bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of clinical markup with CT simulation in whole brain radiation therapy
Authors: Wang Y. , Makhani N. , Tsao M.
Published: March 2020

2043

Background: Two types of clinical markup have been used for whole brain radiation therapy (WBRT), but the extent of dose coverage and sparing of the lens is unknown. This study is designed to evaluate clinical markup with CT simulation. Methods: CT simulation images of the brain from 20 random adult patients were included in this study. Two types of inferior field borders were generated to mimic the 2 types of clinical markup of WBRT: from superior orbital ridge (SOR) to tragus, and from SOR to inferior tragal notch (ITN). A field margin of 1 cm from contoured brain (along base of skull) was used in CT simulation, except near the orbital globe where 0.5 cm margin to eye shielding was used. Two opposed lateral fields with 6 MV photon were used to generate 3 WBRT plans in each patient: clinical markup with SOR to tragus, SOR to ITN, and CT simulation. Dose volume histograms of the brain and lens were generated. The primary end point was dose coverage of whole brain with clinical markup. The secondary end point was sparing of the lens. Results: Patients with clinical markup using SOR to tragus or SOR to ITN had significantly larger median brain volume receiving less than 95% of the prescribed dose, 37.0 mL and 7.8 mL (respectively) compared to CT simulation 0 mL (P < 0.001). All patients with SOR to tragus and most patients (95%) with SOR to ITN clinical markup had underdosing in the regions of inferior frontal lobe, temporal lobe and posterior fossa. There was no significant difference in the dose to the lens between CT simulation and clinical markup using SOR to tragus (P = 0.18) or SOR to ITN (P = 0.90). Conclusions: Whole brain radiation therapy with clinical markup using either SOR to tragus or SOR to ITN results in underdosing at the inferior frontal lobe, temporal lobe and posterior fossa. Sparing of the lens is adequately achieved with clinical markup.

No significant financial relationships to disclose.
Phase III study of paclitaxel (Pac) versus pegylated liposomal doxorubicin (PLD) for the treatment of advanced human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS): An Eastern Cooperative Oncology Group (ECOG) and AIDS Malignancy Consortium
Authors: Von Roenn J. H. , Lee S. , Cianfrocca M. , Tulpule A. , Scadden D. , Aboulafia D. , Sparano J.
Published: March 2020

20503

Background: PLD (doxorubicin HCL liposome injection, Doxil®, Tibotec Therapeutics, Raritan, NJ) and paclitaxel (Taxol®, Bristol Myers, Inc, New York, NY) are active in the treatment of HIV-associated KS; however, optimal therapy is undefined. Methods: A randomized phase III, multicenter trial was initiated to compare the efficacy of Pac (100 mg/m2) every 2 weeks to PLD (20 mg/m2) every 3 weeks for chemotherapy-naïve AIDS-related KS. Treatment continued until disease progression or unacceptable toxicity; concurrent antiretrovirals were permitted. 216 pts were required to detect at least a 3-month improvement in median progression free survival (PFS) for Pac compared with PLD (80% power, 2-sided alpha 0.05). Response was assessed using KS response and clinical benefit criteria, and global assessment of quality of life (QOL) using the Functional Assessment of Health Index (FAHI; version 3) plus 3 supplemental questions concerning pain, swelling, and satisfaction with physical appearance (measured at baseline and during/after treatment). Results: The trial was terminated early due to poor accrual; 46 pts were randomized to PLD, 43 to Pac. 11 pts were ineligible, 4 never started therapy and 6 lacked disease assessment or progression data, resulting in 68 pts for the efficacy analysis (34 in each arm) and 82 in the toxicity analysis. After a median follow-up of 35.8 months (mo.), there was no significant difference in PFS, response rate, or overall survival. Due to early termination, the study was not adequately powered to detect the hypothesized difference in PFS. There was no significant difference in QOL between the two arms. Grade 3–4 toxicity was comparable, including grade 4 neutropenia (34% vs. 27%) and infection (13% vs. 11%). Conclusions: Paclitaxel and PLD have comparable efficacy and toxicity in patients with HIV-associated KS.

