bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epithelial to mesenchymal markers and clinical outcomes on erlotinib in stage IV non-small cell lung cancer patients.
Authors: Pool Mark , Fidler Mary J. , Basu Sanjib , Mahon Brett , Buckingham Lela , Walters Kelly Kaiser , Batus Marta , Hensing Thomas A. , Borgia Jeffrey A , Bonomi Philip D. 
Published: March 2020

e19117 Background: An epithelial phenotype in NSCLC is associated with improved sensitivity to EGFR tyrosine kinase inhibitors (TKI). The best method to identify this subset is unknown (Richardson Anticancer Research 2012, Byers Clin Cancer Res 2012). This retrospective study correlates E-cadherin (Ecad) and vimentin (vim) immunohistochemistry (IHC) expression with outcomes in advanced NSCLC patients (pts) treated with erlotinib (E). Methods: Advanced NSCLC pts that received E were included if sufficient tumor was available from diagnosis. IHC scores for E-cad and vim were generated by multiplying frequency (0-4) by intensity (0-4). Log Rank was used to correlate IHC expression with progression free and overall survival (PFS, OS). Results were compared to a subset of pts with tissue from primary surgical NSCLC resection who later received E for recurrent disease. Results: 159 advanced NSCLC pts treated with E had tissue from diagnosis and IHC analysis. There was no correlation with PFS or OS on E and high/low vim or Ecad expression. Subtracting the IHC scores (vim minus ecad) created a difference score. A low difference score (n = 62) correlated with prolonged PFS (2.6 vs 1.9 months, p = .014 HR 1.52) compared with a high score, n = 97. Low difference score trended toward prolonged OS (p=.46) 33 of the patients had tissue available from primary surgical resection. The invasive front was examined for membranous E-cad and cytoplasmic vim (Allred score 0-8). Patients with low vim (< 4) and Ecad (>5), n= 19, trended toward prolonged PFS and OS on E compared with patients with high vim (>5) and low Ecad (<6), n=10 (4.2 vs 1.6 months and 15.5 vs 6.5 months, respectively, p=NS). Conclusions: In this retrospective analysis, using unselected, frequently small tissue specimens, the expression of ecad or vim alone by IHC did not correlate with outcomes for E treated patients. A complicated difference score (vimentin score minus ecadherin score) did correlate with PFS on E. Examining EMT markers at the invasive edge of resected NSCLC tumors might more accurately assess EMT activity and its relationship to outcomes when these pts are recommended EGFR-TKIs.
Clinical experience of oxaliplatin-based regimen for patients with relapsed or refractory B-cell lymphoma: A Bangladesh perspective.
Authors: Hoque Ehteshamul 
Published: March 2020

e19501 Background: We performed a clinical study to evaluate the efficacy and toxicity of R-GemOx in the treatment of patients with relapsed or refractory B-cell lymphoma in Bangladeshi patient population. Methods: A total number of twenty (male 13, female 7, average age 60) patients with recurrent or refractory CD20 positive lymphoma, previously treated with CHOP of any performance status were eligible for inclusion. No primary and new cases were included. Treatment regimen consisting of rituximub 375 mg/m2, Gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2on day 1. Cycle was repeated every 3 weekly for six cycles. The patients were enrolled at our institution between December 2009 and December 2011. The primary endpoint was overall response rate and toxicity, assessed by Response Evaluation Criteria, secondary endpoints included both event free survival (EFS), and overall survival (OS). Results: A total of 20 patients were evaluable for efficacy and toxicity. The overall response rate was 75%. The EFS and OS under follow-up. No fatal toxicity was observed. Treatment was generally well tolerated. 13% patients complained about GIT upset (nausea, vomiting). Grade 3/4 neutropenia occurred in 8% of patients. Grade 2 neurotoxicity occurred in 5% of patients. No renal toxicity was observed. No other grade ¾ non hematological toxicity was observed. Conclusions: The combination of R-GemOx was effective in Bangladeshi patient population with Refractory B-cell lymphoma, with a predictable and manageable safety profile similar to that observed in Western patients.
Clinicopathologic features and treatment outcome of primary intestinal non-Hodgkin lymphoma: A single center experience.
Authors: Hsu Wei-Hsun , Yeh Kun-Huei , Lin Chung-Wu , Hsu Chih-Hung , Cheng Ann-Lii , Kuo Sung Hsin 
Published: March 2020

