bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin-like growth factor (IGF)-II in gastrointestinal stromal tumors (GIST): expression, secretion, and clinical relevance
Authors: Rikhof B. , van Doorn J. , Suurmeijer A. , Rautenberg M. , Jager P. , Gietema J. , Meijer C. , de Jong S. , van der Graaf W. 
Published: March 2020

20504 Background: Non-islet cell tumor induced hypoglycemia (NICTH) has been reported anecdotically in patients with a GIST and is associated with increased plasma levels of ‘big’-IGF-II, a high molecular weight form of IGF-II. The role of IGF-II in GIST is unknown. In non- GIST cancer, it has been suggested to be an autocrine growth factor, mainly acting by its major growth promoting receptors IGF-1 receptor (IGF- 1R) and the isoform A of the insulin receptor (IR). We investigated the clinical and biological relevance of (‘big’-)IGF-II in GIST. Methods: Plasma levels of ‘big’-IGF-II, and their relationship with disease status and NICTH, were determined in 25 consecutive GIST patients treated with imatinib (n=24) or sunitinib (n=1). Plasma samples were collected prior to, 1 week, and median 5 months after start of treatment. The levels of ‘big’-IGF-II were measured by specific radioimmunoassay (RIA). Results were compared with those obtained from healthy subjects and expressed as standard deviation scores (SDS). Paraffin-embedded GISTs (n=69) were analyzed for IGF-II, IGF-1R and IR expression by RNA in situ hybridization and immunohistochemistry (IHC). IGF-II secretion by the GIST882 cell line was analyzed by ELISA and western blotting. Results: Before treatment and/or during follow-up, 4 of 25 patients (16%) showed increased (i.e. SDS >2.0) plasma levels of ‘big’-IGF-II. Three of them developed NICTH. Patients with metastatic disease, high serum LDH, or total tumor size >12 cm had the highest ‘big’-IGF-II levels (for all p<0.05). 87% of GISTs expressed IGF-II mRNA, being excessive in tumors from patients with NICTH. These results were confirmed by IHC. GIST882 cells secreted mainly high molecular weight forms of IGF-II. The various GISTs and GIST882 cells did not express IGF-1R or IR. Conclusions: NICTH seems not to be a rare phenomenon in GIST patients. We showed for the first time that most GISTs express and secrete (‘big’-)IGF-II. Therefore, it is likely that many patients are at risk of developing NICTH, presumably especially in case of high tumor bulk. The exact role of (‘big’-)IGF-II in GIST is still not elucidated, as it does not seem to act as an autocrine growth factor since IGF-IR and IR isoform A are lacking. No significant financial relationships to disclose.
The role of surgery and radiotherapy in treatment of soft tissue sarcomas of the head and neck region: Review of 30 cases
Authors: Tas F. , Fayda M. , Aksu G. , Agaoglu F. Y. , Karadeniz A. , Darendeliler E. , Altun M. , Uygun K. 
Published: March 2020

20507 Background: To evaluate the role of surgery and radiotherapy in the treatment of soft tissue sarcomas of the head and neck region Methods: Thirty adult patients with head and neck soft tissue sarcoma were retrospectively analyzed. The most frequent histopathologic subtypes were chondrosarcomas (27%) and malignant fibrous histiocytoma (20%). The surgical resection was performed in 25 of the 30 patients (83%). Negative surgical margins could be achieved only in 9 of 25 patients (36%). Ten patients had marginal resection (40%) and 6 patients (24%) had gross residual disease after the surgery. All patients in the surgical resection arm received postoperative radiotherapy except two patients. Results: Five-year local control rates for patients with negative surgical margins (n=9), microscopically positives (n=10), gross residual disease (n=6) and inoperable (n=5) cases were 64%, 70%, 20% and 0% respectively. The median disease free survivals were 26.6 months, 17.7 months, 8.4 and 5.5 months. However, there was no significant difference in local control between patients with negative or microscopically positive disease who receive postoperative radiotherapy (71% vs 70%). The higher dose of radiotherapy (= 60Gy) was found to be associated with a longer local control (p=0.048). The local control rates were lower in patients with grade 2–3 tumors as compared with grade 1 tumors (44% vs. 83%). The median overall survival of whole group was 31 months. Median survivals of patients receiving both surgery and radiotherapy with negative and microscopically positive margins were significantly better than patients who were not treated with surgery (34.8 and 36 months vs. 13.3 months). In univariate analysis grade 1–2 vs. 3, had statistically significant 5-year survival difference (64% vs. 14%, p=0.003). The presence of local relapse had clear negative effect on survival (absent vs. present 66% vs. 7%, p=0.0003). Conclusions: Our results and the findings in the literature confirm that the optimal treatment of head and neck soft tissue sarcomas is complete surgical excision. Postoperative adjuvant radiotherapy clearly improves local control however the high locoregional failure rates still indicate the need for improved treatment strategies. No significant financial relationships to disclose.
Analysis of a United States observational registry of gastrointestinal stromal tumor (GIST) patients (pts): reGISTry
Authors: Blanke C. , Pisters P. W. , Trent J. C. , von Mehren M. , Levine E. , Ruxer R. , Earley M. , Hochwald S. N. , McWhorter L. T. , Williams D. ,   reGISTry Investigator Group
Published: March 2020

