bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteosarcoma pulmonary metastasis: Prognostic factors of 88 patients submitted to surgical resection
Authors: Schutz F. A. , Younes R. N. , Borges J. A. , Gross J. L. 
Published: March 2020

20502 Background: Pulmonary metastasis from Osteosarcoma occurs in 30% to 40% of cases. Chemotherapy and surgical resection are the current preferred options for these patients, although overall outcome remains poor, with few patients achieving long term overall survival. Prognostic factors for better selecting these patients are needed. Methods: We reviewed the survival and the prognostic factors from 88 consecutive patients with pulmonary metastasis from osteosarcoma, submitted to metastasectomy at a single institution. Clinical and demographic variables, related to the primary tumor as well as to the pulmonary metastases and treatment procedures were registered. Univariate ( Log-rank and Breslow tests) and multivariate analysis (Cox-regression) were performed to identify significant prognostic factors related to overall survival. Results: Median follow-up time was 34 months, and 12.5% were alive without disease, 14.8% were alive with disease, 58% were dead of disease, 1,1% were dead from other causes, and 14.8% were lost to follow-up. The overall 5- year survival was 19%. Disease free interval (DFI), number of thoracotomies and complete resection at last thoracotomy were significant prognostic factors at univariate analysis. Median survival from first thoracotomy for patients with DFI = 12 months was 24.6 months, compared to 9.6 months for DFI < 12 months (p= 0.0014). Complete resection at last thoracotomy significantly improved median overall survival (19.1 versus 9.6 months) (p=0.0117). Cox-regression analysis showed only disease free interval more than 12 months (p=0.014) and complete resection at last thoracotomy (p=0.003) to be independent significant prognostic factors. Sex, age, site and stage of primary tumor, number of lung nodules, bilateral nodules, and chemotherapy treatment for lung metastases did not significantly impact on survival. Conclusion: Disease free interval and complete resection at last thoracotomy are significant prognostic factors for patients with resected pulmonary metastasis from osteosarcoma. No significant financial relationships to disclose.
Combination of pegylated-liposomal doxorubicin (PLD) and bevacizumab (B) (PLD-B) in sarcoma (SAR)
Authors: Skubitz K. M. , Haddad P. A. 
Published: March 2020

20506 Background: Vascular endothelial growth factor (VEGF) plays an important role in many tumors including SAR. Because of the known efficacy of PLD in SAR and the presumed importance of VEGF in SAR, we have treated SAR patients with PLD-B. It is possible that the addition of B to PLD might alter the toxicity profile. The toxicities of this combination are not well described. Methods: To better define the toxicity of the combination of PLD-B in SAR, we reviewed our experience with PLD-B in patients treated between 2004 and 2006. Results: We identified 20 patients with SAR treated with PLD-B at our institution. There were 9 men and 11 women, with a median age of 47.5 years (range 23–77). Ten patients initiated therapy with PLD q28 days at a median dose of 45 mg/m2 (range 45–50), and 10 q14 days at a median dose of 21.2 mg/m2 (range 20–25), in combination with B at 5 mg/kg q14 days. A median of 5 cycles was given (range 1–15). Dose delay was required in 3 patients for the second cycle, and dose reduction was required in 9 patients by cycle 3. Of the 10 patients starting with monthly PLD, 7 were changed to q14 day PLD by cycle 4. Mucositis and skin toxicity were the dose limiting toxicities (DLT) in 14/20 patients, and myelosuppression was the DLT in 1/20 patients. Nine patients were felt to have clinical benefit; 3 had a PR and 6 had SD. Notably, 2/4 recurrent Ewing sarcoma patients had symptomatic improvement and at least SD for 10 and 11 months, respectively, with minor toxicity allowing a good quality of life. Conclusions: This report describes the toxicity profile of PLD-B in 20 patients with SAR. The toxicities observed were similar to those seen with PLD alone, however, these toxicities appeared more pronounced with the addition of B. Since VEGF is important for wound healing, the known effects of B on this process may contribute to more skin and mucosal toxicity of PLD at a given dose. Future studies of PLD-B should consider the potential of increased mucosal and skin toxicity. The use of q14 day PLD to allow more control over toxicity is suggested; a maximal starting dose of 20 mg/m2 is reasonable, although dose reduction will be common due to skin or mucosal toxicity. This combination can be given with limited toxicity, and meaningful responses were observed in recurrent sarcomas, including 2/4 Ewing sarcomas. No significant financial relationships to disclose.
Non-methotrexate based triple drug combination chemotherapy for untreated osteosarcoma
Authors: Hingmire S. S. , Pai S. K. , Bakshi A. V. , Bharath R. , Agarwal M. , Puri A. , Dangi U. , Mandhaniya S. , Maksud T. , Parikh P. M. 
Published: March 2020

