tbuckley/cabot-search huggingface dataset:
Cardiovascular morbidity and mortality in patients treated for ductal carcinoma in situ of the breast.
Authors: Naomi B. Boekel, Michael Schaapveld, Jourik A. Gietema, Emiel J. Rutgers, Michel I.M. Versteegh, Otto Visser, Berthe M. Aleman, Flora E. van Leeuwen
Journal: Journal of Clinical Oncology (2013)

58 Background: Recent concerns about potential overdiagnosis and overtreatment of ductal carcinoma in situ of the breast (DCIS) render evaluation of late effects of treatment, such as cardiovascular disease (CVD), of great importance. We studied cardiovascular morbidity and mortality in a large population-based cohort of DCIS patients. Methods: Data on all incident DCIS diagnosed before the age of 75 years between 1989 and 2004 in the Netherlands were obtained (n = 10,468). Cardiovascular morbidity and mortality data was acquired through linkage with population-based registries. Risk of CVD in the study cohort was compared with general population rates and evaluated in Cox proportional hazards regression models. Results: Compared with the general population, five-year survivors of DCIS had a similar risk of dying due to any cause (standardized mortality ratio (SMR)=1.04 95% confidence interval (CI) 0.97-1.11), but a lower risk of dying of CVD (SMR=0.77 95% CI 0.67-0.89). When comparing treatment groups within the cohort, no difference in risk of CVD was found when comparing patients treated with radiotherapy to surgery only. Left- versus right-sided radiotherapy did also not increase this risk (hazard ratio (HR)=0.93 95% CI 0.67-1.30). In a subgroup analysis of patients diagnosed between 1997 and 2005, accounting for overall history of CVD before DCIS diagnosis, we did not observe a risk difference between treatment groups (left- versus right-sided radiotherapy HR=0.95 95% CI 0.69-1.30). When taking into account CVD that occurred two years prior to DCIS diagnosis only, however, a statistically non-significantly increased risk was seen for patients with a history of CVD (HR=1.84 95% CI 0.45-7.50). Conclusions: After a median follow-up of ten years, we did not find an increased risk for cardiovascular morbidity or mortality after radiotherapy for DCIS when comparing surgery and radiotherapy versus surgery only, nor when comparing radiotherapy for left- versus right-sided DCIS. Compared to the general population, DCIS patients have a decreased risk of cardiovascular death, independent of treatment.
Phase I/II study of tumor-infiltrating lymphocyte (TIL) infusion and low-dose interleukin-2 (IL-2) in patients with advanced malignant pleural mesothelioma (MPM).
Authors: Mark Doherty, Natasha B. Leighl, Ronald Feld, Penelope Ann Bradbury, Lisa Wang, Jessica Nie, P Yen, Michael Pniak, Linh T. Nguyen, Marcus O. Butler, Marc de Perrot
Journal: Journal of Clinical Oncology (2015)

TPS7586 Background: MPM is a disease with poor outcomes, and only modest benefits from existing systemic therapies. Preclinical studies have shown that MPM often contains populations of TILs, and that these can be expanded ex vivo. Therapy using autologous TIL infusions and IL-2 following lymphodepleting chemotherapy has been successfully used in advanced melanoma. The therapeutic potential for TILs in MPM has not yet been explored. Methods: This is a single arm, phase I/II study to evaluate the feasibility, safety, and efficacy of TIL therapy for advanced MPM at the Princess Margaret Cancer Centre. Eligibility criteria include: advanced MPM, suitable surgical candidate for TIL harvesting from tumor, ECOG performance status 0-1, adequate organ function, and successful expansion of TILs. TILs are harvested from fresh tumor tissue, evaluated for suitability, and expanded ex-vivo. Patients are treated with a lymphodepleting chemotherapy regimen containing cyclophosphamide (60mg/m2 x 2 days) and fludarabine (25mg/m2 x 5 days), followed by infusion of expanded TILs. This is followed by low-dose IL-2 therapy (125000 IU/kg/day subcutaneously) for 2 weeks. The treatment protocol is adapted from that used in melanoma TIL studies, and no dose exploration is planned. The primary objective is determining the feasibility and safety of the regimen. Efficacy as measured by objective response rate (modified RECIST) is a secondary objective. The planned sample size is 10 patients. An informal interim analysis will be performed after 6 patients have been treated to review treatment toxicities and feasibility, given the lack of previous experience with this treatment in MPM. Correlative studies include analysis of peripheral blood mononuclear cells and assessment of persistence of infused TILs. Patients are currently being screened for TIL expansion at the Princess Margaret Cancer Centre.