e19523 Background: Primary intestinal non-Hodgkin lymphoma (NHL) is a rare but heterogeneous disease in East Asia. However, the benefit of multidisciplinary treatment is still in debate. We characterized the clinicopathologic features, and treatment outcome in a single institute database. Methods: Patients with NHL primarily involving the intestine and treated during 1992 to 2008 were selected from the Cancer Registry of National Taiwan University Hospital. The medical charts and pathology records were carefully reviewed. Results: There were 64 men and 17 women with a median age of 51.5 years. Sites involved were colon/rectum (53.2%), small intestine (30.9%), and duodenum (13%). Histopathology subclassification included diffuse large B-cell lymphoma (DLBCL) (61.7%), mucosa-associated lymphoid tissue lymphoma (11.1%), Burkitt’s lymphoma (8.6%), T cell lymphoma (6.2%), follicular lymphoma (2.5%), mantle cell lymphoma (1.2 %) and others (8.6%). Ann Arbor stage IE to IIE accounted for 61.7%, whereas lower IPI score (1-2) were 54.8%. Among them, 27 patients received surgery plus chemotherapy, 60 received chemotherapy, and 4 had radiotherapy. At average follow-up of 48.7 months, 5 year survival rate were 59%, 43% and 51% for colon/rectum, small intestine, and duodenal NHL, respectively (p=0.45). Surgery plus chemotherapy versus chemotherapy alone showed no survival benefit in lower IPI group (p=0.682) nor in higher IPI (3-5) group (p=0.939). A trend of better median overall survival (mOS) was seen in rituximab group than in non-rituximab group in DLBCL subtypes (not reach vs. 39.8mo, p=0.075). In univariate analysis, stage III/IV (p=0.008), IPI score greater than 2 (p=0.011), and T cell histology (p<0.001) were significant prognostic factors for poor OS. In multivariate analysis, T cell histology remained the independent prognostic factor for inferior OS (p<0.001, HR: 20.3, 95% CI: 5.1-80.4). Conclusions: Although B cell NHL was the majority of primary intestinal NHL in our institute, T cell histology has significant inferior survival. Chemotherapy is still the backbone of treatment for primary intestinal NHL. The benefit of rituximab to intestinal DLBCL needs further confirmation.
Clinical features and outcome of follicular lymphoma: 17 years experience from All-India Institute of Medical Sciences (AIIMS), New Delhi, India.
Authors: Gogia Ajay , Raina Vinod , Sharma Atul , Kumar Lalit , Sharma Mehar C , Gupta Ritu , Das Prasenjit 
Published: March 2020

e19524 Background: Follicular lymphoma (FL) is second most common lymphoma in adult, constituted 20% of all lymphoma cases in the west. There is limited information is available on FL from India. Methods: The clinic-pathological profile, treatment outcome and prognostic factors for survival were assessed in 181 patients of FL seen at AIIMS, New Delhi, a large tertiary referral centre, over a period of 17 years (1996-2012). Results: There were 120 males and 61 females. The median age was 51 years (24-80 years). The common presenting features were lymphadenopathy 71%, fatigue 23% and fever 20%. Ann Arbor Rai stage distribution was: stage I - 9%, stage II - 11%, stage III -22 % and stage IV - 58%. Thirty six patients (20%) had ECOG performance status III/IV. Extra nodal involvement and bulky disease were present in 40 (22%) and 31 (19%) patients respectively. Follicular Lymphoma International Prognostic Index (FLIPI) 1 score : Low -25%, Intermediate-45% and high risk in 30% of cases. FL grade 1, 2 and 3 were seen in 63 ( 35%), 63 (35%) and 55 (30%) patients respectively. One forty five patients (80%) received treatment at presentation. Chemotherapeutic regimen used were: CHOP-45 , CVP-51, chlorambuil and prednisolone -7 , BR ( bendamustine and rituximab)-12, RCHOP- 14 and RCVP in 7 cases. The overall response (ORR) and complete remission (CR) rates were 70% and 35% respectively. Relapse occurred in 54 patients, 50 patients died and progression was observed in 63(35%) patients. Median overall survival (OS) and event free survival (EFS) was 5.5 years and 3.5 years respectively, with median follow up period of 3 years. Grade 3 histology, failure to attain CR, low serum albumin, PS III/IV, bulky disease and high risk FLIPI were significantly associated with lower event free survival. High risk FLIPI (HR 1.46, 95% CI 1.03-2.10, p=0.003) and failure to attain CR (HR 2.64, CI 1.10-4.30, p=0.001) were predictors of poor OS. Conclusions: FL represents 9 % of all lymphoma in adult. This is the largest data from single institute from India. Eighty percentage of patients presented in stage III/IV disease. High risk FLIPI and failure to attain CR were important prognostic variables for OS.
Pediatric hepatic angiosarcoma treated with chemotherapy and partial hepatectomy: A case report.
Authors: Faria Flavia Watusi 
Published: March 2020