20508 Background: Most data on treatment of GIST pts were derived from clinical studies, reflecting practice at academic referral centers. The reGISTry, an observational, internet-based database initiated in 2004, was designed to characterize evolving patterns of care for pts with GIST in both community and university practice settings. It also provides site feedback to allow comparison of site management practices to the aggregate reGISTry data. Methods: Physicians may serially enter data on any enrolled pt with confirmed GIST. Pts must give written informed consent. Collected data include pt demographics, clinical characteristics, clinical/economic outcomes and therapy provided for GIST. Analyses are performed every 6 months. Results: As of Oct 2006, there were 353 pts enrolled from 78 centers. 228 pts (65%) were from community-based practices; 184 pts (52%) were male, and 283 pts (80%) were Caucasian, with a median age of 65 years (range 18–92). Median time from diagnosis to enrollment was 1.1 years (range 0–11.7). At diagnosis, 282 pts (80%) had a localized tumor and 71 (20%) presented with metastatic disease. 335 pts (95%) had immunohistochemical KIT testing, and 1% had genotyping. 274 pts had surgery as first-line treatment (78%), including 84% of pts with primary disease and 52% with metastatic cancer. 14 % and 42% of pts with localized and metastatic disease respectively had systemic therapy as initial treatment. Of the 202 pts with follow-up, 170 (82%) retained the same primary decision-maker, usually the medical oncologist and/or surgeon (57%, 56% respectively). 3 patients reported missing days from work or school due to GIST in their first year since diagnosis. Therapeutic efficacy was assessed by tumor size on CT (53%), tumor size and radiodensity on CT (33%), clinical assessment only (14%) and PET (9%). 161 pts (46%) had been treated with imatinib mesylate and 20 pts (6%) sunitinib malate. Conclusions: The reGISTry remains a useful tool for determining evolving patterns in the management of GIST, and it points out important differences in official practice guidelines and community standards. KIT testing is common in the community, but mutational analysis is rare. Assessment by CT is customary, but PET imaging is rarely utilized in clinical practice. [Table: see text]
Phase II prospective study of dose-dense doxorubucin and ifosfamide in high-grade, locally advanced or metastatic soft tissue sarcoma (STS) patients
Authors: Almeida G. F. , Castro G. , Snitcovsky I. , Siqueira S. A. , Oliveira C. R. , Camargo O. P. , Federico M. H. 
Published: March 2020