20512 Background: Considering the high cost of intensive high-dose methotrexate based chemotherapy, a non-methotrexate based chemotherapy regimen was evaluated in newly diagnosed osteosarcoma patients Methods: A total of 54 patients of newly diagnosed osteosarcoma (2000 to 2005) were included in the study. Chemotherapy protocol included 3 drugs viz. Doxorubicin (20 mg/m2 on Day1 to Day3), Cisplatin (100 mg/m2 on Day 1) and Ifosfamide (2000 mg/m2 on Day1 to Day 5) in combination as A1 cycle - Ifosfamide + Doxorubicin, B1 cycle - Doxorubicin + Cisplatin, C1 cycle - Cisplatin + Ifosfamide. The sequence was repeated as A2, B2 and C2 (total 6 cycles). Surgical excision of primary tumor was done after 3 cycles of chemotherapy Results: The median age at diagnosis was 15.5 years with a slight male preponderance (n=38, 70.4 %). Axial skeleton (maxillary) was affected only in one patient. Lower end of femur was the most common appendicular skeletal site for the primary tumor (n=27, 50 %). Forty two out of 54 (77.8 %) patients had nonmetastatic disease at diagnosis. Lung was the most common site of distant metastasis at diagnosis (11 out of 12 patients). Fifty patients received all 6 chemotherapy cycles as planned. Limb salvage with reconstruction surgery was performed in 35 (64.8 %) patients. Complete (100%) tumor necrosis was seen in 18 (33.3 %) patients. The median duration of follow-up was 16 months. The actuarial disease free and overall survival at 3 years would be 41.4 % and 43.6 % respectively. The incidence of febrile neutropenia was 11.85 % and of grade III/IV thrombocytopenia was 10 % of all chemotherapy cycles. Easily controllable emesis was the commnoest non-hematological toxicity, experienced by 31.5 % of patients. Two patients died due to post chemotherapy neutropenic sepsis. With univariate analysis, complete histological response (100 % tumor necrosis) alone could be identified as independent favorable prognostic factor (3 year OS of 73.6 %, P=0.003). The overall survival outcome was not statistically different in subgroups of sex, age group and pathological tumor size. Conclusions: Non-methotrexate based triple drug combination chemotherapy is an effective treatment option for patients with newly diagnosed osteosarcoma in developing countries like India. No significant financial relationships to disclose.
ET 743 is an effective agent against sarcoma
Authors: Boyle H. , Favier B. , Lurkin A. , Ray-Coquard I. , Ranchère D. , Decouvelaere A. , Blay J. , Fayette J. 
Published: March 2020

20516 Background: ET-743 has shown clinical activity in soft tissue sarcoma after failure of anthracyclines and ifosfamide. We propose to assess these results in our institution. Methods: We reviewed the patients treated (in phase II studies or on a compassionate basis) until June 2006 Results: Median age of the 99 patients was 53 years (18–82, with 20% leiomyosarcomas, 18% other spindle cell sarcomas, 12% liposarcomas, 9% osteosarcomas and 4% Ewing's sarcomas. The initial tumor was in the lower limbs in 31% of cases, and 70% had lung metastases. Patients had received anthracyclines (72%) or ifosfamide (61%), but 12% received ET-743 as their 1st chemotherapy. Most patients received ET-743 as a single agent, but 7 received it in combination with doxorubicin. After a median of 4 cycles (1–25), 50% of patients responded: 0 CR, 12 patients with PR, 4 MR (minor response), 34 SD and 49 progressed. Median time to progression for patients with a clinical benefit (PR+MR+SD) was 7 months (1.5 to 66 months). Among the 29 patients who didn't progress in the first six months, 10 had leiomyosarcomas and 8 spindle cell sarcomas. Grade3/4 toxicity, mainly hematological (42% neutropenia, 16% anemia, 11% thrombocytopenia) and hepatic (33%), was noted in 69 patients (28 needed a dose reduction). Main cause of treatment discontinuation was progression (70%) but 7 patients had to stop treatment because of toxicity. Conclusions: ET- 743 can benefit some patients with sarcomas, especially leiomyosarcomas, even pretreated. Some patients have long lasting responses. Grade ¾ toxicity is frequent but rarely leads to treatment discontinuation No significant financial relationships to disclose.
Phase 2 dose multi-center, open-label study of ARQ 501, a checkpoint activator, in adult patients with persistent, recurrent or metastatic leiomyosarcoma (LMS)
Authors: Hartner L. P. , Rosen L. , Hensley M. , Mendelson D. , Staddon A. P. , Chow W. , Kovalyov O. , Ruka W. , Skladowski K. , Jagiello-Gruszfeld A. , Byakhov M. 
Published: March 2020