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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.
Clinical response to imatinib mesylate in recurrent and metastatic gastrointestinal stromal tumors
Authors: Villalobos R. , Hernández G. , Martinez-Prieto M. , Silva A.
Published: March 2020

20528

Background: We analyzed the efficacy and safety of imatinib mesylate in GIST (Gastrointestinal Stromal Tumors) in various anatomic sites. Methods: Out of 24 patients with recurrent or metastatic disease receiving treatment, clinical and tomographic evaluation was possible only in 21 pts. RECIST criteria were used to evaluate response and NCI guidelines were used for evaluation of toxicity. The treatment given between March 2003 and December 2006 was imatinib mesylate 200mg twice daily until disease progression or drug intolerance. All included patients had histopathologic confirmation and CD 117 positive inmunohistochemistry. Results: Patient characteristics were as follows: 19 females, 2 males, average age: 37.8 years (range: 36 - 80), Functional status according to ECOG: 0 in 19 pts, 1 in one patient and 3 in one patient. Anatomic sites were: 4 stomach, 7 small intestine, 3 rectum-sigmoid, 4 carcinomatosis from unknown primary, 2 peripancreatic and one esophageal. Nine patients had recurrent disease, 12 unresectable disease and 11 pts had liver metastases and 13 had retroperitoneal metastatic disease. Comorbidities: 3 pts with Type 2 Diabetes Mellitus one patient with Systemic Hypertension, and deep vein thrombosis each, two patients with a previous diagnosis of cancer: Thyroid and Lung Cancer respectively. Responses:2 (9.5%)CR, 6 (28.5%) PR, 12 (57.1%) stable disease, one (4.7%) pt. with progressive disease. Toxicity: one patient had rash, one patient presented bone pain, one patient with face discoloration, one with cephalea and nausea, and two patients with bipalpebral edema. Median duration for response was 5.7 months (range 2–30) at the moment. Conclusions: Efficacy of imatinib mesylate in recurrent and metastatic GIST's is high with overall response rates of 95% and adequate tolerance. Studies as adyuvant and second line therapy are needed in our population.

No significant financial relationships to disclose.
Phase II trial of imatinib mesylate and hydroxyurea for adults with recurrent/progressive low-grade glioma
Authors: Bota D. A. , Desjardins A. , Quinn J. A. , Rich J. N. , Vredenburgh J. J. , Sathornsumetee S. , Goli K. , Salvado A. , Friedman H. S. , Reardon D. A.
Published: March 2020

2053

Background: We evaluated the combination of imatinib mesylate and hydroxyurea in recurrent/progressive low-grade gliomas (LGG) following the encouraging response of this combination demonstrated among adults with recurrent malignant glioma. Methods: Key eligibility criteria: age over 18 yrs; histologically confirmed grade II LGG that is recurrent/progressive following at least prior surgical resection; Karnofsky = 60% and adequate organ function. Imatinib plus hydroxyurea were given on a continuous oral daily schedule for 28 day cycles; imatinib was administered at 400 mg daily to patients not on CYP3A-enzyme inducing antiepileptic drugs (EIAED) while those on EIAED received 500 mg twice a day. All patients received 500 mg twice a day of hydroxyurea. Patients were evaluated every other month with physical and MRI examinations. Results: Twenty-seven patients with recurrent or progressive LGG have enrolled including 17 with astrocytoma and 10 with oligodendroglioma. Eleven (40.7%) are on EIAED. Median age was 42 years (range 24–66 years). 26% of patients had received prior therapy other than surgery (XRT, n=2; chemotherapy, n=5). The most frequent toxicities possibly related to the study regimen were fatigue (grade 2, n=5; grade 3, n=1), neutropenia (grade 2, n=1; grade 3, n=2), anemia (grade 2, n=2), rash (grade 2, n=2), nausea (grade 3, n=1), anorexia (grade 2, n=1), and AST elevation (grade 2, n=1). There were no grade 4 or 5 treatment-related toxicities. Among patients evaluable for response, 17 (85%) achieved stable disease and 3 (15%) had progression. Twenty patients continue on study having received 2–16 months of therapy. Additional accrual and follow-up is ongoing. Conclusions: Continuous daily treatment of imatinib plus hydroxyurea is well tolerated and associated with encouraging preliminary activity among adults with recurrent/progressive LGG.

[Table: see text]
High grade unclassified sarcoma of the broad ligament: A case report and literature review
Authors: Mauricio D. D. , Vanderlee G.
Published: March 2020

20536

Background: The incidence of primary sarcoma of the broad ligament is very rare. From the first reported finding in 1968, there are only 17 documented cases worldwide of this very progressive and highly malignant gynecologic neoplasm. We present the 18th case of this aggressive tumor to add to the scarce knowledge about this disease and to contribute in characterizing its behavior and its reasonable management. Methods: Case report and case review/series Results: This is the 18th case of broad ligament sarcoma found on routine physical examination in a woman who had previous hysterectomy for benign leiomyoma. Treatment consisted of resection of the broad ligament mass, bilateral salpingo-oophorectomy, omental and peritoneal biopsies with pelvic cytology. She is disease-free on strict clinical surveillance. An updated extensive review of previous reports was done as well. Conclusions: The scarcity of the cases of leiosarcoma of the broad ligament prevents the understanding of its biologic nature. Thus, there were different approaches on its staging, surgical management and adjuvant therapy, and tumor surveillance producing unpredictable prognosis. It appears TAH-BSO with rigid disease follow-up and subsequent chemotherapy or radiotherapy prolongs survival.

