tbuckley/cabot-search huggingface dataset:
Second malignant tumors in childhood cancer survivors.
Authors: R. Kebudi, I. Ayan, O. Gorgun, F. Y. Agaoglu, G. N. Ozdemir, Y. Dizdar, B. Zulfikar, E. Darendeliler
Journal: Journal of Clinical Oncology (2011)

9573 Background: The risk of second malignancies is 3-6 times more in childhood cancer survivors. The 20 year cumulative risk of secondary malignancies in 14,193 chilhood cancer survivors followed for >5 years was 3.2% (Cancer 2005). Methods: 1,500 childhood cancer survivors treated between 1990-2010 in the Istanbul University, Oncology Institute were evaluated for second malignancies. Results: 16 second malignancies were identified in 15 childhood cancer survivors in a median time of 6 years. The 16 second malignancies were: 4 acute myeloblastic leukemias (AML), 2 malignant nerve sheath tumors (MNST), 8 sarcomas, 2 breast cancers. AML was diagnosed in 4 children in a median of 31 months (13-60 mo): The primary diagnosis were Ewing’s sarcoma, osteosarcoma, non-Hodgkin’s lymphoma and neuroblastoma. Two of these children had recieved multiple therapies for recurrences. Two children with a primary diagnosis of medulloblastoma and neuroblastoma developed MNST in the radiation field after 9 years. A Ewing sarcoma patient developed sarcoma after 6 years, an osteosarcoma patient developed breast cancer after 8 years, an ALL patient developed Ewing sarcoma after 3 years, a mesenchymal chondrosarcoma patient developed breast cancer after 11 and osteosarcoma after 16 years. These were not in the radiation field. A soft tissue sarcoma, and an osteosarcoma developed in two bilateral retinoblastoma patients both after 14 years, a sarcoma developed in a rabdomyosarcoma patient after 6 years and in a patient treated for nasopharyngeal carcinoma after 3.5 years all in the radiation field. An extremity osteosarcoma developed in another bilateral retinoblastoma patient after 4 years. The two patients that developed breast cancer and the six patients that developed sarcoma are alive. All others are dead of disease. Conclusions: The risk of secondary malignancies in our series is 1% and low in comparison to the literature. However, it has increased within years and may still increase as the follow-up time increases. Since, the risk of second malignancies is associated with the cumulative dose of some chemotherapeutics, the radiation dose/field, the use of minimal therapy that has the maximum efficacy according to the diagnosis, age, stage and risk of the patient is important.
Peripheral primitive neuroectodermal tumors: Analysis of 23 Chinese cases
Authors: H. Song, L. Chen
Journal: Journal of Clinical Oncology (2008)

21514 Background: The objective was to investigate the clinical feature of Chinese peripheral primitive neuroectodermal tumor (pPNET). Methods: Collected the medical records of 23 Chinese pPNETs, summarized the clinical feature and followed up the survival time. Results: There were 13 males and 10 females, median age 27.3 years. Trunks, limbs and the soft tissues of central axis, such as chest wall, vertebral column and abdominal cavity were often the primary lesions with gradually increasing tumors. Diagnosis depended on pathology, and there were no specificity indexes on laboratory or imageology examinations. Surgery was the most important treatment, combined with chemotherapy and radiotherapy. Mean survival time was 15.9 months. Patients who were younger than 16 years, localized on abdominal cavity or received nonstandard treatment had a relatively poor prognosis. Conclusions: PPNET was an extremely malignant tumor which often happened to adolescents. Diagnosis depended on pathology. Surgery combined with chemotherapy and radiotherapy in time could prolong the survival time. No significant financial relationships to disclose.
Effect of metformin on survival of diabetic patients with pancreatic adenocarcinoma.
Authors: N. Sadeghi, J. L. Abbruzzese, S. J. Yeung, M. Hassan, D. Li
Journal: Journal of Clinical Oncology (2011)