e21001 Background: Hepatic angiosarcoma is a high-grade malignant neoplasm, extremely rare in children and associated with a poor prognosis. It is reported in English language less than fifty cases in children between 2 months and 15- year-old at presentation. Due to the rarity of this tumor type, little is known about effective systemic therapy. Many diferent schedules have been reported, comprising surgery only, neoadjuvant chemotherapy, surgery wih adjuvant radiotherapy and hepatic transplantation. The median survival rate stays between 10 to 48 months, independently of the treatment chosen, with inconsistent results. Methods: retrospective medical records review. Objective: We present our experience wih a female 3-year-old child presenting wih a huge unressectable liver angiosarcoma at diagnosis, treated with neoadjuvant intensive chemotherapy based on ifosfamide, carboplatine and etoposide and right hepatectomy. The child remained in complete remission for 5 years, after that presenting with local relapse treated again with the same intensive chemotherapy, resulting in a very good response. Conclusion: the children is alive after a relapsed hepatic angiosarcoma treated with neoadjuvant chemotherapy and partial hepatectomy. In this case, neoadjuvant chemotherapy based in carboplatine, ifofamide and etoposide was an effective strategy to treat pediatric hepatic angiosarcoma.
Prognostic factor and outcome of 32 patients with classic and iatrogenic Kaposi sarcoma: A monoinstitutional experience.
Authors: Rescigno Pasquale , Palmieri Giovannella , Nappi Lucia , Buonerba Carlo , Federico Piera , Ottaviano Margaret , Matano Elide , Bosso Davide , Policastro Tania , Izzo Michela , Di Lorenzo Giuseppe 
Published: March 2020

e21500 Background: Classic Kaposi Sarcoma (CKS) is a rare and mild form of the disease that primarily affects men, older than 50 years in the endemic areas. Iatrogenic KS (IKS) is associated with the use of steroids, immunosuppressive agents in patients with autoimmune diseases, inflammatory disorders, or organ transplantation. We have conducted a retrospective analysis from January 2008 to December 2012 for CKS and IKS to evaluated outcomes and potential prognostic factors in this rare disease. Methods: Patients with histologically proven KS lesions of the skin and negative HIV-1/2 were enrolled. In some cases diagnosis was completed by immunohistochemical tests for HHV-8 staining. Eligible patients received different systemic chemotherapy for disease at stage IIb and in all variants of stage III and IV, according Mediterranean KS staging. Results: 32 cases of non-AIDS KS were identified in this study. Mean age at diagnosis of the group was 70 year-old. Approximate male/female ratio was 2:1. 78.2% of cases was classic KS. All patients received systemic chemotherapy containing one of this agent: alkaloid of vinca, taxane, pegylated lyposomial doxorubicin. Ten patients (31.5%) experienced a partial response, a complete response was achieved in 4 patients (12.4%) and stability in 16 cases (50%). Two patients (6.2%) developed multiple local recurrences. PFS was 11.7 months while OS resulted 28.5 months. At multivariate analysis nodular lesions were related to lower PFS compared to macular lesions (HR: 2,5817, 95% CI 1,2911 to 5,1624; p: 0,0049), and HHV8 status (positive vs. negative) had a statistically significant correlation with a worse response to treatment (HR: 5,0289 95% CI 1,6540 to 15,2901; p: 0,0046). Conclusions: Classic and iatrogenic KS patients appears less aggressive, mostly limited to the skin and well-responsive on local or systemic therapeutic strategies. Our data show as positivity to HHV8 and nodular lesions correlate with a worse response to treatment.
Predictive and prognostic factors in locally advanced and metastatic sarcomas: A single institution experience.
Authors: El Mekkeoui Zineb Benbrahim , Arifi Samia , Boudahna Lamiae , Mellas Nawfel , El Mesbahi Omar 
Published: March 2020