Enhanced overexpression of hypoxia-related miRNA-210 in primary tumor of metastatic prostate cancer.
Authors: Okyaz Eminaga, Jochen Fries, Fabian Woetzel, Ute Warnecke-Eberz, Susanne Neiss, Michaela Heitmann, Jan Herden, Udo Engelmann, Axel Heidenreich
Journal: Journal of Clinical Oncology (2016)

166 Background: miR-210 is a known transcriptional target of the hypoxia-responsive HIF-1α signaling pathway. However, the association between the expression of miR-210 and the tumor progression in prostate cancer (PCa) remains unclear. Methods: We isolated miRNA by miRNeasy FFPE kit (Qiagen, Hilden, Germany) from paraffin-embedded tissues of 87 prostate specimens with adenocarcinoma of the prostate cancer in different tumor stages, with high-grade prostatic intraepithelial neoplasia (HGPIN) and normal tissues. Organ-confined PCa was defined as PCa with pT2 tumor stage, Gleason score ≤ 7a and PSA level &lt; 10 ng/ml. PCa with pT3/4 or Gleason &gt; 7a was defined as advanced PCa. PCa with pN1 were considered as metastatic diseases. Additionally, 3 cases with castration-resistant prostate cancer (CRPC) were considered. Quantitative miR-210 expression data were acquired and analyzed using a real-time TaqMan-based PCR with the ABI Prism 7900HT (Life Technologies, Darmstadt, Germany). ANOVA and post hoc analysis according to Turkey were performed using SPSS 22 (IBM, Armonk, USA). For silico analysis, Diana tools were applied to determine target genes of miR-210 and related functions and pathways. All the statistical tests were two-sided, and the level of statistical significance was set at P &lt; 0.05. The small nuclear U6 RNA was used as an endogenous control. Results: ANOVA revealed significant differences in expression levels of miR-210 according to the tumor progression. Interestingly, organ-confined PCa showed the lowest expression level of miR-210 in our analysis. No sig. differences in miR-210 expression between normal tissues, HGPIN and organ-confined PCa and between advanced PCa, metastatic diseases and CRPC were observed. However, miR-210 expression was significantly higher in metastatic diseases and CRPC in comparison to organ-confined PCa. The silico analysis showed that genes regulated by miR-210 were associated with homologous recombination, non-homologous end-joining, the cell cycle regulation and synthesis of DNA. Conclusions: We observed an enhanced overexpression of hypoxia-related miRNA-210 in primary tumor of metastatic prostate cancer and CRPC in comparison to organ-confined PCa.
Racial and sex disparities in changing trends of squamous cell cancer of the anus (SSCA).