20509 Background: High grade STS is expected to benefit from dose-dense doxorubicin/ifosfamide (doxo/ifo) sequential chemotherapy. This trial was designed using the two-stage Minimax design, in which 6 responses were needed among the first 19 pts to proceed to the second stage of the trial (a=0.05, β=0.20) to detect a 20% difference in RR as compared to expected 30%. Preliminary results of the first 20 pts are presented. Patients and Methods: Eligible pts had untreated, metastatic or locally advanced, high-grade STS, > 5 cm; age 18- 60 y; ECOG-PS 0–2; normal cardiac, renal and hepatic function; and signed informed consent. Pts were treated with doxo 30 mg/m2/d, D1–3, every 14 d, 3 cycles, followed by ifo 2.5 g/m2/d, D1–5, every 21 d, 3 cycles, with mesna and G-CSF support. Results: 20 pts were enrolled (7 in the neo-adjuvant setting with curative intent, 13 palliative). Median age: 39y (23–60); 5 synovial, 5 leiomyo, 4 sarcoma NOS, 2 MFH, 4 others. Primary site: 11 lower extremity; mean tumor size 13 cm. Median number of cycles was 3 for both drugs. 12 pts completed all planned chemotherapy cycles, and the mean relative dose intensity was 92±15% and 89±16% for doxo and ifo, respectively. Anemia was the most frequent toxicity (18 pts). 75 cycles were administered and grade 3/4 toxicities (CTC NCI 2.0) were observed in 27. G3 neutropenia was observed in 4 pts, none fatal. Thromboembolic events occurred in 4 pts (2 DVT, 2 PE). One pt presented a LVEF drop from 60% to 34% and developed symptomatic cardiac failure. Among 10 evaluable pts who completed chemotherapy, no response (CR or PR) was observed; eight pts had stable and 2 progressive disease. Surgery was performed in 6 pts, 4 of them limb-sparing, without changing the previous surgical plan. None of these pts presented complete pathologic response, with rate of necrosis ranging from 0–60%. At a median follow-up of 6 mo (1–16), 6 pts had died: 4 of disease progression, one sudden death (unknown cause) after 2 wks from the last chemotherapy cycle, and one patient died from pulmonary embolism. Conclusion: Sequential high-dose doxorubicin followed by ifosfamide failed in demonstrating any response in high grade STS, in addition to an unacceptable toxicity profile. Results of overall survival are pending. No significant financial relationships to disclose.
Exhaustive prospective collection of new sarcomas: Report of an unexpectedly high incidence
Authors: Ducimetiere F. , Lurkin A. , Ranchere-Vince D. , Biron P. , Peoch M. , Istier L. , Salameire D. , Chalabreysse P. , Blay J. Y. , Ray-Coquard I. 
Published: March 2020

20513 Background: Sarcomas are rare malignant tumors reported to account for 1% of all adult tumors - respectively 1–3 per 100,000 persons per year for soft tissue sarcomas (STS) and less than 0.5 for bone sarcomas (BS). There are more than 50 histological subtypes of STS, each with its own clinical management. Within the context of an evaluation of medical practices, we decided to assess the medical management of all sarcoma patients seen in one year in the Rhone-Alpes (RA) region which represents 10% of the total French population. One of the secondary objectives was to assess the incidence of sarcomas. About 1,800 STS cases are diagnosed each year in France, hence 200 new sarcomas (STS, BS, visceral) were expected in the region. Methods: A prospective and exhaustive collection of pathology data was launched in direct collaboration with the network of pathologists in the RA region. All patients in primary care, above 15 years old, and diagnosed with sarcoma from March 2005 to Feb 2006 in RA were included. Collection comprehensiveness was checked. Results: In one year, 417 patients met inclusion criteria and were analyzed: 65% STS (n=270), 20% visceral sarcomas (Gastro Intestinal Stromal Tumor (GIST), uterine sarcomas) (n=84), 12% BS (n=49) and 3% undifferentiated malignant tumors (n=14). The most frequent histological subtypes were GIST (17% n=72), liposarcomas (17% n=71), leiomyosarcomas (9% n=38). 27% og sarcomas were not otherwise specified (NOS) (n=74). 5 patients were between 15 and 18 years old at diagnosis. Conclusions: The first year of inclusion showed an incidence of sarcomas twice higher than reported in the literature. French registris classify tumours per organ site, leading to an underestimation of the number of cases. This is partly due to the non-identification of GIST or uterine sarcomas. This study raises the question of a need for a national registry of these rare tumors. Similarly, a histological classification is necessary to obtain accurate and specific incidence rates. Financial support: Merck KGgA, Ligues Ain et Rhône, CONTICANET network. No significant financial relationships to disclose.
Decompression surgery and intraoperative radiation therapy (IORT) for metastatic spinal tumors
Authors: Karasawa K. , Hanyu N. , Chang T. , Kuga G. , Yoshida D. , Kiguchi Y. , Takahashi M. , Hozumi T. , Kondo T. 
Published: March 2020