No significant financial relationships to disclose.
Plasma pharmacokinetics and cerebrospinal fluid concentrations of erlotinib in high-grade gliomas: A novel, phase I, dose escalation study
Authors: Buie L. W. , Lindley C. , Shih T. , Ewend M. , Smith J. K. , Skelton M. , Kwock L. , Morris D. , Tucker C. , Collichio F.
Published: March 2020

2054

Background: Erlotinib (ERL) is an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase. EGFR is overexpressed in glioblastoma multiforme (GBM). The primary objectives of this study were to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT) and to evaluate plasma and cerebrospinal fluid (CSF) ERL concentrations using a novel every 72 hour ERL dosing schedule. Methods: Patients = 18 years of age with GBM or high grade glioma with evidence of disease progression following first line therapy (surgery/XRT/chemotherapy) and Karnofsky performance status = 60 % were included. Patients were stratified based on use of enzyme-inducing antiepileptic drugs (EIAED). Patients not on EIAED were initiated on ERL 450 mg PO every 72h, while those on EIAED were initiated on 900 mg PO every 72 h. Results: Six patients have been enrolled and assessed for safety, 5 for plasma PK and 3 for CSF concentrations. For ERL, the area under the plasma concentration versus time curve (AUC) was greater and the half-life longer in patients not receiving EIAED. However, the AUC of OSI-420, the major metabolite of ERL, was lower in patients not receiving EIAED. The OSI-420 AUC: ERL AUC ratio was increased 3 fold among patients receiving EIAED, indicative of increased hepatic metabolism and increased clearance. CSF concentrations were detectable and ranged from 1 to 3% of peak plasma concentrations. Neither group has experienced a DLT or reached the MTD. The most common side effects (grade 1/2) have been diarrhea (83%), rash (100%) and fatigue (33%). To date, there has been 1 partial response, 1 patient with stable disease and 4 patients with disease progression. The partial response and stable disease have occurred in patients with GBM. Conclusions: ERL is a well tolerated therapy. Patient enrollment and subsequent dose escalation is ongoing and updated results will be presented at the ASCO 2007 meeting.

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No significant financial relationships to disclose.
Pegylated liposomal doxorubicin in recurrent high-grade glioma: Comparison of clinical trial results and compassionate use
Authors: Glas M. , Koch H. , Hirschmann B. , Jauch T. , Steinbrecher A. , Bogdahn U. , Hau P.
Published: March 2020

2073

Background: Results from prospective clinical studies may not always be reproduced in clinical practice. Therefore it is important to compare data from clinical trials with data from compassionate use of the same treatment. Here, we present patients with relapsed high-grade glioma treated outside a clinical trial with liposomal pegylated doxorubin (PEG-DOX). Methods: This data was documented prospectively and compared to our earlier published study results. Forty-nine patients with recurrent high-grade glioma (WHO III: n=18; IV: n=31) were treated with PEG-DOX (days 1 and 14/28, 20 mg/m2) alone or in combination therapy with temozolomide (TMZ) (days 1 to 5/28, 200 mg/m2). The clinical response rate, time to progression, progression free survival and overall survival were evaluated. Results: The overall response rate including disease stabilization was 53% (WHO III: 61; IV: 48). PFS-6 was 27% (WHO III: 33%; IV: 23%). The median OS after initiation of PEG-DOX was 35 weeks (WHO III: 68; IV: 31). Comparison of PEG-DOX monotherapy and combination therapy revealed no significant difference. Both regimens were well tolerated, with the main side effect being hematologic toxicity (grade 1–2: 8%, grade 3–4: 18%). Conclusion: These data compare favorably with published data and underline the potential of PEG-DOX in this setting. In addition, the prolonged median OS after initiation of PEG-DOX for grade III-tumors (68 weeks) merits additional focus.