Authors: Arjun Gupta, Hong Zhu, Alana Christie, Jeffrey John Meyer, Saad A. Khan, Muhammad Shaalan Beg
Journal: Journal of Clinical Oncology (2016)

520 Background: Squamous cell carcinoma of the anus (SSCA) is one of only few cancers with rising incidence in the United States (US). This is believed to represent changing epidemiology of human papillomavirus (HPV) and Human Immunodeficiency Virus (HIV). We explored the racial and sex disparities in the rising incidence of SSC. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify subjects with SCCA from 2000-2012. Age-standardized incidence rates (IR) per 100,000 for 2000-2012 time period were generated in Rate Session in SEER for white males (WM), white females (WF), black males (BM) and black females (BF). The 2000 US standard population was used for age standardization. The trend of change of IR between groups was compared by testing the interaction between time and group in the linear regression model. SAS 9.4 was used for analysis Results: Among 11,739 new cases of SSCA racial and sex distribution of cases was WM:32%, WF:54%, BM:5.4%, BF:5.4%. Median overall survival (OS) was WM:101 months (m), WF:139 m, BM: 71 m, BF 103 m (p &lt; 0.005). The IR had the highest rate of increase for WF and BM (0.06/100,000 cases annually) while rates for BF and WM increased by 0.04 and 0.02/100,000 cases annually respectively. The overall test for difference in trend among WF, WM, BF and BM groups had a p-value of 0.0099. Conclusions: The rate of increase of SSCA IR is highest for WF and BM. Additionally WF have the highest age standardized incidence of SCCA as well as the highest OS compared to other groups. These data support disparities in epidemiology and survival of anal cancer.
Clinical Significance of Positive Clostridium Difficile (CD) Toxin in the Stool of Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT).
Authors: Yoshiki Terada, Yasushi Onishi, Sung-Won Kim, Masahiro Kami, Shin-ichiro Mori, Yuji Heike, Yoichi Takaue, Ryuji Tanosaki
Journal: Blood (2004)
Gallbladder cancer: The forgotten medical oncologist.
Authors: M. Teo, M. O'Keeffe, E. Moylan, S. O'Reilly, B. R. Bird, D. G. Power
Journal: Journal of Clinical Oncology (2011)

354 Background: Gallbladder cancer (GBC) is rare, is often diagnosed at an advanced stage, and survival &gt;1 yr is uncommon. Recent randomized trials have demonstrated improved survival with well-tolerated chemotherapies. In this light, we retrospectively reviewed referral patterns to medical oncology services in our region. Methods: Prospectively maintained departmental databases from three hospitals serving 480,000 people were reviewed. Patient demographics, disease and treatment details, and outcomes were analyzed. Regional figures were obtained from National Cancer Registry data. Results: Between March 2003 and September 2010, 17 GBCs were referred to medical oncology, representing 25.5% of total GBC diagnosed in the region (Table). Median age at diagnosis was 63.6 years (range 47.0–72.5) and 65% (n=11) were female. The majority (n=13) initially presented with metastatic or locally advanced disease and 6 of these patients underwent cholecystectomy. Of those with early-stage disease, 2 patients were referred with relapsed disease and 2 were referred for adjuvant treatment. Sites of involvement were liver (10), lymph nodes (3), peritoneum (3), duodenum (2), gallbladder bed (1), and pancreas (1). No extra-abdominal metastases were noted. All patients were scheduled for chemotherapy, but 3 were not treated due to worsening performance score. Of the 14 patients who received chemotherapy, 7 received gemcitabine, 5 received 5FU and 2 received cisplatin/gemcitabine. Median duration of chemotherapy was 3.8 months (range 0.7–8.1) and 3 patients (21%) received second-line chemotherapy. 13 patients (76.5%) had died at the time of analysis. Median follow-up was 6.7 months (range 1.7-73.9) and median overall survival was 6 months. Conclusions: A minority of patients with GBC were referred to medical oncology. Given the emergence of level 1 evidence reporting a survival benefit with well-tolerated combination chemotherapy and the potential for adjuvant treatment, higher referral rates may lead to improved outcome. [Table: see text] No significant financial relationships to disclose.
Epstein-Barr Virus Status Correlates with Poor Outcome and Is an Independent Prognostic Variable in De Novo Nodal Diffuse Large B Cell Lymphoma in Peru.
Authors: Brady Beltran, Domingo Morales, Luis Riva, Fernando Hurtado de Mendoza, Pilar Quinones, Alejandro Yabar, Antonio A. Carrasco-Yalan
Journal: Blood (2007)
Clinical activity of the oral ALK inhibitor PF-02341066 in ALK-positive patients with non-small cell lung cancer (NSCLC).