20521 Background: ARQ 501 selectively induces apoptosis in cancer cells by inducing a rapid and sustained increase of the pro- apoptotic protein E2F-1. ARQ 501 has been studied in three phase 1 studies, demonstrating acceptable toxicity and encouraging signs of efficacy. A 54 y/o female with metastatic LMS who failed 7 previous therapies achieved a prolonged PR on ARQ 501 monotherapy. This was consistent with preclinical data, where induction of E2F-1 and corresponding efficacy in human leiomyosarcoma xenografts was observed. Methods: A phase 2 study in adult LMS patients (>3 prior systemic therapies) was initiated to assess ORR, TTP and further characterize the safety of ARQ 501. ORR included CR, PR and SD=4 mo. Four week cycles (ARQ 501 450mg/m2) were repeated until progression, unacceptable toxicity, or another discontinuation criterion. Results: 49 patients were enrolled and 45 received ARQ 501. Data is available for 43 patients (4M/39F, median age, 54). Of the 43, 10 did not reach a protocol defined tumor assessment (4 deaths, 5 PD and 1 lost to follow-up prior to week 8), 19 have been assessed for response per RECIST at eight weeks (7 SD of 8–28+ weeks, 1 PR, 11 PD) and 14 active patients yet to reach first tumor assessment. The most common AEs were: anemia (68%, 21%=G3), hyperbilirubinemia (35%, 6%=G3), fatigue (35%, 0%=G3), nausea (30%, 0%=G3), constipation (24%), hemolysis (21%, 6%=G3), dyspnea (21%), and vomiting (21%). One treatment related death was reported in a 47 y/o Asian male with severe hemolysis following a single infusion of ARQ 501 at 450 mg/m2. The pt was hospitalized, but severe hemolysis led to acute renal failure and the patient expired after 4 days. Conclusions: ARQ 501 was administered to 45 patients with advanced, recurrent or persistent leiomyosarcoma. Several patients have achieved some clinical benefit (1 PR, 3 prolonged SD), further analysis of efficacy data is warranted prior to additional clinical investigation. No significant financial relationships to disclose.
Tumours associated with gastrointestinal stromal tumors (GIST): A case report
Authors: Fayaz S. , George T. , Mohammad M. , Samir S. 
Published: March 2020

20529 Background: Much progress has been made in the diagnosis and treatment of GIST but the rarity of second neoplasms in association with gastro intestinal tumours (GIST) have rarely been reported. Methods: We present three case reports of breast cancer, Hodgkin's disease and thyroid cancer associated with GIST Results: The first pt, aged 50 underwent left lumpectomy and axillary clearance for infiltrating ductal carcinoma. Estrogen and Progesterone receptors were positive. Adjuvant chemotherapy , radiotherapy and tamoxifen was administered .Three years later patent was operated for a sub mucous nodule in the stomach which was reported as GIST, CD117+ve,CD34 positive and the patient was followed up. The second pt, male aged 50 was operated for a large intrabdominal GIST tumour (16x16cm) arising from the stomach and later on referral found to have a Rt Supraclavicular node with a nodule in the thyroid. He under went total thyroidectomy with functional node dissection for papillary carcinoma. This was followed Radioactive iodine ablation and eltroxin. Three months later he presented with thoraco abdominal metastasis and treatment with Imatnib was begun, but he soon progressed and succumbed to his disease. The third pt, female, with a history of Hodgkin's disease treated with chemotherapy on follow up. Twelve years later the pt was subjected to extensive debulking for pelvic GIST (16cmx15cm).CD117 positve.She was kept on follow up. A ct chest abdomen and pelvis eight months following surgery was unremarkable. Conclusions: Very few cases have been reported in literature regarding association of second tumours with GIST .And no correlation can be made to generate a hypothesis regarding these associations. No significant financial relationships to disclose.
Phase I study of gadolinium texaphyrin in newly diagnosed glioblastoma
Authors: Shaw E. G. , Grossman S. A. , Carson K. A. , Fisher J. D. , Kleinberg L. 
Published: March 2020