20515 Background: Metastatic spinal tumors often cause spinal cord compression and jeopardize the quality of life of the patients much. To decrease the local symptomatic recurrence rate, we have been adding IORT to decompression surgery. Methods: For those patients whose life expectancy was more than 6 months were eligible for this treatment. Posterior decompression by laminectomy of the involved vertebrae was performed. Following decompression, the patient was irradiated the lesions intraoperatively with electrons generated from Microtron by shielding the spinal cord with lead plate. The central aspects of the vertebrae were irradiated by scattered electrons detouring from the edge of the lead shield up to 40% of the administered dose. Following IORT, posterior instrumentation was performed. External beam radiotherapy might be added pre- and/or postoperatively when considered necessary. Results: 108 patients were treated between 1992–2005. There were 58 males and 50 females. Age ranged from 26 to 85 with a median of 62.5. By primary sites, 26 breast, 24 kidney, 18 colorectum, 17 lung 12 prostate and 11 thyroid cases were included. Irradiated spines were cervical in 6, thoracic in 76, and lumbar/sacral in 27. Overall median follow-up period was 12.7months. Median IORT dose was 20Gy (range 15–26Gy) and median electron energy was 16MeV (range 11–22MeV). There were 37 cases with preoperative RT and 41 cases with postoperative RT. Overall median survival time was 14.5months (breast 15.3, kidney 22.6, colorectum 5.7, lung 6.2, prostate 31.6, thyroid 60.6months). Neurological response rate was 73.1%. Ambulatory rates were 87.0% for success and 80.6% for rescue by Klimo's definition(2005). There were only 8 symptomatic relapses (7%). As for major complications, only one myelopathy has been observed. Conclusions: Decompression surgery and IORT for metastatic spinal tumors with impending spinal cord compression was a promising treatment modality with excellent local control and neurological response rate and with minimal toxicity especially for those patients with long-term prognosis. No significant financial relationships to disclose.
Geographic variation in soft tissue sarcoma patient follow-up
Authors: Virgo K. S. , Sarkar S. , Beitler A. L. , Gibbs J. F. , Sakata K. , Goel A. , Christy M. E. , Audisio R. A. , Kraybill W. G. , Johnson F. E. 
Published: March 2020

20518 Background: Of all newly diagnosed malignancies, 1% are soft tissue sarcomas (STS) and 59% of STS occur in the extremities. Most patients (80%) suffer recurrence within two years of potentially curative resection. Late recurrences at five years and beyond are not uncommon. Surveillance programs are designed to identify recurrence or new primaries early enough to positively impact survival and quality of life. Though published guidelines exist for extremity STS follow-up, adherence varies among physicians. Geographic factors were hypothesized to be potential predictors of this variation. Methods: The SSO membership (N=1592) was surveyed regarding postoperative STS surveillance using standardized clinical vignettes. Practice patterns were analyzed by metropolitan statistical area (MSA), managed care organization (MCO) penetration rate, and U.S. census region using repeated measures analysis of variance. The study endpoint was surveillance intensity. Results: Forty-five percent of SSO members (714) completed the survey; 343 (48%) performed sarcoma surgery. Of those who perform surgery, 318 (93%) follow their patients long-term. Mean follow-up intensity for the 12 modalities was highly correlated by tumor size, grade, and years after surgery. Controlling for tumor stage, grade, and year after surgery, geographic factors infrequently predicted surgeon self-reported surveillance intensity (p < .05). MSA was a significant predictor of office visit frequency. MCO penetration rate significantly predicted the frequency of urinalysis and site MRI. U.S. census region significantly predicted the frequency of LFTs. Two-way interaction effects were frequently significant. Few three-way interactions were examined due to sample size limitations. Conclusion: Geographic factors were generally not predictive of surgeon self-reported surveillance practice patterns for patients after curative-intent sarcoma surgery. Internship, residency, and fellowship locations may be important surgeon-specific aspects for future surveys. No significant financial relationships to disclose.
18FDG-PET in the management of malignant peritoneal mesothelioma: A retrospective review of 145 scans in 37 patients
Authors: Uldrick T. , Hesdorffer M. , Rasiej M. J. , Austin J. H. , Taub R. N. 
Published: March 2020

20519 Background: Malignant peritoneal mesothelioma is a rare tumor best managed by an interdisciplinary approach. The role of 18FDG-PET scans in monitoring patients with peritoneal mesothelioma has not been defined. Methods: Patients with peritoneal mesothelioma treated at Columbia University (October, 1997 - October, 2006) who had a PET scan were reviewed. Data were gathered on modes of therapy, imaging, and clinical outcome. The frequency with which PET scans led to a change in management, defined as scans that led to a biopsy or initiation of chemotherapy, was evaluated. Results: 37 patients, 21 women (57%) and 16 men (43%), were reviewed. The median age was 50 (range 14 - 79) years. All patients underwent surgery, 35 (95%) intraperitoneal chemotherapy, 15 (41%) external beam radiation, and 17 (46%) intravenous chemotherapy. At 43 (range 8.5 - 127) months median follow-up, 27 (73 %) are alive. Among 145 PET scans, 66 (46%) were PET/CT scans, 52 (26%) were PET scans with a CT scan performed within one month, and 27 (19%) were PET scans only. 8 (6%) of PET scans were for initial staging, and 137 (95%) for monitoring. A change in management based on findings in PET imaging occurred in 11 (30%) patients and 14 (10%) scans. Two patients were started on salvage chemotherapy without further evaluation. Two were diagnosed with peritoneal recurrence, 1 with lung metastasis, 1 with lymph node metastasis, 1 with a second malignancy, and 3 with colon polyps. One had a false positive scan, proven by negative surgical biopsy. PET provided early detection of disease progression in 6 (16%) of patients evaluated. One patient (3%) had biopsy proven progressive disease despite no 18FDG uptake on PET scan. Conclusions: 18FDG-PET findings changed management in 30% of patients with peritoneal mesothelioma undergoing multimodality therapy, and provided early detection of recurrence in 16% of patients. Further evaluation of test characteristics and prognostic value of 18FDG-PET in the setting of peritoneal mesothelioma is warranted. No significant financial relationships to disclose.
Atypical fibroxanthoma
Authors: Stadler R. 
Published: March 2020