Authors: Y. Bang, E. L. Kwak, A. T. Shaw, D. R. Camidge, A. J. Iafrate, R. G. Maki, B. J. Solomon, S. I. Ou, R. Salgia, J. W. Clark
Journal: Journal of Clinical Oncology (2010)

3 Background: PF-02341066 (PF-1066) is a selective, ATP-competitive, small molecule, orally bioavailable inhibitor of the ALK and MET/HGF receptor tyrosine kinases. EML4-ALK fusion oncogenes have been reported in approximately 4% of NSCLC. Patients with NSCLC harboring an ALK fusion were recruited into an expanded cohort at the recommended phase II dose within the first-in-patient monotherapy trial of PF-1066. Methods: Patients with ALK fusions, as determined by FISH using a break-apart probe to ALK, were enrolled into the expanded cohort irrespective of prior therapy. Treated brain metastases were allowed. PF-1066 was given orally at a dose of 250 mg BID. Responses were determined using RECIST with radiographic studies repeated every 8 weeks. The disease control rate (DCR) was determined based on the frequency of patients with RECIST CR, PR and stable disease at 8 weeks. Results: To date, 76 ALK+ NSCLC patients have been treated. The median number of prior treatments was 3 (range, 0-7). Most patients had adenocarcinoma histology and were never or former smokers. Mean plasma C trough was 292 ng/mL, which was above the predicted efficacious concentration from preclinical models (120 ng/mL). The median t 1/2 was ∼53 hours. To date, 50 patients are evaluable for response; ORR is 64% and DCR 90%. The median progression-free survival is not yet mature. The median duration of treatment is 25.5+ weeks. Radiological responses typically were observed at the first or second restaging CT scan. Gastrointestinal toxicities, including nausea (55%) and vomiting (39%), were the most frequent adverse events. Conclusions: The oral ALK inhibitor, PF-1066, demonstrated a high response rate in patients selected for ALK fusions and was associated with a good safety profile. A phase III study has been initiated. This study supports the concept of molecular selection of NSCLC patients for appropriately designed treatment. [Table: see text]
Once per cycle combination of long-acting hematopoietic growth factors (HGFs) pegfilgrastim and darbepoetin alfa (Peg-G + DPO) to reduce multi-lineage hematopoietic toxicity of chemotherapy with doxorubicin and ifosfamide (AI) in patients with sarcoma
Authors: S. Vadhan-Raj, J. Trent, M. A. Burgess, S. Patel, M. L. Collard, G. Zachariah, G. Hangoc, M. Johnson, H. E. Broxmeyer, R. S. Benjamin
Journal: Journal of Clinical Oncology (2005)

8225 AI results in cumulative multi-lineage toxicity. In our previous study of filgrastim and epoetin alfa (G + EPO) with AI in chemo-naïve pts, the incidence of neutropenic fever (NF) was 33% and red cell transfusions (PRBC Tx) 40% of cycles. The purpose of the present study was to evaluate safety, hematopoietic effects on progenitors, and efficacy of the new long-acting HGFs Peg-G + DPO in reducing the incidence of NF and PRBC Tx. AI (A 90 mg/m2; I 10 gm/m2) was administered on days 0–3. HGFs were administered SC once per cycle, with DPO (initial dose, 500 mcg) prior to (day 0) and Peg-G (6 mg) post (day 4) completion of AI. Cycles were repeated q 21 days (max 6 cycles). Bone marrow (BM) and peripheral blood progenitor cells were examined in cycle 1. The data for NF and PRBC Tx are shown below for both studies. The median duration of neutropenia during all 6 cycles remained ≤3 days with Peg-G as compared