4063 Background: There is increasing epidemiological and experimental evidence that the common antidiabetic drug, metformin, has antitumor activity. Methods: We conducted a retrospective cohort study to examine the survival benefit of metformin in diabetic patients with pancreatic cancer (PC). A total of 190 patients who carried the diagnosis of diabetes mellitus and PC at the time of their initial visit were identified from a case control study conducted at MD Anderson Cancer Center (MDACC) during 2000 to 2009. An additional 112 cases were identified from the MDACC tumor registry during the same study period. Information on diabetes history was obtained by personal interview and medical record review for the two groups, respectively. Because most patients received combination therapies for glycemic control, we compared metformin ever-users and never-users regardless other antidiabetics in this study. Multivariate Cox proportional hazard regression model was used to evaluate the influence of metformin therapy on overall survival (OS). Results: There was no significant difference in the distribution of age, sex, race, stage, tumor size, resection status, ECOG performance status (PS), serum CA19-9, or cancer treatment between metformin ever-users (n=117) and never-users (n=185). Prevalence of tumors involving pancreatic tail, however, was higher in metformin ever-users than never-users (20.9% vs. 11.5%, p=0.029). Patients with lower surgical stage, metformin use, low serum CA19-9 (< population median), better PS, resected tumor, negative surgical margins, and smaller tumor, had longer OS. The median survival was 16.6 vs. 11.5 months for metformin ever-users vs. never-users, respectively (p=0.0044). Metformin users had a 33% decrease in risk of death; hazard ratio (HR) = 0.67 (95% CI: 0.51-0.88, p=0.005). The HR remained significant even after adjusting all other clinical predictors (HR=0.63, 95%CI=0.46-0.85, p=0.003) or exclusion of insulin user (HR=0.58, 95%CI=0.40-0.83, p=0.003). Conclusions: Our study suggests that metformin may improve the outcome in diabetic patients with PC independent of other known prognostic factors. Further prospective studies are required to validate results of this study.
A model of comparative effectiveness research (CER): The impact of biologic agents in a cohort of patients from ethnic minorities with metastatic colorectal cancer (mCRC).
Authors: Umang Shah, Ashish Abhay Khot, Dharmendra Goyal, Shuang Guo, Andreas Kaubisch, Lakshmi Rajdev, Sanjay Goel, Santiago Aparo
Journal: Journal of Clinical Oncology (2014)

591 Background: The role of biologic agents in the treatment of mCRC has been studied in clinical trials. These studies included ≥ 90% patients (pts) of white race. Hispanics and blacks were largely underrepresented. CER allows exploration of the impact of biologic agents in a cohort composed largely of pts from minorities. We present the results of a cohort of pts served by Montefiore Einstein Cancer Center (MECC) in Bronx, NY. Methods: Pts diagnosed and treated for mCRC from January 2000 to December 2011 were identified using data from the MECC Cancer Registry. Pts demographic and clinical characteristics were extracted from pts medical records. A Cox proportional–hazard model was used to assess survival differences between pts treated with chemotherapy alone vs. pts treated with chemotherapy plus biologics. Results: A total of 293 pts where identified; 45% were black, 27% were Hispanic, and 28% were white. Of the pts receiving biologics, 90% received bevacizumab and 50% received cetuximab or panitumumab. The median overall survival was 15.2 months in the chemotherapy alone group and 25.6 months chemotherapy + biologics group (p=0.003). Univariate analysis showed that 1 metastatic site vs. ≥ 2, CEA &lt;40 ng/mL, receiving ≥ 2 lines of chemotherapy and exposure to biologics were independently associated with longer survival. Multivariate analysis of the whole cohort (n=290), which included all ethnic groups, showed that exposure to biologics offered a survival benefit (HR of 0.70, 95%CI 0.52–0.93, p=0.02), after adjusting for gender, age, CEA, number of metastatic sites and lines of chemotherapy received. Subgroup analysis based on ethnicity showed survival benefit for Whites (HR of 0.38, 95%CI 0.22–0.66, P=0.001) but not for Hispanics (HR of 0.65, 95%CI 0.35–01.23, p=0.18) nor Blacks (HR of 1.04, 95%CI 0.63–1.70, p=0.87). Conclusions: In this cohort weighted heavily towards ethnic minorities, the addition of biologics to chemotherapy was associated with longer survival, an effect mainly driven by whites. Hispanics and blacks did not seem to benefit from exposure to biologics. An effort should be made to include minority pts in ongoing clinical trials.
Content analysis of postings in a stomach cancer survivor and caregiver support group on Facebook.
Authors: James Randolph Hillard
Journal: Journal of Clinical Oncology (2015)