20522 We report on 15 patients who were diagnosed and treated with atypical fibroxanthoma in the Department of Dermatology Minden since 1994. The patients were between 35 and 85 years old with a mean age of 69.9 years. Of the 13 males and 2 females solitary tumours were observed at the ear in 5 patients, at the capillitium in 5 patients, in the face in 3 patients and in the shoulder/axilla area in 2 patients. The lesion were 0.5 to 15 mm in size and half of them ulcerated in severely damaged actinic skin. Histologically, the tumours showed pleomorphic histiocyte proliferation and atypical giant cells often with bizarre nuclei and numerous mitotic figures. Immunohistologically, the tumours were vimentin positive and HMB45, S100, keratin, desmin, EMA, CD34, and actin negative. The clinical evaluation showed no metastatic lesions. The tumours were treated by radical surgery and followed up every half year. The mean observation time is now 24 months without any recurrence. The atypical fibroxanthoma was first reported in 1963 by Helwig. Nowadays, it is thought to be a low grade malignancy as the superficial variant of malignant fibrous histiocytoma. Important is that this tumour follows an indolent behaviour but locally an aggressive course. Small numbers of metastases have been reported. The differential diagnoses includes dermatofibrosarcoma protuberans, malignant melanoma, spindle-cell squamous cell carcinoma and other rare tumour entities The clinical picture should be known not to underestimate this fibrous histiocytic neoplasm as a benign lesion. No significant financial relationships to disclose.
Utility of endometrial sampling in the detection of uterine sarcomas
Authors: Bansal N. , Herzog T. J. , Cohen C. J. , Wright J. D. 
Published: March 2020

20527 Objective: Uterine sarcomas are aggressive tumors that are often not recognized prior to surgical exploration. The goal of this study was to determine the utility of endometrial sampling in the detection of uterine sarcomas and to examine factors associated with diagnostic inaccuracy. Methods: All uterine tumors identified in hysterectomy specimens from 1990 to 2006 were accessioned. Study participation required a preoperative endometrial sampling (biopsy or curettage) that was reviewed at our center. Pathologic data and follow-up was documented through review of hospital records. Statistical analysis was performed using Fisher's exact test. Results: A total of 938 patients were identified. A preoperative biopsy was available for review in 730 (78%) subjects. Uterine sarcomas were noted in 142 patients; 72 (51%) underwent preoperative sampling. Overall, endometrial sampling correctly identified an invasive tumor in 88% (642/730). The correct histologic diagnosis was rendered in 80% (585/730). Among women with sarcomas, the preoperative sampling suggested a tumor in 86% (62/72) and predicted the correct histologic diagnosis in 64% (46/72). Among patients with epithelial carcinomas, biopsy suggested a tumor in 88% (569/644) and made the correct histologic diagnosis in 84% (539/644). Preoperative endometrial sampling was less accurate in patients with uterine sarcomas than in women with epithelial carcinomas (missed diagnosis 36% vs. 16%) (p < 0.0001). Subgroup analysis indicated that the histologic diagnosis was incorrect in 39% of the sarcoma patients who underwent office biopsy compared to 34% of those who underwent endometrial curettage (p=0.8). Patients with carcinosarcomas were more likely to undergo preoperative sampling than those with leiomyosarcomas (77% vs. 33%) (p=0.001). Conclusions: Endometrial sampling has a significantly lower predictive value in the diagnosis of uterine sarcomas. There is no difference in accuracy between office endometrial biopsy and uterine curettage. Novel diagnostic techniques are needed to accurately identify uterine sarcomas preoperatively. No significant financial relationships to disclose.