e21513 Background: Ifosfamide is frequently applied in first line systemic therapy in sarcoma. Several, and sometimes, contradictory data have been reported in the literature regarding predictive factors of response and prognostic factors. The aim of this study was to assess predictive factors and factors associated with PFS and OS in patients with locally advanced and metastatic sarcoma treated with ifosfamide. Methods: We reviewed retrospectively 50 cases of sarcomas treated between January 2007 to June 2012 at the Medical Oncology Department at Hassan II University Hospital. Clinical, histopathologic and prognostic features were evaluated. Results: Median age was 30.9 ± 13 years. 56 % of patients were men. Synovialosarcoma was the predominant histologic type (23%). In 85% of cases, Ifosfamide was associated with Doxorubicine. The total dose of ifosfamide was 9g/m2 in 96% of cases. After A median duration of follow up of 15 months [3-26], the overall response rate was 57.7%. The median PFS was 6.1 months [3-13] and median OS was 10.04 months [3-23]. The Predictive factor of response was high grade (78% vs 41%; p=0.03). For PFS, the prognostic factor was high LDH level (5 vs 12 months p=0.01). For OS, prognostic factors were localization in upper extremity (8.5 vs 13 months ; p=0.03) presence of metastasis (7 vs 11 months; p=0.02) and high LDH level (7 vs 13 months; p=0.02). Conclusions: In patients with sarcoma treated with ifosfamide, the response rate is influenced by tumour grade. High LDH level was prognostic for both PFS and OS whereas upper extetermity site and presence of metastases were prognostic for OS only.
The use of new diagnostic tests for the monitoring of new and existing therapies for breast cancer patients.
Authors: Rotmann Andre 
Published: March 2020

e22006^ Background: Impaired glucose metabolism and elevated blood glucose levels have been linked with increased cancer risk and cancer mortality. Furthermore a diet with a high glycemic load and carbohydrate intake is positively associated with an increased cancer risk in a subgroup of breast cancer patients. New therapies have been established addressing new targets controlling glucose metabolism. Upregulation of glucose metabolism in cancer can be in vivo visualized by the imaging technique FDG-PET. Recently it has been shown that the detection of the biomarker transketolase-like-1 (TKTL1) in macrophages allows the non-invasive detection of upregulated glucose metabolism in cancer patients. The epitope detection in macrophages (EDIM) has been established as a new technology for a non-invasive biomarker based detection and characterization of tumors as well as early detection of recurrence and/or metastasis. The biomarker Apo10 is highly specifically expressed in tumor cells irrespective of the tumor entity. Apo10 and TKTL1 offers the possibility to detect abnormal cell proliferation and up-regulated glucose metabolism, indicating neoplasias and the degree of malignancy. This new technology could be used to identify patients that will benefit from existing and new approved therapies. Recently the mTOR inhibitor everolimus has been approved for a subgroup of advanced breast cancer. Metformin, a drug addressing glucose metabolism, has been shown to reduce the incidence of invasive breast cancer in postmenopausal women. Methods: We use the EDIM-tests for early detection, monitoring and in aftercare. Additional we use the test to monitor new therapies. The results where compared to clinical observations and laboratory data. Results: Up to now we have tested more than 100 women with breast cancer for a period up to 4 years. Our results show a good concordance between the EDIM-tests and the clinical observations. Conclusions: Our data from patients with breast cancer are promising results worth to be further validated. The combination of the biomarkers Apo10 and TKTL1 with EDIM-technology could be a useful tool to identify and monitor cancer patients and the use of new therapies.
Treatment implications for immunohistochemistry-based diagnoses with low positive predictive value.
Authors: Pillai Raji , Handorf Charles , Henner William David 
Published: March 2020