223 Background: Patients diagnosed with cancer are increasingly turning to patient created social media groups to connect with others suffering from similar conditions. These groups allow sharing of information and support between their members, without involving medical or mental health professionals. This study examines the content of communications within one of these groups in order to identify the needs these groups are addressing, and in order to explore implications for mental health. Methods: This study focuses on a single Facebook group for stomach cancer patients and caregivers which has grown from 239 members a year ago to 1,128 members now and which has been operating for about four years. Two thirds of members are cancer patients, and the rest are caregivers. About 75% of members are from the US. The age range is 40-79, with a mean of 54. Members are 55% women, and 80% are middle class. Most members have been in the group for six to twelve months. The site averages about five original posts and about 50 responses a day. 100 consecutive posts were assigned to one of 12 pre-selected content categories. Results: Primary purpose of each of 100 consecutive posts (1) Sharing updates on their condition: 14 (2) Questions about treatment side effects: 13 (3) General requests for information: 13 (4) Requests for support or prayers: 11 (5) Sharing good news: 11 (6) Welcoming new members: 11 (7) Giving general support: 9 (8) Announcing a death: 5 (9) Sharing information about new treatments: 5 (10) Sharing humor: 4 (11) Sharing bad news: 2 (12) Asking "How are you?": 2. Conclusions: This Facebook group served many of the same functions that are served by face to face support groups for cancer patients. Members routinely shared intimate details with each other, and they routinely asked questions about their illness that they could not get answers to anywhere else. Leaderless Facebook groups such as this one are an important, and little studied, psychological resource for patients suffering from cancer.
HER2 testing in esophageal adenocarcinoma (EAC) using parallel tissue-based methods.
Authors: Harry H. Yoon, Qian Shi, William R. Sukov, Christopher A. Sattler, Anne E. Wiktor, Tsung-Teh Wu, Robert B. Diasio, Robert B. Jenkins, Frank A. Sinicrope
Journal: Journal of Clinical Oncology (2013)

2 Background: Testing for HER2 in EAC has become routine given its ability to predict benefit from HER2-targeted therapy. HER2 protein analysis by immunohistochemistry (IHC) is more rapid and generally less expensive than assessment of gene amplification by fluorescence in situ hybridization (FISH). However, the accuracy of IHC for predicting HER2 amplification has not been examined in a large EAC cohort. Methods: Surgical EAC specimens were examined from 675 patients who underwent curative resection at a single institution without preoperative therapy. Tumors were located in the esophagus (47%) or gastroesophageal junction (53%); most were node-positive (73%). Every tumor was evaluated by IHC in parallel with FISH in a blinded manner using FDA-approved assays. A consensus IHC score was determined by 2 pathologists using tumor-specific criteria (negative, 0 or 1+; equivocal, 2+; positive, 3+). Gene amplification by FISH was defined as a HER2/CEP17ratio ≥ 2. Results: HER2 amplification was detected in 89% of IHC 3+ cases, 13% of IHC 2+ cases, and 4% of IHC 0-1+ cases (Table). Accordingly, using FISH as the reference standard, the positive predictive value (PPV) of a positive IHC test (3+) was 89% (79/89 [95% CI 82%-95%]), and the negative predictive value of a negative IHC test (0-1+) was 96% (401/417 [94%-98%]). Importantly, the PPV of an equivocal IHC score (2+) for detecting HER2 amplification was 13% (22/169 [8%-18%]). Conclusions: In the largest study to date comparing HER2 testing methods in EAC, a negative IHC result (0 or 1+) nearly excludes the presence of gene amplification by FISH. Whereas a positive IHC result (3+) strongly predicts for the presence of amplification, an equivocal IHC result (2+) is a weak predictor. These findings in EAC support a HER2 testing algorithm where IHC is used for initial screening and FISH testing is restricted to cases with equivocal IHC results. [Table: see text]
Phase I study of aflibercept (VEGF Trap) and temozolomide in newly diagnosed, high-grade glioma.
Authors: J. F. De Groot, T. Cloughesy, F. S. Lieberman, S. M. Chang, A. M. P. Omuro, J. Drappatz, T. Batchelor, L. M. DeAngelis, M. R. Gilbert, W. K. A. Yung, J. D. Fisher, X. Ye, K. Lamborn, A. P. Chen, S. A. Grossman, M. Prados, P. Y. Wen
Journal: Journal of Clinical Oncology (2011)