No significant financial relationships to disclose.
Correlation between VEGF expression and MVD in sporadic and NF2-related schwannomas
Authors: Ditomaso E. , Stemmer-Rachamimov A. , Potts A. , Drottar M. , Jain R. K. , Plotkin S. R.
Published: March 2020

2083

Background: Neurofibromatosis 2 (NF2) is a tumor suppressor syndrome characterized by the presence of bilateral vestibular schwannomas (VS) and multiple meningiomas for which alternative treatments are desperately needed. Currently there are no well- tolerated agents that are clinically active. Previous groups have shown VEGF expression in small series of VS. In this study, we expand these findings and show a significant relationship between VEGF bound to the vascular endothelium and microvascular density (MVD) in NF2-related VS. This observation providing a strong rationale for the use of VEGF blockade in this patient population. Methods: Formalin-fixed, paraffin-embedded specimens were obtained from surgical resections of 22 patients with sporadic VS and from 21 patients with NF2 VS. Sections were stained with anti-VEGF polyclonal antibody and with anti-CD31 monoclonal antibody. Intensity of immunostaining of tumor cells for VEGF was scored in semi-quantitative fashion (0-none, +1-mild, +2-moderate, +3-strong); MVD was calculated by averaging the number of CD31-positive vessels in 5–15 high -powered fields (20x). MVD in tumors with and without VEGF bound to the vascular endothelium were compared using t-test. Results: Expression of VEGF was detected in all sporadic and NF2 VS. Strong expression of VEGF in tumor cells was more common in sporadic VS (45%) than in NF2-related VS (5%). In contrast, endothelial-bound VEGF was more common in NF2- related VS (75%) than in sporadic VS (45%). There was no difference in mean MVD between sporadic (6.2%) and NF2-related tumors (6.1%). However, in NF2-related VS, MVD was significantly greater in tumors with endothelial bound VEGF (7.4%) than without (4.6%) (p < 0.05). Conclusions: VEGF expression in tumor cells was universal in this series of sporadic and NF2-related VS. Although the intensity of VEGF expression appears greater in sporadic tumors, endothelial- bound VEGF is more common in NF2-related lesions and is associated with greater MVD. This finding indicates a potential activity of the VEGF angiogenic pathway in this patient population. Therefore anti-VEGF therapy, such as bevacizumab, sunitinib, or sorafinib, represents a rationale approach to treating NF2 patients with VS in which surgical approach is not possible or has failed.

No significant financial relationships to disclose.
Analysis of MGMT promoter methylation status in high grade glioma patients with long term and conventional survival times: A retrospective study
Authors: Preusser M. , Hassler M. , Elandt K. , Gelpi E. , Hainfellner J. , Baur M. , Marosi C.
Published: March 2020

2084

Background: Response to alkylating chemotherapy in patients with high grade gliomas (HGG) has been found correlated to epigenetic silencing of the DNA repair gene MGMT (O6-methylguanine-DNA methyltransferase) in the tumor tissue. Patients with HGG expressing a methylated MGMT promoter benefited from alkylating chemotherapy in terms of a prolonged survival as compared to patients with unmethylated MGMT promoter. Methods: Our study cohort comprised 47 patients with HGG, all treated with concomitant chemotherapy and radiotherapy in our institution. 23/47 patients (8 women, 15 men, aged 22.4–64.5 years, median 36.3) survived longer than 36 months (range of survival times 36–137 months, in median 46.9 months) and were defined as long term survivors (LS). 24/47 patients (5 women and 19 men, aged 18.3–73.3 years, median 47.7) with early tumor relapse who survived in median for 23.5 months were defined as HGG patients with conventional survival (CS). In all cases, we extracted DNA from formalin-fixed and paraffin-embedded tumor tissue samples. The methylation status of the MGMT promoter was determined by bisulfide modification of the DNA and methylation-specific polymerase-chain- reaction (MSP). MSP results were rated by 4 independent observers. Results: There was high interobserver agreement at interpretation of MSP results (range of kappa values: 0.71–0.87). Among LS, we found MGMT promoter methylation in 13/24 (81.5%) patients and an unmethylated MGMT promoter in 3 patients, whereas the MSP results were not interpretable in 7 patients of this patient subgroup. Among CS, we found promoter methylation in 16 patients (66.6%), unmethylated promoter in 6 patients and uninterpretable results in one patient. There was no statistically significant difference in MGMT promoter methylation rate between LS and CS. Conclusions: The proportion of gliomas with methylated MGMT promoter in this series is unexpectedly high, particularly for CS patients. Potential explanations for this finding are methodological differences due to the use of paraffin-embedded tumors instead of frozen tumor material as in most published series and a potential random accumulation of MGMT positive tumors in the patients with CS survival.