to a progressive increase in the duration with G (days ANC <500/mm3: 3, 3, 4, 5, 6, and 6 for C1–6, respectively). The frequency of BM erythroid and multipotential progenitors increased (p=0.06), however, the proportion in s-phase was not increased on day 14 (n=12). Treatment resulted in marked mobilization of CD 34+cells and multi-lineage progenitors (p=0.003). These results indicate that once per cycle new HGFs are effective in reducing multi-lineage toxicity and simplify the patient management. Our findings also suggest the interesting biologic differences and potential advantage for Peg-G observed in the setting of more myelosuppressive regimen with cumulative toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen
Salvage esophagectomy after definitive chemotherapy and radiotherapy for advanced esophageal cancer
Authors: A. Takeda
Journal: Journal of Clinical Oncology (2005)

4276 Background: Local recurrence or residual tumor of advanced esophageal cancer is frequent following definitive chemoradiotherapy (CRT), the clinical benefit of salvage surgery has not been elucidated. Methods: We reviewed 7 patients (6 men, 1 woman, age 54–69) who underwent salvage surgery at our department for esophageal squamous cell carcinoma after definitive CRT from July 2002 through December 2004. According to Japanese Society for esophageal disease, clinical stage before first treatment was as follows: stage2; 3, stage3; 2 and stage4; 2. Our definitive CRT regimen for advanced esophageal cancer was fluorouracil (5-Fu) 400mg/m2/24 hours on day 1 to 5 and 8–12, cisplatin (CDDP) 40mg/m2/2hours on day1 and 8, and concurrent radiation therapy (2Gy/day on day 1 to 5, 8 to 12 and 15 to 19). This regimen was repeated in 5 weeks, followed by 5-Fu 800mg/m2/24 hours on day 1 to 5 and CDDP 80mg/m2/2 hours on day 1, which was repeated in 4 weeks. After these radical CRT, patients who were confirmed to have local recurrence after complete remission (2 cases) or residual tumor (5 cases) underwent salvage operation. Results: All patients underwent surgically curative operation by radical esophagectomy with two-field lymphadenectomy. The operation time may range from 198 to 300 minutes. Intraoperative mean blood loss was 316 ml. Postoperative complications were anastomosis leakage in 1 patient, radiation pneumonia 1 and acute cardiac failure 1. One patient resulted in postoperative hospitalized death. Two patients died due to respiratory failure 4 months later. But two patients are alive more than 2 years after salvage operation without recurrence. Conclusions: The outcomes of salvage esophagectomy after definitive CRT is not necessarily satisfactory, but there found some cases that have fulfilled the promise of this treatment. Less-invasive salvage procedure and evaluation of indication for salvage operation might be required because of the high operation risk. No significant financial relationships to disclose.
Monocytes/Macrophages Are the Major Targets of the CCL3 Chemokine Produced by CD38+CD49d+ Chronic Lymphocytic Leukemia Cells.
Authors: Antonella Zucchetto, Dania Benedetti, Claudio Tripodo, Riccardo Bomben, Fleur Bossi, Michele Dal-Bo, Daniela Marconi, Massimo Degan, Giovanni Del Poeta, Silvia Deaglio, Gianluca Gaidano, Francesco Tedesco, Fabio Malavasi, Valter Gattei
Journal: Blood (2009)
Loss of succinate dehydrogenase (SDHB) in midgut carcinoids as a prognostic factor: A new marker of personalized cancer medicine in neuroendocrine tumors?