2043 Background: Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGFA, VEGF-B and placental growth factor (PlGF), depleting circulating levels of these growth factors. Methods: The Adult Brain Tumor Consortium (ABTC) conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed high-grade gliomas (HGG). Three cohorts were examined: Cohort 1: Aflibercept with radiotherapy and concomitant temozolomide; Cohort 2: Aflibercept and adjuvant temozolomide using the 5/28 regimen; and Cohort 3: Aflibercept and adjuvant temozolomide using the 21/28 day regimen. Eligibility criteria included histologically proven newly-diagnosed glioblastoma (GBM) or anaplastic glioma (AG), > 18 yrs old, KPS > 60, adequate bone marrow reserve and organ function. Patients initially received 2 mg/kg of aflibercept every 2 weeks. If no dose-limiting toxicities (DLT's) were observed the dose was increased to the single agent dose of 4mg/kg every 2 weeks in the next cohort of patients. No further dose escalation was permitted. Dose-finding used a standard 3 + 3 design with the MTD defined as the dose where DLT's occurred in fewer than 1/6 patients. At least 6 patients were treated at the MTD. Once this was defined, an additional 9 patients were treated for a total of 15 patients. Results: To date 48 patients have been enrolled, of whom 43 were evaluable. Median age was 56.9 years (23.91-69.19); median KPS 90 (70-100). The MTD of aflibercept for all 3 cohorts was 4mg/kg every 2 weeks. DLTs at the MTD were: Cohort 1: 0/6 patients; Cohort 2: 2/15 patients (G3 DVT, G4 ANC; Cohort 3: 3/15 patients (G4 biopsy-confirmed thrombotic microangiopathy; G3 rash, G4 thrombocytopenia). Conclusions: The combination of aflibercept and TMZ was generally well tolerated. The recommended phase II dose of aflibercept with radiotherapy and concomitant and adjuvant temozolomide is 4mg/kg every 2 weeks.
Observational study of first-line therapy, including cetuximab in cases of nonresectable colorectal cancer: CORAL (interim report).
Authors: Hiroki Hashida, Kei Muro, Michio Itabashi, Yasuo Ohashi, Kenichi Sugihara
Journal: Journal of Clinical Oncology (2015)

681 Background: Cetuximab (Cmab) + chemotherapy is now indicated in various treatment guidelines as a first-line therapy for non-resectable metastatic colorectal cancer (mCRC). The efficacy of Cmab + FOLFIRI has been demonstrated in CRYSTAL, but its efficacy and safety in combination with other regimens is unclear. There are few reports on Cmab combination therapy as first-line chemotherapy in Japan, and there are no reports of treatment results in the ESMO guideline groups 1, 2, and 3. Therefore an observational study was planned to evaluate the efficacy and safety of first-line therapy including Cmab, and to clarify the treatment results by group. This study received support from the Public Health Research Foundation’s Comprehensive Support Project for Oncology Research (CSPOR). Methods: The subjects were mCRC patients who received Cmab as first-line therapy either as combination therapy or monotherapy. Endpoints were response rate, PFS, and reason for discontinuation of first-line treatment (curative resection, PD, adverse events). To evaluate safety, skin conditions (incidence, degree, previous history) and other adverse events were investigated. Results: Among 579 patients enrolled at 158 institutes from January 2012 until June 2013, 575 were subjected to analysis. Background factors were PS 0/1/2 at 406/143/26, males females at 368/207, median age of 65 (31-88), groups 1/2/3 at 172/229/174, and concomitant drugs were oxaliplatin/irinotecan/others at 377/173/25. Response rate in the evaluable cases was 57%, and in groups 1/2/3 was 65%/54%/53%. The 1-year survival rate in groups 1/2/3 was 93%/61%/78%. In adverse events, the incidence of skin conditions (rash acneform) at 8 weeks/16 weeks was 69%/60% in patients with no history of acne vulgaris (2%/8% at G3 or higher) and 83%/81% in those with a previous history (13%/14% at G3 or higher). Conclusions: We reported treatment results according to ESMO guideline groups on the efficacy and safety of Cmab as first-line therapy in mCRC patients. Response rate and survival were higher in group 1. Survival outcomes after 1 year will be followed up. Clinical trial information: UMIN000007275.
Distinguishing between nodular and superficial spreading melanoma using specific microRNA alterations.
Authors: L. Poliseno, A. Haimovic, D. Hanniford, M. F. Segura, P. J. Christos, R. L. Shapiro, A. C. Pavlick, R. S. Berman, E. Hernando, J. Zavadil, I. Osman
Journal: Journal of Clinical Oncology (2011)