e22033 Background: In a recent study (Handorf, C. et al., Am. J. Surg. Pathol., in press), the accuracy of tumor diagnoses using immunohistochemistry (IHC) (83%) was directly compared to accuracy of gene expression profiling (GEP) (89%). However, in clinical practice, IHC is more commonly used initially and GEP is used secondarily in difficult-to-diagnose cases. For this reason, it is important to identify which IHC-based diagnoses have a low positive predictive value (PPV) and therefore might benefit from the addition of GEP or other diagnostic procedures. Methods: The direct comparison study included 157 metastatic tumors of known origin that represented 15 possible tumor types. A panel of four board-certified anatomic pathologists was blinded to the primary site and each pathologist used IHC to render final tumor diagnoses. 472 specimen reviews and diagnoses were performed. The fraction correct (PPV) for the diagnoses rendered for each of the 15 tumor types in the study were compared. Results: The PPV for each of the 15 tissue types diagnoses was either: low (gastric, 29%; pancreatic, 31%; non-small cell lung, 55%), moderate (prostate, renal, hepatocellular, ovarian and colorectal, 85-90%) or high (bladder, breast, testicular germ cell, non-Hodgkin’s lymphoma, melanoma, sarcoma and thyroid, 94-100%). Among the 90 diagnoses of tissues with low PPVs (gastric, pancreatic and non-small lung cancer) there were 59 incorrect diagnoses. For 23 of those 59 diagnoses, the actual tumor type is treatable for prolonged survival including: breast (N=11), colorectal (N=6), ovarian (N=3) and prostate (N=3) cancer. Conclusions: The PPV for IHC-based diagnoses of primary site varies substantially depending of the type of tissue diagnosed. Pathologists should consider the likely PPV of their IHC-based diagnoses of primary site when considering the use of GEP or other methods to refine their diagnosis. For many of the IHC-based primary site diagnoses with low PPVs, the correct primary site diagnosis may allow treatment for prolonged survival.
ALK-immunohistochemistry (IHC) standardization with D5F3 antibody in non-small cell lung carcinoma (NSCLC): An international consensus study.
Authors: Hirsch Fred R. , Yatabe Yasushi , Dietel Manfred , Sholl Lynette M. , Tsao Ming Sound , Schuuring Ed , Tubbs Raymond R. 
Published: March 2020

e22042 Background: The outcome of patients with advanced NSCLC with ALK fusions detected by ALK FISH has improved significantly when treated with crizotinib. ALK IHC*, which is a relatively inexpensive assay, correlates well with ALK FISH. An international ALK IHC project was initiated to formulate scoring standardization and assess reproducibility of an ALK IHC assay. Methods: Using ALK FISH status (Abbott, Des Plaines, IL) as the enrollment criteria, formalin-fixed paraffin-embedded tumors from 103 NSCLC patients from 6 different institutes were stained and analyzed for ALK protein expression using a recently developed fully automated ALK IHC assay (Ventana, Tucson, AZ). Seven international observers blindly assessed the specimens as “positive” or “negative” after two training sessions and the use of an assessment manual. Results: The agreement between ALK IHC and ALK FISH for evaluable cases where 4/7 or 6/7 readers agreed on ALK status was 92/98 cases (93.9%, 95%CI 87.3-97.2) and 90/96 cases (93.8%, 95%CI 87.0-97.1) overall; positive IHC agreement was 39/43 cases (90.7%, 95%CI 78.4-96.3) for both methods; negative IHC agreement was 53/55 cases (96.4%, 95%CI 87.7-99.0) and 51/53 cases (96.2%, 95%CI 87.2-99.0), respectively. Average inter-observer agreement was 1987/2032 reads (97.8%, 95%CI 95.9-99.1) overall; average positive agreement was 1,710/1,755 reads (97.4%, 95%CI 95.0-99.1); average negative agreement was 2,264/2,309 reads (98.1%, 95%CI 96.4-99.3). Of the 6 discrepant cases, 4 were unanimously scored as ALK IHC negative with ALK FISH being positive. Two were confirmed by chromogenic ISH to be ALK rearranged, one was unevaluable, and one was genomically heterogeneous. The remaining 2 discrepant cases were discordant among scorers relating to ALK IHC cellular compartment staining in one case and a minute sample size showing ALK IHC staining in the other. Conclusions: ALK IHC standardized assessment achieved high inter-observer reproducibility among an international panel of participants and high correlation with ALK FISH. A screening strategy using ALK IHC should be considered.*ALK IHC has not been approved for use in the US as a diagnostic for crizotinib.