Authors: Filippo G. De Braud, Sara Pusceddu, Massimo Milione, Roberto Buzzoni, Vincenzo Mazzaferro, Jorgelina Clara Coppa, Angela Damato, Ettore Seregni, Barbara Formisano, Giuseppe Pelosi
Journal: Journal of Clinical Oncology (2013)

186 Background: Gene mutations of the succinate dehydrogenase (SDH) complex have recently been involved in the pathogenesis of cancer cells. These mutations often are associated with SDH subunity B loss of activity and overexpression of HIF-1α. The immunoistochemical (IHC) loss of SDHB expression has recently been reported to be a surrogate marker of malignancy in pheocromocytomas and paragangliomas. The aim is the evaluation of SDHB levels expression in advanced midgut carcinoids and investigate its potential role as prognostic marker. Methods: 31 advanced midgut carcinoids were treated in our Istitution, including 24 males and 7 females, aged 55.5 yrs on average (range 19-75). All patients were G1 tumors with stage IV for synchronous liver metastases. 25/31 patients underwent surgical primary resection. IHC evaluation of the SDHB and MIB1 expression were carried out in 20 primary tumors (T) and 19 liver metastases (M). In 11 patients SDHB and MIB1 were tested in both T and M. SDHB was assessed according to the staining intensity scored 1 (low) or 2 (high) on the basis of the internal control represented by normal intestinal cells. Results: Loss of SDHB expression (IHC +1) was detected in 70% of T and in 90% of M. The value of MIB 1 labeling index: 1,3% represent a cut-off for distinguish low or high SDHB expression within these G1 midgut category (MIB 1≥ 1.3, SDHB +1: 90%; MIB 1 &lt;1.3, SDHB +1: 10%). No difference in term of median OS was found between these 2 groups, 113 vs 103 mts respectively. In 11 pts the combined analysis (T+M) confirmed the loss of SDHB expression in 82% of metastases compared to 18% of primary tumors. These findings were inversely proportional to Mib-1 distribution that was 1,54% in metastastic sites and 0.7% in the primaries, respectively. Conclusions: This preliminary analysis suggests a possible correlation between SDHB expression loss, MIB1 increase and biological aggressiveness of advanced midgut carcinoids. A more extensive clinico-biological evaluation is warranted to clarify its relationship with survival and explore the role of SDHB as predictive marker to response of antiangiogenetic agents.
PLX4032 (RG7204), a selective mutant RAF inhibitor: Clinical and histologic characteristics of therapy-associated cutaneous neoplasms in a phase I trial.
Authors: M. E. Lacouture, G. A. McArthur, P. B. Chapman, A. Ribas, K. T. Flaherty, R. J. Lee, K. B. Nolop, K. B. Kim, M. Duvic, J. A. Sosman
Journal: Journal of Clinical Oncology (2010)

8592 Background: Tumor regressions have been observed in a significant proportion of advanced melanoma patients treated with PLX4032 (RG7204), in a phase I trial with BRAF V600E mutated tumors. Treatment by other targeted agents (Sorafenib, XL281) has been associated with cutaneous keratoacanthomas (KA) and squamous cell carcinomas (SCC), or a combination. We evaluated clinical and histologic characteristics of cutaneous neoplasms following PLX4032 administration. Methods: Fifty-five patients were enrolled in the dose escalation portion of this study, and 32 additional patients with metastatic melanoma harboring a BRAF mutation were enrolled in an extension cohort. All 32 patients in the extension cohort were assessed by a dermatologist pre-therapy, at day 22-30, and every 3 months thereafter. Lesions developing during therapy were biopsied and reviewed centrally. Results: To date, 20% of patients developed cutaneous neoplasms including 9% with multiple lesions. All lesions were localized and usually occurred within 8-12 weeks of beginning therapy. In the dose escalation cohorts, 8 (15%) developed lesions, whereas of those receiving the MTD of 960 mg BID in the melanoma extension cohort, 9 (28%) were affected. Body distribution included head/neck (41%), upper extremities (16%), trunk/back/abdomen (19%) and lower extremities (25%) in sun-exposed skin. A total of 35 lesions were analyzed by central pathology review, showing KA type SCC (n = 19), SCC suggestive of KA (n = 8), SCC with some KA features (n = 4), SCC (n = 1), and verruca-like lesions (n = 3). All patients without melanoma progression continued PLX4032 after removal of these lesions. Conclusions: PLX4032 is associated with the development of skin lesions including KA and rarely SCC as confirmed by central review. Overall, these are well-differentiated neoplasms with likely low probability of invasive and metastatic potential. Frequent dermatological and head, neck, and chest evaluations are ongoing for all patients in PLX4032 clinical trials. Immunohistochemical, genetic and preclinical investigations of these events are being performed by numerous investigators and will not be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Plexxikon, Roche Roche Plexxikon Roche