8540 Background: Distinct molecular alterations in acral, mucosal and uveal melanoma subtypes have been recently reported and have prompted the development of tailored treatment approaches. Superficial spreading melanoma (SSM) and nodular melanoma (NM), the 2 most common types of cutaneous melanoma (70% and 20% respectively), are currently perceived as sequential phases of linear progression from radial to vertical growth. However, clinicopathological data from our group and others suggest that SSM and NM might be two biologically different entities. In this study, we used microRNA profiling to identify the signature that distinguishes SSM from NM. We further determined the association between decreased expression of SSM-specific microRNAs and loss of the corresponding genomic loci. Methods: miRCURY LNA microRNA Arrays were used to profile RNA isolated from 82 micro and macrodissected primary melanomas (26 SSM and 56 NM) and 9 congenital nevi. Differentially expressed microRNAs were identified using T test (p<0.05) and SAM (FDR<10%) analyses. The genomic loci corresponding to specific microRNAs were examined in 4 “radial growth phase-SSM like” and 6 “vertical growth phase–NM like” melanoma cell lines, as well as in an independent validation cohort of 25 primary melanomas. Results: We identified a signature of 134 microRNAs that distinguishes SSM from NM (59 microRNAs showed higher expression in SSM compared to NM and 75 microRNAs showed lower expression in SSM compared to NM). 31 of the microRNAs that were expressed at lower level in SSM compared to NM showed lower expression compared to nevi as well (p<0.05). Downregulation of 7 known tumor-suppressive microRNAs (let-7g, miR-15a, miR-16, miR-138, miR-181a, miR-191 and miR-933) was associated with selective loss of the corresponding genomic loci in SSM but not NM in the melanoma cell lines and in the independent validation cohort (p<0.05). Conclusions: Our data support a new molecular classification model in which SSM and NM are molecularly distinct phenotypes as opposed to sequential phases of melanoma progression. New therapeutic strategies taking into account the subtype-specific alterations that we have identified might improve the outcome of melanoma patients.
Effect of denileukin diftitox on serum GM-CSF and clinical responses in stage IV melanoma.
Authors: J. Chesney, M. A. Rasku, A. C. Klarer, D. M. Miller, S. Telang
Journal: Journal of Clinical Oncology (2011)

2507 Background: We have previously demonstrated that administration of a recombinant interleukin 2/diphtheria toxin conjugate (DAB/IL2; ONTAK; Denileukin Diftitox) to melanoma patients transiently depletes T cells, including regulatory T cells, and promotes the expansion of melanoma-specific effector T cells. The goals of this study were to examine the effects of DAB/IL2 on additional lymphocyte subsets, monocytes, neutrophils and GM-CSF and assess clinical efficacy in stage IV melanoma patients. Methods: We first administered DAB/IL2 (12 µg/kg; daily x 4 days; 21 day cycles) to 10 stage IV melanoma patients and measured effects on lymphocyte subsets and myeloid-derived cells by flow cytometry and serum GM-CSF by ELISA. We then determined objective response rates (using FDG-PET and CT) and one year survival in a total of 60 patients given DAB/IL2. Results: We found that DAB/IL2 transiently depleted total lymphocytes, NK, B and T cells and conversely increased monocyte and neutrophil counts with a coincident increase in serum GM-CSF (baseline, 0.54 ± 0.27; day 7, 1.38 ± 0.19 pg/ml, p value <0.01). 16.7% of patients had partial responses, 5% stable disease and 15% mixed responses (83% of these patients were pre-treated with 1-5 prior systemic regimens). However, 45.5% of the chemo/immune-naïve patients, the majority with visceral metastases (stage M1C), had partial responses including delayed tumor regressions and durable stability of residual metastases, indicating a potential immunotherapeutic mechanism. While the total 1 year survival was 40 ± 6.2%, the partial responder 1 year survival was 80 ±11.9% ( p value < 0.001). Conclusions: Taken together, these data indicate that DAB/IL2 demonstrates significant clinical activity in chemo/immune-naïve stage IV melanoma patients that may be due to a combination of transient depletion of multiple lymphocyte subsets including regulatory T cells, stimulation of GM-CSF secretion and myeloid cell expansion. The high partial response rate in naïve patients coupled to the improved 1 year survival in responders supports the conduct of additional trials of DAB/IL2 for the treatment of metastatic melanoma.