2064 Background: Gadolinium texaphyrin (Gad Tex) is a putative radiosensitizer which inhibits cellular respiration resulting in the production of reactive oxygen species and induces apoptosis (Drugs R D. 2004; 5(1):52–7). Methods: The New Approaches to Brain Tumor Therapy (NABTT) consortium conducted a prospective phase I dose-escalation trial to determine the maximum tolerated dose of Gad Tex along with brain radiation therapy (RT) in newly diagnosed glioblastoma multiforme with KPS > 60. RT was 60 Gy in 30 fractions, 5 days per week over 6 weeks, to localized treatment fields. Two different dosing regimens of Gad Tex were utilized. In regimen A, the initial dose was 2.5 mg/kg with each daily fraction of RT whereas in regimen B it was 5.5 mg/kg with every fraction of RT. Gad Tex was administered 2–5 hours before each radiation treatment. Results: The initial dose in both regimen A and B was found not to be tolerable. Of three patients treated at 2.5 mg/kg/dose on regimen A (daily dosing), one completed planned therapy (30 doses of Gad Tex), one had treatment stopped after 16 doses of Gad Tex when diffuse pulmonary infiltrates with shortness of breath developed and returned after rechallenge with an additional dose of Gad Tex, and one patient developed an allergic reaction after 15 doses of Gad Tex which returned on rechallenge. Of three patients treated at 5.5 mg/kg/dose (qod dosing) on regimen B, one completed planned therapy (15 doses of Gad Tex) after a dose reduction related for skin blisters, and the other two patients discontinued treatment after 9 doses of Gad Tex for debilitating skin blisters. Conclusions: Gad Tex was poorly tolerated as administered in this small phase I study as 4 of 6 patients experienced dose limiting toxicities. As such, NABTT elected not to pursue this drug in subsequent clinical trials. However, similar or more intensive regimens utilizing Gad Tex in combination with brain RT have been successfully administered in patients with newly diagnosed glioblastoma and brain metastases. No significant financial relationships to disclose.
Retrospective analysis of glioblastoma multiforme (GBM) patients treated initially with BCNU compared to temozolomide (TMZ) with concomitant radiation therapy
Authors: Vinjamuri M. , Adumala R. , Altaha R. , Hobbs J. , Crowell E. 
Published: March 2020

2071 Background: TMZ and radiation as initial treatment has become the standard of care for GBM. There are no randomized studies comparing TMZ to BCNU in GBM. Methods: We did a retrospective analysis of all 100 GBM patients (pts) diagnosed by our pathology department in the last 10 years. 20 pts were excluded, in 12 pts no chemotherapy was given and there was no data available for 8 pts. BCNU treatment was given in earlier years than TMZ generally. Overall survival (OS), progression free survival (PFS) and four prognostic factors were compared between BCNU and TMZ treated groups. Results: Results show that there is no significant difference in OS and PFS between the two groups. Survival curves were superimposable. This is despite the fact that tumor size and ECOG performance status were worse, though not significantly so in the BCNU group. Age was the only variable that correlated with survival. After correcting for age there was still no difference in PFS and OS between the BCNU and TMZ group. Conclusions: Our study fails to shows superiority of TMZ over BCNU despite the fact that the BCNU group had worse prognostic factors. A randomized comparison of these two agents seems justifiable. [Table: see text] No significant financial relationships to disclose.
The topoisomerase I inhibitor gimatecan exhibits anti-tumor activity against malignant glioma xenografts as single agent and in combination
Authors: Vassal G. , Hamelin N. , Opolon P. , Versace R. , Geoerger B. 
Published: March 2020

