (23 males, median age 54 years [21-69]) underwent surgery for LM of well-differentiated DET in our center. The primary tumor was resected. After R0 resection of LM, patients were considered for adjuvant CT if the primary tumor was pancreatic, if LM was >or=10, or if the patient was <50 years old, in patients with other primary tumors. Twenty-nine patients received adjuvant CT and 23 were in the observation group. Adjuvant CT included 4 postoperative courses of i.v. streptozotocin-5-FU (500 and 400 mg/m(2), respectively, daily for 5 days every 42 days). RFS, OS and toxicity were evaluated. Log rank and chi-square analysis were used to identify prognostic factors. RESULTS: Median post-operative follow-up was 47 months (4-162). In the adjuvant CT group, all patients except one received the 4 cycles. Two patients had grade 3-4 toxicity, including 1 febrile neutropenia resulting in death. Recurrence occurred in 43% and 65% of patients in the observation and adjuvant CT groups, respectively. RFS at 3 and 5 years was 51% and 38% in the observation group and 40% and 20% in the adjuvant CT group, respectively (P = .36). In univariate analysis, the significant prognostic factors associated with RFS were the number of LM (>or=10) and synchronous LM. Administration of adjuvant CT was not correlated with RFS. OS at 3 and 5 years was 90% and 76% in the observation group and 96% and 96% in the adjuvant CT group, respectively (P = .58). CONCLUSION: RFS in patients receiving adjuvant CT was similar to that reported in the observation group and in historical cohorts without adjuvant CT. Thus, administration of streptozotocin-5-FU cannot be recommended in this indication.

Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution.

PURPOSE: Unequivocal pathologic markers for the prognosis of pancreatic endocrine tumors are often lacking. Suggestions for prognostic guidance include the WHO classification. Recently, a tumor-node-metastasis (TNM) staging system was proposed. We evaluate this system, as well as assess other potential prognostic factors such as tumor Ki67, size, endocrine syndrome, heredity, body mass index (BMI), and plasma chromogranin A, in a large patient material treated at a single institution. EXPERIMENTAL DESIGN: A total of 324 patients with pancreatic endocrine tumor, consecutively diagnosed and treated at a tertiary referral center, were retrospectively evaluated. Median follow-up was 54 months (range, 1-423 months). Patient and tumor data were extracted from medical records. Univariate and multivariate analyses were done to recognize factors of prognostic value. RESULTS: The median overall survival was 99 months (95% confidence interval, 81-117). Five- and 10-year survival rates were 64% and 44%, respectively. In univariate analysis, TNM stage, radical surgery, WHO classification, nonfunctioning tumor, Ki67 > or = 2%, chromogranin A > or = 3 times the upper normal limit, BMI < 20 kg/m2, sporadic tumor, tumor size, and referral from our primary uptake area had a significant prognostic effect. In multivariate analysis, TNM stage, WHO classification, radical surgery, and Ki67 > or = 2% retained their significance. Having a nonfunctioning tumor was not an independent marker of poor prognosis and neither was heredity. CONCLUSIONS: The recently suggested TNM staging system emerged as a useful clinical tool.

Treatment with combined streptozotocin and liposomal doxorubicin in metastatic endocrine pancreatic tumors.

UNLABELLED: Treatment with combined streptozotocin and liposomal doxorubicin is safe and efficient in patients with endocrine pancreatic tumors (EPTs). No cardiac toxicity was reported. BACKGROUND: The combination of streptozotocin and doxorubicin has been shown to be superior to streptozotocin and fluorouracil in the treatment of metastatic EPTs. However, the risk of cardiac toxicity from anthracyclins hampers the usefulness of the drug combination. Liposomal doxorubicin has a lower frequency of cardiac adverse events compared to doxorubicin. We wanted to assess the efficacy and safety of combined streptozotocin and liposomal doxorubicin in patients with metastatic EPTs. METHODS: Thirty patients with metastatic EPTs were recruited from three medical centers in Norway and Sweden during a time period of 3 years. All patients had histopathologically confirmed diagnoses and bidimensionally measurable lesions. 30 mg/m(2) of liposomal doxorubicin was administered on day 1 of each cycle. During the first course, 1 g of streptozotocin was given on 5 consecutive days. Thereafter, 2 g of streptozotocin was given on day 1 only. Treatment was repeated every 3 weeks. RESULTS: Twelve of 30 patients (40%) achieved an objective radiological response with a median duration of 9 months. Stabilization of disease was achieved in 17 of 30 patients (57%) for a median duration of 11 months. Only one patient had progressive disease as best response. The 2-year progression-free survival was 18% and the 2-year overall survival was 72%. The treatment was well tolerated. None of the patients experienced cardiac toxicity. CONCLUSION: We conclude that combined streptozotocin and liposomal doxorubicin is a safe and efficient treatment for EPTs. The efficacy seems to be comparable to that of combined streptozotocin and doxorubicin, whereas the cardiac toxicity clearly favors using the liposomal drug combination.