No significant financial relationships to disclose.
Prognosis of sub-types of cancer of unknown primary (CUP) compared to metastatic cancer
Authors: Bishop J. F. , Tracey E. , Glass P. , Jelfs P. , Roder D.
Published: March 2020

21010

Background: The aim is to study the clinical characteristics and outcomes of a complete cohort of presentations of Cancer of Unknown Primary (CUP) compared with patients presenting with metastatic cancer of known primary site. Methods: All persons diagnosed with cancer in New South Wales, Australia, from 1980 to 2004 were studied using a population based cancer registry. Patients classified as CUP were documented, compared to those with initial metastatic presentations of a known primary, for the same period. Results: There were 65,239 histologically or cytologically confirmed metastatic cancers presented. Of these 46,435 (77%) were metastatic with a known primary site and 13,280 (22%) were CUP. The median survival (ms) of all patients presenting with CUP was 3 months compared with 7 months for metastatic cancers of known primary site (p<0.0001). Patients with CUP with adenocarcinoma had significantly worse prognosis compared to metastatic adenocarcinoma of known primary site. However patients with squamous cell CUP had a significantly better outcome (ms 12 months) than metastatic squamous histology with a known primary site (ms 5 months, p<0.0001) with 31% of squamous cell CUP alive at 6 years. For those with CUP and adenocarcinoma the risk of dying was 80% greater compared to those with a known primary and adenocarcinoma (HR 1.8 95%CI 1.7–1.8). For those with CUP and squamous cell carcinoma the risk of dying was 50 % less (HR 0.49 95%CI 0.46–0.53). CUP with small cell, (HR 0.77 95%CI 0.71–0.85) and undifferentiated histology (HR 0.84, 95%CI 0.76–0.93) after controlling for sex and age, had a significantly better prognosis than other metastatic cancers. Germ cell CUP represented only 0.2% of all CUP presentations. Conclusions: CUP is a heterogeneous classification of cancer with a poorer prognosis overall when compared to metastatic cancer of known primary site especially if adenocarcinoma. However, squamous cell and small cell CUP had a better prognosis suggesting a need for specific and more focused treatment. Lack of trends for less CUP presentations compared to reducing metastatic cancer over this 24 year period suggests that CUP is in part a distinct clinico-pathological entity rather than a missed primary diagnosis.

No significant financial relationships to disclose.
Low Foxp3 cells infiltrate is a marker of pathological complete response to neoadjuvant chemotherapy in breast carcinoma
Authors: Ladoire S. , Arnould L. , Apetoh L. , Coudert B. , Martin F. , Chauffert B. , Fumoleau P. , Ghiringhelli F.
Published: March 2020

21011

Background: T cell infiltration is associated with tumor prognosis in many cancer types. To assess the capacity of neoadjuvant chemotherapy to impact on T cell infiltration in breast cancer, we investigated if pathological complete response (pCR) to neoadjuvant chemotherapy correlated with T cell infiltration Methods: CD3, CD8 and Foxp3 positive cells were detected by immunohistochemistry in a series of 56 breast cancer patients treated by neoadjuvant chemotherapy. Infiltrates were analysed before and after the end of the treatment. Cytotoxic cells were stained using anti-Granzyme b and TiA1 antibodies Results: Poor prognosis factors (negative hormonal receptors, high tumor grade and nodal involvement) correlated with a significant higher number of CD3, CD8 and Foxp3 cells infiltrates before chemotherapy. Chemotherapy only induced a decrease in the number of Foxp3 cells (p<0.01) while the level of CD8 and CD3 cells were maintained (p=0.8). pCR were observed in 12 patients who had a drastic decrease of Foxp3 positive cells (mean:1.6±1.4 versus 0.08 ± 0.2; p<0.001) while these cells remained elevated in non responders (mean: 1.5±1 versus 1 ± 1 p=0.2). Furthermore, using a cutoff criterion that combined high CD8 infiltration and no Foxp3 cell infiltration on surgical specimens we could predict pCR with a sensitivity of 75% and a specificity of 93%. Cytotoxic effector cells infiltrate was only enhanced in pCR. In multivariate analysis, only high tumor grade and low Foxp3 cell infiltration on final histological specimens were independent predictors of a pCR (HR (95% CI): 17,7394 (1,1 to 272,5) p=0.04 and 0,0132 (0,0002 to 0,9) p=0.04 respectively). The Kaplan Meier estimate of metastasis-free survival indicated a trend toward higher percentage of metastases-free patients in pCR and combined immunological criterion (Log rank test, p=0.1 and p = 0.12 respectively) Conclusions: These findings indicate that pathological complete response to neoadjuvant chemotherapy is associated with an immunological profile consisting in absence of immunosuppressive Foxp3 cells, presence of high number of CD8 T cells, and an increased number of cytotoxic cells. These results argue for the induction of an antitumor immune response by chemotherapy in this group of patients

No significant financial relationships to disclose.