2081 Background: Gimatecan, a novel oral lipohilic camptotecan (ST1481; NVP-LBQ707), has shown to irinotecan and topotecan superior anti-tumor activity against several cell lines and human xenografts. We evaluated gimatecan in microemulsion in vivo alone and in combination with temozolomide and the EGFR and VEGF tyrosine kinase inhibitor AEE788 against subcutaneous malignant glioma xenografts derived from primary tumors. Results: Gimatecan exhibited dose-dependent activity against all three advanced tumor stage glioma models with IGRG93 being the most sensitive: 0.10 to 0.25 mg/kg gimatecan daily orally in a protracted schedule 5 days/week during 4 weeks resulted in 100% partial and complete tumor regressions, significant tumor growth delays (TGD; 48 to >100 days), log cell kills of 4.3 to 9.1, and were thus considered as ++++ highly active according to the SRI activity criteria. Anti-tumor activity in the TP53 wild-type IGRG93 correlated with significant induction of apoptotic cell death, as measured by TUNEL and cell cycle analysis, and lack of induction of p21. Moreover, combination of gimatecan and temozolomide resulted in synergistic activity against the TP53 wild-type IGRG121 glioblastoma and gimatecan at the MTD could be combined with temozolomide without enhanced toxicity. Gimatecan 0.19 mg/kg q5/wx4w combined with AEE788 50 mg/kg q3/wx4w was evaluated against the TP53 mutant, EGFR gene amplified IGRG88 glioma. Both agents were highly active resulting in 100% tumor regression. Gimatecan treated tumors started to grow 2–3 weeks after treatment end, while tumors treated with AEE788 regrew directly after treatment stop resulting in less significant TGD. Gimatecan and AEE788 given simultaneously during 4 weeks yielded less significant TGD compared to gimatecan alone, thus antagonistic effects. AEE788 induced G1 cell growth arrest which may reduce sensitivity to gimatecan, necessitating S-phase to be most efficient. An alternative schedule with gimatecan followed by AEE788 may be more appropriate. Conclusions: Gimatecan is highly active against malignant glioma xenografts and has synergistic activity with temozolomide suggesting this new topoisomerase I inhibitor for the treatment of malignant glioma. No significant financial relationships to disclose.
Estrogen receptor (ER) status of disseminated tumor cells in the bone marrow of breast cancer patients
Authors: Tanja F. N. , Krawczyk N. , Wallwiener D. , Becker S. , Solomayer E. 
Published: March 2020

21013 Background: The presence of disseminated tumor cells (DTC) in bone marrow (BM) of primary breast cancer patients is associated with poor prognosis. These patients may benefit from adjuvant endocrine therapy since cytotoxic agents are not able to completely eliminate DTCs as previously shown. Only patients with hormone receptor positive breast cancer are eligible for hormonal treatment. The ERa status is routinely defined in primary tumor tissue. However, the ERa status of DTC may differ compared to the primary tumor. Therefore, the aims of this study were (1) to determine the ERa status of DTC in BM of breast cancer patients, (2) and to compare the ERa status of DTC and corresponding primary tumors. Methods: BM aspirates from 251 primary breast cancer patients were included into the study. A double immunofluorescence staining procedure was established for the identification of cytokeratin-positive (CK)/ERa positive cells. ERa status of the primary tumor was immunohistochemically assessed using the same antibody against ERa. Results: In 105 of 251 (42%) breast cancer patients CK-positive cells could be detected in BM. The number of detected cells ranged between 1 and 13 / cells per 2*106 mononuclear cells. Disseminated tumor cells demonstrated ERa positivity in 13 (12%) of these 105 patients. The ERa expression on DTC was heterogeneous in 10 of 13 (79%) patients. Concordance rate of ERa status between primary tumor and DTC was 27%. Only 11 of 83 patients with ER a positive tumors had also ERa positives DTC. Conclusions: (1)The hormone receptor status between primary tumor and corresponding DTC is disconcordant. (2)This discrepancy may explain the rate of non-responders to adjuvant endocrine therapy despite ER-positive primary tumors. (3)These patients may benefit from adjuvant therapy regimens based on antibody strategies or bisphosphonates. No significant financial relationships to disclose.